Computational Intelligence Method for Detection of White Blood Cells Using Hybrid of Convolutional Deep Learning and SIFT.

Infection diseases are among the top global issues with negative impacts on health, economy, and society as a whole. One of the most effective ways to detect these diseases is done by analysing the microscopic images of blood cells. Artificial intelligence (AI) techniques are now widely used to detect these blood cells and explore their structures. In recent years, deep learning architectures have been utilized as they are powerful tools for big data analysis. In this work, we are presenting a deep neural network for processing of microscopic images of blood cells. Processing these images is particularly important as white blood cells and their structures are being used to diagnose different diseases. In this research, we design and implement a reliable processing system for blood samples and classify five different types of white blood cells in microscopic images. We use the Gram-Schmidt algorithm for segmentation purposes. For the classification of different types of white blood cells, we combine Scale-Invariant Feature Transform (SIFT) feature detection technique with a deep convolutional neural network. To evaluate our work, we tested our method on LISC and WBCis databases. We achieved 95.84% and 97.33% accuracy of segmentation for these data sets, respectively. Our work illustrates that deep learning models can be promising in designing and developing a reliable system for microscopic image processing.

Ferritin - from iron, through inflammation and autoimmunity, to COVID-19.

While it took decades to arrive to a conclusion that ferritin is more than an indicator of iron storage level, it took a short period of time through the COVID-19 pandemic to wonder what the reason behind high levels of ferritin in patients with severe COVID-19 might be. Unsurprisingly, acute phase reactant was not a satisfactory explanation. Moreover, the behavior of ferritin in patients with severe COVID-19 and the subsequent high mortality rates in patients with high ferritin levels necessitated further investigations to understand the role of ferritin in the diseases. Ferritin was initially described to accompany various acute infections, both viral and bacterial, indicating an acute response to inflammation. However, with the introduction of the hyperferritinemic syndrome connecting four severe pathological conditions such as adult-onset Still's disease, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and septic shock added another aspect of ferritin where it could have a pathogenetic role rather than an extremely elevated protein only. In fact, suggesting that COVID-19 is a new member in the spectrum of hyperferritinemic syndrome besides the four mentioned conditions could hopefully direct further search on the pathogenetic role of ferritin. Doubtlessly, improving our understanding of those aspects of ferritin would enormously contribute to better coping with severe diseases in terms of treatment and prevention of complications. The origin, history, importance, and the advances of searching the role of ferritin in various pathological and clinical processes are presented hereby in our article. In addition, the implications of ferritin in COVID-19 are addressed.

Lactate dehydrogenase to albumin ratio as a prognostic factor for patients with severe infection requiring intensive care.

ABSTRACT: This study was performed to verify whether lactate dehydrogenase to albumin (LDH/ALB) ratio could be used as an independent prognostic factor in patients with severe infection requiring intensive care.We reviewed electronic medical records of patients hospitalized to the intensive care unit via the emergency department with a diagnosis of infection between January 2014 and December 2019. From the collected data, ALB-based ratios (LDH/ALB, blood urea nitrogen to albumin, C-reactive protein to albumin, and lactate to albumin ratios) and some severity scores (modified early warning score, mortality in emergency department sepsis score [MEDS], and Acute Physiology And Chronic Health Evaluation II [APACHE II] score) were calculated. LDH/ALB ratio for predicting the in-hospital mortality was compared with other ALB-based ratios and severity scales by univariable and receiver-operating characteristics curve analysis. Modified severity scores by LDH/ALB ratio and multivariable logistic regression were used to verify the independence and usefulness of the LDH/ALB ratio.The median LDH/ALB ratio was higher in non-survivors than survivors (166.9 [interquartile range: 127.2-233.1] vs 214.7 [interquartile range: 160.2-309.7], P < .001). The area under the receiver-operating characteristics curve of the LDH/ALB ratio (0.642, 95% confidence interval: 0.602-0.681, P < .001) was not lower than that of other ALB-based ratios and severity scores. From multivariable logistic regression, LDH/ALB ratio was independently associated with in-hospital mortality (odds ratio = 1.001, 95% confidence interval: 1.000-1.002, P = .047). Area under the receiver-operating characteristics curves of MEDS and APACHE II scores were improved by modification with LDH/ALB ratio (MEDS: 0.643 vs 0.680, P < .001; APACHE II score: 0.675 vs 0.700, P = .003).LDH/ALB ratio may be useful as the prognostic factor in patients with severe infection requiring intensive care.

