The systemic inflammatory response of the body to invading microorganisms, termed sepsis, leads to pro- found activation of the complement system. Pathophysiological concepts suggest that complement activation occurs very early in this syndrome. Thus, we discuss whether the determination of concentrations of the complement components C3a, C5a, and C3 in plasma as well as of the C3a/C3 ratio might be helpful to diagnose sepsis early. For this purpose, 33 patients from an intensive care unit were monitored for 10 days. In comparison with healthy donors, C3a levels and the C3a/C3 ratio of intensive-care-unit patients were signif- icantly elevated (P < 0.0001) on admission. In contrast, C3 levels were significantly reduced (P < 0.0001) but increased during the study. C5a levels in the plasma of healthy donors and patients were identical. Twenty-two of 33 patients fulfilled microbiological and clinical criteria of sepsis. Eleven patients had signs of systemic inflammatory response syndrome but no microbiological evidence of sepsis. The groups could be differentiated from each other by their C3a levels or their C3a/C3 ratios during the first 24 h after the clinical onset of sepsis (P < 0.05). Septic patients in shock had higher C3a levels than normotensive septic patients, although the differences were not significant. Nonsurvivors had significantly higher C3a levels on admission than survivors (P 5 0.0185). No differences were found between septic patients who developed adult respiratory distress syndrome and those who did not. Thus, determination of C3a concentrations in plasma may prove useful (i) to diagnose sepsis early, (ii) to differentiate between patients with sepsis and those with systemic inflammatory response syndrome, and (iii) to assess prognosis.
The date the positive blood culture was drawn was deemed Day 0 in the tracking of BSI. The patients' physi- ologic condition prior to the BSI and on the day of BSI were assessed using the APACHE II score. A cut-point of greater than 18 was used to stratify the severity of clinical condition. This methodology was used to be consistent with our previous studies in this area. The clinical condi- tion of each patient during the bloodstream infection was classified daily as SIRS, sepsis, severe sepsis or septic shock using criteria previously published by the American Col- lege of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM).  Systemic inflammatory response syndrome (SIRS) was defined as two or more of the fol- lowing: (1) temperature >38°C or <36°C, (2)heart rate >90 beats per minute, (3) respiratory rate >20 breaths per minute or a PaCO 2 <32 mmHg, or (4) white blood cell count >12 × 10 9 /L or <4 × 10 9 /L or the presence of more
ACCP: American College of Chest Physicians; AUROC: Area under the receiver operating characteristic curve; CAD: Coronary artery disease; CI: Confidence Interval; COPD: Chronic obstructive pulmonary disease; DNR: Do not rescue; ED: Emergency department; ICU: Intensive care units; NPV: Negative predictive value; OR: Odds ratio; qSOFA: Quick sepsis-related organ failure; SCCM: Society of Critical Care Medicine; SD: Standard deviation; SIRS: Systemic Inflammatory Response Syndrome; Third International Consensus Definitions for Sepsis and Septic Shock: Sepsis-3; TM: Tympanic temperature; WBC: White blood cell
escape the immune response of the host and survive in various tissues, giving rise to systemic disease in some cases. Leptospira was shown to cause septicemia and vessel injury by an unexplained mechanism . Histo- pathological changes, including generalized vasculitis affecting the kidney, lung, liver, brain, and meninges, were observed in microscopic examinations . Coagula- tion disorders resulting in hemorrhages and multi-organ failure can occur in patients with leptospirosis and sepsis . Systemic Inflammatory Response Syndrome (SIRS) is a systemic response to infection trauma burns or other conditions such as cancer with symptoms including fever tachycardia, tachypnea and leukocytosis. Sepsis is
The systemic inflammatory response syndrome (SIRS) is a systemic inflammatory reaction in response to various severe damaging effects of infectious and noninfectious nature, i.e. it "model, multisensory, fazospecificnam pathological process that develops in system damage and characterized by the total inflammatory reactivity of endothelial cells, plasma and cellular blood factors, connective tissue, and in the final stages of microcirculatory disorders in vital organs and tissues" (academician V. A. Chernyshev). I. N. Leiderman is convinced that the systemic inflammatory response (SVO) is a symptom complex that characterizes the severity of the inflammatory reaction in the endothelial cell system. Thus, SVO is the response of organs and systems to inflammation, and SIRS is the symptom complex of the main pathological conditions (respiratory failure, cardiovascular failure, acute renal failure, etc.). It follows that the syndrome of endogenous intoxication (SEI) and CIRS are identical. Both concepts are based on systemic inflammation .
