Monocyte Distribution Width (MDW) as a useful and cost-effective biomarker for sepsis prediction

Sepsis is a life-threatening condition; it is a major cause of hospital mortality worldwide and it constitutes a global health problem. This research investigates the use of MDW as a predictor for septic patients. This was a double-center prospective cohort study of adult septic patients. Septic patients were identified and were categorized into two categories: those who improved and those who died. Blood was drawn from the patients three times, on the first, third, and fifth day of their admission to the hospital. MDW was evaluated as a biomarker to predict patient outcome. In addition, existing inflammatory markers were recorded in all patients. The MDW was able to predict patient's outcome. The average MDW was found to be significantly higher in patients who died in all records. For example, an MDW value of 28.4 on the first day of admission to the hospital was shown to be the best cut-off value in determining fatal outcomes; receiver operating characteristic (ROC) analysis revealed an area under the curve value of 0.71 (95% Confidence Interval-CI: 0.57-0.84) with a sensitivity of 64.7% and a specificity of 88.2%. In conclusion, MDW, in addition to being a marker that can quickly detect sepsis more effectively than other biomarkers, which is proven by numerous studies, could also be used as an indicator to predict patient outcome. This work is an attempt in that direction.

Sepsis is a life-threatening condition arising from a dysregulated host response to infection leading to organ dysfunction. Traditional clinical signs are often unreliable for detecting sepsis, necessitating the exploration of more accurate biomarkers. Furthermore, currently, recommended screening scores perform poorly, necessitating more effective biomarkers to identify sepsis. Therefore, in this study, we evaluated the predictive capabilities of six inflammatory biomarkers - C-reactive protein (CRP), red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR), monocyte distribution width (MDW), mean neutrophil volume (MNV), and mean monocyte volume (MMV) - measured from samples taken for complete blood count (CBC) for the development of sepsis in ICU patients. We conducted a prospective observational study involving ICU patients at a tertiary-care hospital in Hyderabad, India, over a one-year period to primarily assess the predictability of these six biomarkers for sepsis. As a secondary outcome, we also analyzed the predictiveness of the biomarkers with respect to mortality, the need for vasopressors, invasive mechanical ventilation or renal replacement therapy (RRT), the presence of organ failure, and hospital length of stay. Blood samples were collected for CRP and CBC on the first day of admission, from which RDW, NLR, MDW, MNV, and MMV were measured. Demographic data, including Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, clinical progression (recovery or mortality), requirement for vasopressors, invasive mechanical ventilation, RRT, presence of organ failure, and overall length of hospital stay, were documented. We analyzed data from 84 patients after one patient withdrew consent. The study sample had a mean age of 65.83 years, with 60 (71.4%) patients >60 years of age and a male predominance (n = 50; 59.5%). About 57 (67.85%) patients had three or more comorbidities. About 71 (84.5%) patients met the sepsis-3 criteria. Mean APACHE II and SOFA scores were 18.73 and 5.36, respectively. Primary outcome analysis showed that CRP and MDW were the most sensitive, with sensitivities of 81.75% and 81.7%, respectively, whereas MDW, MNV, and MMV had the highest specificity at 100% each. Correlation analysis revealed that MDW had the best area under the curve (AUC) of 0.932 in predicting sepsis. Multivariate logistic regression identified both MDW and MMV to have a significant positive correlation in the prediction of sepsis. The overall mortality rate was 9.5%. About 82 (97.6%) patients had organ failure, 35 (41.7%) required vasopressors, 20 (23.8%) required invasive mechanical ventilation, 16 (19%) required RRT, and 59 (70.2%) had a hospital stay exceeding five days, with an average length of hospital stay of eight days. No biomarkers showed strong AUC or specificity compared to the SOFA score (0.710, 94.74% specificity in predicting mortality). However, among the six biomarkers, MDW was the most specific (86.84%). A CRP of >65 mg/L was the best indicator for prolonged hospital stay, vasopressor use, and RRT. An MMV of >179 and MDW of >21.86 U were the most sensitive markers for vasopressor requirements. Our findings suggest that easily accessible biomarkers derived from routine CBC tests, particularly MDW and MMV, may serve as valuable tools for early sepsis diagnosis in resource-limited settings.

