Rheumatoid Arthritis is a Risk Factor for Refracture in Patients with Fragility Fractures

Abstract Objectives To determine whether patients with rheumatoid arthritis (RA) who have had fragility fractures are at an increased risk of refractures. Methods Patients with fragility fractures who were treated surgically at ten hospitals from 2008 to 2017 and who underwent follow-up for more than 24 months were either categorized into a group comprising patients with RA or a group comprising patients without RA (controls). The groups were matched 1:1 by propensity score matching. Accordingly, 240 matched participants were included in this study. The primary outcome was the refracture rate in patients with RA as compared to in the controls. Multivariable analyses were also conducted on patients with RA to evaluate the odds ratios (ORs) for the refracture rates. Results Patients with RA were significantly associated with increased rates of refractures during the first 24 months (OR: 2.714, 95% confidence interval [95% CI]: 1.015–7.255; P = 0.040). Multivariable analyses revealed a significant association between increased refracture rates and long-term RA (OR: 6.308, 95% CI: 1.195–33.292; P=0.030). Conclusions Patients with RA who have experienced fragility fractures are at an increased risk of refractures. Long-term RA is a substantial risk factor for refractures.

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Abstract 15934: Higher Midlife Serum Levels of Kidney-injury Molecule-1 (KIM-1) are Associated With Incident Fatal CHD Over Very Long-term Follow-up Among Men

Circulation ◽

10.1161/circ.132.suppl_3.15934 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Rachel H Mackey ◽

Greg G Grandits ◽

Lewis H Kuller ◽

Joel Estis ◽

John A Todd ◽

...

Keyword(s):

Risk Factor ◽

Limit Of Detection ◽

Kidney Injury ◽

Multiple Risk Factor ◽

Serum Samples ◽

Increased Risk ◽

Long Term Follow Up ◽

Kidney Injury Molecule 1

Introduction: Higher levels of kidney-injury molecule-1 (KIM-1) measured in urine are associated with presence and progression of acute renal disease. A recent study reported similar results for KIM-1 measured in blood. Hypothesis: We hypothesized that KIM-1 measured in stored serum from middle-aged men who participated in the Multiple Risk Factor Intervention Trial (MRFIT) would differentiate very long-term risk of fatal CHD vs. survival to a mean age of 80 over approximately 30 year follow-up. Methods: We conducted a nested case-control study within MRFIT, which in 1973-76 randomized 12,866 high risk but CVD free men ages 35-57 to risk factor intervention vs. usual care. Serum samples were collected at baseline and stored for future use. The trial concluded in 1982 but long-term mortality follow-up was ascertained through 2005 using the National Death Index. From MRFIT participants with stored serum from baseline, we sampled 100 men who died of CHD (mean age 47.3 at baseline and 73.9 at death), and 100 men who survived to 2005 (mean age =48.4 at baseline and 80.1 in 2005.) KIM-1 was assayed from stored serum samples using high sensitivity single-molecule counting technology (Erenna ® Immunoassay System, Singulex), with limit of detection (LoD)=0.5 pg/ml, and lower limit of quantification (LLoQ)=2.0 pg/ml. Results were compared between cases and controls using Wilcoxon rank tests and logistic regression. Results: Inter-assay %CVs were 8%. Median KIM-1 was higher for smokers vs. non-smokers and for men with vs. without hypertension, but was not associated with high cholesterol. KIM-1 was significantly higher in cases (183 pg/ml (IQR: 137-239) versus controls, (161 pg/ml (IQR:109-212), p=0.03; OR (95%CI)for Q4 versus Q1 was 2.26 (1.02 - 5.02) Adjusted for age and smoking the OR(95%CI) of fatal CHD for Q4 vs. Q1 was 2.34 (1.02- 5.37), and further adjusted for diastolic BP and serum cholesterol at baseline, was 2.0 (95% CI: 0.8-4.7). Conclusions: Higher serum KIM-1 levels at midlife were associated with a ∼2-fold increased risk of fatal CHD vs. survival over ∼30 years of follow-up. This is the first report of a longitudinal association of circulating KIM-1 levels with fatal CHD in long-term follow-up.