Plasma calprotectin in the emergency department: a potential clinical biomarker for patients with infectious diseases.

Increased levels of plasma calprotectin are reported in patients with infectious diseases. However, the clinical usefulness of calprotectin as a biomarker to identify patients with infectious diseases in the emergency department (ED) setting has not been investigated. To study the ability of calprotectin to discriminate patients with acute infectious diseases and dyspnea from patients with other causes of acute dyspnea in the ED setting. Patients aged ≥18 years seeking ED during daytime on weekdays between March 2013 and July 2018, with acute dyspnea, were included. Participants (n = 1287) were triaged according to Medical Emergency Triage and Treatment System-Adult score (METTS-A) or Rapid Emergency Triage and Treatment System (RETTS), and blood samples were collected. The association between calprotectin and other markers of infectious diseases, i.e. biomarkers (CRP, leucocytes) and body temperature, was studied. The predictive value of calprotectin for the outcome of acute infection was evaluated with receiver operating characteristic (ROC) analysis. Univariate cross-sectional regression showed significant associations between calprotectin and leucocytes, CRP and body temperature. Patients with severe infections including pneumonia (n = 119) had significantly higher concentrations of calprotectin compared to patients with heart failure (n = 162) or chronic obstructive pulmonary disease (n = 183). When tested for the outcome of acute infection (n = 109), the area under the ROC curve (AUROC) was for CRP 0.83 and for calprotectin 0.78. Plasma calprotectin identifies infectious diseases in ED patients with acute dyspnea, and the clinical usefulness of Calprotectin in the ED has to be further studied.

Unboxing dendritic cells: Tales of multi-faceted biology and function.

Often referred to as the bridge between innate and adaptive immunity, dendritic cells (DCs) are professional antigen-presenting cells (APCs) that constitute a unique, yet complex cell system. Among other APCs, DCs display the unique property of inducing protective immune responses against invading microbes, or cancer cells, while safeguarding the proper homeostatic equilibrium of the immune system and maintaining self-tolerance. Unsurprisingly, DCs play a role in many diseases such as autoimmunity, allergy, infectious disease and cancer. This makes them attractive but challenging targets for therapeutics. Since their initial discovery, research and understanding of DC biology have flourished. We now recognize the presence of multiple subsets of DCs distributed across tissues. Recent studies of phenotype and gene expression at the single cell level have identified heterogeneity even within the same DC type, supporting the idea that DCs have evolved to greatly expand the flexibility of the immune system to react appropriately to a wide range of threats. This review is meant to serve as a quick and robust guide to understand the basic divisions of DC subsets and their role in the immune system. Between mice and humans, there are some differences in how these subsets are identified and function, and we will point out specific distinctions as necessary. Throughout the text, we are using both fundamental and therapeutic lens to describe overlaps and distinctions and what this could mean for future research and therapies.

Determining seropositivity-A review of approaches to define population seroprevalence when using multiplex bead assays to assess burden of tropical diseases.

