In addition to the routine bedside ultrasound for the detection of postoperative sepsis, CT is useful to find out the infection in the abdominal wall and abscess in the psoas muscle. By CT, abscesses are characteristically well defined, low attenuated masses that may displace the adjacent organs and obliterate nearby fat planes. Differentiation of an abscess from a collection of inflammatory liquid may not be possible by CT alone, but CT guided aspiration with gram-stain and culture is often definitive. Special stains and cultures, as for acid-fast bacteria or fungi, may occasionally be helpful, although postoperative wound infections are usually caused by bacteria. CT-guided percutaneous drainage may be the preferred therapy because the risks of anaesthesia and surgery are avoided. Generally, CT scans are not helpful in identifying collections of liquid in the first week postoperatively, but they may be very helpful thereafter.
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The experiment was set up to mimic a clinical scenario of postoperative sepsis, in which the impact of ventilator settings initiated before and after the experimental complication (endotoxemia) could be evaluated. The inflammatory response from the surgery was considered more important than the occurrence of an actual surgical intervention, such as colectomy, in this model. Therefore, the preparatory surgery (comprising skin incisions in the neck for tracheostomy and bilateral vessel access, a small laparotomy for bladder access and a larger laparotomy for access to the splenic vessels for catheterisation of the portal vein) had the additional task of generating a standardised systemic trauma response. The magnitude of response is presented in an earlier publication .
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aggregation through the TLR4/MyD88 signal- ing pathway . Penders et al. showed that the interaction between genes and the environ- ment can affect the incidence of allergic dis- eases, as the risk of allergic diseases induc- ed by Escherichia coli colonization is reduced in children with the TT genotype at the rs10759932 locus and in children without a C allele . The results of this study showed that the TLR4 rs10759932 locus was associ- ated with the occurrence of sepsis. Compared with the TT genotype, the TC+CC genotype showed an increased risk of sepsis, suggesting that at the TLR4 rs10759932 locus, the TC+CC genotype was closely related to the susceptibil- ity of postoperative sepsis. Duan et al. showed that non-coding region SNPs can alter gene expression, which in turn affects the release of inflammatory factors . Chen et al. showed that SNPs in the promoter and coding region of TLR4 can change gene expression levels and the mRNA structure, thus affecting protein function . The TLR4 polymorphic locus rs10759932 is located in an upstream regula- tory region for the TLR4 gene, and differences in this region may change the secondary struc- ture of the mRNA and TLR4 expression levels, thereby changing the response of TLR4 to LPS . The results of this study showed that the MyD88 rs6853 locus was associated with the occurrence of sepsis. Compared with the AA genotype, the GG+AG genotype showed an increased risk of sepsis, suggesting that the MyD88 rs6853 locus genotype GG+AG was closely related to the susceptibility of postop- erative sepsis. The rs6853 locus is located in the 3’UTR, and mutations in the 3’UTR can affect gene expression and cause disease. Thus, mutations may affect the biological func- tion of MyD88. Through further research, we showed that patients carrying the IL-10 rs1800896 AA, GG and AG genotypes, the TLR4 rs10759932 TT, TC and CC genotypes, and the MyD88 AA, GG and AG genotypes were not significantly correlated with septic shock, organ dysfunction, or survival. Septic shock, organ dysfunction, and survival are complex processes likely involving more factors and like- ly influenced by additional genes. Environmental factors had a greater impact on susceptibility to sepsis, and locus changes in IL-10, TLR4 and MyD88 may primarily affect pathogen identifi- cation by the immune system and the inflam- matory processes during the initial innate immune response.
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In order to better understand the parameters that were associated with the greater incidence of septicemia among orthopedic trauma patients, preoperative risk factors that significantly predicted septic complications were identified. Several of these predictors are consistent with the existing literature examining the risk factors for sepsis, although no prior studies have done so for orthopedic trauma. In par- ticular, associations between male gender [23, 38, 39], age greater than 65 , and sepsis-related complications have been reported in a number of studies. In their analysis of the risk factors of sepsis after multiple trauma, Wafaisade et al. utilized a multivariate regression to identify male gender, increased age, and pre-existing conditions as sig- nificant predictors . However, their cohort comprised an array of trauma patients, only a fraction of whom experienced orthopedic injuries. Additionally, individual preoperative comorbidities were not evaluated, making it difficult to identify potential avenues for clinical change. Preoperative mechanical ventilation, which was reported as a risk factor for sepsis in this study, has also been associ- ated with increased risk of postoperative sepsis in pediatric cardiothoracic surgery . To our knowledge, this is one of the very few studies to report hypertension, prior pain at rest, history of sepsis, and corticosteroid use as predictive risk factors for septicemia, and the first to do so for orthopedic surgery.
