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Acinetobacter baumannii causes healthcare-associated infections worldwide. Capsular polysaccharide (CPS) is shown an important virulence factor of A. baumannii both in vitro and in vivo. Capsule locus 2 (KL2) for CPS is the most common KL type and is associated with carbapenem resistance. It is unclear whether KL2 is related to the clinical outcome of invasive A. baumannii infection. Here we had followed patients with A. baumannii bacteraemia prospectively between 2009 and 2014. One-third of the unduplicated blood isolates were randomly selected each year for microbiological and clinical studies. The KL2 gene cluster was identified using polymerase chain reaction. A total of 148 patients were enrolled randomly. Eighteen isolates (12.2%) carried KL2, and 130 isolates (87.8%) didn't. Compared with non-KL2 isolates, KL2 isolates had significantly higher resistance to imipenem, sulbactam, and tigecycline. Compared with the non-KL group, in the KL2 group, the hospital stay before development of bacteraemia was longer (P

INTRODUCTION: Organs procured following brain stem death (BSD) are the main source of organ grafts for transplantation. However, BSD is associated with inflammatory responses that may damage the organ and affect both the quantity and quality of organs available for transplant. Therefore, we aimed to investigate plasma and bronchoalveolar lavage (BAL) pro-inflammatory cytokine profiles and cardiovascular physiology in a clinically relevant 6-hour ovine model of BSD. METHODS: Twelve healthy female sheep (37‒42 Kg) were anaesthetized and mechanically ventilated prior to undergoing BSD induction and then monitored for 6 hours. Plasma and BAL endothelin-1 and cytokines (IL-1β, 6, 8 and tumour necrosis factor alpha (TNF-α)) were assessed by ELISA. Differential white blood cell counts were performed. Cardiac function during BSD was also examined using echocardiography, and cardiac biomarkers (A-type natriuretic peptide and troponin I were measured in plasma. RESULTS: Plasma concentrations big ET-1, IL-6, IL-8, TNF-α and BAL IL-8 were significantly (p < 0.01) increased over baseline at 6 hours post-BSD. Increased numbers of neutrophils were observed in the whole blood (3.1×109 cells/L [95% confidence interval (CI) 2.06 - 4.14] vs. 6×109 cells/L [95%CI 3.92 - 7.97]; p < 0.01) and BAL (4.5×109 cells/L [95%CI 0.41 - 9.41] vs. 26 [95%CI 12.29 - 39.80]; p=0.03) after 6 hours of BSD induction vs baseline. A significant increase in ANP production (20.28 pM [95%CI 16.18 - 24.37] vs. 78.68 pM [95%CI 53.16 - 104.21];p < 0.0001) and cTnI release (0.039 ng/mL vs. 4.26 [95%CI 2.69 - 5.83] ng/mL; p < 0.0001), associated with a significant reduction in heart contractile function, were observed between baseline and 6 hours. CONCLUSIONS: BSD induced systemic pro-inflammatory responses, characterized by increased neutrophil infiltration and cytokine production in the circulation and BAL fluid, and associated with reduced heart contractile function in ovine model of BSD.

The present study aimed to explore the efficacy and safety of roxadustat in patients with renal anemia and erythropoietin (EPO) hyporesponsive who are receiving continuous ambulatory peritoneal dialysis (CAPD).This is a single center, before and after treatment, self-controlled study; 55 CAPD patients with renal anemia and EPO hyporesponsiveness were enrolled. The main follow-up parameters included routine blood, liver and kidney function, electrolyte, blood lipid, high-sensitivity C-reactive protein, and iron tests. Serum samples were used to determine interleukin-6 and tumor necrosis factor-α levels via enzyme linked immunosorbent assay. The Modified Quantitative Subjective Global Assessment Score and Malnutrition-Inflammation Score before and after treatment, and adverse events during treatment were recorded. The follow-up observation time was 12 weeks. Preliminary data 12-24 weeks before the enrollment as well as post-follow-up data at 36 weeks were also collected.Fifty patients completed the 12-week follow-up. The hemoglobin levels were 8.0 ± 1.2 g/dL at baseline and 11.2 ± 2.0 g/dL after 12 weeks of roxadustat treatment. The hemoglobin increases at all measured time points and was statistically significant compared with the baseline value (P .05). The overall hemoglobin response rate (hemoglobin increase ≥ 1.0 g/dL) was 80%, and 50% of the patients reached the hemoglobin target (hemoglobin ≥ 11.0 g/dL) at 12 weeks. Transferrin was higher at 12 weeks (2.2 ± 0.5 g/L) than at baseline (1.7 ± 0.5 g/L) (P .05), while serum ferritin levels slightly decreased compared with the baseline value (P .05). The median high-sensitivity C-reactive protein level and other inflammation-related indicators, such as white blood cell counts, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, interleukin-6, and tumor necrosis factor-α, were not significantly different from their baseline values. Nutrition-related biochemical indices such as albumin, creatinine, and blood lipids were also not significantly changed. The Modified Quantitative Subjective Global Assessment Score and Malnutrition-Inflammation Score were slightly lower at 12 weeks than at baseline. No serious adverse events were observed during the follow-up period. Post-follow-up data revealed a maintained hemoglobin level in patients who remained on roxadustat treatment while those switched back to EPO treatment after 12 weeks resulted in a decreased hemoglobin at 36 weeks.In patients with EPO hyporesponsiveness on CAPD, roxadustat can efficiently and safely improve anemia and nutritional status without promoting inflammation.

Background Necrotizing fasciitis (NF) is a life-threatening and acute progressive soft tissue infection and needs early surgical intervention, that is, debridement or amputation. Surgical strategy or prognosis is influenced by the speed of progression and patients’ general condition, which can be calculated by the Charlson Comorbidity Index (CCI). The purpose of this study was to investigate the association between the CCI scores and prognosis of patients with NF of the upper/lower extremities. Methods In the retrospective cohort study, we analyzed patients with NF of the upper/lower extremities who were determined to undergo surgery by orthopedic surgeons at four tertiary hospitals between August 2003 and April 2016. We divided the patients into two groups, Group L (low CCI scores of 0–2) and Group H (high CCI scores of ≥3). The primary event of this study was defined as death or amputation. Mortality cases were included when amputation was informed with documented certification but patients died while waiting for surgery. We compared the patients’ background, laboratory data on admission, the laboratory risk indicator for necrotizing fasciitis (LRINEC) score, and primary outcome between the two groups. Results Of the 56 patients, 28 patients were classified into Group L and the other 28 patients into Group H. The data in this study showed that patients in Group H had lower white blood cell counts and hemoglobin and higher creatinine than Group L, but there was no difference in LRINEC scores between the two groups. Streptococcus pyogenes was the most common infectious agent in Group L (54%) but not in Group H (11%). Poorer outcome was observed in Group H compared with Group L (4 mortality and 16 amputation vs. no mortality and 9 amputation, P = 0.007). Conclusions Laboratory data and causative microorganisms were different between high CCI and low CCI patients with NF. High CCI scores were associated with limb amputation or death caused by NF of the upper/lower extremities; whereas, low CCI scores were more likely associated with S. pyogenes monoinfection.

For early detection of surgical site infection (SSI) following spinal decompression surgery, we compared temporal changes in the values of laboratory markers that are not affected by operative parameters.The study included 302 patients, which were divided into an SSI group (patients who developed deep SSI) and a non-SSI group for analysis. We reviewed data on C-reactive protein level, total white blood cell (WBC) count, and WBC differential percentage and count before spinal decompression, on postoperative day 1, and on postoperative day 4. We identified laboratory markers that are not affected by operative parameters (operating time, intraoperative blood loss, and number of operative segments). Laboratory markers with a significant difference observed between the peak or nadir value and the value in the subsequent survey day were considered as an indicator of SSI. We examined the utility of each indicator by calculating sensitivity and specificity. Furthermore, we investigated the utility of the combination of all five indicators (wherein the recognition of one marker was considered positive).Temporal changes in five laboratory markers were considered indicators of SSI. The changes from postoperative day 1 to postoperative day 4 were as follows: (1) increased WBC count (42% sensitivity, 88% specificity), (2) increased neutrophil percentage (25% sensitivity, 96% specificity), (3) increased neutrophil count (25% sensitivity, 94% specificity), (4) decreased lymphocyte percentage (25% sensitivity, 95% specificity), and (5) decreased lymphocyte count (25% sensitivity, 85% specificity). The combination of these five markers showed a 50% sensitivity, 81% specificity, and 0.65 AUC.Five markers were found to be reliable indicators of SSI following spinal decompression surgery because they were not affected by operative parameters. The combination of all five indicators had moderate sensitivity and high specificity. Therefore, this may be reliable and useful for the early detection of SSI.

Background and aim Plantago major has long been used for medical purposes in Indonesia. However, reports on the anti-arthritic activities of P. major are limited. Experimental procedure The anti-arthritic properties of an n-hexane-insoluble fraction of dichloromethane extracts of P. major (IPM) were evaluated using Complete Freund's Adjuvant (CFA)-induced arthritis induced in female Wistar rat by CFA. Diclofenac was used as a positive control. The volume of paw oedema, white blood cell count, lymphocytes, neutrophils, expression of TNF-α and Interleukin-6 and the histopathological features of the joint tissues were assessed to characterise IPM activity. Results The IPM extract at doses of 280 and 420 mg/kg BW and diclofenac inhibited paw oedema by 15.70 %, 15.94 % and 19.71 % respectively. IPM also reduced the incidence of arthritis and arthritic index. Unlike untreated rats, animals treated with IPM showed a significant decrease in the number of neutrophils and decreased expression of TNF-α and Interleukin-6. Histopathological examination showed a reduction in the number of inflammatory cells and hyperplasia of the synovium after IPM treatment. Conclusion This study showed that P. major displays anti-rheumatoid arthritis activity.

