The role of Killer immunoglobulin-like receptors (KIRs) in the genetic susceptibility to non-celiac wheat sensitivity (NCWS).

OBJECTIVES: Non-celiac wheat sensitivity (NCWS) is an emerging clinical condition characterized by gastrointestinal and extraintestinal symptoms following the ingestion of gluten-containing foods in patients without celiac disease (CD) or wheat allergy. Despite the great interest for NCWS, the genetic risk factors still need to be fully clarified. In this study, we first assessed the possible contribution of KIR genes and KIR haplotypes on the genetic predisposition to NCWS. METHODS: Fifty patients with NCWS, 50 patients with CD, and 50 healthy controls (HC) were included in this study. KIR genes and KIR genotyping were investigated in all subjects by polymerase chain reaction with the sequence oligonucleotide probe (PCR-SSOP) method using Luminex technology. RESULTS: We found a statistically different distribution of some KIR genes among NCWS, CD, and HC. Specifically, NCWS showed a decreased frequency of KIR2DL1, -2DL3, -2DL5, -2DS2, -2DS3, -2DS4, -2DS5, and -3DS1 genes, and an increased frequency of -3DL1 gene respect to both CD and HC. No difference was detected in the KIR haplotype expression. At the multivariate analysis, KIR2DL5, -2DS4, and -2DS5 were independent predictors of NCWS. CONCLUSIONS: Our findings suggest a role of KIR genes in NCWS susceptibility, with KIR2DL5, -2DS4, and -2DS5 having a protective effect. Further large-scale multicentric studies are required to validate these preliminary findings.

Molecular Biomarkers of Neurodegenerative Disorders: A Practical Guide to Their Appropriate Use and Interpretation in Clinical Practice.

Neurodegenerative disorders (NDs) represent a group of different diseases characterized by the progressive degeneration and death of the nervous system's cells. The diagnosis is challenging, especially in the early stages, due to no specific clinical signs and symptoms. In this context, laboratory medicine could support clinicians in detecting and differentiating NDs. Indeed, biomarkers could indicate the pathological mechanisms underpinning NDs. The ideal biofluid for detecting the biomarkers of NDs is cerebrospinal fluid (CSF), which has limitations, hampering its widespread use in clinical practice. However, intensive efforts are underway to introduce high-sensitivity analytical methods to detect ND biomarkers in alternative nonivasive biofluid, such as blood or saliva. This study presents an overview of the ND molecular biomarkers currently used in clinical practice. For some diseases, such as Alzheimer's disease or multiple sclerosis, biomarkers are well established and recommended by guidelines. However, for most NDs, intensive research is ongoing to identify reliable and specific biomarkers, and no consensus has yet been achieved.

Microglial Activation and Priming in Alzheimer's Disease: State of the Art and Future Perspectives.

Alzheimer's Disease (AD) is the most common cause of dementia, having a remarkable social and healthcare burden worldwide. Amyloid ß (Aß) and protein Tau aggregates are disease hallmarks and key players in AD pathogenesis. However, it has been hypothesized that microglia can contribute to AD pathophysiology, as well. Microglia are CNS-resident immune cells belonging to the myeloid lineage of the innate arm of immunity. Under physiological conditions, microglia are in constant motion in order to carry on their housekeeping function, and they maintain an anti-inflammatory, quiescent state, with low expression of cytokines and no phagocytic activity. Upon various stimuli (debris, ATP, misfolded proteins, aggregates and pathogens), microglia acquire a phagocytic function and overexpress cytokine gene modules. This process is generally regarded as microglia activation and implies that the production of pro-inflammatory cytokines is counterbalanced by the synthesis and the release of anti-inflammatory molecules. This mechanism avoids excessive inflammatory response and inappropriate microglial activation, which causes tissue damage and brain homeostasis impairment. Once the pathogenic stimulus has been cleared, activated microglia return to the naïve, anti-inflammatory state. Upon repeated stimuli (as in the case of Aß deposition in the early stage of AD), activated microglia shift toward a less protective, neurotoxic phenotype, known as "primed" microglia. The main characteristic of primed microglia is their lower capability to turn back toward the naïve, anti-inflammatory state, which makes these cells prone to chronic activation and favours chronic inflammation in the brain. Primed microglia have impaired defence capacity against injury and detrimental effects on the brain microenvironment. Additionally, priming has been associated with AD onset and progression and can represent a promising target for AD treatment strategies. Many factors (genetics, environmental factors, baseline inflammatory status of microglia, ageing) generate an aberrantly activated phenotype that undergoes priming easier and earlier than normally activated microglia do. Novel, promising targets for therapeutic strategies for AD have been sought in the field of microglia activation and, importantly, among those factors influencing the baseline status of these cells. The CX3CL1 pathway could be a valuable target treatment approach in AD, although preliminary findings from the studies in this field are controversial. The current review aims to summarize state of the art on the role of microglia dysfunction in AD pathogenesis and proposes biochemical pathways with possible targets for AD treatment.

