scholarly journals Stroke in hemodialysis patients randomized to different intravenous iron strategies: a prespecified analysis from the PIVOTAL trial

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0004272021
Author(s):  
Patrick B. Mark ◽  
Pardeep S. Jhund ◽  
Matthew R. Walters ◽  
Mark C. Petrie ◽  
Albert Power ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stroke Risk ◽  
Controlled Trial ◽  
Intravenous Iron ◽  
Hemodialysis Patients ◽  
High Dose ◽  
Pivotal Trial ◽  
Increased Risk ◽  
Iv Iron

Background: People with kidney failure treated with hemodialysis (HD) are at increased risk of stroke compared to similarly aged people with normal kidney function. One concern is that treatment of renal anemia might increase stroke risk. We studied risk factors for stroke in a prespecified secondary analysis of a randomized controlled trial of intravenous iron treatment strategies in HD. Methods: We analyzed data from the Proactive IV IrOn Therapy in HaemodiALysis Patients (PIVOTAL) trial focusing on variables associated with risk of stroke. The trial randomized 2,141 adults, who had started hemodialysis <12 months earlier and who were receiving an erythropoiesis-stimulating agent (ESA), to high-dose IV iron administered proactively or low-dose IV iron administered reactively in a 1:1 ratio. Possible stroke events were independently adjudicated. We performed analyses to identify variables associated with stroke during follow-up and assessed survival following stroke. Results: During a median 2.1 years follow-up, 69 (3.2%) patients experienced a first post randomization stroke. 57 (82.6%) were ischemic strokes and 12 (17.4%) hemorrhagic strokes. There were 34 post randomization strokes in the proactive arm and 35 in the reactive arm (hazard ratio (95% confidence interval): 0.90 (0.56, 1.44), p=0.66). In multivariable models, female gender, diabetes, history of prior stroke at baseline, higher baseline systolic blood pressure, lower serum albumin and higher C-reactive protein were independently associated with stroke events during follow up. Hemoglobin, total iron or ESA dose were not associated with risk of stroke. 58% of patients with a stroke event died during follow-up, compared to 23% without a stroke. Conclusions: In hemodialysis patients, stroke risk is broadly associated with risk factors previously described to increase cardiovascular risk in this population. Proactive intravenous iron does not increase stroke risk.

scholarly journals The Risk of Stroke Using CHA2 DS2 -VASc Score in Hemodialysis Patients at a Tertiary Hospital in Riyadh, Saudi Arabia

2019 ◽  
Vol 4 (7) ◽  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Stroke Risk ◽  
Hemodialysis Patients ◽  
Low Risk ◽  
High Risk Patients ◽  
Stroke Risk Factors ◽  
Increased Risk ◽  
Risk Patients ◽  
History Of

Introduction: Patients undergoing hemodialysis are at increased risk of stroke. However, less known about the impact of some of the stroke risk factors, and the value of stroke risk scores in determining the risk in those patients. Our main goal. To assess the risk factors for stroke in hemodialysis patients and the use of the new CHA2DS2-VASc score for stroke assessment. Methods: Single center, retrospective cohort study of 336 patients undergoing hemodialysis from June 24, 2018, to September 6, 2018, was recruited. Baseline demographics, clinical, and laboratory data were collected. We calculated the CHA2 DS2 -VASc score for stroke assessment in all patients and categorized them into high, moderate and low risk patients according to CHA2 DS2 - VASc score and subcategorized them to two groups atrial fibrillation (AFib) and Non- Atrial fibrillation (Non AFib) patients. Results: 336 patients were included in our study; the majority of patients were at high risk with a CHA2 DS2 -VASc Score mean of 2.9± 1.5, although history of stroke was observed only in 15 patients (4.46%). According to CHA2 DS2 - VASc score, 280 patients were at high risk, 172 (51.19%) were high-risk patients on treatment (anticoagulant or antiplatelet) and 108(32.14%) patients were high risk patients not on treatment 48 were at moderate risk (14.28%) and 8 were at low risk (2.38 %). Patients were divided into subgroups as non-AFib and AFib. In non-AFib patients 320 (95.23%), high-risk patients 103 (32.18%) were not treated; high-risk patients with treatment are 162 (50.62%), moderate patients were 47 (14.68%), 8(2.5%) was in low risk. AFib patients were 16 with a mean CHA2 DS2 -VASc score of 4.4±1.1. Patients with AFib were all at high risk except 1 was at moderate risk (6.25%). There were 11 (68.75%) patients on treatment and 5 (31.25%) patients not on treatment. The risk factors for stroke that were statistically significant in increasing score risk for all patients were: age > 65 (95% CI, -2.04– -1.29; p = 0.000), being female (95% CI, -1.36– -0.68; p = 0.000) hypertension (95% CI, -2.59– -1.37; p = 0.000), diabetes (95% CI, -2.10– -1.50; p = 0.000), CVD (95% CI, -2.07– -1.24; p=0.000), history of stroke or TIA (95% CI, -3.70– -2.03; p = 0.000), CHF or LVEF (95% CI, -2.28– - 0.91; p = 0.000). Conclusions: The risk of stroke in hemodialysis patients is significant according to the use of CHA2 DS2 -VASc score in Non-AFib hemodialysis patients shows supportive evidence of increased risk of stroke in those patients, which suggest the importance of close monitoring of patients with stroke risk factors by the nephrologist and the stroke team which will lead to the initiation of early prophylaxis in those patients.