Background Postoperative lymphopenia (PL) after spine surgery is reported to be an indicator of surgical-site infection (SSI). PL without SSI is often encountered, resulting in a treatment dilemma. We focused on PL, so as to improve the accuracy of detecting SSI. Methods In total, 329 patients underwent spine surgery, including nine patients presenting with SSI. The complete blood cell counts, differential counts, and C-reactive protein (CRP) level were measured pre-surgery and on postoperative days 2, 7, and 14. The relationships between PL and SSI were evaluated, and PL and non-PL conditions were compared among all cases. We then divided the patients into two groups: PL and non-PL, and determined the useful serological markers using receiver operating characteristic curves. Results Sixty-one patients presented with PL, including four with SSI. However, PL was not directly suggested as a biomarker of SSI (p = 0.067). We revealed PL as a risk factor for SSI (p = 0.004, Odds ratio: 7.54). Among all cases, the lymphocyte count and CRP level differed significantly between the PL and non-PL groups at all perioperative time-points. The white blood cell count, neutrophil count, and CRP levels on postoperative day 7 significantly differed between the SSI and non-SSI cases in the PL group. The area under the curve (AUC) for CRP was greater than that of the other parameters. The neutrophil count was only effective as a marker in the non-PL group. The combination of two cutoff values (CRP: 3.7 mg/dL (PL group) and neutrophil count: 6172/μL (non-PL group)) presented high specificity (87.2%) and sensitivity (88.9%), while only one cutoff value (CRP: 2.9 mg/dL) had a specificity of 77.4% and sensitivity of 77.8%. Conclusions Approximately one-fifth of patients developed PL post-surgery, which was a risk factor for SSI, with constant high inflammation. Grouping based on PL and establishing diagnostic cutoff values are more appropriate than establishing only one cutoff value for overall cases.

Background and aims White blood cell (WBC) count is an easily obtainable biomarker of systematic inflammation. Our study aimed to investigate the associations of differential WBC count with all-cause and cause-specific mortality in a general Asian population. Methods and Results Cox proportional hazards model was used to evaluate the associations of WBC count with mortality separately for men and women, with adjustment for multiple variables including age, smoking, and other lifestyle factors. Stratified analyses by age, smoking, diabetes, and hypertension were conducted to explore potential effect modification. Elevated WBC count was significantly associated with increased mortality risk. The adjusted hazard ratios of total WBC (10th decile compared to decile of lowest risk) for all-cause mortality were 1.42 (95% CI: 1.33, 1.53) for men and 1.54 (95% CI: 1.42, 1.68) for women. Similar risks were observed for neutrophils, monocytes, and neutrophil/lymphocyte (NL) ratio. The highest deciles of neutrophils, monocytes, and NL ratio were also positively associated with risk of cardiovascular/cerebrovascular, cancer, and respiratory mortality after adjusting for covariates. Results for all-cause mortality remained statistically significant for participants who were Conclusions Total and differential WBC counts (neutrophils, monocytes, and NL ratios) are positively associated with increased risk of all-cause mortality, cardiovascular and cerebrovascular, cancer, and respiratory mortality among Taiwanese adults.

BACKGROUND As the complication of infective endocarditis (IE), embolic events are associated with increased mortality and morbidity. However, there are no reliable indicators to predict embolism. The aim of this study was to evaluate neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker to identify IE patients at high risk of embolism. METHODS We conducted a prospective observational study of IE patients from January 2018 to December 2020. Plasma NGAL levels were measured in 88 IE patients (37 patients with embolic events and 51 patients without embolic events), 91 noninfectious heart valve disease patients, and 20 healthy blood donors by enzyme-linked immunosorbent assay. Native valve tissue was obtained from 16 IE patients and 16 noninfectious heart valve disease patients. Western blot and immunohistochemical staining were performed to detect NGAL and matrix metalloproteinase-9. RESULTS Higher levels of NGAL were observed in IE patients than in noninfectious heart valve disease patients (P < .001) or healthy blood donors (P < .01). In addition, NGAL levels were higher in IE patients with embolic events compared with patients not having embolic events (P < .001). Receiver-operating characteristics analysis demonstrated that NGAL acted as a potential embolic events predictor with the cutoff value of 166.78 ng/mL. The IE patients with higher NGAL levels had significantly more severe native valve morphologic changes. The NGAL was colocalized with matrix metalloproteinase-9, and their expression in the valves of IE patients was higher than in those of noninfectious heart valve disease patients. CONCLUSIONS Neutrophil gelatinase-associated lipocalin is a potential predictor of embolic events in IE. That may be attributed to its potency of increasing the proteolytic activity of matrix metalloproteinase-9, which leads to valve morphologic impairment.

Introduction Leg ulcers (LUs) are relatively common in patients with sickle cell anemia (SCA). The role of inflammation and nitric oxide (NO) pathways in the pathophysiology of the LU is not understood. Objective The aim of this study was to verify the association between inflammatory molecules and nitric oxide metabolites (NOx) and the occurrence of the LU in patients with SCA. Method It was a cross-sectional study on adult participants with SCA followed at Fundacao Hemominas, a public blood center in Brazil. Eligible participants were recruited and included in one of two groups: Group 1, comprised of cases with SCA (Hb SS) and at least one LU at the time of inclusion in the study and Group 2, comprised of controls with SCA without a history of LU, matched by sex and age to cases. Participants were interviewed to obtain sociodemographic data and blood samples were collected. Clinical and laboratory data were abstracted from medical records. Nitric oxide metabolites (NOx) and inflammatory molecules were quantified using an immunoassay and Multiplex xMAP® technology, respectively. Eighty-seven individuals were included, ranging in age from 17 to 61 years (mean 40 ± 10.7 years); 30 had LU and 57 were controls without LU. Results Participants with LU had significantly higher levels of interleukin 8 (IL-8), IL-10, IL-15, NOx and platelet and white blood cell (WBC) counts, when compared to those without LU. Participants with LU had a significantly higher risk of having a history of osteomyelitis and a higher use of antiseptic soap in bathing, when compared to those without LU. Conclusion In conclusion, our results showed that NOx, inflammatory molecules and hematological features were associated with LU in Brazilian adults with SCA.

Background There is limited literature on the role of percutaneous transhepatic biliary drainage (PTBD) as an adjunct to endoscopic retrograde cholangiopancreatography (ERCP). This study evaluates the role of PTBD in patients with failed ERCP or post-ERCP cholangitis. Methods Retrospective evaluation of clinical and intervention records of patients with biliary obstruction referred for PTBD following failed ERCP or post-ERCP cholangitis was performed. The cause of biliary obstruction, baseline serum bilirubin, white blood cell (WBC) count, serum creatinine, and procalcitonin were recorded. Technical success and clinical success (resolution of cholangitis, reduction in bilirubin levels, WBC count, creatinine, and procalcitonin) were assessed. Results Sixty-three patients (35 females, mean age 51.4 years) were included. Indications for ERCP included malignant causes in 47 (74.6%) cases and benign causes in 16 (25.4%) cases. Indications for PTBD were failed ERCP in 21 (33.3%) and post-ERCP cholangitis in 42 (66.7%). PTBD was technically successful in all patients. Clinical success rate was 68.2% in the overall group. Mild hemobilia was noted in five (7.9%) patients. There were no major complications or PTBD related mortality. Cholangitis and acute kidney injury resolved following PTBD in 63.1% and 80% of the patients, respectively. Total serum bilirubin reduced by 47.8% and 69.4% after one week and one month of the PTBD, respectively. The average fall in procalcitonin was 5.17 ng/mL after one week of the PTBD. Conclusion PTBD is an important adjunctive drainage procedure in patients with ERCP failure or post-ERCP cholangitis.

Background Diagnosing early periprosthetic joint infection (PJI) after primary total hip arthroplasty (THA) remains challenging. We sought to validate optimal laboratory value cutoffs for detecting early PJIs in a series of primary THAs from one institution. Methods We retrospectively identified 22,795 primary THAs performed between 2000 and 2019. Within 12 weeks, 43 hips (43 patients) underwent arthrocentesis. Patients were divided into 2 groups: evaluation ≤6 weeks or 6-12 weeks following THA. The 2011 Musculoskeletal Infection Society major criteria for PJI diagnosed PJI in 15 patients. Mann-Whitney U-tests were used to compare median laboratory values and receiver operating characteristic curve analysis was used to evaluate optimal cutoff values. Results Both within 6 weeks and between 6 and 12 weeks postoperatively, median C-reactive protein (CRP), erythrocyte sedimentation rate, synovial white blood cell (WBC) count, neutrophil percentage, and absolute neutrophil count (ANC) values were significantly higher in infected THAs. Optimal cutoffs within 6 weeks were: CRP ≥100 mg/L, synovial WBCs ≥4390 cells/μL, neutrophil percentage ≥74%, and ANC ≥3249 cells/μL. Between 6 and 12 weeks, optimal cutoffs were: CRP ≥33 mg/L, synovial WBCs ≥26,995 cells/μL, neutrophil percentage ≥93%, and ANC ≥25,645 cells/μL. Conclusion Early PJI following THA should be suspected within 6 weeks with CRP ≥100 mg/L or synovial WBCs ≥4390 cells/μL. Between 6 and 12 weeks postoperatively, cutoffs of CRP ≥33 mg/L, synovial fluid WBC ≥26,995 cells/μL, and neutrophil percentage ≥93% diagnosed PJI with high accuracy. Level of Evidence Level IV Diagnostic.

