Reactive hemophagocytic lymphohistiocytosis and Crimean-Congo hemorrhagic fever
Bibliographic record
Abstract
We read a manuscript entitled ‘Increased serum ferritin levels in patients with Crimean-Congo hemorrhagic fever: can it be a new severity criterion?’ by Barut et al. published in your journal (May 30, 2009). The authors stated that increased serum ferritin levels may be a useful marker for diagnosis, disease activity, and prognosis of Crimean-Congo hemorrhagic fever (CCHF), and that reactive hemophagocytic lymphohistiocytosis (HLH) has been seen in patients with CCHF. Serum ferritin levels were a diagnostic marker of HLH and 77.3% of the patients had abnormal serum ferritin levels. A significant negative correlation was observed between serum ferritin levels and platelet counts.1Barut S. Dincer F. Sahin I. Ozyurt H. Akkus M. Erkorkmaz U. Increased serum ferritin levels in patients with Crimean-Congo hemorrhagic fever: can it be a new severity criterion?.Int J Infect Dis. 2009; (May 30 [Epub ahead of print])Google Scholar The authors suggested that the cause of the increased ferritin level in patients with CCHF was due to HLH, however they did not carry out bone marrow aspirations (BMA), nor did they observe the erythrocytes, lymphocytes, neutrophils or thrombocytes phagocytosed by macrophages on BMA smear. As mentioned by the authors, a cytokine storm initiates and triggers the development of HLH and the serum ferritin level increases as an acute phase substance.2Papa A. Bino S. Velo E. Harxhi A. Kota M. Antoniadis A. Cytokine levels in Crimean-Congo hemorrhagic fever.J Clin Virol. 2006; 36: 272-276Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 3Ergonul O. Tuncbilek S. Baykam N. Celikbas A. Dokuzoguz B. Evaluation of serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha in patients with Crimean-Congo hemorrhagic fever.J Infect Dis. 2006; 193: 941-944Crossref PubMed Scopus (169) Google Scholar The pathogenesis of CCHF is complex and various factors are responsible. The majority of patients have died as a result of hemorrhage. The causes of hemorrhage are disseminated intravascular coagulation (DIC), thrombocytopenia, and endothelial damage.1Barut S. Dincer F. Sahin I. Ozyurt H. Akkus M. Erkorkmaz U. Increased serum ferritin levels in patients with Crimean-Congo hemorrhagic fever: can it be a new severity criterion?.Int J Infect Dis. 2009; (May 30 [Epub ahead of print])Google Scholar, 4Ergonul O. Treatment of Crimean-Congo hemorrhagic fever.Antiviral Res. 2008; 78: 125-131Crossref PubMed Scopus (132) Google Scholar DIC may develop due to direct damage of the endothelial cells by the virus, immune-mediated liver dysfunction during the acute phase, and cytokine storm (increase in interleukin (IL)-1, IL-6, IL-12, IL-18, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ). An inappropriate Th1 response and lack of viral clearance are the main causes of this cytokine storm.2Papa A. Bino S. Velo E. Harxhi A. Kota M. Antoniadis A. Cytokine levels in Crimean-Congo hemorrhagic fever.J Clin Virol. 2006; 36: 272-276Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 3Ergonul O. Tuncbilek S. Baykam N. Celikbas A. Dokuzoguz B. Evaluation of serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha in patients with Crimean-Congo hemorrhagic fever.J Infect Dis. 2006; 193: 941-944Crossref PubMed Scopus (169) Google Scholar, 5Tasdelen Fisgin N. Fisgin T. Tanyel E. et al.Crimean-Congo hemorrhagic fever: five patients with hemophagocytic syndrome.Am J Hematol. 2008; 83: 73-76Crossref PubMed Scopus (50) Google Scholar Thrombocytopenia develops in the majority of patients and the causes of thrombocytopenia are DIC and HLH. We believe that high serum lactate dehydrogenase (LDH) levels and soluble CD25 levels, or decreased natural killer (NK) cell activity, which are indicative of macrophage activation syndrome and HLH, are early indicators of CCHF as good as high serum ferritin levels. In addition, thrombocytopenia and increased serum D-dimer are early findings of DIC6Oberhofer D. Kusices-Tepes N. Skok J. Vusic N. Cala K. Coagulation test in septic surgical patients.Acta Med Croatica. 2004; 58: 389-394PubMed Google Scholar. We think that when a patient with CCHF has thrombocytopenia and an increase in serum D-dimer, DIC has developed. The patient then receives fresh frozen plasma for factor replacement and corticosteroid therapy, such as mega-dose methylprednisolone (20–30 mg/kg/day p.o. or i.v., before 6 a.m.), for inhibiting the cytokine storm, stabilization of the cell membrane, and vascular endothelial integrity. Ribavirin treatment is controversial in the hemorrhagic period; it has been found to be effective in the early stage of the disease.7Tasdelen Fisgin N. Ergonul O. Doganci L. Tulek N. The role of ribavirin in the therapy of Crimean-Congo hemorrhagic fever: early use is promising.Eur J Clin Microbiol Infect Dis. 2009; 28: 929-933Crossref PubMed Scopus (77) Google Scholar No conflict of interest to declare. Corresponding Editor: William Cameron, Ottawa, Canada.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".