Effect of Monthly High-Dose Vitamin D Supplementation on Acute Respiratory Infections in Older Adults: A Randomized Controlled Trial

2019 ◽  
Vol 71 (2) ◽  
pp. 311-317 ◽  
Author(s):  
Carlos A Camargo ◽  
John Sluyter ◽  
Alistair W Stewart ◽  
Kay-Tee Khaw ◽  
Carlene M M Lawes ◽  
...  
Keyword(s):  
Older Adults ◽  
Vitamin D ◽  
Clinical Trials ◽  
Controlled Trial ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Randomized Controlled ◽  
Increased Risk ◽  
High Dose Vitamin

Abstract Background Although adults with low vitamin D status are at increased risk of acute respiratory infection (ARI), randomized controlled trials of vitamin D supplementation have provided inconsistent results. Methods We performed a randomized, double-blinded, placebo-controlled trial of 5110 adults aged 50–84 years. In 2011–2012, participants were randomized to an initial oral dose of 200 000 IU vitamin D3 followed by 100 000 IU monthly (n = 2558) or placebo (n = 2552) until late 2013 (median follow-up, 1.6 years). Participants reported upper and lower ARIs on monthly questionnaires. Cox models analyzed time to first ARI (upper or lower) by treatment group. Results Participants’ mean age was 66 years and 58% were male; 83% were of European/other ethnicity, with the rest Maori, Polynesian, or South Asian. Mean (SD) baseline blood 25-hydroxyvitamin D [25(OH)D] level was 63 (24) nmol/L; 25% were &lt;50 nmol/L. In a random sample (n = 441), vitamin D supplementation increased mean 25(OH)D to 135 nmol/L at 3 years, while those on placebo remained at 63 nmol/L. During follow-up, 3737 participants reported ≥1 ARI: 74.1% in the vitamin D group versus 73.7% in the placebo group. The hazard ratio for vitamin D compared with placebo was 1.01 (95% CI, 0.94, 1.07). Similar results were seen in most subgroups, including those with baseline 25(OH)D &lt;50 nmol/L and in analyses of the upper/lower components of the ARI outcome. Conclusions Monthly high-dose vitamin D supplementation does not prevent ARI in older adults with a low prevalence of profound vitamin D deficiency at baseline. Whether effects of daily or weekly dosing differ requires further study. Clinical Trials Registration Australian New Zealand Clinical Trials Registry, identifier ACTRN12611000402943.

Abstract P222: Serum fibroblast growth factor-23 and risk of incident stroke: The Atherosclerosis Risk in Communities Study (ARIC)

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Pamela L Lutsey ◽  
Elizabeth Selvin ◽  
Jeffrey R Misialek ◽  
Erin D Michos ◽  
Casey M Rebholz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vitamin D ◽  
Cardiovascular Risk ◽  
Growth Factor ◽  
Kidney Function ◽  
Stroke Risk ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Increased Risk