BackgroundColonic diverticulitis is a leading cause of abdominal pain. The monocyte distribution width (MDW) is a novel inflammatory biomarker with prognostic significance for coronavirus disease and pancreatitis; however, no study has assessed its correlation with the severity of colonic diverticulitis.MethodsThis single-center retrospective cohort study included patients older than 18 years who presented to the emergency department between November 1, 2020, and May 31, 2021, and received a diagnosis of acute colonic diverticulitis after abdominal computed tomography. The characteristics and laboratory parameters of patients with simple versus complicated diverticulitis were compared. The significance of categorical data was assessed using the chi-square or Fisher’s exact test. The Mann–Whitney U test was used for continuous variables. Multivariable regression analysis was performed to identify predictors of complicated colonic diverticulitis. Receiver operator characteristic (ROC) curves were used to test the efficacy of inflammatory biomarkers in distinguishing simple from complicated cases.ResultsOf the 160 patients enrolled, 21 (13.125%) had complicated diverticulitis. Although right-sided was more prevalent than left-sided colonic diverticulitis (70% versus 30%), complicated diverticulitis was more common in those with left-sided colonic diverticulitis (61.905%, p = 0.001). Age, white blood cell (WBC) count, neutrophil count, C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and MDW were significantly higher in the complicated diverticulitis group (p < 0.05). Logistic regression analysis indicated that the left-sided location and the MDW were significant and independent predictors of complicated diverticulitis. The area under the ROC curve (AUC) was as follows: MDW, 0.870 (95% confidence interval [CI], 0.784–0.956); CRP, 0.800 (95% CI, 0.707–0.892); NLR, 0.724 (95% CI, 0.616–0.832); PLR, 0.662 (95% CI, 0.525–0.798); and WBC, 0.679 (95% CI, 0.563–0.795). When the MDW cutoff was 20.38, the sensitivity and specificity were maximized to 90.5% and 80.6%, respectively.ConclusionsA large MDW was a significant and independent predictor of complicated diverticulitis. The optimal cutoff value for MDW is 20.38 as it exhibits maximum sensitivity and specificity for distinguishing between simple and complicated diverticulitis The MDW may aid in planning antibiotic therapy for patients with colonic diverticulitis in the emergency department.

Aim: Acute pancreatitis is a common disease that can be fatal at advanced stages. Therefore, early evaluation of the prognosis of acute pancreatitis is important. The aim of this study was to evaluate the importance of monocyte distribution width in defining the prognosis of acute pancreatitis. Materials and Methods: The study included patients hospitalized with the diagnosis of acute biliary pancreatitis between December 2019 and October 2020. The cases were evaluated in 2 groups as mild pancreatitis and non-mild pancreatitis. The groups were compared in terms of age, white blood cell, neutrophil count, C-reactive protein, length of hospital stay, neutrophil to lymphocyte ratio, Monocyte Distribution Width, amylase, Aspartate Aminotransferase, albumin, and lactate dehydrogenase. Results: A statistically significant difference was determined between the mild pancreatitis group (n:59) and non-mild pancreatitis group (n:48) in terms of white blood cell, neutrophil count, C-reactive protein, Monocyte Distribution Width and length of hospital stay (p &amp;lt;0.05). When the cut-off value for Monocyte Distribution Width was taken as 703.00, sensitivity was 50.94% and specificity was 61.11.8%. Conclusion: The Monocyte Distribution Width value is a parameter that can be used to differentiate mild pancreatitis from non-mild pancreatitis. More extensive studies are needed for a clearer evaluation.

