Cytokine Expression of Lung Bacterial Infection in Newly Diagnosed Adult Hematological Malignancies

Adult patients with hematological malignancies are frequently accompanied by bacterial infections in the lungs when they are first diagnosed. Sputum culture, procalcitonin (PCT), C-reactive protein (CRP), body temperature, and other routinely used assays are not always reliable. Cytokines are frequently abnormally produced in adult hematological malignancies associated with a lung infection, it is uncertain if cytokines can predict lung bacterial infections in individuals with hematological malignancies. Therefore, we reviewed 541 adult patients newly diagnosed with hematological malignancies, of which 254 patients had lung bacterial infections and 287 patients had no other clearly diagnosed infections. To explore the predictive value of cytokines for pulmonary bacterial infection in adult patients with hematological malignancies. Our results show that IL-4, IL-6, IL-8, IL-10, IL-12P70, IL-1β, IL-2, IFN-γ, TNF-α, TNF-β and IL-17A are in the lungs The expression level of bacterially infected individuals was higher than that of patients without any infections (P<0.05). Furthermore, we found that 88.89% (200/225) of patients with IL-6 ≥34.12 pg/ml had a bacterial infection in their lungs. With the level of IL-8 ≥16.35 pg/ml, 71.67% (210/293) of patients were infected. While 66.10% (193/292) of patients had lung bacterial infections with the level of IL-10 ≥5.62 pg/ml. When IL-6, IL-8, and IL-10 were both greater than or equal to their Cutoff-value, 98.52% (133/135) of patients had lung bacterial infection. Significantly better than PCT ≥0.11 ng/ml [63.83% (150/235)], body temperature ≥38.5°C [71.24% (62/87)], CRP ≥9.3 mg/L [53.59% (112/209)] the proportion of lung infection. In general. IL-6, IL-8 and IL-10 are abnormally elevated in patients with lung bacterial infections in adult hematological malignancies. Then, the abnormal increase of IL-6, IL-8 and IL-10 should pay close attention to the possible lung bacterial infection in patients.

Download Full-text

Ruxolitinib Combined with Dexamethasone in Adult Patients with Secondary HLH：a Single-Centre Pilot Trial

Blood ◽

10.1182/blood-2021-152921 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 198-198

Author(s):

De Zhou ◽

Xianbo Huang ◽

Mixue Xie ◽

Hong-Hu Zhu ◽

Jie Jin ◽

...

Keyword(s):

Overall Survival ◽

Bacterial Infections ◽

Conflicts Of Interest ◽

Pilot Trial ◽

Adult Patients ◽

Unknown Etiology ◽

Massive Hemoptysis ◽

Rapid Progression ◽

Newly Diagnosed

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a cytokine-driven inflammatory syndrome associated with hereditary or acquired immune-dysregulation. The frontline therapy for secondary HLH in adult patients is HLH-1994 regimen, however overall survival of these patients remains suboptimal. Janus family kinases JAK1 and JAK2 are hallmarks of the final common pathway in HLH, and ruxolitinib (an oral JAK inhibitor) has shown favorable efficacy and safety in murine models and clinical trials. Recently, Lauren K. Meyer et al demonstrate that hypercytokinemia of HLH reduces the apoptotic potential of CD8 T cells leading to relative dexamethasone resistance, and this apoptotic potential is restored both in vitro and vivo when exposure to ruxolitinib. This finding provide rationale for combining dexamethasone and ruxolitinib to enhance the lymphotoxic effects of dexamethasone and thus improve the outcomes for patients with HLH. We were very interested in this finding and conducted this pilot trial in adult patients with secondary HLH. Methods We managed 8 newly diagnosed HLH patients with ruxolitinib combined with dexamethasone or methylprednisolone from April 1, 2021 to May 31, 2021 in the First Affiliated Hospital of Medical School of Zhejiang University. All patients fulfilled at least five of the eight HLH-2004 diagnostic criteria and the etiology was not identified at the time. The regimen in detail was ruxolitinib 15mg po. bid d1-56, dexamethasone 10mg/m 2 d1-14, 5mg/ m 2 d15-28, 2.5 mg/m 2 d29-42, 1.25mg/m 2 d43-49, reduce the dosage until withdrawal d50-56 (For patients with liver insufficiency, dexamethasone is replaced with the same equivalent of methylprednisolone). Once the patient's primary cause had been identified, we wound begin primary disease treatment immediately. Results Eight newly diagnosed HLH patients without previous treatment were enrolled in this study with a median follow-up of 102 (2-122) days, including 5 cases of lymphoma-associated HLH, one case of bacterial infections-associated HLH, and 2 cases of unknown etiology. The overall response rate at the end of HLH treatment was 87.5% (7/8), with 50% (4/8) in complete response (CR), 37.5% (3/8) in partial response (PR), and 12.5% (1/8) in no response. Among the patients achieving CR, 100% (4/4) maintained CR condition for＞2 months. 2-month overall survival was 75% (6/8), one patient was dead because of lymphoma associated HLH progression, another patient was dead because of bronchiectasis with massive hemoptysis after the HLH was under control. For the lymphoma-associated HLH subgroup, 4 of 5 patients responded to ruxolitinib combined with dexamethasone, three patients successfully bridged to chemotherapy after diagnosis of lymphoma; One patient defused to chemotherapy because she was 77 years old and had severe bronchiectasis; the patient with NR was dead in 2 days due to the rapid progression of disease. No treatment-related deaths were observed. Conclusions In our trial, ruxolitinib combined with dexamethasone regimen initially demonstrated favorable efficacy in newly diagnosed adult patients with secondary HLH. Especially for patients with lymphoma-associated hemophagocytic syndrome, it is an efficient and safe bridging therapy while waiting for pathological diagnosis. This novel treaiment is promising, and should be evaluated in larger sample size studies. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Download Full-text