Purpose 1) To assess the efficacy of C reactive protein (CRP) and white blood cell count (WBC) levels as a diagnostic, prognostic, and monitoring tools for determining the severity of bacterial orofacial infections, length of hospital stay (LOS), and the effectiveness of treatment. 2) To evaluate the sensitivity and specificity of CRP and WBC as an inflammatory markers in bacterial orofacial infections. Methods This prospective study included 30 patients. The predictor variables were serial readings of CRP and WBC that were correlated with clinical course of orofacial infection including severity of infection, length of hospital stay, and effectiveness of treatment. P value was set at ( Results The sample composed of 30 patients with a mean age of 26.7 years, 47% female. Predrainage CRP and WBC were significantly positive in predicting severity of infection and length of hospital stay. Predrainage CRP readings were elevated in 93% of patients whereas WBC predrainage readings were elevated in only 56% of patients with orofacial infections. Sensitivity and specificity of CRP are 87.5 and 68%, respectively while sensitivity and specificity of WBC are 62.6 and 86.4%, respectively. Conclusion The results of this study suggest that CRP and WBC are useful diagnostic and prognostic, as well as monitoring, tools in bacterial orofacial infections CRP being more sensitive than WBC.

Objectives: To evaluate the incidence and causes of occult bacteremia and whether clinical profiles and complete blood count could reliably identify high-risk-for-bacteremia children aged 3 to 36 months who had fever without source (FWS).Material and Methods: The medical data of children aged 3 to 36 months who presented with FWS for 1 to 7 days but with no clinical signs of sepsis and were subsequently hospitalized between January 2007 and December 2017 with one or more of the following high risk features, body temperature >39 degrees Celsius, inactive behavior, white blood cell (WBC) count >15,000 cells per cubic millimeter (cells/mm3 ), absolute neutrophil count >10,000 cells/mm3 , or absolute band count >1,500 cells/mm3 , were recorded.Results: Bacteremia was found in 12 of 160 (7.5%) children with one or more of the high-risk features. The pathogens were non-typhoidal Salmonella (5 patients), Streptococcus pneumoniae (4 patients), and Salmonella Typhi (3 patients). None of the high-risk features could differentiate between children with and without bacteremia. Five of the 8 patients with Salmonella septicemia had normal WBC counts leading to delays in prescribing empirical antibiotics and none of them had complications. None of the 117 patients in the non-bacteremia group who did not receive antibiotics or discontinued them after negative hemoculture had complications during hospitalization.Conclusion: High-risk features could not help to identify occult bacteremia in children aged 3-36 months who had FWS.

BACKGROUND The relationship of early catheter-related bloodstream infections (CRBSIs) with perioperative neutropenia and antibiotic prophylaxis is not well established. We sought to evaluate perioperative factors associated with early CRBSIs in newly diagnosed pediatric cancer patients, particularly hematological indices and antibiotic use. METHODS We retrospectively reviewed national registry records of newly diagnosed pediatric cancer patients with port-a-caths inserted using standardized perioperative protocols where only antibiotic use was not regulated. Thirty-day postoperative CRBSI incidence was correlated with preoperative factors using logistic regression and with postoperative blood counts using linear trend analysis. RESULTS Among 243 patients, 17 CRBSIs (7.0%) occurred at median 14 (range, 8-28) postoperative days. Early CRBSIs were significantly associated with cancer type [acute myeloid leukemia and other leukemias (AML/OLs) vs. solid tumors and lymphomas (STLs): odds ratio (OR), 5.09; P = 0.0036; acute lymphoblastic leukemia vs. STL: OR 0.83; P = 0.0446] but not preoperative antibiotics, absolute neutrophil counts and white blood cell counts. Thirty-day postoperative absolute neutrophil counts and white blood cell trends differed significantly between patients with acute lymphoblastic leukemia and STLs (OR 0.83, P < 0.05) and between AML/OLs and STLs (OR 5.09, P < 0.005), with AML/OL patients having the most protracted neutropenia during this period. CONCLUSIONS Contrary to common belief, low preoperative absolute neutrophil counts and lack of preoperative antibiotics were not associated with higher early CRBSI rates. Instead, AML/OL patients, particularly those with prolonged neutropenia during the first 30 postoperative days, were at increased risk. Our findings do not support the use of empirical preoperative antibiotics and instead identify prolonged postoperative neutropenia as a major contributing factor for early CRBSI.

Background: Insulin resistance is a well-known predictor and risk factor for Type 2 Diabetes Mellitus (T2DM). Higher hematocrit induced by higher insulin resistance affects blood rheology. Objective: This study intended to reveal the association between indices of insulin resistance and hemorheological parameters during a 75 g oral glucose tolerance test (75-g OGTT). Methods: A total of 575 healthy young Japanese participants took 75-g OGTT. We then analyzed the association between insulin resistance indices and hematological parameters. Results: The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly correlated with hematocrit (Ht), hemoglobin (Hb), Red Blood Cell (RBC), White Blood Cell (WBC), platelet count, lipid parameters, and Body Mass Index (BMI). The Matsuda index was negatively correlated with RBC count, WBC count, platelet count, Total Cholesterol (TC), Low-Density Lipoprotein-Cholesterol (LDL-C), triglyceride (TG), and positively correlated with High-Density Lipoprotein-Cholesterol (HDL-C). The disposition index was negatively correlated with Hb, RBC count, LDL-C, and BMI, while remaining positively correlated with HDL-C. The Homeostasis Model Assessment of beta cell (HOMA- IR ) was positively correlated with WBC count, platelet count, TC, LDL-C, and TG. The insulinogenic index was positively correlated with WBC count, platelet count, and TC. Multiple regression analysis revealed that HOMA-IR was independently associated with TG, and the Matsuda index was independently associated with TG, WBC count, and platelet count. The insulinogenic index was independently associated with WBC count. Conclusion: Cardinal rheological parameters reflected insulin resistance and were released even in the young, healthy Japanese individuals within the physiological range of glycemic control.

Aims The aim of this study was to investigate the efficacy and safety of ticagrelor monotherapy in patients undergoing percutaneous coronary intervention (PCI) stratified according to the baseline white blood cell (WBC) count. Methods and results This is a post hoc analysis of the GLOBAL LEADERS trial, a multi-centre, open-label, randomized all-comer trial in patients undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual anti-platelet therapy [DAPT]) with the reference strategy (12-month aspirin monotherapy following 12-month DAPT). Patients were stratified into two WBC groups, either < or ≥median WBC count of 7.8 × 109 cells/L (lower or higher WBC group, respectively). The primary endpoint was a composite of all-cause mortality or new Q-wave myocardial infarction at 2 years. Of 14 576 patients included in the present study, 7212 patients (49.5%) were classified as the lower WBC group, who had a significantly lower risk of both ischaemic and bleeding outcomes at 2 years. At 2 years, the experimental strategy was associated with a significant lower incidence of the primary endpoint compared with the reference strategy in the lower WBC group [2.8% vs. 4.2%; hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.52–0.86] but not in the higher WBC group (4.8% vs. 4.7%; HR: 1.01; 95% CI: 0.82–1.25; Pinteraction=0.013). There were no significant differences in the risks of Bleeding Academic Research Consortium type 3 or 5 bleeding between two anti-platelet strategies regardless of the WBC groups. Conclusion Increased WBC counts, which may reflect degree of inflammation, at the time of index procedure may attenuate the anti-ischaemic benefits of ticagrelor monotherapy observed in patients with lower WBC counts.

BACKGROUND: Studies have suggested that automated synovial cell counting may overestimate the white blood cell (WBC) count, resulting in false positive tests when evaluating patients for the possibility of periprosthetic joint infection (PJI) after THA. However, associations between WBC counts high enough to mimic PJI in patients whose arthroplasties are not infected but rather are experiencing a variety of aseptic problems—including but not limited to metallosis, polyethylene wear, and recurrent dislocation—have not, to our knowledge, been adequately addressed. In addition, there is a lack of analyses about the polymorphonuclear percentage (PMN%) when assessed by automated analyzers in this context. QUESTIONS/PURPOSES: In the context of different indications for aseptic revision and different periprosthetic hip pathologic findings, we asked: (1) What were the synovial WBC count levels, and what proportion of values were above the 2018 International Consensus Meeting (ICM) cutoff (3000 cells/μL)? (2) What were the synovial PMN% levels, and what proportion of values were above the 2018 ICM (70%)? METHODS: We retrospectively studied the preoperative cell count analyses of synovial fluid in patients who underwent revision THA for aseptic reasons at our tertiary referral arthroplasty center between January 2015 and December 2017. We considered all revisions performed on patients during that time potentially eligible, and after prespecified exclusions were applied (exclusions mainly included 15% [197 of 1306] sporadic missing data and 12% [155 of 1306] insufficient synovial fluid obtained in the aspirate), a total of 702 patients undergoing revision THA for aseptic reasons remained for the final analysis. As far as we know, no patients underwent re-revision for PJI at a mean follow-up of 46 ± 11 months, which tends to confirm our impression that indeed these hips did not have PJI. Cell count analyses were conducted using an automated analyzer. Clinical findings, preoperative radiographs, and surgical reports––confirmed by available histologic results––were used to establish diagnoses. We evaluated these hips considering the recommendations of the 2018 ICM (WBC count of 3000 cells/μL and PMN% of 70%) to see what proportion of them would have been characterized as likely having PJI on basis of those cutoff values. The mean WBC count for the entire cohort was 2120 ± 2395 cells/μL. The mean PMN% for the entire cohort was 36% ± 22%. RESULTS: Compared with aseptic loosening and recurrent dislocation, polyethylene wear had the highest mean WBC count (3817 ± 3711 cells/μL; p < 0.001). Of the investigated periprosthetic conditions, wear-induced synovitis had the highest value (4464 ± 3620 cells/μL; p < 0.001). Considering the ICM threshold, polyethylene wear showed the highest proportion of WBC counts above 3000 cells/μL among the indications for aseptic revision (60% [25 of 42]; p < 0.001). Of the periprosthetic conditions, wear-induced synovitis showed the highest proportion beyond the ICM cutoff (60% [50 of 83]; p < 0.001). The mean PMN% for aseptic causes ranged between 28% and 44% without differences among them (p = 0.12). Patients with metallosis had the highest mean PMN% of the periprosthetic conditions investigated (45% ± 25%; p = 0.007). Regarding the ICM threshold, metallosis resulted in the largest proportion of patients with a PMN% above 70% (21% [10 of 47]; p = 0.003), and that for wear-induced synovitis was 6% (5 of 83; p = 0.42) and for osteolysis was 3% (1 of 33; p = 0.51). There were no differences among aseptic loosening, recurrent dislocation, and polyethylene wear in terms of the proportion above 70% among the aseptic revision causes. CONCLUSION: Using automated cell counting, we found that WBC counts differ widely across indications for aseptic revision THA, and a high proportion of patients who underwent revision THA for aseptic reasons had WBC counts above the commonly used threshold of 3000 cells/μL. However, the PMN% was much less affected in several common indications for aseptic revision THA, making this measure more reliable for interpreting aspiration results using an automated analyzer. Based on the data distributions we observed, manual counting techniques might be considered in particular among patients with polyethylene wear, metal-on-metal bearing surfaces, or suspected metallosis. However, an elevated WBC count alone, observed using an automated analyzer in the context of polyethylene wear, should not be considered to be strongly suggestive of PJI, since that finding occurred so commonly among patients without infection. LEVEL OF EVIDENCE: Level III, diagnostic study.

