Presepsin (soluble CD14 subtype) Is Available in Febrile Neutropenic Patients with Hematological Malignancy As Diagnosis and Assesment Biomarker of Infections

Abstract BACKGROUND: Febrile neutropenia (FN) is often observed in hematological malignancy (HEM). Although most are considered to be due to bacterial infections, it is often difficult to specify the focuses and pathogens of infections in FN patients. Presepsin (Pre-SEP) is a subtype of soluble CD14, which is a receptor for lipopolysaccharide (LPS)/LPS-binding protein complexes and is expressed on the myeloid and monocytic cells' surface. Recently, Pre-SEP has been shown to be a useful biomarker for assessing the severity of sepsis. However, little is known about the biological characteristics of Pre-SEP in FN patients. Therefore, we compared the Per-CEP to the established infection markers including procalcitonin (PCT) and C-reactive protein (CRP) continually in FN patients. METHODS: We measured Pre-SEP concentration in the plasma, PCT and CRP on Day 0, 2, 4, 7 and 14 after the onset of FN and compared them to those of non-febrile neutropenic patients. Furthermore we evaluated the impact of Pre-SEP, PCT and CRP on the diagnosis and assessment of active infection status in FN, using the cut-off value by setting to 314 pg/ml, 0.50 ng/ml and 0.30 mg/ml. Correlation analysis was performed using Peason's correlation coefficient test. RESULTS: Sixty-two hospitalized FN patients with HEM (AML 14, ALL 9, MDS 14, NHL 13, MM 8, ATL 2, others 2 cases) were treated according to IDSA guideline. Figure 1 showed the each data in Pre-SEP, PCT and CRP value on day 0, 2, 4, 7 and 14. The frequency of less than the cut-off value at day 0 of FN onset were 33.8 %, 77.4 % and 37.1 % in Pre-SEP, PCT and CRP respectively, indicating that Pre-SEP showed the highest sensitivity. On day 0, a significant correlation was not observed between Pre-SEP and PCT (P=0.457, correlation coefficient: 0.096) but it was observed between Pre-SEP and CRP (P<0.01, correlation coefficient: 0.599). However, on day 2 and 4, significant correlations were observed between Pre-SEP and PCT (P<0.01, correlation coefficient: 0.650, p<0.01, correlation coefficient: 0.702 respectively) as well as between Pre-SEP and CRP (P<0.01, correlation coefficient: 0.542, p<0.01, correlation coefficient: 0.722 respectively). These data strongly suggested that Pre-SEP and CRP were available early in FN for a diagnosis and assessment of infection. On day 7, the negative frequencies were 43.5 %, 88.7 % and 45.1 % in Pre-SEP, PCT and CRP. These data strongly suggested that more sensitive assessment of infection would be possible using Pre-SEP. CONCLUSION: (1) Pre-SEP is available even in neutropenia. (2) Pre-SEP is a useful biomarker for infection on the onset of FN as well as CRP. (3) Pre-SEP can help more sensitive assessment of infection. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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Abdominal Obesity, IL-6 Levels and the Risk of Venous Thromboembolism Among Women: a Case-Control Study

Blood ◽

10.1182/blood.v116.21.477.477 ◽

2010 ◽

Vol 116 (21) ◽

pp. 477-477

Author(s):

Christiane Pereira Gouveia ◽

Dayse Maria Lourenço ◽

Marinez Farana Matos ◽

Cristina Mary Orikaza ◽

Maria Aparecida Eiko Noguti ◽

...