C-Reactive Protein Is an Independent Predictor of 30-Day Bacterial Infection Post-Liver Transplantation

Biomolecules ◽

10.3390/biom11081195 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1195

Author(s):

Jiong Yu ◽

Xiaowei Shi ◽

Jing Ma ◽

Ronggao Chen ◽

Siyi Dong ◽

...

Keyword(s):

Liver Transplantation ◽

Bacterial Infection ◽

Systemic Inflammation ◽

Bacterial Infections ◽

Cox Regression ◽

Prognostic Models ◽

C Reactive Protein ◽

Reactive Protein ◽

Clinically Significant ◽

The Relationship

The relationship between aseptic systemic inflammation and postoperative bacterial infection is unclear. We investigated the correlation of systemic inflammation biomarkers with 30-day clinically significant bacterial infections (CSI) after liver transplantation (LT). This retrospective study enrolled 940 patients who received LT and were followed for 30 days. The primary end point was 30-day CSI events. The cohort was divided into exploratory (n = 508) and validation (n = 432) sets according to different centers. Area under the receiver operated characteristic (AUROC) and Cox regression models were fitted to study the association between baseline systemic inflammation levels and CSI after LT. A total of 255 bacterial infectious events in 209 recipients occurred. Among systemic inflammation parameters, baseline C-reactive protein (CRP) was independently associated with 30-day CSI in the exploratory group. The combination of CRP and organ failure number showed a good discrimination for 30-day CSI (AUROC = 0.80, 95% CI, 0.76–0.84) and the results were confirmed in an external verification group. Additionally, CRP levels were correlated with bacterial product lipopolysaccharide. In conclusion, our study suggests that pre-transplantation CRP is independent of other prognostic factors for 30-day CSI post-LT, and can be integrated into tools for assessing the risk of bacterial infection post-LT or as a component of prognostic models.

Download Full-text

Type I Interferon in Children with Viral or Bacterial Infections

Clinical Chemistry ◽

10.1093/clinchem/hvaa089 ◽

2020 ◽

Vol 66 (6) ◽

pp. 802-808 ◽

Cited By ~ 2

Author(s):

Sophie Trouillet-Assant ◽

Sébastien Viel ◽

Antoine Ouziel ◽

Lucille Boisselier ◽

Philippe Rebaud ◽

...

Keyword(s):

Bacterial Infection ◽

Bacterial Infections ◽

Viral Infections ◽

Type I Interferon ◽

Area Under The Curve ◽

Pediatric Emergency ◽

Type I ◽

Discriminative Performance ◽

Antibiotic Overuse ◽

Reactive Protein

Abstract Background Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians’ decisions and limit antibiotic overuse. Methods Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. Results Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). Conclusions IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. Clinical Trials Registration clinicaltrials.gov (NCT03163628).

Download Full-text

Approach to Neonates and Young Infants with Fever without a Source Who Are at Risk for Severe Bacterial Infection

Mediators of Inflammation ◽

10.1155/2018/4869329 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Susanna Esposito ◽

Victoria Elisa Rinaldi ◽

Alberto Argentiero ◽

Edoardo Farinelli ◽

Marta Cofini ◽

...

