We retrospectively evaluated 18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans in 172 patients with lymphoma and correlated results with pathologic diagnosis using the World Health Organization (WHO) classification system. In total, FDG-PET detected disease in at least one site in 161 patients (94%) and failed to detect disease in 11 patients (6%). The most frequent lymphoma diagnoses were diffuse large Bcell lymphoma (LBCL; n ؍ 51), Hodgkin lymphoma (HL; n ؍ 47), follicular lymphoma (FL; n ؍ 42), marginal zone lymphoma (MZL; n ؍ 12), mantle cell lymphoma (MCL; n ؍ 7), and peripheral T-cell lymphoma (PTCL; n ؍ 5
Hypertension in renal transplant recipients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular morbidity and mortality and shortened allograft survival are important consequences of inadequate control of hypertension. In this review, we examine the epidemiology, pathophysiology, and management considerations of post-transplant hypertension. Donor and recipient factors, acute and chronic allograft injury, and immunosuppressive medications may each explain some of the pathophysiology of post-transplant hypertension. As observed in other patient cohorts, renal artery stenosis and adrenal causes of hypertension may be important contributing factors. Notably, BP treatment goals for renal transplant recipients remain an enigma because there are no adequate randomized controlled trials to support a benefit from targeting lower BP levels on graft and patient survival. The potential for drugdrug interactions and altered pharmacokinetics and pharmacodynamics of the different antihypertensive medications need to be carefully considered. To date, no specific antihypertensive medications have been shown to be more effective than others at improving either patient or graft survival. Identifying the underlying pathophysiology and subsequent individualization of treatment goals are important for improving long-term patient and graft outcomes in these patients.
Pre-transplant donor biopsy (PTDB)-based marginal-donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the highest range (e.g. >80 or >90), whose discard rate approximates 50% in the US. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score <4 [median KDPI:87; interquartile range(IQR):78-94] and 62 with a score =4 [median KDPI:87; IQR:76-93]; 102 dual transplants [median KDPI: 93; IQR:86-96]) and 248 single standard transplant controls [median KDPI:36; IQR:18-51]. PTDB-based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80-90 and of 37% for kidneys with a KDPI of 91-100. Although 1-year eGFRs were significantly lower in recipients of marginal kidneys (-9.3, -17.9, and -18.8ml/min, for dual transplants, single kidneys with PTDB score <4, and =4, respectively; P<0.001), graft survival (median follow-up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 [95% confidence interval: 0.80 to 1.79; P=0.38]). In conclusion, PTDB-based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.
BACKGROUNDIntensity‐modulated radiation therapy (IMRT) is a novel approach to the planning and delivery of radiation therapy. The prevalence of IMRT use among radiation oncologists in the U.S. appears to be increasing, despite limited data evaluating its risks and benefits.METHODSA random sample of radiation oncologists in the U.S., including a cohort of 441 physicians who were surveyed in 2002, was surveyed regarding IMRT use. IMRT users were questioned regarding their frequency of use, clinical applications, and reasons for adopting IMRT. IMRT nonusers were asked their reasons for not using IMRT, whether they planned to use it in the future, and reasons for wanting to adopt IMRT. Differences in responses between 2002 and 2004 were compared.RESULTSThe survey was conducted between July 1, 2004 and August 31, 2004. Of 368 evaluable participants, 239 physicians (64.9%) responded. The proportion of respondents who used IMRT was 73.2% (175 physicians), compared with 32.0% in 2002. The adoption rate of IMRT among nonusers from 2002 to 2004 was 62.7% (95% confidence interval, 51.9–73.5%). Many IMRT users (81.0%) had used IMRT to deliver higher than conventional doses of radiation, predominantly in patients with genitourinary and head and neck tumors. Major reasons cited for IMRT adoption were permitting normal tissue sparing (88.0%), dose escalation (85.1%), and economic competition (62.4%). Ninety‐one percent of nonusers planned to adopt IMRT in the future.CONCLUSIONSIMRT use among radiation oncologists in the U.S. has increased significantly since 2002. Standardized guidelines and careful, prospective analyses evaluating its risks and benefits are needed. Cancer 2005. © 2005 American Cancer Society.