Keyword(s):

Venous Thromboembolism ◽

Abdominal Obesity ◽

Prospective Studies ◽

Conflicts Of Interest ◽

Continuous Variable ◽

Geographic Region ◽

Reactive Protein ◽

The Metabolic Syndrome ◽

Simultaneous Adjustment ◽

The Impact

Abstract Abstract 477 Background: abdominal obesity is one of the components of the metabolic syndrome (MS), which is a cluster of cardiovascular risk factors. Recent prospective studies demonstrated that among the components of the MS, abdominal obesity was the only independent risk factor for venous thromboembolism (VTE). However, it remains unclear to what extent inflammation contributes to the risk of VTE from abdominal obesity. The aim of this study was to investigate the association of abdominal obesity and VTE in women and the effect of inflammation on this association. Material and methods: 94 female patients were included with a first objectively confirmed episode of VTE, with a median age of 39 years (range: 21–60). Exclusion criteria were malignancy, autoimmune diseases, chronic renal or liver diseases and arterial thrombosis. Patients were seen at least 1 month after the discontinuation of the anticoagulant treatment and > 7 months after the event of VTE. Controls were comprised of 100 healthy women, with a median age of 37 years (range: 18–63), recruited via the patients from the same geographic region and ethnic background. Controls were matched for age. Waist circumference (WC) was measured at the umbilical line. A WC ≥ 88 cm in women defined abdominal obesity according to the National Cholesterol Education Program. Plasma level of IL-6 was measured by a highly sensitive ELISA, fibrinogen by Clauss method and high-sensitive C-reactive protein (CRP) by immunoturbidimetry. High levels of IL-6 (> 2.01 pg/mL), CRP (> 6.66 mg/L) and fibrinogen (> 3.59 g/L) were dichotomized at the 90th percentile of the control values. Result: median WC was higher in patients (89 cm; range: 65–126) than in controls (84 cm; range: 62–131), P<0.01. In both groups, WC significantly correlated (P<0.01) with body mass index as expected, but also with age, fibrinogen, CRP and IL-6. Fifty-five patients and 43 controls had abdominal obesity, yielding an odds ratio (OR) of 1.87 [95% Confidence Interval (CI) 1.06 – 3.31]. The association of VTE and abdominal obesity was not affected after adjustment for potential confounders, as high levels of CRP (OR 1.86; 95% CI 1.05 – 3.30) and fibrinogen (OR 1.94; 95% CI 1.08 – 3.48), and it was of borderline significance when adjusted for age (OR 1.76; 95% CI 0.97–3.20). However, the risk was no longer significant after adjustment for high levels of IL-6 (OR 1.57; 95% CI 0.87–2.84). Simultaneous adjustment for age and high levels of CRP, fibrinogen and IL-6 yielded an OR of 1.60 (95% CI 0.85 – 3.00). The impact of abdominal obesity on the risk of VTE was more pronouncedly affected when IL-6 entered into the logistic regression model as a continuous variable (OR 1.33; 95% CI 0.72 – 2.47). Conversely, high IL-6 levels increased the risk of VTE even after adjustment for age, abdominal obesity and high levels of CRP and fibrinogen (OR 3.65; 95%CI 1.56 – 8.50). Conclusion: in this study abdominal obesity was associated with VTE in crude analysis in a relatively young population composed of women. However, the association was no longer significant after adjustment for IL-6. There is evidence that visceral adipose tissue, assessed by WC, is metabolic active, releasing cytokines. To our knowledge this is the first study that evaluated in the same population the effect of IL-6 and abdominal obesity on the risk of VTE. More data, including prospective studies, are required to elucidate the role of inflammation in the association of VTE and abdominal obesity. This study was supported by FAPESP (2005/56799-0). Disclosures: No relevant conflicts of interest to declare.

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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.

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The Innate Immune System Favors Emergency Monopoiesis at the Expense of DC Differentiation to Control Bacterial Infections

Blood ◽

10.1182/blood.v124.21.2722.2722 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2722-2722

Author(s):

Kristin Bieber ◽

Karina A. Pasquevich ◽

Manina Günter ◽

Matthias Grauer ◽

Oliver Pötz ◽

...