However, sepsis is actually a syndrome of severe infec- tion with a complicated pathogenesis beyond the scope of our recognition . Many experts and specialists have attempted to use the clinical criteria of SIRS to de- scribe the pathophysiological process and nature of in- flammatory syndromes caused by severe infection, but the outcomes have been unsatisfactory . A new defin- ition of sepsis derived from a database of developed countries has been validated for use in these developed countries . However, it is necessary to be further val- idated for the concept whether can be generalized to de- veloping countries. Certainly, some studies evaluated SEPSIS-3 in developing countries have aroused our at- tention [13, 14]. In the present study, we used data from developing countries to compare the SIRS criteria with the SOFA criteria to predict a high risk of in-hospital death among critically ill patients with sepsis according to the new definition.
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discovered as a nonhistonal nuclear DNA binding protein . The essential importance of HMGB1 as a pleiotropic cytokine became apparent in a series of experiments showing that HMGB1 was actively secreted from monocytes and macro- phages in response to challenges with lipopolysaccharide and by a TNFα-dependent mechanism . Furthermore, the study found that HMGB1 levels were significantly elevated in patients who succumbed to sepsis, and that the administration of HMGB1 in murine models caused sepsis-like symptoms and death . In experimental murine models of endotoxemia  and sepsis, administration of anti-HMGB1 antibodies decreased mortality significantly [9,10], even when administra- tion was delayed for 24 hours , providing a window for therapeutic intervention if transferred into a clinical setting. These experiments showed that HMGB1 – in contrast to other inflammatory cytokines, such as TNFα – is a late mediator of inflammation. Besides being actively secreted, HMGB1 is passively released from necrotic cells but not from apoptotic cells, creating a signal for the organism to distinguish between these two types of cell death . Several studies have now been published on HMGB1 and infection, and the general consensus is that HMGB1 levels are increased in patients with sepsis as compared with healthy control individuals [9,12-17]. There is, however, evidence that HMGB1 is also involved in the pathophysiology of a variety of other diseases with no obvious infectious etiology: rheumatoid arthritis [18,19], hemorrhagic shock , cerebral and myocardial ischemia , acute lung injury  and acute pancreatitis .
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Abstract: To investigate the occurrence of systemic inflammatory response syndrome (SIRS) after ureteroscopy (URS)-guided lithotripsy and the application value of c-reaction protein (CRP) and procalcitonin (PCT) in serum to predict the occurrence of SIRS. We retrospectively summarized 86 cases of patients with urinary calculi who were treated with URS-guided lithotripsy. The patients were divided into two groups after operation, including the SIRS group (n = 22) and non-SIRS group (n = 64). On the first day after operation, the levels of CRP and PCT in serum in the SIRS group were significantly higher than those in the non-SIRS group. We performed ROC analysis and found that the diagnostic accuracy of CRP level was 0.864 (95% CI = 0.812 to 0.965, p = 0.009), the sensitivity was 86.9%, the specificity was 76.5% and the cutoff value was 8.3 mg/L. The diagnostic accuracy of PCT level was 0.881 (95% CI = 0.823 to 0.958, p = 0.005), the sensitivity was 88.2%, the specificity was 83.6% and the cutoff value was 7.5 μg/L. The results showed that levels of CRP and PCT in serum on the first day after operation could improve the diagnostic accuracy, sensitivity and specificity, and predict the occurrence of SIRS.
The international consensus criteria were entailed to early recognition of sepsis . Early recognition and treatment of sepsis can decrease mortality [19, 20]. However, the SIRS criteria have low specificity to iden- tify infected patients at risk of exacerbation to severe sepsis or septic shock [22–24] and may miss one in eight adult patients with sepsis . In our study, 76 (4.7%) cases of SNS had normal temperature and WBC, and did not meet SIRS criteria for presumed sepsis. This may be similar to the group identified by Kaukonen and colleagues as having sepsis but not meeting the inter- national consensus criteria , and provides further evidence that using the SIRS criteria for sepsis screening is suboptimal [13–16]. In addition, in resource limited environments the use of SIRS for the criteria of sepsis may result in about 33% false-positives and has led to seeking alternatives to the traditional SIRS criteria in these settings . We speculate that SIRS may be altered by response to medications such as antibiotics for a limited period, especially at level I clinics in this cohort (Table 2). However, if the SIRS persists, then clin- ical deterioration follows, leading to severe sepsis . Patients in the SNS group had no history of SIRS, or any other explanation except sepsis for their clinical status, a phenomenon which has been previously reported . It revealed that pediatric sepsis patient population may not share common clinical features and laboratory findings but SIRS-negative as a small proportion as those of adults [13, 14, 28].
