Getting the invite list right: a discussion of sepsis severity scoring systems in severe complicated intra-abdominal sepsis and randomized trial inclusion criteria.
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ABSTRACT: Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent. An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database.All consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality.Predictive systems with an area under-the-receiving-operating characteristic (AUC) curve >?0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score ??2 (78.4%), followed by the WSESSSS score ??8 (73.1%), SOFA ??3 (75.2%), and APACHE II ??14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS ??8 increased detection to 80%. Including CPIRO score ??3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA ??4 and WSESSSS ??8 with or without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality).No one scoring system behaves perfectly, and all are largely dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to offer the widest "inclusion-criteria" to recognize patients with a high chance of mortality and ICU admission.https://clinicaltrials.gov/ct2/show/NCT03163095; Registered on May 22, 2017.
Getting the invite list right: a discussion of sepsis severity scoring systems in severe complicated intra-abdominal sepsis and randomized trial inclusion criteria.
World journal of emergency surgery : WJES 20180406
<h4>Background</h4>Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent. An eval ...[more]
Project description:BackgroundSevere complicated intra-abdominal sepsis (SCIAS) has high mortality, thought due in part to progressive bio-mediator generation, systemic inflammation, and multiple organ failure. Treatment includes early antibiotics and operative source control. At surgery, open abdomen management with negative-peritoneal-pressure therapy (NPPT) has been hypothesized to mitigate MOF and death, although clinical equipoise for this operative approach exists. The Closed or Open after Laparotomy (COOL) study (https://clinicaltrials.gov/ct2/show/NCT03163095) will prospectively randomize eligible patients intra-operatively to formal abdominal closure or OA with NPTT. We review the ethical basis for conducting research in SCIAS.Main bodyResearch in critically ill incapacitated patients is important to advance care. Conducting research among SCIAS is complicated due to the severity of illness including delirium, need for emergent interventions, diagnostic criteria confirmed only at laparotomy, and obtundation from anaesthesia. In other circumstances involving critically ill patients, clinical experts have worked closely with ethicists to apply principles that balance the rights of patients whilst simultaneously permitting inclusion in research. In Canada, the Tri-Council Policy Statement-2 (TCPS-2) describes six criteria that permit study enrollment and randomization in such situations: (a) serious threat to the prospective participant requires immediate intervention; (b) either no standard efficacious care exists or the research offers realistic possibility of direct benefit; (c) risks are not greater than that involved in standard care or are clearly justified by prospect for direct benefits; (d) prospective participant is unconscious or lacks capacity to understand the complexities of the research; (e) third-party authorization cannot be secured in sufficient time; and (f) no relevant prior directives are known to exist that preclude participation. TCPS-2 criteria are in principle not dissimilar to other (inter)national criteria. The COOL study will use waiver of consent to initiate enrollment and randomization, followed by surrogate or proxy consent, and finally delayed informed consent in subjects that survive and regain capacity.ConclusionsA delayed consent mechanism is a practical and ethical solution to challenges in research in SCIAS. The ultimate goal of consent is to balance respect for patient participants and to permit participation in new trials with a reasonable opportunity for improved outcome and minimal risk of harm.
Project description:The potential for conservation of individual species has been greatly advanced by the International Union for Conservation of Nature's (IUCN) development of objective, repeatable, and transparent criteria for assessing extinction risk that explicitly separate risk assessment from priority setting. At the IV World Conservation Congress in 2008, the process began to develop and implement comparable global standards for ecosystems. A working group established by the IUCN has begun formulating a system of quantitative categories and criteria, analogous to those used for species, for assigning levels of threat to ecosystems at local, regional, and global levels. A final system will require definitions of ecosystems; quantification of ecosystem status; identification of the stages of degradation and loss of ecosystems; proxy measures of risk (criteria); classification thresholds for these criteria; and standardized methods for performing assessments. The system will need to reflect the degree and rate of change in an ecosystem's extent, composition, structure, and function, and have its conceptual roots in ecological theory and empirical research. On the basis of these requirements and the hypothesis that ecosystem risk is a function of the risk of its component species, we propose a set of four criteria: recent declines in distribution or ecological function, historical total loss in distribution or ecological function, small distribution combined with decline, or very small distribution. Most work has focused on terrestrial ecosystems, but comparable thresholds and criteria for freshwater and marine ecosystems are also needed. These are the first steps in an international consultation process that will lead to a unified proposal to be presented at the next World Conservation Congress in 2012.