Keyword(s):

Immune System ◽

Bacterial Infection ◽

Bacterial Infections ◽

Conflicts Of Interest ◽

Bacterial Load ◽

Innate Immune ◽

General Response ◽

The Impact ◽

Myeloid Progenitors

Abstract Dendritic cells (DCs) are critical in host defense against infection, bridging the innate and adaptive immune system. Patients with sepsis display reduced circulating and splenic DCs and impaired DC function that may contribute to prolonged immune suppression and exacerbation of infection. However, the mechanisms of pathogen-induced DC depletion remain poorly understood. Here, a mouse model of systemic bacterial infection was employed to analyze the impact of different bacterial pathogens on DC development in vivo. We found that the numbers of bone marrow (BM) hematopoietic progenitors committed to the DC lineages were reduced following systemic infection with different Gram-positive and Gram-negative bacteria. In parallel, a TLR4-dependent increase of committed monocyte progenitors in the BM as well as mature monocytes in the spleen was observed. In line, adoptively transferred FLT3+ myeloid progenitors (MPs) developed preferentially to monocytes at the expense of DCs in infected animals. Analyses performed on mixed BM chimeras suggested that both the reduction of DC progenitors and the induction of monopoiesis following infection were dependent on extrinsic TLR4 signaling driving the secretion of IFN-g regulated chemokines. Consistently, these effects were completely abrogated by suppression of IFN-g signaling. Elevated monocyte numbers in the spleen triggered by infection were due to a CCR2-dependent egress from the BM. In CCR2-deficient mice, in which monocytosis reportedly is abrogated, we observed a significantly increased bacterial load in the spleen and a reduced survival rate, highlighting the importance of monocytes for bacterial clearance. Together, our data provide evidence for a general response of myeloid progenitors upon bacterial infection to enhance monocyte production, thereby increasing the availability of innate immune cells as a first line of defense against invading pathogens. Concomitantly the development of DCs is impaired, which may be responsible for transient immunosuppression in e.g. bacterial sepsis. Disclosures No relevant conflicts of interest to declare.

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The Experience of the Cooperation in Science and Technology European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias (COST EuNet-INNOCHRON) Action and the Sweden Experience in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Era

Blood ◽

10.1182/blood-2021-150486 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3125-3125

Author(s):

Michail Spanoudakis ◽

David C. Dale ◽

Emily Tran ◽

Marije Bartels ◽

Suncica Kapor ◽

...

Keyword(s):

