Journal articles on the topic '(477.54) "1917'

Background The current advancement and increasing use of diagnostic imaging has led to increased detection of abdominal aortic aneurysms (AAA). Many of these patients are unfit for elective AAA surgery. Aim To investigate the outcome of conservative management of unfit patients with large AAA (>5.5 cm) who are turned down for elective surgical intervention. Patients and methods Between January 2006 and April 2017, 457 patients presented with AAA >5.5 cm. Seventy-six patients (M: F 54:22) were deemed unfit for elective repair. Mean age was 79.8 years (range 64–96). Mean AAA size was 60.22 mm (55–83). Results Forty-nine of the 76 patients (64%) had died by April 2017. Fifteen (19.7%) patients died directly because of their aneurysm rupture. A further 34 (44.7%) patients died from non-aneurysm-related causes. Conclusion Patients with large AAA deemed unfit for elective surgery have an overall poor prognosis and die mainly from other causes than AAA. Surgical intervention when rupture occurs results in poor survival.

Context.— Biomedical terminologies such as Logical Observation Identifiers, Names, and Codes (LOINC) were developed to enable interoperability of health care data between disparate health information systems to improve patient outcomes, public health, and research activities. Objective.— To ascertain the utilization rate and accuracy of LOINC terminology mapping to 10 commonly ordered tests by participants of the College of American Pathologists (CAP) Proficiency Testing program. Design.— Questionnaires were sent to 1916 US and Canadian laboratories participating in the 2018 CAP coagulation (CGL) and/or cardiac markers (CRT) surveys requesting information on practice setting, instrument(s) and test method(s), and LOINC code selection and usage in the laboratory and electronic health records. Results.— Ninety of 1916 CGL and/or CRT participants (4.7%) responded to the questionnaire. Of the 275 LOINC codes reported, 54 (19.6%) were incorrect: 2 codes (5934-2 and 12345-1) (0.7%) did not exist in the LOINC database and the highest error rates were observed in the property (27 of 275, 9.8%), system (27 of 275, 9.8%), and component (22 of 275, 8.0%) LOINC axes. Errors in LOINC code selection included selection of the incorrect component (eg, activated clotting time instead of activated partial thromboplastin time); selection of panels that can never be used to obtain an individual analyte (eg, prothrombin time panel instead of international normalized ratio); and selection of an incorrect specimen type. Conclusions.— These findings of real-world LOINC code implementation across a spectrum of laboratory settings should raise concern about the reliability and utility of using LOINC for clinical research or to aggregate data.

e17081 Background: Biomarkers to select mRCC patients most likely to benefit to immunotherapy are needed. The retrospective multicentre Meet-URO-15 study evaluated the prognostic role of peripheral blood cells in mRCC patients treated with Nivolumab. Methods: Complete blood count was assessed at the first four cycles of Nivolumab. The primary endpoint was median overall survival (mOS) according to bNLR. NLR was defined as neutrophil / lymphocyte (cutoff = 3) and ΔNLR the difference between NLR at 2nd cycle and bNLR (median as cutoff = 1.1). Results: From October 2015 to October 2019, 470 patients started Nivolumab as 2nd (67%), 3rd (22%) and > 3rd (11%) line. Median age was 66 years, 71% were male and 83% had clear cell histology. Baseline IMDC group was favorable in 25%, intermediate in 63% and poor in 12%. Lymph-nodes, visceral and bone metastases were present in 54%, 91% and 36%. mOS and progression-free survival (PFS) were 34.8 and 7.5 months. Overall response rate (ORR) and disease control rate (DCR) were 30% and 61%. bNLR was available in 404 patients: bNLR < 3 (54%) correlated with statistically significant longer PFS [11.4 vs 5.4 months; HR 1.69 (1.33-2.15)] and OS [46.2 vs 17.2 months; HR 2.37 (1.72-3.26)] (both p< 0.001), with similar ORR (35% vs 30%, p= 0.28) but higher DCR (71% vs 52%, p< 0.001). ΔNLR was available in 360 patients: ΔNLR < 1.1 (73%) correlated with a statistically significant improvement of PFS [11.2 vs 4.9 months; HR 1.53 (1.16-2.03), p= 0.03], OS [Not Reached vs 19.7 months; HR 1.83 (1.28-2.61), p= 0.001], ORR (37% vs 23%, p= 0.011) and DCR (68% vs 53%, p= 0.008). Multivariate analyses adjusted for IMDC group, line of therapy and metastatic sites, confirmed the statistically significant correlation of bNLR and ΔNLR with OS, PFS and DCR. Conclusions: Our study showed the statistically significant correlation of lower bNLR and early ΔNLR with longer OS, PFS and higher DCR in mRCC patients treated with Nivolumab.

