Inflammatory Response Syndrome Research Articles

NIR Absorbing Organic Chromophores Combination with NSAIDs for Remodeling of the Inflammatory Microenvironment to Amplify Tumor Ferroptosis-Photothermal Synergistic Therapy.

Photothermal therapy has emerged as a promising approach for cancer treatment, which can cause ferroptosis to enhance immunotherapeutic efficacy. However, excessively generated immunogenicity will induce serious inflammatory response syndrome, resulting in a discounted therapeutic effect. Herein, a kind of NIR absorption small organic chromophore nanoparticles (TTHM NPs) with high photothermal conversion efficiency (68.33%) is developed, which can induce mitochondria dysfunction, generate mitochondrial superoxide, and following ferroptosis. TTHM NPs-based photothermal therapy is combined with Sulfasalazine (SUZ), a kind of nonsteroidal anti-inflammatory drugs, to weaken inflammation and promote ferroptosis through suppressing glutamate/cystine (Glu/Cys) antiporter system Xc- (xCT). Additionally, the combination of SUZ with PTT can induce immunogenic cell death (ICD), followed by promoting the maturation of DCs and the attraction of CD8+ T cell, which will secrete IFN-γ and trigger self-amplified ferroptosis via inhibiting xCT and simulating Acyl-CoA synthetase long-chain family member 4 (ACSL4). Moreover, the in vivo results demonstrate that this combination therapy can suppress the expression of inflammatory factors, enhance dendritic cell activation, facilitate T-cell infiltration, and realize effective thermal elimination of primary tumors and distant tumors. In general, this work provides an excellent example of combined medication and stimulates new thinking about onco-therapy and inflammatory response.

Analysis of adverse events with lumen apposing metal stents for drainage of pancreatic fluid collections

Abstract Background and study aims Innovations in endoscopic management of pancreatic fluid collections (PFCs) using lumen apposing metal stents (LAMS) have rendered it a preferred approach for drainage of PFCs. These advances have not come without concern for adverse events (AEs). We present our experience with LAMS for drainage of PFCs and analyze factors that contribute to LAMS-related AEs. Patients and methods From November 2015 to October 2021, a retrospective analysis was performed of patients undergoing endoscopic management of PFCs using LAMS. All AEs were classified as either early (<48 hours) or late (>48 hours). Univariate and multivariate analysis were performed using logistic regression to assess the relationship between independent variables and AEs. Results A total of 119 patients with symptomatic PFCs underwent endoscopic drainage with LAMS. There were 16 AEs (12.4%). These included systemic inflammatory response syndrome (SIRS) (n=2), stent occlusion (n=5), bleeding (n=7), and stent migration (n=2). Univariate analysis of risk of AEs showed that no variables approached statistical significance. Of the seven patients who developed bleeding, five had pseudoaneurysms following LAMS placement and underwent angioembolization by an interventional radiologist. The average time to bleeding was 9.3 days (standard deviation 7.3) with all bleeding events occurring within 3 weeks. In a multivariate model, pseudocysts and presence of paracolic gutter extension were associated with an increased risk of bleeding. Conclusions Endoscopists should be aware of the risk factors for LAMS-related bleeding and tailor their drainage strategy, including utilization of plastic stents for drainage of pseudocysts and adherence to a strict imaging interval and follow-up protocol.

Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

The impact of secondary pulmonary hypertension in elderly patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is considered an important disease in the structure of morbidity and mortality and a rising public health problem with increasing global age prevalence. Exacerbation of COPD in the elderly has a significant negative impact on the clinical and paraclinical picture, daily activity capacity, and quality of life. The need for correct diagnostic management is dictated by the severity of the pathology in the elderly and the high frequency of cardiac complications. Studying the clinical-paraclinical picture and the diagnostic capacity of natriuretic peptides in COPD patients with cardiovascular complications was the aim of the present research. Material and methods. We conducted an analytical, observational, case-control study with the use of modern research methods. The study included 194 elderly patients (≥ 65 years old) divided into two study groups: those with only COPD (COPD group) and those with associated pulmonary hypertension (PHCOPD group). Patients underwent clinical, paraclinical, and functional investigation methods with subsequent mathematical-statistical data processing. Results. The study groups were similar according to socio-demographic data. The clinical assessment revealed that PHCOPD patients had, in comparison with COPD patients, statistically significantly more frequent and severe complaints. The objective examination determined that in PHCOPD patients, the values of the objective examination indices were much more affected than in the COPD group. At the complex geriatric assessment, the COPD group of patients shows a lower degree of dependence and less cognitive impairment. The multidimensional assessment of COPD reflected more severe impairment according to the CAT, SGRQ, CCQ, mMRC, BODE questionnaires, and 6MWT test in the PHCOPD group compared to the COPD group. Spirographic, radiographic, ultrasonographic, and echocardiographic evaluations correlated with age, inflammatory syndrome, and natriuretic peptide level. Conclusions. The PHCOPD group patients present a clinical picture, exercise capacity, objective data, complex geriatric assessment scores, and a multidimensional assessment of COPD that is statistically more frequent and severely affected compared to the COPD group. The impact of hemodynamic disturbances in COPD could be confirmed by the correlation of paraclinical data, such as the inflammatory response syndrome, increased natriuretic peptides, echocardiography data, and indices of internal organ ultrasound examination.

Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome.

Gut-brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide. We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete-linkage hierarchical cluster analysis of metabolites discriminant for PD-status was performed. Longer colonic transitwas linked to deficits in faecal short-chain-fatty acids outside PD, to a 'tryptophan-containing metabolite cluster' overall. Phenotypic cluster analysisaggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan-cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole-ring compound (anti-fungals) and vitamin B3 (anti-inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid-cluster deficit was linked to (well-recognised) lower caffeine and alcohol intakes, tryptophan-cluster deficit to higher maltose intake. Free-sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton-pump inhibitors (p = .001)], with 16% of PD-probands exceeding a cut-point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut-point. Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory responsesyndrome.

Selected hematology ratios in cats with non-septic effusions highly suspected of feline infectious peritonitis

In veterinary medicine, knowledge about hematologic ratios (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume-to-platelet ratio (MPV/PLT)) is limited, particularly in cats. While the roles of these ratios have been proven in oncology, systemic inflammation with or without systemic inflammatory response syndrome (SIRS), and sepsis, information is lacking about their alterations in non-septic effusions, like feline infectious peritonitis (FIP). This study aimed to describe whether NLR, PLR, and MPV/PLT were changed and whether they correlated with routine hematologic and biochemical parameters in 16 cats with non-septic effusions, highly suspected to be the effusive form of FIP without SIRS, compared to nine clinically healthy cats. The NLR was calculated as the absolute count of neutrophils divided by the absolute count of lymphocytes, PLR by calculating the absolute platelet divided by the absolute lymphocyte count, and MPV/PLT by dividing mean platelet volume by absolute platelet count. The NLR, MPV, and MPV/PLT ratios were higher in cats with non-septic effusions suspected to be FIP, but PLR did not differ, when compared to healthy cats. Correlation analysis did not show any association between the selected ratios and hematological and biochemical parameters. In the absence of leukocytosis, increased NLR could help us to confirm the presence of systemic inflammation in cats with non-septic effusions indicative of FIP. However, a high MPV/PLT ratio should be interpreted with caution, especially in cats.

Neonatal Multisystem Inflammatory Syndrome Consequent to Perinatal SARS-COVID-2- Infection: A Narrative Review Study