Postoperative mortality of PD for periampullary tumor was close to 10% in the 1980s, justifying several clinical studies to improve postoperative course. It was suggested that preoperative jaundice as a strong determinant factor of postoperative complications and should be treated preoperatively.But neither randomized controlled trials nor retrospective comparative studies gave clear evidence that preoperative biliary drainage improves postoperative course after Pancreatocoduodenectomy. Additionally, in 1999, Povoski and associates reported a higher rate of infectious complications in patients with preoperative biliary drainage, which has not been confirmed in two other large retrospective studies. Povoski and coworkers explained their results by the negative effect of bile contamination, which has also been reported as a major risk factor of postoperative sepsis after cholecystectomy and hepatectomy
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Sepsis is a common complication following serious trauma/burn, shock, infection or major surgery, and also is a systemic inflammation response syndrome (SIRS) in the presence of infectious factors. Furthermore, sepsis can develop into septic shock and multiple organ dys- function syndrome (MODS), which is largely responsible for the extremely high mortality. Nowadays, although great progress has been made in the pathogenesis, diag- nosis and prevention of sepsis, the incidence and morta- lity rate of sepsis still remain high. Studies reveal the mortality rate of sepsis is as high as 28% ~ 56% [1-4]. Once infected with human immunodeficiency virus (HIV), humans will develop immune dysfunction. HIV infected patients with surgical conditions require surgical treat- ment in certain environments. Because of the immune dysfunction, HIV infected patients are susceptible to postoperative sepsis that go along with different clinical manifestations. At present plenty of comprehensive hos- pitals take the HIV testing as a regular program before surgery. Once HIV infection test index is positive, pa- tients will be euphemistically advised against/denied op- erations by surgeons. One of the reasons against the sur- gical operation is that patients with HIV infection are susceptible to infectious complication after surgery.
Despite NO effects in the circulation, reduced levels of NO in sepsis might be harmful for another reason. Cecal ligation reduces survival in NOS knockout mice compared to wild-type animals ; and bone marrow transplant- ation of wild-type to NOS knockout mice increases release of cytokines such as TNF-α and was found to improve survival in a model of idiopathic pneumonia . To- gether with the discovery that mouse macrophages pro- duce large amounts of nitrite (NO2-) and nitrate (NO3-) upon LPS stimulation, it has been suggested that de- creased NO levels may impair the innate immune re- sponse , which is characteristic of sepsis progression in humans. Human monocytes show diminished defense mechanisms. For instance, the reduced ability to release pro-inflammatory cytokines after endotoxin stimulation has been referred to as monocyte “anergy” . In this context it has been shown that hArg can serve exclusively as a substrate for NOS in macrophages . Interestingly, the pharmacological transformation of hArg to the NOS inhibitor NH2-homoarginine results in significantly de- creased NO production by macrophages . One may speculate that decreased hArg levels may indicate mono- cyte “anergy” and this may explain why the hArg:ADMA ratio may be better than the lArg:ADMA ratio for diag- nosing sepsis severity.
Of the three sepsis categories defined in the international pediatric sepsis consensus conference (sepsis, severe sepsis, and septic shock), all require laboratory tests (eg, leukocyte count). In addition, severe sepsis and septic shock require complex organ dysfunction criteria that could only be deter- mined at highly resourced institutions. In many developing countries, even simple laboratory tests, such as leukocyte counts, are often not measured because neither public sector systems nor patients can afford them. A further limitation in using the traditional sepsis definition is the requirement for a core temperature measurement. While probably ideal, the additional time and care required to obtain this, coupled with potential complications of rectal measurements, make a strong case for validation of axillary or oral temperature measurements. With this in mind, sepsis research aiming to influence clinical practice must consider the definitions being used and their applicability to the population being studied. Because sepsis forms the final common pathway of infectious disease mortality, a more pragmatic alternative for identification of children at high risk of mortality related to infectious disease may be justified.
