29 research outputs found
Soluble Serum CD81 Is Elevated in Patients with Chronic Hepatitis C and Correlates with Alanine Aminotransferase Serum Activity
Aim: Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity.
Patients and Methods: Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry.
Results: Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p>0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027).
Conclusion: CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis
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Impact of national guidelines on brachytherapy monotherapy practice patterns for prostate cancer.
BackgroundIn 1999 and 2000, 2 national guidelines recommended brachytherapy monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high-risk prostate cancer. This study examined rates of BT use before and after publication of these guidelines, as compared with 4 other treatment options.MethodsFrom 1990 to 2011, 8128 men with localized prostate cancer (≤ T3cN0M0) were treated definitively within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry with 1 of 5 primary treatments: BT, external beam radiotherapy (EBRT), EBRT with androgen deprivation therapy, EBRT+BT, or radical prostatectomy. Men were categorized into low-, intermediate-, and high-risk groups based on the guidelines' risk-group definitions. Within each risk group, logistic regression was used to estimate odds ratios (OR) comparing BT with other treatment options between the 1990-1998 and 1999-2011 periods, adjusting for age, disease characteristics, and clinic type.ResultsIn total, 1117 men received BT alone for low- (n = 658), intermediate- (n = 244), or high-risk disease (n = 215). BT comprised 6.1% of all treatments in 1990-1998 versus 16.6% in 1999-2011 (P < .01). The odds of BT use remained increased after adjusting for potential confounders (OR = 3.06; P < .001) and was seen among low- (OR = 4.52; P < .001), intermediate- (OR = 2.67; P < .001), and even high-risk groups (OR = 2.11; P < .001).ConclusionsNational guidelines did not appear to influence practice patterns, as BT monotherapy use increased relative to other treatments from the 1990-1998 to 1999-2011 periods in unfavorable risk groups including men with high-risk prostate cancer
Impact of national guidelines on brachytherapy monotherapy practice patterns for prostate cancer.
BackgroundIn 1999 and 2000, 2 national guidelines recommended brachytherapy monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high-risk prostate cancer. This study examined rates of BT use before and after publication of these guidelines, as compared with 4 other treatment options.MethodsFrom 1990 to 2011, 8128 men with localized prostate cancer (≤ T3cN0M0) were treated definitively within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry with 1 of 5 primary treatments: BT, external beam radiotherapy (EBRT), EBRT with androgen deprivation therapy, EBRT+BT, or radical prostatectomy. Men were categorized into low-, intermediate-, and high-risk groups based on the guidelines' risk-group definitions. Within each risk group, logistic regression was used to estimate odds ratios (OR) comparing BT with other treatment options between the 1990-1998 and 1999-2011 periods, adjusting for age, disease characteristics, and clinic type.ResultsIn total, 1117 men received BT alone for low- (n = 658), intermediate- (n = 244), or high-risk disease (n = 215). BT comprised 6.1% of all treatments in 1990-1998 versus 16.6% in 1999-2011 (P < .01). The odds of BT use remained increased after adjusting for potential confounders (OR = 3.06; P < .001) and was seen among low- (OR = 4.52; P < .001), intermediate- (OR = 2.67; P < .001), and even high-risk groups (OR = 2.11; P < .001).ConclusionsNational guidelines did not appear to influence practice patterns, as BT monotherapy use increased relative to other treatments from the 1990-1998 to 1999-2011 periods in unfavorable risk groups including men with high-risk prostate cancer
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Radiographic Response of Solitary Plasmacytomas After Conformal Radiotherapy May Be Delayed: Outcomes in the 3D Era
OBJECTIVE: Although recurrence rates after radiotherapy for solitary plasmacytoma (SP) are well established, little is known about how SP responds radiographically, as most historical patients were treated in the 2D era. We evaluated the response to radiotherapy among SP patients staged and treated with 3D techniques, including proton therapy, which has not yet been previously reported. METHODS AND MATERIALS: Between 2007 and 2021, 15 SP patients (4 extramedullary, 11 bone) staged with 3D imaging and bone marrow evaluation were consecutively treated with definitive radiotherapy. The best response was categorized in 9 evaluable patients according to response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST). RESULTS: With a median follow-up of 34 months, 4 patients relapsed. The median time to the best response was ~2 years (26.6 mo RECIST, 25.4 mo PERCIST). Response rates differed based on response assessment criteria. PERCIST was associated with higher rates of complete (85.7%) or partial response (14.3%) compared with RECIST (16.7% complete, 33.3% partial). Two-year and 4-year PFS for extramedullary SP were 100% and 75%, compared with 91% and 55% for bone ( P =0.75). Patients treated with proton therapy (n=5) did not appear to have different patterns of relapse (1 marginal, 1 distant) compared with those treated with photons or electrons (n=10; 2 distant). CONCLUSIONS: More conformal dose distribution with proton therapy does not appear to alter patterns of recurrence. Although response rates differ based on criteria by both RECIST and PERCIST assessments, the radiographic response may be slow and requires validation in other cohorts
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Safety and Toxicities of Radiotherapy As Consolidation or Cytoreduction Around the Time of Autologous Stem Cell Transplantation for Multiple Myeloma Patients: A Single Center Retrospective Report
The efficacy and safety of palliative radiotherapy (RT) is well established for patients with multiple myeloma (MM). However, little is known regarding the safety of RT as consolidation or cytoreduction among MM patients undergoing autologous stem cell transplant (ASCT).
Given that many MM patients undergo ASCT as part of treatment, we sought to characterize the safety and toxicity profile of peri-transplant RT among patients with MM that underwent ASCT at a large, tertiary-care stem cell transplant center.
Eligible patients included those 18 years or older with a confirmed diagnosis of MM that underwent ASCT between January 2009 and June 2018 at the Fred Hutchinson Cancer Research Center. Peri-transplant RT was defined as RT deployed within 3 months of ASCT for the explicit purpose of disease consolidation or cytoreduction, including treating lesions at risk for pathologic fracture. We excluded patients that underwent tandem autologous-allogeneic stem cell transplant and patients that received RT for disease relapse post-transplant. Transplant-related toxicity and infectious complications were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Of 785 MM patients that underwent ASCT, 23 (2.9%) received RT, post-stem cell collection, at our institution in the peri-transplant setting. Demographics, disease characteristics, and treatment data are depicted in figure 1. Seven patients (30%) received RT to treat lesions at risk for pathologic fracture. A total of 18 patients (78%) were hospitalized within 30 days of transplant. Among these patients, 12 patients (52%) experienced grade 3 regimen-related toxicities requiring hospitalization, most frequently nausea, vomiting, and mucositis; 2 patients (9%) experienced grade 2 autologous-pseudo GVHD requiring oral steroids. Twelve patients (52%) experienced grade 3 infectious complications, the majority of which were neutropenic fever. The median time to neutrophil engraftment was 16 days (range 13-20), and the median time to platelet engraftment was 11 days (range 8-14); within this group, subjects who received RT to the hip or pelvic region had similar engraftment times.
In this analysis of the MM patients who underwent ASCT at our institution, we observed the expected degree of transplant-related toxicity among peri-transplant RT recipients, with most patients requiring hospitalization post-transplant for gastrointestinal toxicity. Peri-transplant RT, including irradiation of the hip or pelvic region (where the majority of hematopoiesis occurs), did not impact on engraftment or incidence of infectious complications. Future work is needed to evaluate whether peri-transplant RT improves disease remission among MM patients that undergo ASCT, and we are in the process of updating disease response rates in these patients