Several studies have described multisystem inflammatory syndrome (MIS) in children, but very few investigations presented this syndrome among neonates (MIS-N). The present study has reviewed the current knowledge about MIS-N, its etiology, symptoms, and outcomes to attract special attention with an eye on earlier diagnosis and treatment of newborns affected by perinatal SARS-CoV-2-infection. A narrative review study was conducted (Tehran, Iran, 2021). All types of full English articles (up to October 1 2021) were included. Detailed research on academic search engines was performed. The implemented Mesh-based keywords were "SARS-COVID-2" OR "COVID-19" OR "coronavirus" AND "Neonate" OR "Neonatal" OR "Newborn" AND "Multisystem Inflammatory Syndrome" OR "MIS-N" OR "inflammatory response syndrome" AND "Pregnancy" OR "Perinatal" OR "prenatal". Finally, 15 Full-text articles were included that met the eligibility criteria. Available data related to the disease, its etiology, presentations, and its outcome were collected and discussed. The cause of MIS-N is the transmission or production of SARS-CoV2 antibodies in response to SARS-CoV2 infection. By involving different organs, the clinical manifestations of MIS-N may mimic sepsis, toxic shock syndrome, RDS, Kawasaki disease, necrotizing enterocolitis, myocarditis, meningitis/encephalitis, aortic thrombosis, ETC. Besides the clinical presentations, detecting reactive anti-SARS-CoV-2 IgG antibodies could be a notable clue in MIS-N diagnosis. Supportive therapy, suppressing the autoimmune and inflammatory responses, anti-platelet agents, and anticoagulants were reported as effective therapeutic agents to improve the outcome. The present study highlighted the possibility of MIS-N as an infrequent but severe syndrome consequent to perinatal COVID-19 infection. Although the diagnosis is still controversial, clinical suspicion, laboratory findings, and early treatment initiation could improve the outcome of this immunological disease.

Involvement of the Liver in COVID-19: A Systematic Review.

ABSTRACT.COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver manifestations of COVID-19 and discussed the possible underlying pathophysiological mechanisms and their diagnosis and management. Factors that may contribute to hepatic involvement in COVID-19 include direct viral cytopathic effects, exaggerated immune responses/systemic inflammatory response syndrome, hypoxia-induced changes, vascular changes due to coagulopathy, endothelitis, cardiac congestion from right heart failure, and drug-induced liver injury. The majority of COVID-19-associated liver symptoms are mild and self-limiting. Thus management is generally supportive. Liver function tests and abdominal imaging are the primary investigations done in relation to liver involvement in COVID-19 patients. However, imaging findings are nonspecific. Severe acute respiratory syndrome coronavirus 2 RNA has been found in liver biopsies. However, there is limited place for liver biopsy in the clinical context, as it does not influence management. Although, the management is supportive in the majority of patients without previous liver disease, special emphasis is needed in those with nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, hepatitis B and C infections, and alcoholic liver disease, and in liver transplant recipients.

До питання щодо способів діагностики і прогнозування розвитку ускладнень у постраждалих з опіками (огляд літератури)

The aim. The article is devoted to the methods used in combustiology practice to assess the condition of patients and predict general and local complications. Results. With severe thermal trauma, there is a risk of developing life-threatening conditions in the victims, in particular, sepsis and multiple organ failure. Informative for assessing the course of burn disease is a modified scale of physiological disorders, which takes into account the syndrome of systemic inflammatory response, endogenous intoxication during periods of toxemia and septicotoxemia, and concomitant pathology. The development of intoxication in severe burn injuries requires determining the degree of severity of the process and its assessment in dynamics. The toxicity of blood plasma is studied by the resistance of red blood cell membranes in the acid hemolysis reaction, indicators of the red blood cell intoxication index, and the content of universal markers of intoxication, in particular, medium-weight molecules. Methods for biosensor indication of cytotoxic factors have also been developed. Assessment of the severity of the condition of victims with burns and monitoring the effectiveness of therapy is carried out taking into account the level of procalcitonin and presepsin. To determine the effect of the wound process on the formation of early sepsis in patients with burns in the capillary zone of thermal damage, the content of homocysteine, endothelin and nitric oxide is studied. To assess the severity of the condition of burn patients and predict the development of complications, the values of integral hematological indices are informative. Reliable data on the depth of a burn wound are obtained using thermotopometry and pH measurement of burn wounds, the method of magnetic resonance imaging. In order to assess violations and dynamics of blood supply restoration in the area of thermal damage, the method of laser Doppler flowmetry and optical tissue oximetry is used. Determination of interstitial pressure in burns of the extremities and intra-abdominal pressure in common burns is a way to predict the development of compartment syndrome. To monitor the patient's glycemic status, it is proposed to determine the level of glycosylated hemoglobin. Microbiological research data is used to predict the risk of developing general complications of burn disease, as well as – together with cytological data and methods for determining the maturity of granulation tissue – to assess the readiness of granulating wounds for autodermoplasty. Conclusion. The development of new effective ways to predict and prevent the development of complications in burns is promising

Dietary Flavone Baicalein Combinate with Genipin Attenuates Inflammation Stimulated by Lipopolysaccharide in RAW264.7 Cells or Pseudomonas aeruginosa in Mice via Regulating the Expression and Phosphorylation of AKT.

