Differential Diagnosis Of Sepsis Research Articles

Early prediction of sepsis-induced respiratory tract infection using a biomarker-based machine-learning algorithm

Early and differential diagnosis of sepsis is essential to avoid unnecessary antibiotic use and further reduce patient morbidity and mortality. Here, we aimed to identify predictors of sepsis and advance a machine-learning strategy to predict sepsis-induced respiratory tract infection (RTI). Patients with sepsis and RTI were selected via retrospective analysis, and essential population characteristics and laboratory parameters were recorded. To improve the performance of the primary model and avoid over-fitting, a recursive feature elimination with cross-validation (RFECV) strategy was used to screen the optimal subset of biomarkers and construct nine machine-learning models based on this subset; the average accuracy, precision, recall, and F1-score were used for evaluation of the models. We identified 430 patients with sepsis and 686 patients with RTI. A total of 39 features were collected, with 23 features identified for initial model construction. Using the RFECV algorithm, we found that the XGBoost classifier, which only needed to include seven biomarkers, demonstrated the best performance among all prediction models, with an average accuracy of 89.24 ± 2.28, while the Ridge classifier, which included 11 biomarkers, had an average accuracy of only 83.87 ± 4.69. The remaining models had prediction accuracies greater than 88%. We developed nine models for predicting sepsis using a strategy that combined RFECV with machine learning. Among these models, the XGBoost classifier, which included seven biomarkers, showed the best performance and highest accuracy for predicting sepsis and may be a promising tool for the timely identification of sepsis.

High-mortality epizootic Mycobacterium ulcerans ecovar Liflandii in a colony of Zaire Dwarf Clawed Frogs (Hymenochirus boettgeri).

Mycobacterium ulcerans ecovar Liflandii (MuLiflandii) was identified as the causative agent of mycobacteriosis in a research colony of Zaire dwarf clawed frogs (Hymenochirus boettgeri) at the University of Michigan. Clinical presentation included lethargy, generalized septicemia, cutaneous granulomas, coelomic effusion, and acute mortality. Identification of the mycobacterial species was based on molecular, microbiological, and histopathologic characteristics. These findings indicate that MuLiflandii is a primary cause of morbidity and mortality in Zaire dwarf clawed frogs and should be considered in the differential diagnosis of sepsis and coelomic effusion in amphibians. Mycobacterial speciation is important given the variability in pathogenesis within the family Mycobacteriaceae and the implications for both animal and human health as potential zoonoses. The Zaire dwarf clawed frog is a species common in the pet trade, and these findings provide consideration for this pathogen as a potentially important public health concern. This is the first report of MuLiflandii infection in the genus Hymenochirus and illustrates the diagnostic challenges of differentiating among both mycolactone-producing mycobacteria and Mycobacterium marinum. Furthermore, we demonstrate the utility of environmental sampling for this pathogen within the tank system, suggesting this mode of sampling could replace the need for direct frog surveillance.

Metabolomics-based study of potential biomarkers of sepsis

The purpose of our study was to explore potential characteristic biomarkers in patients with sepsis. Peripheral blood specimens from sepsis patients and normal human volunteers were processed by liquid chromatography-mass spectrometry-based analysis. Outlier data were excluded by principal component analysis and orthogonal partial least squares-discriminant analysis using the metabolomics R software package metaX and MetaboAnalyst 5.0 (https://www.metaboanalyst.ca/home.xhtml) online analysis software, and differential metabolite counts were identified by using volcano and heatmaps. The obtained differential metabolites were combined with KEGG (Kyoto Gene and Kyoto Encyclopedia) analysis to screen out potential core differential metabolites, and ROC curves were drawn to analyze the changes in serum metabolites in sepsis patients and to explore the potential value of the metabolites in the diagnosis of sepsis patients. By metabolomic analysis, nine differential metabolites were screened for their significance in guiding the diagnosis and differential diagnosis of sepsis namely: 3-phenyl lactic acid, N-phenylacetylglutamine, phenylethylamine, traumatin, xanthine, methyl jasmonate, indole, l-tryptophan and 1107116. In this study, nine metabolites were finally screened based on metabolomic analysis and used as potential characteristic biomarkers for the diagnosis of sepsis.