BACKGROUND: Serological surveys with multiplex bead assays can be used to assess seroprevalence to multiple pathogens simultaneously. However, multiple methods have been used to generate cut-off values for seropositivity and these may lead to inconsistent interpretation of results. A literature review was conducted to describe the methods used to determine cut-off values for data generated by multiplex bead assays. METHODOLOGY/PRINCIPAL FINDINGS: A search was conducted in PubMed that included articles published from January 2010 to January 2020, and 308 relevant articles were identified that included the terms "serology", "cut-offs", and "multiplex bead assays". After application of exclusion of articles not relevant to neglected tropical diseases (NTD), vaccine preventable diseases (VPD), or malaria, 55 articles were examined based on their relevance to NTD or VPD. The most frequently applied approaches to determine seropositivity included the use of presumed unexposed populations, mixture models, receiver operating curves (ROC), and international standards. Other methods included the use of quantiles, pre-exposed endemic cohorts, and visual inflection points. CONCLUSIONS/SIGNIFICANCE: For disease control programmes, seropositivity is a practical and easily interpretable health metric but determining appropriate cut-offs for positivity can be challenging. Considerations for optimal cut-off approaches should include factors such as methods recommended by previous research, transmission dynamics, and the immunological backgrounds of the population. In the absence of international standards for estimating seropositivity in a population, the use of consistent methods that align with individual disease epidemiological data will improve comparability between settings and enable the assessment of changes over time.

Clinical application of cell-free next-generation sequencing for infectious diseases at a tertiary children's hospital.

BACKGROUND: Children affected by infectious diseases may not always have a detectable infectious etiology. Diagnostic uncertainty can lead to prolonged hospitalizations, inappropriately broad or extended courses of antibiotics, invasive diagnostic procedures, and difficulty predicting the clinical course and outcome. Cell-free plasma next-generation sequencing (cfNGS) can identify viral, bacterial, and fungal infections by detecting pathogen DNA in peripheral blood. This testing modality offers the ability to test for many organisms at once in a shotgun metagenomic approach with a rapid turnaround time. We sought to compare the results of cfNGS to conventional diagnostic test results and describe the impact of cfNGS on clinical care in a diverse pediatric population at a large academic children's hospital. METHODS: We performed a retrospective chart review of hospitalized subjects at a tertiary pediatric hospital to determine the diagnostic yield of cfNGS and its impact on clinical care. RESULTS: We describe the clinical application of results from 142 cfNGS tests in the management of 110 subjects over an 8-month study period. In comparison to conventional testing as a reference standard, cfNGS was found to have a positive percent agreement of 89.6% and negative percent agreement of 52.3%. Furthermore, 32.4% of cfNGS results were directly applied to make a clinical change in management. CONCLUSIONS: We demonstrate the clinically utility of cfNGS in the management of acutely ill children. Future studies, both retrospective and prospective, are needed to clarify the optimal indications for testing.

Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases.

Galectin-9 (Gal-9) is a ß-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.

Serum leptin level as a diagnostic and prognostic marker in infectious diseases and sepsis: A comprehensive literature review.

BACKGROUND: Infections and sepsis are common causes of morbidity and mortality, with an increasing incidence worldwide. Leptin is involved in the inflammatory process and may modulate the cytokine production, immune cell proliferation and endothelial function. There are conflicting results regarding alterations of leptin levels in infectious diseases and the outcome from sepsis.The aim of the current article is to provide an overview of the medical literature on the correlations between variations of leptin levels and infectious diseases and sepsis. METHODS: We performed an extensive literature search in PubMed and Google Scholar databases, using keywords to identify articles related to leptin in infectious diseases and sepsis. Searches were referenced using medical subject headings that included "leptin," "adipokines," "sepsis," "infectious diseases," "leptin deficiency," "leptin resistance" or "hyperleptinemia." The language of publication, journal, or country were not included as limitation criteria.Articles or abstracts containing adequate information, such as age, sex, anthropometric indices, clinical presentation, comorbidities, and management were included in the study, whereas articles with insufficient clinical and demographic data were excluded. We assessed the quality of the studies selected.The final review of all databases was conducted on June 18, 2020. RESULTS: We find the results from the current review to be of great importance due to the possible therapeutic role of leptin analogs in states of leptin deficiency associated with infectious diseases or sepsis.In hyperleptinemia, a therapeutic plan for obtaining leptin neutralization also needs further investigations. This could lead to the reduction of proinflammatory responses.There is a need for further studies to demonstrate the specificity and sensitivity of leptin in the early diagnosis of sepsis and the need to measure serum leptin levels in routine evaluation of the critical patient. CONCLUSION: The multiple effects of leptin are of growing interest, but further studies are needed to elucidate the role of leptin signalling in infectious diseases and sepsis. Because very few human studies are reported, we recommend the need for further research.Better understanding of the pathophysiology of sepsis and the implication of circulating total leptin in this process could help physicians in managing this life-threatening condition.

