Systemic Inflammatory Complications Research Articles

Maternal COVID-19 Infection Associated with Fetal Systemic Inflammatory Complications in COVID-19-Negative Neonates: A Case-Series.

This study aimed to examine fetal and neonatal inflammatory and neurologic complications associated with maternal coronavirus disease 2019 (COVID-19) infection. Case-series using a convenience sample of neonates cared for in a large referral-based children's hospital neonatal intensive care unit between September 2021 and May 2022. We identified seven neonates with exposure to maternal severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) and a presentation consistent with inflammatory complications. All had some degree of neurologic injury with neuroimaging findings including restricted diffusion indicating injury in the white matter, cortex, deep gray structures, and splenium of the corpus callosum as well as intracranial hemorrhage. In addition, many infants had cytopenia and abnormal coagulation studies. Placental pathology, when available, revealed inflammation, clot with calcifications, and hematomas with associated infarcts. Neonates born to mothers with SARS-CoV-2, even when negative for the virus themselves, may have complications consistent with a systemic inflammatory syndrome. Placental pathology as well as neurologic imaging in infants with neurologic findings may help to support this diagnosis. · A systemic inflammatory response may cause illness in babies born to mothers with a history of COVID-19.. · Inflammatory markers and placental pathology are helpful in supporting this diagnosis.. · Consider neuroimaging in infants of mothers with a history of COVID-19 with neurologic findings..

Cytokine regulation disbalance: the basis for COVID-19 immunopathogenesis

Coronavirus infection activates two main signaling pathways for type I and III IFN and the gene expression and synthesis of proinflammatory cytokines. These cytokines are required for antiviral defense and inflammatory reaction formation. SARS-CoV-2 coronavirus could inhibit the IFN system by depressing signaling pathways for IFN gene expression, synthesis, and secretion. IFN inhibition should be considered the primary reason for coronavirus escape from the immune system and a key factor for COVID-19 immunopathogenesis. Cytokine regulation disbalance in patients with severe COVID-19 is closely associated with low and delayed IFN synthesis, while proinflammatory cytokine production by macrophages and T-lymphocytes continues simultaneously with intensive virus replication. Thus, the reason for COVID-19 immunopathogenesis is the cytokine regulation disbalance where IFN inhibition and intensive proinflammatory cytokine synthesis lead to cytokine storm, inadequate inflammation, respiratory distress syndrome development, respiratory failure, systemic inflammatory complications, and polyorganic failure.

The Predictive Value of Systemic Immune-Inflammation Index and Symptom Severity Score for Sepsis and Systemic Inflammatory Response Syndrome in Odontogenic Infections.

Acute Odontogenic Infections (OI) are the leading cause of emergency visits and hospitalizations to the maxillofacial department, and may induce systemic inflammatory complications. Increasing numbers of OI patients need extended hospitalizations, various treatments, and intensive care. The Symptom Severity score (SS) helps doctors assess the likelihood of infection and admission complications. Systemic Immune-inflammation Index (SII) is a biomarker-based inflammatory prognosis score. It was hypothesized that greater SII and SS values might suggest a higher risk for sepsis and systemic inflammatory response syndrome (SIRS). Therefore, this research aims to discover whether SII and SS scores can reliably predict odontogenic infection severity and prognosis, and if they can be used to predict the development of SIRS and sepsis in OI using admission features. The study was designed as a retrospective cohort, with patients' data being retrieved from medical records between January 2017 to April 2022. A total of 108 OI patients were matched 1:1 as low-severity and high-severity groups. Most individuals with severe infections had diabetes and smoking as comorbidities. Severe patients had longer hospital stays (12.0 days vs. 4.1 days), although mortality rates did not significantly differ. A total of 11.1% lower-severity patients (Group A) had SIRS during hospitalization, compared to Group B with 25.9%. Group A had 7.4% of patients that developed sepsis compared to Group B's rate of 22.2%. The correlation between OI's SS and SII index values was positive and statistically significant (r = 0.6314). The total SII index mean was 1303, whereas the mean values by severity were 696.3 in Group A and 2312.4 in Group B. Group A's mean SS score was 6.1, while Group B's was 13.6. According to the calculated AUC plots, SII and SS scores were accurate predictors of sepsis and SIRS development using OI admission parameters. The adjusted odds ratio for SIRS in OI patients was 2.09, and 2.27 for sepsis. Medical professionals and dentistry teams should be encouraged to use the SII and SS scores to diagnose and anticipate sepsis and SIRS, hence improving disease management decisions.

Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review.

Generalized pustular psoriasis (GPP) is a rare auto-inflammatory skin disease characterised by acute episodes of sterile pustule formation. Diagnosis and treatment of the disease have historically been complicated by a lack of awareness, and no consistent global definition or clinical coding standards. Now acknowledged as a distinct clinical entity with a recognised genetic component, GPP can take a serious and life-threatening course due to systemic inflammatory complications and its association with various comorbidities. As with other rare diseases, there are significant challenges to understanding the epidemiology of GPP, notably a small patient population, non-standardised study methodologies and ethnic differences in its presentation. A clearer understanding of GPP is therefore required for clinicians to better manage patients with this rare condition. In this review article, we present an overview of the available data on GPP prevalence estimates in key demographics and report the frequency of genetic mutations associated with the disease. We detail the incidence of known comorbidities and summarise the data on mortality and assigned causes of death. Lastly, we discuss the various factors that impact the collection, interpretation and comparison of these data.

Introducing a Novel Experimental Model for Osseo-Disintegration of Titanium Dental Implants Induced by Monobacterial Contamination: An In-Vivo Feasibility Study.

Background and Objectives: The aim of the current study was to establish an osseo-disintegration model initiated with a single microorganism in mini-pigs. Materials and Methods: A total of 36 titanium dental implants (3.5 mm in diameter, 9.5 mm in length) was inserted into frontal bone (n: 12) and the basis of the corpus mandible (n: 24). Eighteen implants were contaminated via inoculation of Enterococcus faecalis. Six weeks after implant insertion, bone-to-implant contact (BIC) ratio, interthread bone density (ITBD), and peri-implant bone density (PIBD) were examined. In addition to that, new bone formation was assessed via fluorescence microscopy, histomorphometry, and light microscopical examinations. Results: Compared to the sterile implants, the contaminated implants showed significantly reduced BIC (p < 0.001), ITBD (p < 0.001), and PBD (p < 0.001) values. Around the sterile implants, the green and red fluorophores were overlapping and surrounding the implant without gaps, indicating healthy bone growth on the implant surface, whereas contaminated implants were surrounded by connective tissue. Conclusions: The current experimental model could be a feasible option to realize a significant alteration of dental-implant osseointegration and examine novel surface decontamination techniques without impairing local and systemic inflammatory complications.

MicroRNA-150 affects endoplasmic reticulum stress via MALAT1-miR-150 axis-mediated NF-κB pathway in LPS-challenged HUVECs and septic mice

AimsSepsis is a systemic inflammatory complication, which is the common cause of death in critical patients. This study aimed to evaluate the potential regulatory mechanisms of miR-150 in lipopolysaccharide (LPS)-challenged HUVECs and cecal ligation and puncture (CLP)-induced septic mice. Materials and methodsHuman umbilical vein endothelial cells (HUVECs) were challenged with LPS. Pulmonary arterial endothelial cells (PAECs) were isolated from CLP-induced septic mice. The mRNA and protein levels of target molecules were detected by RT-qPCR and Western blotting. Apoptosis of HUVECs was determined by Annexin V/PI staining on a flow cytometry. The interaction between miR-150 and MALAT1 was assessed by luciferase reporter assay, RIP and RNA pull-down assay. Key findingsMiR-150 was downregulated in LPS-induced HUVECs. MiR-150 mimics restrained LPS-induced inflammatory response by reducing TNF-α and IL-6 levels, but increasing IL-10 level. Moreover, miR-150 mimics downregulated endoplasmic reticulum (ER) stress-related proteins, GRP78 and CHOP levels in LPS-exposed HUVECs. Additionally, LPS-induced apoptosis was suppressed by miR-150 mimics via decreasing cleaved caspase-3 and Bax levels, while enhancing Bcl-2 level. Mechanistically, MALAT1 could competitively bind to miR-150. LPS-induced apoptosis, ER stress and inflammation were promoted by MALAT1 overexpression, but reversed by siMALAT1. Furthermore, miR-150 inhibitor strengthened LPS-induced apoptosis, ER stress and inflammation, which could be attenuated by siMALAT1 via regulating NF-κB pathway. Finally, agomiR-150 repressed ER stress and inflammatory response in PAECs isolated from septic mice via decreasing MALAT1 level. SignificanceOur findings suggest that miR-150 affects sepsis-induced endothelial injury by regulating ER stress and inflammation via MALAT1-mediated NF-κB pathway.