Background: Fibroblast growth factor-23 (FGF23), a hormone involved in phosphorous regulation and vitamin D metabolism, has been associated with risk of coronary heart disease and heart failure and is a potential target for intervention. FGF23 may influence stroke risk through several pathways: suboptimal vitamin D levels, impaired kidney function, endothelial dysfunction, and/or inflammation. We tested whether elevated FGF23 is associated with increased risk of incident stroke, independent of traditional stroke risk factors and kidney function. Methods: Biologically active intact FGF23 was measured in stored samples collected at baseline, in 1990-1992, from 12,432 stroke-free ARIC participants. Participants were followed through 2010. Incident stroke events (both ischemic and hemorrhagic) were identified during follow-up and adjudicated using medical chart review. Multivariable Cox proportional hazards regression models were used to evaluate the independent association of baseline serum FGF23 with risk of incident stroke. Results: Over a median follow-up of 19 years, 766 participants (median age 56, 24% black) developed incident stroke. A significant association of baseline FGF23 with incident stroke was only observed in the highest quintile of serum FGF23. Compared to those in the lowest quintile of FGF23, those in the highest quintile were at 37% greater risk of incident stroke (Table), after adjustment for demographics, behaviors, and body mass index. Additional adjustment for cardiovascular risk factors and eGFR categories completely attenuated the association. There was no evidence of interaction by age, sex, race, or eGFR category. Conclusions: Elevated levels of serum FGF23 were associated with modestly increased risk of incident stroke in this large, biracial, community-based cohort in minimally-adjusted models, however this association was not independent of cardiovascular risk factors and kidney function.

Abstract TP200: Independent Contribution of HbA1c, Systolic Blood Pressure, and LDL Cholesterol Control to Risk of Ischemic Stroke Hospitalizations in Type 2 Diabetes

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Gregory A Nichols ◽  
Shreekant Parasuraman ◽  
Sandra Joshua-Gotlib
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Ischemic Stroke ◽  
Stroke Risk ◽  
Density Lipoprotein ◽  
Increased Risk ◽  
Hba1c Control

Risk of ischemic stroke is approximately doubled in patients with diabetes. To reduce risk, managing diabetes includes optimizing glycemic, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) control. We studied which risk factors alone or in combination were most strongly associated with stroke hospitalizations. We identified 26,924 Kaiser Permanente Northwest members with type 2 diabetes and no known prior cardiovascular disease hospitalization. Beginning in 2002, we identified the earliest point patients had glycosolated hemoglobin (HbA1c), systolic BP (SBP), and LDL-C measurements within 6 months of each other and followed them until they died, disenrolled, or 31 December 2011. Outcome was hospitalization with primary diagnosis of ischemic stroke. Using mean HbA1c, SBP, and LDL-C between baseline and end of follow-up, we identified dichotomous categories of control of HbA1c (<7%), SBP (<130 mm Hg) and LDL-C (<100 mg/dL) and estimated the relative risk of stroke hospitalization independently associated with all combinations of risk factors controlling for age, sex, diabetes duration, comorbidities, body mass index, smoking, and pharmacotherapy. Mean (SD) age of patients was 59 (12) years; 50% were men. Over mean (SD) follow-up of 6.2 (2.8) years, 606 (2.3%) patients were hospitalized for ischemic stroke. Compared with patients with all 3 risk factors in control, patients who had no risk factors controlled or only HbA1c controlled had >2-fold increased risk of ischemic stroke. Patients who controlled both SBP and LDL-C had significantly lower risk relative to control of all 3 risk factors. In this observational study, maintaining control of SBP over 6.2 years was essential to reduction of ischemic stroke risk. Simultaneous control of LDL-C further reduced risk, but HbA1c control <7% did not mitigate stroke risk beyond SBP and LDL-C control. Further research is needed to evaluate the relationship between HbA1c control and stroke risk.

scholarly journals Characteristics and Outcomes of Therapy Related Myeloid Neoplasms in Patients with Multiple Myeloma Following Autologous Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4560-4560 ◽  
Author(s):  
Kalyan Nadiminti ◽  
M Hasib Sidiqi ◽  
Kapil Meleveedu ◽  
Hassan B. Alkhateeb ◽  
Aref Al-Kali ◽  
...  
Keyword(s):  
Risk Factors ◽  
Research Funding ◽  
Survival Advantage ◽  
High Dose ◽  
Term Survival ◽  
Myeloid Neoplasms ◽  
Pathologic Features ◽  
Increased Risk