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P1748PARATHYROIDECTOMY REMAINS EFFECTIVE FOR TREATING TERTIARY HYPERPARATHYROIDISM: LONG-TERM RESULTS OF A RANDOMIZED STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1748 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Ana Coloma Lopez ◽

Pablo Moreno ◽

Jose-Vicente Torregrosa ◽

Nuria Montero ◽

Anna Manonelles ◽

...

Keyword(s):

Kidney Transplant ◽

Serum Calcium ◽

Randomized Study ◽

Fragility Fractures ◽

Long Term Results ◽

Subtotal Parathyroidectomy ◽

Tertiary Hyperparathyroidism ◽

Increased Risk

Abstract Background and Aims Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant (KT) and has been associated with renal dysfunction, loss bone mineral density and increased risk of fracture, vascular calcification, and increased risk of cardiovascular events. Long clinical management remains controversial. The aim of this study is to evaluate the long-term effectiveness and safety of parathyroidectomy versus cinacalcet in patients with persistent hyperparathyroidism. Method A 12-month prospective, multicenter, randomized study demonstrated than subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia. Now, we evaluate in the same cohort of patients if this effect is maintained after 5 years of follow-up. Laboratory assessment included serum calcium, serum phosphate, intact parathyroid hormone (iPTH), calcidiol levels, estimated glomerular filtration rate and proteinuria at 2, 3, 4 and 5 year follow-up. Therapeutic details about the use of vitamin D, calcium supplementation and phosphate binders were compiled. Fragility fractures were also collected. Results In total, 24 patients had data available at 5 years, 13 in the cinacalcet group and 11 in the parathyroidectomy group. At 5 years, six of 13 patients in the cinacalcet group and ten of 11 patients in the parathyroidectomy group (p=0.015) showed normocalcemia (Figure 1). Subtotal parathyroidectomy retained a greater reduction of iPTH compared with cinacalcet group (Figure 2). No differences were observed in kidney function and incidence of fragility fractures between both groups. In relation of treatment, 8 of 13 patients in cinacalcet group maintained treatment with cinacalcet after 5 years follow-up. Conclusion Subtotal parathyroidectomy is more effective in long term to maintain normal serum calcium and iPTH compared with cinacalcet in kidney transplant patients with tertiary hyperparathyroidism.

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Abstract 12428: Efficacy of a Risk Reduction Program to Improve Cardiovascular Outcomes in Patients With Peripheral Arterial Disease: A Propensity Score-Matched Study

Circulation ◽

10.1161/circ.132.suppl_3.12428 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Mohamad A Hussain ◽

Mohammed Al-Omran ◽

Muhammad Mamdani ◽

Xuesong Wang ◽

Subodh Verma ◽

...

Keyword(s):

Risk Factor ◽

High Risk ◽

Propensity Score ◽

Peripheral Arterial Disease ◽

Risk Reduction ◽

Primary Outcome ◽

Arterial Disease ◽

Reduction Program ◽

Peripheral Arterial

Introduction: Patients with peripheral arterial disease (PAD) are often undertreated for cardiovascular (CV) risk factors, and they are at high risk for CV events. Hypothesis: A program that focuses on guideline-based risk factor management reduces adverse CV and limb events in PAD patients. Methods: A propensity-score matched observational cohort study with up to 7 years of follow-up was conducted using administrative databases in Ontario, Canada. Symptomatic PAD patients that were enrolled in the Systematic Assessment of Vascular Risk (SAVR) program between July 2004 and April 2007 were matched with up to 2 (control) patients with PAD from other Ontario tertiary vascular centers not enrolled in the program. The primary outcome was a composite of death, stroke or myocardial infarction (MI). Secondary outcomes included lower limb amputation and revascularization procedures. Cox proportional hazards regression analysis was used to compare outcomes between the groups. Results: A total of 791 patients were studied. During follow-up, the SAVR group (n=290) experienced the primary outcome at a significantly lower rate than the control group (adjusted HR, 0.64 [95% CI, 0.52 to 0.78]; P<0.001) (Figure). SAVR patients were also less likely to undergo major amputation (adjusted HR, 0.47 [95% CI, 0.29 to 0.77]; P=0.002), minor amputation (adjusted HR, 0.26 [95% CI, 0.13 to 0.54]; P<0.001), arterial bypass surgery (adjusted HR, 0.47 [95% CI, 0.30 to 0.73]; P<0.001), and less likely to have a hospitalization due to heart failure (adjusted HR, 0.73 [95% CI, 0.53 to 0.998]; P=0.048). The rate of peripheral angioplasty was higher among the SAVR group (adjusted HR, 3.0 [95% CI, 2.2 to 4.1]; P<0.001). Conclusions: A multifactor risk reduction program targeted to patients with PAD is associated with fewer adverse CV and limb events over the long-term. Greater focus is needed on developing structured programs for risk factor control in these high-risk patients.