Serum amyloid A and C-reactive protein levels and erythrocyte sedimentation rate are important indicators in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic disabling inflammatory disease of the follicular unit especially affecting apocrine gland-bearing skin areas. Little is known about systemic inflammatory complications of the disease. This study aimed to evaluate systemic inflammation in patients with HS by assessing serum amyloid A protein (SAA) and C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) and to identify potential risk factors for HS. Forty-four patients (M/F: 28/16) and 44 age- and sex-matched controls (M/F: 28/16) were enrolled. Demographic, clinical, laboratory, and therapeutic data, including smoking status, body mass index (BMI), waist circumference (WC), serum fasting lipid profile, fasting blood glucose, SAA, and CRP levels, and ESR were assessed. Associations were investigated by univariate and multivariate analyses. Patients with HS showed significantly higher levels of pack-years of cigarette smoking, weight, BMI, and WC (P = 0.01, P < 0.001, P = 0.001) and elevated SAA and CRP levels and ESR (P = 0.008, P = 0.01 and P < 0.001). SAA and CRP levels and ESR were significantly associated with Hurley staging in patients with HS (P = 0.03, P = 0.003, P = 0.02). Multivariate logistic regression analysis revealed that each unit increase in the ESR increased the HS risk by 1.08-fold (95% CI 1.02-1.13). HS is significantly associated with SAA, CRP, and ESR. Among these inflammatory parameters, ESR was an independent risk factor for HS. We recommend assessment of SAA, CRP, and ESR as biomarkers that reflect the disease severity in HS patients likely to develop complications.

Efficacy of Recombinant Human Soluble Thrombomodulin in Treating Disseminated Intravascular Coagulation Complicating Allogeneic Hematopoietic Stem Cell Transplantation

The prognosis for patients who experience hemostatic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. However, no report has investigated disseminated intravascular coagulation (DIC) caused by the complications of allo-HSCT without infection. Recombinant human soluble thrombomodulin (rhTM) was used to treat 12 episodes of DIC (n = 10; group 1) caused by allo-HSCT complications such as acute graft-versus-host disease (aGVHD) or thrombotic microangiopathy (TMA), and the clinical outcomes were compared with those of historical controls (n = 9; group 2) treated for DIC without rhTM. In group 1, the mean DIC score was significantly improved after using rhTM. Fibrinogen degeneration product (FDP), C-reactive protein (CRP), and the inflammatory cytokine high-mobility group box 1 (HMGB1) were also significantly decreased. Serial changes from the baseline values of platelet counts and levels of FDP were significantly better in group 1 than in group 2. The recovery rate from DIC was significantly higher in group 1 than in group 2. These findings suggest that rhTM is effective against both DIC and systemic inflammatory complications after allo-HSCT.

The Effects of Prednisolone Treatment on Cytokine Expression in Patients with Erythema Nodosum Leprosum Reactions.