Objective Agranulocytosis is a rare but serious adverse drug reaction (ADR) of thionamide antithyroid drugs (ATDs). We explored the characteristics of ADRs in patients with hyperthyroidism. Methods This retrospective study included 3558 inpatients with Graves disease treated in a Class A Grade 3 hospital between 2015 and 2019. The clinical presentation and laboratory workup of patients with antithyroid drug (ATD)-induced agranulocytosis was analyzed. Results Agranulocytosis was thought to be caused by ATDs in 36 patients. The hospital length of stay was 12 (10-16) days, and hospitalization costs were approximately $2810.89 ($2156.50-$4164.67). The median duration of ATD therapy prior to agranulocytosis development was 30 (20-40) days. Fever (83.33%) and sore throat (75%) were the most common symptoms as early signs of agranulocytosis. The lowest neutrophil counts were 0.01 (0.00-0.03) × 109/L and 0.14 (0.02-0.29) × 109/L in the methimazole and propylthiouracil groups, respectively (P = .037). The recovery times of agranulocytosis were 9.32 ± 2.89 days and 5.60 ± 4.10 days in the methimazole and propylthiouracil groups, respectively (P = .016). Patients with severe agranulocytosis required a longer time to recover (P Conclusions Patients with agranulocytosis needed a long hospital length of stay and incurred high costs. Methimazole was prone to causing a more serious agranulocytosis than propylthiouracil. High thyroid hormone was unlikely to play a role in adverse drug reactions. Patient education is important.

Background JAK2 mutation status is a well-known risk factor for thrombosis in patients with myeloproliferative neoplasms. However, the clinical usefulness of JAK2 allele burden is under investigation. Methods We retrospectively evaluated the impact of the JAK2 V617F allele burden on clinical characteristics and outcomes of JAK2 V617F-positive polycythemia vera (PV) and essential thrombocythemia (ET). The JAK2 V617F allele burden was measured using sequencing. Results Altogether, 127 patients with JAK2 V617F mutation (PV, N=61; ET, N=66) were included in this study. JAK2 V617F allele burdens were positively correlated with white blood cell counts, hemoglobin values, lactate dehydrogenase levels, and platelet counts. The median values of JAK2 V617F allele burden in patients with PV and ET were 58% and 30%, respectively. A JAK2 V617F allele burden of ≥30%, older age, and a higher hemoglobin level were risk factors for thrombotic events in ET. In patients with PV, older age was the only thrombotic risk factor. The 8-year probabilities of overall survival (OS) were 82.9% in all patients. A high JAK2 V617F allele burden (≥58%) was associated with poor OS in patients with PV. For the patients with ET, the difference in 8- year OS based on the JAK2 V617F allele burden was not significant. Conclusion The JAK2 V617F allele burden was correlated with hematologic parameters and clinical outcomes. Assessing the JAK2 V617F allele burden can be helpful in predicting the thrombotic risk and disease course in patients with JAK2 V617F-positive PV and ET.

Background. Glucose metabolism is frequently impaired in patients with Cushing’s syndrome (CS) due to chronic exposure to excess glucocorticoids. Inflammation plays an essential role in the pathophysiology of diabetes mellitus (DM). The present study aimed to investigate the potential associations of inflammatory blood cell parameters, including white blood cell (WBC) count, neutrophil count, neutrophilic granulocyte percentage (NEUT%), lymphocyte count (LYM), and lymphocyte proportion (LYM%), with diabetes mellitus in Cushing's syndrome patients. Materials and Methods. The cross-sectional study was conducted in Zhongshan Hospital of Fudan University, China. A total of 150 patients with Cushing’s syndrome were retrospectively screened from 2017 to 2019. The demographic data, clinical data, and blood samples (lipids, adrenal, glucose, and inflammatory blood cell parameters) were recorded. Statistical analyses were carried out by using the SPSS software package, version 13.0. Results. In this study, the prevalence of diabetes mellitus was 38.7% in patients with Cushing’s syndrome. Patients with DM had higher WBC, neutrophil, NEUT% levels than patients without DM (p<0.05). As the NEUT% increased, a stepwise increase in glucose and glycated hemoglobin (HbA1c) level was observed. In addition, in the multivariate logistic regression, NEUT% was a significant independent risk factor for DM, regardless of gender, age, body mass index (BMI), and triglyceride and 12 midnight cortisol (12 MN cortisol) level (OR = 2.542, 95% CI 1.337–4.835,p<0.001). Conclusions. In conclusion, elevated NEUT% level was linked to diabetes in patients with Cushing’s syndrome. The neutrophilic granulocyte percentage may be referred to as a new predictor for diabetes in Cushing’s syndrome patients.

Aim To evaluate the efficacy and safety of brachytherapy with double-strand 125I seeds and biliary drainage for malignant obstructive jaundice. Methods and materials 42 patients with obstructive jaundice because of extrahepatic cholangiocarcinoma were enrolled. 22 patients (group A) received a biliary stent with common drainage tube implantation, and 20 patients (group B) received a biliary stent with double-strand 125I seeds radiotherapy drainage tube placement. The length, location and pathological stage of biliary stricture were recorded in the two groups. Total bilirubin (TBIL), direct bilirubin (DBIL), IgA, IgG, IgM, alanine aminotransferase and white blood cell (WBC) count were measured before and after percutaneous transhepatic cholangial drainage (PTCD). Tumor diameter was measured before and three months after PTCD, and the difference were calculated. Stent patency time, survival time, and complications were recorded. Results There was no significant difference in the length, location and pathological stage of biliary stenosis between the two groups. There was no significant difference in TBIL, DBIL, IgA, IgG, IgM, alanine aminotransferase and WBC count between the two groups before or after PTCD (P > 0.05). Three months after PTCD, tumors growth in group A and tumors shrinkage in group B. The difference in tumor size between the two groups before and after PTCD was statistically significant (P 0.05). Conclusion Double-strand 125I seeds radiotherapy biliary drainage tubes can safely and effectively control tumors, prolong the patency of biliary stents, and prolong patient survival.

Introduction: In dialysis patients, cardiovascular disease (CVD) and infectious disease contribute to poor clinical outcomes. We investigated if a higher monocyte/lymphocyte ratio (MLR) is associated with an increased risk of CVD events and infectious disease hospitalizations in incident dialysis patients. Methods: In an ongoing observational prospective cohort study, 132 Japanese dialysis patients (age 58.7 ± 11.7 years; 70% men) starting dialysis therapy were enrolled and followed up for a median of 48.7 months. Laboratory biomarkers, including white blood cell count and its differential count, were determined at baseline. Event-free time and relative risks (RRs) were calculated using the Kaplan-Meier curves and Cox models, respectively. Results: When divided into 2 groups according to median MLR (0.35 [range, 0.27–0.46]), the periods without CVD events were significantly shorter in the high MLR group than in the low MLR group (log-rank test = 5.60, p = 0.018). The RR of CVD events, after adjusting for age, sex, and diabetes, was 2.43 (1.22–4.84) in the high MLR group compared to the low MLR group. The periods without infections requiring hospitalization were also shorter (log-rank test = 4.16, p = 0.041). The RR of infections requiring hospitalization was 1.98 (1.02–3.83) after the same adjustments. The number of CVD events was higher in the high MLR group (18.6 events per 100 person-years at risk [pyr]) than the low MLR group (11.1 events per 100 pyr). The duration of infectious disease hospitalization was longer in the high MLR group (6.3 days per pyr) than in the low MLR group (2.8 days per pyr). Conclusion: A higher MLR is associated with increased risks of both CVD events and infectious disease hospitalization in dialysis patients.

