Добірка наукової літератури з теми "004.89: 621.396"

Abstract Background: Total lymphocyte count (TLC) has been shown to correlate with outcomes in patients (pts) with acute leukemia. The clinical correlation to TLC in pts with chronic myeloid leukemia in chronic phase (CML-CP) who were treated with a tyrosine-kinase inhibitor (TKI) is unclear. Methods: Lymphocyte data in pts with newly diagnosed CML-CP who were enrolled in consecutive or parallel clinical trials with front-line imatinib (IM), nilotinib (Nilo), or dasatinib (Dasa) were collected at the time of diagnosis, and 3 and 6 months (M) after the start of TKI. Relative lymphocytrosis (RLC) was defined as lymphocyte >150% at 3 or 6M compared with baseline at diagnosis. Absolute lymphocytosis (ALC) was defined as lymphocyte > 4,000 /µL at 3 or 6M after the start of TKI. Pts were assessed for response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS) based on ALC and RLC. The Kaplan-Meier method was used to calculate OS, EFS, TFS, and FFS. A log-rank test and Cox regression were used for univariate (UVA) and multivariate analysis (MVA), respectively. Results: A total of 483 pts were enrolled in this study: 271 in IM, 105 in Nilo, and 107 in Dasa. Patient characteristics and outcomes are summarized in Table 1. Median age at diagnosis was 48 years, and median follow-up was 85M and ongoing (5-154+). Time from diagnosis to start of TKI, Sokal risk score, and ALC at baseline between groups did not differ clinically. Of 481 pts, 93 (19%) developed RLC at 3 or 6M; IM, 38 (14%); Nilo, 23 (22%); Dasa, 32 (30%) (p= .001). ALC at 3 or 6M was observed in 15 (3%); IM, 3 (1%); Nilo, 1 (1%); Dasa, 11 (10%) (p<.001). Overall, cumulative incidence of complete cytogenetic response (CCyR) at 6M, major molecular response (MMR) at 12M, molecular response with 4.5 log reduction by IS (MR4.5) at 24M did not differ significantly between RLC and non-RLC (3 or 6M), or between ALC and non-ALC (3 or 6M). 5-y TFS, EFS and OS in ALC group were significantly worse than those in non-ALC group (p= .002, p=.016, p=.008, respectively). By UVA and MVA related to OS, age [p <.001; Hazard ratio (HR), 1.062; 95% confidence interval (95%CI), 1.036-1.089], presence of ALC at 3 or 6M [p = .028; HR, 10.948; 95%CI, 1.297-92.415], absence of MMR at 24M [p=.016; HR, 2.263; 95%CI, 1.165-4.393] were identified as adverse prognostic factors for OS. Conclusion: The presence of ALC ≥4,000/µL at 3 or 6M of TKI therapies is rare but is adversely associated with overall survival. Table 1. Patient Characteristics and Outcomes (N=483)a Overall [n= 481] IM [n= 271] Nilo [n= 105] Dasa [n= 107] Age, (year) 48 (15-85) 48 (15-85) 49 (17-82) 48 (16-83) Sokal Risk, No. (%) Low 334 (69) 175 (65) 79 (75) 80 (75) Intermediate 114 (24) 74 (27) 18 (17) 22 (21) High 32 (7) 20 (7) 8 (8) 4 (4) Time from diagnosis to start of TKI, (M) 0.9 (0-12.6) 1.0 (0-12.6) 0.5 (0-5.6) 0.7 (0.1-7.8) ALC at baseline, (/109L) 2.5 (0-86.6) 2.4 (0-16.7) 2.6 (0.4-9.2) 2.7 (0.3-86.6) Incidence of Relative Lymphocytosis, No. (%) At 3M 65 (14) 25 (9) 16 (15) 24 (22) At 6M 76 (16) 32 (12) 20 (19) 24 (22) Overall 93 (19) 38 (14) 23 (22) 32 (30) Incidence of Absolute Lymphocytosis, No. (%) At 3M 8 (2) 1 (0) 0 7 (7) At 6M 11 (2) 3 (1) 1 (1) 7 (7) Overall 15 (3) 3 (1) 1 (1) 11 (10) Outcomes of RLC and ALC at any time in each group, +/- (%/%) (p) <10% BCR-ABL/ABL at 3M RLC 36/40 (.596) 22/44 (.213) 50/37 (.280) 31/38 (.537) ALC 38/39 (.952) 0/42 (.394) 100/39 (.214) 36/35 (.952) Cumulative CCyR at 6M RLC 75/75 (.288) 50/66 (.063) 96/90 (.413) 90/87 (.628) ALC 67/75 (.711) 33/64 (.276) 0/92 (.001) 82/89 (.599) Cumulative MMR at 12M RLC 67/74 (.406) 53/70 (.030) 83/82 (.921) 72/74 (.903) ALC 60/73 (.488) 33/68 (.197) 0/83 (.033) 73/74 (.745) Cumulative MR4.5 at 24M RLC 46/52 (.564) 37/50 (.139) 57/55 (.889) 50/57 (.729) ALC 33/52 (.332) 33/48 (.610) 0/56 (.264) 36/57 (.252) 5-y FFS RLC 61/71 (.133) 56/69 (.167) 62/70 (.710) 61/74 (.285) ALC 50/69 (.076) 0/68 (<.001) 0/70 (<.001) 71/70 (.974) 5-y TFS RLC 90/93 (.369) 88/93 (.597) 91/88 (.115) 91/99 (.213) ALC 72/93 (.002) 67/93 (.014) 0/90 (<.001) 80/97 (.121) 5-y EFS RLC 80/86 (.213) 71/83 (.154) 84/87 (.450) 86/93 (.486) ALC 64/85 (.016) 33/82 (<.001) 0/87 (<.001) 80/92 (.574) 5-y OS RLC 89/93 (.068) 81/94 (.007) 100/84 (.126) 96/99 (.207) ALC 82/93 (.008) 67/93 (.001) 100/88 (.847) 83/99 (.040) a Two in IM and 1 in Dasa were not evaluable due to lack of differential data at 3 and 6M. Figure 1. OS in Pts with ALC Figure 1. OS in Pts with ALC Disclosures O'Brien: Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding.

Abstract Introduction: Evidence establishes that COVID-19 patients with DM2 are at increased risk for severe disease and worse outcomes. Peer reviewed data is sparse comparing glycemic control and clinical outcomes among COVID-19 patients with vs. without DM2, and thus we sought to address this gap. Methods: We selected patients at least 18 years old who expired or were discharged between March 16, 2020 through September 15, 2020. Principal analysis compared glycemic patterns among patients with DM2 vs. non-DM2. Median, coefficient of variation (CV), maximum and minimum glucose parameters were computed to characterize longitudinal glycemic patterns. Logistic regression modeling identified significant (p<.05) associations between composite outcome vs. glycemic parameters and putative risks for progression to severe COVID-19. Receiver operating characteristic (ROC) curve identified cut points for glycemic parameters. Cox regression models were employed to control for significant confounders. Continuous data summarized as median was compared using Kruskal-Wallis test. Discrete data were compared with Pearson’s chi-square test. Two-tailed p<.05 was significant. Results: Among 494 patients, 157 (32%) had DM2 with no intergroup differences in age (68 [56–79]), sex (52% male, 48% female), or race (68% Caucasian, 19% Other, 13% African American). Insulin was administered to DM2 (93%) and non-DM2 (54%) patients (p<.0001). Comorbidities were more prevalent in DM2, including cardiovascular (68% vs. 54%, p=.003), renal (72% vs. 52%, p<.0001) and obesity (51% vs. 38%, p<.0001). Markers including D-dimer (0.98 [0.61–1.95] mg/L), lactate dehydrogenase (308 [230–392] U/L), ferritin (436 [174–856] ng/mL), and triglycerides (172 [109–239] mg/dL), were not different in DM2 vs. non-DM2 (p>.05). CRP was greater in patients with (8.6 [3.6–14.6]) vs. without (6.1 [2.0–12.6]) DM2 (p=.005). Baseline glucose in DM2 (163 [121–253] mg/dL) vs. non-DM2 (107 [96–124] mg/dL) was significantly greater, with former an independent predictor of composite outcome (p=.0005). Cox modeling of other glucose parameters in DM2 vs. non-DM2 demonstrated various impact regarding risk for composite outcome including median (155 [128–209], p=.46) vs. (103 [94–118], p=.09); coefficient of variation (28 [19–38], p=.08) vs. (15 [9–20], p=.002); maximum (252 [187–362], p=.0005) vs. (129 [110–156], p=.002); and minimum (99 [79–128], p=.95) vs. (89 [81–98], p=.02). The unified baseline glucose cut point for composite outcome risk controlled for significant covariates was 138 gm/dL (p<.0001), which included respectively 20% and 10% of patients with and without DM2. Conclusion: Glycemic dysregulation in COVID-19 patients is independently associated with ICU admission and/or hospital mortality. Presence of DM2 amplifies glycemic dysregulation, but risk stratification appears warranted in all COVID-19 patients.

