Anemia of Inflammation

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 276-280 ◽  
Author(s):  
Cindy N. Roy
Keyword(s):  
Inflammatory Diseases ◽  
Underlying Disease ◽  
Comorbid Condition ◽  
Regulatory Pathways ◽  
Hepcidin Expression ◽  
Disease States ◽  
Poor Outcomes ◽  
The Impact ◽  
Inflammatory Insult ◽  
Anemia Of Inflammation

Abstract Inflammation arising from various etiologies, including infection, autoimmune disorders, chronic diseases, and aging, can promote anemia. The anemia of inflammation (AI) is most often normocytic and normochromic and is usually mild. Characteristic changes in systemic iron handling, erythrocyte production, and erythrocyte life span all contribute to AI. The preferred treatment is directed at the underlying disease. However, when the inflammatory insult is intractable, or the cause has not been diagnosed, there are limited options for treatment of AI. Because anemia is a comorbid condition that is associated with poor outcomes in various chronic disease states, understanding its pathogenesis and developing new tools for its treatment should remain a priority. Hepcidin antimicrobial peptide has taken center stage in recent years as a potent modulator of iron availability. As the technology for quantitative hepcidin analysis improves, hepcidin's role in various disease states is also being revealed. Recent insights concerning the regulatory pathways that modify hepcidin expression have identified novel targets for drug development. As the field advances with such therapeutics, the analysis of the impact of normalized hemoglobin on disease outcomes will confirm whether anemia is a reversible independent contributor to the morbidity and mortality associated with inflammatory diseases.

Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2461-2463 ◽  
Author(s):  
Elizabeta Nemeth ◽  
Erika V. Valore ◽  
Mary Territo ◽  
Gary Schiller ◽  
Alan Lichtenstein ◽  
...  
Keyword(s):  
Acute Phase ◽  
Inflammatory Diseases ◽  
Acute Phase Reactant ◽  
Iron Loading ◽  
Type Ii ◽  
Hepcidin Expression ◽  
Hepcidin Mrna ◽  
Anemia Of Inflammation

Hepcidin is a liver-made peptide proposed to be a central regulator of intestinal iron absorption and iron recycling by macrophages. In animal models, hepcidin is induced by inflammation and iron loading, but its regulation in humans has not been studied. We report that urinary excretion of hepcidin was greatly increased in patients with iron overload, infections, or inflammatory diseases. Hepcidin excretion correlated well with serum ferritin levels, which are regulated by similar pathologic stimuli. In vitro iron loading of primary human hepatocytes, however, unexpectedly down-regulated hepcidin mRNA, suggesting that in vivo regulation of hepcidin expression by iron stores involves complex indirect effects. Hepcidin mRNA was dramatically induced by interleukin-6 (IL-6) in vitro, but not by IL-1 or tumor necrosis factor α (TNF-α), demonstrating that human hepcidin is a type II acute-phase reactant. The linkage of hepcidin induction to inflammation in humans supports its proposed role as a key mediator of anemia of inflammation.

scholarly journals Induction of activin B by inflammatory stimuli up-regulates expression of the iron-regulatory peptide hepcidin through Smad1/5/8 signaling

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 431-439 ◽  
Author(s):  
Céline Besson-Fournier ◽  
Chloé Latour ◽  
Léon Kautz ◽  
Jessica Bertrand ◽  
Tomas Ganz ◽  
...  
Keyword(s):  
Underlying Disease ◽  
Type I ◽  
Protein Signaling ◽  
Regulatory Peptide ◽  
Primary Hepatocytes ◽  
Hepcidin Expression ◽  
Morphogenetic Protein ◽  
Receptor Like Kinase ◽  
Inflammatory Stimuli ◽  
Anemia Of Inflammation

