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The goal of this study was to investigate if there is an independent linear relationship between body mass index and gallbladder stone disease in obese people. In the years 2013-2019, 870 patients were recruited with new-onset asymptomatic gallbladder stone disease, and 870 healthy individuals at our university's affiliated hospital for annual medical examinations were also included. We examined weight, height, blood pressure, fasting blood glucose, and serum lipid indices, and used logistic multivariate regression analysis to assess their relationships. Multivariate analysis revealed that body mass index, waist-to-height ratio, and hypercholesterolemia were all significant risk variables for gallbladder stone disease (P < 0.01, all) in pre-initial overweight subjects. In both overweight and obese subjects, waist-to-height ratio had a significantly positive relationship with gallbladder stone disease (P < 0.01, both); hypercholesterolemia had a similar effect on overweight participants (P < 0.01). After stratification by gender, serum total cholesterol and low-density lipoprotein cholesterol were significant risk factors in male overweight-obese participants (P < 0.05, both), but waist-to-height ratio and low-density lipoprotein cholesterol were equivalent in female overweight-obese subjects (P < 0.05, both). In conclusion, body mass index may be the best predictor for new-diagnosed asymptomatic gallbladder stone disease risk in the pre-initial overweight population without diagnosed diabetes, whereas abdominal adiposity may be during each phase. [ABSTRACT FROM AUTHOR]

Background: The components of donor blood themselves have the potential to initiate a systemic inflammatory response and exacerbate neuroinflammation, resulting in subsequent cerebral injury. The aim of this study was to establish the role of transfusion in the development of cerebral injury during the correction of congenital heart defects in children. Material and Methods: A total of 78 patients aged from 1 to 78 months, with body weights ranging from 3.3 to 21.5 kg, were investigated. Biomarkers of cerebral injury and systemic inflammatory response were studied at three time points. First: prior to the surgical intervention. Second: after the completion of cardiopulmonary bypass. Third: 16 h after the conclusion of the surgery. Results: The strongest correlation was found for S-100-β protein with the volume of transfusion at the second (Rho = 0.48, p = 0.00065) and third time points (Rho = 0.36, p = 0.01330). Neuron-specific enolase demonstrated a similar trend: Rho = 0.41 and p = 0.00421 after the completion of cardiopulmonary bypass. Conclusions: The use of red blood cell suspension and its dosage per kilogram of body weight correlated with the biomarkers of cerebral injury and systemic inflammatory response with moderate to significant strength. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic adenocarcinoma (PDAC) is becoming a public health issue with a 5-years survival rate around 10%. Patients with PDAC are often sarcopenic, which impacts postoperative outcome. At the same time, overweight population is increasing and adipose tissue promotes tumor related-inflammation. With several studies supporting independently these data, we aimed to assess if they held an impact on survival when combined. Methods: We included 232 patients from two university hospitals (CHU de Lille, Institut Paoli Calmette), from January 2011 to December 2018, who underwent Pancreaticoduodenectomy (PD) for resectable PDAC. Preoperative CT scan was used to measure sarcopenia and visceral fat according to international cut-offs. Neutrophil to lymphocyte (NLR) and platelet to lymphocyte ratios (PLR) were used to measure inflammation. For univariate and multivariate analyses, the Cox proportional-hazard model was used. P-values below 0.05 were considered significant. Results: Sarcopenic patients with visceral obesity were less likely to survive than the others in multivariate analysis (OS, HR 1.65, p= 0.043). Cutaneous obesity did not influence survival. We also observed an influence on survival when we studied sarcopenia with visceral obesity (OS, p= 0.056; PFS, p = 0.014), sarcopenia with cutaneous obesity (PFS, p= 0.005) and sarcopenia with PLR (PFS, p= 0.043). This poor prognosis was also found in sarcopenic obese patients with high PLR (OS, p= 0.05; PFS, p= 0.01). Conclusion: Sarcopenic obesity was associated with poor prognosis after PD for PDAC, especially in patients with systemic inflammation. Pre operative management of these factors should be addressed in pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

Abstract Introduction Pancreatic adenocarcinoma (PDAC) is becoming a public health issue with a 5-years survival rate around 10%. Patients with PDAC are often sarcopenic, which impacts postoperative outcome. At the same time, overweight population is increasing and adipose tissue promotes tumor related-inflammation. With several studies supporting independently these data, we aimed to assess if they held an impact on survival when combined. Methods We included 232 patients from two university hospitals (CHU de Lille, Institut Paoli Calmette), from January 2011 to December 2018, who underwent Pancreaticoduodenectomy (PD) for resectable PDAC. Preoperative CT scan was used to measure sarcopenia and visceral fat according to international cut-offs. Neutrophil to lymphocyte (NLR) and platelet to lymphocyte ratios (PLR) were used to measure inflammation. For univariate and multivariate analyses, the Cox proportional-hazard model was used. P-values below 0.05 were considered significant. Results Sarcopenic patients with visceral obesity were less likely to survive than the others in multivariate analysis (OS, HR 1.65, p= 0.043). Cutaneous obesity did not influence survival. We also observed an influence on survival when we studied sarcopenia with visceral obesity (OS, p= 0.056; PFS, p = 0.014), sarcopenia with cutaneous obesity (PFS, p= 0.005) and sarcopenia with PLR (PFS, p= 0.043). This poor prognosis was also found in sarcopenic obese patients with high PLR (OS, p= 0.05; PFS, p= 0.01). Conclusion Sarcopenic obesity was associated with poor prognosis after PD for PDAC, especially in patients with systemic inflammation. Pre operative management of these factors should be addressed in pancreatic cancer patients.

Abstract Background Extracorporeal circulation causes a systemic inflammatory response, that may cause postoperative haemodynamic instability and end-organ dysfunction. This study aimed to investigate the impact of minimal invasive extracorporeal circulation (MiECC) on the systemic inflammatory response compared with conventional extracorporeal circulation (CECC). Methods Patients undergoing coronary artery bypass grafting were randomized to MiECC (n = 30) and CECC (n = 30). Primary endpoint was tumor necrosis factor-α. Secondary endpoints were other biochemical markers of inflammation (IL1β, IL6 and IL8, C-reactive protein, leukocytes), and markers of inadequate tissue perfusion and tissue damage (lactate dehydrogenase, lactate and creatine kinase-MB). In addition, we registered signs of systemic inflammatory response syndrome, haemodynamic instability, atrial fibrillation, respiratory dysfunction, and infection. Results Patients treated with MiECC showed significantly lower levels of tumor necrosis factor-α than CECC during and early after extracorporeal circulation (median: MiECC 3.4 pg/mL; CI 2.2–4.5 vs. CECC 4.6 pg/mL; CI 3.4–5.6; p = 0.01). Lower levels of creatine kinase-MB and lactate dehydrogenase suggested less tissue damage. However, we detected no other significant differences in any other markers of inflammation, tissue damage or in any of the clinical outcomes. Conclusions Lower levels of TNF-α after MiECC compared with CECC may reflect reduced inflammatory response, although other biochemical markers of inflammation were comparable. Our results suggest better end-organ protection with MiECC compared with CECC. Clinical parameters related to systemic inflammatory response were comparable in this study. Clinical registration number NCT03216720.

Purpose: Systemic inflammatory response markers are reported to be prognostic for patients with cancer. The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index has been established as an immuno-nutritional scoring system. The aim of this study was to clarify the impact of the preoperative CALLY index on the outcome of patients undergoing gastrectomy for gastric cancer. Methods: We analyzed the data of 826 patients who underwent gastrectomy for stage I, II, or III gastric cancer between 2010 and 2017. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 104). Results: The cut-off of the CALLY index was 2. The 147 patients with a preoperative CALLY index < 2 had significantly worse overall survival (OS) and relapse-free survival (RFS) than those with a CALLY index ≥ 2 (P < 0.01, P < 0.01, respectively). Multivariate analysis identified that a CALLY index < 2 (P = 0.02), intraoperative blood loss (P < 0.01), and stage II or III disease (P < 0.01) were independent and significant predictors of worse RFS. A CALLY index < 2 (P = 0.01), intraoperative blood loss (P < 0.01), postoperative complications (P = 0.02), and stage II or III disease (P < 0.01) were independent and significant predictors of worse OS. Conclusion: The preoperative CALLY index was independently associated with a poor prognosis for patients after gastrectomy for gastric cancer. [ABSTRACT FROM AUTHOR]