This study has several limitations. First, we are un- likely to have enrolled all sepsis patients presenting dur- ing the study period. Although study staff consecutively screened all patients admitted to the general medical wards and ICUs, screening was based upon a clinical diagnosis of suspected infection listed in the patient’s chart, and some patients with sepsis may have been ini- tially misdiagnosed with non-infectious conditions. Add- itionally, surgical, obstetric, and pediatric patients were not enrolled. Second, unique characteristics of this study population, such as low HIV prevalence and a very high proportion of patients who were transferred from other facilities, may limit external validity. Third, as an obser- vational study, most of the data were limited to those routinely collected by clinicians in the study hospital. Fourth, as this was a single-center study, our findings may not reflect the management of patients with sepsis elsewhere in Thailand.
25(OH)D 3 concentrations seen reflected changes associated with sepsis rather than the cause. Second, this is a retrospective study of a small number of patients that could not control for patient comorbidities. The effects of sepsis and critical illness on the vitamin D metabolome are unknown and this complex interplay needs prospective large-scale studies that consider other prein- sult comorbidities, chronic illness, nutritional status, and other confounders. It was for this reason we did the murine studies. In our CLP model, we studied early sepsis due to restrictions from the animal ethics committee. This meant that our animals had limited alveolar damage, which was why we undertook addi- tional studies in the IT-LPS model. Although the VDD induced by diet design investigated whether pre-existing VDD is causal and a mechanistic driver to the severity of sepsis rather than the consequence of the sepsis insult in the murine model, it may not wholly explain the findings of the human study due to the lack of vitamin D status before sepsis and its effects on vitamin D status as discussed above. Finally, we have shown the effects of VDD in only two models of murine lung injury. Further work in other models related to sepsis particularly experimental pneu- monia need to be undertaken.
40–50% of patients with prolonged septic shock develop cardiac dysfunction  and newer studies indicate that cardiac dysfunction can occur in all stages of sepsis . The underlying molecular mechanisms are not fully understood yet, but a notable cause is mitochondrial dysfunction which contributes to cardiac dysfunction by causing myocardial energy depletion . Here AQP1 might be important because Aqp1 knockout causes car- diac hypertrophy in mice  (Fig. 2b). Another animal study tested the hypothesis if Aqp1 may play a role in cardiac dysfunction during sepsis. They found that Aqp1 expression is increased after LPS exposure in cardiac tis- sue and that this might influence cardiac function .
An alternative hypothesis is that some sepsis phenomena are functional, regulated traits. Clinical trials in sepsis offer tests of the potential function of phenotypes in sepsis. In molecular biology, uncovering the function of a gene or protein is often accomplished by using knock-out mice, animals in which a genetic coding region is altered or deleted. By comparing those phenotypes to those of unaltered animals, a gene or protein’s function can be inferred. Immunomodulatory drugs are not the same as knock-outs, but they can have similar effects by blocking downstream effects of gene expression. Like knock-out models, many sepsis trials shed light on the question of function of the underlying traits. If those traits are functional, then blocking them should fail to improve outcomes, and might do more harm than good.
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On the other hand, our study also has several strengths. To our knowledge, this is the first investigation to use this method in an attempt to stage the host immune response in sepsis; therefore, our findings are important when viewed as thought provoking and hypothesis generating. Furthermore, patients in our study classified as immuno- compromised based on clinical criteria had significantly different assay results than those who were immunocom- petent, which is similar to prior published data . This observed difference further supports the notion that this assay is an objective marker of the global cell-mediated immune status of an individual, and therefore, provides useful information, particularly in the setting of sepsis.
In 2016, Valentina first reported on plasma mtDNA levels in the pediatric population, including a small sam- ple of 28 patients with sepsis, 20 healthy controls, and 10 critically ill non-septic patients. In the current study, we expanded the sample size to include 123 children with sepsis, 30 children with non-sepsis infection, and 30 healthy children. Our findings were consistent with the results reported by Valentina, demonstrating that plasma mtDNA concentrations were significantly ele- vated in patients with sepsis compared to those without sepsis and the control group . We further revealed that higher mtDNA levels correlated significantly with organ dysfunction, by analyzing organ damage based on enzyme levels and comparing mtDNA levels to patients without organ dysfunction. A separate study in adult sepsis showed that mtDNA levels increased on day 1 and remained constant until day 5 in patients diagnosed with sepsis . The mechanisms for mtDNA release in- volve two steps: cytosolic followed by extracellular Table 1 Baseline characteristics of patients
A majority (656 of 1058, 62%) of physicians believed that their definition of sepsis is commonly accepted within their speciality. More than four in five (905 of 1058, 86%) physi- cians agreed (strongly or somewhat) that the symptoms of sepsis can easily be misattributed to other conditions. There was concern (ranging from 'somewhat' to 'extremely con- cerned') about the lack of a common definition for sepsis in 67% (708 of 1058) of the physicians. Of the physicians who were concerned about the lack of a common definition, 83% (199 of 708) stated that it is at least somewhat likely that the diagnosis of sepsis is missed. This figure was 53% (29 of 350) for the physicians who were not concerned about the lack of a common definition for sepsis. Although physicians are divided over whether the lack of a common definition for sepsis hinders proper diagnosis, they are not divided over whether a common definition would be a significant step towards better treatment.