Prostate health index (PHI) as a reliable biomarker for prostate cancer: a systematic review and meta-analysis.

OBJECTIVES: Prostate cancer (PCa) represents the second most common solid cancer in men worldwide. In the last decades, the prostate health index (PHI) emerged as a reliable biomarker for detecting PCa and differentiating between non-aggressive and aggressive forms. However, before introducing it in clinical practice, more evidence is required. Thus, we performed a systematic review and meta-analysis for assessing the diagnostic performance of PHI for PCa and for detecting clinically significant PCa (csPCa). METHODS: Relevant publications were identified by a systematic literature search on PubMed and Web of Science from inception to January 11, 2022. RESULTS: Sixty studies, including 14,255 individuals, met the inclusion criteria for our meta-analysis. The pooled sensitivity and specificity of PHI for PCa detection was 0.791 (95%CI 0.739-0.834) and 0.625 (95%CI 0.560-0.686), respectively. The pooled sensitivity and specificity of PHI for csPCa detection was 0.874 (95%CI 0.803-0.923) and 0.569 (95%CI 0.458-0.674), respectively. Additionally, the diagnostic odds ratio was 6.302 and 9.206, respectively, for PCa and csPCa detection, suggesting moderate to good effectiveness of PHI as a diagnostic test. CONCLUSIONS: PHI has a high accuracy for detecting PCa and discriminating between aggressive and non-aggressive PCa. Thus, it could be useful as a biomarker in predicting patients harbouring more aggressive cancer and guiding biopsy decisions.

Monocyte distribution width (MDW) as a screening tool for early detecting sepsis: a systematic review and meta-analysis.

OBJECTIVES: Monocyte distribution has recently emerged as a promising biomarker of sepsis, especially in acute setting, such as Emergency Department and Intensive Care Unit. This study aimed to evaluate the accuracy of monocyte distribution width (MDW) for early detecting patients with sepsis by performing a systemic review and meta-analysis of published studies. METHODS: Relevant publications were identified by a systematic literature search on PubMed and Google Scholar from inception to September 07, 2021. Studies were divided into two groups based on the sepsis criteria applied, namely sepsis-2 or sepsis-3. RESULTS: Ten studies including 9,475 individuals, of whom 1,370 with sepsis (742 according Sepsis-2 and 628 according to Sepsis-3), met the inclusion criteria for our meta-analysis. The pooled sensitivity and specificity were 0.789 and 0.777 for Sepsis-2 criteria, 0.838 and 0.704 for Sepsis-3 criteria. CONCLUSIONS: MDW represents a reliable biomarker for sepsis screening.

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer's Disease from Other Neurological Disorders.

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aß42/Ng and Aß42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn alone. Regression analyses showed an association of higher Ng concentrations with MMSE < 24, pathological Aß 42/40 ratios, pTau, tTau and the ApoEε4 genotype. Aß 42/Ng was associated with MMSE < 24, an AD-related FDG-PET pattern, the ApoEε4 genotype, pathological Aß 42 levels and Aß 42/40 ratios, pTau, and tTau. Moreover, APO-Eε4 carriers showed higher Ng concentrations than non-carriers. Our results support the idea that the Aß 42/Ng ratio is a reliable index of synaptic dysfunction/degeneration able to discriminate AD from other neurological conditions.