Mounting evidence has shown that single-targeted therapy might be inadequate to achieve satisfactory effects. Thus, drug combinations are gaining attention as they can regulate multiple targets to obtain more beneficial effects. Heat shock protein 90 (HSP90) is a molecular chaperone that assists the protein assembly and folding of client proteins and maintains their stability. Interfering with the interaction between HSP90 and its client proteins by inhibiting the latter’s activity may offer a new approach toward combination therapy. The HSP90 client protein AKT plays an important role in the inflammatory response syndrome caused by infections. In this study, the dietary flavone baicalein was identified as a novel inhibitor of HSP90 that targeted the N-terminal ATP binding pocket of HSP90 and hindered the chaperone cycle, resulting in AKT degradation. Combining baicalein with genipin, which was extracted from Gardenia jasminoides, could inhibit the pleckstrin homology domain of AKT, significantly increasing the anti-inflammatory effects both in vitro and in vivo. This synergistic effect was attributed to the reduction in AKT expression and phosphorylation. Thus, elucidating the mechanism underlying this effect will provide a new avenue for the clinical application and development of synergistic anti-inflammatory drugs.

Oxidative Stress in ICU Patients: ROS as Mortality Long-Term Predictor.

Lipid peroxidation, protein oxidation, and mutations in mitochondrial DNA generate reactive oxygen species (ROS) that are involved in cell death and inflammatory response syndrome. ROS can also act as a signal in the intracellular pathways involved in normal cell growth and homeostasis, as well as in response to metabolic adaptations, autophagy, immunity, differentiation and cell aging, the latter of which is an important characteristic in acute and chronic pathologies. Thus, the measurement of ROS levels of critically ill patients, upon admission, enables a prediction not only of the severity of the inflammatory response, but also of its subsequent potential outcome. The aim of this study was to measure the levels of mitochondrial ROS (superoxide anion) in the peripheral blood lymphocytes within 24 h of admission and correlate them with survival at one year after ICU and hospital discharge. We designed an observational prospective study in 51 critical care patients, in which clinical variables and ROS production were identified and correlated with mortality at 12 months post-ICU hospitalization. Oxidative stress levels, measured as DHE fluorescence, show a positive correlation with increased long-term mortality. In ICU patients the major determinant of survival is oxidative stress, which determines inflammation and outlines the cellular response to inflammatory stimuli.

Da-Huang-Fu-Zi-Tang Ameliorates Severe Acute Pancreatitis by Elevation of M2 Kupffer Cells in Rats.

Introduction Severe acute pancreatitis (SAP) is a clinical emergency often accompanied by inflammatory response syndrome (SIRS), which eventually leads to acute lung injury and failure of other organs. The activation of liver Kupffer cells (KCs) plays a major role in the process of SIRS and multiorgan damage caused by SAP. Da-Huang-Fu-Zi-Tang (DHFZT), a traditional Chinese prescription, has been widely used for SAP in the clinic. The present study investigated the activation state of KCs in SAP and the potential mechanism of DHFZT. Methods A total of 24 Sprague Dawley rats were randomly assigned to four groups: SH (sham operation group + saline enema), SH-DHFZT (sham operation group + DHFZT enema), SAP (model group + saline enema), and SAP-DHFZT (model group + DHFZT enema). Blood samples were drawn from the abdominal aorta for measuring serum endotoxin, amylase, calcium ion, IL-1β, TNF-α, iNOS, and IL-10. Then, the pancreas, lung, liver, and ileum were harvested for histological observation, and the liver was used to detect the level of F4/80, CD86, and CD163 in KCs with immunohistochemistry and western blot. Results In the SAP group, the CD86+ KCs were significantly increased with a high level of IL-1β, TNF-α, and iNOS, and the organs were impaired. In the SAP-DHFZT group, CD163+ KCs were significantly increased with the high level of IL-10, and the damage to organs was alleviated. Conclusion These phenomena suggested that the SIRS and multiple organ damage in SAP might be related to the excessive activation of M1 KCs, and DHFZT might alleviate the SIRS by inducing the differentiation of KCs into the M2-type and promote the expression of anti-inflammatory factor IL-10.