Erythema nodosum leprosum (ENL) is a systemic inflammatory complication occurring mainly in patients with lepromatous leprosy (LL) and borderline lepromatous leprosy. Prednisolone is widely used for treatment of ENL reactions but clinical improvement varies. However, there is little good in vivo data as to the effect of prednisolone treatment on the pro-inflammatory cytokines in patients with ENL reactions. As a result, treatment and management of reactional and post-reactional episodes of ENL often pose a therapeutic challenge. We investigated the effect of prednisolone treatment on the inflammatory cytokines TNF, IFN-γ, IL-1β, IL-6, and IL-17 and the regulatory cytokines IL-10 and TGF-β in the skin lesion and blood of patients with ENL and compared with non-reactional LL patient controls. A case–control study was employed to recruit 30 patients with ENL and 30 non-reactional LL patient controls at ALERT Hospital, Ethiopia. Blood and skin biopsy samples were obtained from each patient before and after prednisolone treatment. Peripheral blood mononuclear cells from patients with ENL cases and LL controls were cultured with M. leprae whole-cell sonicates (MLWCS), phytohemagglutinin or no stimulation for 6 days. The supernatants were assessed with the enzyme-linked immunosorbent assay for inflammatory and regulatory cytokines. For cytokine gene expression, mRNA was isolated from whole blood and skin lesions and then reverse transcribed into cDNA. The mRNA gene expression was quantified on a Light Cycler using real-time PCR assays specific to TNF, IFN-γ, IL-β, TGF-β, IL-17A, IL-6, IL-8, and IL-10. The ex vivo production of the cytokines: TNF, IFN-γ, IL-1β, and IL-17A was significantly increased in untreated patients with ENL. However, IL-10 production was significantly lower in untreated patients with ENL and significantly increased after treatment. The ex vivo production of IL-6 and IL-8 in patients with ENL did not show statistically significant differences before and after prednisolone treatment. The mRNA expression in blood and skin lesion for TNF, IFN-γ, IL-1β, IL-6, and IL-17A significantly reduced in patients with ENL after treatment, while mRNA expression for IL-10 and TGF-β was significantly increased both in blood and skin lesion after treatment. This is the first study examining the effect of prednisolone on the kinetics of inflammatory and regulatory cytokines in patients with ENL reactions before and after prednisolone treatment. Our findings suggest that prednisolone modulates the pro-inflammatory cytokines studied here either directly or through suppression of the immune cells producing these inflammatory cytokines.

хирургическая тактика при остром холецистите, осложнённом холедохолитиазом и механической желтухой

Objective: To improve the results of surgical treatment of acute cholecystitis complicated by both choledocholithiasis and obstructive jaundice. Methods: The study is based on the results of complex diagnosis and treatment of 140 patients with acute cholecystitis (AC), with complicated choledocholithiasis and mechanical jaundice. Seventy-six of patients (54.3%) had medium and severe obstructive jaundice, and 64 (45.7%) had slight mechanical jaundice. In 28 (43.75%) observations cholecystocholedocholithiasis, complicated by mechanical jaundice, was not accompanied by systemic inflammatory complications, in the remaining 36 (56.25%) observations there was cholangitis (n = 16) and biliary sepsis (n = 20). Results: Surgical approach consisted of the step-by-step approach in all 140 patients. Thus, in 64 (45.7%) observations in the presence of choledocholithiasis and mechanical jaundice, endoscopic retrograde cholangiopancreatography was performed in the first stage with an attempt of endoscopic papillosphincterotomy (EPST) and lithoextraction. In 18 cases, with phlegmonous-calculous cholecystitis and choledocholithiasis with mechanical jaundice, combined interventions were performed – percutaneous transhepatic cholecystostomy with EPST and lithoextraction. Of the 38 patients with slight mechanical jaundice, in 20 cases, the first stage was performed by percutaneoustranshepatic cholecystostomy, in 18 – by percutaneous cholecystomy through infiltration (n = 10) and drainage techniques for perivesical abscess (n = 8). In 38 cases, with gangrenous cholecystitis (n = 28), gallbladder empyema (n = 6) and local biliary peritonitis (n = 4), cholecystectomy was performed from mini-laparotomy access followed by choledocholithotomy. Conclusion: Surgical approach with AC, in complicated choledocholithiasis and in obstructive jaundice, should be differentiated and justify the implementation of phased minimally invasive surgical procedures. Keywords: Acute cholecystitis, choledocholithiasis, obstructive jaundice.