ObjectiveTo evaluate the cost–utility of 100 days of antibiotics in patients with chronic low back pain (LBP) and type I or II Modic changes included in the Antibiotic treatment In patients with chronic low back pain and Modic changes (AIM) study.DesignA cost–utility analysis from a societal and healthcare perspective alongside a double-blinded, parallel group, placebo, multicentre trial.SettingHospital outpatient clinics at six hospitals in Norway. The main results from the AIM study showed a small effect in back-related disability in favour of the antibiotics group, and slightly larger in those with type I Modic changes, but this effect was below the pre-defined threshold for clinically relevant effect.Participants180 patients with chronic LBP, previous disc herniation and Modic changes type I (n=118) or type II (n=62) were randomised to antibiotic treatment (n=89) or placebo-control (n=91).InterventionsOral treatment with either 750 mg amoxicillin or placebo three times daily for 100 days.Main outcome measuresQuality-adjusted life years (QALYs) by EuroQoL-5D over 12 months and costs for healthcare and productivity loss measured in Euro (€1=NOK 10), in the intention-to-treat population. Cost–utility was expressed in incremental cost-effectiveness ratio (ICER).ResultsMean (SD) total cost was €21 046 (20 105) in the amoxicillin group and €19 076 (19 356) in the placebo group, mean difference €1970 (95% CI; −3835 to 7774). Cost per QALY gained was €24 625. In those with type I Modic changes, the amoxicillin group had higher healthcare consumption than the placebo group, resulting in €39 425 per QALY gained. Given these ICERs and a willingness-to-pay threshold of €27 500 (NOK 275 000), the probability of amoxicillin being cost-effective was 51%. Even when the willingness-to-pay threshold increased to €55 000, the probability of amoxicillin being cost-effective was never higher than 53%.ConclusionsAmoxicillin treatment showed no evidence of being cost-effective for people with chronic LBP and Modic changes during 1-year follow-up.Trial registration numberClinicalTrials.gov NCT02323412.

Abstract Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.

There is some evidence that male gender could have a negative impact on the prognosis and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the present study was to compare the characteristics of coronavirus disease 2019 (COVID-19) between hospitalized men and women with confirmed SARS-CoV-2 infection. This multicenter, retrospective, observational study is based on the SEMI-COVID-19 Registry. We analyzed the differences between men and women for a wide variety of demographic, clinical, and treatment variables, and the sex distribution of the reported COVID-19 deaths, as well as intensive care unit (ICU) admission by age subgroups. This work analyzed 12,063 patients (56.8% men). The women in our study were older than the men, on average (67.9 vs. 65.7 years; p < 001). Bilateral condensation was more frequent among men than women (31.8% vs. 29.9%; p = 0.007). The men needed non-invasive and invasive mechanical ventilation more frequently (5.6% vs. 3.6%, p < 0.001, and 7.9% vs. 4.8%, p < 0.001, respectively). The most prevalent complication was acute respiratory distress syndrome, with severe cases in 19.9% of men (p < 0.001). In men, intensive care unit admission was more frequent (10% vs. 6.1%; p < 0.001) and the mortality rate was higher (23.1% vs. 18.9%; p < 0.001). Regarding mortality, the differences by gender were statistically significant in the age groups from 55 years to 89 years of age. A multivariate analysis showed that female sex was significantly and independently associated with a lower risk of mortality in our study. Male sex appears to be related to worse progress in COVID-19 patients and is an independent prognostic factor for mortality. In order to fully understand its prognostic impact, other factors associated with sex must be considered.