Keyword(s):

At Risk ◽

Bacterial Infection ◽

Bacterial Infections ◽

Laboratory Data ◽

Unknown Origin ◽

Clinical Findings ◽

Reactive Protein ◽

Young Infants ◽

High Risk Infants ◽

The Impact

Introduction. Among neonates and infants <3 months of age with fever without a source (FWS), 5% to 15% of cases are patients with fever caused by a serious bacterial infection (SBI). To favour the differentiation between low- and high-risk infants, several algorithms based on analytical and clinical parameters have been developed. The aim of this review is to describe the management of young infants with FWS and to discuss the impact of recent knowledge regarding FWS management on clinical practice. Materials and Methods. PubMed was used to search for all of the studies published over the last 35 years using the keywords: “fever without source” or “fever of unknown origin” or “meningitis” or “sepsis” or “urinary tract infection” and “neonate” or “newborn” or “infant <90 days of life” or “infant <3 months”. Results and Discussion. The selection of neonates and young infants who are <3 months old with FWS who are at risk for SBI remains a problem without a definitive solution. The old Rochester criteria remain effective for identifying young infants between 29 and 60 days old who do not have severe bacterial infections (SBIs). However, the addition of laboratory tests such as C-reactive protein (CRP) and procalcitonin (PCT) can significantly improve the identification of children with SBI. The approach in evaluating neonates is significantly more complicated, as their risk of SBIs, including bacteremia and meningitis, remains relevant and none of the suggested approaches can reduce the risk of dramatic mistakes. In both groups, the best antibiotic must be carefully selected considering the clinical findings, the laboratory data, the changing epidemiology, and increasing antibiotic resistance of the most common infectious bacteria.

Download Full-text

Cytokines and Chemokines as Biomarkers of Community-Acquired Bacterial Infection

Mediators of Inflammation ◽

10.1155/2013/190145 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 27

Author(s):

Michal Holub ◽

David A. Lawrence ◽

Nancy Andersen ◽

Alžběta Davidová ◽

Ondřej Beran ◽

...

Keyword(s):

Bacterial Infection ◽

Bacterial Infections ◽

Viral Infections ◽

Elevated Serum ◽

Serum Concentrations ◽

C Reactive Protein ◽

Reactive Protein ◽

Cytokines And Chemokines ◽

Luminex Technology ◽

Limited Usefulness

Routinely used biomarkers of bacterial etiology of infection, such as C-reactive protein and procalcitonin, have limited usefulness for evaluation of infections since their expression is enhanced by a number of different conditions. Therefore, several inflammatory cytokines and chemokines were analyzed with sera from patients hospitalized for moderate bacterial and viral infectious diseases. In total, 57 subjects were enrolled: 21 patients with community-acquired bacterial infections, 26 patients with viral infections, and 10 healthy subjects (control cohorts). The laboratory analyses were performed using Luminex technology, and the following molecules were examined: IL-1Ra, IL-2, IL-4, IL-6, IL-8, TNF-α, INF-γ, MIP-1β, and MCP-1. Bacterial etiology of infection was associated with significantly (P<0.001) elevated serum concentrations of IL-1Ra, IL-2, IL-6, and TNF-αin comparison to levels observed in the sera of patients with viral infections. In the patients with bacterial infections, IL-1Ra and IL-8 demonstrated positive correlation with C-reactive protein, whereas, IL-1Ra, TNF-α, and MCP-1 correlated with procalcitonin. Furthermore, elevated levels of IL-1Ra, IL-6, and TNF-αdecreased within 3 days of antibiotic therapy to levels observed in control subjects. The results show IL-1Ra as a potential useful biomarker of community-acquired bacterial infection.

Download Full-text

C-reactive protein and procalcitonin for antimicrobial stewardship in COVID-19

Infection ◽

10.1007/s15010-021-01615-8 ◽

2021 ◽

Author(s):

Isabell Pink ◽

David Raupach ◽

Jan Fuge ◽

Ralf-Peter Vonberg ◽

Marius M. Hoeper ◽

...

Keyword(s):