Autoimmunity Features in Patients With Non-Celiac Wheat Sensitivity.

INTRODUCTION: Nonceliac wheat sensitivity (NCWS) is characterized by intestinal and extraintestinal manifestations consequent to wheat ingestion in subjects without celiac disease and wheat allergy. Few studies investigated the relationship between NCWS and autoimmunity. The aim of this study is to evaluate the frequency of autoimmune diseases (ADs) and autoantibodies in patients with NCWS. METHODS: Ninety-one patients (13 men and 78 women; mean age of 40.9 years) with NCWS, recruited in a single center, were included. Seventy-six healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls. Autoantibodies levels were measured. Human leukocyte antigen haplotypes were determined, and duodenal histology performed in all patients carrying the DQ2/DQ8 haplotypes. Participants completed a questionnaire, and their medical records were reviewed to identify those with ADs. RESULTS: Twenty-three patients with NCWS (25.3%) presented with ADs; autoimmune thyroiditis (16 patients, 17.6%) was the most frequent. The frequency of ADs was higher in patients with NCWS than in HBD (P = 0.002) and in patients with IBS (P = 0.05). In the NCWS group, antinuclear antibodies tested positive in 71.4% vs HBD 19.7%, and vs patients with IBS 21.8% (P < 0.0001 for both). The frequency of extractable nuclear antigen antibody (ENA) positivity was significantly higher in patients with NCWS (21.9%) than in HBD (0%) and patients with IBS (3.6%) (P = 0.0001 and P = 0.004, respectively). Among the patients with NCWS, 9.9% tested positive for antithyroglobulin, 16.5% for antithyroid peroxidase, and 14.3% for antiparietal cell antibodies; frequencies were not statistically different from controls. The presence of ADs was related to older age at NCWS diagnosis, female sex, duodenal lymphocytosis, and eosinophil infiltration. DISCUSSION: One in 4 patients with NCWS suffered from AD, and serum antinuclear antibodies were positive in a very high percentage of cases. These data led us to consider NCWS to be associated to ADs.

Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: To test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study in a large cohort of ALS patients and controls. METHODS: We enrolled 196 ALS patients and 91 controls, who included patients with ALS-mimicking diseases and those with non-neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic evaluation or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay. RESULTS: Patients with ALS showed significantly higher levels of CSF tTau and a lower pTau/tTau ratio than controls (tTau: 245 vs. 146 pg/ml; p < 0.001; pTau/tTau ratio: 0.12 vs. 0.18; p < 0.001, respectively). No differences in pTau levels were detected. Receiver-operating characteristic curve analysis showed a good diagnostic accuracy of tTau and pTau/tTau ratio (tTau: area under the curve [AUC] 0.685, 95% confidence interval [CI] 0.616-0.754, p = 0.039; pTau/tTau ratio: AUC 0.777, 95% CI 0.707-0.848, p < 0.001). Among ALS patients, increased tTau levels were associated with advanced age of onset, increased revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) score (ΔFS) rate of progression, and spinal onset. Multivariate analysis showed that in ALS patients, this biomarker was an independent negative predictor of overall survival. CONCLUSIONS: Our findings suggest that tTau and pTau/tTau ratio can be diagnostic biomarkers of ALS. In addition, CSF tTau level at diagnosis might play a relevant prognostic role in the disease.

A new tool for sepsis screening in the Emergency Department.