Glaesserella parasuis (GPS) can cause severe systemic inflammation in pigs, resulting in huge economic losses to the pig industry. At present, no effective method is available for the prevention and control of GPS infection. Molecular breeding for disease resistance is imminent, but disease-resistance genes have not been identified. To study the mechanism of systemic acute inflammation caused by GPS, we established three in vitro infection models (3D4/21 cells, PK15 cells, and PAVEC cells) according to its infection path. There was no significant difference in apoptosis among the three kinds of cells after 12 h of continuous GPS stimulation, while inflammatory factors were significantly upregulated. Subsequent transcriptome analysis revealed 1969, 1207, and 3564 differentially expressed genes (DEGs) in 3D4/21 cells, PK15 cells, and PAVEC cells, respectively, after GPS infection. Many of the DEGs were predicted to be associated with inflammatory responses (C3, CD44, etc.); cell proliferation, growth and apoptosis; gene expression; and protein phosphorylation. Key signaling pathways, including S100 family signaling, bacteria and virus recognition, and pathogen-induced cytokine storm signaling, were enriched based on Ingenuity Pathway Analysis (IPA). Furthermore, a total of three putative transmembrane receptors and two putative G-protein-coupled receptors, namely F3, ICAM1, PLAUR, ACKR3, and GPRC5A, were identified by IPA among the three types of cells. ACKR3 and GPRC5A play pivotal roles in bacterial adhesion, invasion, host immune response and inflammatory response through the S100 family signaling pathway. Our findings provide new insights into the pathological mechanisms underlying systemic inflammation caused by GPS infection in pigs, and they lay a foundation for further research on disease-resistance breeding to GPS. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal circulation causes a systemic inflammatory response, that may cause postoperative haemodynamic instability and end-organ dysfunction. This study aimed to investigate the impact of minimal invasive extracorporeal circulation (MiECC) on the systemic inflammatory response compared with conventional extracorporeal circulation (CECC). Methods: Patients undergoing coronary artery bypass grafting were randomized to MiECC (n = 30) and CECC (n = 30). Primary endpoint was tumor necrosis factor-α. Secondary endpoints were other biochemical markers of inflammation (IL1β, IL6 and IL8, C-reactive protein, leukocytes), and markers of inadequate tissue perfusion and tissue damage (lactate dehydrogenase, lactate and creatine kinase-MB). In addition, we registered signs of systemic inflammatory response syndrome, haemodynamic instability, atrial fibrillation, respiratory dysfunction, and infection. Results: Patients treated with MiECC showed significantly lower levels of tumor necrosis factor-α than CECC during and early after extracorporeal circulation (median: MiECC 3.4 pg/mL; CI 2.2–4.5 vs. CECC 4.6 pg/mL; CI 3.4–5.6; p = 0.01). Lower levels of creatine kinase-MB and lactate dehydrogenase suggested less tissue damage. However, we detected no other significant differences in any other markers of inflammation, tissue damage or in any of the clinical outcomes. Conclusions: Lower levels of TNF-α after MiECC compared with CECC may reflect reduced inflammatory response, although other biochemical markers of inflammation were comparable. Our results suggest better end-organ protection with MiECC compared with CECC. Clinical parameters related to systemic inflammatory response were comparable in this study. Clinical registration number: NCT03216720. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammatory response is significant prognostic indicator in patients with various diseases. The relationship between prognostic scoring systems based on the modified Glasgow Prognostic Score (mGPS) and achalasia in patients treated with laparoscopic Heller‑myotomy with Dor‑fundoplication (LHD) remains uninvestigated. This study aimed to examine the role of mGPS in patients with achalasia. Methods: 457 patients with achalasia who underwent LHD as the primary surgery between September 2005 and December 2020 were included. We divided patients into the mGPS 0 and mGPS 1 or 2 groups and compared the patients' background, pathophysiology, symptoms, surgical outcomes, and postoperative course. Results: mGPS was 0 in 379 patients and 1 or 2 in 78 patients. Preoperative vomiting and pneumonia were more common in patients with mGPS of 1 or 2. There were no differences in surgical outcomes. Postoperative upper gastrointestinal endoscopy revealed that severe esophagitis was more frequently observed in patients with mGPS of 1 or 2 (P < 0.01). The clinical success was 91% and 99% in the mGPS 0 and mGPS 1 or 2 groups, respectively (P < 0.01). Conclusions: Although severe reflux esophagitis was more common in patients with achalasia with a high mGPS, good clinical success was obtained regardless of the preoperative mGPS. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis even after curative-intent hepatic resection due to a high recurrence rate. The aim of this study was to investigate preoperative risk factors for early recurrence after surgery for ICC, which may help to identify patients who need preoperative chemotherapy. Methods: We retrospectively analyzed 51 patients who had undergone primary surgery for ICC. We investigated the association of preoperative clinical variables with recurrence within 1 year after resection for ICC. We then created a high-risk ICC score using the identified preoperative factors and investigated the association of the score with disease-free and overall survival. Results: Recurrence within 1 year after surgery for ICC was significantly associated with poor overall survival (P <.01). In the multivariate analysis, preoperative tumor size > 5 cm (P =.03) and elevated C-reactive protein-to-albumin ratio (CAR) (P =.04) were significantly associated with recurrence within 1 year after surgery. A high-risk ICC score of 2 was associated with poor disease-free survival (P <.01) and overall survival (P =.02) compared with a score of 0 or 1. Conclusions: Our high-risk ICC score, combining preoperative tumor size and CAR, can be an indicator of early recurrence and poor survival in patients after hepatic resection for ICC. Our findings may provide better preoperative risk stratification of patients with ICC, and the high-risk ICC patients may benefit from preoperative therapy. [ABSTRACT FROM AUTHOR]

Aim and background: Tropical infections have a high prevalence in India. Mostly, coinfection with more than one tropical infection makes the diagnosis difficult and increases mortality and morbidity. To increase more awareness regarding tropical infections which can turn into life threatening situations and the need for aggressive management for that. Case description: We present a case of a 51-year-old lady admitted with vomiting and diarrhea, which rapidly progressed into sepsis and multiorgan dysfunction. Blood investigations showed coinfection with hepatitis E, scrub typhus, and dengue. She was treated aggressively with all conservative and interventional measures. Conclusion: Despite our best efforts, she had a persistent high-grade fever, severe anemia, thrombocytopenia, and markedly increased liver enzymes with raised D-dimer, fibrinogen, and ferritin, leading to secondary hemophagocytic lymphohistiocytosis (HLH) syndrome. She succumbed to the illness ultimately. Clinical significance: triple coinfection of dengue, hepatitis E, and scrub typhus, which, to our knowledge, has not been previously reported in the literature, making it an exceptionally rare presentation. [ABSTRACT FROM AUTHOR]

The neuroinflammation is a crucial component of virtually all neurodegenerative disorders, including Alzheimer’s disease (AD). The bacterial lipopolysaccharide (LPS), a potent activator of the innate immune system, was suggested to influence or even trigger the neuropathological alterations in AD. LPS-induced neuroinflammation involves changes in transcription of several genes, thus controlling these molecular processes may be a potentially efficient strategy to attenuate the progression of AD. Since genome-wide association studies showed that the majority of AD-related genetic risk factors (AD-GRF) are connected to the immune system, our aim was to identify AD-GRF affected in the hippocampus by LPS-induced systemic inflammatory response (SIR). Moreover, we analysed the role of bromodomain and extraterminal domain (BET) proteins, the readers of the acetylation code, in controlling the transcription of selected AD-GRF in the brain during neuroinflammation. In our study, we used a mouse model of LPS-induced SIR and mouse microglial BV2 cells. JQ1 was used as an inhibitor of BET proteins. The level of mRNA was analysed using microarrays and qPCR. Our data demonstrated that among the established AD-GRF, only the expression of Cd33 was significantly upregulated in the hippocampus during SIR. In parallel, we observed an increase in the expression of Brd4, a BET family member. JQ1 prevented an LPS-evoked increase in Cd33 expression in the hippocampus of mice. Moreover, JQ1 reduced Cd33 expression in BV2 microglial cells stimulated with blood serum from LPS-treated mice. Our study suggests that LPS-evoked SIR may increase Cd33 gene expression in the brain, and inhibition of BET proteins through suppression of Cd33 expression could be a promising strategy in prevention or in slowing down the progression of neuroinflammation and may potentially affect the pathomechanism of AD.

The aim of the study. To study the effect of ley-enkephalin synthetic analogue on the dynamics of inflammatory response markers and organ dysfunction in patients with severe combined trauma.Materials and methods. A prospective clinical study with historical control from two clinical centers — N. I. Pirogov State Clinical Hospital No. 1 and N.V. Sklifosovsky Clinical and Research Institute for Emergency Medicine — included men and women with severe combined trauma and the ISS scores values of 18–44, aged 18 to 70 years. Diagnostic and therapeutic approaches in all patients followed current international, national& local protocols and 2022 clinical recommendations of the Russian Society of Surgeons «Combined and multiple trauma in combination with shock (Polytrauma)». In the study group, treatment was supplemented with extended (72 hours from the admission) infusion of the test drug through a syringe dispenser following the study protocol. Effects of the test drug prolonged infusion were evaluated for the following laboratory parameters: levels of cortisol, procalcitonin, interleukin 6, NTproBNP and leukocyte count. Laboratory tests were performed at 4 time points: prior to test drug infusion, 24 hours and 72 hours after initiation of infusion, and on Day 7. The study evaluated patient’s dynamics using APACHE II, SOFA and SAPS II scales and percentage of patients developing organ dysfunction (renal, respiratory, cardiovascular), rates of sepsis complications and mortality.Results. Patients who received the test drug had significantly lower concentrations of systemic inflammatory response markers, i. e. PCT (P=0.001) and IL-6 (P=0.010) after 24 hours of follow-up vs the control group patients. The incidence of ARDS has also decreased in the study group (P=0.011 vs control). Acute kidney injury (AKI) rate was insignificantly higher in the control group (P=0.349). The duration of hospital stay in the control group was 35 (17; 51) days vs 18 (14; 30) days in the study group (P=0.140)Conclusion. The use of ley-enkephalin synthetic analogue inhibits production of such key systemic inflammatory response markers as PCT and IL-6, and reduces PCT concentrations within 24 hours in patients with severe combined trauma. ARDS developed less frequently in the study group, but there was no significant difference in the incidence of AKI, AHF and infectious complications between the groups.