Reliability of dried blood spot (DBS) cards in antibody measurement: A systematic review.

BACKGROUND: Increasingly, vaccine efficacy studies are being recommended in low-and-middle-income countries (LMIC), yet often facilities are unavailable to take and store infant blood samples correctly. Dried blood spots (DBS), are useful for collecting blood from infants for diagnostic purposes, especially in low-income settings, as the amount of blood required is miniscule and no refrigeration is required. Little is known about their utility for antibody studies in children. This systematic review aims to investigate the correlation of antibody concentrations against infectious diseases in DBS in comparison to serum or plasma samples that might inform their use in vaccine clinical trials. METHODS AND FINDINGS: We searched MEDLINE, Embase and the Cochrane library for relevant studies between January 1990 to October 2020 with no language restriction, using PRISMA guidelines, investigating the correlation between antibody concentrations in DBS and serum or plasma samples, and the effect of storage temperature on DBS diagnostic performance. We included 40 studies in this systematic review. The antibody concentration in DBS and serum/plasma samples reported a good pooled correlation, (r2 = 0.86 (ranged 0.43 to 1.00)). Ten studies described a decline of antibody after 28 days at room temperature compared to optimal storage at -20°C, where antibodies were stable for up to 200 days. There were only five studies of anti-bacterial antibodies. CONCLUSIONS: There is a good correlation between antibody concentrations in DBS and serum/plasma samples, supporting the wider use of DBS in vaccine and sero-epidemiological studies, but there is limited data on anti-bacterial antibodies. The correct storage of DBS is critical and may be a consideration for longer term storage.

HMGB1, anti-HMGB1 antibodies, and ratio of HMGB1/anti-HMGB1 antibodies as diagnosis indicator in fever of unknown origin.

To evaluate the feasibility of serum HMGB1, anti-HMGB1 antibodies, and HMGB1/anti-HMGB1 ratio as a diagnosis indicator of initial clinical classification in patients with fever of unknown origin (FUO). Ninety-four patients with classical FUO and ninety healthy controls were enrolled in this study. The subjects' clinical data and serum were collected. The serum concentration of HMGB1 was detected by a commercial HMGB1 ELISA kit, while the serum concentration of anti-HMGB1 antibodies were detected by an in-house built anti-HMGB1 antibodies ELISA kit and further confirmed by immunoblotting. According to the hospital diagnosis on discharge, ninety-four FUO patients were divided into four groups, Infectious disease subgroup, autoimmune disease subgroup, malignant tumor subgroup, and undetermined subgroup. The concentrations of HMGB1 in the infectious disease subgroup and autoimmune disease subgroup were higher than those in the malignant tumor subgroup, undetermined subgroup, and healthy control group. The concentration of anti-HMGB1 antibodies in autoimmune disease subtype group was higher than those in other subgroups as well as healthy control group. According to the distribution of HMGB1 and anti-HMGB1 in scatter plots of the patients with FUO, we found that the ratio of serum HMGB1/anti-HMGB1 is an ideal clinical indicator for differential diagnosis of different subtypes of FUO. The best cut-off was 0.75, and the sensitivity, specificity, and AUC were 66.67%, 87.32%, and 0.8, respectively. Correlation analysis showed that serum concentration of HMGB1 was moderately correlated with CRP in infectious diseases subgroup, and the serum concentration of anti-HMGB1 antibodies was strongly correlated with erythrocyte sedimentation rate in autoimmune disease subgroup. Our study had showed that serum HMGB1/anti-HMGB1 antibodies ratio can help clinicians identify FUO subtypes, thereby avoiding many unnecessary examinations and tests, and improving the effectiveness of clinical diagnosis and treatment of FUO.

A retrospective cross-sectional study for predicting 72-h mortality in patients with serum aspartate aminotransferase levels ≥ 3000 U/L.