Introduction: Patients who develop therapy-related myeloid neoplasms (t-MN) have dismal outcomes. Previous studies reported the incidence and risk factors associated with t-MN development. Lenalidomide, in the setting of oral, but not intravenous, melphalan is associated with a higher risk of t-MN (Palumbo et. al, Lancet Oncology, 2014). We carried out this study to evaluate the clinical and pathologic features of t-MN, therapies employed, and factors that predict long-term survival after diagnosis. Patients and methods: We identified patients who received the first ASCT 1998-2016 at our institution. t-MN was defined per the WHO 2016 classification. Median overall survival (OS) was calculated from the time of t-MN diagnosis to last follow-up or death. Statistical analyses were performed using SAS (JMP v14.1) or GraphPad Prism (v7). Results: Out of 2115 patients that underwent at least one ASCT, 53 (2.5%) developed t-MN. Thirty-five of 53 (66%) patients who developed t-MN had received lenalidomide. Among 2062 patients that did not develop t-MN, 916 (44.4%) patients received lenalidomide. Lenalidomide exposure was associated with development of t-MN (χ2 with Yate's correction 8.9, p=0.003). Ten patients were excluded from further analyses due to lack of follow up. Clinical characteristics are shown in Table 1a (N=43). Median age at t-MN diagnosis was 70 years (range 44-79). Median time from ASCT to t-MN was 5 years (range 1-15). After a median follow-up of 70 months (95% CI, 38-134), the median OS was 12 months (95% CI, 9-17, Figure). Primary causes of death were t-MN (71%), MM (12%), both (6%), and other including infection, GVHD, and unknown (12%). Seven (16%) had t-AML and 36(84%) had t-MDS. Three (42%) of 7 patients with t-AML had pure erythroid phenotype. At the time of last follow-up, 9 (21%) were alive. Seven (17%) underwent two ASCT, 16 (36%) received more than 2 years cumulative dose of lenalidomide. Median number of cycles of alkylator therapy including high-dose melphalan (HDM) used for ASCT was 2 (range 1-6). On univariate analysis, factors predicting OS from t-MN diagnosis were ≥ 2 alkylator vs. < 2 cycles (11 vs. 27 months, p=0.02), ≥10% vs. <10% blast at the time of t-MN diagnosis (5.5 vs. 17 months, p=0.01), and the presence of complex karyotype (CK) vs. not (11 vs. 17 months, p=0.03). There was no difference in survival among t-MDS patients who transformed to t-AML vs. those who did not, those who received 1 vs. 2 ASCT, and those with lenalidomide duration ≥ 2 vs. <2 years. On multivariate analysis, the number of alkylator therapies and CK, but not % blasts predicted OS from t-MN diagnosis (Figure). Eight (19%) patients proceeded to receive an autologous (n=4) or allogeneic (n=4) transplant for t-MN (Table 1b). There was no survival advantage for patients who underwent SCT for t-MN, compared to those who did not (17 vs. 10 months, p=0.3). Similarly, there was no survival advantage for patients who received allo SCT compared to auto SCT (21 vs. 16 months, p=0.7). Survival for t-MDS and t-AML was also not different (15 vs. 6 months, p=0.2). There is only one long-term survivor in the transplant group (s/p allogeneic SCT). Four of seven (57%) patients died of progressive t-MN, 1 died of progressive MM, progressive MM and t-MN, and TRM each. Conclusions: Lenalidomide, in the setting of HDM, is associated with an increased risk of t-MN. Increased exposure to alkylators, a higher tumor burden, and the presence of CK predict poor survival in t-MN. As HDM/ASCT followed by lenalidomide maintenance remains the standard of care for eligible patients, minimizing exposure to other alkylator regimens may be prudent. While considered the standard, only a minority undergo transplant; and post-transplant outcomes remain poor. Studies to identify prognostic genetic and epigenetic risk factors are ongoing. Disclosures Al-Kali: Astex Pharmaceuticals, Inc.: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Patnaik:Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees.

The Impact of Incorporating Targeted Radioimmunotherapy (RIT) into Transplant Preparative Regimens on the Incidence of Therapy Related Myelodysplasia (t-MDS) or AML (t-AML) Following Autologous Stem Cell Transplant (ASCT) for Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1082-1082 ◽  
Author(s):  
Amrita Y. Krishnan ◽  
Joycelynne M. Palmer ◽  
Smita C. Bhatia ◽  
Auayporn Nademanee ◽  
Stephen J. Forman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chromosomal Abnormalities ◽  
Univariate Analysis ◽  
Case Series ◽  
High Dose ◽  
Cell Transplant ◽  
Bone Marrow Biopsies ◽  
Increased Risk ◽  
The Impact