Abstract Objective The aim of this study is to investigate the clinical value and potential prognostic significance of lung function assessment and Testin expression in non-small cell lung cancer (NSCLC) patients. Methods The NSCLC patients were classified into three groups according to lung function: group of normal lung function, group of PRISm (preserved ratio impaired spirometry) (FEV1, forced expiratory volume during the first second

Objective: The aim of this study is to investigate the clinical value and potential prognostic significance of lung function assessment and Testin expression in non-small cell lung cancer (NSCLC) patients. Methods: The NSCLC patients were classified into three groups according to lung function: group of normal lung function, group of PRISm (preserved ratio impaired spirometry) (FEV1, forced expiratory volume during the first second < 80% predicted and FEV1/FVC (forced vital capacity) ≥ 70%) and group of COPD (chronic obstructive pulmonary disease) (FEV1/FVC < 70%). The pre-operational clinicopathological characteristics of these patients were recorded and the markers of systemic inflammatory response, including neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) and eosinophils (EOS), were compared between three groups. The expression of Testin in NSCLC samples was detected by IHC and we further explored the correlation between Testin expression and clinicopathological characteristics and prognosis of NSCLC patients. Finally, Cox regression analysis was conducted to study the prognostic factors of NSCLC patients. Results: Of the 158 NSCLC patients, percentages of normal lung function, PRISm and COPD were 41.4%, 22.8% and 36.1%, respectively. Patients with tumor in the left lung were more likely to have pulmonary dysfunction (PRISm and COPD) than the right lung. The markers of systemic inflammatory response showed differences to various degree in the three groups and NSCLC patients with PRISm or COPD presented more unfavorable prognosis than patients with normal function. The expression of Testin correlated with lymph node metastasis, TNM stage and tumor invasion of NSCLC patients. Moreover, patients with low Testin expression exhibited poorer disease-free survival and overall survival than those with high Testin expression. In Cox regression analysis, we found that PRISm, COPD and Testin expression served as prognostic factors in NSCLC patients. Conclusions: The presence of COPD or PRISm influenced systemic inflammatory response and prognosis of NSCLC patients. Testin expression correlated with clinicopathological features and could be potentially used as a prognostic marker in NSCLC. [ABSTRACT FROM AUTHOR]

Background: The present work aimed to determine whether a relationship exists between inflammatory parameters and the development of vasospasm (VS) and Takotsubo cardiomyopathy (TTC), as well as clinical outcome, in patients suffering from spontaneous subarachnoid hemorrhage (SAH). Methods: In this study, the authors processed the prospectively collected laboratory and clinical data of spontaneous SAH patients admitted to the neurointensive care unit between March 2015 and October 2023. The highest values of neutrophils (NEUpeak), monocytes (MONOpeak), neutrophil-to-lymphocyte ratio (NLRpeak), and CRP (CRPpeak) during the initial 7 days were correlated with the occurrence of VS and TTC, and with the outcome measures at day 30 after onset. Results: Data were collected from 175 SAH patients. Based on ROC analysis, for the development of VS, MONOpeak was the most accurate indicator (AUC: 0.619, optimal cut-off: 1.45 G/L). TTC with severe left ventricular dysfunction (ejection fraction < 40%) was indicated most sensitively by NEUpeak (ROC: 0.763, optimal cut-off: 12.34 G/L). Both for GOS and Barthel Index at day 30, CRPpeak was the best predictor for the outcome (GOS: ROC: 0.846, optimal cut-off: 78.33 mg/L and Barthel Index: ROC: 0.819, optimal cut-off: 78.33 mg/L). Conclusions: Laboratory parameters referring to inflammation during the initial 7 days after SAH correlate with the development of VS and TTC, and thus may predict functional outcome. [ABSTRACT FROM AUTHOR]

The neuroinflammation is a crucial component of virtually all neurodegenerative disorders, including Alzheimer’s disease (AD). The bacterial lipopolysaccharide (LPS), a potent activator of the innate immune system, was suggested to influence or even trigger the neuropathological alterations in AD. LPS-induced neuroinflammation involves changes in transcription of several genes, thus controlling these molecular processes may be a potentially efficient strategy to attenuate the progression of AD. Since genome-wide association studies showed that the majority of AD-related genetic risk factors (AD-GRF) are connected to the immune system, our aim was to identify AD-GRF affected in the hippocampus by LPS-induced systemic inflammatory response (SIR). Moreover, we analysed the role of bromodomain and extraterminal domain (BET) proteins, the readers of the acetylation code, in controlling the transcription of selected AD-GRF in the brain during neuroinflammation. In our study, we used a mouse model of LPS-induced SIR and mouse microglial BV2 cells. JQ1 was used as an inhibitor of BET proteins. The level of mRNA was analysed using microarrays and qPCR. Our data demonstrated that among the established AD-GRF, only the expression of Cd33 was significantly upregulated in the hippocampus during SIR. In parallel, we observed an increase in the expression of Brd4, a BET family member. JQ1 prevented an LPS-evoked increase in Cd33 expression in the hippocampus of mice. Moreover, JQ1 reduced Cd33 expression in BV2 microglial cells stimulated with blood serum from LPS-treated mice. Our study suggests that LPS-evoked SIR may increase Cd33 gene expression in the brain, and inhibition of BET proteins through suppression of Cd33 expression could be a promising strategy in prevention or in slowing down the progression of neuroinflammation and may potentially affect the pathomechanism of AD. [ABSTRACT FROM AUTHOR]

Up to 57% of patients develop postoperative delirium after surgery for congenital heart defects (CHD). To reduce cerebral damage in pediatric patients during CHD surgery it is important to find out what inflicts the worse damage: would it be a systemic inflammatory response (SIR) triggered by transfusion, or hypoxia developed in non-transfused patients? In vitro evaluation of hypoxia and SIR effects on the neurovascular unit (NVU) cells might contribute to finding the answer.The aim of the study was to compare the effect of varying severity hypoxia and SIR on the functional activity of NUV cells in vitro.Materials and methods. An in vitro NVU model was designed including neurons, astrocytes and endotheliocytes. The effect of hypoxia on NVU was evaluated in the control (C) and 4 study groups (H 1–4), formed based on O₂ content in the medium. The C group NVU were cultivated in standard conditions: N₂ — 75%, O₂ — 20%, CO₂ — 5%; H1: N₂ — 99%, O₂ — 1%; H2: N₂ — 98%, O₂ — 2%; H3: N₂ — 97%, O₂ — 3%; H4: N₂ — 96%, O₂ — 4%. The significance of the differences was 0.0125. The effect of interleukin-6 (IL-6) content on NVU was measured by adding to culture medium pediatric patients’ serum with known minimal or maximal SIRS-response. The assessment was made in the Control — an intact NVU model, and 2 study groups — «Minimum» and «Maximum», i. e. samples with minimum or maximum IL-6 content in culture, respectively. The significance of the differences was 0.017. The cells were incubated at a normothermia regimen for 30 minutes. Then, the functional activity of NVU cells was evaluated by measuring transendothelial resistance (TER) for 24 hours and Lucifer Yellow (LY) permeability test at 60 and 90 minutes after the start of the experiment.Results. After incubation under hypoxic conditions, TER changes occurred in all studied groups. However, they were statistically significant only in the group with 1% oxygen content in the medium. TER decrease in this group was observed after 2, 4 and 24 hours. LY permeability also changed at 60 and 90 minutes, similarly — in NVU cultivated with 1% oxygen in the medium. Minimal TER values were documented at 4 hours after patients’ serum was added to NVU cells culture medium, and TER increased at 24 hours in both study groups. Cellular permeability to LY changed significantly after 1 hour exposure in both groups — with minimum and maximum IL-6 content in the medium. Although at 90 minutes, there was no difference between the 3 groups in LY permeability tests.Conclusion. Intensive SIR demonstrated short-term but more deleterious than hypoxia, effect on cells in the NVU model. Hypoxia disrupted functional activity of NUV cells only at 1% O₂ concentration in the medium.