Risk factors associated with 72-h mortality in patients with extremely high serum aspartate aminotransferase levels (AST; ≥ 3000 U/L) are unknown. This single-centre, retrospective, case-controlled, cross-sectional study obtained data from medical records of adult patients treated at Saitama Medical Center, Japan, from 2005 to 2019. We conducted a multivariate logistic after adjusting for age, sex, height, weight, body mass index, Brinkman Index, vital signs, biochemical values, updated Charlson Comorbidity Index (CCI) score, CCI components, and underlying causes. A logistic regression model with selected validity risks and higher C-statistic for predicting 72-h mortality was established. During the 15-year period, 428 patients (133 non-survivors and 295 survivors [cases and controls by survival < 72 and ≥ 72 h, respectively]) with AST levels ≥ 3000 U/L were identified. The 72-h mortality rate was 133/428 (31.1%). The model used for predicting 72-h mortality through the assessment of alkaline phosphatase, creatine kinase, serum sodium, potassium, and phosphorus levels had a C-statistic value of 0.852 (sensitivity and specificity, 76.6%). The main independent risk factors associated with 72-h mortality among patients with AST levels ≥ 3000 U/L included higher serum values of alkaline phosphatase, creatine kinase, serum sodium, potassium, and phosphorus.

Seroprevalence of human herpesvirus 8 in Ireland among blood donors, men who have sex with men, and heterosexual genitourinary medicine and infectious diseases clinic attendees.

Human herpesvirus 8 (HHV-8) seroprevalence varies geographically and between subpopulations. High seroprevalence rates have been ascribed to men who have sex with men (MSM), African migrants, and HIV-infected individuals. The objective of this study was to determine the seroprevalence of HHV-8 in an Irish population, including specific risk groups. A cross-sectional study of 200 blood donors and 200 genitourinary medicine (GUM) and infectious diseases (ID) clinic patients was performed, with testing for Immunoglobulin G (IgG) antibodies to HHV-8 lytic antigens using a commercial indirect fluorescence assay (Scimedx Corp.). Verification was performed at the Centers for Disease Control and Prevention (CDC). All 200 blood donor samples were negative for HHV-8 IgG antibodies. 21% of GUM and ID patients were positive for HHV-8 IgG antibodies. One hundred of these patients were MSM, 35% of whom were HHV-8 seropositive (46% of HIV-positive MSM and 24% of HIV-negative MSM). Of 100 heterosexual patients, only 7% were HHV-8 seropositive. The absence of seropositivity in 200 Irish blood donors may suggest that Ireland has a low overall population HHV-8 seroprevalence. The proportion of HHV-8 seropositivity in the MSM population was significantly higher than in the heterosexual population and most marked in HIV-positive MSM.

Dose Optimization of Vancomycin Using a Mechanism-based Exposure-Response Model in Pediatric Infectious Disease Patients.

PURPOSE: This study aimed to determine the appropriate vancomycin dosage, considering patient size and organ maturation, by simulating the bacterial count and biomarker level for drug administration in pediatric patients with gram-positive bacterial (GPB) infections. METHODS: Natural language processing for n-gram analysis was used to detect appropriate pharmacodynamic (PD) markers in infectious disease patients. In addition, a mechanism-based model was established to describe the systemic exposure and evaluate the PD marker simultaneously in pediatric patients. A simulation study was then conducted by using a mechanism-based model to evaluate the optimal dose of vancomycin in pediatric patients. FINDINGS: C-reactive protein (CRP) was selected as a PD marker from an analysis of ~270,000 abstracts in PubMed. In addition, clinical results, including the vancomycin plasma concentrations and CRP levels of pediatric patients (n = 93), were collected from electronic medical records. The vancomycin pharmacokinetic model with allometric scaling and a maturation function was built as a one-compartment model, with an additional compartment for bacteria. Both the effects of vancomycin plasma concentrations on the destruction of bacteria and those of bacteria on CRP production rates were represented by using a maximum achievable effect model (Emax model). Simulation for dose optimization was conducted not only by using the final model but also by exploring the possibility of therapeutic failure based on the MICs of vancomycin for GPB. Clinical cure was defined as when the CRP level fell below the upper limit of the normal range. Our dose optimization simulations suggested a vancomycin dosage of 10 mg/kg every 8 h as the optimal maintenance dose for pediatric patients with a postconceptual age <30 weeks and 10 mg/kg every 6 h for older children, aged up to 12 years. In addition, the MIC of 3 µg/mL was assessed as the upper concentration limit associated with successful vancomycin treatment of GPB infections. IMPLICATIONS: This study confirmed that the changes in bacterial counts and CRP levels were well described with mechanistic exposure-response modeling of vancomycin. This model can be used to determine optimal empiric doses of vancomycin and to improve therapeutic outcomes in pediatric patients with GPB.

