scholarly journals Osteopontin and Transplantation: Where Are We Now?

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Beata Kaleta
Keyword(s):  
Graft Function ◽  
Treatment Strategies ◽  
Innate Immune Responses ◽  
Hematopoietic Stem ◽  
Non Invasive ◽  
Increased Risk ◽  
Wide Range ◽  
New Treatment ◽  
End Stage ◽  
Hsc Transplantation

AbstractOrgan transplantation represents the optimal therapeutic tool for patients with end-stage organ failure. Hematopoietic stem cell transplantation (HSCT) is likewise an effective therapy for a wide range of malignant and non-malignant diseases. Better understanding of transplantation immunology and the use of multi-modal immunosuppression protocols, can decrease the risk of graft failure and graft-versus-host disease (GVHD) after HSCT. Nevertheless, a major challenge of modern transplantology still seems to be finding non-invasive biomarkers for recipients selection, monitoring of allograft function, and diagnosis of rejection. Since proinflammatory cytokine osteopontin (OPN) is closely involved in regulating both adaptive and innate immune responses, as well as the pathogenesis of inflammatory and autoimmune diseases, it is likely to play an important role in organ and HSC transplantation. This review is to summarize recent advances in our knowledge about OPN function in the kidney, heart, liver, lung, and HSC transplantation. Most studies found that elevated OPN is associated with poorer graft function in kidney, heart, liver and lung recipients. Moreover, some reports suggested that this protein can play role in GVHD pathogenesis. However, due to relatively small number of similar studies, as well as some inconclusive results, future investigation in this field is needed to verify if OPN can serve as a biomarker of organ and HSC transplantation. The knowledge about such markers will promote our understanding of the mechanisms underlying graft dysfunction and posttransplant mortality. In addition, such knowledge may be helpful in the development of new treatment strategies and identification of recipients with increased risk of allograft failure.

scholarly journals Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage

2020 ◽  
Vol 11 ◽  
Author(s):  
Rossana Franzin ◽  
Alessandra Stasi ◽  
Marco Fiorentino ◽  
Giovanni Stallone ◽  
Vincenzo Cantaluppi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Complement System ◽  
Kidney Diseases ◽  
Critical Role ◽  
Graft Function ◽  
Kidney Injury ◽  
Increased Risk ◽  
Wide Range ◽  
Renal Aging

The aberrant activation of complement system in several kidney diseases suggests that this pillar of innate immunity has a critical role in the pathophysiology of renal damage of different etiologies. A growing body of experimental evidence indicates that complement activation contributes to the pathogenesis of acute kidney injury (AKI) such as delayed graft function (DGF) in transplant patients. AKI is characterized by the rapid loss of the kidney’s excretory function and is a complex syndrome currently lacking a specific medical treatment to arrest or attenuate progression in chronic kidney disease (CKD). Recent evidence suggests that independently from the initial trigger (i.e., sepsis or ischemia/reperfusions injury), an episode of AKI is strongly associated with an increased risk of subsequent CKD. The AKI-to-CKD transition may involve a wide range of mechanisms including scar-forming myofibroblasts generated from different sources, microvascular rarefaction, mitochondrial dysfunction, or cell cycle arrest by the involvement of epigenetic, gene, and protein alterations leading to common final signaling pathways [i.e., transforming growth factor beta (TGF-β), p16ink4a, Wnt/β-catenin pathway] involved in renal aging. Research in recent years has revealed that several stressors or complications such as rejection after renal transplantation can lead to accelerated renal aging with detrimental effects with the establishment of chronic proinflammatory cellular phenotypes within the kidney. Despite a greater understanding of these mechanisms, the role of complement system in the context of the AKI-to-CKD transition and renal inflammaging is still poorly explored. The purpose of this review is to summarize recent findings describing the role of complement in AKI-to-CKD transition. We will also address how and when complement inhibitors might be used to prevent AKI and CKD progression, therefore improving graft function.