COMPLIANCE TO SURVIVING SEPSIS CAMPAIGN HOUR–1 BUNDLE–A CROSS SECTIONAL STUDY AMONG PHYSICIANS INVOLVED IN CRITICAL CARE IN PAKISTAN

Objective: To determine physician’s compliance to surviving sepsis campaign updated Hour-one bundle incritically ill patients in Pakistan.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Department of Anaesthesiology, Combined Military Hospital Lahore MedicalCollege, from Jun to Aug 2019.
 Methodology: This study was carried out among physicians managing critical patients in intensive care units.Participants were asked to fill out a 16-questions survey (work experience, qualification and individual components of surviving sepsis campaign hour-1 bundle. Data was collected using online access to survey and by sending hard copies.
 Results: Questionnaire was sent to 230 physicians while only 63 responses were received (response rate 27%).Only 45 (71%) respondents were aware of the updated Hour-1 bundle. There was no institutional protocolfor compliance to sepsis bundles in thirty three (55%) responses. 52% respondents used Systemic inflammatoryresponse syndrome (SIRS) criteria to diagnose sepsis while quick Sequential Organ Failure Assessment (qSOFA)was used by 36% respondents. Overall compliance to hour-1 bundle components was only 60%. Lactate levelswas not measured by 35 (55%) respondents while 24 (38%) did not obtain blood cultures before administeringantibiotics. Crystalloid and nor epinephrine was used by all respondents. Overall compliance with all the components of sepsis bundle had strong correlation with post-graduate qualification (p-value 0.001-0.049).
 Conclusion: Poor compliance to updated sepsis guidelines was one of the major reasons of high sepsis relatedmortality in Pakistan.

СИНДРОМ НЕДОСТАТОЧНОСТИ ПИТАНИЯ В КЛИНИЧЕСКОЙ ПРАКТИКЕ

The article provides information on syndrome of undernutrition in internal diseases according to current concepts. The authors characterize endogenous and exogenous factors contributing to the weight loss, adverse changes in various body systems of patients with undernutrition, their physical, physiological and mental disorders, causes of diseases-associated undernutrition and describe the international classification of undernutrition based on phenotypic and etiological criteria, which was worked out by the Global Leadership Initiative on Malnutrition in 2018. Particular attention is paid to the weight loss in elderly, chronic heart failure, chronic obstructive pulmonary disease, oncopathology, liver cirrhosis, chronic kidney disease, diabetes mellitus and thyroid hyperfunction. The authors describe the causes of undernutrition in the systemic inflammatory response, characterize hypermetabolism and refeeding syndrome, which occurs as a result of reintroducing food after malnourishment. The article outlines that undernutrition can be associated with such side effects of drugs as impairment of taste, smell, development of anorexia, dry mouth, dysphagia, nausea and vomiting and claims the importance of diagnosing of undernutrition associated with somatic pathology and contributing to the course and outcomes of diseases.

Vantagens da cirurgia do controle de danos comparada aos métodos tradicionais de abordagem ao paciente politraumatizado

Este trabalho relatou as alterações fisiológicas e metabólicas graves que são comumente observadas ao tratar pacientes politraumatizados, as quais culminam na tríade letal do trauma, isto é, coagulopatia, acidose metabólica e hipotermia. Nesse contexto, foram abordados os procedimentos definitivos, ou seja, cirurgia definitiva segura, reconstrução e reabilitação. E os temporários, isto é, intervenções radiológicas, enxerto de stents e o controle de danos. Com isso, ter o êxito de cessar os acometimentos relacionados ao indivíduo politraumatizado, como a tríade letal. Buscou-se, também, evidenciar a importância e os benefícios da utilização do controle de danos em pacientes politraumatizados, cuja técnica é considerada uma inovação significativa em relação aos cuidados desses pacientes, apresentando as situações em que essa abordagem é mais indicada. Esta revisão tem o objetivo de expor as possíveis complicações que podem ser evitadas pela escolha e utilização correta do controle de danos, propiciando, assim, um melhor prognóstico para o paciente.