Abstract Anemia is very common in patients suffering from infections or chronic inflammation and can add substantially to the morbidity of the underlying disease. It is mediated by excessive production of the iron-regulatory peptide hepcidin, but the signaling pathway responsible for hepcidin up-regulation in the inflammatory context is still not understood completely. In the present study, we show that activin B has an unexpected but crucial role in the induction of hepcidin by inflammation. There is a dramatic induction of Inhbb mRNA, encoding the activin βB-subunit, in the livers of mice challenged with lipopolysaccharide, slightly preceding an increase in Smad1/5/8 phosphorylation and Hamp mRNA. Activin B also induces Smad1/5/8 phosphorylation in human hepatoma–derived cells and, synergistically with IL-6 and STAT-3 signaling, up-regulates hepcidin expression markedly, an observation confirmed in mouse primary hepatocytes. Pretreatment with a bone morphogenic protein type I receptor inhibitor showed that the effect of activin B on hepcidin expression is entirely attributable to its effect on bone morphogenetic protein signaling, most likely via activin receptor-like kinase 3. Activin B is therefore a novel and specific target for the treatment of anemia of inflammation.

scholarly journals Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Peptides: When Is the Assessment of Cer-Tain Factors Warranted?

Antibodies ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 1
Author(s):  
Iftekhar Mahmood ◽  
Mark Pettinato
Keyword(s):  
Small Molecules ◽  
Inflammatory Diseases ◽  
The Body ◽  
Extrinsic Factors ◽  
Peptide Bonds ◽  
Substantial Impact ◽  
Disease States ◽  
Low Toxicity ◽  
The Impact ◽  
Intrinsic And Extrinsic Factors

Peptides are short chains of 2 to 50 amino acids (molecular weight of less than 10 kDa) linked together by peptide bonds. As therapeutic agents, peptides are of interest because the body naturally produces many different peptides. Short-chain peptides have many advantages as compared with long-chain peptides (e.g., low toxicity). The first peptide corticotropin was approved in 1952 for multiple inflammatory diseases and West syndrome. Since then, more than 60 peptides have been approved by the FDA. Pharmacokinetics (PK) is widely used in modern-day drug development for designing a safe and efficacious dose to treat a wide variety of diseases. There are, however, several factors termed as “intrinsic” or “extrinsic” which can influence the PK of a drug, and as a result, one has to adjust the dose in a patient population. These intrinsic and extrinsic factors can be described as age, gender, disease states such as renal and hepatic impairment, drug–drug interaction, food, smoking, and alcohol consumption. It is well known that these intrinsic and extrinsic factors can have a substantial impact on the PK of small molecules, but for macromolecules, the impact of these factors is not well established. This review summarizes the impact of intrinsic and extrinsic factors on the PK of peptides.

Glucose Levels and Outcome After Primary Intraventricular Hemorrhage

2019 ◽  
Vol 16 (1) ◽  
pp. 40-46
Author(s):  
Rui Guo ◽  
Ruiqi Chen ◽  
Chao You ◽  
Lu Ma ◽  
Hao Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Incidence Rate ◽  
Glucose Level ◽  
Intraventricular Hemorrhage ◽  
Laboratory Data ◽  
History Of ◽  
Poor Outcomes ◽  
The Impact

Background and Purpose: Hyperglycemia is reported to be associated with poor outcome in patients with spontaneous Intracerebral Hemorrhage (ICH), but the association between blood glucose level and outcomes in Primary Intraventricular Hemorrhage (PIVH) remains unclear. We sought to identify the parameters associated with admission hyperglycemia and analyze the impact of hyperglycemia on clinical outcome in patients with PIVH. Methods: Patients admitted to Department of Neurosurgery, West China Hospital with PIVH between 2010 and 2016 were retrospectively included in our study. Clinical, radiographic, and laboratory data were collected. Univariate and multivariate logistic regression analyses were used to identify independent predictors of poor outcomes. Results: One hundred and seventy patients were included in the analysis. Mean admission blood glucose level was 7.78±2.73 mmol/L and 10 patients (5.9%) had a history of diabetes mellitus. History of diabetes mellitus (P = 0.01; Odds Ratio [OR], 9.10; 95% Confidence Interval [CI], 1.64 to 50.54) was independent predictor of admission critical hyperglycemia defined at 8.17 mmol/L. Patients with admission critical hyperglycemia poorer outcome at discharge (P < 0.001) and 90 days (P < 0.001). After adjustment, admission blood glucose was significantly associated with discharge (P = 0.01; OR, 1.30; 95% CI, 1.06 to 1.59) and 90-day poor outcomes (P = 0.03; OR, 1.27; 95% CI, 1.03 to 1.58), as well as mortality at 90 days (P = 0.005; OR, 1.41; 95% CI, 1.11 to 1.78). In addition, admission critical hyperglycemia showed significantly increased the incidence rate of pneumonia in PIVH (P = 0.02; OR, 6.04; 95% CI 1.27 to 28.80) even after adjusting for the confounders. Conclusion: Admission blood glucose after PIVH is associated with discharge and 90-day poor outcomes, as well as mortality at 90 days. Admission hyperglycemia significantly increases the incidence rate of pneumonia in PIVH.