scholarly journals Recent advances in renal imaging

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1867 ◽  
Author(s):  
Joshua M. Thurman ◽  
Faikah Gueler
Keyword(s):  
Kidney Diseases ◽  
Treatment Strategies ◽  
Blood Oxygen Level Dependent ◽  
Great Promise ◽  
Blood Oxygen Level ◽  
Bold Mri ◽  
Contrast Enhanced ◽  
Radiologic Imaging ◽  
Wide Range ◽  
New Treatment

Kidney diseases can be caused by a wide range of genetic, hemodynamic, toxic, infectious, and autoimmune factors. The diagnosis of kidney disease usually involves the biochemical analysis of serum and blood, but these tests are often insufficiently sensitive or specific to make a definitive diagnosis. Although radiologic imaging currently has a limited role in the evaluation of most kidney diseases, several new imaging methods hold great promise for improving our ability to non-invasively detect structural, functional, and molecular changes within the kidney. New methods, such as dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and blood oxygen level-dependent (BOLD) MRI, allow functional imaging of the kidney. The use of novel contrast agents, such as microbubbles and nanoparticles, allows the detection of specific molecules in the kidney. These methods could greatly advance our ability to diagnose disease and also to safely monitor patients over time. This could improve the care of individual patients, and it could also facilitate the evaluation of new treatment strategies.

scholarly journals Precision medicine and inflammatory bowel diseases: concept, strategies, future

2021 ◽  
Vol 1 (6) ◽  
pp. 121-129
Author(s):  
G. R. Bikbavova ◽  
M. A. Livzan ◽  
D. G. Novikov ◽  
E. A. Bambulskaya
Keyword(s):  
Precision Medicine ◽  
Inflammatory Bowel Diseases ◽  
Scientific Information ◽  
Treatment Strategies ◽  
Wide Range ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
New Treatment ◽  
Personalized Approach ◽  
The Right

With the advent of modern cellular and genomic technologies, we have become participants in the integration of such areas as personalized, predictive, preventive, and precision medicine (referred to as 4P-medicine), into practical healthcare. In replace of the classic methods of diagnosis and treatment of diseases comes medicine, which makes it possible to predict (anticipate) the disease, and a personalized approach to each patient, taking into account their genetic, biochemical and physiological uniqueness. Precision medicine aims to improve the quality of medical care by opening up an individual approach to the patient and covers a wide range of areas, including drug therapy, genetics, and cause-and-effect relationships in order to make the right decisions based on evidence. 4P-medicine combines knowledge in the field of proteomics, metabolomics, genomics, bioinformatics with classical approaches of anatomy, therapy, laboratory and instrumental diagnostics as well as public health. The purpose of this review is to analyze and summarize the information available to date and to present examples of the application of modern approaches of medicine into clinical practice by diving into the example of inflammatory bowel diseases (IBD). The search for literature containing scientific information about relevant studies was conducted in the PubMed and Google Scholar systems with the use of the following keywords: precision medicine, 4P medicine, inflammatory bowel diseases. Despite significant progress in medicine in general, there is still a long way to go before implementing the principles of precision medicine in the field of IBD, since many clinicians continue to treat patients with IBD symptomatically. However, the use of specific biomarkers and new treatment strategies as described in the review, can significantly accelerate this path and contribute to the improvement of diagnostic and therapeutic approaches.

scholarly journals Polycythemia Vera and Heart Failure: Association and Outcomes- a Propensity Matched Analysis in Hospitalized Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4621-4621
Author(s):  
Shivani Dalal ◽  
Krunalkumar Patel ◽  
Daniel Tran ◽  
Akash Patel ◽  
Thanh Nguyen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Length Of Stay ◽  
Polycythemia Vera ◽  
Treatment Strategies ◽  
Hematopoietic Stem ◽  
Coronary Syndrome ◽  
Total Length ◽  
Increased Risk ◽  
Hospitalization Costs ◽  
Baseline Characteristics