Cortisol and laboratory indicators of systemic inflammation in case of bacterial purulent meningitis and viral encephalitis in children

Pediatric bacterial purulent meningitis (BPM) and viral encephalitis (VE) are significant medical and social problems due to their course severity, high frequency of death cases, and formation of neurologic deficiency at the disease outcome. Activation of hormonal regulation and severity syndrome of systemic inflammatory response are important factors to evaluate the character of BPM and VE course.Objective.To study the level of cortisol and laboratory indicators of systemic inflammation in children with various variants of BPM and VE course depending on the period of the disease (acute period, reconvalescence) to specify their role in the pathogenesis of acute neuroinfections.Object and methods.There were investigated hematological indicators, the level of cortisol, C-reactive protein in blood serum of 60 children, 39 of them had BPM and 21 ones VE. The comparison group included 14 children aged from 1 to 14 years old who were undergoing rehabilitation care due to neurologic problems at the Federal State-Financed Institution Pediatric Research and Clinical Center for Infectious Diseasesunder the Federal Medical Biological Agency.Results.The patients were divided into some subgroups according to the severity of their condition at the moment of hospitalization, i.e. urgent condition or critical condition requiring organ replacement therapy. The maximum increase of cortisol level and laboratory markers of systemic inflammation during the acute period was revealed in case of BPM in comparison with VE with a subsequent normalization to the stage of reconvalescence. Thelevel of cortisol during the acute period of BPM was reliably higher in the subgroup with urgent conditions, whereas in case of VE in the subgroup with critical conditions. There were no significant differences in the laboratory indicators of systemic inflammation response among the subgroups. There was established a correlation interrelation of cortisol level and the content of granulocytes and blood lymphocytes.Conclusion.There were identified characteristic features of cortisol content in children with bacterial and viral neuroinfections depending on the course of the disease.

Selective Apheresis of C-Reactive Protein for Treatment of Indications with Elevated CRP Concentrations

Almost every kind of inflammation in the human body is accompanied by rising C-reactive protein (CRP) concentrations. This can include bacterial and viral infection, chronic inflammation and so-called sterile inflammation triggered by (internal) acute tissue injury. CRP is part of the ancient humoral immune response and secreted into the circulation by the liver upon respective stimuli. Its main immunological functions are the opsonization of biological particles (bacteria and dead or dying cells) for their clearance by macrophages and the activation of the classical complement pathway. This not only helps to eliminate pathogens and dead cells, which is very useful in any case, but unfortunately also to remove only slightly damaged or inactive human cells that may potentially regenerate with more CRP-free time. CRP action severely aggravates the extent of tissue damage during the acute phase response after an acute injury and therefore negatively affects clinical outcome. CRP is therefore a promising therapeutic target to rescue energy-deprived tissue either caused by ischemic injury (e.g., myocardial infarction and stroke) or by an overcompensating immune reaction occurring in acute inflammation (e.g., pancreatitis) or systemic inflammatory response syndrome (SIRS; e.g., after transplantation or surgery). Selective CRP apheresis can remove circulating CRP safely and efficiently. We explain the pathophysiological reasoning behind therapeutic CRP apheresis and summarize the broad span of indications in which its application could be beneficial with a focus on ischemic stroke as well as the results of this therapeutic approach after myocardial infarction.