Our results demonstrated improved hemostasis with respect to hemostasis time, chest tube output, and need for PRBC transfusion in the first 48 hours postopera- tively. However, we do acknowledge that chest output in the first 8–12 hours may be more meaningful as it re- lates to post-operative bleeding and there may be a serous component after 24–48 hours. Due to the retro- spective nature of our study and availability of data, chest tube output was recorded at least on a 24 hour basis and earlier drainage was not available in all patients. Postoperative bleeding complications in cardiac surgery can have multiple etiologies. Invasiveness of the procedure, induced hypothermia, extended use of CPB, and increasing age, are major reasons for increased blood loss and the higher incidence of blood transfu- sions . Concomitant postoperative complications, such as stroke, renal dysfunction, and systemic inflammatory response syndrome (SIRS) also increase incidence of post- operative bleeding . Topical hemostatic agents are valuable adjuncts to cardiothoracic surgical procedures because they can decrease intraoperative bleeding, and may reduce the need for postoperative blood transfusion. In their study of 1,118 patients, Christensen et al. demon- strated that average hospital costs were substantially related to excessive postoperative hemorrhage in cardiac surgery . Also in their study, postoperative bleeding was a significant risk factor for morbidity and mortality. Clin- ical interventions that can effectively prevent or address excessive postoperative hemorrhage in cardiac surgery are likely to have substantial cost-effectiveness potential. Table 1 Baseline characteristics of the study and control
Background: Sepsis is still a major cause of death in both human and veterinary medicine. Early diagnosis is essential for appropriate treatment. Identification of patients at risk for developing sepsis is already possible in human medicine through the measurement of plasma IL-6 levels. In veterinary medicine, however, this has only been investigated in canine experimental models. Objectives: The purpose of this study was to measure IL-6 plasma levels in dogs with naturally occurring systemic inflammatory response syndrome (SIRS) and sepsis and to analyse the value of IL-6 as a predictive parameter for severity and mortality. Methods: Included in the study were 79 dogs that had been admitted to the small animal clinics of Munich and Berlin from July 2004 to July 2005 and which satisfied the diagnostic criteria for SIRS and sepsis as defined using established parameters. Measurement of plasma IL-6 levels on day 0, 1, and 2 was performed by the use of a colorimetric bioassay based on IL-6 dependent cell growth. Results: Septic foci were identified in 43 patients (septic group), and 36 patients were enrolled in the SIRS group. The frequency of positive blood cultures was 11%. The overall mortality rate was 48%. Higher IL-6 plasma levels on the day of admission were significantly correlated with a more severe degree of disease, increased mortality rates and earlier fatality. Conclusions: In this study we show that plasma IL-6 qualifies as an interesting and predictive laboratory parameter in canine SIRS and sepsis.
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Background: Canine pyometra is a life-threatening disease common in countries where spaying of dogs is not routinely performed. The disease is associated with endotoxemia, sepsis, systemic inflammatory response syndrome (SIRS) and a 3–4% mortality rate. Blood lactate analysis is clinically valuable in predicting prognosis and survival, evaluating tissue perfusion and treatment response in human and veterinary critical care settings. The aims of the present study were to investigate 1) the blood lactate levels of female dogs with pyometra by a hand-held analyser and 2) if these levels are related with the clinical status or other biochemical or hematological disorders.