Background:BAFF, APRIL and BAFFR are genes that encode cytokines with a key role in the development and survival of B-lymphocytes [1-4]: The B cell-activating factor (BAFF, also known as BLyS), a proliferation-inducing ligand (APRIL) and BAFF receptor (BAFF-R), respectively. Previous genetic studies have revealed that the BAFF-APRIL-BAFFR pathway is implicated in the genetic predisposition to several immune-mediated diseases [5].Objectives:To determine whether the BAFF-APRIL-BAFFR pathway represents a novel genetic risk factor for the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory disease in which IgA deposits and B-lymphocytes are crucial [6, 7].Methods:A functional BAFF polymorphism (rs374039502) and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients (the largest series of Caucasian patients with IgAV ever assessed for genetic studies) and 806 sex and ethnically matched healthy controls by TaqMan assays.Results:No statistically significant differences in the genotype and allele frequencies between patients with IgAV and healthy controls were observed when each genetic variant of BAFF APRIL and BAFFR was analyzed independently (Table 1). Likewise, no statistically significant differences in genotype and allele frequencies of BAFF APRIL or BAFFR were found when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Similar results were disclosed when haplotype frequencies of APRIL and BAFFR were compared between patients with IgAV and healthy controls as well as patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations.Conclusion:Our results suggest that the BAFF-APRIL-BAFFR pathway does not contribute to the genetic network underlying IgAV.References:[1]J Exp Med 1999;190:1697-710; [2] Science 1999;285:260-3; [3] Nat Genet 2005;37:829-34; [4] Nat Immunol 2002;3:822-9; [5] N Engl J Med 2017;376:1615-26; [6] N Engl J Med 2013;368:2402-14; [7] Autoimmun Rev 2018;17:301-315.Table 1.Genotype and allele frequencies of BAFF, APRIL and BAFFR genes in patients with IgA vasculitis and healthy controls.PolymorphismLocus1/2Data set1/11/22/212rs374039502BAFFT/APatients91.9 (353)8.1 (31)095.9 (737)4.1 (31)Controls91.5 (733)8.1 (65)0.4 (3)95.6 (1531)4.4 (71)rs11552708APRILG/APatients78.1 (299)20.6 (79)1.3 (5)88.4 (677)11.6 (89)Controls77.9 (625)20.4 (1641.6 (13)88.1 (1414)11.9 (190)rs6608APRILC/TPatients71.9 (277)26.0 (100)2.1 (8)84.9 (654)15.1 (116)Controls70.0 (561)27.6 (221)2.5 (20)83.7 (1343)16.3 (261)rs7290134BAFFRA/GPatients58.0 (224)36.3 (140)5.7 (22)76.2 (588)23.8 (184)Controls57.2 (459)36.4 (292)6.5 (52)75.3 (1210)24.6 (396)rs77874543BAFFRG/CPatients82.7 (316)16.0 (61)1.3 (5)90.7 (693)9.3 (71)Controls83.0 (666)16.6 (133)0.4 (3)91.3 (1465)8.7 (139)Acknowledgements:This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CM20/00006]; SR-M is supported by funds of the RETICS Program co-funded by the European Regional Development Fund (ERDF) [grant number RD16/0012/0009]; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; BA-M is a recipient of a `López Albo´ Post-Residency Programme funded by Servicio Cántabro de Salud; LL-G is supported by funds of IDIVAL [grant number INNVAL20/06]; RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CP16/00033].Disclosure of Interests:Diana Prieto-Peña Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Verónica Pulito-Cueto: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Leticia Lera-Gómez: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, J. Narváez: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda-Filloy: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Javier Sanchez Perez: None declared, Diego de Argila: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galindez: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Miguel A González-Gay Speakers bureau: Pfizer, Abbvie, MSD, Grant/research support from: Pfizer, Abbvie, MSD, Raquel López-Mejías: None declared

Background There have been well-documented implications of race/ethnicity on the outcome of various vascular diseases. Little literature has examined the effect of race/ethnicity on venous disease. Iliac vein stenting is an emerging technology in treating chronic venous insufficiency. To further characterize this disease and its treatment, we chose to study the effect of selected clinical factors including race/ethnicity on the early complications of non-thrombotic iliac vein stenting. Methods In this observational study, data analysis was performed for 623 patients with chronic venous insufficiency who underwent iliac vein stenting during the time period from August 2012 to September 2014. Patients were categorized by Caucasians ( n = 396), African Americans ( n = 89), Hispanics ( n = 138), and others ( n = 23). These were correlated with the age, gender, presenting sign according to CEAP classification, percentage of iliac vein stenosis, post-operative thrombosis and pain score. Pain