No abstract
Patients with Hodgkin's disease have higher a prevalence of thyroid function abnormalities and, perhaps, orbitopathy than the general population, but the pathophysiology of this association and its relationship to Hodgkin's disease treatment remain unclear. We analyzed the frequency of thyroid function abnormalities, autoantibodies against thyroid antigens, and autoimmunity against extraocular muscle cell antigens by Western blot analyses and antibody-dependent cellular cytotoxicity (ADCC) assays in patients with Hodgkin's disease (n = 20) and controls (n = 10). Hodgkin's disease patients were subdivided into those treated with thyroidal external beam radiation therapy (XRT, n = 15) or chemotherapy (MOPP/ABVD, n = 5). The ADCC assay against extraocular muscle cells was increased in patients with Hodgkin's disease (5.5% vs. <1.0%, p = .026) when compared with controls. In addition, Hodgkin's disease patients treated with XRT (with or without chemotherapy) had significantly higher ADCC tests than controls (9.7% vs. <1.0%, p = .010), In contrast, ADCC assays were not different between Hodgkin's disease patients treated with chemotherapy alone and controls (<1.0% vs. <1.0%, p = .53). Hodgkin's patients treated with XRT had higher ADCC assays than those treated with chemotherapy alone (p = .087), although this difference did not achieve statistical significance. Serum measurements of antithyroid peroxidase (TPO) antibodies, antithyroglobulin (Tg) antibodies, thyroid binding inhibitory immunoglobulins (TBII), and thyroid stimulating immunoglobulin (TSI) were similar in all groups. Antibodies against the 64 kDa orbital antigen were detected in 1 patient and 1 control subject. Excluding patients already treated with L-thyroxine for hypothyroidism (n = 5), free T3, but not free T4, was lower in the Hodgkin's disease group than in controls (2.2 pg/mL vs. 2.7 pg/mL, p = .008). Thyrotropin (TSH) concentrations were not statistically different between these groups. In summary, these data show: (1) ADCC against human orbital muscle cells is increased in patients with Hodgkin's disease compared with controls: (2) these differences were noted among Hodgkin's disease patients treated with thyroidal XRT, with or without chemotherapy, and not among those patients treated with chemotherapy alone; and (3) no statistically significant differences in the frequency of thyroid autoantibodies were found. These data suggest that patients with Hodgkin's disease display altered antibody-dependent immune function toward extraocular muscle cells that may possibly be related to by XRT. Larger, prospective studies assessing thyroid and orbital-related immunologic abnormalities in Hodgkin's disease are warranted.
Despite nearly 30 years of treatment guidelines for cardiovascular diseases and risk factors and a parallel growth in the understanding of cardiovascular disease disparities by sex and race/ethnicity, such disparities persist. The goals of this review are to consider the possible role of three factors: the one-size-fits-all approach of most treatment guidelines, adoption of guideline-recommended treatments in clinical practice, and patient adherence to recommended practice, especially the relationship between adherence and patient perceptions. Guideline authors repeatedly call for more inclusion of women and minorities in the clinical trials that make guidelines possible, but despite challenges, guidelines are largely effective when implemented, as shown by a wealth of post hoc analyses. However, the data also suggest that one-size-fits-all treatment guidelines are not sufficiently generalizable and there is evidence of a distinct lag time between definitive clinical evidence and its widespread implementation. Patient perspectives may also play both a direct and indirect role in adherence to treatments. What emerges from the literature is an important continuing need for increased inclusion of women and minority subgroups in clinical trials to allow analyses that can provide evidence for differential treatments when needed. Increased effort is needed to implement definitive clinical improvements more rapidly. Patient input and feedback may also help inform clinical practice and clinical research with a better understanding of how to enhance patient adherence, but evidence for this is lacking for the groups most affected by disparities.
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