Abstract Background Systemic inflammatory response represented by C‐reactive protein and albumin ratio (CAR) and modified albumin‐bilirubin (mALBI) grade both have been associated with long‐term outcome in patients with hepatocellular carcinoma (HCC). In this study, we investigated the prognostic utility of combined score of CAR and mALBI score to predict the prognosis of HCC patients after hepatic resection. Methods This study included 214 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. Systemic inflammatory response and mALBI were evaluated preoperatively and patients were classified into three groups based on the combination of CAR and mALBI score: low CAR and low mALBI grade (score 0), either high CAR or high mALBI grade (score 1), and both high CAR and high mALBI grade ≥2b (score 2). Multivariate Cox proportional hazard models were conducted to assess disease‐free and overall survival. Results In multivariate analysis, sex (p

To prospectively evaluate the relationship between Mean Platelet Volume (MPV) levels and short-term mortality outcomes in critically ill patients aged ≥85 years. We hypothesized that abnormal MPV levels could offer actionable insights for predicting mortality risk in this highly vulnerable group, thereby improving therapeutic decision-making processes in the ICU setting. This study included patients aged ≥85 years. The participants were categorized into two groups based on their MPV levels at admission: group 1 (MPV≤12.5, normal range) and group 2 (MPV>12.5, elevated).A comprehensive set of variables, including demographic information, clinical indices, biochemical parameters, and respiratory metrics, were recorded. In a cohort of 475 participants, patients were stratified into two distinct groups based on MPV values: group 1 (n=400, 84.2%) and group 2 (n=75, 15.8%). The mean age was 89 (SD=7.7) and 88 (SD=6.2) years for group 1 and group 2, respectively, with a statistically significant difference (p=0.035). Significant differences were found in key biochemical parameters such as urea (p=0.045) and sodium (p=0.005). The most profound disparity was observed in platelet counts, with a highly significant p-value [Med-Science 2023; 12(4.000): 1269-73]

Background and Aims: The mortality rate associated with malignant tumors remains high and there is a lack of effective diagnostic and tumor progression markers. Neutrophil extracellular traps (NETs) can promote tumor‐associated thrombosis, invasive metastasis, and inflammatory responses, but there is a lack of research on the value of measuring NETs in the peripheral blood of patients with malignancies. Methods: We included 263 patients with malignancies (55 gliomas, 101 ovarian, 64 colorectal, and 43 lung cancers) and 75 healthy controls in this study. We compared the levels of citrullinated histone H3 (citH3), cell‐free DNA (cfDNA), and systemic inflammation‐related parameters, including neutrophils, lymphocytes, monocytes, platelets, neutrophil‐to‐lymphocyte ratio, monocyte‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, systemic immune inflammation index, and systemic inflammation response index. We assessed the value of changes in NETs in peripheral blood to determine the diagnosis, venous thromboembolism, clinical staging, and systemic inflammatory response in patients with malignancy. Results: The levels of citH3 and cfDNA in peripheral blood can distinguish between healthy controls and tumor patients. The levels of citH3 and cfDNA before clinical intervention did not predict the risk of combined venous thromboembolism in oncology patients in the short‐term after clinical intervention. The levels of citH3, cfDNA, and systemic inflammation‐related parameters in the peripheral blood of tumor patients increased with the clinical stage. There was a correlation between cfDNA levels in peripheral blood and systemic inflammation‐related parameters in tumor patients, and this correlation was more significant in patients with advanced tumors. Conclusions: Changes in NETs in the peripheral blood differ between healthy controls and patients with malignant tumors. NETs may be involved in tumor‐induced systemic inflammatory responses through interaction with circulating inflammatory cells, thus promoting tumor progression. NETs may be used as markers to assist in the diagnosis and progression of tumor malignancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Routine blood parameters (e.g., the neutrophil-to-lymphocyte ratio, NLR) are valuable tools for diagnosing inflammatory, infectious, and metabolic conditions. Dogs with congenital liver shunts show evidence of generalized inflammation and clinical signs that may overlap with those of other diseases. Therefore, the potential diagnostic and prognostic value of blood cell ratios, including the NLR, was investigated in 106 dogs with congenital liver shunts and compared to two other disease groups. An association was detected between the blood NLR and systemic inflammation but not with any characteristics of the liver shunt or clinical correlates. The NLR could not distinguish the three disease groups, dogs with liver shunts that were either medically or surgically treated, or dogs either with successful shunt surgery or those with surgical complications. However, lower NLRs (<2.53) were predictive of dogs with liver shunt surgery requiring only one PSS closure session rather than two consecutive surgeries. Thus, evaluating the blood NLR might be clinically useful in dogs with liver shunts. Although this parameter may have little value in distinguishing dogs with a liver shunt from dogs with other diseases, it appears to be predictive for the number of surgical sessions required for shunt closure via ligation. The neutrophil-to-lymphocyte ratio (NLR) can help in assessing inflammatory diseases, sepsis, and chronic hepatic conditions in humans. Dogs with congenital portosystemic shunts (PSSs) have signs of generalized inflammation, and the clinical signs can overlap with other conditions, including hypoadrenocorticism (HOC). Thus, the potential diagnostic and prognostic value of leukocyte ratios as surrogate markers was assessed in a retrospective case–control study including 106 dogs diagnosed with PSSs. The disease control groups were dogs with parenchymal hepatopathy (PH; n = 22) or HOC (n = 31). In the PSS dogs, the blood NLRs were associated with the severity of systemic inflammation but not with the shunt type, hepatoencephalopathy, systemic infection, or hypoglycemia. The baseline NLRs did not differ between the three disease groups, between medically and surgically treated PSS dogs, or between those with successful PSS ligation and dogs experiencing peri-/post-surgical complications. However, dogs requiring two consecutive surgical interventions had significantly higher NLRs, and an NLR of <2.53 distinguished dogs with successful shunt ligation in one surgery from those requiring two consecutive surgeries for PSS closure. The blood NLR might be a useful clinicopathologic variable in PSS, but its value in helping differentiate PSS from HOC cases appears low. Integrating the NLR into a diagnostic algorithm may allow for a prediction of the number of surgical interventions required. [ABSTRACT FROM AUTHOR]

Case presentation: A pregnant woman developed hepatitis due to a herpes simplex virus 2 primary infection with a severe systemic inflammatory response. Treatment with acyclovir and human immunoglobulin was given and both mother and baby survived. Purpose: We provide the first description of the inflammatory response associated with herpetic hepatitis in pregnancy. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the association between microsatellite instability (MSI) status and inflammatory indicators in patients with cancer. Patients & methods: A total of 204 patients with various cancer diagnoses, including 102 with MSI-high (MSI-H) and 102 with microsatellite stable tumors, were enrolled. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein (CRP)-to-albumin ratio and systemic immune-inflammation index were evaluated. Results: In microsatellite stable patients, NLR, LMR, PLR and systemic immune-inflammation index were significantly linked to worse survival in univariate analysis, and having a LMR ≤2.6 negatively affected survival in multivariate analysis, although these indicators did not affect the survival of MSI-H patients. Conclusion: The impact of chronic inflammation on survival varies with MSI status. Further research is needed for targeted therapies in different tumors. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammatory response represented by C‐reactive protein and albumin ratio (CAR) and modified albumin‐bilirubin (mALBI) grade both have been associated with long‐term outcome in patients with hepatocellular carcinoma (HCC). In this study, we investigated the prognostic utility of combined score of CAR and mALBI score to predict the prognosis of HCC patients after hepatic resection. Methods: This study included 214 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. Systemic inflammatory response and mALBI were evaluated preoperatively and patients were classified into three groups based on the combination of CAR and mALBI score: low CAR and low mALBI grade (score 0), either high CAR or high mALBI grade (score 1), and both high CAR and high mALBI grade ≥2b (score 2). Multivariate Cox proportional hazard models were conducted to assess disease‐free and overall survival. Results: In multivariate analysis, sex (p < 0.01), HBsAg positivity (p < 0.01), serum AFP level ≥20 ng/mL (p < 0.01), microvascular invasion (p = 0.02), multiple tumors (p < 0.01), type of resection (p < 0.01), and CAR‐mALBI score ≥2 (HR 2.19, 95% CI 1.39–3.44, p < 0.01) were independent prognostic factors of disease‐free survival, while sex (p = 0.01), HBsAg positivity (p < 0.01), poor tumor differentiation (p = 0.03), multiple tumors (p < 0.01), CAR‐mALBI score ≥2 (HR 2.70, 95% CI 1.51–4.83, p < 0.01) were independent prognostic factors of overall survival. Conclusions: CAR‐mALBI score is associated with disease‐free and overall survival in patients with HCC after hepatic resection, suggesting the importance of evaluating both hepatic functional reserve and host‐inflammatory state in the risk assessment of HCC patients. [ABSTRACT FROM AUTHOR]

To prospectively evaluate the relationship between Mean Platelet Volume (MPV) levels and short-term mortality outcomes in critically ill patients aged ≥85 years. We hypothesized that abnormal MPV levels could offer actionable insights for predicting mortality risk in this highly vulnerable group, thereby improving therapeutic decision-making processes in the ICU setting. This study included patients aged ≥85 years. The participants were categorized into two groups based on their MPV levels at admission: group 1 (MPV≤12.5, normal range) and group 2 (MPV>12.5, elevated).A comprehensive set of variables, including demographic information, clinical indices, biochemical parameters, and respiratory metrics, were recorded. In a cohort of 475 participants, patients were stratified into two distinct groups based on MPV values: group 1 (n=400, 84.2%) and group 2 (n=75, 15.8%). The mean age was 89 (SD=7.7) and 88 (SD=6.2) years for group 1 and group 2, respectively, with a statistically significant difference (p=0.035). Significant differences were found in key biochemical parameters such as urea (p=0.045) and sodium (p=0.005). The most profound disparity was observed in platelet counts, with a highly significant p-value <0.001. The clinical outcomes showed a substantial divergence in the 30-day mortality rates between the two MPV-based cohorts (p<0.001). Additionally, a higher incidence of sepsis was recorded in the Group 2 (p=0.024). MPV is a significant prognostic indicator for mortality, 30-day mortality, and sepsis incidence, advocating its inclusion in routine clinical assessments to optimize patient care. Routinely accessible platelet indices serve as robust indicators for assessing both morbidity and mortality in critically ill patients. [ABSTRACT FROM AUTHOR]

