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Biomedical Papers of the Medical... Mar 2015The treatment of malignancies like acute myeloid leukemia (AML) is often complicated by the heterogeneity of the disease and the mechanisms of the disease progression.... (Review)
Review
BACKGROUND
The treatment of malignancies like acute myeloid leukemia (AML) is often complicated by the heterogeneity of the disease and the mechanisms of the disease progression. This heterogeneity is often not reflected in standard treatment approaches which provide predictable outcomes in the majority of patients but fail in individual cases even with high-dose multi-agent chemotherapy regimens and allogeneic stem cell transplantation. Further, the unselective effect of chemotherapy causes high treatment-related toxicity and accelerates the risk of infection during prolonged pancytopenia, preventing further dose escalation. Despite rapid progress in therapeutic strategies, the fatality of high-grade malignancies remains enormous.
OBJECTIVES
Adhesive interactions trigger signal transduction pathway activation and this prevents the apoptosis of both normal and malignant cells. A correlation between expression of defined adhesion molecules and patient outcome has been found for several malignant diseases including AML. We aim to describe how disruption of these signalling pathways can overcome the high resistance to treatment and increase the selectivity of targeting malignant cells. This could effectively reduce the overall treatment-related toxicity and improve the general outcome.
CONCLUSIONS
Adhesion molecules facilitate growth of malignant diseases. This review provides a deeper insight into these processes. Modulation of adhesion molecules-mediated interactions is an innovative and feasible approach in treatment of AML and many other malignancies. Due to expected low toxicity it is an acceptable addition to standard chemotherapeutical regimens for all age groups of patients. This approach could improve the overall treatment outcome in the future.
Topics: Cell Adhesion Molecules; Combined Modality Therapy; Humans; Leukemia, Myeloid, Acute; Prognosis
PubMed: 25270108
DOI: 10.5507/bp.2014.049 -
World Journal of Hepatology Sep 2018To systematically review liver disease associated with hemophagocytic lymphohistiocytosis (HLH), propose reasonable contraindications for liver transplantation for liver...
AIM
To systematically review liver disease associated with hemophagocytic lymphohistiocytosis (HLH), propose reasonable contraindications for liver transplantation for liver failure in HLH, and report an illustrative case.
METHODS
Systematic review according to PRISMA guidelines of hepatic manifestations of HLH using computerized literature search PubMed of articles published since 1980 with keywords ("hemophagocytic lymphohistiocytosis" or "HLH") AND ("liver" or "hepatic"). Two authors independently performed literature search and incorporated articles into this review by consensus. Illustrative case report presented based on review of medical chart, and expert re-review of endoscopic photographs, radiologic images, and pathologic slides.
RESULTS
A 47-year-old Caucasian male, was hospitalized with high-grade pyrexia, rash, total bilirubin = 45 g/dL, moderately elevated hepatic transaminases, ferritin of 3300 ng/dL, leukopenia, and profound neutropenia (absolute neutrophil count < 100 cells/mm³). Viral serologies for hepatitis A, B, and C were negative. Abdominal computed tomography scan and magnetic resonance imaging revealed no hepatic or biliary abnormalities. Pathologic analysis of liver biopsy revealed relatively well-preserved hepatic parenchyma without lymphocytic infiltrates or macrophage invasion, except for sparse, focal hepatocyte necrosis. Bone marrow biopsy and aspirate revealed foamy macrophages engulfing mature and precursor erythrocytes, consistent with HLH. Interleukin-2 receptor (CD25) was highly elevated, confirming diagnosis of HLH according to Histiocytic Society criteria. Patient initially improved after high-dose prednisone therapy. Patient was judged not to be a liver transplant candidate despite model for end stage liver disease (MELD) score = 33 because liver failure was secondary to severe systemic disease from HLH, including septic shock, focal centrilobular hepatocyte necrosis from hypotension, bone marrow failure, and explosive immune activation from HLH. The patient eventually succumbed to overwhelming sepsis, progressive liver failure, and disseminated intravascular coagulopathy. Systematic review reveals liver injury is very common in HLH, and liver failure can sometimes occur. Data on liver transplantation for patients with HLH are very limited, and so far the results have shown a generally much worse prognosis than for other liver transplant indications. Liver transplantation should not be guided solely by MELD score, but should include liver biopsy results and determination whether liver failure is from intrinsic liver injury multisystem (extrahepatic) organ failure from HLH.