Modulation of L-arginine-induced acute pancreatitis by meloxicam and/or L-carnitine in rats

Background: Acute pancreatitis (AP) is an inflammatory disease, where oxidative stress, subsequently inflammatory mediators activation play a pivotal role. Currently, no definite treatment exists and therapy is mainly supportive that directed to inhibit local pancreatic injury and systemic inflammatory complications. This study is presented to explore whether anti-inflammatory and/or antioxidant drug could ameliorate L-arginine-induced AP. Methods: Rats were sub-grouped randomly into five groups. Control group, AP was provoked by a single intraperitoneal injection of L-arginine (250 mg/100g), rat treated with meloxicam (4 mg/kg, IP), animals treated with L-carnitine (500 mg/kg, IP), and rats were treated with both meloxicam and L-carnitine. All treatments were once daily for 7 consecutive days and started 1 hr later after L-arginine administration. Serum and tissues samples were prepared for biochemical analysis. Histopathological examination for the other pancreatic tissues was done. Results: L-arginine significantly elevated serum activity of amylase and lipase enzymes, while notably reduced serum calcium level. Moreover, L-arginine markedly increased the pancreatic tissues content of tumor necrosis factor-α, malondialdehyde, and nitric oxide. In addition, L-arginine significantly increased pancreatic activity of myeloperoxidase, while markedly depleted glutathione level. Treatment with either meloxicam or L-carnitine significantly attenuated L-arginine-induced biochemical changes. On the other hand, co-administration of both meloxicam and carnitine has an ameliorative effect greater than each drug alone. Conclusion: Treatment with both meloxicam and L-carnitine is a more effective than each of them alone which is attributed to augmentation their antioxidant, anti inflammatory effects.

1,8-cineole (eucalyptol) ameliorates cerulein-induced acute pancreatitis via modulation of cytokines, oxidative stress and NF-κB activity in mice

AimsAcute pancreatitis (AP) is an inflammatory condition wherein pro-inflammatory mediators, oxidative stress, and NF-κB signaling play a key role. Currently, no specific therapy exists and treatment is mainly supportive and targeted to prevent local pancreatic injury and systemic inflammatory complications. This study was aimed to examine whether 1,8-cineole, a plant monoterpene with antioxidant and anti-inflammatory properties could ameliorate cerulein-induced acute pancreatitis. Main methodsAP was induced in Swiss mice by six one hourly injections of cerulein (50μg/kg, i.p.). 1,8-cineole (100, 200 and 400mg/kg, p.o.) was administered 1h prior to first cerulein injection, keeping vehicle and thalidomide treated groups as controls. Blood samples were taken 6-h later to determine serum levels of amylase and lipase, and cytokines. The pancreas was removed for morphological examination, myeloperoxidase (MPO) and malondialdehyde (MDA) assays, reduced glutathione (GSH) levels, and for nuclear factor (NF)-κB immunostaining. Key findings1,8-cineole effectively reduced the cerulein-induced histological damage, pancreatic edema and NF-κB expression, levels of MPO activity and MDA, and replenished the GSH depletion. Cerulein increased serum levels of amylase and lipase, and pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were also decreased by 1,8-cineole pretreatment, similar to thalidomide, a TNF-α inhibitor. The anti-inflammatory IL-10 cytokine level was, however, enhanced by 1,8-cineole. SignificanceThese findings indicate that 1,8-cineole can attenuate cerulein-induced AP via an anti-inflammatory mechanism and by combating oxidative stress. Further studies are needed to clearly elucidate its benefits in patients on acute pancreatitis.

Endothelial activation as main trigger for systemic inflammatory complications after CPB?

Endothelial activation as main trigger for systemic inflammatory complications after CPB?