Abstract Polycythemia Vera (PV) is a rare chronic myeloproliferative disorder (MPN), a hematopoietic stem cell-derived malignancy that is characterized by clonal proliferation of myeloid cells with variable degrees of morphologic maturity. PV is distinguished from other MPNs by the presence of an elevated red blood cell mass (ie, erythrocytosis), and is associated with an increased risk for thromboembolic events, leukemic transformation, and/or myelofibrosis. This translates to sludging of blood flow due to hyperviscosity. Patients with PV have increased risk of both arterial and venous thrombosis as well as hemorrhage. Acute coronary syndrome and cardiac thrombotic events are well known complications of PV, however there is insufficient data on PV associated with heart failure (HF) and its repercussions. Through this study we aim to determine baseline characteristics of PV patients with and without HF and its impact on morbidity, mortality and overall hospital length of stay. We identified all hospitalized adult patients with PV from the National Inpatient Sample Database between January 2016 to December 2018 using ICD-10-CM codes, and divided them into groups with and without heart failure. We compared patient's baseline characteristics, associated comorbidities, mortality, length of stay and hospitalization costs among PV patients with and without HF. Propensity-score 1:1 matching for age, sex, race, and co-morbidities was performed among both groups. SAS 9.4 software was used for statistical analysis. Out of 61265 patients hospitalized with PV, 16900(27.6%) patients were found to have HF. The patients in HF group were noted to have higher mean age (74.7±12.3 vs 69±14.3 years), and higher prevalence of comorbidities such as diabetes mellitus (27.5 vs 20.4%), coronary artery disease (47.2 vs 22.4%), peripheral vascular disease (12.1 vs 9.9%), chronic pulmonary obstructive disease (33.9 vs 20.6%), Renal failure (20.2 vs 9.4%) and obesity (13.6 vs 10.5%). In terms of propensity matched outcomes, the group with PV and coexisting HF had higher inpatient mortality (5.9 vs 3.6%), higher total length of stay (6.5 ± 7.3 vs 5.2 ± 5.3 days), and higher total hospitalization cost (18081 ± 27506 vs 14529 ± 18412 $) (p<0.001). Our study noted that almost 27.6% of hospitalized PV patients had concurrent HF. We observed that presence of HF in patients with PV significantly increased mortality, hospitalization costs and total length of stay. Despite major advances in Heart failure (HF) treatment strategies, morbidity and mortality remains high. With regard to the etiology, there are different causes of HF, and their recognition can be crucial for treatment optimization. With mounting epidemiological evidence of association and fatal outcomes, our study also shines light on a significant knowledge gap in the field of MPN such as PV and concurrent HF, and warrants further studies to better delineate pathogenesis and early diagnostic and treatment strategies specifically curated for PV associated HF. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Management of Acute Myeloid Leukemia in Elderly Patients

1999 ◽  
Vol 17 (11) ◽  
pp. 3569-3576 ◽  
Author(s):  
Wolfgang Hiddemann ◽  
Wolfgang Kern ◽  
Claudia Schoch ◽  
Christa Fonatsch ◽  
Achim Heinecke ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
Treatment Strategies ◽  
Hematopoietic Growth Factors ◽  
Hematopoietic Stem ◽  
Mdr1 Expression ◽  
New Treatment ◽  
Acute Myeloid

ABSTRACT: Acute myeloid leukemia (AML) at older age is associated with several biologic and clinical characteristics. Hence, it may arise from an early level of hematopoietic stem cells and has a high frequency of blast cells with multidrug resistance glycoprotein MDR1 expression and particularly a high incidence of poor prognostic karyotypes. These factors, rather than age per se, underlie the poorer outcome as compared with younger cases. Prospective randomized studies clearly demonstrate, however, that elderly patients benefit from more intensive induction therapy and particularly from full-dose application of anthracyclines and possibly also cytarabine. Hematopoietic growth factors accelerate the recovery from treatment-induced neutropenia and may improve the remission rate, remission duration, and even overall survival. New treatment strategies need to be developed, however, for poor-prognosis AML subtypes in order to further improve the therapeutic perspectives for elderly patients with AML.

scholarly journals Posttransplant Lymphoproliferative Disease after Pediatric Solid Organ Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Martin Mynarek ◽  
Tilmann Schober ◽  
Uta Behrends ◽  
Britta Maecker-Kolhoff
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Treatment Strategies ◽  
Lymphoproliferative Disease ◽  
Treatment Modalities ◽  
Solid Organ ◽  
Increased Risk ◽  
Posttransplant Lymphoproliferative Disease ◽  
New Treatment ◽  
Anti Cd20