EP-157 Pyocystis: A silent complication of a supravesical urinary diversion

Abstract Aim Pyocystis is an important yet overlooked rare complication of a non-functioning urinary bladder. It is due to collection, liquefaction and decomposition of shed bladder epithelium, resulting in accumulation of pus in the bladder causing sepsis. We describe a case of Pyocystis in a patient with bilateral nephrostomies who presented with urosepsis multiple times due to this complication. Case Report A 78-year-old man, known case of Ca Prostate wit bilateral nephrostomies warranted multiple subsequent hospital admissions in one month due to urosepsis presenting with fever, urethral discharge, suprapubic pain and very high inflammatory markers. He underwent a CT Abdomen & Pelvis which revealed markedly distended bladder despite nephrostomies in place. Upon catheterization, no urine output was observed which raised concerns. An attempt at bladder washout displayed a large amount of thick foul-smelling pus which was aspirated. This was sent for culture and patient was commenced on appropriate IV antibiotics. After a thorough bladder wash out under flexible cystoscopy, patient was eventually discharged on a long-term catheter with regular bladder washouts in community as required. Patient was successfully managed on conservative treatment. Conclusion Pyocystis can sometimes be a missed complication of urinary diversion or a non-functioning bladder that can present silently under sepsis and should therefore be considered as a differential diagnosis of sepsis in patient with supravesical urinary diversion. We wanted to highlight this condition which if left undiagnosed will progress to severe sepsis and possible death. Hence prompt intervention and aggressive management is vital. Treatment for this complication requires catheterization, bladder irrigation and antibiotics.

In the differential diagnosis of sepsis and hemophagocytic lymphohistiocytosis, procalcitonin and C-reactive protein (CRP) may be as determinant as ferritin

Background: Hemophagocytic lymphohistiocytosis (HLH) and sepsis frequently appear as overlapping diagnoses in intensive care units. It is necessary to distinguish HLH, which has a very high mortality, from sepsis. In this study, we wanted to draw attention to the potential of procalcitonin (PCT) and C-Reactive Protein (CRP) as a marker like ferritin in differential diagnosis. Thus, HLH can be diagnosed as early as possible and the necessary aggressive immunosuppressive therapy can be added to the existing treatment.
 Methods: All of the patients in the sepsis clinic who meet the HLH criteria Group HLH; patients not meeting the HLH criteria were defined as Group non-HLH. Files of all patients were reviewed in regard to HLH diagnosis criteria and H score.
 Results: There were 16 patients in Group HLH and 15 in Group non-HLH. CRP and PCT levels were significantly lower (p: 0.007 and p

Early congenital syphilis, an old disease still occurring in the modern era: case report and literature review

Introduction. Congenital syphilis is a well-known infectious disease caused by the passing of Treponema pallidum from the infected mother to the fetus. In most cases, it leads to fetal death. Still, in the survivors, it can manifest clinically as early congenital syphilis in the first two years of life or late congenital syphilis afterward. Current epidemiological data suggest that the incidence is very low in developed coun­tries due to screening. Case report. We report the case of a 2-month-old male infant who presented with a sepsis-like picture, generalized edema, and hepatosplenomegaly. He had elevated inflammatory markers (C-reactive protein and procalcitonin), acute kidney injury, and fulminant liver failure. The radiographic exam revealed periostitis of the long bones. The brain magnetic resonance imaging (MRI) revealed encephalitis, ventriculomegaly and cerebral atrophy, suggesting neurosyphilis. The diagnosis of con­ge­ni­tal syphilis was confirmed by the positive Venereal Disease Research Laboratory (VDRL) test. We initiated the treatment with penicillin, then we associated ceftriaxone for neurological involvement. He also needed blood trans­fu­sions due to severe anemia and thrombocytopenia, diu­re­tics, and hydrocortisone treatment. Conclusions. There are cases when screening methods are omitted, therefore congenital syphilis should always be considered in the differential diagnosis of sepsis in young infants.