More than two decades ago, sepsis was defined as the combination of infection and Systemic Inflammatory Response Syndrome (SIRS) . However, subsequent research revealed that sepsis is not an exclusively pro- inflammatory condition; rather, it may involve early anti- inflammatory responses . Moreover, SIRS criteria were found to be too sensitive and insufficiently specific to identify infected patients at risk for a complicated course [3, 4]. In the light of such developments, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Task Force recently rede- fined sepsis . Sepsis is accordingly viewed as a “life- threatening organ dysfunction caused by a dysregulated host response to infection” . Organ dysfunction was characterized by the acute increase of at least two points in the Sequential (Sepsis-related) Organ Failure Assess- ment (SOFA) score . Given that SOFA requires laboratory testing and is rarely performed outside the intensive care unit (ICU), for patients in a non-ICU setting, the Sepsis-3 Task Force introduced a simpler algorithm, named quick SOFA (qSOFA) .
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It was a 16-year-old boy, sickle-cell of type SS, who consulted on February 2017, for fever and abdominal pain progressing since 72 hours before admission. The unquantified fever (initial symptom) was accompanied by chills and food vom- iting, as well as epigastric and right hypochondrium pain. The transit was re- tained. He had benefited in town of multiple treatments made of quinine, am- picillin, and phloroglucinol. The initial examination had noted: alteration of general condition, systemic inflammatory response syndrome, respiratory dis- tress syndrome, bilateral pulmonary condensation syndrome, the volume of the abdomen is normal and depressible as a whole, but sensitive in the right hypo- chondrium and the epigastrium, presence of a slight hepatomegaly and a nega- tive Murphy sign. He had a hypochromic microcytic anemia at 3.2 g/dL and hy- perleucocytosis at 28.2 G/l predominantly neutrophilic at 22.8 G/l. Pulmonary X-ray showed diffuse flocculent opacities of the two pulmonary fields and pneumoperitoneum under the right hemidiaphragm (Figure 1). Plain abdomi- nal radiography had objectified a clarity projected on the right hypochondrium with some hydro-aeric images, multiple calcic opacities projected on the vesicu- lar area (Figure 2(a)). In the course of exploring the pneumoperitoneum, an oesogastroduodenal fibroscopy performed showed a congestive and erosive bul- bitis without perforation of the upper digestive tract (Figure 3). The CT scan of the abdomen showed a giant pneumoperitoneum without fluid effusion, calcifi- cations in the gallbladder without thickening of the wall, and homogeneous hepatomegaly (Figure 4 and Figure 5). The diagnosis of pulmonary (bron- cho-pneumonia) and digestive (angiocholitis) sepsis was discussed. Under tri-antibiotic IV therapy (thiamphenicol, amoxicillin and azithromycin), recovery was progressively favourable. The fever and abdominal pain regressed with leu- cocytosis passing from 28.2 G/l to 10.7 G/l. The patient left the hospital 15 days
Currently, i.v. AA is used extensively by “alternative medicine” practitioners in the USA (11,233 patients treated in 2006 and 8876 patients in 2008) , although the basis for this practice has not been adopted into mainstream medicine. It is our belief that, in the practice of medicine, opinion should not hold greater weight than evidence - either a treatment has beneficial effects or it does not, and it is that consideration that must drive practice. We therefore sought, not to address the controversial area of whether AA shrinks tumors (which is currently being addressed in ongoing FDA approved trials [26-31]), but instead in an area that we feel has been highly under-explored: that is, suppression of inflammation in the cancer patient. In the context of cancer, inflammation may be seen as a continuum of possible degrees of severity ranging from low level, chronic inflammatory response to acute, highly severe inflammation. At the chronic end, low grade inflamma- tion causes a variety of pathologies to the patient, per- haps most profound of which is cachexia [32-35], but also other effects such as poor post-surgical outcomes [36,37]. At the other end of the spectrum is the acute inflammation observed in the systemic inflammatory response syndrome (SIRS), a major cause of death of cancer patients and especially patients with hematologi- cal malignancies [38-40]. While we focus in this paper on SIRS and cancer, some of the concepts discussed are also applicable to chronic inflammatory conditions.
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Introduction The diagnosis of sepsis in critically ill patients is challenging because traditional markers of infection are often misleading. The present study was conducted to determine the procalcitonin level at early diagnosis (and differentiation) in patients with systemic inflammatory response syndrome (SIRS) and sepsis, in comparison with C-reactive protein, IL-2, IL-6, IL-8 and tumour necrosis factor- α . Method Thirty-three intensive care unit patients were diagnosed with SIRS, sepsis or septic shock, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria. Blood samples were taken on the first and second day of hospitalization, and on the day of discharge or on the day of death. For multiple group comparisons one-way analysis of variance was applied, with post hoc comparison. Sensitivity, specificity and predictive values for PCT and each cytokine studied were calculated.