OBJECTIVES: In this study, we developed and evaluated the diagnostic accuracy of the Sepsis Index for early sepsis screening in the Emergency Department (ED). METHODS: Sepsis Index is based on the combination of monocyte distribution width (MDW) and mean monocyte volume (MMV). Sepsis Index≥1 was selected to define sepsis. We tested its diagnostic accuracy in an ED population stratified in four groups: controls, Systemic Inflammatory Response Syndrome (SIRS), infection, and sepsis, according to Sepsis-2 criteria. RESULTS: Patients with sepsis displayed higher median Sepsis Index value than patients without sepsis. At the receiver operating characterictis (ROC) curve analysis for the prediction of sepsis, the area under the curve (AUC) of MDW and Sepsis Index were similar: 0.966 (95%CI 0.947-0.984), and 0.964 (95%CI 0.942-0.985), respectively. Sepsis Index showed increased specificity than MDW (94.7 vs. 90.6%), without any decrease in sensitivity (92.0%). Additionally, LR+ increased from 9.8 (MDW) to 17.4 (Sepsis Index), without any substantial change in LR- (respectively 0.09 vs. 0.08). Finally, PPV increased from 0.286 (MDW) to 0.420 (Sepsis Index). CONCLUSIONS: Sepsis Index improves the diagnostic accuracy of MDW alone for sepsis screening.

Sicilian centenarian offspring are more resistant to immune ageing.

BACKGROUND: Immunosenescence constitutes a major indirect cause of morbidity and mortality in the elderly. Previous analysis of immune signatures in a cohort of centenarian offspring showed an intermediate immunophenotype between age-matched and younger controls. AIMS: To confirm and extend the previous studies performing further phenotypical analysis in centenarian offspring and controls. METHODS: Analysis of Treg cells, γδ T cells, mucosal-associated invariant T cells, and senescent immune T cells was performed in centenarian offspring and controls. RESULTS: We report significant differences between elderly and centenarian offspring in most of the studied subsets, showing that centenarian offspring subsets present an intermediate phenotyping between elderly and younger people. CONCLUSION: The whole present data confirm and extend the previous results showing that centenarian offspring retain more youthful immunological parameters and that the exhaustion of the immune system is less evident than in elderly without centenarian parents, though further investigations are warranted.

Role of Immunogenetics in the Outcome of HCMV Infection: Implications for Ageing.

The outcome of host-virus interactions is determined by a number of factors, some related to the virus, others to the host, such as environmental factors and genetic factors. Therefore, different individuals vary in their relative susceptibility to infections. Human cytomegalovirus (HCMV) is an important pathogen from a clinical point of view, as it causes significant morbidity and mortality in immunosuppressed or immunosenescent individuals, such as the transplanted patients and the elderly, respectively. It is, therefore, important to understand the mechanisms of virus infection control. In this review, we discuss recent advances in the immunobiology of HCMV-host interactions, with particular emphasis on the immunogenetic aspects (human leukocyte antigens, HLA; killer cell immunoglobulin-like receptors, KIRs; immunoglobulin genetic markers, GM allotypes) to elucidate the mechanisms underlying the complex host-virus interaction that determine various outcomes of HCMV infection. The results, which show the role of humoral and cellular immunity in the control of infection by HCMV, would be valuable in directing efforts to reduce HCMV spurred health complications in the transplanted patients and in the elderly, including immunosenescence. In addition, concerning GM allotypes, it is intriguing that, in a Southern Italian population, alleles associated with the risk of developing HCMV symptomatic infection are negatively associated with longevity.

Association of immunoglobulin GM allotypes with longevity in long-living individuals from Southern Italy.

BACKGROUND: The aim of this study was to analyse the role of GM allotypes, i.e. the hereditary antigenic determinants expressed on immunoglobulin polypeptide chains, in the attainment of longevity. The role played by immunoglobulin allotypes in the control of immune responses is well known as well as the role of an efficient immune response in longevity achievement. So, it is conceivable that particular GM allotypes may contribute to the generation of an efficient immune response that supports successful ageing, hence longevity. METHODS: In order to show if GM allotypes play a role in the achievement of longevity, we typed the DNA of 95 Long-living individuals (LLIs) and 96 young control individuals (YCs) from South Italy for GM3/17 and GM23+/- alleles. RESULTS: To demonstrate the role of GM allotypes in the attainment of longevity we compared genotype and allele frequencies of GM allotypes between LLIs and YCs. A global chi-square test (3 × 2) shows that the distribution of genotypes at the GM 3/17 locus is highly significantly different in LLIs from that observed in YCs (p < 0.0001). The 2 × 2 chi-square test shows that the carriers of the GM3 allele contribute to this highly significant difference. Accordingly, GM3 allele is significantly overrepresented in LLIs. No significant differences were instead observed regarding GM23 allele. CONCLUSION: These preliminary results show that GM3 allotype is significantly overrepresented in LLIs. To best of our knowledge, this is the first study performed to assess the role of GM allotypes in longevity. So, it should be necessary to verify the data in a larger sample of individuals to confirm GM role in the attainment of longevity.