Malaria congénita por Plasmodium falciparum

La malaria congénita (MC) es la infección por Plasmodium spp adquirida in útero o durante el parto y sus manifestaciones clínicas son inespecíficas. Puede causar enfermedad grave en la embarazada y en el recién nacido.Objetivo: describir dos casos de MC causados por Plasmodium falciparum, diagnóstico diferencial de sepsis en recién nacidos de gestantes que hayan visitado o residan en áreas endémicas para malaria.Casos Clínicos: Neonatos de sexo femenino, nacidos en área no endémica para malaria, diagnosticados con sepsis neonatal y tratados con antibióticos sin respuesta clínica. Después de la primera semana de vida la gota gruesa identificó trofozoítos de Plasmodium falciparum y los neonatos recibieron tratamiento con quinina intravenosa con mejoría. Las madres de las recién nacidas tuvieron malaria en el embarazo, una de ellas recibió tratamiento y estaba asintomática y otra tenía malaria complicada al momento del parto.Conclusiones: La MC puede causar enfermedad neonatal grave con manifestaciones clínicas inespecíficas y similares a la sepsis, el tratamiento oportuno disminuye el riesgo de malaria complicada. Es un diagnóstico diferencial en recién nacidos de mujeres con malaria durante el embarazo o gestantes que visiten o residan en áreas endémicas.

Improvement in detecting sepsis using leukocyte cell population data (CPD).

Background The cell population data (CPD) parameters reported by XN analyzers (Sysmex Corporation, Kobe, Japan) reflect the size and internal structure of leukocytes. We explored whether CPD values could contribute to recognize those patients with fever at risk to develop sepsis. A profile of sepsis was developed combining CPD parameters and other markers. Methods We recruited 295 patients at the onset of fever, with infection confirmed by positive cultures. We studied the diagnostic performance of the CPD parameters in the differential diagnosis of sepsis vs. non-systemic bacterial infection using receiver operating characteristic (ROC) curve analysis. Additionally, the K-means unsupervised clustering method was applied. Once the clusters had been defined, the relationship between them and the CPD parameter values was assessed with the non-parametric Wilcoxon test. Lastly, the relationship between the clusters obtained and the categorical variables was examined with the χ2-test (or Fisher's exact test). Results ROC analysis demonstrated that NE-FSL, NE-WY, NE-WZ and MO-WZ had areas under the curve (AUCs) >0.700 for predicting sepsis. Using the K-means clustering algorithm, 80 patients (66.67%) were assigned to Cluster 1 and the others to Cluster 2. Out of 80 of patients in Cluster 1, 45 (56.25%) presented a PCT value ≥2 ng/mL, whereas almost 80% of Cluster 2 patients had a PCT <2 ng/mL. Cluster 1 was characterized by high NE-SFL, NE-WY, MO-X, MO-WX and MO-Z values (p<0.05). Conclusions CPD related to monocyte complexity and neutrophil activation were found to be significant, with high values suggesting sepsis.

Клинико-морфологическая дифференциация сепсиса во время родов и в послеродовом периоде

Клинико-морфологическая дифференциация сепсиса во время родов и в послеродовом периоде

Comparison of Procalcitonin and C-reactive Protein in Differential Diagnosis of Sepsis and Severe Sepsis in Emergency Department

Objective: Sepsis and severe sepsis (sepsis accompanied by acute organ dysfunction) are leading causes of death worldwide. In this study, our aim was to investigate utility of biomarkers commonly used in diagnosis of sepsis in discriminating these two entities. Methods: Two-hundred and three patients involved were divided into 2 subgroups as sepsis and severe sepsis according to Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Then groups were compared according to clinical and laboratory (including C-reactive protein (CRP) and procalcitonin (PCT) levels) characteristics. Results: Of 203 patients included into the study, 124 (61.1%) were male and 79 (38.9%) were female. The most common reason for sepsis was urinary tract infection (n=64, 31.5%), followed by catheter infection (n=16, 7.9%) and pneumonia (n=14, 6.9%). Escherichia coli was the most common agent in both blood and urinary cultures. Majority of the patients were treated with ceftriaxone (n=33, 16.3%), followed by meronem/dapson (n=25, 12.3%). In both groups, CRP and PCT levels were high, even higher in severe sepsis group. However, any statistical significance could not be determined between groups. Mortality rate in sepsis patients was 6.4%. Conclusion: Plasma levels of both markers elevate in sepsis and severe sepsis. It was determined that CRP and PCT is higher in severe sepsis than in sepsis. However, the difference is not statistically significant. Plasma levels of CRP and PCT are not useful in differential diagnosis of sepsis and severe sepsis.

Delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen: a case report

BackgroundHigh-dose chemotherapy with autologous stem cell rescue is commonly used for the treatment of relapsed germ cell tumors. We report the first case of delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen.Case presentationWe report a case of a 21-year-old African-American man diagnosed with relapsed non-seminomatous germ cell tumor who received high-dose chemotherapy with carboplatin and etoposide following TIGER trial arm B off-protocol. His course was complicated by muscle pain and rhabdomyolysis after cycle 4 on day +12 after infusion of autologous stem cells. To the best of our knowledge, this complication has not been reported with this regimen. A differential diagnosis of sepsis and neutropenic fever along with side effects of high-dose chemotherapy were considered, but based on the timing of events, it was concluded that the etiology of rhabdomyolysis is high-dose chemotherapy. Rhabdomyolysis was successfully treated with hydration and did not recur during subsequent cycle 5.ConclusionsDelayed rhabdomyolysis after high-dose chemotherapy with paclitaxel, ifosfamide, carboplatin, and etoposide regimen has not been previously reported and needs to be considered for preventive strategy and prompt diagnosis and treatment to avoid renal complications. Physicians should have a low threshold to check creatine kinase enzymes in patients with unexplained muscle pain or renal insufficiency after high-dose chemotherapy.

Pediatric Fulminant Leptospirosis Complicated by Pericardial Tamponade, Macrophage Activation Syndrome and Sclerosing Cholangitis.

Leptospirosis is a zoonotic infectious disease caused by pathogenic spirochetes of the genus Leptospira. Although it is usually asymptomatic and self-limited, severe potentially fatal illness accompanied by multi-organ failure may occur. Here we report an unusual case of severe leptospirosis successfully treated with continuous venovenous hemofiltration (CVVHF) and therapeutic plasma exchange (TPE). The patient presented with pericardial tamponade, renal failure and macrophage activation syndrome, and later suffered prolonged jaundice and sclerosing cholangitis during hospitalization in the pediatric intensive care unit (PICU). To the best of our knowledge, sclerosing cholangitis due to leptospirosis has not been reported in the literature. Leptospirosis should be kept in mind in the differential diagnosis of sepsis and septic shock with fever, thrombocytopenia, jaundice and renal failure. TPE and CVVHF should start early after the diagnosis of leptospirosis with multiorgan failure.

Diagnostic and prognostic value of procalcitonin and sTREM-1 levels in sepsis

Sepsis is still a major cause of morbidity and mortality despite the improvements in diagnosis and treatment. The aim of this study was to investigate the values of procalcitonin and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the differential diagnosis of patients with sepsis and noninfectious systemic inflammatory response syndrome (NI-SIRS) and measure their importance in the prognosis of patients with sepsis. This prospective study included 41 NI-SIRS and 33 sepsis patients hospitalized in Celal Bayar University Hospital, Manisa, Turkey. Blood samples were taken from NI-SIRS patients on days 0 and 3 and from sepsis patients on days 0, 3, 4, 7, and 14. Clinical status of the patients was determined with the SOFA scoring system. The SOFA scoring system and procalcitonin and sTREM-1 measurements were significant in the differential diagnosis of sepsis and NI-SIRS patients. The SOFA scoring system was considered the most important indicator in determining the prognosis of sepsis patients. Procalcitonin and sTREM-1 levels increased progressively in nonsurvivors and decreased in survivors, but changes were statistically insignificant. In the differentiation of sepsis and NI-SIRS, and evaluation of the prognosis of sepsis, combined measurements of procalcitonin and sTREM-1 levels are important.

