Prevalence and Risk Factors for Adrenal Insufficiency in Patients with Multiple Myeloma Receiving Long-Term Chemotherapy including Corticosteroids: A Retrospective Cohort Study

Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18 μg/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid ( odds ratio OR = 0.99 , 95% confidence interval (CI) 0.98–0.99; P = 0.020 ) and megestrol acetate use ( OR = 2.63 , 95% CI 1.48–4.67; P = 0.001 ) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI ( OR = 2.54 , 95% CI 1.41–4.60; P = 0.002 ). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.

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OP0133 THE PREVALENCE AND RISK FACTORS OF RETINAL TOXICITY ASSOCIATED WITH LONG-TERM HYDROXYCHLOROQUINE USE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.328 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 77-78

Author(s):

S. Do ◽

J. H. Du ◽

J. X. An ◽

J. Wang ◽

A. Lin

Keyword(s):

Risk Factors ◽

Cumulative Dose ◽

Daily Intake ◽

Retinal Toxicity ◽

Factors Associated ◽

Duration Of Therapy ◽

Increased Risk ◽

Hydroxychloroquine Retinopathy ◽

Risk Of Retinopathy

Background:Hydroxychloroquine (HCQ) is commonly used for the treatment of various autoimmune diseases. The medication is generally well-tolerated. However, long-term use after 5 years may increase the risk of retinopathy. One study in 2014 has demonstrated the risk can be as high as 7.5%. Optical Coherence Tomography (OCT) has become a major modality in screening retinopathy.Objectives:To evaluate the prevalence of retinal toxicity among patients using hydroxychloroquine and to determine various risk factors associated with hydroxychloroquine-associated retinal toxicity.Methods:We performed a retrospective chart review on a cohort of adult patients with long-term use (≥ 5 years cumulative) of HCQ between January 1st, 2011 to December 31st, 2018 from the Kaiser Permanente San Bernardino County and Riverside medical center areas in Southern California, USA. Patients were excluded if they had previously been diagnosed with retinopathy prior to hydroxychloroquine use, were deceased, or had incomplete OCT exam. Our primary endpoint was the prevalence of patients who developed retinal toxicity detected by OCT, and later confirmed by retinal specialist. Potential risk factors (age, duration of therapy, daily consumption per actual body weight, cumulative dose, confounding diseases and medication) for developing retinopathy were also evaluated. Univariable and multivariable logistic regression analyses were used to determine risk factors associated with retinal toxicity.Results:Among 676 patients exposed to more than 5 years of HCQ, the overall prevalence of retinal toxicity was 6.8%, and ranged from 2.5% to 22.2% depending on the age, weight-based dosing, duration of use and cumulative dose. Duration of therapy for 10 years or more increased risk of retinopathy by approximately 5 to 19 folds. Similarly, weight-based dose of 7 mg/kg/day or greater was assciated with increased risk of retinopathy by approximately 5 times. Patients with cumulative dose of 2000 grams or more had greater than 15 times higher risk of developing retinopathy. Duration of use for10 years or more (odd ratio 4.32, 95% CI 1.99 – 12.49), age (odd ratio 1.04; 95% CI 1.01 - 1.08), cumulative dose of more than 1500 g (odd ratio 7.4; 95% CI 1.40 – 39.04) and atherosclerosis of the aorta (odd ratio 2.59; 95% CI, 1.24 – 5.41) correlated with higher risk of retinal toxicity.Conclusion:The overall prevalence of retinopathy was 6.8%. Regular OCT screening, especially in patients with hydroxychloroquine use for more than 10 years, daily intake > 7 mg/kg, or cumulative dose > 1500 grams is important in detecting hydroxychloroquine-associated retinal toxicityReferences:[1]Hobbs HE. Sorsby A, & Freedman A. Retinopathy Following Chloroquine Therapy. The Lancet. 1959; 2(7101): 478-480.[2]Levy, G. D., Munz, S. J., Paschal, J., Cohen, H. B., Pince, K. J., & Peterson, T. Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice. Arthritis & Rheumatism: 1997; 40(8): 1482-1486.[3]Ding, H. J., Denniston, A. K., Rao, V. K., & Gordon, C. Hydroxychloroquine-related retinal toxicity. Rheumatology. 2016; 55(6): 957-967.[4]Stelton, C. R., Connors, D. B., Walia, S. S., & Walia, H. S. Hydrochloroquine retinopathy: characteristic presentation with review of screening. Clinical rheumatology. 2013; 32(6): 895-898.[5]Marmor, M. F., Kellner, U., Lai, T. Y., Melles, R. B., & Mieler, W. F. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016; 123(6): 1386-1394.[6]Melles, R. B., & Marmor, M. F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA ophthalmology. 2014; 132(12): 1453-1460.Disclosure of Interests:None declared