Introduction: Bai-Hu-Tang (BHT), a classical prescription of traditional Chinese medicine, has been extensively used to treat many infectious diseases and high fever syndrome. However, the specific mechanisms and molecular targets affected by BHT have not been thoroughly investigated in the context of treating systemic inflammatory response. This study aimed to explore the comprehensive protein mechanism of BHT during treatment of the lipopolysaccharide (LPS) systemic inflammatory response. Methods: The rabbit model of the systemic inflammatory response was established by LPS intravenous injection (15 μg/kg·bw), and aqueous extract of BHT was administrated by gavage to the model rabbits. At the same time, a group of normal rabbits were also gavaged with BHT alone. Based on liver histopathological study, total liver protein was extracted, and two-dimensional liquid chromatography (LC) - tandem mass spectrometry (MS) coupled with isobaric tags for relative and absolute quantification (iTRAQ) labeling analysis was employed to identify and quantify the liver proteome. Differentially expressed proteins (DEPs) were screened through comparing with control animals, and bioinformatics analysis was conducted to explore kyoto encyclopedia of genes and genomes (KEGG) pathways enrichment and protein clustering among different groups. Real time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of 4 ribosomal proteins to verify the proteomic results. Results: The results showed that ribosome biogenesis is the most significant biological process and ribosomal DEPs mainly distribute in the large subunit of ribosome during the BHT treatment to the LPS systemic inflammatory response. RT-PCR confirmed that BHT had an effect on mRNA expression of ribosome proteins. Discussion: Therefore, the biological pathway of ribosome biogenesis and the regulation of ribosomal proteins may be the cruicial factors when employing BHT for the treatment of the systemic inflammatory response induced by LPS.

Abstract Acute-on-chronic liver failure (ACLF) has been recognized as a severe clinical syndrome based on the acute deterioration of chronic liver disease and is characterized by organ failure and high short-term mortality. Heterogeneous definitions and diagnostic criteria for the clinical condition have been proposed in different geographic regions due to the differences in aetiologies and precipitating events. Several predictive and prognostic scores have been developed and validated to guide clinical management. The specific pathophysiology of ACLF remains uncertain and is mainly associated with an intense systemic inflammatory response and immune-metabolism disorder based on current evidence. For ACLF patients, standardization of the treatment paradigm is required for different disease stages that may provide targeted treatment strategies for individual needs.

Abstract Background and Aims The mortality rate associated with malignant tumors remains high and there is a lack of effective diagnostic and tumor progression markers. Neutrophil extracellular traps (NETs) can promote tumor‐associated thrombosis, invasive metastasis, and inflammatory responses, but there is a lack of research on the value of measuring NETs in the peripheral blood of patients with malignancies. Methods We included 263 patients with malignancies (55 gliomas, 101 ovarian, 64 colorectal, and 43 lung cancers) and 75 healthy controls in this study. We compared the levels of citrullinated histone H3 (citH3), cell‐free DNA (cfDNA), and systemic inflammation‐related parameters, including neutrophils, lymphocytes, monocytes, platelets, neutrophil‐to‐lymphocyte ratio, monocyte‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, systemic immune inflammation index, and systemic inflammation response index. We assessed the value of changes in NETs in peripheral blood to determine the diagnosis, venous thromboembolism, clinical staging, and systemic inflammatory response in patients with malignancy. Results The levels of citH3 and cfDNA in peripheral blood can distinguish between healthy controls and tumor patients. The levels of citH3 and cfDNA before clinical intervention did not predict the risk of combined venous thromboembolism in oncology patients in the short‐term after clinical intervention. The levels of citH3, cfDNA, and systemic inflammation‐related parameters in the peripheral blood of tumor patients increased with the clinical stage. There was a correlation between cfDNA levels in peripheral blood and systemic inflammation‐related parameters in tumor patients, and this correlation was more significant in patients with advanced tumors. Conclusions Changes in NETs in the peripheral blood differ between healthy controls and patients with malignant tumors. NETs may be involved in tumor‐induced systemic inflammatory responses through interaction with circulating inflammatory cells, thus promoting tumor progression. NETs may be used as markers to assist in the diagnosis and progression of tumor malignancy.

Objective: To examine the association between tumor/host factors (including the systemic inflammatory response), mode of presentation, and short/long-term outcomes in patients undergoing curative resectional surgery for TNM I to III colon cancer. Background: Emergency presentations of colon cancer are associated with worse long-term outcomes than elective presentations despite adjustment for TNM stage. A number of differences in tumor and host factors have been identified between elective and emergency presentations and it may be these factors that are associated with adverse outcomes. Methods: Patients undergoing curative surgery for TNM I to III colon cancer in the West of Scotland from 2011 to 2014 were identified. Tumor/ host factors independently associated with the emergency presentation were identified and entered into a subsequent survival model to determine those that were independently associated with overall survival/ cancer-specific survival (OS/CSS). Results: A total of 2705 patients were identified. The emergency presentation was associated with a worse 3-year OS and CSS compared with elective presentations (70% vs 86% and 91% vs 75%). T stage, age, systemic inflammatory grade, anemia (all P < 0.001), N stage (P = 0.077), extramural venous invasion (P = 0.003), body mass index (P = 0.001), and American Society of Anesthesiologists Classification classification (P = 0.021) were independently associated with emergency presentation. Of these, body mass index [hazard ratio (HR), 0.82], American Society of Anesthesiologists Classification (HR, 1.45), anemia (HR, 1.29), systemic inflammatory grade (HR. 1.11), T stage (HR, 1.57), N stage (HR, 1.80), and adjuvant chemotherapy (HR, 0.47) were independently associated with OS. Similar results were observed for CSS. Conclusions: Within patients undergoing curative surgery for colon cancer, the emergency presentation was not independently associated with worse OS/CSS. Rather, a combination of tumor and host factors account for the worse outcomes observed. [ABSTRACT FROM AUTHOR]

Morphological and molecular biological features of LPS-induced systemic inflammatory response were assessed in old male Wistar rats with high (HR) and low (LR) resistance to hypoxia. The systemic inflammatory response was modeled by intraperitoneal injection of E. coli O26:B6 LPS; the animals were sacrificed after 6 h. In histological sections, the number of neutrophils in the interalveolar septa and the area of necrosis in the liver were determined. The expression levels of Hif1a, Hif2a, Nfkb, Vegf, Il1b, Il6, Il10, and Tgfb mRNA in the liver and serum concentrations of HIF-1α and IL-1β were determined. In 4-6 h after LPS injection, 3 (43%) of 7 HR rats died, whereas no deaths were observed among LR rats. At 6 h after LPS injection, the number of neutrophils in the interalveolar septa of the lungs in LR rats was significantly higher than in HR rats, while the area of necrosis in the liver did not differ. At the same time, the mRNA expression levels of the proinflammatory cytokine genes Il1b and Il6 increased in the liver of both HR and LR rats, whereas the expression of Il10 increased only in HR rats. The expression of the Hif1a gene in the liver was higher in LR rats, but the content of HIF-1α protein in blood serum was higher in HR animals. These data should be taken into account when developing new approaches to the therapy of systemic inflammatory response in infectious and inflammatory diseases in the elderly. [ABSTRACT FROM AUTHOR]

It is unknown whether the well-known association between vitamin D deficiency and mortality could be explained by the immune system modulating effects of vitamin D, which may protect from a systemic inflammatory response (SIR) to adverse health conditions. This study aims to investigate the interrelationships of vitamin D deficiency, biomarkers of SIR, and mortality. We used multivariate logistic regression with adjustment for 51 covariates to assess the associations of vitamin D deficiency with disadvantageous levels of nine biomarkers of SIR in the UK Biobank cohort. Furthermore, we tested with Cox regression and mediation analysis whether biomarkers of SIR and vitamin D deficiency were independently associated with mortality. We included 397,737 participants aged 37–73 years. Vitamin D deficiency was associated with disadvantageous levels of all blood cell count-based biomarkers, but not with C-reactive protein (CRP)-based biomarkers after adjustment for body weight. Vitamin D deficiency and all biomarkers of SIR were significantly associated with all-cause mortality and mortality from cancer, cardiovascular and respiratory disease. The strength of these associations was unaltered if vitamin D deficiency and biomarkers of SIR were put in the same model. This finding was further supported by the mediation analyses. This study showed that vitamin D deficiency is associated with disadvantageous levels of blood cell count-based but not CRP-based biomarkers of SIR. Vitamin D deficiency and systemic inflammation were independently and strongly associated with mortality. The potential of clinical interventions against both vitamin D deficiency and underlying causes of systemic inflammation should be explored. [ABSTRACT FROM AUTHOR]