Podocyte injury is the inciting event in primary glomerulopathies, such as minimal change disease and primary FSGS, and glucocorticoids remain the initial and often, the primary treatment of choice for these glomerulopathies. Because inflammation is not readily apparent in these diseases, understanding the direct effects of glucocorticoids on the podocyte, independent of the immunomodulatory effects, may lead to the identification of targets downstream of glucocorticoids that minimize toxicity without compromising efficacy. Several studies showed that treatment with glucocorticoids restores podocyte differentiation markers and normal ultrastructure and improves cell survival in murine podocytes. We previously determined that Krüppel-like factor 15 (KLF15), a kidney-enriched zinc finger transcription factor, is required for restoring podocyte differentiation markers in mice and human podocytes under cell stress. Here, we show that in vitro treatment with dexamethasone induced a rapid increase of KLF15 expression in human and murine podocytes and enhanced the affinity of glucocorticoid receptor binding to the promoter region of KLF15 In three independent proteinuric murine models, podocyte-specific loss of Klf15 abrogated dexamethasone-induced podocyte recovery. Furthermore, knockdown of KLF15 reduced cell survival and destabilized the actin cytoskeleton in differentiated human podocytes. Conversely, overexpression of KLF15 stabilized the actin cytoskeleton under cell stress in human podocytes. Finally, the level of KLF15 expression in the podocytes and glomeruli from human biopsy specimens correlated with glucocorticoid responsiveness in 35 patients with minimal change disease or primary FSGS. Thus, these studies identify the critical role of KLF15 in mediating the salutary effects of glucocorticoids in the podocyte.
Correction of anemia with erythropoietin (EPO) is associated with improved kidney transplant outcomes. Emerging evidence, predominantly from animal models, indicates that these observations may be erythropoiesis-independent and that EPO exhibits immunosuppressive properties. We examined the effects of EPO on human T-cell alloimmunity by first documenting that CD4 + and CD8 + T cells express EPO receptor (EPO-R) on their surfaces. In mixed lymphocyte reactions, EPO induced a dose-dependent decrease in allogeneic CD4 + T-cell proliferation (EPO 1000 U/ml: 44.6%622.9% of vehicle, P,0.05; 2000 U/ml: 11.1%64% of vehicle, P,0.001) without inducing cell death. The effects required signals transmitted directly through the EPO-R expressed on T cells, resulting in diminished Th1 differentiation without effects on regulatory T-cell induction. Mechanistic studies revealed that EPO prevented IL-2-induced proliferation by uncoupling IL-2 receptor signaling, inhibiting phosphorylation of the intracellular intermediaries AKT and extracellular signal-regulated kinase that are known to mediate T-cell expansion. EPO treatment reduced expansion of human naïve CD4 + T cells after adoptive transfer into NOD scid gc null mouse recipients, verifying the effects in vivo. Although activated T cells expressed CD131, an alternative EPO receptor, addition of a specific CD131 agonist peptide, ARA290, did not alter T-cell proliferation or cytokine production. Our findings link EPO-R signaling on T cells to inhibition of T-cell immunity, providing one mechanism that could explain the observed protective effects of EPO in kidney transplant recipients. The anemia that commonly occurs in kidney transplant recipients has been hypothesized to contribute to chronic allograft injury, in part by limiting oxygen delivery to the tubulointersitium and as a consequence, enabling fibrogenesis. 1 In support of a link between anemia and kidney allograft injury, results of a 2012 randomized controlled study of erythropoietin (EPO) therapy after transplantation showed that targeting hemoglobin values to a normal range of $13 g/dl slowed progression of chronic allograft nephropathy and prolonged graft survival compared with partial correction of anemia. 2 Although the above-cited clinical study and selected studies in rodents indicate correlations between EPO-induced increases in hematocrit and reduced tubulointerstitial damage as well as preserved renal tubular cells and improved kidney function, 3 direct evidence linking EPO-induced erythropoiesis to better transplant outcomes is lacking. In fact, experiments performed in a fully mismatched rat kidney transplant model showed that EPO, but not the correction of anemia by blood transusion, limits chronic allograft injury, 4,5 supporting the conclusion that the transplant-protective effects of EPO do not require an EPO-induced increase in hematocrit. Among potential alternative mechanisms, emerging evidence from animal models suggests that
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