Objective. To observe the clinical effect of Xiaozheng Decoction combined with bladder perfusion with hydroxycamptothecin in the treatment of bladder cancer. Methods. A total of 92 bladder cancer patients admitted to our hospital from January to December 2018 were selected and divided into an observation group and a control group according to the random number table method, with 46 cases in each group. The observation group was given Xiaozheng Decoction combined with bladder perfusion with hydroxycamptothecin, and the control group was given hydroxycamptothecin. The levels of serum-related factors (intercellular adhesion molecule-1 (ICAM-1), E-cadherin, cell adhesion molecules (CAM), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF)), white blood cell (WBC) level, immune function indexes, short-term total response rate, and incidence of adverse reactions were compared between the two groups before and after treatment. Results. After 2 years of postoperative treatment, the levels of ICAM-1, E-cadherin, CAM-1, FGF, and VEGF (a, b, c) in both groups were improved compared with those before treatment and the observation group was better than the control group p < 0.01 . The number of WBCs was significantly higher than in the control group after Traditional Chinese Medicine (TCM) treatment. The observation group was better than the control group in increasing CD3+ and CD4+ levels and decreasing CD8+ level p < 0.05 , indicating that this prescription could improve the immune function of patients. The recurrence rate in the observation group was 6.52% after 2 years of treatment, lower than 17.39% in the control group. Color ultrasound parameters showed that there were no statistically significant differences in arrive time (AT) and time to peak (TTP) between patients with and without recurrence and peak intensity (PI) and washout time (WT) were higher in patients with recurrence than in patients without recurrence p < 0.01 . The incidence of adverse reactions was significantly lower than that of the control group p < 0.01 . Conclusion. The clinical effect of Xiaozheng Decoction combined with hydroxycamptothecin on the treatment of bladder cancer was clear and superior to that of hydroxycamptothecin, which could effectively improve the serological indicators of patients with a low incidence of adverse reactions and prolong the survival cycle of patients. Therefore, it is worthy of promotion and application.

We investigated the efficiency of mitoxantrone (MIT) and high-dose cytarabine (Ara-C) chemotherapy followed by G-CSF and G-CSF/GM-CSF treatments for the mobilization of peripheral blood stem cells (PBSCs) in patients with leukemia and lymphoma. MIT was intravenously injected at 10 mg/(m2·d) for 2 to 3 days, followed by Ara-C injected intravenously at 2 g/m2 every 12 hours for 1 to 2 days. When white blood cell count recovered from the lowest value, 5 to 7.5 μg/ (kg·d) G-CSF was administered in 23 patients for 5 to 7 successive days. Another 27 patients received 3-5 μg/ (kg·d) G-CSF and 3-5μg/ (kg·d) GM-CSF. Autologous peripheral blood mononuclear cells were collected. Levels of CFU-GM and CD34+ cells were determined after unfreezing. The CD34+ cells and CFU-GM yields of 27 patients in G-CSF plus GM-CSF combination group [(8.79±3.11)×106/kg, (3.52±1.34)×105/kg, respectively] were significantly higher than those of patients receiving G-CSF alone (n=23) [(6.14±2.06)×106/kg, (2.03±1.06)×105/kg, respectively (P < 0.05)]. No obvious changes of T lymphocyte subsets in patients were observed when using G-CSF/GM-CSF, but levels of CD34+ cells increased gradually (P>0.05). The end-point separation blood volume was all above trebling TBV. No severe complications were observed during the mobilization and collection. Autologous PBSCT obtained quick hematopoietic reconstitution. In conclusion, MA chemotherapy combined with G-CSF alone and G-CSF/GM-CSF can safely and effectively mobilize autologous PBSCs, while G-CSF plus GM-CSF is superior to G-CSF alone. Large volume leukapheresis is an important method to enhance the production rate of stem cells and decrease harvesting time.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that commonly manifests as cutaneous rashes, renal disease, gastrointestinal dysfunction, and cytopenia. Hematological anomalies are frequently associated with drug-induced toxicity in SLE patients. Colony-stimulating factors have been used to treat drug-induced cytopenia in past case reports; however, evidence suggests that colony-stimulating factors can exacerbate autoimmune disorders, including SLE. This case report presents two patients with SLE exacerbations after colony-stimulating factor administration. The first case is a young male with SLE who developed pancytopenia with a white blood cell count (WBC) of 1 × 109 cells/L. The patient was administered filgrastim during his initial admission and presented to the hospital 2 days after discharge in cardiac arrest with a WBC of 66.7 × 109 cells/L. The second case is a 49-year-old female with SLE who was administered sargramostim in response to a WBC count of 9 × 109 cells/L. The patient experienced a drastic increase in WBC followed by a cardiac arrest. These cases highlight the need for more research regarding the safe use of colony-stimulating factors in SLE patients.

Background: Immunoglobulin A vasculitis (IgAV) is the most common vasculitis in children. Although childhood IgAV is generally considered as a self-limited disease, progressive course and poor prognosis could occur in some cases which mostly result from severe renal involvement and gastrointestinal (GI) involvement. Methods: We performed a retrospective study of pediatric patients diagnosed as IgAV in our institution from 2016 to 2019. Patients were divided into groups based on the occurrence and severity of GI and renal involvement. Analysis of variance (ANOVA) and Kruskal-Wallis test were used to compare results of laboratory parameters among groups and prediction models were built by using logistic regression analysis. Results: A total of 286 patients were enrolled. GI involvement occurred in 148 (51.7%) patients, 30 (20.3%) of which were severe cases. Renal involvement developed in 120 (42.0%) patients, 22 (18.3%) of which were severe cases. Compared with patients with only cutaneous manifestations, white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), and D-dimer levels were higher in those with GI involvement, and D-dimer level was found to be positively associated with severity. Increased NLR and lower complement 3 (C3) were found in patients with renal involvement, but only C3 was relevant in distinguishing moderate and severe cases. The prediction model for severe renal involvement was: Logit (P) = 6.820 + 0.270 (age) + 0.508 (NLR) − 16.130 (C3), with an AUC of 0.914. The prediction model for severe GI involvement was: Logit (P) = −5.459 + 0.005 (WBC) + 1.355 (D-dimer) – 0.020 (NLR), with an AUC of 0.849. Conclusion: Our data suggest C3 to be an exclusive predictor for severe renal involvement and D-dimer level to be positively associated with the severity of GI involvement. Prediction models consisting of the above parameters were built for obtaining prognostic information in the early phase of IgAV.

Background The aim of this large multicenter study was to determine variations in cerebrospinal fluid (CSF) HIV-RNA in different phases of untreated human immunodeficiency virus type 1 (HIV-1) infection and its associations with plasma HIV-RNA and other biomarkers. Methods Treatment naive adults with available CSF HIV-RNA quantification were included and divided into groups representing significant disease phases. Plasma HIV-RNA, CSF white blood cell count (WBC), neopterin, and albumin ratio were included when available. Results In total, 1018 patients were included. CSF HIV-RNA was in median (interquartile range [IQR]) 1.03 log10 (0.37–1.86) copies/mL lower than in plasma, and correlated with plasma HIV-RNA (r = 0.44, P plasma discordance was found in 126 of 972 individuals (13%) and varied between groups, from 1% in primary HIV, 11% in neuroasymptomatic groups, up to 30% of patients with HAD. Conclusions Our study confirms previous smaller observations of variations in CSF HIV-RNA in different stages of HIV disease. Overall, CSF HIV-RNA was approximately 1 log10 copies/mL lower in CSF than in plasma, but CSF discordance was found in a substantial minority of subjects, most commonly in patients with HAD, indicating increasing CNS compartmentalization paralleling disease progression.

BACKGROUND: To analyze the effect of early enteral nutrition on serum inflammatory factors and intestinal mucosal permeability in patients with severe acute pancreatitis. METHODS: A total of 55 patients with severe acute pancreatitis were divided into 2 groups: the control group (n = 27), who received routine treatment and the observation group (n = 28), who received early enteral nutrition. The expression of serum inflammatory factors and the permeability of the intestinal mucosa were compared between the 2 groups before and after treatment, and rates of infection and mortality within 30 days were statistically analyzed. RESULTS: The recovery duration of serum and urine amylase and the length of hospital stay in the observation group were shorter than those in the control group. The white blood cell counts, levels of procalcitonin, and the expression of interleukin-6 (IL-6) in the observation group were lower than those in the control group 7 days after the treatment was commenced, and the differences were statistically significant (P < .05). The concentration of diamine oxidase in the serum and the urinary lactulose to mannitol (L/M) ratio in the observation group were lower than those in the control group 7 days after treatment was commenced. The infection rate in the observation group (21.43%) was lower than that in the control group (51.85%) (P < .05). There was no difference in the 30-day mortality between the 2 groups (P > .05). CONCLUSION: Early enteral nutrition may reduce the expression of serum inflammatory factors, decrease the permeability of the intestinal mucosa, and improve the prognosis of patients with severe acute pancreatitis.

Perfluorocarbon emulsions (PFCs) are intravenous artificial oxygen carriers with enhanced gas solubility. As lipid micelle nanoparticle emulsions, PFCs may have a class effect that causes degrees of thrombocytopenia. Understanding the extent of the platelet effects, including mechanism and potential inflammation after PFC infusion, is important for safe human trials.Normal sheep (Dorper) were infused with 5 mL/kg of Oxygent (w/v 60% PFC) or Perftoran (w/v 20% PFC). Controls received 6% Hetastarch or were naive. Blood samples were analyzed from baseline, time 0 (the end of infusion), 3 and 24 hours, and 4 and 7 days. Platelet count, plateletcrit, mean platelet volume, platelet distribution width, and CD-62p (a platelet activation-dependent membrane protein) were measured. Neutrophils, monocytes, and total white blood cell counts were analyzed.In these inflammatory cell lines, there were no consistent changes or cellular activation after PFC infusion. A decrease (10% from baseline and naive controls) in platelet count was seen on day 4 after Oxygent infusion (3 g/kg), which recovered by day 7. No platelet effect was seen in Perftoran (1 g/kg). Plateletcrit, mean platelet volume, and platelet distribution width did not change significantly at any time point among the groups. CD-62p, ADP, and collagen aggregometry showed no significant change in platelet function.There was no evidence of overall reduction in platelet number, or any correlation with the change in platelet activation or inhibition. Therefore, the risk of increased thrombosis/bleeding after PFC intravenous infusion is low in this non-trauma sheep model.