Guanxiang Huang,1– 3,&ast; Hangjing Gao,1– 3,&ast; Yanlin Chen,1,2 Wenyu Lin,1– 3 Jun Shen,4 Shuxia Xu,5 Dabin Liu,6 Zhihui Wu,7 Xite Lin,1– 3 Tingting Jiang,1– 3 Binhua Dong,1– 3 Pengming Sun1– 3 1Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China; 2Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital (Fujian Women and Children’s Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 3Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 4Fujian Provincial Cervical Disease Diagnosis and Treatment Health Center, Fujian Maternity and Child Health Hospital, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 5Department of Pathology, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 6Department of Gynecology, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 7Department of Clinical Laboratory, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengming Sun; Binhua Dong, Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-591-87558732 ; +86-13599071900, Fax +86-591-87551247, Email fmsun1975@fjmu.edu.cn; sunfemy@hotmail.com; dongbinhua86@fjmu.edu.cn; dbh18-jy@126.comPurpose: The platelet-to-lymphocyte ratio (PLR) is considered correlated with cancer prognosis including cervical cancer, in addition to high-risk papillomavirus (HR-HPV) infection, of which the predictive value in prognosis of high-grade squamous intraepithelial lesions (HSILs) remains unknown. Here, the prognostic predictive value of PLR in HSIL after loop electrosurgical excision procedure (LEEP) was evaluated.Patients and Methods: This study included 335 nonpregnant participants with histopathologically confirmed HSIL and 3- and 5-year follow-ups from the Fujian Cervical Lesions Screening Cohorts (FCLSCs) between September 2016 and September 2018. PLR and other variables were evaluated to identify the factors related to the recurrence/residual cervical intraepithelial neoplasia (CIN)-free survival (RFS), namely, the time from LEEP at baseline to first detection of recurrence/residual CIN or end of follow-up, by logistic and Cox regression.Results: In the Kaplan‒Meier analysis, HR-HPV infection (p=0.049/0.012), higher PLR (p=0.031/0.038), and gland invasion (p=0.047) had a higher risk for recurrence/residual CIN at the 3-/5-year follow-up. The univariate logistic and Cox regression analyses showed significant differences and a higher cumulative risk in patients with HR-HPV infection (OR=3.917, p=0.026; HR=3.996, p=0.020) and higher PLR (OR=2.295, p=0.041; HR=2.161, p=0.030) at the 5-year follow-up. The findings by multivariate Cox regression analysis were similar, indicating a poor prognosis for patients with HR-HPV infection (HR=3.901, p=0.023) and higher PLR (HR=2.082, p=0.038) at the 5-year follow-up. The calibration plot showed a better model fit for RFS at the 3-year follow-up.Conclusion: Preoperative PLR level and HR-HPV infection could be available markers for predicting recurrence/residual disease of HSIL after LEEP. Clinically, combining PLR with HR-HPV tests may provide novel evaluation method and reference for management in post-treatment patients with cervical precancerous lesions.Keywords: systemic inflammatory response, cervical intraepithelial neoplasia, human papillomavirus, HPV, conization, prognosis

Acute-on-chronic liver failure (ACLF) has been recognized as a severe clinical syndrome based on the acute deterioration of chronic liver disease and is characterized by organ failure and high short-term mortality. Heterogeneous definitions and diagnostic criteria for the clinical condition have been proposed in different geographic regions due to the differences in aetiologies and precipitating events. Several predictive and prognostic scores have been developed and validated to guide clinical management. The specific pathophysiology of ACLF remains uncertain and is mainly associated with an intense systemic inflammatory response and immune-metabolism disorder based on current evidence. For ACLF patients, standardization of the treatment paradigm is required for different disease stages that may provide targeted treatment strategies for individual needs. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was to evaluate the reliability of peak interleukin-6 (IL-6) level within 24 hours after delivery as a predictor for early-onset sepsis (EOS) in very preterm neonates. Interleukin-6 was assessed at 2 hours and at 12 to 24 hours after delivery. The highest level was considered a peak value. The definition of EOS was based on positive blood culture and clinical signs of infection or negative blood culture, clinical signs of infection, and C-reactive protein >10 mg/L. Among 445 enrolled infants, 53 developed EOS. A peak IL-6 level of more than 200 ng/L had a sensitivity of 89% and specificity of 77% for the presence of EOS. The negative predictive value was 98%. Receiver operating characteristics curve had area under the curve of 0.92. Peak IL-6 is a reliable marker of systemic inflammatory response and might be useful to exclude EOS within the first 24 hours. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical findings and case progression in a dog presenting with severe systemic inflammatory response, refractory shock, progressive metabolic acidosis, and respiratory failure that was ultimately diagnosed with hypertrophic osteodystrophy (HOD). Case Summary: A 4‐month‐old male intact Mastiff presented with a 24‐hour history of lethargy and generalized ostealgia. On examination, the dog was recumbent, febrile, and tachycardic with pain on palpation of the abdomen, right femur, and mandible. Appendicular joint radiographs showed changes consistent with osteochondrosis and ulnar‐retained cartilaginous cores, with no overt evidence of HOD. Initial treatment included IV fluid therapy, multimodal analgesia, and broad‐spectrum antimicrobials. Vasopressor therapy was initiated following hemodynamic decompensation. Synovial fluid cytological analysis and culture revealed nonseptic suppurative inflammation and no bacterial growth, respectively. Blood and urine cultures also yielded no growth. Viscoelastic testing was consistent with hypercoagulability. The dog initially had a metabolic acidosis with appropriate respiratory compensation that progressed to a mixed metabolic and respiratory acidosis despite aggressive therapies that included antimicrobials, vasopressors, positive inotropes, and corticosteroids. Humane euthanasia was elected approximately 32 hours after admission. Necropsy yielded a diagnosis of HOD. New or Unique Information Provided: This is the first report detailing the occurrence of refractory shock and hypercoagulability associated with HOD in a dog without evidence of another identified comorbidity. HOD should be considered in any young, large‐breed dog with generalized ostealgia and signs of systemic illness, even in the absence of classic radiographic abnormalities. Further investigation of coagulation status in dogs with HOD and a secondary systemic inflammatory response is warranted. [ABSTRACT FROM AUTHOR]

The neutrophil-to-lymphocyte ratio (NLR) can help in assessing inflammatory diseases, sepsis, and chronic hepatic conditions in humans. Dogs with congenital portosystemic shunts (PSSs) have signs of generalized inflammation, and the clinical signs can overlap with other conditions, including hypoadrenocorticism (HOC). Thus, the potential diagnostic and prognostic value of leukocyte ratios as surrogate markers was assessed in a retrospective case–control study including 106 dogs diagnosed with PSSs. The disease control groups were dogs with parenchymal hepatopathy (PH; n = 22) or HOC (n = 31). In the PSS dogs, the blood NLRs were associated with the severity of systemic inflammation but not with the shunt type, hepatoencephalopathy, systemic infection, or hypoglycemia. The baseline NLRs did not differ between the three disease groups, between medically and surgically treated PSS dogs, or between those with successful PSS ligation and dogs experiencing peri-/post-surgical complications. However, dogs requiring two consecutive surgical interventions had significantly higher NLRs, and an NLR of

The association between serum albumin and post-operative outcomes among patients undergoing common surgical procedures: an analysis of a multi-specialty surgical cohort from the national surgical quality improvement program (NSQIP). Keywords: nutritional assessment; serum albumin; systemic inflammatory response EN nutritional assessment serum albumin systemic inflammatory response 824 826 3 09/08/23 20230901 NES 230901 Fifty years ago, we originally used anthropometric measures of weight/height and upper arm anthropometry and serum albumin levels to define and document the high prevalence of protein energy malnutrition in adult surgical patients in a municipal hospital in Boston[1] based on my experience with similar practices in pediatric patients in Haiti during an elective rotation in a philanthropic hospital during my medical training. Similarly, it almost certainly would be found that between two patient groups with similar degrees of protein energy malnutrition, that the one with hypoalbuminemia is more at nutrition risk in terms of poorer outcome and likely to receive more clinical benefit from feeding. 2 Bistrian BR, Blackburn GL, Vitale J, Cochran D, Naylor J. Prevalence of malnutrition in general medical patients. [Extracted from the article]

One of the adverse outcomes of acute inflammatory response is progressing to the chronic stage or transforming into an aggressive process, which can develop rapidly and result in the multiple organ dysfunction syndrome. The leading role in this process is played by the Systemic Inflammatory Response that is accompanied by the production of pro- and anti-inflammatory cytokines, acute phase proteins, and reactive oxygen and nitrogen species.The purpose of this review that highlights both the recent reports and the results of the authors' own research is to encourage scientists to develop new approaches to the differentiated therapy of various SIR manifestations (low- and high-grade systemic inflammatory response phenotypes) by modulating redox-sensitive transcription factors with polyphenols and to evaluate the saturation of the pharmaceutical market with appropriate dosage forms tailored for targeted delivery of these compounds.Redox-sensitive transcription factors such as NFκB, STAT3, AP1 and Nrf2 have a leading role in mechanisms of the formation of low- and high-grade systemic inflammatory phenotypes as variants of SIR. These phenotypic variants underlie the pathogenesis of the most dangerous diseases of internal organs, endocrine and nervous systems, surgical pathologies, and post-traumatic disorders.The use of individual chemical compounds of the class of polyphenols, or their combinations can be an effective technology in the therapy of SIR. Administering natural polyphenols in oral dosage forms is very beneficial in the therapy and management of the number of diseases accompanied with low-grade systemic inflammatory phenotype. The therapy of diseases associated with high-grade systemic inflammatory phenotype requires medicinal phenol preparations manufactured for parenteral administration.