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Digoxin treatment and long-term mortality depending on left ventricular ejection fraction and atrial fibrillation: a propensity score matched analysis

European Heart Journal ◽

10.1093/eurheartj/ehab724.0502 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

M.R Grubler ◽

N.D Verheyen ◽

A Meinitzer ◽

L Fiedler ◽

M Tscharre ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Coronary Angiography ◽

Propensity Score ◽

Ejection Fraction ◽

Propensity Score Matching ◽

Increased Risk ◽

All Cause Mortality

Abstract Background/Introduction Atrial fibrillation (AF) is a common heart rhythm disturbance, associated with an increased risk of stroke, hospital admissions and mortality, especially in patients with reduced ejection fraction. Among the oldest medications used for heart-rate control is digitalis, but largely due to observational studies showing an increased risk of death it has fallen out of favour. Recently newer clinical trials reported that the treatment with digitalis in permanent AF might be superior to beta blocker therapy in regard to functional status and symptom burden. Given this diverging results we attempt to analysis a large cohort of patients facilitating a propensity score matching algorithm. Purpose To assess the associations of digitalis treatment with mortality in patients with increased cardiovascular risk. Methods Patients were derived from a large cohort study including participants from a tertiary care centre who were referred to coronary angiography. The propensity score matching is based on a predefined list of variables, with digitalis as treatment. Matching strategy is nearest neighbour matching and to prove consistency, radius matching (radius = 0.1). For survival analysis we used a Cox proportional hazard regression comparing patients with and without digitalis for all-cause mortality. The analysis is conducted using STATA 13 MP. All patients provided written informed consent and the study was approved by the ethics committee. Results A total of 2457 patients (median age: 63.5 [IQR = 56.3–70.6] years, 30.1% women) referred to coronary angiography, with a median follow up of 9.9 (IQR = 8.5–10.7) years were included. The matching process and the resulting propensity score fulfilled all statistical assumptions and resulted in a balanced cohort. The risk for all-cause mortality was higher among propensity score matched participants not treated with digitalis compared to patients on treatment (n=514) HR 3.03 (95% CI 2.5 to 3.7). Total mortality in patients with AF on digitalis after a median follow-up of 9.9 years was 27.6%. At baseline, only 42.4% of patients with AF were on oral anticoagulation. Conclusions In the present cohort treatment with digitalis was associated with a lower risk of all-cause mortality after long-term follow-up. The patient population has a clinically significant 10-year mortality risk. The results may not apply to other cohorts but may help inform future clinical trials. FUNDunding Acknowledgement Type of funding sources: None.

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Long-term outcomes and secondary prevention after acute coronary events in patients with rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211608 ◽

2017 ◽

Vol 76 (12) ◽

pp. 2017-2024 ◽

Cited By ~ 4

Author(s):

Ängla Mantel ◽

Marie Holmqvist ◽

Tomas Jernberg ◽

Solveig Wållberg-Jonsson ◽

Johan Askling

Keyword(s):