Bacterial Infections ◽

Clinical Course ◽

Age Distribution ◽

Gastrointestinal Symptoms ◽

Significant Risk ◽

Autoimmune Neutropenia ◽

Congenital Neutropenia ◽

History Of ◽

Neutropenic Patients ◽

The Impact

Abstract Background-Aim: Infection from SARS-CoV-2 has emerged as new pathological entity within the global medical community. One of the earliest questions was in relation to the ability of the immunocompromised patients to clear the infection. In COST EuNet-INNOCHRON we were interested in the impact of SARS-CoV-2 infection in patients with different types of chronic neutropenia (CNP). The aim of the current study is to understand the impact of SARS-CoV-2 infection and to identify any possible characteristic patterns of the clinical course in patients with CNP. Patients and Methods: The COST EuNet-INNOCHRON Action in collaboration with the European Haematology Association - Scientific Working Group (EHA-SWG) on Granulocytes and Constitutional Marrow Failure Syndromes has conducted an online survey on SARS-CoV-2 infection in patients with CNP. The EuNet-INNOCHRON participants from different countries got access to an on-line platform fulfilling the General Data Protection Regulation (GDPR) and could register adult and paediatric CNP patients who had been infected by SARS-CoV-2 from March 2020 to June 2021. Data on demographic characteristics, type of CNP, patients' background and SARS-CoV-2 infection history (symptoms, laboratory features, radiological appearance, therapeutic approach and outcome) were collected. Results: Twenty-six patients with diagnosis of CNP, 7 males and 19 females were registered. Patient age distribution as follows: 16 patients >18 years old (y.o.)5 patients 5-18 y.o, 4 patients < 5 y.o whereas age was not available for one of the patients. Nine of the patients were diagnosed with idiopathic CNP, 7 patients with congenital neutropenia (6 of them with severe congenital neutropenia), 3 with secondary CNP, 2 with suspected autoimmune neutropenia of infancy (although antineutrophil Ab were negative), one with autoimmune neutropenia, one with drug induced neutropenia and 3 with other types of CNP. Twelve patients were on treatment with G-CSF and 6 patients had a history of previous viral or bacterial infections. Clonal Cytopenia(s) of Undetermined Significance (CCUS) was excluded in the eight patients who were investigated. Twenty-four out of 26 patients had positive PCR and one was found incidentally with positive antibodies for SARS-CoV-2. One more patient was symptomatic with history of close contact with SARS-CoV-2 infected family members. The commonest observed symptoms were fever >38 oC (19 patients), cough (10 patients), rhinorrhoea (10 patients), sore throat (6 patients), musculoskeletal pains (7 patients), taste/smell loss (5 patients), headache (5 patients), dyspnoea (4 patients), chest pain (one patient) and none of them had gastrointestinal symptoms. No other associated respiratory viral or bacterial infections were reported. Four patients who had one or more underlying conditions (immune deficiency, heart/respiratory/kidney disease) were admitted in hospital and needed anti SARS-CoV-2 treatment. Two of them had non-invasive ventilation and one of them needed admission in intensive care unit (ICU); both recovered. Another patient with Fallot's tetralogy needed mechanical ventilation in ICU and sadly passed away. No other deaths were observed. Deterioration of the pre-existing neutropenia was seen in two patients, two patients developed thrombocytopenia, one patient developed worsening lymphopenia and one anaemia. Twelve patients had chest X-ray and consolidation was found in two of them. All three patients who had chest CT scans were found with ground-glass changes. During the observation period (up to two months), no re-infection from SARS-CoV-2 was found. The Stockholm, Sweden experience is similar to the above data. One hundred fifty-four patients with CNP were followed up, for 10 months (March 1 to December 31, 2020) for SARS-CoV-2. Seventeen of these (i.e. 11 %) were infected. None needed hospitalization and there were no fatalities. Conclusion: Although the relative susceptibility of neutropenic patients to contract SARS-CoV-2 needs to be assessed with further studies, the clinical course and severity of SARS-CoV-2 infection doesn't seem to be worse in CNP patients (regardless the type of neutropenia and the need for GCSF treatment) compared to the general population. Also, like what has been observed in non-neutropenic patients, underlying comorbidities is a significant risk factor for severe disease and adverse outcome. Disclosures Dale: X4 Pharmaceuticals: Consultancy, Honoraria, Research Funding. Palmblad: Chiesi Ltd Sweden: Honoraria; Roche Sweden: Speakers Bureau; Chiesi Ltd Candada,: Honoraria.

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Impact of Pretransplant Neutropenia on Post-Transplant Outcome in Patients with Myelodysplastic Syndrome (MDS).

Blood ◽

10.1182/blood.v108.11.599.599 ◽

2006 ◽

Vol 108 (11) ◽

pp. 599-599

Author(s):

Bart L. Scott ◽

J.Y. Park ◽

B. Storer ◽

K.A. Marr ◽

M. Boeckh ◽

...

Keyword(s):