BackgroundTo evaluate the efficacy of the enhanced recovery after surgery (ERAS) programs on the systemic inflammatory response (SIR) of patients following gynecological surgery, a randomized controlled trial was performed to compare the ERAS programs with the conventional perioperative care programs. Furthermore, novel SIR markers could be identified to evaluate the ERAS programs of gynecological surgery.MethodsPatients undergoing gynecological surgery were randomly allocated to either the ERAS group or the conventional group. The correlations between the elements of ERAS protocols and SIR markers following gynecological surgery were evaluated.ResultsA total of 340 patients who underwent gynecological surgery were enrolled (ERAS = 170; conventional = 170). First, we identified whether the ERAS programs after gynecological surgery reduced the perioperative difference between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Interestingly, first flatus time postoperatively, visual analog scale (VAS) score of patients was positively correlated with the perioperative difference NLR or PLR. Moreover, we discovered that the perioperative difference NLR or PLR was correlated with elements of ERAS protocol, including first sips of water, first semifluid diet postoperatively, pelvic drain duration, and out-of-bed time of patients.ConclusionWe originally reveal that certain elements of ERAS programs alleviated SIR to operation. The implementation of ERAS programs enhances postoperative recovery after gynecological surgery via improving system inflammatory status. NLR or PLR could be the novel and inexpensive marker to assess ERAS programs in gynecological surgery.Clinical trial registration:ClinicalTrials.gov, identifier, NCT03629626.

Congenital heart defect (CHD) surgeries are performed with cardiopulmonary bypass (CPB) and are complicated by several factors that affect the child's brain. However, to date, the number of studies on brain protection in cardiac surgery remains small. The aim of this study was to assess the impact of refraining from using packed red blood cells (PRBCs) in priming solutions in children with congenital defects (CHDs) who require surgical interventions using CPB to prevent brain injury in the postoperative period. Material and methods: This study included 40 children, and the mean age was 14 (12–22.5) months and the mean weight was 8.8 (7.25–11) kg. All patients underwent CHD closure using CPB. The patients were divided into two groups depending on the use of PRBCs in the priming solution. Brain injury was assessed using three specific blood serum markers, namely S100 calcium-binding protein β (S100β), neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) before surgery, after the completion of CPB and 16 h after surgery (first, second and third control points). Markers of systemic inflammatory response were also analyzed, including interleukin-1, -6, -10 and tumor necrosis factor alpha (TNF-α). A clinical assessment of brain injury was carried out using a valid, rapid, observational tool for screening delirium in children of this age group, i.e., "Cornell Assessment of Pediatric Delirium". Results: Factors of the intra- and postoperative period were analyzed, such as hemoglobin levels, oxygen delivery (cerebral tissue oxygenation, blood lactate level and venous oxygen saturation) and indicators of organ dysfunction (creatinine, urea, bilirubin levels, duration of CPB and length of stay in the ICU). Following the procedure, there were no significant differences between the groups and all indicators were within the reference values, thus demonstrating the safety of CHD closure without transfusion. Moreover, the highest level of specific markers of brain injury were noted immediately after the completion of CPB in both groups. The concentration of all three markers was significantly higher in the group with transfusion after the completion of CPB. Moreover, GFAP levels were higher in the transfusion group and 16 h after surgery. Conclusions: The results of the study show the safety and effectiveness of brain injury prevention strategies that consist of not conducting PRBC transfusion. [ABSTRACT FROM AUTHOR]

(1) Background: Hemoadsorption is a method of blood purification with a wide spectrum of indications. Pre-emptive use of hemoadsorption in patients undergoing heart surgery with cardiopulmonary bypass is considered to reduce the risk of postoperative systemic inflammatory response syndrome. The current study aimed to identify the spectrum of blood proteins adsorbed on the polymer matrix of the CytoSorb hemoadsorption system and to investigate their influence on cultured endothelial cells in vitro. (2) Methods: Adsorbers used for intraoperative hemoadsorption were obtained from patients undergoing on-pump valve surgery in acute endocarditis. Proteins were extracted from the adsorbers, purified, identified with mass-spectrometry and applied to cultured human aortic endothelial cells. (3) Results: A broad range of blood proteins were identified in the material eluted from the CytoSorb adsorber. When added to cultured ECs, these protein extracts caused severe reduction in cell viability and migration. After 24 h exposure, transcriptional changes with up-regulation of multiple metabolic regulators were observed and verified on the protein level. Genes responsible for control of mitosis were significantly down-regulated. (4) Conclusions: In summary, our data reveal that intraoperative hemoadsorption allows broad spectrum removal of a wide range of molecules eliciting endothelial damage. [ABSTRACT FROM AUTHOR]

Calciprotein particles (CPPs) represent an inherent mineral buffering system responsible for the scavenging of excessive Ca2+ and PO43− ions in order to prevent extraskeletal calcification, although contributing to the development of endothelial dysfunction during the circulation in the bloodstream. Here, we performed label-free proteomic profiling to identify the functional consequences of CPP internalisation by endothelial cells (ECs) and found molecular signatures of significant disturbances in mitochondrial and lysosomal physiology, including oxidative stress, vacuolar acidification, accelerated proteolysis, Ca2+ cytosolic elevation, and mitochondrial outer membrane permeabilisation. Incubation of intact ECs with conditioned medium from CPP-treated ECs caused their pro-inflammatory activation manifested by vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1) upregulation and elevated release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1/ C-C motif ligand 2 (MCP-1/CCL2). Among the blood cells, monocytes were exclusively responsible for CPP internalisation. As compared to the co-incubation of donor blood with CPPs in the flow culture system, intravenous administration of CPPs to Wistar rats caused a considerably higher production of chemokines, indicating the major role of monocytes in CPP-triggered inflammation. Upregulation of sICAM-1 and IL-8 also suggested a notable contribution of endothelial dysfunction to systemic inflammatory response after CPP injections. Collectively, our results demonstrate the pathophysiological significance of CPPs and highlight the need for the development of anti-CPP therapies. [ABSTRACT FROM AUTHOR]

Assess the level of mitochondrial DNA depending on the presence of multiple organ failure in patients after heart surgery. The study included 60 patients who underwent surgical treatment of valvular heart disease using cardiopulmonary bypass. Uncomplicated patients were included in the 1st group (n = 30), patients with complications and multiple organ failure (MOF) were included in the 2nd group (n = 30). Serum mtDNA levels were determined by quantitative real-time polymerase chain reaction with fluorescent dyes. Mitochondrial DNA gene expression did not differ between group before surgery. Immediately after the intervention, cytochrome B gene expression was higher in the group with MOF, and it remained high during entire follow-up period. A similar trend was observed in cytochrome oxidase gene expression. Increased NADH levels of gene expressions during the first postoperative day were noted in both groups, the expression showed tendency to increase on the third postoperative day. mtDNA gene expression in the "MOF present" group remained at a higher level compared with the group without complications. A positive correlation was reveled between the severity of MOF according to SOFA score and the level of mtDNA (r = 0.45; p = 0.028) for the end-point "First day". The ROC analysis showed that mtDNA circulating in plasma (AUC = 0.605) can be a predictor of MOF development. The level of mtDNA significantly increases in case of MOF, irrespective of its cause. (2) The expression of mtDNA genes correlates with the level of MOF severity on the SOFA score. [ABSTRACT FROM AUTHOR]

Background: The tumor-node-metastasis (TNM) staging system does not take the patient's physiological status into consideration, reportedly making it insufficient for predicting survival outcomes in frail cancer patients. We assessed the prognostic values of several nutrition- and inflammation-based markers in combination with pTNM stage in gastric carcinoma (GC) patients. Methods: In total, 1166 patients undergoing GC surgery were studied. The prognostic capabilities of 3 nutritional and 3 systemic inflammatory parameters were examined. We developed new staging systems by adding these markers, individually, to the pTNM stage. We then compared the prognostic capabilities of our new systems with that of pTNM stage alone. We also assessed the prognostic values of these systems by dividing our patient cohort into elderly (≥ 65 years) and non-elderly groups. Results: Our novel staging systems had greater predictive capabilities for overall survival (OS) than pTNM alone. Most notably, survival discrimination was significantly increased for pTNM when it was combined with albumin-based nutritional indices (geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI)). Our new staging systems incorporating GNRI or PNI into pTNM had significantly better predictive capability for OS, especially non-GC mortality, than pTNM alone in elderly GC patients. In the non-elderly patients, the predictive capabilities of the new staging systems for OS differed minimally from that of pTNM. Conclusions: The predictive capability of pTNM stage was particularly enhanced when this parameter was combined with nutritional markers. Our new approach aids in predicting survival outcomes, especially non-GC-related death, in elderly GC patients. [ABSTRACT FROM AUTHOR]

Abstract Background Pancreatic cancer is an aggressive malignancy, surgery being the only potentially curative treatment. The systemic inflammatory response is an important factor in the development of cancer. There is still controversy regarding its role in pancreatic cancer. Methods Our study is a retrospective observational cohort study. We included patients diagnosed with pancreatic ductal adenocarcinoma (PDAC), who underwent surgical resection in our hospital, between January 2012 and December 2019. We gathered information from preoperative and postoperative blood tests. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) were determined. Results We included 312 patients. All the immune-inflammatory scores assessed significantly changed after the surgery. The impact on overall survival of these markers showed that only some of the postoperative scores predicted survival: high PLR had a negative prognostic impact, while high lymphocyte and PNI values had a positive effect on overall survival. Discussion The circulating immune cells and their values integrated in the assessed prognostic scores suffer statistically significant changes after curative pancreatic surgery. Only the postoperative values of lymphocyte count, PLR, and PNI seem to influence the overall survival in PDAC. Trial registration ClinicalTrials.gov–identifier NCT05025371 .