Project description:ObjectivesSepsis-3 defines organ dysfunction as an increase in the Sequential Organ Failure Assessment score by greater than or equal to 2 points. However, some Sequential Organ Failure Assessment score components are not routinely recorded in all hospitals' electronic health record systems, limiting its utility for wide-scale sepsis surveillance. The Centers for Disease Control and Prevention recently released the Adult Sepsis Event surveillance definition that includes simplified organ dysfunction criteria optimized for electronic health records (eSOFA). We compared eSOFA versus Sequential Organ Failure Assessment with regard to sepsis prevalence, overlap, and outcomes.DesignRetrospective cohort study.SettingOne hundred eleven U.S. hospitals in the Cerner HealthFacts dataset.PatientsAdults hospitalized in 2013-2015.InterventionsNone.Measurements and main resultsWe identified clinical indicators of presumed infection (blood cultures and antibiotics) concurrent with either: 1) an increase in Sequential Organ Failure Assessment score by 2 or more points (Sepsis-3) or 2) 1 or more eSOFA criteria: vasopressor initiation, mechanical ventilation initiation, lactate greater than or equal to 2.0 mmol/L, doubling in creatinine, doubling in bilirubin to greater than or equal to 2.0 mg/dL, or greater than or equal to 50% decrease in platelet count to less than 100 cells/μL (Centers for Disease Control and Prevention Adult Sepsis Event). We compared area under the receiver operating characteristic curves for discriminating in-hospital mortality, adjusting for baseline characteristics. Of 942,360 patients in the cohort, 57,242 (6.1%) had sepsis by Sequential Organ Failure Assessment versus 41,618 (4.4%) by eSOFA. Agreement between sepsis by Sequential Organ Failure Assessment and eSOFA was good (Cronbach's alpha 0.81). Baseline characteristics and infectious diagnoses were similar, but mortality was higher with eSOFA (17.1%) versus Sequential Organ Failure Assessment (14.4%; p < 0.001) as was discrimination for mortality (area under the receiver operating characteristic curve, 0.774 vs 0.759; p < 0.001). Comparisons were consistent across subgroups of age, infectious diagnoses, and comorbidities.ConclusionsThe Adult Sepsis Event's eSOFA organ dysfunction criteria identify a smaller, more severely ill sepsis cohort compared with the Sequential Organ Failure Assessment score, but with good overlap and similar clinical characteristics. Adult Sepsis Events may facilitate wide-scale automated sepsis surveillance that tracks closely with the more complex Sepsis-3 criteria.
Project description:Gene-gene epistatic interactions likely play an important role in the genetic basis of many common diseases. Recently, machine-learning and data mining methods have been developed for learning epistatic relationships from data. A well-known combinatorial method that has been successfully applied for detecting epistasis is Multifactor Dimensionality Reduction (MDR). Jiang et al. created a combinatorial epistasis learning method called BNMBL to learn Bayesian network (BN) epistatic models. They compared BNMBL to MDR using simulated data sets. Each of these data sets was generated from a model that associates two SNPs with a disease and includes 18 unrelated SNPs. For each data set, BNMBL and MDR were used to score all 2-SNP models, and BNMBL learned significantly more correct models. In real data sets, we ordinarily do not know the number of SNPs that influence phenotype. BNMBL may not perform as well if we also scored models containing more than two SNPs. Furthermore, a number of other BN scoring criteria have been developed. They may detect epistatic interactions even better than BNMBL.Although BNs are a promising tool for learning epistatic relationships from data, we cannot confidently use them in this domain until we determine which scoring criteria work best or even well when we try learning the correct model without knowledge of the number of SNPs in that model.We evaluated the performance of 22 BN scoring criteria using 28,000 simulated data sets and a real Alzheimer's GWAS data set. Our results were surprising in that the Bayesian scoring criterion with large values of a hyperparameter called ? performed best. This score performed better than other BN scoring criteria and MDR at recall using simulated data sets, at detecting the hardest-to-detect models using simulated data sets, and at substantiating previous results using the real Alzheimer's data set.We conclude that representing epistatic interactions using BN models and scoring them using a BN scoring criterion holds promise for identifying epistatic genetic variants in data. In particular, the Bayesian scoring criterion with large values of a hyperparameter ? appears more promising than a number of alternatives.