CONCLUSION
This case report illustrates that liver transplantation may not be warranted when liver failure associated with HLH is primarily from multisystem failure from HLH. Liver biopsy may be very helpful in determining the severity and pathophysiology of the liver disease.
PubMed: 30310541
DOI: 10.4254/wjh.v10.i9.629 -
Seminars in Arthritis and Rheumatism Jun 2015Systemic lupus erythematosus (SLE) is an autoimmune disease that may present manifestations that resemble other diseases. Visceral leishmaniasis (VL) is a parasitic... (Review)
Review
OBJECTIVE
Systemic lupus erythematosus (SLE) is an autoimmune disease that may present manifestations that resemble other diseases. Visceral leishmaniasis (VL) is a parasitic infection whose hallmarks may mimic SLE symptoms. Here, we report a case series and evaluate the published, scientific evidence of the relationship between SLE and VL infection.
METHODS
To assess original studies reporting cases of VL-infected patients presenting manifestations that are capable of leading to inappropriate suspicions of SLE or mimicking an SLE flare, we performed an extensive search in several scientific databases (MEDLINE, LILACS, SciELO, and Scopus). Two authors independently screened all citations and abstracts identified by the search strategy to identify eligible studies. Secondary references were additionally obtained from the selected articles.
RESULTS
The literature search identified 53 eligible studies, but only 17 articles met our criteria. Among these, 10 lupus patients with VL mimicking an SLE flare and 18 cases of VL leading to unappropriated suspicions of SLE were described. The most common manifestations in patients infected with VL were intermittent fever, pancytopenia, visceromegaly, and increased serum level of acute phase reactants. The most frequent autoantibodies were antinuclear antibodies, rheumatoid factor, and direct Coombs' test.
CONCLUSION
In endemic areas for VL, the diagnosis of SLE or its exacerbation may be a clinical dilemma. Hepatosplenomegaly or isolated splenomegaly was identified in the majority of the reported cases where VL occurred, leading to unappropriated suspicions of SLE or mimicking an SLE flare. Furthermore, the lack of response to steroids, the normal levels of complement proteins C3 and C4, and the increased level of transaminases suggest a possible infectious origin.
Topics: Adolescent; Adult; Antibodies, Antinuclear; Coombs Test; Diagnosis, Differential; Female; Fever; Humans; Leishmaniasis, Visceral; Lupus Erythematosus, Systemic; Pancytopenia; Rheumatoid Factor
PubMed: 25704907
DOI: 10.1016/j.semarthrit.2014.12.004 -
Tropical Doctor Jan 2021Visceral leishmaniasis is a tropical parasitic disease caused by the species of the genus The clinical picture includes fever, splenomegaly, leucopenia, anaemia and...
Visceral leishmaniasis is a tropical parasitic disease caused by the species of the genus The clinical picture includes fever, splenomegaly, leucopenia, anaemia and hypergammaglobulinaemia. There may also be a drop in plasma fibrinogen levels or an increase in plasma fibrinolytic activity. Furthermore, visceral leishmaniasis may be the trigger for secondary haemophagocytic lymphohistiocytosis. On the other hand, disseminated intravascular coagulation may also result. The International Society of Thrombosis and Hemostasis has recommended the use of a scoring system for disseminated intravascular coagulation. An association between visceral leishmaniasis and consumption coagulopathy is not frequent. Our systematic literature review from 1967 to 2019 pointed to the report of only 16 cases. Our case demonstrates that it is necessary to be aware of the existence of this association.
Topics: Adult; Disseminated Intravascular Coagulation; Humans; Leishmania infantum; Leishmaniasis, Visceral; Male
PubMed: 33108965
DOI: 10.1177/0049475520967239