Patients after solid organ transplantation (SOT) carry a substantially increased risk to develop malignant lymphomas. This is in part due to the immunosuppression required to maintain the function of the organ graft. Depending on the transplanted organ, up to 15% of pediatric transplant recipients acquire posttransplant lymphoproliferative disease (PTLD), and eventually 20% of those succumb to the disease. Early diagnosis of PTLD is often hampered by the unspecific symptoms and the difficult differential diagnosis, which includes atypical infections as well as graft rejection. Treatment of PTLD is limited by the high vulnerability towards antineoplastic chemotherapy in transplanted children. However, new treatment strategies and especially the introduction of the monoclonal anti-CD20 antibody rituximab have dramatically improved outcomes of PTLD. This review discusses risk factors for the development of PTLD in children, summarizes current approaches to therapy, and gives an outlook on developing new treatment modalities like targeted therapy with virus-specific T cells. Finally, monitoring strategies are evaluated.

scholarly journals Mechanisms of Bone Metastasis of Malignancies of the Genito-Mammary Area

2018 ◽  
Vol 1 (Supplement) ◽  
pp. 42
Author(s):  
R. Bohîlțea ◽  
N. Turcan ◽  
T.A. Georgescu ◽  
M.M. Cîrstoiu
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Molecular Mechanisms ◽  
Bone Matrix ◽  
Cell Activity ◽  
Hematopoietic Stem ◽  
Wnt Proteins ◽  
Increased Risk ◽  
Wide Range

Abstract Bone metastasis is a frequent complication of advanced genito-mammary cancer patients. Skeletal involvement is particularly common in breast cancer. Bone metastases induce a wide range of symptoms, lowering the quality of life and shortening survival. The normal bone remodeling process is deeply affected in all types of metastases: osteolytic, osteoblastic, and mixed. The main mechanisms involved in bone metastatic dissemination are the expression of adhesion tumor molecules and corresponding receptors within bone marrow and bone matrix cells; local growth factors, molecular mechanisms of remodeling the hematopoietic stem cell activity, and alteration of the expression of the post-transcriptional regulatory microRNAs of the gene expression are the new theories developed from recent studies. Abnormalities in the number of copies of the 16q23 gene explain the increased risk of bone metastasis of breast cancer compared to its dissemination to the other organs; the mutual interaction between tumor cells and the bone microenvironment constitutes the element that stimulates both bone destruction and tumor development. Endothelin -1, bone morphogenic proteins, platelet-derived growth factor, Wnt proteins stimulate proliferation and osteoblastic activity. Genomic and proteomic studies underlie the development of new therapeutic agents for the treatment and prevention of bone metastases.

Non-Invasive Assessment of Liver Fibrosis Progression and Prognosis in Primary Biliary Cholangitis

2015 ◽  
Vol 33 (Suppl. 2) ◽  
pp. 115-117 ◽  
Author(s):  
Raoul Poupon
Keyword(s):  
Liver Fibrosis ◽  
Transient Elastography ◽  
Early Stage ◽  
Acoustic Radiation Force Impulse ◽  
Primary Biliary Cholangitis ◽  
Biliary Cirrhosis ◽  
Early Stage Disease ◽  
Non Invasive ◽  
Increased Risk ◽  
Wide Range

PBC (formerly known as primary biliary cirrhosis and now named primary biliary cholangitis) is a disease with a wide range of severity and variable rate of progression. The diagnosis of advanced liver fibrosis/cirrhosis portends an increased risk of liver-related morbidity and mortality. Because of its invasiveness, liver biopsy tends to be replaced by non-invasive tools for assessing liver fibrosis, making prognosis and optimising risk stratification for selection of patients, requiring new medical approaches. Many direct or indirect biomarkers have been found to correlate with the severity of liver fibrosis in PBC. They are easy to use but lack sensitivity and reproducibility in individuals with early stage disease. Three main radiologic approaches are currently proposed to assess liver fibrosis: vibration controlled transient elastography (VCTE), acoustic radiation force impulse and magnetic resonance elastography. Data using VCTE are available only for the longitudinal evaluation of liver fibrosis and prognosis in PBC. VCTE outperformed all other non-invasive current surrogate markers of liver fibrosis in PBC. Because of its high acceptability and its ability to predict hepatic decompensation, VCTE could be a useful tool to help allocate cirrhotic patients into different categories of risk. None of the radiologic and serum markers have a perfect accuracy in studies so far published. Concordance between VCTE and serum biomarkers is a prerequisite for a correct prognosis assessment in individuals in clinical practice.