Mechanism of the Protective Effect of Sesamin on Sepsis-Induced Acute Lung Injury

Sepsis is the syndrome of systemic inflammatory response caused by infection. Over 20 million people worldwide suffer from sepsis each year, of whom about 6 million die, with a case-fatality rate of more than 25%. Therefore, to develop a rational plan for the management of sepsis, there is an urgent need to understand the mechanism of pathogenesis. Sesamin is a kind of sesame lignin isolated from sesame that exhibits multiple biological functions including antiviral, antidyslipidemic, and antihypertensive to name a few. An antioxidant and anti-inflammatory activity of sesamin appears to be a common denominator in all of its biologic activities. However, the mechanism of sesamin on septic-induced acute pulmonary inflammation still needs further study. Herein, we have established a sepsis model of C57BL/6 mice by cecal ligation and perforation. Using this model, we have shown that sesamin could reduce the levels of several inflammatory factors as well as oxidative stress response. Furthermore, sesamin could repress NLRP3 inflammasome and activate Nrf2/HO-1 pathway, and further inhibit acute pulmonary inflammation. This study reveals the mechanism of the diminution of septic-induced acute pulmonary inflammation by sesamin. This opens a theoretical basis for the development of drugs for treatment of sepsis.

Platelet Membrane-Camouflaged Magnetic Nanoparticles for Ferroptosis-Enhanced Cancer Immunotherapy.

Although cancer immunotherapy has emerged as a tremendously promising cancer therapy method, it remains effective only for several cancers. Photoimmunotherapy (e.g., photodynamic/photothermal therapy) could synergistically enhance the immune response of immunotherapy. However, excessively generated immunogenicity will cause serious inflammatory response syndrome. Herein, biomimetic magnetic nanoparticles, Fe3 O4 -SAS @ PLT, are reported as a novel approach to sensitize effective ferroptosis and generate mild immunogenicity, enhancing the response rate of non-inflamed tumors for cancer immunotherapy. Fe3 O4 -SAS@PLT are built from sulfasalazine (SAS)-loaded mesoporous magnetic nanoparticles (Fe3 O4 ) and platelet (PLT) membrane camouflage and triggered a ferroptotic cell death via inhibiting the glutamate-cystine antiporter system Xc- pathway. Fe3 O4 -SAS @ PLT-mediated ferroptosis significantly improves the efficacy of programmed cell death 1 immune checkpoint blockade therapy and achieves a continuous tumor elimination in a mouse model of 4T1 metastatic tumors. Proteomics studies reveal that Fe3 O4 -SAS @ PLT-mediated ferroptosis could not only induce tumor-specific immune response but also efficiently repolarize macrophages from immunosuppressive M2 phenotype to antitumor M1 phenotype. Therefore, the concomitant of Fe3 O4 -SAS @ PLT-mediated ferroptosis with immunotherapy are expected to provide great potential in the clinical treatment of tumor metastasis.

Temporal trends in in-hospital complications of acute coronary syndromes: Insights from the nationwide AMIS Plus registry

BackgroundAcute coronary syndrome (ACS)-related morbidity and mortality remain substantial. Data on temporal trends in in-hospital complications of ACS patients are scarce. This study sought to investigate whether the incidence of in-hospital complications of ACS patients changed over time. MethodsAcute coronary syndrome patients prospectively enrolled in the National Registry of Acute Myocardial Infarction in Switzerland (AMIS Plus) between 2003 and 2018 and with available data on in-hospital complications were included in the analysis. Rates of in-hospital complications, including recurrent angina, recurrent myocardial infarction, cerebrovascular events, cardiogenic shock, bleeding, acute renal failure, sepsis/systemic inflammatory response syndrome (SIRS)/multiorgan dysfunction syndrome (MODS), AV block needing pacing and new-onset atrial fibrillation, were assessed for each 2-year period. ResultsAmong 47,845 ACS patients, in-hospital complications significantly decreased from 22.0% in 2003/2004 to 18.9% in 2017/2018 (p for trend <0.001). An initial decline in rates of in-hospital complications to 15.7% in 2009/2010 (p for trend <0.001) was followed by a constant increase thereafter (p for trend = 0.002). While rates of recurrent angina, recurrent myocardial infarction, and cardiogenic shock decreased over time, rates of bleeding events, acute renal failure, sepsis/SIRS/MODS, and new-onset atrial fibrillation increased. Rates of in-hospital complications were higher in women, mainly due to a constantly increased risk of bleeding and AV block needing pacing. ConclusionsThe decrease in ischemic complications was paralleled by a concomitant increase in non-ischemic events. These findings emphasize that advanced strategies targeting non-ischemic complications are warranted to further improve quality of care of ACS patients.