Systemic inflammatory complications after cardiopulmonary bypass (CPB): Influence of cytokines and complement system in correlation to endothelial activation

Objective: To investigate the role of cytokines and complement system in the inflammatory response after CPB we looked for correlations between cytokine-/complement-levels and clinical parameters. Methods: 40 consecutive CABG-patients were included in a prospective study. Blood samples were analyzed for CRP, PCT and for C3a and C5a. We also determined TNF-a, interleukin-1,-6,-8 and -10, as well as ET1, ICAM-1, ICAM-3, VCAM-1 and ELAM-1. Results: IL-1b was not elevated in the plasma at any sample time point. TNF-a was significantly increased in 4 patients after onset of CPB. 3 patients showed a significant TNF-elevation already preoperatively (268.5 pg/ml vs. <10 pg/ml in the other patients). In these 3 patients, which were the only to develop a severe SIRS, we also found significantly higher preoperative levels of ET1 (2.5±0.3 vs. 1.2±0.4 pg/ml), ICAM-1, ICAM-3 and ELAM-1. IL-6 and IL-10 rose significantly and peaked 88 respectively 50 minutes after end of CPB. C3a and C5a were significantly elevated during CPB with maximum levels 30 minutes after CPB. Peak values of IL-6 and -10 could be correlated to the duration of aortic crossclamping. Conclusions: CPB does not induce systemic release of TNF-a and IL-1b. A preoperative TNF-elevation in combination with an activation of the endothelium seems to be an indicator of an increased risk for systemic inflammation. Furthermore our results confirm the presence of complement activation preceding the production of IL-6 and IL-10. IL-6 may contribute to adverse systemic reactions after CPB, since its release could be correlated to the duration of myocardial ischemia.

Systemic inflammatory complications in cardiac surgery – role of cytokines and complement

Objective: To investigate the role of cytokines and complement system in the inflammatory response after cardiopulmonary bypass we looked for physiological correlations between cytokine-/complement-levels and clinical parameters.

Neutrophils from Brazilian patients with Graves' disease: some biochemical and functional aspects

Graves' disease shows important systemic inflammatory complications and has been considered to be systemic autoimmune thyroid, skeletal muscle and connective tissue syndrome. Neutrophils participate in the pathophysiology of the two major immune and inflammatory manifestations of the disease, ophthalmopathy and myxedema, and may worsen the inflammatory picture. In this study we analysed some biochemical and functional aspects of neutrophils in Graves' disease patients to assess their participation in these processes. The results show that the complement and/or Fcgamma receptor-mediated oxygen radical production by neutrophils was increased when patient cells were compared with controls. However the percentage of cells expressing complement and IgG receptors and the per-cell fluorescence, were similar, indicating that the increased oxidative burst was not due to an abnormal expression of mediating receptors. The production of hydrogen peroxide was also increased in hyperthyroid patient neutrophils as compared to controls. Conversely, antioxidant defences (superoxide dismutase activity and reduced glutathione content) in neutrophils from patients were not significantly different from healthy controls. The liberation of potent oxidative compounds together with the absence of adequate quenching of them by antioxidant mechanisms could be responsible for greater tissue damage in inflammatory conditions, as is the case in ophthalmopathy and myxedema patients. Considering our results and those of other workers, we encourage and suggest an associated antioxidant therapy to complement the conventional anti-thyroid therapy, especially in obvious inflammatory cases and in individuals who smoke.

Systemic Inflammatory Complications Following Jejuno-Ileal Bypass

The clinical and laboratory features of three patients with systemic inflammatory complications following jejuno-ileal bypass surgery for morbid obesity are described. The constellation of an asymmetrical polyarthritis, tenosynovitis, sterile skin pustules, mucous membrane ulceration and retinal vasculitis resembled Behçet's syndrome. Serum complement levels were normal and circulating immune complexes not regularly detected, although hypocomplementaemia, elevations in Clq and rheumatoid factor binding materials were noted prior to clinical relapse in one patient. Antibiotic therapy proved disappointing, whereas dapsone produced a sustained remission. Bacterial overgrowth was not invariably found which together with recurrence of symptoms following bypass reversal, suggest that bacteria may only be required to initiate, not perpetuate inflammatory complications.