Abstract The reported incidence of t-MDS/t-AML following traditional ASCT for lymphoma ranges between 0–12%. Previously identified risk factors include older age, prior alkylator therapy and use of radiation either prior to ASCT or as part of the preparative regimen. It is unclear whether novel conditioning regimens for ASCT that utilize targeted RIT with the potential to deliver higher radiation doses to the marrow are associated with a higher risk of t-MDS/t-AML. We identified a case-series of 83 pts who underwent RIT based ASCT between 06/00 and 01/06 to evaluate the incidence of t-MDS/t-AML; Forty-one pts received standard dose 90Y ibritumomab tiuxetan (0.4mci/kg: median dose 32.9 mci (range 20–40)) in combination with high dose BEAM (BCNU 450mg/m2, etoposide 800mg/m2, cytarabine 800mg/m2, melphalan 140mg/m2) and 42 pts received high dose 90Y based on dosimetry (median 70.8 mci range 36–105) in combination with etoposide 60mg/kg plus cyclophosphamide 100mg/kg. Pts were followed prospectively post ASCT with serial bone marrow biopsies approximately annually. The median age at ASCT was 54 years (range 19–78). Disease histology included diffuse large cell n=40, follicular NHL n=17, mantle cell n=21, transformed n=4, SLL n=1. Disease status at ASCT was 1st CR n=17, 1stPR n=14, induction failure n=14, 1st relapse or greater n=38. With a median follow-up of 39 months (range, 1.4–83), three patients (3.61%) have developed t-MDS/t-AML. The three pts also had associated complex chromosomal abnormalities including de1(13q), del(5q), del (20q). The median time to t-MDS/t-AML was 2.63 years (range, 1.51 – 8.41) post NHL diagnosis and 1.99 years (range, 0.56 – 5.10) post ASCT. The cumulative incidences of t-MDS/t-AML at 1 and 2 years were 1.20% (95%CI, 0.17– 8.1%) and 2.60% (95%CI 0.64–9.9%). None of the potential risk factors including age(>50 at ASCT) (p=0.33), prior radiotherapy (p=0.99), number of prior regimens (p=0.5) and 90Y dose (p=0.99) were statistically significant by univariate analysis. As 82/83 pts had received prior alkylator therapy this was not analyzed as a separate risk factor. Two year overall survival for the entire cohort is 90% (95%CI 83–95). Although the follow up is relatively short, the incidence of t-MDS/t-AML is consistent with our previous institutional experience in ASCT patients who received non-RIT based conditioning (Krishnan et al. Blood 2000) and with the 2.5% incidence of t-MDS/t-AML observed in pts receiving 90Y in registration and compassionate use trials (Czuczman et al JCO 2007 in press). In conclusion RIT based conditioning does not appear to confer an increased risk of t-MDS/t-AML above what has been previously reported with traditional ASCT preparative regimens. Incidence of t-MDS/t-AML Incidence of t-MDS/t-AML

scholarly journals Nasal symptoms increase the risk of snoring and snoring increases the risk of nasal symptoms. A longitudinal population study

2021 ◽  
Author(s):  
Maria Värendh ◽  
Christer Janson ◽  
Caroline Bengtsson ◽  
Johan Hellgren ◽  
Mathias Holm ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Health ◽  
Smoking Status ◽  
Northern Europe ◽  
Nasal Breathing ◽  
Nasal Symptoms ◽  
Increased Risk ◽  
Study Population ◽  
Independent Risk Factors

Abstract Purpose Humans have a preference for nasal breathing during sleep. This 10-year prospective study aimed to determine if nasal symptoms can predict snoring and also if snoring can predict development of nasal symptoms. The hypothesis proposed is that nasal symptoms affect the risk of snoring 10 years later, whereas snoring does not increase the risk of developing nasal symptoms. Methods In the cohort study, Respiratory Health in Northern Europe (RHINE), a random population from Denmark, Estonia, Iceland, Norway, and Sweden, born between 1945 and 1973, was investigated by postal questionnaires in 1999–2001 (RHINE II, baseline) and in 2010–2012 (RHINE III, follow-up). The study population consisted of the participants who had answered questions on nasal symptoms such as nasal obstruction, discharge, and sneezing, and also snoring both at baseline and at follow-up (n = 10,112). Results Nasal symptoms were frequent, reported by 48% of the entire population at baseline, with snoring reported by 24%. Nasal symptoms at baseline increased the risk of snoring at follow-up (adj. OR 1.38; 95% CI 1.22–1.58) after adjusting for age, sex, BMI change between baseline and follow-up, and smoking status. Snoring at baseline was associated with an increased risk of developing nasal symptoms at follow-up (adj. OR 1.22; 95% CI 1.02–1.47). Conclusion Nasal symptoms are independent risk factors for development of snoring 10 years later, and surprisingly, snoring is a risk factor for the development of nasal symptoms.

scholarly journals Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Radiation Induced ◽  
Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

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