scholarly journals Immunoglobulin A Nephropathy: Advances in Understanding of Pathogenesis and Treatment

2018 ◽  
Vol 47 (Suppl. 1) ◽  
pp. 43-52 ◽  
Author(s):  
Richard A. Lafayette ◽  
Ellie Kelepouris
Keyword(s):  
Iga Nephropathy ◽  
Association Studies ◽  
Treatment Options ◽  
Immunoglobulin A ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Wide Range ◽  
New Treatment ◽  
Stage Renal Disease ◽  
End Stage

Background: Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis and has clinical associations with a wide range of inflammatory and infectious diseases. There is a substantial variation in clinical course and outcomes, with many patients not diagnosed until they present with sequelae, which may include gross hematuria, hypertension, renal insufficiency, and/or significant proteinuria. Treatment options are currently limited and directed mainly toward control of these sequelae and have limited ability to reduce the incidence of end-stage renal disease or treat the primary IgA defect. Summary: Growing knowledge about the pathogenesis of IgA nephropathy and research into its genetic basis are helping to elucidate the course of this widely variable disease. IgA accumulation in the kidneys is thought to be the result of a number of different pathways in a “multi-hit” process that includes an initial traumatic trigger (often infection related) and subsequent memory responses that are amplified in those with a genetic predisposition to the disease and lead to an inflammatory response in susceptible individuals. Genome-wide association studies are providing new insights into the genetic variance of this autoimmune disease and are yielding information that may address both its causes and consequences. Key Messages: New treatment approaches are urgently required for the management of patients with IgA nephropathy. Novel interventions based around its inflammatory nature and “multi-hit” pathogenesis are being investigated to potentially limit disease progression.

scholarly journals Hodgkin’s Lymphoma- a Review: Future Directions in the Era of Targeted Therapy

2020 ◽  
Vol 3 (02) ◽  
pp. 50-59
Author(s):  
Amin Islam ◽  
Md. Mahabubur Rahman ◽  
Paul Cervi ◽  
J H Yeo
Keyword(s):  
Early Stage ◽  
Therapeutic Option ◽  
Treatment Strategies ◽  
High Dose ◽  
Combined Modality Treatment ◽  
Antibody Drug Conjugate ◽  
Hematopoietic Stem ◽  
Chemotherapeutic Regimen ◽  
Increased Risk ◽  
Risk Patients

Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells in an inflammatory background. Patients are commonly diagnosed in their 20s with a small proportion of patients in their 70s. Patients usually present with supra-diaphragmatic lymphadenopathy with or without associated systemic B symptoms. Even in advanced disease, HL is highly curable with combination chemotherapy, or combined-modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk-adapted approaches have helped de-escalate therapy in low-risk patients while intensifying treatment for higher risk patients. Limited stage disease without risk factors (RFs), are frequently treated with two cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) followed by 20Gy involved-field or -site radiotherapy (IF/IS-RT). In patients with early-stage unfavorable disease, four cycles of chemotherapy are usually consolidated with 30Gy IF/IS-RT. Compared to 4xABVD, 2 cycles of escalated BEACOPP followed by 2 cycles of ABVD ("2+2") improved 5-year progression-free survival with similar 5-year overall survival. Recently, treatment strategies based on 18FDG positron emission tomography response were evaluated. PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity. There are an increasing number of salvage therapies available to patients who are not cured with initial therapy. These include alternative chemotherapy combinations, the novel antibody-drug conjugate brentuximab, or high-dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death-1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL.

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