Background Many real‐world studies of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) are restricted to single centers, limiting the generalizability of their insights. This study aimed to identify important population‐based predictors for survival in patients diagnosed with mPDAC in a broader setting. Methods Data between 1 January 2017 and 31 December 2019 were extracted from the Flatiron Health EHR database. Treatment‐specific predictive models were generated for patients treated with first‐line gemcitabine+nab­paclitaxel (GNP), FOLFIRINOX, gemcitabine monotherapy (gem‐mono), and second‐line liposomal irinotecan‐based regimens. The holdout method was used for cross‐validation. Age at diagnosis, sex, BMI, smoking status, and ECOG performance score were included in all models with additional demographic, clinical characteristics, and hematological function assessed for inclusion. Results Of the 3625 patients, 43% received GNP, 26% received FOLFIRINOX, 7% received gem‐mono, and 23% received other regimens; 40% (n = 1448) advanced to the second line. Among all first‐line patients, the following were included in the final model: prior surgery, white blood cell (WBC) counts, serum albumin (SA), liver function tests (LFTs), serum bilirubin, serum carbohydrate antigen 19–9, and ascites. Models for patients receiving specific therapies differed from the overall model, GNP (ascites removed), FOLFIRINOX (stage at initial diagnosis added), and gem‐mono (LFTs omitted). Alkaline phosphatase (ALP), SA, and WBC counts were important predictors of survival among patients treated with second‐line liposomal irinotecan. Across all regimens, the strongest predictors of survival were ECOG score, SA, and ALP. Conclusions In this real‐world study of patients with mPDAC, important population prognostic factors of survival were identified in a large cohort of patients receiving systemic treatment., This retrospective observational analysis of US patient‐level electronic health record data identified a sample of 3625 patients who initiated first‐line systemic therapy for metastatic pancreatic ductal adenocarcinoma from 2017 to 2019. Important population prognostic factors of survival were identified that applied across all regimens including performance status, serum albumin, and alkaline phosphatase levels. Additional patient characteristics were identified as prognostic factors of survival in the context of specific therapies.

Shuangjun He,&ast; Jun Ma,&ast; Chenyu Fan, Chao Tang, Yi Chen, Cuiying Xie Department of Emergency, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Chen; Cuiying XieDepartment of Emergency, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, 2000 Jiangyue Road, Minhang District, Shanghai, 200025, People’s Republic of ChinaEmail chenyirenji@163.com; xiecuiyingrenji@163.comPurpose: To evaluate the performance of serum procalcitonin (PCT) concentrations to diagnose fungal infection in patients with systemic lupus erythematosus (SLE).Patients and Methods: From January 2017 to October 2020, SLE patients hospitalized for serious infection with an identified single bacterial or fungal pathogen, as well as PCT measured within 24h after admission were included. The diagnostic performance of PCT was evaluated independently and in combination with the white blood cell (WBC) count, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). The analysis included the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and the crude and adjusted area under the receiver operating characteristic curve (AUROC).Results: Sixty-nine patients were included; 26 had a fungal infection (38%) and 43 had a bacterial infection (22 gram-positive and 21 gram-negative). Fungal infection patients were mainly distributed in the respiratory group (88.5%), and bacterial infection distribution were more prevalent in respiratory group (44.2%) and abdominal/urinary group (23.3%). The PCT concentration was significantly lower in fungal infections than bacterial infections (fungal: 0.22 ng/mL, interquartile range [IQR], 0.09– 0.44 vs bacterial: 0.60 ng/mL, IQR, 0.16– 5.74; p = 0.016) and differed significantly between different infection sites (p = 0.022). PCT had better diagnostic performance for predicting fungal infection (AUROC = 0.731) than the WBC count (AUROC = 0.581), the CRP level (AUROC = 0.716), and ESR (AUROC = 0.583). PCT and ESR together had the best diagnostic performance, with 46.2% sensitivity and 88.4% specificity. Further, the AUROC increased compared to PCT alone but was statistically insignificant (p = 0.693).Conclusion: For SLE patients with serious infection, the PCT concentration had better diagnostic accuracy for predicting fungal infection than the WBC count, the CRP level, and ESR. Combining PCT and ESR obtained the highest AUROC and provided an acceptable discrimination performance.Keywords: diagnostic markers, emergency department, microorganisms, autoimmune disease

SARS-CoV-2 infection results in a spectrum of outcomes from no symptoms to widely varying degrees of illness to death. A better understanding of the immune response to SARS-CoV-2 infection and subsequent, often excessive, inflammation may inform treatment decisions and reveal opportunities for therapy. We studied immune cell subpopulations and their associations with clinical parameters in a cohort of 26 patients with COVID-19. Following informed consent, we collected blood samples from hospitalized patients with COVID-19 within 72 h of admission. Flow cytometry was used to analyze white blood cell subpopulations. Plasma levels of cytokines and chemokines were measured using ELISA. Neutrophils undergoing neutrophil extracellular traps (NET) formation were evaluated in blood smears. We examined the immunophenotype of patients with COVID-19 in comparison to that of SARS-CoV-2 negative controls. A novel subset of pro-inflammatory neutrophils expressing a high level of dual endothelin-1 and VEGF signal peptide-activated receptor (DEspR) at the cell surface was found to be associated with elevated circulating CCL23, increased NETosis, and critical-severity COVID-19 illness. The potential to target this subpopulation of neutrophils to reduce secondary tissue damage caused by SARS-CoV-2 infection warrants further investigation.

Purpose Aim of this study was to determine the rate of low-grade infection in patients with primarily as aseptic categorized tibial shaft nonunion and lack of clinical signs of infection. Methods In a retrospective study between 2006 and 2013, all patients who underwent revision surgery for treatment of tibial shaft nonunion without clinical evidence of infection were assessed. Bacterial cultures harvested during nonunion revision, C-reactive protein (CRP) and/or white blood cell (WBC) values at hospital admission, outcome, and epidemiological data were analyzed. Results In 88 patients with tibial shaft nonunion without any clinical signs of infection, bacterial samples remained negative in 51 patients. In 37 patients, microbiological diagnostic studies after long-term culturing demonstrated positive bacterial cultures whereas after short-term culturing for 2 days only 17 positive cultures were observed. In 12 cases a mixed culture with 2.3 different bacteria on average was detected. Among patients with negative bacterial cultures bone healing was achieved after 13.2 months. Nonunion with positive bacterial cultures required 19 (range 2-42) months until osseous healing (p = 0.009). Furthermore, nonunion with positive bacterial cultures require statistically more surgical revisions to achieve healing (2.9 ± 0.5 vs. 1.3 ± 0.1 additional procedure; (p = 0.003). Hematological studies carried out before surgical intervention did not demonstrate significant differences in CRP values (negative vs. positive cultures: 0.3 (range 0.3-2.8) mg/dl vs. 0.5 (range 0.3-5.7) mg/dl (p = 0.181) and in WBC values (negative vs. positive cultures: 7.4 (range 3.5-11.9) /nl vs. 7.3 (range 3.7-11.1) /nl (p = 0.723). Limitations of this study may include the varying amount of the at least four samples for microbiological diagnostics as well as the circumstance that for diagnosing low-grade infection swabs and tissue samples were included in this evaluation as being equivalent. Conclusion The pathogenesis of nonunion may originate from low-grade infection even in patients without clinical signs of infection. In addition, nonunion with positive bacterial cultures require statistically more surgical revisions to achieve healing. Therefore, during any revision surgery, multiple bacterial samples are intended to be harvested for long-term culturing. Particularly, in tibial shaft nonunion following Gustilo-Anderson type III open fractures, low-grade infection should be suspected. Trial registration number DRKS00014657. Date of registration 04/26/2018 retrospectively registered

Key Points Expression of CALCRL is an independent prognostic factor and a potential therapeutic target in pediatric AML.CALCRL is linked with relapse risk in p ediatric AML, which supports its role as a master regulator of relapse-initiating drug-tolerant cells., Visual Abstract, We have recently identified the G protein-coupled neuropeptide receptor calcitonin receptor‐like (CALCRL) as an independent prognostic biomarker and a therapeutic target in more than 1500 adult patients with acute myeloid leukemia (AML). Here, we confirmed CALCRL expression as a prognostic factor in a cohort of 284 pediatric patients with AML. High CALCRL expression was independently associated with event-free survival (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.36-2.57; P = .0001), overall survival (HR, 1.55; 95% CI, 1.06-2.27; P = .025), and cumulative incidence of relapse (HR, 2.10; 95% CI, 1.49-1.96; P < .0001) when adjusting for age, white blood cell count, and genetic risk. Despite its association with leukemia stem cell signatures, CALCRL expression remained associated with all end points when compared with the 17-gene leukemic stem cell score. The strong association of CALCRL expression with the risk of relapse also in the pediatric population supports its role as novel age-independent master regulator of relapse-initiating, drug-tolerant AML cells in humans.