ABSTRACT 321

Background and aims: Vein of Galen Malformation (VGAM) is a rare condition. VGAM is hallmarked by multiple arterio-venous shunts from choroidal vessels into median prosencephalic vein of Markoswki. Arterial-venous shunt at choroidal vessels leads to overload of venous system and high cardiac output failure. When untreated, this malformation has poor outcome leading to death. Aims: We present two newborn cases of VGAM who presented with signs of cardiomegaly and a normally structured heart. Methods: Case I: One-day old newborn who presented with tonic-clonic seizures and cardiac failure (cardiomegaly and hepatomegaly). Initial cranial ultrasound scan (CUSS) revealed arterio-venous malformation (AVM) confirmed in Head CT with areas of cerebral infarction. Patient underwent endovascular embolisation which was complicated with diffuse subarachnoid hemorrhage. Patient developed fixed pupils, extensive brain injury and died. Case II: Four-day old baby who presented with poor feeding and signs of cardiac failure (cardiomegaly and refractory metabolic acidosis). Routine CUSS revealed a midline AVM suggesting VGAM. Patient underwent endovascular embolisation complicated by pulmonary embolism and extensive hypoxic brain injury leading to death. Results: We had differentialdiagnosis of sepsis, congenital heart defect, AVM and metabolic disorder. Echocardiographyshowed normally structured heart. Case I had neurological symptoms but Case IIhad normal neurological examination and AVM was found in a routine CUSS. Both cases confirmed the poor prognosis of this congenital condition. Conclusions: We recommend routine CUSS in newborns with unclear diagnosis of cardiac failure. Complete neurological examination (including auscultation of the fontanel) and CUSS as a non-invasive screening method should be performed in all cardiac patients.

Emergence of sporadic non-clustered cases of hospital-associated listeriosis among immunocompromised adults in southern Taiwan from 1992 to 2013: effect of precipitating immunosuppressive agents.

BackgroundSporadic non-clustered hospital-associated listeriosis is an emerging infectious disease in immunocompromised hosts. The current study was designed to determine the impact of long-term and precipitating immunosuppressive agents and underlying diseases on triggering the expression of the disease, and to compare the clinical features and outcome of hospital-associated and community-associated listeriosis.MethodsWe reviewed the medical records of all patients with Listeria monocytogenes isolated from sterile body sites at a large medical center in southern Taiwan during 1992–2013. Non-clustered cases were defined as those unrelated to any other in time or place. Multivariable regression analysis was used to determine factors associated with prognosis.ResultsThirty-five non-clustered cases of listeriosis were identified. Twelve (34.2%) were hospital-associated, and 23 (65.7%) were community-associated. The 60-day mortality was significantly greater in hospital-associated than in community-associated cases (66.7% vs. 17.4%, p = 0.007). Significantly more hospital-associated than community-associated cases were treated with a precipitating immunosuppressive agent within 4 weeks prior to onset of listeriosis (91.7% vs. 4.3%, respectively p < 0.001). The median period from the start of precipitating immunosuppressive treatment to the onset of listeriosis-related symptoms was 12 days (range, 4–27 days) in 11 of the 12 hospital-associated cases. In the multivariable analysis, APACHE II score >21 (p = 0.04) and receipt of precipitating immunosuppressive therapy (p = 0.02) were independent risk factors for 60-day mortality.ConclusionsSporadic non-clustered hospital-associated listeriosis needs to be considered in the differential diagnosis of sepsis in immunocompromised patients, particularly in those treated with new or increased doses of immunosuppressive agents.

Bacillus cereus septicemia in a patient with acute lymphoblastic leukemia: A case report and review of the literature

Bacillus cereus is an aerobic Gram-positive, spore-forming, rod-shaped bacterium that is responsible for foodborne illnesses. We report on a 15-year-old girl with B-cell acute lymphoblastic leukemia, who fell into a somnolent state after presenting with a 12-hour history of fever, muscle soreness, myalgia in both calves, sore throat, and vomiting. Fulminant septicemic syndrome caused by B. cereus was finally identified. The aim of this work is the introduction of B. cereus as a differential diagnosis of sepsis in patients with acute leukemia in induction chemotherapy, to prevent delayed treatment.