Nutraceutical effects of table green olives: a pilot study with Nocellara del Belice olives.

BACKGROUND: The aim of this study was to analyse the nutraceutical properties of table green olives Nocellara del Belice, a traditional Mediterranean food. The Mediterranean Diet has as key elements olives and extra virgin olive oil, common to all Mediterranean countries. Olive oil is the main source of fat and can modulate oxidative stress and inflammation, whereas little is known about the role of olives. Moreover, emerging evidences underline the association between gut microbiota and food as the basis of many phenomena that affect health and delay or avoid the onset of some age-related chronic diseases. METHODS: In order to show if table green olives have nutraceutical properties and/or probiotic effect, we performed a nutritional intervention, administering to 25 healthy subjects (mean age 38,3), 12 table green olives/day for 30 days. We carried out anthropometric, biochemical, oxidative stress and cytokines analyses at the beginning of the study and at the end. Moreover, we also collected fecal samples to investigate about the possible variation of concentration of Lactobacilli, after the olives consumption. RESULT: Our results showed a significant variation of one molecule related to oxidative stress, malondialdehyde, confirming that Nocellara del Belice green olives could have an anti-oxidant effect. In addition, the level of interleukin-6 decreased significantly, demonstrating how this food could be able to modulate the inflammatory response. Moreover, it is noteworthy the reduction of fat mass with an increase of muscle mass, suggesting a possible effect on long time assumption of table olives on body mass variation. No statistically significant differences were observed in the amount of Lactobacilli, although a trend towards an increased concentration of them at the end of the intervention could be related to the nutraceutical effects of olives. CONCLUSION: These preliminary results suggest a possible nutraceutical effect of daily consumption of green table olives Nocellara del Belice. To best of our knowledge, this is the first study performed to assess nutraceutical properties of this food. Of course, it is necessary to verify the data in a larger sample of individuals to confirm their role as nutraceuticals.

Prostate Health Index (PHI) as a triage tool for reducing unnecessary magnetic resonance imaging (MRI) in patients at risk of prostate cancer.

INTRODUCTION: The aim of this study is to assess the usefulness of the Prostate Health Index (PHI) as a triage tool for selecting patients at risk of prostate cancer (PCa) who should undergo multiparametric Magnetic Resonance Imaging (mpMRI). MATERIAL AND METHODS: We enrolled 204 patients with suspected PCa. For each patient, a blood sample was collected before mpMRI to measure PHI. Findings on mpMRI were assessed according to the Prostate Imaging Reporting & Data System version 2.0 (PI-RADSv2) category scale. RESULTS: According to PI-RADSv2, patients were classified into two groups: PI-RADS < 3 (48 %) and ≥ 3 (52 %). PHI showed the best performance for predicting PI-RADS ≥ 3 [AUC: 0,747 (0,679-0,815), 0,680(0,607-0,754), and 0,613 (0,535-0,690) for PHI, PSA ratio, and total PSA, respectively]. The best PHI cut-off was 30, with a sensitivity of 90%. At the univariate logistic regression, total PSA (p = 0.007), PSA ratio (p = 0.001), [-2]proPSA (p = 0.019) and PHI (p < 0.001) were associated with PI-RADS ≥ 3; however, at the multivariate analysis, only PHI (p < 0.001) was found to be an independent predictor of PI-RADS ≥ 3. CONCLUSION: PHI could represent a reliable noninvasive tool for selecting patients to undergo mpMRI.

Clinical usefulness of presepsin and monocyte distribution width (MDW) kinetic for predicting mortality in critically ill patients in intensive care unit.