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Non Malignant Late Complications After Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT); Korean Experience

Blood ◽

10.1182/blood.v120.21.4462.4462 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4462-4462

Author(s):

Silvia Park ◽

Su Jin Lee ◽

Won jin Chang ◽

Chi Hoon Maeng ◽

Jung Yong Hong ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Risk Factor ◽

Side Effects ◽

Adrenal Insufficiency ◽

Univariate Analysis ◽

Late Complications ◽

Post Transplant ◽

Long Term Survivors

Abstract Abstract 4462 Introduction: Allo-HSCT is the curative treatment for hematologic fatal diseases, and survival rates have been substantially improved since its introduction. With steadily growing number of long term survivors after transplantation, late physiologic side effects are also increasingly reported in these patients. However, the incidence and the risk factors for post transplant late complications were rarely reported so far. Methods: Medical records of post transplant long term survivors from 3 institutes in Seoul, Korea were retrospectively reviewed. Long term survivors were defined as those who were still alive at least 2 year after allo-HSCT. Data from a total of 634 consecutive patients who received transplantation between July 1988 and Jan 2010 were collected and analyzed. Results: The median age was 37 (14–70), and there were more male patients (57.6%). Sibling donor was most common (64.5%), and PB rather than BM was frequently used as a source of stem cells (PB=51.5%; BM=48.6%). Majority of patients received transplantation from HLA full-matched donors (90.2%). AML was the most common reason for allo-HSCT (39.9%); SAA (16.9%), ALL (12.6%) and MDS (11.5%) came next. During transplantation, ATG was used in 33.3% of patients, and 10.3% received TBI. RIC transplantation comprised 35.6%. Acute GVHD and chronic GVHD occurred in 26.5% and 57.6% of patients. Among the endocrine dysfunction, hypothyroidism, gonadal failure, and adrenal insufficiency were observed with an incidence of 1.4%, 95.9% and 2.2%. In multivariate analysis, only TBI attained statistical significance for hypothyroidism (HR=7.1) and adrenal insufficiency (HR=9.7). BO/BOS was the most common pulmonary complication (7%) and then the BOOP (2%) and the interstitial pneumonitis (1%). Age≥40, PB source, myeloablative conditioning, no use of ATG and cGHVD (at any organ) were the risk factors for lung complications in univariate analysis; PB source and cGHVD were significant in multivariate analysis (PB, HR=2.3; cGHVD, HR=7.9). Osteoporosis and avascular necrosis (AVN) were observed in 4.1% and 3.9% of patients. Female sex, age≥40, and cGHVD were the significant risk factors for osteoporosis in multivariate analysis with a HR of 9.6, 4.9 and 7.2, respectively. No use of ATG had significance for AVN in univariate analysis but not in multivariate analysis. Among the long term survivors, 6.2% of patients experienced cataract; age≥40, PB source, no use of ATG and cGHVD were significant in univariate analysis, of which, only age≥40 was significant in multivariate analysis (HR=5.5). Nephropathy was observed in 7.4%, and male sex was the risk factor with a HR of 2.3. Cardiovascular diseases involving cardiomyopathy, CHF, arrhythmia and pericarditis were reported from 1.4% of patients, and unrelated donor was the risk factor in multivariate analysis (HR=12.1). Conclusion: This retrospective data showing the incidence and risk factors for late physiologic side effects could serve as a basis for optimal approach in long term survivors after allogeneic HSCT. Disclosures: Jang: Alexion Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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

Blood ◽

10.1182/blood-2019-123065 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4560-4560 ◽

Cited By ~ 1

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.