score was obtained post-operatively on a Likert scale of 0–10. Follow-up was performed after completion of the procedure, through post-operative visits and duplex exams every three months for the first year. Statistical analysis was performed using Chi-square and Student’s t-test, Pearson’s test and multivariate regression. Results The average age of the study patients was 67.8 years (age range 23–96 years, ± 14.2 SD). Sixty-seven patients were women. The presenting sign according to CEAP classification was (C3 = 331, C4 = 175, C5 = 51, C6 = 66). The average pain score was 2.6 (±2.9 SD). The average degree of stenosis was 64.9% (±3.8 SD). There were insufficient numbers in the “other” race/ethnicity group for further analysis. The number of patients with iliac vein stent thrombosis was 14 (2.2%). When analyzing each race/ethnicity in our dataset with univariate analysis, we found that Caucasians were significantly older than the African Americans and Hispanics ( P < 0.0001). There tended to be more women in the Caucasian group as compared to the Hispanics ( P = 0.04). There were no differences in presenting sign according to CEAP classification or degree of stenosis between the three groups. Hispanics tended to have higher pain scores post-operatively than Caucasians ( P = 0.01). It was found that 1.8% of Caucasians, 3.4% of African Americans and 2.9% of Hispanics had post-operative iliac vein stent thrombosis ( P = 0.55). Men have higher CEAP score than women regardless of race/ethnicity ( P = 0.0001). On the other hand, women tended to have higher pain score than men ( P = 0.04). There were no differences between men and women regarding age, degree of stenosis, and stent thrombosis. Linear multivariate regression test and Pearson’s test revealed that age is inversely related to pain score ( P < 0.0001). ANOVA multivariate regression statistical analysis showed no relation between race/ethnicity and pain score ( P = 0.98), and one-way ANOVA showed that the Caucasians were the eldest ethnic group in the study ( P < 0.0001). Linear multivariate regression test and Pearson’s correlation test revealed that race/ethnicity is not correlated with thrombosis of iliac vein after stenting ( P = 0.8). Conclusion Race/ethnicity is not significantly associated with CEAP score, degree of iliac vein stenosis, or post-operative thrombosis or pain scores. Age was inversely associated with pain score after iliac vein stenting.

Background:Cardiovascular (CVS) diseases are the leading cause of death worldwide and patients with rheumatic diseases have an increased CVS risk including stroke and myocardial infarction (MI) (1-3). CVS risk factors and CVS events are common in SpA (4). Delineating the CVS risk and the association with medications in patients with SpA would be useful.Objectives:The objective of this study was to delineate the CVS risk and the association with medications in patients with SpA.Methods:Patients with SpA and patients with non-specific back pain (NSBP) were identified in rheumatology and orthopedics clinics respectively. Clinical information and CVS events were retrieved. Incidence rates were calculated. Association analysis was performed to determine the CVS risk of SpA and other modifiable risk factors.Results:A total of 5046 patients (SpA 2616 and NSBP 2430) were included from eight centers. Over 56 484 person-years of follow-up, 160 strokes, 84 MI and 262 major adverse cardiovascular events (MACE) were identified. Hypercholesterolemia was more prevalent in SpA (SpA 34.2%, NSBP 28.7%, P<0.01). Crude incidence rates of stroke and MI were higher in SpA patients. SpA was associated with a higher risk of MACE (HR 1.66, 95%CI 1.22-2.27, P<0.01) and cerebrovascular events (HR 1.42, 95%CI 1.01-2.00, p=0.04). The use of anti-tumor necrosis factor (TNF) drugs was associated with a reduced risk of MACE (HR 0.37, 95%CI 0.17-0.80, P=0.01) and cerebrovascular events (HR 0.21, 95%CI 0.06-0.78, P=0.02).Conclusion:SpA is an independent CVS risk factor. Anti-TNF drugs were associated with a reduced CVS risk in these patients.References:[1]Crowson CS, Liao KP, Davis JM, 3rd, Solomon DH, Matteson EL, Knutson KL, et al. Rheumatoid arthritis and cardiovascular disease. Am Heart J. 2013;166(4):622-8 e1.[2]Verhoeven F, Prati C, Demougeot C, Wendling D. Cardiovascular risk in psoriatic arthritis, a narrative review. Joint Bone Spine. 2020;87(5):413-8.[3]Liew JW, Ramiro S, Gensler LS. Cardiovascular morbidity and mortality in ankylosing spondylitis and psoriatic arthritis. Best Pract Res Clin Rheumatol. 2018;32(3):369-89.[4]Molto A, Etcheto A, van der Heijde D, Landewe R, van den Bosch F, Bautista Molano W, et al. Prevalence of comorbidities and evaluation of their screening in spondyloarthritis: results of the international cross-sectional ASAS-COMOSPA study. Ann Rheum Dis. 2016;75(6):1016-23.Disclosure of Interests:None declared.