INTRODUCTION Differential counts of leukocytes are frequent, and often several automated blood cell counters are needed in contemporary laboratories. However, these modules are often individually quality assured. Our aim was therefore to validate the interchangeability of five hematology modules in a large modern laboratory and to compare them with our gold standard (GS) manual white blood cell differential count. METHODS At Copenhagen University Hospital, we compared five Sysmex XN-modules for neutrophils, lymphocytes, monocytes, eosinophils, basophils, and immature granulocytes (IG). We analyzed control samples in three levels to evaluate intra- and intermodular precision. Bias between modules was evaluated by analyzing 93 random patient samples within reference intervals. XN-modules' mean counts were compared with GS. RESULTS We found acceptable intramodular CV% (0.92%-8.76%), only neutrophils and eosinophils exceeded state-of-the-art imprecision or desirable specifications for medium control levels. Intermodular CV% showed significance difference for only monocytes (ANOVA, P

Little is known about B-lymphoblastic leukemia (B-ALL) that lacks expression of terminal deoxynucleotidyl transferase (TdT). To address this, we performed the largest study to date of TdT-negative B-ALL using data from St. Jude Total XV and XVI clinical trials. Compared to TdT-positive B-ALL (n = 896), TdT-negative B-ALL (n = 21) was associated with younger age (median, 1.4 versus 6.8 years, P

Purpose To investigate the expression of the receptor protein ACE-2 alongside the urinary tract, urinary shedding and urinary stability of SARS-CoV-2 RNA. Methods Immunohistochemical staining was performed on tissue from urological surgery of 10 patients. Further, patients treated for coronavirus disease (COVID-19) at specialized care-units of a university hospital were assessed for detection of SARS-CoV-2 RNA in urinary samples via PCR, disease severity (WHO score), inflammatory response of patients. Finally, the stability of SARS-CoV-2 RNA in urine was analyzed. Results High ACE-2 expression (3/3) was observed in the tubules of the kidney and prostate glands, moderate expression in urothelial cells of the bladder (0–2/3) and no expression in kidney glomeruli, muscularis of the bladder and stroma of the prostate (0/3). SARS-CoV-2 RNA was detected in 5/199 urine samples from 64 patients. Viral RNA was detected in the first urinary sample of sequential samples. Viral RNA load from other specimen as nasopharyngeal swabs (NPS) or endotracheal aspirates revealed higher levels than from urine. Detection of SARS-CoV-2 RNA in urine was not associated with impaired WHO score (median 5, range 3–8 vs median 4, range 1–8, p = 0.314), peak white blood cell count (median 24.1 × 1000/ml, range 5.19–48.1 versus median 11.9 × 1000/ml, range 2.9–60.3, p = 0.307), peak CRP (median 20.7 mg/dl, 4.2–40.2 versus median 11.9 mg/dl, range 0.1–51.9, p = 0.316) or peak IL-6 levels (median: 1442 ng/ml, range 26.7–3918 versus median 140 ng/ml, range 3.0–11,041, p = 0.099). SARS-CoV-2 RNA was stable under different storage conditions and after freeze–thaw cycles. Conclusions SARS-CoV-2 RNA in the urine of COVID-19 patients occurs infrequently. The viral RNA load and dynamics of SARS-CoV-2 RNA shedding suggest no relevant route of transmission through the urinary tract.

OBJECTIVE To examine whether serum procalcitonin (PCT) is useful for differentiating acute pyelonephritis (APN) from asymptomatic bacteriuria and acute cystitis during pregnancy. METHODS A multicenter prospective observational study was conducted to compare serum white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and PCT level among pregnant women with asymptomatic bacteriuria, acute cystitis, and APN and healthy pregnant women (controls). Utility of WBC count, ESR, CRP, and PCT biomarkers for the prediction of APN during pregnancy were measured. RESULTS Area under the curve (AUC) values of PCT, CRP, ESR, and WBC count for predicting asymptomatic bacteriuria were 0.576, 0.628, 0.542, and 0.532, respectively; those for predicting acute cystitis were 0.766, 0.735, 0.681, and 0.597, respectively; and those for predicting acute pyelonephritis 0.859, 0.763, 0.711, and 0.732, respectively. Compared with the other inflammatory markers used to predict APN, PCT exhibited the highest AUC (0.859 [95% confidence interval (CI) 0.711-0.935]). A cutoff value of >0.25 ng/ml had a sensitivity of 87% and a specificity of 79%. CONCLUSION Serum PCT can be a valuable addition to existing methods of differentiating asymptomatic bacteriuria, acute cystitis, and APN during pregnancy and can facilitate the early identification of APN during pregnancy.

Coronavirus is affecting millions of people world-wide. Coronavirus disease 2019 (COVID-19) is declared a pandemic by WHO. Severe acute respiratory syndrome corona virus 2(SARS-CoV-2) is the causative agent. The clinical presentations of SARS-CoV-2 infection range from febrile illness to pneumonia, ARDS and multi organ failures. Increasing scientific evidences have shown that abnormalities in routine laboratory test, particularly haematological parameters influence the outcome of the disease. Here variations in WBC profile in several clinical forms of COVID-19 patients are observed, The clinical course of the disease may change with haematological parameters such as lower total count of WBC, lymphocyte, higher neutrophil count, eosinophil count etc. By investigating haematological parameters of different clinical stage of RT-PCR positive 100 COVID-19 patients, statistically significant association (p value 0.001) of lymphocyte count with disease severity was found. It is also found that higher level of total count WBC, neutrophil count in severe group in comparison to mild and moderate groups but failed to reach any statistical significance. Moreover total count WBC and neutrophil count showed positive correlations but lymphocyte count, eosinophil count and monocyte count showed negative correlation with severity of disease. So, complete analysis of the haematological parameters will be very much helpful for early detection of complications & better control of the disease.

Eosinophilic leukocytosis can be attributed to a number of clinical conditions such as parasitic infection, allergies, and neoplasms. Parasitic infection is the main cause of eosinophilia; however, a marked leukocytosis with hypereosinophilia secondary to Trichuris trichiura in adults has not been previously reported. We describe a case of a 39-year-old man who presented with fever and diarrhea. The investigation revealed a white blood cell (WBC) count of 20.69 × 109/L with an absolute eosinophil count of 12.44 × 109/L. Fecal microscopic examination demonstrated T. trichuria eggs. The WBC count returned to normal following treatment with albendazole. The literature pertaining to hematological findings associated with Trichuris trichiura is explored in this report. This case highlights that a significant elevation of leukocyte count with hypereosinophilia can be one of the manifestations of trichuriasis infection in adults. Empirical treatment with anti-helminthic agents may play a role in suspected cases to avoid severe complications, such as Trichuris dysentery syndrome.

Background: Early identification of risk factors for short-term mortality in patients with in-hospital cardiac arrest (IHCA) is crucial for early prognostication. This study aimed to explore the association of early dynamic changes in inflammatory markers with 30-day mortality in IHCA patients.Methods: This study retrospectively collected demographic and clinical characteristics and relevant laboratory indicators within 72 h after recovery of spontaneous circulation (ROSC) of IHCA patients from December 2015 to December 2020 at the First Affiliated Hospital of Chongqing Medical University. The outcome was 30-day mortality. A linear mixed model was used to analyze the dynamic changes in laboratory indicators within 72 h after ROSC, and Cox regression was used to identify the independent risk factors for 30-day mortality.Results: Overall, 85 IHCA patients were included. The 0-72h and 0-30day cumulative mortality rates were 25.88% and 57.65%, respectively, and the median survival time was 13.79 days. There was no association of inflammatory markers before IHCA with mortality. Within 72 h after ROSC, inflammatory markers showed various changes: the absolute monocyte count (AMC) showed no significant change trend, and the absolute lymphocyte count (ALC) showed an overall upward trend, while the absolute neutral count (ANC), white blood cell (WBC) count, platelet (PLT) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) showed an overall downward trend. Cox multivariate analysis showed that Charlson comorbidity index (CCI) (HR = 2.366, 95%CI (1.084, 5.168)), APACHE II score (HR = 2.550, 95% CI (1.001, 6.498)), abnormal Cr before IHCA (HR = 3.417, 95% CI (1.441, 8.104)) and PLR within 72 h after ROSC (HR = 2.993, 95% CI (1.442, 6.214)) were independent risk factors for 30-day mortality. When PLR ≥ 180, the risk of 30-day mortality increased by 199.3%.Conclusions: This study clarified the dynamic change trends of inflammatory markers within 72 h after ROSC. The PLR was an independent risk factor for 30-day mortality in IHCA patients; it can be used as a predictor of short-term mortality and provide a reference for early prognostication.Trial registration: ChiCTR1800014324

We analyzed the serum zinc levels of 37 patients with 40 phlegmon lesions. The mean serum zinc level was 52.1 ± 16.4 μg/dL. The serum zinc level was negatively correlated with the C-reactive protein (CRP) level (r = -0.66) and white blood cell (WBC) count (r = -0.56). It was also positively correlated with the serum levels of albumin, hemoglobin, and hematocrit (r = 0.57, 0.50, and 0.50, respectively). Patients with serum zinc levels of60 μg/dL had higher CRP levels and WBC counts (p 0.005 and p 0.05, respectively) and lower albumin, hemoglobin, and hematocrit levels (p 0.001, p 0.01, and p 0.01, respectively), and were more likely to be hospitalized (p 0.05) than those with serum zinc levels of ≥60 μg/dL. Patients with low serum zinc levels were given zinc tablets. Three of the seven patients who developed recurrent phlegmons did not develop any further lesions after taking zinc tablets for10 months. Of the remaining patients, one only developed a minimal lesion, and another two experienced recurrence twice but did not have any further lesions for 10 and 15 months, respectively. These findings indicate that in patients with phlegmons the serum zinc level is a suitable marker of the severity of infection, and zinc supplementation reduces the risk of further recurrence in patients whose lesions relapse.