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Complications and survival after subcutaneous ureteral bypass device placement in 24 cats: a retrospective study (2016–2019)

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x20975374 ◽

2020 ◽

pp. 1098612X2097537

Author(s):

Emily Vrijsen ◽

Nausikaa Devriendt ◽

Femke Mortier ◽

Emmelie Stock ◽

Bart Van Goethem ◽

...

Keyword(s):

Risk Factors ◽

Perioperative Complications ◽

Univariate Analysis ◽

Binary Logistic Regression ◽

P Value ◽

Short Term ◽

Lower Urinary Tract Infection ◽

Term Survival ◽

Increased Risk

Objectives The aim of this study was to document survival, complications and risk factors for the development of complications and mortality prior to discharge after placement of a subcutaneous ureteral bypass (SUB) device in cats. Methods The medical records of cats with SUB placement between January 2016 and August 2019 were retrospectively analysed. The development of complications (overall, intraoperative, perioperative, short- and long-term complications) and risk factors for mortality prior to discharge were statistically assessed with univariate binary logistic regression. All variables with a P value ⩽0.10 in the univariate analysis were assessed in a multivariate model. Variables were significant if P <0.05. Results Twenty-four cats were included; 12 (50.0%) received a unilateral SUB, 11 (45.8%) a bilateral nephrostomy tube with single cystostomy catheter and the remaining cat (4.2%) two unilateral SUBs. Nearly 80% of the cats developed complications, ranging from mild to fatal, including (partial) SUB obstruction (33.3% of complications), lower urinary tract infection (20.8%), pyelonephritis (20.8%) and sterile cystitis (12.5%). Five cats (20.8%) died prior to discharge. Six cats (25.0%) underwent revision surgery. The overall median survival time (MST) was 274 days (range 1–311 days). Complications were most common in the long-term period (14/16 cats), followed by the short-term (9/18 cats), perioperative (10/23 cats) and intraoperative (4/24 cats) periods. Older cats had an increased risk for developing perioperative complications ( P = 0.045) and were less likely to survive to discharge ( P = 0.033). An increased haematocrit at presentation was a risk factor for the occurrence of short-term complications ( P = 0.03). Conclusions and relevance Although complications similar to those previously described were observed, the complication rate was higher and the MST shorter than previously reported in cats undergoing SUB placement. Despite good short-term survival, the development of complications may necessitate regular and intensive control visits. Owners that consider SUB placement should be informed that follow-up can be strenuous and expensive.

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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 ◽

10.1182/blood.v110.11.1082.1082 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1082-1082 ◽

Cited By ~ 1

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

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Thromboembolic Events (TEE) with Lenalidomide-Based Therapies for Multiple Myeloma (MM): Emory Experience.

Blood ◽

10.1182/blood.v114.22.3888.3888 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3888-3888 ◽

Cited By ~ 1

Author(s):