and expression of pro-inflammatory cytokines in LPS-stimulated RAW264.7 cells . So, in this study we detected the production of NO, iNOS and the activity of NOS in serum and lung tissues of differentially treated ALI mice respec- tively. We found bisabolol treatment decreased the production of NO (Figure 3A) and the expression of iNOS (Figure 3C) in vivo and reduced the NOS activity (Figure 3B) in lung tis- sue compared with the vehicle control group. Moreover, the expression of inflammatory cyto- kines was also inhibited in bisabolol treated ALI mice (Figure 5). These results indicated that bisabolol have a potentially protective effect on the sepsis-induced ALI through its antioxidative and anti-inflammatory activity.
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Changes to the way responsibilities for initiating and completing the Sepsis Six were allocated could improve implementation by reducing the need for coordination and task-switching. The use of a response team to man- age patients with suspected sepsis was a common model. These teams were usually led by an advanced nurse practitioner and were on standby to respond to deterior- ating patients; this team would take over the responsibil- ity for diagnosing sepsis and initiating the Sepsis Six. The team could be called by a ward-based nurse or doc- tor when a patient was identified as deteriorating. Add- itionally, in one site, members of the response team described ‘trawling the wards’ to identify deteriorating patients that they had not been alerted to. By concen- trating the skills in one place and placing responsibility in a single team with clear responsibilities and without the distractions faced by other staff on wards and in emergency departments, this approach had promise in overcoming some of the operational challenges that faced others in delivering the Sepsis Six.
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When interrogated against a cohort of SCIAS patients recruited from an advanced health-care system, each predictive model performed with different attributes. Even considering a specific scoring tool, the specific tool may have varying sensitivity and specificity for identify- ing patients of interest depending on the threshold value of the tool selected. Thus, no one scoring system be- haved perfectly, and all appear to be largely dominated by organ dysfunction with a modest increase in detection provided by the inclusion of further patient characteristics some of which may not be readily avail- able pre-operatively before potential surgery and admis- sion to ICU. Nonetheless in this population, patients identified by the Sepsis-3 septic shock definition in addition to the WSESSS criteria with a score of 8 or greater had a detection rate of 80%. Adding the potential increased detection of the CPIRO score ≥ 3 increased the detection rate to 83%. Thus, the COOL investigators decision to include any of the three identifying cri- teria of Sepsis-3 septic shock criterion, WSESSSS ≥ 8, or CPIRO ≥ 3 seems statistically justified based on this analysis.
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The present study has limitations. The number of patients in the cohort was limited, and the sensitivity and specifity of thromboelastometry values and of con- ventional biomarkers for the diagnosis of sepsis might differ in other cohorts and require further studies. Furthermore, the clinical use of thromboelastometry variables as a biomarker for severe sepsis might be lim- ited by the fact that citrated whole-blood samples have to be processed within a short time frame, and that the method is time consuming when compared with auto- mated laboratory methods. It is a fact that the groups in the present study were heterogeneous. However, we compared several biomarker and the best biomarker, the lysis index, showed an exceedingly high odds ratio of 85.3.
There are, nevertheless, several limitations to be addressed, in light of which our findings should be inter- preted. First, the retrospective nature of this study makes it difficult to elucidate known confounders that could have biased the outcome measures, such as differences in sepsis treatment. Second, this was a single-center study consisting mainly of medical patients and our results may not be generalizable to other centers, including from other developing countries, since there is wide variation in outcomes even within Brazil when comparing differ- ent settings [29, 30]. Third, we evaluated only patients admitted to the ICU and, therefore, our findings cannot be extrapolated to patients treated in wards and in the emergency room. This also threatens the generalizability of our results, since the original study captured a popula- tion with presumed infection not only in the ICU. Fourth, the validity of Sepsis-3 criteria in this study was assessed based on ICU mortality. Although ICU mortality is not the most appropriate endpoint to be evaluated, it reflects the pre-ICU and ICU care of septic patients, and in our scenario, identified a more specific point to improve the care of septic patients [31, 32].