scholarly journals POS1180 TREATMENT COMPLIANCE OF PATIENTS WITH RHEUMATOID ARTHRITIS DURING THE FIRST WAVE OF THE SARS-CoV-2/COVID-19 PANDEMIC IN PORTUGAL: RESULTS FROM THE COVID IN RA (COVIDRA) SURVEY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 871.2-871
Author(s):  
F. Araujo ◽  
N. Gonçalves ◽  
A. F. Mourão
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Immunosuppressive Treatment ◽  
Treatment Compliance ◽  
Web Based ◽  
Symptoms Of Depression ◽  
Immune Mediated ◽  
Attending Physician ◽  
The Impact ◽  
E Mail

Background:The outcomes of the infection by the SARS-CoV-2 in patients with immune-mediated inflammatory diseases were largely unknown during the early days of the COVID-19 pandemic. It was hypothesized that these patients were at higher risk of morbidity and mortality due to their inherent immune dysfunction and immunosuppressive therapy. Several rheumatology societies issued recommendations urging patients not to stop their anti-rheumatic treatments.Objectives:To assess treatment compliance of patients with rheumatoid arthritis (RA) during the first wave of the SARS-CoV-2/COVID-19 pandemic in Portugal.Methods:The web-based survey COVIDRA (COVID in RA) was developed to assess the impact of the first wave mandatory confinement in patients with RA focusing on 5 domains: RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Descriptive statistics were generated by the survey software and were afterwards transported and evaluated using appropriate biostatistics software.Results:We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%), with a mean age of 58 (+/-13) years. The majority (57.6%) had longstanding disease (>10 years) and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23,7%). Only 14% (N=61) discontinued or reduced the dosage or frequency of their RA treatment. Most of these changes were previously planned by the attending physician (27.9%). Only 11 patients (18%) discontinued their immunosuppressive medication out of fear of becoming infected with SARS-CoV-2 (corresponding to 2.5% of total responders). Another 11 patients did so because they had no prescription, couldn’t go to the community/hospital pharmacy or couldn’t afford the medication. Although these numbers preclude any statistical analysis, when compared to patients who persisted on their treatment, those discontinuing due to fear of contagion were younger (56.4 vs 58.5 years), all female (100 vs 86.8%), with long-lasting disease (≥ 11 years) (90.9% vs 57.5%), more frequently treated with bDMARDs (36.4 vs 23.1%) and presenting more symptoms of depression (54.5 vs 49.7%).Conclusion:Most RA patients complied with their treatment during the first wave of the SARS-CoV-2 pandemic in Portugal. Only a minority changed their immunosuppressive treatment due to fear of SARS-CoV-2 infection. Very similar rates of immunosuppressive discontinuation due to fear of contagion were reported by other authors (such as Schmeiser et al, Pineda-sic et al and Fragoulis et al).Disclosure of Interests:Filipe Araujo Speakers bureau: Pfizer, Biogen, Novartis, Menarini, Consultant of: MSD, Nuno Gonçalves: None declared, Ana Filipa Mourão: None declared.

Does Infection Site Matter? A Systematic Review of Infection Site Mortality in Sepsis

2016 ◽  
Vol 32 (8) ◽  
pp. 473-479 ◽  
Author(s):  
Christine A. Motzkus ◽  
Roger Luckmann
Keyword(s):  
Hospital Mortality ◽  
Respiratory Infections ◽  
Source Control ◽  
Soft Tissue Infections ◽  
Infection Site ◽  
Treatment Protocols ◽  
Disease States ◽  
Pubmed Database ◽  
The Impact ◽  
Lower Mortality Risk