Abstract Background: To describe the clinical characteristics (CC) and survival predictors in NHL pts at a VA medical center. Methods: We performed a retrospective chart review of all pts diagnosed with Non Hodgkin’s lymphoma at the VANJHCS from January 1, 1997 through December 31, 2006. Records were reviewed for demographic, clinical, pathological data and survival. Statistical analyses were performed using STATA. The study was approved by the IRB. Results: 1. Clinical characteristics. There were 92 pts, with 57 deaths(62%). The median (M) age was 62 years (range 27–89). The race distribution was Caucasian 66(72.5%), African American 19(21%), other (6, 6.5%). The overall M survival (MS) was 698 days(13–3825). The M Hemoglobin(Hgb) was 12.3 g/dl (7.3–17.4) The M LDH was 203 IU/L(88–1905). The M Albumin was 3.6 g/dl (1.2–5.4). Beta 2 microglobulin (B2M) and HIV status were not available on all patients. The M Zubrod Performance Status (PS) was 1(0–4). The PS for 46 pts (50%) was 1(0–4). By Ann Arbor Stage, 44 pts(49%) were in stage I–II, and 46 pts(51%) had stages III–IV. MS for pts in stage I–II were 887.5(range 13–3713) days and 552(range 22–3825) days in stages III–IV. 2. Survival by histology is summarized in the accompanying table. Histological categories were low grade (CLL, follicular, MALT, marginal zone), diffuse large cell lymphoma, mantle cell lymphoma (MCL) and other(2 pts). The most common class of pts was low grade 49(53%), followed by intermediate 34(36.9%) and mantle cell lymphoma 9(9.7%). 3. Clinical Prognostic indicators: Charlson Comorbidity Index (CMI), the International Prognostic Index (IPI) and the Follicular Lymphoma International Prognostic Index (FLIPI) scores were tabulated. For pts with intermediate lymphoma, the M IPI score was 3 (range 0–5), and for low grade lymphoma M IPI score 2 (0–5). The 47 pts with low grade lymphomas had median FLIPI score of 1 (0–4). The M CMI was 6(1–12). 4. For all pts, univariate predictors of survival were lymphoma class, hemoglobin, PS, LDH, albumin. The IPI was a significant predictor on univariate analysis. In multivariate analysis, the PS(p<0.02), Albumin (p<0.02), CMI (p<0.05), LDH (p<0.06) and lymphoma class (p<0.02) were significant predictors. For low grade lymphoma pts, univariate predictors were LDH, albumin, IPI, and PS, but not the FLIPI. On multivariate analysis, the predictors were PS (p<0.02), and albumin (p<0.018). For intermediate grade lymphoma pts, univariate predictors were albumin, but not the IPI. On multivariate analysis, the PS (p<.006), albumin (p<0.03), and CMI (p<.02) were significant predictors. Conclusions: In this sample, prognostic factors differed for low grade and intermediate grade lymphomas. IPI did not predict survival in intermediate lymphoma pts. Comorbidity emerged as a potential prognostic factor for pts with intermediate grade lymphomas. The VA provides care for a large veteran population characterized by low socioeconomic status and higher comorbidity. These findings should be confirmed in larger VA and general populations. Survival by Histology Lymphoma type Number of pts Median survival(days) Range(days) Diffuse large 32(37%) 466 17–3402 CLL 14(15%) 1711 25–3541 Follicular 19(20%) 943 13–3825 Mantle cell 9(10%) 748 62–1231 Marginal zone 8(9%) 627 197–2686 MALT 8(9%) 1311 393–3194