Rheumatoid Arthritis ◽

Standard Of Care ◽

Long Term Outcomes ◽

Short Term ◽

Coronary Syndrome ◽

Relative Risks ◽

Increased Risk ◽

Coronary Events

ObjectivesPatients with rheumatoid arthritis (RA) are at increased risk of acute coronary syndrome (ACS) and suffer from poorer short-term outcomes after ACS. The aims of this study were to assess long-term outcomes in patients with RA with ACS compared with non-RA patients with ACS, and to investigate whether the use of secondary preventive drugs could explain any differences in ACS outcome.MethodsWe performed a cohort study based on 1135 patients with RA and 3184 non-RA patients who all developed an incident ACS between 2007 and 2010. We assessed 1-year and overall relative risks for ACS recurrence and mortality, as well as prescriptions of standard of care secondary preventive drugs.ResultsThe risk of ACS recurrence, and of mortality, was increased in RA, both at 1 year after adjusting for baseline comorbidities (HR=1.30(95% CI 1.04 to 1.62) and 1.38(95% CI 1.20 to 1.59), respectively) and throughout the complete (mean 2 years) follow-up (HR=1.27(95% CI 1.06 to 1.52) and 1.50(95% CI 1.34 to 1.68), respectively). Among certain subgroups of ACS, there was a tendency of lower usage of statins, whereas there were no apparent differences in others. The increased rates of ACS recurrence and mortality remained in subgroup analyses of individuals whose prescription pattern indicated both adequate initiation and persistence to secondary preventive treatments.ConclusionsPatients with RA suffer from an increased risk of ACS recurrence and of death following ACS compared with general population, which in the present study could not readily be explained by differences in usage of secondary preventive drugs.

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O06 Baseline predictors of methotrexate-related adverse events in methotrexate-naïve patients with RA

Rheumatology ◽

10.1093/rheumatology/keab246.005 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Ahmad A Sherbini ◽

James M Gwinnutt ◽

Kimme L Hyrich ◽

Suzanne M M Verstappen ◽

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Health Assessment ◽

Prevalence Rates ◽

Clinical Predictors ◽

Research Support ◽

Related Data ◽

Increased Risk ◽

One Year

Abstract Background/Aims Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs. Methods The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression. Results A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (> upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT >1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up. Conclusion In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness. Disclosure A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.

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Intracameral Bevacizumab Versus Sub-Tenon’s Mitomycin C as Adjuncts to Trabeculectomy: 3-Year Results of a Prospective Randomized Study

Journal of Clinical Medicine ◽

10.3390/jcm10102054 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2054

Author(s):

Gerasimos Kopsinis ◽

Dimitrios Tsoukanas ◽

Dimitra Kopsini ◽

Theodoros Filippopoulos

Keyword(s):

Mitomycin C ◽

Primary Outcome ◽

Randomized Study ◽

Primary Outcome Measure ◽

Complication Rates ◽

Filtration Surgery ◽

Significant Difference ◽

Exfoliative Glaucoma

Conjunctival wound healing determines success after filtration surgery and the quest for better antifibrotic agents remains active. This study compares intracameral bevacizumab to sub-Tenon’s mitomycin C (MMC) in trabeculectomy. Primary open-angle or exfoliative glaucoma patients were randomized to either bevacizumab (n = 50 eyes) or MMC (n = 50 eyes). The primary outcome measure was complete success, defined as Intraocular Pressure (IOP) > 5 mmHg and ≤ 21 mmHg with a minimum 20% reduction from baseline without medications. Average IOP and glaucoma medications decreased significantly in both groups at all follow-up points compared to baseline (p < 0.001), without significant difference between groups at 3 years (IOP: bevacizumab group from 29 ± 9.4 to 15 ± 3.4 mmHg, MMC group from 28.3 ± 8.7 to 15.4 ± 3.8 mmHg, p = 0.60; Medications: bevacizumab group from 3.5 ± 0.9 to 0.5 ± 1, MMC group from 3.6 ± 0.7 to 0.6 ± 1.1, p = 0.70). Complete success, although similar between groups at 3 years (66% vs. 64%), was significantly higher for bevacizumab at months 6 and 12 (96% vs. 82%, p = 0.03; 88% vs. 72%, p = 0.04, respectively) with fewer patients requiring medications at months 6, 9 and 12 (4% vs. 18%, p = 0.03; 6% vs. 20%, p = 0.04; 8% vs. 24%, p = 0.03, respectively). Complication rates were similar between groups. In conclusion, intracameral bevacizumab appears to provide similar long-term efficacy and safety results as sub-Tenon’s MMC after trabeculectomy.