Purpose: Sepsis treatment protocols emphasize source control with empiric antibiotics and fluid resuscitation. Previous reviews have examined the impact of infection site and specific pathogens on mortality from sepsis; however, no recent review has addressed the infection site. This review focuses on the impact of infection site on hospital mortality among patients with sepsis. Methods: The PubMed database was searched for articles from 2001 to 2014. Studies were eligible if they included (1) one or more statistical models with hospital mortality as the outcome and considered infection site for inclusion in the model and (2) adult patients with sepsis, severe sepsis, or septic shock. Data abstracted included stage of sepsis, infection site, and raw and adjusted effect estimates. Nineteen studies were included. Infection sites most studied included respiratory (n = 19), abdominal (n = 19), genitourinary (n = 18), and skin and soft tissue infections (n = 11). Several studies found a statistically significant lower mortality risk for genitourinary infections on hospital mortality when compared to respiratory infections. Conclusion: Based on studies included in this review, the impact of infection site in patients with sepsis on hospital mortality could not be reliably estimated. Misclassification among infections and disease states remains a serious possibility in studies on this topic.

565 POST-OPERATIVE WEIGHT LOSS AND OUTCOMES FOLLOWING ESOPHAGECTOMY

2020 ◽  
Vol 33 (Supplement_1) ◽  
Author(s):  
R Khaw ◽  
S Munro ◽  
J Sturrock ◽  
H Jaretzke ◽  
S Kamarajah ◽  
...  
Keyword(s):  
Weight Loss ◽  
Length Of Stay ◽  
Hospital Stay ◽  
Enhanced Recovery ◽  
Length Of Hospital Stay ◽  
Failure To Thrive ◽  
Post Discharge ◽  
Postoperative Weight Loss ◽  
Poor Outcomes ◽  
The Impact

Abstract   Oesophageal cancer is the 11th most common cancer worldwide, with oesophagectomy remaining the mainstay curative treatment, despite significant associated morbidity and mortality. Postoperative weight loss remains a significant problem and is directly correlated to poor prognosis. Measures such as the Enhanced Recovery After Surgery (ERAS) programme and intraoperative jejunostomy feed have looked to tackle this. This study investigates the impact of these on mortality, length of hospital stay and postoperative weight loss. Methods Patients undergoing oesophagectomy between January 1st 2012—December 2014 and 28th October 2015–December 31st 2019 in a national tertiary oesophagogastric unit were included retrospectively. Variables measured included comorbidities, operation, histopathology, weights (pre- and post-operatively), length of hospital stay, postoperative complications and mortality. Pre-operative body weight was measured at elective admission, and further weights were identified from a prospectively maintained database, during further clinic appointments. Other data was collected through patient notes. Results 594 patients were included. Mean age at diagnosis was 65.9 years (13–65). Majority of cases were adenocarcinoma (63.3%), with varying stages of disease (TX-4, NX-3). Benign pathology accounted for 8.75% of cases. Mean weight loss post-oesophagectomy exceeded 10% at 6 months (SD 14.49). Majority (60.1%) of patients were discharged with feeding jejunostomy, and 5.22% of these required this feed to be restarted post-discharge. Length of stay was mean 16.5 days (SD 22.3). Complications occurred in 68.9% of patients, of which 13.8% were infection driven. Mortality occurred in 26.6% of patients, with 1.83% during hospital admission. 30-day mortality rate was 1.39%. Conclusion Failure to thrive and prolonged weight-loss following oesophagectomy can contribute to poor recovery, with associated complications and poor outcomes, including increased length of stay and mortality. Further analysis of data to investigate association between weight loss and poor outcomes for oesophagectomy patients will allow for personalised treatment of high-risk patients, in conjunction with members of the multidisciplinary team, including dieticians.

scholarly journals Molecular functions of ASK family in diseases caused by stress-induced inflammation and apoptosis

2020 ◽  
Author(s):  
Kazuki Kojima ◽  
Hidenori Ichijo ◽  
Isao Naguro
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Adverse Effects ◽  
Er Stress ◽  
Inflammatory Diseases ◽  
Family Members ◽  
Disease States ◽  
Molecular Functions ◽  
Critical Responses ◽  
Proper Response