Abstract Introduction: MCL is a mature B-cell neoplasm characterized by t(11;14) (q13;q32) and cyclin D1 (CCND1) overexpression. Molecular studies have revealed other alterations in cell-cycle regulation, DNA damage response and cell survival pathways, with a landscape of somatic mutations being recently identified. CNS involvement is a well known complication, occurring in 4-26% of MCL at five years, with an ominous significance. Although different clinical variables have been identified as risk factors for CNS infiltration, the biological parameters related to this complication have not been extensively studied. The aim of the study was to explore the biological parameters associated with CNS involvement in a multicentre and retrospective series of MCL patients. Patients and Methods: 285 patients (M:74%; 64 yr) diagnosed of MCL between 1990-2014 (median survival of 4 years) were analysed. In addition to standard clinico-biological variables, IGHV mutational analysis, chromosomal alteration studies and Sanger sequencing of NOTCH1, NOTCH2, TP53, BIRC3, WHSC1, MEF2B, MLL2, TLR2 and PRDM1 were performed. Results: CNS involvement was observed in 15/285 MCL patients (5.2%), with a 5-yr risk of 9.1% (95%CI: 4.6-13.6), one patient at diagnosis, and at first or second/ulterior progressions in 7 cases each. The clinical, pathological and molecular risk factors identified are detailed in the Table. In addition to what has been already described, CNS involvement was usually observed in MCL cases with a clinical nodal presentation (p=0.05). In fact, no indolent MCL with a non-nodal presentation developed this complication during the follow-up period. No differences were observed in the risk of CNS involvement between patients treated in first-line with conventional or high-dose intense treatment (5-yr risk: 6.1%+/-6% vs. 10.7%+/-10.6%, p=ns). Regarding the biological features, no differences in terms of the IGHV mutational status were observed in cases developing CNS involvement compared to the others (75% vs. 68.7%, using 97% identity cut-off). Similarly, the IGHV gene usage of CNS involved cases corresponded to the more frequent IGHV genes observed in MCL (usually IGHV1-18, IGHV3-23, IGHV4-34, IGHV4-59). Although not significant, a predominance of high number copy number alterations (CNA) (>4) could be observed in the genetic study of MCL cases with CNS involvement as could be expected for the enrichment in blastoid variants (up to 50% of these cases). In fact, we did not observe any case with CNS involvement among those cases with 3 or less CNA. CNS involvement was not related to common poor prognosis genetic alterations such as 9p, 11p and 17p losses, but the presence of 8q gains was associated with a higher risk of CNS involvement (p=0.05). We did not find any significant association between CNS involvement and the large number of oncogenic mutations studied. Conclusions: CNS involvement in MCL is associated with initial aggressive clinico-biological characteristics. Non-nodal MCL cases with a low number of genetic alterations did not present CNS involvement. Finally, the presence of 8q gains was associated with a higher risk of CNS infiltration. Table Initial Clinical Features Category N 5 yr-CNS involvement (%, 95%CI) HR p Performance status (ECOG) > 1 8/51 41.5 (+/-28) 4.2 .003 ≤ 1 7/128 9.4 (+/-5.5) Nodal disease Yes 14/185 13.3 (+/-7.6) 6.1 .05 No 1/77 1.4 (+/-2.7) Hemoglobin (g/L) < 105 12/93 24.7 (+/-14.7) 3.2 .05 ≥ 105 3/78 5.3 (+/-6.3) LDH > ULN 4/89 27.1(+/-19.4) 6.7 <.001 < ULN 11/137 5.6 (+/-6.3) B2microglobulin > ULN 11/114 21.6 (+/-14.9) 3.5 .04 < ULN 3/66 8.7(+/-10) Molecular & Pathological data Histological variant Blastoid 6/58 17.3 (+/-13.7) 3.5 .02 Others 8/156 1.3 (+/-7.2) Ki-67 > 30% 5/44 17.5 (+/-14.9) 3.6 .06 ≤ 30% 3/61 6.7 (+/-9.4) SOX11 Positive 8/153 2.9 (+/- 5.7) 2.6 ns Negative 1/42 2.1 (+/-2.4) IGHV ≥97% 6/109 9.5 (+/-9.6) 1.9 ns <97% 2/49 6 (+/-8.2) CNA > 4 2/87 3.9 (+/-5.7) 1.1 ns ≤ 4 1/44 2.3 (+/-4.3) Chromotripsis Yes 1/17 12.5 (+/-22) 3.2 ns No 2/106 1.9 (+/-2.7) 8q gain Yes 2/30 13.1(+/-19) 7.5 .05 No 2/97 1 (+/-1.96) CNA: copy number alteration; IGHV: immunoglobulin heavy chain; LDH: Lactate dehydrogenase Disclosures No relevant conflicts of interest to declare.