Project description:BackgroundThe prognostic role of what a surgeon observes in the abdomen of patients with complicated intra-abdominal infection (cIAI) is largely unknown. The aim of this prospective study was to systemically analyze components of the intra-abdominal view (IAV) and their association to severe complicated intra-abdominal sepsis (SCIAS) or mortality.MethodsThe study cohort consisted of adult patients with cIAI. The operating surgeon filled a paper form describing the intra-abdominal view. Demographics, operative details, and preoperative physiological status were collected. Descriptive, univariate, and multivariate statistical analyses were performed, and a new score was developed based on regression coefficients. The primary outcome was a composite outcome of SCIAS or 30-day mortality, in which SCIAS was defined as organ dysfunctions requiring intensive care unit admission.ResultsA total of 283 patients were analyzed. The primary outcome was encountered in 71 (25%) patients. In the IAV, independent risk factors for the primary outcome were fecal or bile as exudate (odds ratio (OR) 1.98, 95% confidence interval 1.05-3.73), diffuse peritonitis (OR 2.15, 1.02-4.55), diffuse substantial redness of the peritoneum (OR 5.73, 2.12-15.44), and a non-appendiceal source of cIAI (OR 11.20, 4.11-30.54). Based on these factors, an IAV score was developed and its performance analyzed. The area under the receiver operating characteristic for the IAV score was 0.81. The IAV score also correlated significantly with several outcomes and organ dysfunctions.ConclusionsThe extent of peritonitis, diffuse substantial redness of the peritoneum, type of exudate, and source of infection associate independently with SCIAS or mortality. A high IAV score associates with mortality and organ dysfunctions, yet it needs further external validation. Combining components of IAV into comprehensive scoring systems for cIAI patients may provide additional value compared to the current scoring systems.Trial registrationThe study protocol was retrospectively registered on April 4, 2016, right after the first enrolled patient at Clinicaltrials.gov database (NCT02726932).
Project description:Mice underwent cecal ligation and puncture (19 GA with concurrent administration of imipenem), sham operation, or were unoperated. 14 days after operation, microglia were isolated by fluorescent activated cell sorting for CD11b+/CD45mid/CD64+ cells. For each sample, the brains of 3 mice were pooled. RNA was then isolated for transcriptome analysis.
Project description:A 6-year-old girl presented with intermittent abdominal pain, without jaundice and a palpable mass in the epigastrium. Preoperative imaging and upper endoscopy suggested duodenal duplication. During surgery, the patient was diagnosed with a rare type of choledochal cyst-choledochocele (type 3b). The authors emphasize that, in children, choledochocele should be included in the differential diagnosis of cystic lesions located in the duodenal area and the head of the pancreas area, regardless of jaundice or abnormal liver function. Since mucosal histology showing duodenal mucosa did not match the final diagnosis, we suggest that three criteria should be met for the diagnosis of a choledochocele to be diagnosed: (1) a cyst protruding into the duodenal lumen; (2) filling with contrast during cholangiography and (3) a filling defect on X-ray barium meal.
Project description:BackgroundBacteraemia is associated with high morbidity and mortality, with delayed antibiotic treatment associated with poorer outcomes. Early identification is challenging, but clinically important. Multiple scoring systems have been developed to identify individuals in the broader categories of sepsis. We designed this study to assess the performance of existing scoring systems and pathways-CEC SEPSIS KILLS pathway (an Australian sepsis care package), quick sequential organ failure score (qSOFA), systemic inflammatory response syndrome (SIRS) and the Shapiro criteria.MethodsThis was a retrospective cohort study performed in two metropolitan hospitals in NSW, consisting of adult patients (> 18 years) with positive blood cultures containing a true pathogen and patients matched by age without positive blood cultures. Performance (sensitivity, specificity, and mortality prediction) of recognised sepsis and bacteraemia criteria and pathways-qSOFA, SIRS, Shapiro criteria and CEC SEPSIS KILLS pathway in the first 4 h following ED triage was assessed.ResultsThere were 251 patients in each cohort. Sepsis-related mortality was higher in the bacteraemic group (OR 0.4, p = 0.03). Of the criteria studied, the modified Shapiro criteria had the highest sensitivity (88%) with modest specificity (37.85%), and qSOFA had the highest specificity (83.67%) with poor sensitivity (19.82%). SIRS had reasonable sensitivity (82.07%), with poor sensitivity (20.72%). The CEC SEPSIS pathway sensitivity of 70.1% and specificity of 71.1%. The SEPSIS KILLS was activated on only 14% of bacteraemic patients.ConclusionThe performance of all scoring systems and pathways was suboptimal in the identification of patients at risk of bacteraemia presenting to the emergency department.