Summary VCells are constantly exposed to various types of stress, and disruption of the proper response lead to a variety of diseases. Among them, inflammation and apoptosis are important examples of critical responses and should be tightly regulated, as inappropriate control of these responses is detrimental to the organism. In several disease states, these responses are abnormally regulated, with adverse effects. Apoptosis signal-regulating kinase (ASK) family members are stress-responsive kinases that regulate inflammation and apoptosis after a variety of stimuli, such as oxidative stress and endoplasmic reticulum (ER) stress. In this review, we summarize recent reports on the ASK family in terms of their involvement in inflammatory diseases, focusing on upstream stimuli that regulate ASK family members.

scholarly journals LINC-25. BRAF ABERRATIONS IN PEDIATRIC PILOCYTIC ASTROCYTOMAS (PCAs): PREVALENCE AND IMPACT ON CLINICAL OUTCOME

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii383-iii383
Author(s):  
Subramaniam Ramanathan ◽  
Maya Prasad ◽  
Tushar Vora ◽  
Mamta Gurav ◽  
Ayushi Sahay ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Statistical Significance ◽  
Tumor Resection ◽  
Brafv600e Mutation ◽  
Therapeutic Implications ◽  
Pilocytic Astrocytomas ◽  
Ffpe Tissues ◽  
Braf Fusion ◽  
Poor Outcomes ◽  
The Impact

Abstract BACKGROUND Increasing knowledge on pilocytic astrocytoma (PCA) biology now points towards an aberration in BRAF/MAPK/ERK pathway which has both diagnostic and therapeutic implications. This study was done to note the impact of BRAF aberrations on clinical outcome in childhood PCA. METHODS FFPE tissues of all childhood PCA diagnosed during 2011–2017 were evaluated for BRAFV600E mutation by Sanger sequencing and KIAA1549 fusion transcripts (16–9;15–9;16-11) by reverse transcriptase polymerase chain reaction. Children undergoing gross tumor resection received no adjuvant treatment. Unresectable tumors (only biopsy) and NF-1 associated PCAs, were treated if clinically indicated. Only patients with documented therapy details/followup were included for analysis. STUDY RESULTS Ninety-eight patients (median age-7.7yrs; boy:girl ratio-1.4) were included. Major sites were: Cerebellum-37(38%), 3rd Ventricle-26(27%), Cerebrum-15(15%). While BRAFV600E mutation was noted in 7/89(8%) specimens, BRAF-fusions were found in 34/85(40%). Following surgery/biopsy, 23(24%) and 21(22%) received adjuvant chemotherapy and radiotherapy respectively. The 1-year/3-year/5-year-EFS of the overall cohort was 90.7%/81.3%/67.4% respectively. Cerebellar tumors did better vis-à-vis other sites(5yr-EFS:74.3% v/s 66.4%;p=0.403). The 5yr-EFS of BRAF-fusion positive tumors (34), tumors without any BRAF aberration (40) and BRAFV600E mutant tumors (7) was 84.8%/ 69.6%/ 42.9% (p=0.215). CONCLUSIONS BRAF-fusion and BRAFV600E mutation were associated with good and poor outcomes respectively. Lack of statistical significance could be attributed to use of radiation as planned therapy in patients from earlier years. Data on BRAF aberrations in PCAs aids decision making regarding adjuvant therapy and choosing appropriate salvage-therapy especially in relapsed/refractory PCAs.

Idiopathic juvenile osteoporosis in a child: a four-year follow-up with review of literature

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Aashima Dabas ◽  
Rakhi Malhotra ◽  
Ravindra Kumar ◽  
Rajesh Khadgawat
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Underlying Disease ◽  
Bone Fragility ◽  
Management Approach ◽  
Primary Osteoporosis ◽  
Disease States ◽  
Idiopathic Juvenile Osteoporosis ◽  
Density Lipoprotein Receptor

Abstract Objectives Childhood osteoporosis is an uncommon condition that usually develops secondary to underlying disease states. Idiopathic juvenile osteoporosis or early onset osteoporosis is a rare cause of primary osteoporosis in childhood associated with mutations in “bone fragility” genes. Case presentation The index case presented with upper back pain and was detected to have multiple vertebral fractures. Further workup for the cause revealed a homozygous benign mutation in low-density lipoprotein receptor-related protein 5, which was also detected in the mother who remained asymptomatic till presentation. The child was successfully treated with intravenous zoledronate. Conclusions The case report describes the management approach and four-year follow-up of the child.

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