Role of Platelets in Detection and Regulation of Infection.

Platelets are classically known as essential mediators of hemostasis and thrombosis. However, in recent years, platelets have gained recognition for their inflammatory functions, which modulate the immune response during infectious diseases. Platelets contain various immunoreceptors that enable them to act as sentinels to recognize intravascular pathogens. Upon activation, platelets directly limit pathogen growth through the release of AMPs (antimicrobial proteins) and ensure pathogen clearance through activation of immune cells. However, aberrant platelet activation can lead to inflammation and thrombotic events.

Circulating Th1 and Th2 Subset Accumulation Kinetics in Septic Patients with Distinct Infection Sites: Pulmonary versus Nonpulmonary.

BACKGROUND: Persistent peripheral CD4+T cell differentiation towards T helper (Th)2 rather than Th1 has been proved to be related to immunosuppression and poor prognosis in sepsis. However, it is unclear whether these circulating Th1 and Th2 subtype accumulations differed in septic populations of distinct infection sites and presented different associations with outcomes among patients with pulmonary versus nonpulmonary sepsis. METHODS: From a secondary analysis of a prospective observational study, seventy-four previously immunocompetent patients with community-acquired severe sepsis within 24 hours upon onset were enrolled. Whole blood was collected on the admission day (D0), 3rd day (D3), and 7th day (D7). The patients were classified as pulmonary (n = 52) and nonpulmonary sepsis (n = 22). Circulating Th1 and Th2 populations were evaluated by flow cytometry, and clinical data related to disease severity and inflammatory response were collected. The associations of circulating Th1 and Th2 subset accumulations with distinct infection sites or outcomes within subgroups were explored. RESULTS: Patients with pulmonary sepsis held similar disease severity and 28-day mortality with those of nonpulmonary sepsis. Of note is the finding that circulating Th2 levels on D7 (P = 0.04) as well as Th2/Th1 on D3 (P = 0.01) and D7 (P = 0.04) were higher in the pulmonary sepsis compared with nonpulmonary sepsis while Th1 levels were lower on D0, D3, and D7 (P = 0.01, <0.01, and =0.05, respectively). Compared to 28-day survivors, higher Th2/Th1 driven by increased Th2 were observed among 28-day nonsurvivors on D3 and D7 in both groups. The association between circulatory Th2 populations or Th2/Th1 and 28-day death was detected in pulmonary sepsis (P < 0.05, HR > 1), rather than nonpulmonary sepsis. CONCLUSIONS: Circulating Th2 accumulation was more apparent among pulmonary sepsis while nonpulmonary sepsis was characterized with the hyperactive circulating Th1 subset among previously immunocompetent patients. This finding suggested that circulating Th1 and Th2 subset accumulations vary in septic subgroups with different infection sites.

[Clinical and biological features of haptoglobin phenotypes]. / Phénotypes d'haptoglobine : impacts cliniques et biologiques.