Diagnostic Value of Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Critically-Ill, Postoperative Patients With Suspected Sepsis

IntroductionThe lack of specific clinical manifestations for sepsis frequently leads to delayed diagnosis. Identification of sensitive and specific indicators that can be easily assessed, accurately reflect infection severity and prognosis and are clinically important in the differential diagnosis of sepsis, is of great significance. The purpose of this study was to evaluate the diagnostic and prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in high selected, mostly postoperative patients with suspicion of sepsis. MethodsFifty-two consecutive patients hospitalized in a surgical intensive care unit with suspicion of infection included 14 patients with systemic inflammatory response syndrome (SIRS), 9 patients with sepsis, 14 patients with severe sepsis and 15 patients with septic shock. Within 12 hours after enrollment, plasma levels of sTREM-1, procalcitonin (PCT), tumor necrosis factor (TNF)-α, interleukin-6 and C-reactive protein were measured and compared between subgroups to elucidate their diagnostic and prognostic values. ResultsPlasma sTREM-1 levels were higher in patients with sepsis than in patients with SIRS (111.7 versus 64.1 pg/mL, P<0.05), with sensitivity, specificity and a predictive value higher than those of PCT and TNF-α. Plasma sTREM-1 levels were significantly different between the sepsis, severe sepsis and septic shock subgroups (P<0.001). For the receiver operating characteristic for predicting death, the area under the curve of sTREM-1 was 0.861, similar to that of TNF-α, blood lactate and PCT (0.848, 0.719 and 0.706, respectively). ConclusionsIn postoperative patients, plasma levels of sTREM-1 and TNF-α could differentiate sepsis from SIRS. sTREM levels also reflected the severity of sepsis and were noninferior for prognosis compared with other biochemical indexes.

Utilidad de los marcadores biológicos en el diagnóstico diferencial de la sepsis en el postoperatorio del trasplante hepático

The use of biological markers is developing in the field of liver transplant. Biomarkers are being studied in different contexts: 1) detection of tolerant patient; 2) recurrence of hepatitis C virus; 3) diagnosis and prognosis of liver cancers, and 4) diagnosis of infection.The immunological changes occurring in the transplant patient given their previous cirrhotic condition, the immunosuppression received, and possible intercurrent diagnoses (rejection, recurrence of hepatitis C virus…) highlight the importance of finding useful biomarkers in clinical practice to diagnose infection. After a review of the usefulness of biomarkers, we should perhaps add the serial determination of C-reactive protein in the immediate post-operative period, and later on procalcitonin, in the infection diagnosis algorithm. Although the determination of procalcitonin appears to be the most reliable biomarker in the differential diagnosis of sepsis and rejection, the studies carried out make it difficult to establish conclusions on its real clinical usefulness.

A case of systemic-onset juvenile idiopathic arthritis complicated with sepsis -Usefulness of cytokine profile for the differentiation between macrophage activation syndrome and sepsis-

The differential diagnosis of macrophage activation syndrome (MAS) and sepsis must be considered in the clinical course of systemic-onset juvenile idiopathic arthritis (s-JIA) with sudden onset of high-grade fever and abnormal laboratory findings, including leukocytopenia, thrombocytopenia, and coagulopathy. In this report, we describe the case of a 17-month-old girl diagnosed with s-JIA complicated with sepsis. Her serum interleukin (IL)-18 level was significantly elevated throughout the clinical course. Furthermore, compared to other MAS patients, she showed a significantly elevated serum IL-6 level and procalcitonin in sepsis. Therefore, our results suggest that a patient's cytokine profile may be a useful indicator of disease activity and may thus help in the differential diagnosis of sepsis and MAS in s-JIA.

Thrombotic Thrombocytopenic Purpura

THROMBOTIC Thrombocytopenic Purpura (TTP) is characterized by fever, renal failure, thrombocytopenia, neurological involvement and microangiopathic anemia [1,2]. Plasma exchange has improved the prognosis and outcome of diagnosed early [3] of TTP. Since there is no specific marker or diagnotic test for diagnosis of TTP, the index of clinical suspicion has to be high. Here we describe a case with an unusual presentation where we had to consider differential diagnosis of sepsis with DIC, HELLP syndrome, HUS, and vasculitis.