Antibiotic Therapy ◽

Bacterial Infection ◽

Bacterial Infections ◽

Roc Analysis ◽

Secondary Infection ◽

C Reactive Protein ◽

Laboratory Findings ◽

Secondary Bacterial Infection ◽

Reactive Protein ◽

Tract Infections

Abstract Purpose Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread around the world. Differentiation between pure viral COVID-19 pneumonia and secondary infection can be challenging. In patients with elevated C-reactive protein (CRP) on admission physicians often decide to prescribe antibiotic therapy. However, overuse of anti-infective therapy in the pandemic should be avoided to prevent increasing antimicrobial resistance. Procalcitonin (PCT) and CRP have proven useful in other lower respiratory tract infections and might help to differentiate between pure viral or secondary infection. Methods We performed a retrospective study of patients admitted with COVID-19 between 6th March and 30th October 2020. Patient background, clinical course, laboratory findings with focus on PCT and CRP levels and microbiology results were evaluated. Patients with and without secondary bacterial infection in relation to PCT and CRP were compared. Using receiver operating characteristic (ROC) analysis, the best discriminating cut-off value of PCT and CRP with the corresponding sensitivity and specificity was calculated. Results Out of 99 inpatients (52 ICU, 47 Non-ICU) with COVID-19, 32 (32%) presented with secondary bacterial infection during hospitalization. Patients with secondary bacterial infection had higher PCT (0.4 versus 0.1 ng/mL; p = 0.016) and CRP (131 versus 73 mg/L; p = 0.001) levels at admission and during the hospital stay (2.9 versus 0.1 ng/mL; p < 0.001 resp. 293 versus 94 mg/L; p < 0.001). The majority of patients on general ward had no secondary bacterial infection (93%). More than half of patients admitted to the ICU developed secondary bacterial infection (56%). ROC analysis of highest PCT resp. CRP and secondary infection yielded AUCs of 0.88 (p < 0.001) resp. 0.86 (p < 0.001) for the entire cohort. With a PCT cut-off value at 0.55 ng/mL, the sensitivity was 91% with a specificity of 81%; a CRP cut-off value at 172 mg/L yielded a sensitivity of 81% with a specificity of 76%. Conclusion PCT and CRP measurement on admission and during the course of the disease in patients with COVID-19 may be helpful in identifying secondary bacterial infections and guiding the use of antibiotic therapy.

Download Full-text

Evolution of laboratory markers for systemic bacterial infections

Terapevticheskii arkhiv ◽

10.17116/terarkh20178911105-110 ◽

2017 ◽

Vol 89 (11) ◽

pp. 105-110

Author(s):

N L Ryabkova ◽

N N Vezikova

Keyword(s):

Bacterial Infection ◽

Proinflammatory Cytokines ◽

Bacterial Infections ◽

C Reactive Protein ◽

Reactive Protein ◽

Laboratory Markers ◽

Systemic Bacterial Infection

The paper reviews the data available in the literature on existing laboratory markers for systemic bacterial infection, among which C-reactive protein, proinflammatory cytokines, procalcitonin test, and presepsin receive primary emphasis.

Download Full-text

Thrombocytosis as a Predictor of Serious Bacterial Infection in Febrile Infants

Journal of Nepal Health Research Council ◽

10.33314/jnhrc.v16i41.1673 ◽

2019 ◽

Vol 16 (41) ◽

pp. 401-404

Author(s):

Deepak Mishra ◽

Amit Kumar Das ◽

Ram Hari Chapagain ◽

Nitu Kumari Jha ◽

Ganesh Kumar Rai

Keyword(s):

Bacterial Infection ◽

Bacterial Infections ◽

Diagnostic Marker ◽

Common Finding ◽

P Value ◽

C Reactive Protein ◽

Cross Sectional ◽

Reactive Protein ◽

Young Infants

Background: Most of the febrile infants <90 days old will have no more than a mild viral infection but there is a substantial minority that will be diagnosed as having serious bacterial infection at a reported prevalence of 10–14%. A simple, readily available, inexpensive diagnostic marker that yields results quickly and also accurately identifies bacterial infections in febrile infants would be of great value in management of these infants. This study aims to assess the role of thrombocytosis in predicting serious bacterial infection in young febrile infants beyond neonatal period.Methods: A hospital based cross-sectional observational study was conducted from May 2016 to April 2017 on 76 febrile infants of age group 29-90 days in Kanti Children’s Hospital.Results: The incidence of serious bacterial infection was found 43 (56.6%). Thrombocytosis, elevated C-reactive protein and pyuria were significantly higher in serious bacterial infection cases (p value <0.05). Thrombocytosis alone had the sensitivity of only 53.5%, but had specificity of 90.9%. Elevated C-reactive protein had the best sensitivity (81.4%). Combination of leukocytosis, elevated C-reactive protein, pyuria and thrombocytosis had better sensitivity (93.0%) than these parameters alone. The overall ability of platelet count to identify infants with SBI was only moderate (AUC: 0.722). Elevated C-reactive protein was found to have better ability to identify infants with serious bacterial infection (AUC: 0.846).Conclusions: Thrombocytosis is a common finding in young infants diagnosed with serious bacterial infection. It has however, moderate ability in identifying infants with serious bacterial infection. Combining thrombocytosis with elevated C-reactive protein, leukocytosis and pyuria has better sensitivity in diagnosing serious bacterial infection than these individual parameters alone. Hence, combining these parameters may help in early prediction of febrile young infants at risk of serious bacterial infection.Keywords: Febrile young infants; serious bacterial infection; thrombocytosis.