MP40-02 MONOCYTE DISTRIBUTION WIDTH (MDW) TO DIAGNOSE UROSEPSIS IN PATIENTS WITH URINARY STONES AND TO MONITOR THEIR RESPONSES TO THERAPIES IN AN EMERGENCY SETTING

This study aims to investigate whether combining scoring systems with monocyte distribution width (MDW) improves early sepsis detection in older adults in the emergency department (ED). In this prospective observational study, we enrolled older adults aged≥60 years who presented with confirmed infectious diseases to the ED. Three scoring systems-namely quick sepsis-related organ failure assessment (qSOFA), Modified Early Warning Score (MEWS), and National Early Warning Score (NEWS), and biomarkers including MDW, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), were assessed in the ED. Logistic regression models were used to construct sepsis prediction models. After propensity score matching, we included 522 and 2088 patients with and without sepsis in our analysis from January 1, 2020, to September 30, 2021. NEWS≥5 andMEWS≥3 exhibited a moderate-to-high sensitivity anda low specificity for sepsis, whereas qSOFA score≥2 demonstrated a low sensitivity and a high specificity. When combined with biomarkers, the NEWS-based, the MEWS-based, and the qSOFA-based models exhibited improved diagnostic accuracy for sepsis detection without CRP inclusion (c-statistics=0.842, 0.842, and 0.826, respectively). Of the three models, MEWS≥3 with white blood cell (WBC) count≥11×109/L, NLR≥8, and MDW≥20 demonstrated the highest diagnostic accuracy in all age subgroups (c-statistics=0.886, 0.825, and 0.822 in patients aged 60-74, 75-89, and 90-109 years, respectively). Our novel scoring system combining MEWS with WBC, NLR, and MDW effectively detected sepsis in older adults.

Background Sepsis is the leading cause of in-hospital death. Outcome improvement requires rapid detection and early antimicrobial therapy. The complete blood count (CBC) is ordered for more than two-thirds of all patients in the emergency department (ED). Individual CBC components have limited utility for sepsis screening due to low specificity and sensitivity. We sought to create a reliable sepsis screening tool by combining components of the CBC differential. Methods In this single-center retrospective cohort study, all adult patients who had a CBC with differential performed within 6 h of ED arrival during a 20-month period were eligible for inclusion. Repeat ED visits by the same patient were excluded. Our primary outcome was manifestation of sepsis within 72 h of ED arrival, detected from timestamped electronic health records using a previously validated electronic phenotype based on Sepsis-3 consensus criteria. Multivariable logistic regression was performed to identify individual components of the CBC differential that were independently associated with our outcome and to identify optimal cutoffs for discretization. Odds ratios were used to assign weights to each component and to derive a 10-point system for scoring likelihood of sepsis. Results 34 864 patients were included; 1306 (3.7%) met sepsis outcome criteria within 72 h of ED arrival and 181 (0.5%) had septic shock. White blood cell (WBC) count, monocyte distribution width (MDW), and the neutrophil to lymphocyte count ratio were found to predict sepsis. As shown in the figure, there was a linear relationship between our CBC infection severity index and likelihood of developing sepsis and septic shock. Patients with a high risk score (8 or above) had a greater than one in four chance of developing sepsis within 72 h. Conclusion A simple ten-point index derived from the most commonly used laboratory panel in medicine reliably estimated likelihood of developing sepsis.

Objectives The diagnosis of sepsis in the Emergency Department (ED) is challenging and a reliable biomarker is needed. The current study aimed to evaluate the diagnostic accuracy of monocyte distribution width (MDW) for the early identification of sepsis in the ED. Methods We performed a large observational study including consecutive adult patients (≥18 years of age) presenting to the ED between September and November 2019, with an order for complete blood count (CBC) evaluation. A total of 2,215 patients were enrolled and classified based on Sepsis-2 criteria as the control group (1,855), infection group (172), Systemic Inflammatory Response Syndrome (SIRS) group (100), and sepsis group (88). Results MDW levels were higher in patients with sepsis than in all other groups (p<0.001). ROC curve analysis showed an optimal diagnostic accuracy of MDW for sepsis prediction at a cut-off point of 23.5, with an AUC of 0.964, sensitivity and specificity of 0.920 and 0.929, respectively. Conclusions Our findings encourage further investigation to validate the use of MDW as a screening tool for the early identification of patients at risk of sepsis in the ED.