Background: In this study, we explored the accuracy of two new sepsis biomarkers, monocyte distribution width (MDW) and presepsin (PSP), compared to traditional ones, C-reactive protein (CRP) and Procalcitonin (PCT), to identify sepsis and predict intra-hospital mortality by analyzing their kinetic at different time points during hospitalization stay. Methods: We enrolled 104 patients admitted to the intensive care unit (ICU) of University Hospital "Paolo Giaccone", Palermo. Among these, 30 (29%) had a clinical diagnosis of sepsis. MDW, PCT, CRP, and PSP were evaluated at admission (T0), after 24 h (T24), 48 h (T48), 72 h (T72), at day 5 (T5), and at discharge (TD). Results: Patients with sepsis displayed higher levels of PCT and PSP than patients without sepsis at each timepoint; differently, CRP displayed statistically significant differences only at T0, while MDW only at T0 and T24. Patients with increasing levels of PSP displayed lower median survival time than patients with decreasing levels; differences reached statistical significance only at 48 h (20 vs. 29 days, log rank test, p = 0.046). Interestingly, PSP was an independent predictor of ICU mortality at 48 and 72 h after hospital admission. Also, the kinetic of PSP had prognostic value, with increased values at 48 h after admission being associated with reduced survival. Conclusion: Our findings support the role of PSP and its kinetic as a predictor of ICU mortality.

Exploring the effect of APOE ε4 on biomarkers of neurodegeneration in Alzheimer's disease.

BACKGROUND AND AIMS: This study aims to assess the association between APOE genotype and biomarkers of neurodegeneration in Alzheimer's disease (AD). METHODS: We performed a retrospective observational study at the University Hospital "P. Giaccone" in Palermo, Italy. We enrolled patients with cognitive decline, including AD. For each patient, we measured amyloid beta (Aß)42, Aß40, tau protein phosphorylated at threonine 181 (pTau), total tau (tTau), neurogranin, alpha-synuclein, and neurofilament light chain (NfL) in cerebrospinal fluid (CSF). RESULTS: The study population consisted of 194 patients (123 AD and 71 non-AD). AD patients have significantly lower Aß42 levels and Aß42/40 ratio and higher pTau, tTau, and NfLs levels than non-AD patients. In AD patients, the APOEε4 allele is associated with a significantly lower Aß42/40 ratio and higher levels of pTau, tTau, neurogranin, and alpha-synuclein. This association is not observed in non-AD patients. CONCLUSIONS: This study provides evidence of the significant impact of the APOE ε4 allele on neurodegenerative biomarkers in AD patients, highlighting its role in exacerbating amyloid and tau pathology as well as synaptic degeneration.

Monocyte distribution width (MDW) kinetic for monitoring sepsis in intensive care unit.

OBJECTIVES: Monocyte distribution width (MDW) is a measure of monocyte anisocytosis. In this study, we assessed the role of MDW, in comparison to C-reactive protein (CRP), procalcitonin (PCT), and lactate, as a screening and prognostic biomarker of sepsis in intensive care unit (ICU) by longitudinally measuring it in the first 5 days of hospital stay. METHODS: We considered all consecutive patients admitted to the ICU. At admission, patients were classified as septic or not according to Sepsis-3 criteria. MDW, CRP, PCT, and lactate were measured daily in the first 5 days of hospitalization. ICU mortality was also recorded. RESULTS: We included 193 patients, 62 with sepsis and 131 without sepsis (controls). 58% and 26 % of the patients, with and without sepsis respectively, died during ICU stay. MDW showed the highest accuracy for sepsis detection, superior to CRP, PCT, and lactate (AUC of 0.840, 0.755, 0.708, 0.622, respectively). At admission, no biomarker predicts ICU mortality in patients with sepsis. The kinetic of all biomarkers during the first 5 days of hospitalization was associated with ICU mortality. Noteworthy, above all, the kinetic of MDW showed the best accuracy. Specifically, an increase or decrease in MDW from day 1-4 and 5 was significantly associated with mortality or survival, respectively. CONCLUSIONS: MDW is a reliable diagnostic and prognostic sepsis biomarker, better than traditional biomarkers.