The problem of preventing excessive production of pro-inflammatory cytokines in the case of COVID-19 remains unresolved. The use of steroids in the treatment of coronavirus pneumonia remains controversial. To date, there is insufficient literature data for the routine use of steroids in COVID-19 intensive care programs, and this issue remains the subject of continuous research and endless debate. The review of the scientific literature focuses on one of the areas of pathogenetic therapy for COVID-19 — the prevention and elimination of hyperproduction of pro-inflammatory cytokines using glucocorticoid drugs. The review presents modern international recommendations on the use of glucocorticoid drugs in severe COVID-19, examines the pathogenetic mechanisms of their action and side effects.

Background: Aneurysmal subarachnoid hemorrhage (SAH) frequently triggers systemic inflammatory response syndrome (SIRS). SIRS has been associated with inferior outcomes and, specifically, delayed cerebral infarction after aneurysmal SAH. Here, we assess the impact of intracranial blood clearance through stereotactic catheter ventriculocisternostomy on SIRS in patients with aneurysmal SAH.We assessed daily SIRS criteria (heart rate > 90 beats/min, respiratory rate > 20 breaths/min or abnormal respiratory coefficient, temperature > 38 °C or < 36 °C, white blood cell count < 4000 or > 12,000 cells/mm3) between admission and day 21 in 80 consecutive patients who underwent cisternal lavage through stereotactic catheter ventriculocisternostomy from 2015 to 2022. These patients were compared with 80 matched controls who received treatment at our institution between 2010 and 2015. We conducted a mixed effects model analysis using restricted maximum likelihood estimation to assess the effects of treatment groups on the SIRS rate while accounting for repeated measures. Additionally, Bonferroni’s correction was employed to examine specific differences between groups at different time points.The mean percentages of patients meeting SIRS criteria during the first 21 days after aneurysmal SAH were 23% in the matched cohort group and 14% in patients who underwent cisternal lavage (p < 0.001). Additionally, significant differences were observed in the mean leukocyte count (p = 0.047), mean heart rate (p = 0.019), and mean respiratory rate (p = 0.0018) between the two groups. However, there was no significant difference in mean body temperature (p = 0.36).Intracranial blood clearance and cisternal lavage after aneurysmal SAH is associated with a decline in SIRS prevalence and severity.Methods: Aneurysmal subarachnoid hemorrhage (SAH) frequently triggers systemic inflammatory response syndrome (SIRS). SIRS has been associated with inferior outcomes and, specifically, delayed cerebral infarction after aneurysmal SAH. Here, we assess the impact of intracranial blood clearance through stereotactic catheter ventriculocisternostomy on SIRS in patients with aneurysmal SAH.We assessed daily SIRS criteria (heart rate > 90 beats/min, respiratory rate > 20 breaths/min or abnormal respiratory coefficient, temperature > 38 °C or < 36 °C, white blood cell count < 4000 or > 12,000 cells/mm3) between admission and day 21 in 80 consecutive patients who underwent cisternal lavage through stereotactic catheter ventriculocisternostomy from 2015 to 2022. These patients were compared with 80 matched controls who received treatment at our institution between 2010 and 2015. We conducted a mixed effects model analysis using restricted maximum likelihood estimation to assess the effects of treatment groups on the SIRS rate while accounting for repeated measures. Additionally, Bonferroni’s correction was employed to examine specific differences between groups at different time points.The mean percentages of patients meeting SIRS criteria during the first 21 days after aneurysmal SAH were 23% in the matched cohort group and 14% in patients who underwent cisternal lavage (p < 0.001). Additionally, significant differences were observed in the mean leukocyte count (p = 0.047), mean heart rate (p = 0.019), and mean respiratory rate (p = 0.0018) between the two groups. However, there was no significant difference in mean body temperature (p = 0.36).Intracranial blood clearance and cisternal lavage after aneurysmal SAH is associated with a decline in SIRS prevalence and severity.Results: Aneurysmal subarachnoid hemorrhage (SAH) frequently triggers systemic inflammatory response syndrome (SIRS). SIRS has been associated with inferior outcomes and, specifically, delayed cerebral infarction after aneurysmal SAH. Here, we assess the impact of intracranial blood clearance through stereotactic catheter ventriculocisternostomy on SIRS in patients with aneurysmal SAH.We assessed daily SIRS criteria (heart rate > 90 beats/min, respiratory rate > 20 breaths/min or abnormal respiratory coefficient, temperature > 38 °C or < 36 °C, white blood cell count < 4000 or > 12,000 cells/mm3) between admission and day 21 in 80 consecutive patients who underwent cisternal lavage through stereotactic catheter ventriculocisternostomy from 2015 to 2022. These patients were compared with 80 matched controls who received treatment at our institution between 2010 and 2015. We conducted a mixed effects model analysis using restricted maximum likelihood estimation to assess the effects of treatment groups on the SIRS rate while accounting for repeated measures. Additionally, Bonferroni’s correction was employed to examine specific differences between groups at different time points.The mean percentages of patients meeting SIRS criteria during the first 21 days after aneurysmal SAH were 23% in the matched cohort group and 14% in patients who underwent cisternal lavage (p < 0.001). Additionally, significant differences were observed in the mean leukocyte count (p = 0.047), mean heart rate (p = 0.019), and mean respiratory rate (p = 0.0018) between the two groups. However, there was no significant difference in mean body temperature (p = 0.36).Intracranial blood clearance and cisternal lavage after aneurysmal SAH is associated with a decline in SIRS prevalence and severity.Conclusions: Aneurysmal subarachnoid hemorrhage (SAH) frequently triggers systemic inflammatory response syndrome (SIRS). SIRS has been associated with inferior outcomes and, specifically, delayed cerebral infarction after aneurysmal SAH. Here, we assess the impact of intracranial blood clearance through stereotactic catheter ventriculocisternostomy on SIRS in patients with aneurysmal SAH.We assessed daily SIRS criteria (heart rate > 90 beats/min, respiratory rate > 20 breaths/min or abnormal respiratory coefficient, temperature > 38 °C or < 36 °C, white blood cell count < 4000 or > 12,000 cells/mm3) between admission and day 21 in 80 consecutive patients who underwent cisternal lavage through stereotactic catheter ventriculocisternostomy from 2015 to 2022. These patients were compared with 80 matched controls who received treatment at our institution between 2010 and 2015. We conducted a mixed effects model analysis using restricted maximum likelihood estimation to assess the effects of treatment groups on the SIRS rate while accounting for repeated measures. Additionally, Bonferroni’s correction was employed to examine specific differences between groups at different time points.The mean percentages of patients meeting SIRS criteria during the first 21 days after aneurysmal SAH were 23% in the matched cohort group and 14% in patients who underwent cisternal lavage (p < 0.001). Additionally, significant differences were observed in the mean leukocyte count (p = 0.047), mean heart rate (p = 0.019), and mean respiratory rate (p = 0.0018) between the two groups. However, there was no significant difference in mean body temperature (p = 0.36).Intracranial blood clearance and cisternal lavage after aneurysmal SAH is associated with a decline in SIRS prevalence and severity. [ABSTRACT FROM AUTHOR]

Abstract A biomarker describes a measurable indicator of a patient's clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis, prognosis, early disease recognition, risk stratification, appropriate treatment (theranostics), and trial enrichment for patients with sepsis or suspected sepsis. In this narrative review, we aim to answer the question, "Do biomarkers in patients with sepsis or septic shock predict mortality, multiple organ dysfunction syndrome (MODS), or organ dysfunction?" We also discuss the role of pro- and anti-inflammatory biomarkers and biomarkers associated with intestinal permeability, endothelial injury, organ dysfunction, blood–brain barrier (BBB) breakdown, brain injury, and short and long-term mortality. For sepsis, a range of biomarkers is identified, including fluid phase pattern recognition molecules (PRMs), complement system, cytokines, chemokines, damage-associated molecular patterns (DAMPs), non-coding RNAs, miRNAs, cell membrane receptors, cell proteins, metabolites, and soluble receptors. We also provide an overview of immune response biomarkers that can help identify or differentiate between systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and sepsis-associated encephalopathy. However, significant work is needed to identify the optimal combinations of biomarkers that can augment diagnosis, treatment, and good patient outcomes.