We hypothesized that the rising levels of inflammatory markers with aging is explained by cardiovascular risk factors and morbidity becoming progressively more prevalent in older persons. Information ...on inflammatory markers, cardiovascular risk factors, and diseases was collected in 595 men and 748 women sampled from the general population (age, 20-102 years). In both men and women, older age was associated with higher levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra), IL-18, C-reactive protein (CRP), and fibrinogen, while soluble IL-6 receptor (sIL-6r) increased significantly with age only in men. Adjusting for cardiovascular risk factors and morbidity, the age regression coefficients became substantially smaller in models predicting IL-6, IL-1ra, IL-18, and fibrinogen and larger in the model predicting sIL6r. Adjustment for cardiovascular morbidity substantially reduced the effect of age on CRP in men but not in women. Findings were confirmed in a subgroup of 51 men and 45 women with low risk profile and no cardiovascular morbidity. Part of the “proinflammatory state” in older persons is related to the high prevalence of cardiovascular risk factor and morbidity.
Hodgkin lymphoma (HL) is a highly curable B-cell malignancy of germinal center origin. Biologically it is a hematologic malignancy that is highly dependent on the immune microenvironment and utilizes ...immune escape through upregulation of the programmed-death ligands on the neoplastic cells. Despite being highly curable, consensus is lacking nationally and internationally about the optimal approach to management, particularly in limited-stage disease. The addition of brentuximab vedotin and checkpoint inhibitors for the management of HL has led to a rapidly changing treatment landscape. Further studies should be done to include these novel agents at all stages of disease to determine improvements in frontline cure rates and long-term toxicity.
Multiple myeloma is a cancer of plasma cells that has an estimated incidence of 26,850 new patients in 2015 in the United States.
1
In the past few years, dramatic progress has been made in the ...treatment of this disease. New classes of drugs, including proteasome inhibitors (e.g., bortezomib and carfilzomib) and immunomodulatory agents (e.g., lenalidomide and pomalidomide), have improved response rates and survival significantly, and it now appears that immunotherapy is likely to lead to even greater advances.
Results regarding the use of daratumumab, an antibody directed against CD38, in patients with relapsed, refractory multiple myeloma are now reported in . . .
ABSTRACTPrecision medicine is a term used to describe individualized treatment that encompasses the use of new diagnostics and therapeutics, targeted to the needs of a patient based on his/her own ...genetic, biomarker, phenotypic, or psychosocial characteristics. In particular, advances such as cell sorting, epigenetics, proteomics, metabolomics, and more are converging with informatics and other technologies in a manner that is rapidly expanding the scope of this field. This article highlights the variety of breakthroughs in the field and addresses challenges that precision medicine may face.Many current technologies are rapidly enhancing the field of precision medicine. Recombinant biologic agents can now be used as replacement therapies, such as in the treatment of hemophilia, and electronic health records have created a rich and accessible database of clinical information that can be used for research and for clinical care guideline creation. Gene therapy, genetics, and next-generation DNA sequencing methods are perhaps having the greatest effect; this will continue to advance with decreases in costs. Testing for specific abnormalities has aided in the treatment of certain types of cancers. In lung cancer, molecular testing of EGFR, MET, RAS, ALK, and other genetic markers can help identify patients who need treatment and protect patients who do not from costly and toxic therapies. Molecular testing can also screen patients for multiple endocrine neoplasia type 2, which allows for early prophylactic treatment and attention, sparing unaffected family members from unnecessary screening. Such advances decrease harm and create care specific to the individual.However, there are also challenges. One challenge is the misalignment of patient, physician, health system, payer, and industry interests. In greater detail, patients and physicians are primarily concerned with understanding and treating disease, but physicians must also consider utilization of heath care, which affects the health care system, payer, and industry interests and in turn also relates to costs of new diagnostics or finding more profitable therapies. Managing these interests in an efficacious and cost-effective manner may prove difficult. A second challenge is organizing the wealth of growing information. As disease classification trends toward more precise definitions and discrete disease entities, expanded decision algorithms and treatment options will be needed to properly address each type of treatment. Some conditions are caused by multiple different mutations in different genes, whereas in other cases different mutations in a single gene may lead to a range of diseases. As the complexity of disease becomes more apparent to us, physicians, especially primary care providers, will need to utilize informatics all within clinical guidelines in order to navigate these complex and specialized referral pathways.Future trends in precision medicine are most likely in targeting genetic pathways in cancer with medications, cancer immunotherapies, DNA sequencing, and use of technology in acute interventions (eg, automated defibrillator). Should stakeholders adapt to these changes, health providers streamline pathways that facilitate specialist access and proper care, and agencies and payers support a cost-effective field, then the advances in precision medicine may be limitless.