Bacterial Infections ◽

Fungal Infections ◽

International Prognostic Scoring System ◽

Bacillus Species ◽

Fungal Colonization ◽

Probability Of Survival ◽

Transfusion Requirements ◽

Increased Risk ◽

Neutropenic Patients ◽

The Impact

Abstract MDS comprises a spectrum of clonal hematopoietic disorders with very heterogeneous clinical courses. Several classification and scoring systems have been developed in an attempt to define subgroups of patients with similar prognoses. The International Prognostic Scoring System (IPSS) incorporates marrow myeloblast count, karyotype, and peripheral blood cytopenias. The recent addition of transfusion requirements to the IPSS (WPSS) has sharpened this prognostic tool. Isolated neutropenia is not reflected in these classifications, but bacterial and fungal colonization and infection are problems in patients with MDS. Hematopoietic cell transplantation is the only treatment strategy that has been shown to have curative potential, and many patients come to transplantation with neutropenia, particularly when the disease progresses. We wanted to determine the impact of neutropenia before transplantation on transplant success. We reviewed results in 291 patients with MDS (including MDS that had transformed to AML [tAML]), 1 to 66 (median 50) years of age, who from 1994 through 2003 were transplanted from related or unrelated donors following conditioning with myeloablative regimens. There were 178 patients (61%) who had neutropenia, defined as <1,500/microliter; in 16 of these (9%) neutropenia was an isolated finding. Among the 178 patients, 137 (47%) had neutrophil counts below 1,000, and 86 (30%) below 500. Patients with neutropenia following recent chemotherapy were excluded. The risk of clinically relevant bacterial infections after transplantation was significantly increased in patients with neutropenia (p=0.001). Neutropenic patients had an increased risk for infections with gram-positive (relative risk [RR] 1.77, p=0.02), but not gram negative bacteria (RR 1.33, p=0.53). Specific organisms for which the RR was significantly increased included coagulase negative Staphylococcus, Bacillus species and Corynebacterium spp., suggesting that at least part of this risk was associated with intravascular catheters. The RR for invasive fungal infections (Candida and Aspergillus spp.) was 2.56 (p=0.03) for patients with <1,500 neutrophils. The hazard rate (HR) for non-relapse mortality by day 100 (21%) was 1.8 (p=0.03), and by 5 years (42%) was 1.62 (p=0.01). The most frequent causes of death were infections. The HR for 5-year mortality was 1.55 (p=0.007) for neutropenic patients. The pattern for the small group of patients with isolated neutropenia was identical to that for all patients with neutropenia. Pre-transplant neutropenia had no significant impact on engraftment or graft-versus-host disease. The probability of survival did not differ significantly between patients with IPSS scores of 0 and 0.5 with isolated or multiple cytopenias. In summary, only few patients with MDS who undergo transplantation have isolated neutropenia. However, pre-transplant neutropenia in patients with MDS is associated with a significantly increased risk of posttransplant bacterial infections, fungal infections, and non-relapse mortality, and a decreased probability of survival after myeloablative transplantation. A correlation with pre-transplantation colonization remains to be determined. Intensified and possibly extended antibiotic coverage should be considered.

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Dynamics of Procalcitonin and Bacteremia In Adult Acute Myeloid Leukemia with Chemotherapy-Induced Neutropenia

Blood ◽

10.1182/blood.v116.21.4378.4378 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4378-4378

Author(s):

Anne-Claire Gac ◽

Jean-Jacques Parienti ◽

Sylvain Chantepie ◽

Roland Leclercq ◽

Oumedaly Reman

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Bacterial Infections ◽

Conflicts Of Interest ◽

Fungal Infections ◽

Short Term ◽

Neutropenic Patients ◽

Chemotherapy Induced Neutropenia ◽

Sensitive Marker ◽

Acute Myeloid

Abstract Abstract 4378 Sensitive markers of infection are rare or of limited validity in neutropenic patients. Procalcitonin (PCT), a precursor protein of calcitonin, is a specific and sensitive marker of severe bacterial infections during short-term neutropenia. Because the value of PCT measurements among patients undergoing long periods of neutropenia remains uncertain and because several mechanisms, such as bacterial or fungal infections, reactions to drugs or blood products or tumor-associated events, can cause fever, we described the dynamics of PCT in 29 acute myeloid leukemia (AML) patients with 39 instances of chemotherapy-induced neutropenia. Plasma levels of PCT were determined prospectively by an immunoluminometric assay every four days starting at the onset of chemotherapy and continuing until the resolution of fever. We found that bacteremia did increase PCT levels above 0.5 ng/mL and these levels predicted bacteremia at day 15 of chemotherapy. This finding may be relevant in the decision to alter antibiotic regimens to decrease toxicity and cost when patients remain febrile at day 15. Disclosures: No relevant conflicts of interest to declare.