As part of the ACCP/CCM consensus definitions statement, it was noted that SIRS “is seen in associ- ation with a large number of clinical conditions. Be- sides the infectious insults that may produce systemic inflammatory response syndrome, noninfectious pathologic causes may include pancreatitis, ischemia, multitrauma and tissue injury, hemorrhagic shock, immune-mediated organ injury, and the exogenous administration of such puta- tive mediators of the inflammatory process as tumor necrosis factor or other cytokines” . In this patient’s case, RT was the putative mediator of the inflamma- tory process, which elicited increases in tumor necrosis factor-α (TNF-α) and other cytokines, and produced the clinical symptoms and signs observed, which in
Presepsin, sCD14-ST: cluster-of-differentiation 14 subtypes; CI: confidence interval; SROC: the summary receiver operating characteristic curve; AUC: the area under the receiver operating characteristic curve; MODS: multiple organ dysfunction; SIRS: systemic inflammatory response syndrome; LPS: lipopolysaccharide; LPB: lipopolysaccharide-binding proteins; PCT: proc- alcitonin; CRP: C-reactive protein; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement; EMBASE: Excerpta Medica database; MeSH: medical subject headings; ACCP/SCCM: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference; TP: true positive; FP: false positive; FN: false negative; TN: true negative; LR: likeli- hood ratio; OR: odds ratios; I 2 : inconsistency; TREM-1: myeloid cells expressing
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Prevention of severe systolic hypertension (>160 mm Hg) is paramount; recommendations to maintain systolic pressures under 150 mm Hg and diastolic pressures under 100 mm Hg are reasonable goals. Labetolol, hydralazine, or nifedipine are the preferred agents for treatment of acute hypertension . Maternal- fetal status, gestational age, presence of labor, cervical Bishop Score, prior maternal obstetric history, and response to aggressive corticosteroids all impact management of the patient with a preterm viable fetus and HELLP syndrome. Immediate cesarean delivery is not generally indicated or recommended; vaginal or cesarean delivery after 24 to 48 hours of corticosteroids are better options to achieve maximal maternal and fetal benefit. Nevertheless, because vaginal delivery rates with HELLP syndrome are below 50% for gestations less than 30 weeks, some authors advocates elective cesarean delivery for all women diagnosed with HELLP syndrome at a gestation age less than 30 weeks when spontaneous labor is not present and the Bishop score is less than 5. A patient with a low Bishop score in association with fetal growth restriction and/ or oligohydramnios may not be a good candidate for trial of labor. Otherwise, vaginal delivery is attempted in patients in active labor less than 30 weeks with ruptured membranes or with a Bishop score 5 or more in the absence of obstetric contraindications. Once the 30-week gestational age threshold is reached, an attempt at vaginal delivery is usually recommended. Epidural or spinal anesthesia is the preferred anesthetic for patients with preeclampsia. Approximately 50% of patients with HELLP syndrome can be candidates for regional anesthesia during a trial of labor using a threshold of 100,000/µL platelets. In these circumstances, the decision of abdominal versus vaginal delivery becomes more of an obstetric issue rather than a response to a rapidly worsening maternal-fetal condition .
Neurogenic heterotopic ossification (HO), a process by which new bone formation occurs outside of the skel- eton and preferentially around soft tissues, is an irrevers- ible complication of SCI more frequently seen in young patients [132–135]. Cervical and thoracic SCIs induce more HO than do lumbar injuries, and the hip joint is the major ossified area. Regulation of HO development is multifactorial [136–138], and the inflammatory re- sponse is an important contributing factor in the early stage of HO. Among the multiple therapeutic choices, non-steroidal anti-inflammatory drugs are effective prophylactic treatments against HO when administered soon after SCI [134, 139–143]. Estrores and colleagues reported that increased levels of C-reactive protein, a commonly used marker of acute inflammation in SCI [144–146], were associated with early occurrence of HO and the concentration of C-reactive protein declined when HO symptoms were alleviated in later stages . The lack of animal models that reproduce the clinical features of HO observed in SCI patients has long hin- dered the study of underlying HO mechanisms; however, in 2015 a well-characterized mouse HO model showed that phagocytic macrophages play a critical role in driv- ing the development of HO . This study highlighted
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