Antiphospholipid antibodies can induce endothelial-cell, complement, platelet, neutrophil, and monocyte activation, leading to thrombosis, renal failure, heart valve disease, pregnancy loss, and ...neurologic complications. Warfarin is the main treatment option.
Drug-Induced Megaloblastic Anemia Hesdorffer, Charles S; Longo, Dan L
The New England journal of medicine,
10/2015, Letnik:
373, Številka:
17
Journal Article
Recenzirano
Many common drugs induce megaloblastic anemia by interfering with folate or vitamin B
12
absorption, altering B
12
metabolism, or blocking pathways in which these vitamins play a role. Supplements to ...overcome these effects or discontinuation of the drug may be necessary.
More than 50 years ago, Victor Herbert first described the concept that defective nucleoprotein synthesis, attributable to various causes, results in the development of megaloblastic anemia.
1
Megaloblastic anemia is characterized by the presence of a hypercellular marrow with large, abnormal hematopoietic progenitor cells with a characteristic finely stippled, lacy nuclear chromatin pattern. These abnormal progenitor cells, or megaloblasts, were first described by Paul Ehrlich in 1880. Leukopenia and thrombocytopenia are frequently present. Although the marrow is hypercellular, many of the cells die within it in a process called ineffective erythropoiesis. Megaloblastosis usually results from a deficiency of vitamin B
12
. . .
The editors announce a new series focusing on fundamental and emerging concepts in nutrition, from the “pharmacodynamics” of food to the gut and immunity and the role of the gut microbiome in health ...and disease.
The deterioration of the immune system with progressive aging is believed to contribute to morbidity and mortality in elderly humans due to the increased incidence of infection, autoimmunity, and ...cancer. Dysregulation of T‐cell function is thought to play a critical part in these processes. One of the consequences of an aging immune system is the process termed thymic involution, where the thymus undergoes a progressive reduction in size due to profound changes in its anatomy associated with loss of thymic epithelial cells and a decrease in thymopoiesis. This decline in the output of newly developed T cells results in diminished numbers of circulating naïve T cells and impaired cell‐mediated immunity. A number of theories have been forwarded to explain this ‘thymic menopause’ including the possible loss of thymic progenitors or epithelial cells, a diminished capacity to rearrange T‐cell receptor genes and alterations in the production of growth factors and hormones. Although to date no interventions fully restore thymic function in the aging host, systemic administration of various cytokines and hormones or bone marrow transplantation have resulted in increased thymic activity and T‐cell output with age. In this review, we shall examine the current literature on thymic involution and discuss several interventional strategies currently being explored to restore thymic function in elderly subjects.
Background Red cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes with higher values reflecting greater heterogeneity in cell sizes. Recent ...studies have shown that higher RDW is associated with increased mortality risk in patients with clinically significant cardiovascular disease (CVD). Whether RDW is prognostic in more representative community-based populations is unclear. Methods Seven relevant community-based studies of older adults with RDW measurement and mortality ascertainment were identified. Cox proportional hazards regression and meta-analysis on individual participant data were performed. Results Median RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001). For every 1% increment in RDW, total mortality risk increased by 14% (adjusted hazard ratio HR: 1.14; 95% confidence interval CI: 1.11–1.17). In addition, RDW was strongly associated with deaths from CVD (adjusted HR: 1.15; 95% CI: 1.12–1.25), cancer (adjusted HR: 1.13; 95% CI: 1.07–1.20), and other causes (adjusted HR: 1.13; 95% CI: 1.07–1.18). Furthermore, the RDW–mortality association occurred in all major demographic, disease, and nutritional risk factor subgroups examined. Among the subset of 1,603 older adults without major age-associated diseases, RDW remained strongly associated with total mortality (adjusted HR: 1.32; 95% CI: 1.21–1.44). Conclusions RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases. The biologic mechanisms underlying this association merit investigation.
PDF