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Changes in insomnia as a risk factor for the incidence and persistence of anxiety and depression: a longitudinal community study

Sleep Science and Practice ◽

10.1186/s41606-020-00053-z ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Magnus Johansson ◽

Markus Jansson-Fröjmark ◽

Annika Norell-Clarke ◽

Steven J. Linton

Keyword(s):

Risk Factor ◽

Depression Scale ◽

Binary Logistic Regression ◽

Anxiety And Depression ◽

Hospital Anxiety ◽

Dynamic Risk ◽

Increased Risk ◽

Longitudinal Association ◽

Development Of Anxiety

Abstract Background The aim of this investigation was to examine the longitudinal association between change in insomnia status and the development of anxiety and depression in the general population. Methods A survey was mailed to 5000 randomly selected individuals (aged 18–70 years) in two Swedish counties. After 6 months, a follow-up survey was sent to those (n = 2333) who answered the first questionnaire. The follow-up survey was completed by 1887 individuals (80.9%). The survey consisted of questions indexing insomnia symptomatology, socio-demographic parameters, and the Hospital Anxiety and Depression Scale. Change in insomnia status was assessed by determining insomnia at the two time-points and then calculating a change index reflecting incidence (from non-insomnia to insomnia), remission (from insomnia to non-insomnia), or status quo (no change). Multivariate binary logistic regression analyses were used to examine the aim. Results Incident insomnia was significantly associated with an increased risk for the development of new cases of both anxiety (OR = 0.32, p < .05) and depression (OR = 0.43, p < .05) 6 months later. Incident insomnia emerged also as significantly associated with an elevated risk for the persistence of depression (OR = 0.30, p < .05), but not for anxiety. Conclusions This study extends previous research in that incidence in insomnia was shown to independently increase the risk for the development of anxiety and depression as well as for the maintenance of depression. The findings imply that insomnia may be viewed as a dynamic risk factor for anxiety and depression, which might have implications for preventative work.

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Impact of atrial fibrillation pattern on outcomes after left atrial appendage closure: lessons from the prospective LAARGE registry

Clinical Research in Cardiology ◽

10.1007/s00392-021-01874-3 ◽

2021 ◽

Author(s):

Shinwan Kany ◽

Johannes Brachmann ◽

Thorsten Lewalter ◽

Ibrahim Akin ◽

Horst Sievert ◽

...

Keyword(s):

Atrial Fibrillation ◽

Left Atrial Appendage ◽

Systemic Embolism ◽

Long Term Outcomes ◽

Increased Risk ◽

History Of ◽

One Year ◽

The One

Abstract Background Non-paroxysmal (NPAF) forms of atrial fibrillation (AF) have been reported to be associated with an increased risk for systemic embolism or death. Methods Comparison of procedural details and long-term outcomes in patients (pts) with paroxysmal AF (PAF) against controls with NPAF in the prospective, multicentre observational registry of patients undergoing LAAC (LAARGE). Results A total of 638 pts (PAF 274 pts, NPAF 364 pts) were enrolled. In both groups, a history of PVI was rare (4.0% vs 1.6%, p = 0.066). The total CHA2DS2-VASc score was lower in the PAF group (4.4 ± 1.5 vs 4.6 ± 1.5, p = 0.033), while HAS-BLED score (3.8 ± 1.1 vs 3.9 ± 1.1, p = 0.40) was comparable. The rate of successful implantation was equally high (97.4% vs 97.8%, p = 0.77). In the three-month echo follow-up, LA thrombi (2.1% vs 7.3%, p = 0.12) and peridevice leak > 5 mm (0.0% vs 7.1%, p = 0.53) were numerically higher in the NPAF group. Overall, in-hospital complications occurred in 15.0% of the PAF cohort and 10.7% of the NPAF cohort (p = 0.12). In the one-year follow-up, unadjusted mortality (8.4% vs 14.0%, p = 0.039) and combined outcome of death, stroke and systemic embolism (8.8% vs 15.1%, p = 0.022) were significantly higher in the NPAF cohort. After adjusting for CHA2DS2-VASc and previous bleeding, NPAF was associated with increased death/stroke/systemic embolism (HR 1.67, 95% CI 1.02–2.72, p = 0.041). Conclusion Atrial fibrillation type did not impair periprocedural safety or in-hospital MACE patients undergoing LAAC. However, after one year, NPAF was associated with higher mortality. Graphic abstract

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

Scientific Reports ◽

10.1038/s41598-021-89216-1 ◽

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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