Immunosenescence, vascular aging, and brain aging, all characterized by elevated levels of inflammatory markers, are thought to share a common pathogenetic pathway: inflamm-aging. Retrospective cross-sectional analysis was conducted using data from the Mugello study (Tuscany, Italy), a representative Italian cohort of free-living nonagenarians. to assess the association between specific peripheral inflammation markers derived from white blood cell counts, and the diagnosis of dementia. All the variables of interest were reported for 411 subjects (110 males and 301 females) out of 475 enrolled in the study. Anamnestic dementia diagnosis was obtained from clinical certificate and confirmed by a General Practitioner, whereas leukocyte ratios were directly calculated from white blood cell counts. Body mass index and comorbidities were considered potential confounders. Diagnosis of any type dementia was certified in 73 cases (17.8%). Subjects affected by dementia were older, more frequently reported a previous stroke, had lower body mass index, and lower Mini-Mental-State-Examination score. Moreover, they had a higher lymphocyte count and lymphocyte-to-monocyte ratio compared to the non-demented nonagenarians. We found that higher levels of lymphocyte counts are cross-sectionally associated with a clinical diagnosis of dementia. Furthermore, lymphocyte-to-monocyte ratio is directly associated with any type of dementia, independently of age, sex, lymphocyte count, and comorbidities. Lymphocyte-to-monocyte ratio may be considered a marker of immunological changes in the brain of dementia patients; moreover, it is low-cost, and easily available, thus enabling comparisons among different studies and populations, although the timeline and the extent of lymphocyte-to-monocyte ratio role in dementia development must be further investigated.

Objective: We aimed to investigate the relation of platelet count (PLT), mean platelet volume (MPV) and platelet distribution width (PDW) with other acute phase reactants in COVID-19 new corona virus. Material and Methods: Thirty one patients with COVID-19 were included in to study. There were three groups as outpatient (Group 1, OP)(n=6), hospital (Group 2, H)(n=16) and intensive care unit (Group 3, IC)(n=9) in this analytic study. Results: WBC (White Blood Cell), CRP (C-Reactive Protein) values were significantly different in all groups. PDW values were significantly lower in Group 3 than Group 1, 2. The result of ROC analysis was 10.9 as a cut-off value (Area under the curve, AUC)=0.407) Conclusions: This study indicates that lower PDW may frequently develop in COVID-19 cases and there is a relation between thrombocytosis and acute phase reactants, that is, the inflammatory response. So we can offer that PDW should be used as a marker of Covid-19 disease severity, but it needs more studies in the future.

The most common adverse reactions to rituximab are infusion-related reactions (IRR). We evaluated the efficacy of split dosing the first rituximab infusion over two days to reduce IRR incidence in patients with hematological cancer and a high lymphocyte count. This is a retrospective observational study conducted in two healthcare centers in Quebec, Canada. The study enrolled patients with white blood cell counts ≥25.0 × 109/L who received their first rituximab dose for hematological cancer between December 2007 and May 2020. One healthcare center used asymmetrical split dosing, while the other used symmetrical split dosing. A total of 183 treatment episodes were collected from 143 patients. Among patients who received a fractionated dosing schedule, 42% developed an IRR from the first rituximab infusion compared with 50% for the standard protocol (adjusted relative risk, 0.89, p = 0.540). No significant difference was observed in IRR severity between either groups. However, 24% of patients who received the asymmetrical protocol developed an IRR compared to 68% for the symmetrical protocol (adjusted relative risk, 0.32, p = 0.003). These results suggest that an asymmetrical split dosing could be effective in reducing the incidence of IRR and is preferable to a symmetrical one.

BACKGROUND Intracranial hemorrhage (ICH) is a rare, but serious complication in patients with acute leukemia. Little is known about why some patients experience serious bleeding, including ICH, while others do not. MATERIALS AND METHODS Adults between 18 and 80 years old with acute leukemia and ICH between January 1, 2009 and December 31, 2016 were included. Matched controls were identified using the propensity score matching method. Clinical and laboratory characteristics and outcome data were collected to identify variables associated with ICH. RESULTS Of 2578 patients diagnosed with acute leukemia during the study period, 55 cases and 161 matched controls were included. Patients who experienced ICH were older (62 vs. 55 years, p = .004) and more likely to have diabetes mellitus (p = .04). Patients with ICH had a higher baseline white blood cell count (mean 84.5 ± 115.8 vs. 28.7 ± 58.5 × 109 /L, p = .001), peripheral blast count (61.3 ± 96.5 vs. 21.2 ± 50.8 × 109 /L, p = .004), and a longer PT (16.5 ± 2.06 vs. 15.3 ± 3.2 s, p = .002). Neither the platelet count at diagnosis, the platelet nadir, the number of days with a platelet count of less than 10 × 109 /L, or a diagnosis of platelet refractoriness were associated with ICH. CONCLUSIONS Older age and more proliferative disease appear to be associated with ICH, whereas thrombocytopenia alone does not. In patients with newly diagnosed acute leukemia, aggressive cytoreduction in those with leukocytosis may help mitigate the risk of ICH.

AimsRecently, a new automated digital cell imaging analyser (Sysmex CellaVision DC-1), intended for use in low-volume and small satellite laboratories, has become available. The purpose of this study was to compare the performance of the DC-1 with the Sysmex DI-60 system and the gold standard, manual microscopy.MethodsWhite blood cell (WBC) differential counts in 100 normal and 100 abnormal peripheral blood smears were compared between the DC-1, the DI-60 and manual microscopy to establish accuracy, within-run imprecision, clinical sensitivity and specificity. Moreover, the agreement between precharacterisation and postcharacterisation of red blood cell (RBC) morphological abnormalities was determined for the DC-1.ResultsWBC preclassification and postclassification results of the DC-1 showed good correlation compared with DI-60 results and manual microscopy. In addition, the within-run SD of the DC-1 was below 1 for all five major WBC classes, indicating good reproducibility. Clinical sensitivity and specificity were, respectively, 96.7%/95.9% compared with the DI-60% and 96.6%/95.3% compared with manual microscopy. The overall agreement on RBC morphology between the precharacterisation and postcharacterisation results ranged from 49% (poikilocytosis) to 100% (hypochromasia, microcytosis and macrocytosis).ConclusionsThe DC-1 has proven to be an accurate digital cell imaging system for differential counting and morphological classification of WBCs and RBCs in peripheral blood smears. It is a compact and easily operated instrument that can offer low-volume and small satellite laboratories the possibilities of readily available blood cell analysis that can be stored and retrieved for consultation with remote locations.

Purpose of review To date, prognostication of patients after acute traumatic spinal cord injury (SCI) mostly relies on the neurological assessment of residual function attributed to lesion characteristics. With emerging treatment candidates awaiting to be tested in early clinical trials, there is a need for wholistic high-yield prognostic biomarkers that integrate both neurogenic and nonneurogenic SCI pathophysiology as well as premorbid patient characteristics. Recent findings It is becoming clearer that effective prognostication after acute SCI would benefit from integrating an assessment of pathophysiological changes on a systemic level, and with that, extend from a lesion-centric approach. Immunological markers mirror tissue injury as well as host immune function and are easily accessible through routine blood sampling. New studies have highlighted the value of circulating white blood cells, neutrophils and lymphocytes in particular, as prognostic systemic indicators of SCI severity and outcomes. Summary We survey recent advances in methods and approaches that may allow for a more refined diagnosis and better prognostication after acute SCI, discuss how these may help deepen our understanding of SCI pathophysiology, and be of use in clinical trials.

Background Research into new markers has been intensified for early diagnosis, prognosis, and differentiation of SIRS, sepsis, and septic shock in recent years. This study aimed to investigate the role of soluble triggering receptor expressed in myeloid cells-1 (sTREM-1) and interleukin (IL)-6 in distinguishing between systemic inflammatory response syndrome (SIRS), sepsis, and septic shock in pediatric intensive care unit (PICU) patients. Methods Between June 2014 and July 2015, 90 consecutive patients who were treated in the PICU were included in this prospective observational study. Patients were divided into four groups: control (n = 23), SIRS (n = 22), sepsis (n = 23), and septic shock (n = 22). All patients were evaluated for white blood cell (WBC), serum C-reactive protein (CRP), procalcitonin (PCT), IL-6, and sTREM-1 levels at 0, 24, and 72 h of admission. The prognostic evaluations were made using the Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores. Patients were evaluated in terms of age, gender, prognosis, pathogen growth in culture, PRISM III and PELOD score, WBC, CRP, PCT, IL-6, and sTREM-1 levels and a comparison was made between groups. Results There was no significant difference between all groups in terms of the 0-, 24-, and 72-h sTREM-1 values (p = 0.761, p = 0.360, and p = 0.822, respectively). CRP and PCT values did not differ between the septic shock, sepsis, and SIRS groups at 0, 24, and 72 h. In the septic shock group, the 0-h IL-6 value was significantly higher than that of the SIRS group (p = 0.025). The 24-h IL-6 value in the septic shock group was significantly higher than the values of the sepsis and SIRS groups (p = 0.048 and p = 0.043, respectively). No significant difference was detected between the septic shock, sepsis, and SIRS groups in terms of IL-6 values at 72 h. Conclusion sTREM-1 is not useful for the diagnosis of infection and for distinguishing between sepsis, septic shock, and SIRS since it does not offer a clear diagnostic value for PICU patients, unlike other reliable markers such as WBC, CRP, and PCT. Elevated IL-6 levels may indicate septic shock in PICU patients. More research on sTREM-1 is needed in this setting.