OBJECTIVES (BACKGROUND):Monocyte anisocytosis (monocyte distribution width [MDW]) has been previously validated to predict sepsis and outcome in patients presenting in the emergency department and mixed-population ICUs. Determining sepsis in a critically ill surgical/trauma population is often difficult due to concomitant inflammation and stress. We examined whether MDW could identify sepsis among patients admitted to a surgical/trauma ICU and predict clinical outcome.DESIGN:Secondary analysis of three prospective observational clinical studies.SETTING:Single institution ICU.PATIENTS/SUBJECTS:Two hundred thirty-eight participants were included in this study: 107 patients who were admitted to the ICU and adjudicated to have sepsis, 80 patients who were considered critically ill nonseptic (CINS), and 51 healthy control participants.INTERVENTIONS:MDW was measured among hospitalized patients admitted to the ICU with the diagnosis of sepsis or CINS patients at risk of developing sepsis. Blood samples were collected at admission and at intervals during ICU admission.MEASUREMENTS AND MAIN RESULTS:MDW significantly differed between septic and CINS patients on ICU admission (26.4, interquartile range [IQR, 23.5–30.8] vs. 20.1 [IQR, 17.9–21.9]; p < 0.001) and could discriminate with an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.79–0.91; p < 0.001). An MDW of greater than 22.0 at admission to the ICU could identify sepsis with a 78% specificity and a 90% sensitivity but could not discriminate in-hospital, 30-day, or 90-day mortality.LIMITATIONS:Small sample size from a single institution. Our analysis did not include other relevant biomarkers such as procalcitonin, C-reactive protein, and interleukin-6. In the imputation of missing values, linear mixed-effect models were used, risking model misspecification and the violation of the missing-at-random assumption.CONCLUSIONS:Among surgical/trauma ICU patients, MDW can discriminate between sepsis and nonseptic inflammation, but it is a weak predictor of mortality.

Objectives Lactate/albumin (L/A) ratio is a biomarker in sepsis that has been shown to outperform lactate. This prospective study aims to validate the superior prognostic value of the L/A ratio to lactate in sepsis and septic shock. Methods Prospective cohort conducted from September 2018 till February 2021 on adult patients presenting to the Emergency Department (ED) at a tertiary care centre with sepsis or septic shock. The primary outcome was the prognostic value of the L/A ratio compared to lactate with regards to mortality. Results A total of 939 septic patients were included throughout the study period. A total of 236 patients developed septic shock. The AUC value of the L/A ratio in septic patients was 0.65 (95% CI 0.61–0.70) and was higher than that of lactate alone 0.60 (95% CI 0.55–0.64) with a p < .0001. The optimal L/A ratio cut-off threshold that separated survivors from non-survivors was found to be 0.115 for all septic patients. The AUC of the L/A ratio was significantly higher for patients with a lactate ≥2 mmol/L: 0.69 (95% CI 0.64–0.74) versus 0.60 (95% CI 0.54–0.66) with a p < .0001 as well as for patients with an albumin level less than 30 g/L (AUC = 0.69 95% CI= 0.62–0.75 vs AUC= 0.66 95% CI= 0.59–0.73, p = .04). Among septic shock patients there was no statically significant difference in the AUC value of the L/A ratio compared to lactate (0.53 95% CI 0.45–0.61 vs 0.50 95% CI 0.43–0.58 respectively with a p-value = .11). Conclusions The L/A ratio is a better predictor of in-patient mortality than lactate in sepsis patients. This superiority was not found in the septic shock subgroup. Our results encourage the use of the ratio early in the ED as a superior prognostic tool in sepsis patients. Key messages We aimed to assess the prognostic usefulness of the Lactate/Albumin ratio compared to lactate alone in septic and septic shock patients. The L/A ratio proved to be a better predictor of in-patient mortality than lactate alone in sepsis patients. This pattern also applies across various subgroups in our study (malignancy, diabetics, age above 65, lactate level less than 2 mmol/L, albumin less than 30 g/L). Our results favour the use of the L/A ratio over lactate alone in patients with sepsis and the previously mentioned subgroups. Our results do not favour the use of the ratio instead of lactate in septic shock patients as there was no statistically significant difference between the AUCs of the ratio and lactate alone.