Ajay K Nooka ◽

Jonathan L. Kaufman ◽

Leonard T Heffner ◽

Charise L. Gleason ◽

Sagar Lonial

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Research Funding ◽

Risk Model ◽

Univariate Analysis ◽

Parent Compound ◽

Previous History ◽

Significant Risk ◽

Median Number ◽

High Dose

Abstract Abstract 3888 Poster Board III-824 Introduction Lenalidomide is a derivative of thalidomide with an additional amino group at position 4 and removal of a carbonyl group that has enhanced efficacy and reduced toxicity relative to its parent compound. However, studies have reported the incidence of TEE from 3-23.8%. We proceeded to evaluate incidence and risk factors of TEE associated with lenalidomide-based therapies in patients with multiple myeloma at our institution. Methods We reviewed 152 records of patients that were prescribed lenalidomide from prescribing information obtained from Celgene pharmaceuticals as well as reviewing patient information from all clinical trials from 2004 until October 2008. IRB approval was obtained. 146 patients (pts) were included in study after excluding 6 pts in whom lenalidomide was used for non-myeloma indications. Lenalidomide was indicated for induction in 22 (15%) pts and for maintenance/salvage in 124 (85%) pts. Results 81 (55.5%) pts were male and 65 (44.5%) were female. White pts (65%) contributed to majority of our pt population. Median age (range) is 62 months (23-87); stage III disease is seen in 23 pts (22%); median (range) β-2 microglobulin is 2.68 (0.8-43.51) and median (range) creatinine is 1.05 (0.6-21). Pts received a median (range) of 7 (1-58) cycles. Overall ten (6.8%) TEEs were observed including nine venous TEEs (6.12%) and one arterial TEE (0.68%). Nine pts developed TEE despite being on ASA prophylaxis. Median (range) time to event was 17 weeks (4-158). Median (range) cycles of lenalidomide before the event were 3.5 (1-38). 60% of events took place in the first 4 months of initiation of therapy. On univariate analysis, erythropoietin use vs. none (21.4% vs. 5.3% p=0.023); median number of cycles ≥7 vs. <7 (11.1% vs. 2.7% p=0.044) and previous history of DVT vs. none (20% vs. 4.1%; p=0.014) were identified as significant risk factors. Steroid doses, BMI were not identified as risk factors. On multivariate analysis, age <60 (HR 0.11 95%CI 0.00-0.50; p = 0.021) had a significant protective impact on developing TEE. Median survival (range) in pts with TEE is 102 months (100.4-103.6) and pts without TEE is 99 months (79.38-118.62); log rank 0.125. Conclusion Neither high dose steroids nor the BMI were identified as risk factors for TEE. All pts with venous TEE had high risk factors validating the risk model of IMWG. No impact on overall survival was seen between pts with TEE and pts without TEE. Disclosures: Kaufman: Celgene: Consultancy, Research Funding; Millenium: Consultancy; Genzyme: Consultancy; Merck: Research Funding. Heffner:Millenium: Honoraria. Gleason:Millenium: Consultancy. Lonial:Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.

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Association of inflammatory disease and long-term outcomes among young adults with myocardial infarction: the Partners YOUNG-MI registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.1305 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

B Weber ◽

D.W Biery ◽

A Singh ◽

S Divakaran ◽

A.N Berman ◽

...

Keyword(s):