Download Full-text

Infectious complications in children and adults with hematological malignancies

Acta Haematologica Polonica ◽

10.2478/ahp-2019-0027 ◽

2019 ◽

Vol 50 (3) ◽

pp. 167-173 ◽

Cited By ~ 3

Author(s):

Jan Styczyński

Keyword(s):

Fungal Infection ◽

Cell Transplantation ◽

Bacterial Infections ◽

Hematological Malignancies ◽

Hematopoietic Cell Transplantation ◽

Viral Infections ◽

Infectious Complications ◽

Hematopoietic Cell ◽

Newly Diagnosed ◽

Pediatric Hematology

AbstractInfections are the main cause of morbidity and mortality in pediatric hematology and oncology (PHO) and hematopoietic cell transplantation (HCT) settings in children and adults. The analysis of incidence and outcome of bacterial, fungal, and viral infections in Polish PHO/ HCT centers was performed over a period of 72 months (2012–2017). The summary of infections in 5628 patients with newly diagnosed malignancy and 971 HCTs is presented in this paper. Additionally, data of 650 pediatric HCTs from 2012 to 2015 were compared with the data of 3200 HCTs in adults. The risk of any infection per patient was higher in HCT vs PHO patients (2062/971 vs 7115/5628; 2.1 vs 1.3; HR=1.7, p<0.0001). The incidence of bacterial infections was 34,2±0,6% in PHO vs 41,5±1,6% in HCT patients, and the outcome was better in PHO patients: 97,9±0,2% vs 91,8±1,0%. The incidence of patients with fungal infection was 8,8±0,4% vs 21,2±1,3%, and the outcome was better in PHO patients: 95,9±0,7% vs 85,8±2,3%. Incidence of viral infections was 5,0±1,0% in PHO setting, including part of previously transplanted patients, and 47,8±2,2% in HCT setting (60,9±2,3% allo-HCT; 5,6±1,3% auto-HCT). In children, the incidence was higher for bacterial (36.0% vs 27.6%), fungal (25.3% vs 6.3%), and viral (56.3% vs 29.3% allo-HCT; 6.6% vs 0.8% auto-HCT) infections than in adults (p<0.0001), and the outcome was better for bacterial (95.5% vs 91.4%), fungal (88.0% vs 74.9%), and viral (98.6% vs 92.3%) infections. In conclusion, the presented large studies have determined the incidence of infectious complications and their outcomes in HCT and PHO centers in Poland.

Download Full-text

Potential usefulness of C-reactive protein and procalcitonin determination in patients admitted for neurological disorders in rural Democratic Republic of Congo

Scientific Reports ◽

10.1038/s41598-019-51925-z ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Emmanuel Bottieau ◽

Deby Mukendi ◽

Jean-Roger Lilo Kalo ◽

Pascal Lutumba ◽

Barbara Barbé ◽

...

Keyword(s):

Bacterial Infection ◽

Neurological Disorders ◽

Bacterial Infections ◽

Democratic Republic ◽

Democratic Republic Of Congo ◽

Single Case ◽

C Reactive Protein ◽

Republic Of Congo ◽

Reactive Protein ◽

Invasive Bacterial Infection

Abstract In low-resource hospitals of central Africa, neurological disorders are frequent and etiologies very diverse. The difficulty to identify invasive bacterial infections in this setting results in major antibiotic overuse. Biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) may help discriminate these conditions. We retrospectively determined the concentrations of CRP and PCT in the sera of patients consecutively enrolled from 2012 to 2015 in an etiological study on neurological disorders at the rural hospital of Mosango, Democratic Republic of Congo. Invasive bacterial infection had been diagnosed by the demonstration of a bacterial pathogen in cerebrospinal fluid or blood cultures or the presence of radiological pneumonia. Sera of 313 (89.2%) and 317 (90.3%) of the 351 enrolled participants were available for determination of CRP and PCT concentrations respectively. Areas under the receiver operating characteristic curves for invasive bacterial infection, diagnosed in 19 tested cases, were 94.3% for CRP and 91.7% for PCT. No single case had a normal CRP concentration (<10 mg/L). Our data, although limited, suggest that CRP or PCT concentrations may help discriminate invasive bacterial infections in patients with neurological disorders in tropical settings and that normal CRP values could assist in withholding antibiotics.

Download Full-text