Objetivou-se neste estudo diagnosticar o estado nutricional da Equipe Olímpica Permanente de Levantamento de Peso do Comitê Olímpico Brasileiro (COB). A amostra foi composta por 24 atletas, na faixa etária entre 16 e 23 anos, sendo 12 do sexo masculino (19,7 ± 2,4 anos) e 12 do feminino (19,2 ± 1,8 ano). Realizou-se o seguinte procedimento para o diagnóstico do estado nutricional: análise da adequação da ingestão de energia e dos macronutrientes - carboidratos (CHO), lipídios (LIP) e proteínas (PRO) -, por meio dos métodos Recordatório de 24 horas e Questionário de Freqüência de Consumo Alimentar, além da caracterização do perfil antropométrico. Os resultados da avaliação dietética indicaram que a distribuição energética entre os macronutrientes encontra-se adequada sendo de 54 ± 6,8% (CHO); 28,5 ± 5,9% (LIP); e 14,5 ± 3,4% (PRO) para os homens e 56,3 ± 4,7% (CHO); 28,6 ± 4,6% (LIP); e 13,7 ± 2,4% (PRO) para a equipe feminina. Entretanto, quanto ao consumo energético total, 83% dos atletas estavam com ingestão energética abaixo dos valores recomendados, considerando o alto nível de atividade física, promovendo deficiência calórica diária. O percentual de gordura corporal dos atletas do sexo masculino (3,6 ± 0,7%) indicou que todos estavam abaixo do padrão de referência, enquanto 58% dos esportistas do sexo feminino apresentavam excesso de gordura (17,9 ± 5,8%). Tem-se, como conclusão, que, apesar de os desportistas avaliados terem realizado distribuição energética adequada entre os macronutrientes, esta ainda não foi suficiente para suprir as exigências energéticas da modalidade, necessitando assim de orientação nutricional.

Background: Menopause, the point in a woman’s life when permanent cessation of cyclical menstruation occurs for a period of 12 months due to the loss of ovarian activity marking the end of reproductive lifespan and potential. Natural menopause is a physiological event, universal women phenomenon and irreversible part of the entire normal aging process. It brings the menopausal woman for preventive health care services due to its associated health implications. This study sought to investigate the age at menopause and its correlates in southern Nigerian women.Methods: A cross-sectional survey of datasets of women from two different communities attending annual religious conference was conducted using tested semi-structured researcher-administered questionnaire in 2019.Results: Data was analyzed on 152 participants from an urban and a rural communities. Mean chronological age was 58.8±8.8 years and parity was 6.4±2.2. Mean age at menopause was 50.0±4.6 years, median (IQR) 50.0 (47-53) and 49.2±4.7 versus 50.5±4.5 and median (IQR) 49.5 (46-51) and 50.5 (47-54) for urban and rural participants respectively. 1.3%, 9.2%, 69.7% and 19.7% were premature, early, normal and late onset menopause respectively. Risk of early onset menopause was insignificantly increased by higher education, social class, lower BMI and low parity. Forgetfulness (20.3%), irritability (19.5%), hot flushes (17.3%) and insomnia (16.5%) were the leading symptoms. Main complications were chronic hypertension 62 (40.8%), diabetes mellitus 12 (7.9%) and 4 (2.6%) recent fractures.Conclusions: Age at menopause was moderate, early menopause was rather high, programmed preventive healthcare services should address modifiable risk factors. Cancer screening services for late onset women is equally crucial.

Background: COVID-19 pandemic has challenged the healthcare resources globally, inspiring the need for identifying simple, economical biomarkers. COVID-19 is an immune-inflammatory disorder and systemic inflammatory index (SII) derived from the peripheral blood has been proposed as a marker.Methods: Retrospective study of severe COVID-19 hospitalized patients (total N=154 including diabetic subset N=57). Data regarding hematological variables such as absolute neutrophil count (ANC), absolute lymphocyte count (ALC), platelet count along with thrombo-inflammatory proteins, D-dimer, C-reactive protein (CRP) were extracted from medical records. SII was calculated from ANC×platelets/lymphocyte count. Clinically applicable cut-offs were derived using the receiver operating characteristic curve (ROC) analysis for SII, CRP and D-dimer. Correlations between hematological parameters and D-dimer, CRP were analyzed to validate them as biomarkers of thrombo-inflammation and as predictors of clinical outcome.Results: Among 154 severe COVID-19 patients, significant association with mortality was seen with respect to ANC (p<0.001), SII (p=0.01), CRP (p=0.004) and D-dimer (p=0.001). In the total COHORT, based on ROC curve, applicable cut-off for outcome prediction were for SII 14.85×105 (area under curve (AUC)-0.691, sensitivity-67%, specificity-64%,odds ratio (OR)-3.44), CRP 19.7 mg/l (AUC-0.718, OR-5.71), D-dimer 0.285 mcg/ml (AUC-0.773, OR-6.94) respectively. In the diabetic subset, the cut-offs for SII 14.85×105 (AUC-0.68, sensitivity-80%, specificity-54%, OR-4.7), CRP 52.5 mg/l (AUC-0.723, OR-5.36) and D-dimer 0.285 mcg/ml (AUC-0.771, OR-11.3) respectively.Conclusions: Clinically applicable thresholds for SII serve as reliable biomarkers of thrombo-inflammation and prognosis in severe COVID-19 patients. Diabetic patients with similar thresholds had higher risk and prediction for mortality. In the resource constrained health care settings, who might not afford D-dimer, SII may serve as an economical bio-maker.