Risk Factors ◽

Inflammatory Disease ◽

Inflammatory Arthritis ◽

Young Age ◽

Funding Source ◽

Long Term Outcomes ◽

Increased Risk ◽

Systemic Inflammatory Disease ◽

All Cause Mortality

Abstract Background Autoimmune systemic inflammatory diseases are associated with an increased risk of cardiovascular disease, particularly myocardial infarction (MI). However, there are limited data on the prevalence and effects of inflammatory disease among U.S. adults who experience an MI at a young age. Purpose We sought to determine the prevalence and prognostic value of inflammatory disease in U.S. adults who experience an MI at a young age. Methods The YOUNG-MI registry is a retrospective cohort study of consecutive patients who experienced a Type 1 MI at or below the age of 50 years from 2000 to 2016 at two large medical centers. A diagnosis of rheumatoid arthritis (RA), psoriasis (PsO), systemic lupus erythematosus (SLE), or inflammatory arthritis was determined through physician review of electronic medical records (EMR). Demographic information, presence of cardiovascular (CV) risk-factors, medical procedures, and medications upon discharge were also ascertained from the EMR. Incidence of death was determined using a combination of EMR and national databases. Cox proportional hazard modeling was performed on a sub-sample following Mahalanobis Distance matching on age, sex, and CV risk factors. Results The cohort consisted of 2097 individuals (median age 45 years, 19% female, 53% ST-elevation MI). Among these, 53 (2.5%) individuals possessed a diagnosis of systemic inflammatory disease at or before their index MI (23% SLE, 9% RA, 64% PsO, 4% inflammatory arthritis). When compared to the remainder of the cohort, patients with a diagnosis of systemic inflammatory disease were more likely to be female (36% vs 19%, p=0.004) and be diagnosed with hypertension (62% vs 46%, p=0.025). There was, however, no significant difference in the prevalence of other CV risk factors – diabetes, smoking, dyslipidemia – or a family history of premature coronary artery disease. Despite these similarities, patients with inflammatory disease were less likely to be prescribed aspirin (88% vs 95%, p=0.049) or a statin (76% vs 89%, p=0.008) upon discharge. Over a median follow-up of 11.2 years, patients with inflammatory disease experienced an increased risk of all-cause mortality when compared with the full-cohort (Figure). Compared to the matched sample (n=138), patients with systemic inflammatory disease exhibited an increased risk of all-cause mortality (HR=2.68, CI [1.18 to 6.07], p=0.018), which remained significant after multivariable adjustment for length of stay and GFR (HR=2.38, CI [1.02 to 5.54], p=0.045). Conclusions Among individuals who experienced an MI at a young age, approximately 2.5% had evidence of a systemic inflammatory disease at or before their MI. When compared with a population of individuals with similar cardiovascular risk profiles, those with inflammatory disease had higher rates of all-cause mortality. Our findings suggest that the presence of a systemic inflammatory disorder is independently associated with worse long-term outcomes. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. 5T32 HL094301 NIH T32 Training Grant, “Noninvasive Cardiovascular Imaging Research Training Program”

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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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Combining Carcinoembryonic Antigen and Platelet to Lymphocyte Ratio to Predict Brain Metastasis of Resected Lung Adenocarcinoma Patients

BioMed Research International ◽

10.1155/2017/8076384 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Wei Wang ◽

Chao Bian ◽

Di Xia ◽

Jin-Xi He ◽

Ping Hai ◽

...

Keyword(s):

Risk Factors ◽

Brain Metastasis ◽

Lung Adenocarcinoma ◽

Carcinoembryonic Antigen ◽

Roc Curve ◽

Univariate Analysis ◽

Significant Risk ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Increased Risk

We aimed to evaluate the role of pretreatment carcinoembryonic antigen (CEA) and platelet to lymphocyte ratio (PLR) in predicting brain metastasis after radical surgery for lung adenocarcinoma patients. The records of 103 patients with completely resected lung adenocarcinoma between 2013 and 2014 were reviewed. Clinicopathologic characteristics of these patients were assessed in the Cox proportional hazards regression model. Brain metastasis occurred in 12 patients (11.6%). On univariate analysis, N2 stage (P = 0.013), stage III (P = 0.016), increased CEA level (P = 0.006), and higher PLR value (P = 0.020) before treatment were associated with an increased risk of developing brain metastasis. In multivariate model analysis, CEA above 5.2 ng/mL (P = 0.014) and PLR ≥ 120 (P = 0.036) remained as the risk factors for brain metastasis. The combination of CEA and PLR was superior to CEA or PLR alone in predicting brain metastasis according to the receiver operating characteristic (ROC) curve analysis (area under ROC curve, AUC 0.872 versus 0.784 versus 0.704). Pretreatment CEA and PLR are independent and significant risk factors for occurrence of brain metastasis in resected lung adenocarcinoma patients. Combining these two factors may improve the predictability of brain metastasis.

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