Project description:PurposeTo compare the mortality rates between culture-positive and culture-negative sepsis in complicated intra-abdominal infections (cIAI) and investigate the predictors of culture-positivity and their causative microorganisms.Materials and methodsThe medical records of 1581 adult patients who underwent emergency gastrointestinal surgery between January 2013 and December 2018 were reviewed retrospectively. A total of 239 patients with sepsis or septic shock who were admitted to an emergency department, underwent emergency surgery for cIAI, and needed postoperative intensive care unit care were included and divided into two groups according to their initial blood and peritoneal culture results.ResultsAmong the 239 patients, 200 were culture-negative and 39 were culture-positive. The culture-positive group had higher in-hospital (35.9% vs 14.5%; P = .001) and 30-day mortality (30.8% vs 12.0%; P = .003) than the culture-negative group. Colon involvement (OR 4.211; 95% CI 1.909-9.287; P < .001) and higher Sequential Organ Failure Assessment (SOFA) score (OR 1.169; 95% CI 1.065-1.282; P = .001) were shown to be the predictors of culture-positive sepsis for cIAI. Regarding antibiotic sensitivity, 31.6% of the gram-positive bacteria were methicillin-resistant and 42.1% of the gram-negative bacteria were extended spectrum β-lactamase-producing Enterobacteriaceae.ConclusionsPatients with cIAI had higher mortality rates in culture-positive sepsis than in culture-negative sepsis. High SOFA score and colon involvement were the risk factors associated with culture-positivity. The most common single species grown in the blood or peritoneal cultures was Escherichia coli, and the most common group was Gram-positive cocci.
Project description:BackgroundCurrently, there is a lack of clear definition for neonatal sepsis. The Pediatric Committee of the European Medicines Agency (EMA) developed consensus criteria to ensure a standardization for neonatal sepsis definition. However, there is no evidence supporting the accuracy of the EMA sepsis criteria in neonatal sepsis diagnosis. The main objective of this study was to evaluate the diagnostic accuracy of EMA sepsis criteria for proven neonatal sepsis.MethodsA multicenter prospective cohort study was conducted from October 2015 to November 2018. Infants with a gestational age over 34th weeks, diagnosed with clinical sepsis and received antibiotics according to the EMA criteria or experienced neonatologists' opinion were included. Blood culture or multiplex real time-PCR or 16S-rRNA positive infants were accepted as "proven sepsis". The predictive performance of EMA criteria for proven sepsis was evaluated by sensitivity, specificity, accuracy, and area under the curve measures of receiver operator characteristic curves. Data-mining methods were used for further analysis.ResultsAmong the 245 included infants, the EMA criteria were positive in 97 infants (39.6%), while proven sepsis was diagnosed in 113 infants (46.1%). The sensitivity, specificity, and accuracy of the EMA criteria for proven sepsis were 44.2% (95%CI: 34.9-53.9), 64.4% (95%CI: 55.6-72.5), 55.1% (95%CI: 46.6-59.4) respectively. None of the clinical and laboratory parameters had sufficient performance individually in terms of sensitivity, specificity and accuracy measures. The diagnostic performance was similar when different clinical findings were added to the EMA sepsis criteria or assessment of the score was interpreted in different ways.ConclusionsResults highlighted that clinician opinion and standard laboratory tests are limited in the neonatal sepsis diagnosis. The EMA criteria also did not efficiently meet the diagnostic accuracy measures for neonatal sepsis. A predictive sepsis definition and rapid bedside point-of care tests are urgently needed.