Haptoglobin is a late positive acute phase protein of inflammation. Haptoglobin binds to free hemoglobin released from erythrocytes during intravascular hemolysis to form a complex which is removed shortly. Other properties like inhibition of oxidative stress and prostaglandin synthesis have been described. Three main phenotypes of haptoglobin have been identified: Hp1-1, Hp2-1, Hp2-2, which may have an impact in different diseases such as cardiovascular or infectious diseases. Haptoglobins of different phenotypes can be separated by capillary electrophoresis. They may induce a split of the alpha 2-globulin zone in the electrophoretic pattern. Hp1-1 and Hp2-1 phenotypes induce an important and a moderate split of the α2 globulin zone, respectively, whereas Hp2-2 does not. In vitro hemolysis and migration of a monoclonal component (i.e. immunoglobulin free light chain) may also induce a split of the alpha 2-globulin zone. In daily practice, Hp2-1 or Hp1-1 phenotypes could be notified in the electrophoresis report to alert the clinician about the possible physiopathological consequences.

Haematology and blood chemistry in free-ranging quokkas (Setonix brachyurus): Reference intervals and assessing the effects of site, sampling time, and infectious agents.

Quokkas (Setonix brachyurus) are small macropodid marsupials from Western Australia, which are identified as of conservation concern. Studies on their blood analytes exist but involve small sample sizes and are associated with very little information concerning the health of the animals. Blood was collected from free-ranging quokkas from Rottnest Island (n = 113) and mainland (n = 37) Western Australia, between September 2010 and December 2011, to establish haematology and blood chemistry reference intervals. Differences in haematology and blood chemistry between sites (Rottnest Island v mainland) were significant for haematology (HMT, p = 0.003), blood chemistry (BLC, p = 0.001) and peripheral blood cell morphology (PBCM, p = 0.001). Except for alkaline phosphatase, all blood chemistry analytes were higher in mainland animals. There were also differences with time of year in HMT (p = 0.001), BLC (p = 0.001) and PBCM (p = 0.001) for Rottnest Island quokkas. A small sample of captive animals (n = 8) were opportunistically sampled for plasma concentrations of vitamin E and were found to be deficient compared with wild-caught animals. Fifty-eight of the 150 quokkas were also tested for the presence of Salmonella, microfilariae, Macropodid herpesvirus-6, Theileria spp., Babesia spp., trypanosomes, Cryptococcus spp. and other saprophytic fungi. All eight infectious agents were detected in this study. Infectious agents were detected in 24 of these 58 quokkas (41%), with more than one infectious agent detected for all 24 individuals. Salmonella were detected concurrently with microfilariae in 8 of these 24 quokkas, and this mixed infection was associated with lower values across all haematological analytes, with Salmonella having the greater involvement in the decreased haematological values (p < 0.05). There was no evidence for an effect of sex on HMT, BLC and PBCM. Our data provide important haematological and blood chemistry reference intervals for free-ranging quokkas. We applied novel methods of analyses to HMT and BLC that can be used more broadly, aiding identification of potential disease in wildlife.

Systemic inflammatory markers for the detection of infectious complications and safe discharge after cytoreductive surgery and HIPEC.

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in patients with ovarian peritoneal carcinomatosis may be associated with a high postoperative morbidity. An early discrimination of postoperative complications is crucial for both improving clinical outcomes and proposing a safe discharge. MATERIAL AND METHODS: In a cohort of 122 patients with advanced ovarian cancer (FIGO III-IV), we analyzed the diagnostic performance of three systemic inflammatory markers (C-reactive protein, white blood cell count and systemic immune-inflammation index) between the 5th to 8th postoperative days to prediction postoperative infectious complications. An optimal cut-off value was established in order to discriminate between the group of patients who developed infectious complications or not during the postoperative period. RESULTS: The median peritoneal carcinomatosis index (PCI) was 15. The overall infectious morbidity was 25.4% (31 patients out of 122), of which, 32% (10 patients out of 31) had suffered severe postoperative complications (Dindo-Clavien III-IV). The most accurate results for detecting infectious complications were obtained by using C-reactive protein, which presented an excellent diagnostic performance, especially on the 7th and 8th postoperative days (AUC = 0,857 and 0,920; respectively). CONCLUSIONS: These results support that it is safe to discharge patients with C-reactive protein concentrations lower than 88 mg/L and 130 mg/L, on the 7th and 8th postoperative days, respectively.