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The Burden of Anemia and Operational Challenges in Conducting Clinical Research at a Medical Ward in Lilongwe, Malawi

Blood ◽

10.1182/blood.v124.21.3512.3512 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3512-3512

Author(s):

Eric D Strand ◽

Richard Broadhurst ◽

Irving Hoffman ◽

Mlombe Yohannie ◽

Mina Hosseinipour

Keyword(s):

Clinical Research ◽

Medical Service ◽

Hematological Malignancy ◽

Conflicts Of Interest ◽

Macrocytic Anemia ◽

Medical Ward ◽

Sub Saharan Africa ◽

Significant Problem ◽

Nutritional Deficiencies ◽

The Impact

Abstract Background: Anemia in sub-Saharan Africa is a significant problem, but has not been well studied in the general adult population. Factors contributing to anemia include: HIV, malaria, tuberculosis, hematological malignancy and nutritional deficiencies. Often, hematological malignancy presents as an anemia or cytopenia. Understanding the prevalence and types of anemia in this part of the world will help to fully understand the impact of these causes and may help to further identify the prevalence of hematological malignancy in this setting. Methods: We tracked all patients who were admitted to the medical service of Kamuzu Central Hospital (KCH) in Lilongwe, Malawi for a one-month period from 8 June until 9 July 2014. Data collected upon admission included: age, gender, admitting diagnosis, HIV status (if known), Antiretroviral (ARV) status, organomegaly, lymphadenopathy and any known comorbid illnesses. Complete blood counts (CBCs) were ordered on all patients during this period Results: The medical ward admitted372 patients during the study period. Anemia was the admitting diagnosis for 10.75% of patients. Other common admitting diagnoses were: Sepsis (11.83%), Pneumonia or TB (11.02%), and Malaria (7.53%). CBCs were ordered on all patients, but only 38.17% received a result. Of the patients who received a CBC result (n=142), mean Hgb was 9.40 gm/dL and mean WBC was 7.76 gm/dL. Anemia (Hgb<13 gm/dL in men and Hgb<12 gm/dL in women) was present in 73.33% of men and 71.64% of women with a CBC result. Of the patients with anemia, 74.80% had normocytic anemia, 9.76% had macrocytic anemia, and 15.44% had microcytic anemia. Anemia requiring transfusion per ASH guidelines (Hgb≤7 gm/dL) was present in 26.67% of men and 38.80% of women. Overall mortality of patients admitted during the study period was 11.04%. Of patients with a completed CBC, 21.4% of deaths were patients with Hgb<7 gm/dL. For the patients who did not receive a CBC, 68.93% of samples were not drawn or transported to the lab, 26.70% of patients were admitted during a time where there was no reagent for the hematology analyzer, 2.42% of samples arrived clotted, and 1.94% of orders arrived with no sample. Conclusions: Conducting clinical research in the developing world is challenging, but it presents opportunities for quality improvement and capacity building. This was the first time that the medical ward attempted to take blood draws on all patients. There was no department policy regarding responsibility for lab draws on the medical service at KCH, which resulted in many blood draws not being done. Supply of lab reagents ran out during the last week of the study period due to the order not arriving on time. This highlights the importance of all parts of a healthcare system in delivering quality patient care. Anemia was one of the top three admitting diagnoses at the KCH medical ward. This shows that anemia is a significant problem. The majority of patients at KCH had hemoglobin values below the WHO threshold for anemia, regardless of overall health. This, and the low mean hemoglobin, shows that western measurements of anemia may not be appropriate for Malawi. This is especially true given the shortage of blood in Malawi, and the risks of transfusion. The causes of anemia at KCH are still fully not known, which warrants further investigation. Study in hematological malignancy, aplastic anemia, and anemia of chronic disease is ongoing at KCH in order to pursue these underlying causes. Disclosures No relevant conflicts of interest to declare.