SUMMARYOBJECTIVE: Sepsis and septic shock are clinical conditions with high mortality and an ever-increasing prevalence, and early diagnosis is of great importance in treating these diseases. Increase in serum Galectin-3 protein in septic patients is associated with increased inflammation, which in turn is associated with mortality. This study aimed to investigate the diagnostic importance of serum Galectin-3 levels and its relationship with in-hospital mortality in sepsis and septic shock patients.METHODS: This prospective cohort study included 44 sepsis and 44 septic shock patients. Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation 2 score were calculated. In addition, routine clinical and laboratory parameters along with serum Galectin-3 were evaluated.RESULTS: Serum Galectin-3 levels were significantly higher in the septic shock group [4.1 (0.1-10.2) vs. 6.0 (0.1-11.3) ng/mL, respectively; p=0.01]. Moreover, patients with a Galectin-3 level <6.94 ng/mL were associated with longer survival [31.4 vs. 23.1 days; hazards ratio, 1.85; 1.03-3.34, p=0.03]. More importantly, the need for mechanical ventilation, the duration of mechanical ventilation, and serum Galectin-3 levels were independent prognostic factors and predicted poor in-hospital survival in both sepsis and septic shock patients.CONCLUSION: These findings suggest that Galectin-3 levels are higher in septic shock patients and predict mortality. In addition, high serum Galectin-3 levels, together with mechanical ventilation requirement and mechanical ventilation duration, are closely associated with poor in-hospital survival. Therefore, Galectin-3 may be a valuable diagnostic and prognostic biomarker in these patients.

Point: Adherence to Early Goal-Directed Therapy: Does It Really Matter? Yes. After a Decade, the Scientific Proof Speaks for Itself

Background: Sepsis is the leading cause of mortality in intensive care units (ICUs). However, early diagnosis and prognosis of sepsis and septic shock are still a great challenge. Pentraxin-3 (PTX3) was shown to be associated with the severity and outcome of sepsis and septic shock. This study was carried out to investigate the diagnostic and prognostic value of PTX3 in patients with sepsis and septic shock based on Sepsis 3.0 definitions. Methods: In this single-center prospective observational study, all patients’ serum was collected for biomarker measurements within 24 h after admission. Logistic and Cox regression analyses were used to identify the potential biomarkers of diagnosis, severity stratification, and prediction. Results: Serum levels of PTX3 were significantly increased on the first day of ICU admission, while septic shock patients had highest PTX3 levels than other groups. A combination between PTX3 and procalcitonin (PCT) could better discriminate sepsis and septic shock, and PTX3 was an independent predictor of mortality in sepsis and septic shock patients. Conclusion: PTX3 may be a robust biomarker to classify the disease severity and predict the 90-day mortality of sepsis and septic shock based on the latest Sepsis 3.0 definitions.

Sepsis and Myocardial Depression in a Young Woman

IntroductionGuidelines dealing with severe sepsis and septic shock mostly rely on randomized controlled trials (RCTs) to ensure the best standards of care for patients. However, patients included in high-quality studies may differ from the routine population and alter external validity of recommendations. We aimed to determine to what extent non-inclusion criteria of RCTs dealing with severe sepsis and septic shock may affect application of their conclusions in routine care.MethodsIn a first step, the MEDLINE database was searched for RCTs treating severe sepsis and septic shock patients between 1992 and 2008, and non-inclusion criteria for these studies were abstracted. Two reviewers independently evaluated the articles, which were checked by a third reviewer. We extracted data on the study design, main intervention, primary endpoint, criteria for inclusion, and criteria for non-inclusion. In a second step, the distribution of the non-inclusion criteria was observed in a prospective multicenter cohort of severe sepsis and septic shock patients (Cub-Rea network, 1992 to 2008).ResultsWe identified 96 articles out of 7,012 citations that met the screening criteria. Congestive heart failure (35%) and cancer (30%) were frequent exclusion criteria in selected studies, as well as other frequent disorders such as gastrointestinal and liver diseases and all causes of immune suppression. Of the 67,717 patients with severe sepsis and septic shock in the Cub-Rea database, 40,325 (60%) experienced at least one of the main exclusion criteria, including 11% of congestive heart failure patients and 11% of cancer patients. In addition, we observed a significant trend for increasing number of patients with these criteria along time.ConclusionCurrent exclusion criteria for RCTs dealing with severe sepsis and septic shock excluded most patients encountered in daily practice and limit external validity of the results of high-quality studies.