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Value of Procalcitonin Arise Markedly after Use of ATG in Conditioning of HSCT without Value in Differentiating Bacterial and Non-Bacteria Inflammation

Blood ◽

10.1182/blood.v124.21.4979.4979 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4979-4979

Author(s):

Hui Ge ◽

Shengli An ◽

Chunfu Li

Keyword(s):

Bacterial Infection ◽

Bacterial Infections ◽

Viral Infections ◽

Conflicts Of Interest ◽

Hematopoietic Stem ◽

Reactive Protein ◽

Significant Difference ◽

Human T Lymphocyte ◽

Group 2 ◽

Bacteria Culture

Abstract Background It is difficult how to differentiate bacterial infections from viral infections and to differentiate bacterial infections from other non-infective systemic inflammation. Especially in the patients with lack of neutrophil bacteria infection is usually life-threaten. The prognosis for those patients is high dependent on early diagnosis and treatment. We still feel confusing in spite of monitoring serum procalcitonin (PCT) and C-reactive protein (CRP) levels with temperature. Aim To find out whether PCT and CRP are helpful to differentiate bacterial infection and non-bacterial inflammation after use of anti-human T-lymphocyte globulin (ATG) in conditioning of hematopoietic stem cell transplantation (HSCT). Method Total 60 patients were involved in current study, who underwent HSCT and received conditioning included Cyclophosphamide, Fludarabine, ivBusufan, Thiotepa and ATG (at total dose of 5mg/kg for thymoglobulin, and 15-30mg/kg for ATG-Fresenius, respectively, on day-3 to -1). Blood samples were obtained in the morning from day-3 to 0 for testing PCT and CRP associated by daily recording temperature. Patients were grouped into Group 1 (G1, with antibiotics, n=30), Group 2 (G2, without antibiotics, n=30), Group 3 (G3, bacteria culture positive, n=7) and Group 4 (G4, bacteria culture negative, n=47) Results The value of PCT was not significant difference when G1 vs. G2 (p=0.061), and G3 vs. G4 (p=0.891), but CRP value and temperature were of significant difference between G1 and G2 (p=0.001 and 0.000, respectively). When comparing G3 with G4, CRP was significant (p=0.021) but temperature was no (0.377). However, the deference of daily CRP value was proved not to be enough to do a differential diagnosis by ROC (AUROC=0.685, 0.665, 0.643 and 0.643 on day-3 to 0, respectively). Conclusion The current study shows the value of PCT is insignificant to differentiate bacterial infection and non-bacterial inflammation after use of ATG in conditioning of HSCT. Disclosures No relevant conflicts of interest to declare.

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The lung–gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes

Mucosal Immunology ◽

10.1038/s41385-020-00361-8 ◽

2021 ◽

Author(s):

Valentin Sencio ◽

Marina Gomes Machado ◽

François Trottein

Keyword(s):

Gut Microbiota ◽

Bacterial Infections ◽

Respiratory Infections ◽

Critical Role ◽

Good Health ◽

Disease Outcomes ◽

And Function ◽

Viral Respiratory Infections ◽

The Impact ◽

Viral Respiratory

AbstractBacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host’s defense against viral respiratory infections. The gut microbiota’s composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota’s composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung–gut axis in coronavirus disease 2019.

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AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections

Scientific Reports ◽

10.1038/s41598-021-90573-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nathaniel B. Bone ◽

Eugene J. Becker ◽

Maroof Husain ◽

Shaoning Jiang ◽

Anna A. Zmijewska ◽

...

Keyword(s):

Bacterial Infections ◽

Pathogenic Bacteria ◽

Inflammatory Responses ◽

Abdominal Sepsis ◽

Immune Defense ◽

Bacterial Killing ◽

Lung Infections ◽

Sepsis Survivors ◽

The Impact

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

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