Abstract Background. OM is a common toxicity of conditioning regimens for HSCT that has been associated with adverse clinical and economic outcomes. Methods. A retrospective chart review study of ~400 consecutive HSCT recipients was undertaken at a single academic center. OM severity was assessed across eight oropharyngeal sites using a validated scale which was scored as follows: no erythema/ulceration = 0; erythema only = I; ulceration one site = II; two sites = III; three sites= IV; and four or more sites = V. OM assessments began on the day of conditioning and continued bi-weekly until hospital discharge. Outcomes of interest included number of days of fever, total parenteral nutrition (TPN), and parenteral narcotic therapy, incidence of grade III or IV (Common Toxicity Criteria) infection, and inpatient days and charges. We report data here for the 115 MM patients in the study cohort who underwent AU HSCT after high-dose MP conditioning. Results. Mean age was 54 yrs. Seventeen percent of patients received total body irradiation. Bone marrow was the source of most grafts. Forty-eight percent of patients experienced OM ≥ grade II. The relationship between worst recorded grade of OM and each of the outcomes of interest is reported below. Conclusions. OM is associated with worse clinical and economic outcomes in MM patients undergoing AU HSCT following high-dose MP conditioning. Outcomes of AU HSCT following high-dose MP conditioning for MM, by worst recorded grade of OM Worst Grade of OM (N=115) 0 I II III IV V *mean, SD; **test for linear trend; Cochran-Armitage for dichotomous measures, GLM for continuous measures Outcome n=37 n=23 n=24 n=15 n=8 n=8 -value p Fever days* 1.2 (2.8) 2.5 (3.1) 2.1 (2.3) 1.9 (1.4) 3.0 (2.1) 3.6 (6.2) 0.057 TPN days* 0.0 (0.0) 0.1 (0.4) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) 2.3 (6.0) 0.003 Narcotic days* 1.5 (3.1) 4.7 (3.8) 4.6 (4.4) 4.4 (3.7) 7.9 (3.3) 9.9 (7.4) <0.001 Infection, % 51.4 73.9 62.5 80.0 100.0 75.0 0.014 Mortality, % 0.0 0.0 4.2 0.0 0.0 12.5 0.085 Inpatient days* 18.6 (3.4) 21.0 (3.5) 19.6 (3.6) 19.7 (2.3) 23.3 (2.4) 23.4 (5.6) <0.001 Inpatient charges* (x 1,000 USD) 119 (36) 130 (35) 118 (25) 121 (28) 141 (31) 184 (92) <0.001

Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting the musculoskeletal system as well as skin and nails. The prevalence of depression in psoriasis and PsA is high and ranges from 7-40% [1]. Persistent depressive mood may influence disease activity outcome in PsA, especially patient-reported outcomes.Objectives:To assess the correlation of depressive symptoms with PsA-specific outcome parameters.Methods:RABBIT-SpA is a prospective longitudinal cohort study including PsA patients enrolled at start of a new conventional treatment or b/tsDMARD treatment. In regularly provided follow-up questionnaires, physician- and patient-reported information on the disease course including the depression screening tool WHO-5 to assess mental health is collected. For the current analysis, the WHO-5 score was categorised into 4 groups using validated cut-offs: severe depressive symptoms <13, moderate depressive symptoms 13-28, mild depressive symptoms 29-50, well-being >50. Spearman correlation coefficient was calculated to analyse the relationship between the WHO-5 score and various PsA related outcome parameters.Results:936 PsA patients were included. Baseline characteristics are shown in Table 1. In 411 patients (43.9%) the WHO-5 score indicated well-being, 249 (26.6%) had mild depressive, 203 (21.7%) moderate depressive and 73 patients (7.8%) severe depressive symptoms. WHO-5 results correlated with patient reported skin involvement (DLQI: -0.25, patient assessment skin: -0.17), and the composite scores DAPSA (-0.33) and DAS28 (-0.28) as well as with patient reported pain (-0.43) and patient global disease assessment (-0.42). The highest correlation was found for physician assessed global health status (-0.51) and PSAID (-0.62). No significant correlation was found with CRP, swollen joint count and physician assessed skin involvement including body surface area (BSA).Table 1.Baseline characteristics of patients included in the analysis stratified by WHO-5 categories.ParameterWHO-5 (<13) severeN=73WHO-5 (13-28) moderateN=203WHO-5 (29-50) mildN=249WHO-5 (>50) well-beingN=411TotalN=936Age, mean (SD)52.6 (11.4)51 (11.3)51.4 (12.5)52.8 (12.7)52 (12.2)Female, n (%)52 (71.2)127 (62.6)157 (63.1)227 (55.2)563 (60.1)Disease duration, years, mean (SD)8.3 (8.7)6 (7.9)6.2 (6.7)6.4 (7.5)6.4 (7.5)Dactylitis, n (%)14 (19.7)31 (15.5)46 (18.5)77 (18.8)168 (18.1)Axial involvement, n (%)14 (19.7)54 (26.9)49 (19.7)71 (17.3)188 (20.2)Nail involvement, n (%)34 (47.2)85 (42.3)106 (42.6)158 (38.6)383 (41.1)BMI>=30, n (%)37 (51.4)75 (37.1)98 (39.5)125 (30.9)335 (36.2)CRP of >=5 mg/L, n (%)33 (51.6)84 (45.4)99 (46.5)138 (39.1)354 (43.4)BSA (0-100), mean (SD)10.1 (18.3)9.5 (16.8)8.5 (14.9)8.1 (14.6)8.7 (15.5)Physician assessed global health (NRS 0-10), mean (SD)6.3 (1.5)5.6 (1.8)5.2 (1.7)4.9 (1.9)5.2 (1.9)TJC68, mean (SD)9.9 (7.1)8.6 (7.6)8.2 (7.6)7.3 (8.2)8 (7.8)SJC66, mean (SD)6 (5.2)4.8 (4.9)4.7 (4.4)4.3 (3.8)4.6 (4.4)DAPSA, mean (SD)29.3 (11.1)25.1 (12.9)23.4 (12.1)18.9 (12.4)22.3 (12.8)DAS28-CRP, mean (SD)4.1 (1)3.8 (1.2)3.7 (1.1)3.2 (1.1)3.6 (1.2)Patient assessed global health (NRS 0-10), mean (SD)7.9 (2.1)6.6 (2.1)5.9 (2)4.8 (2.3)5.7 (2.4)Patient assessed pain (NRS 0-10), mean (SD)7.8 (1.8)6.4 (2.1)5.8 (2)4.6 (2.4)5.5 (2.4)DLQI (0-30), mean (SD)8.5 (8.2)7.8 (7.2)5.4 (5.7)4.1 (4.9)5.6 (6.2)PSAID (0-10), mean (SD)6.9 (1.8)5.5 (1.8)4.4 (1.7)3 (1.7)4.2 (2.2)Conclusion:The impact of depressive symptoms on outcome parameters used in rheumatology is increasingly being recognised. Interestingly, direct measures of inflammatory disease activity of joint and skin disease such as BSA, CRP, and swollen joint count were not correlated with depressive symptoms. The highest correlation was found for broader assessments like global health status and PSAID.References:[1]Haugeberg et al. Arthritis research & Therapy, 2020, 22:198Acknowledgements:RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris.We thank all participating rheumatologists and patients.Disclosure of Interests:Anne Regierer Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris., Anja Weiß Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris., Martin Bohl-Buehler: None declared, Xenofon Baraliakos: None declared, Frank Behrens: None declared, Georg Schett: None declared, Anja Strangfeld Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris.

This research is a part of the analysis of the collection of articles of the Latvian Literary Society (Lettisch-literärische Gesellschaft) Magazin, herausgegeben von der Lettisch-Literärischen Gesellschaft (so-called “Magazin”) with special emphasis to the materials important in the history of Latvian language, especially, of the development of terminology in Latvian. This paper deals with the almost forgotten author Pēteris Zēvalds (Peter Seewald) (ca. 1838/1839–1910), a schoolteacher in Jelgava (Mitau) and active contributor of “Magazin” from 1865 to 1877. In 12 sequels (published in eight issues of “Magazin”), he collected 2198 words and expressions from his native place, now Birzgale parish, originally, from the private manor in Linde parish (aus Privatgut Lindenschen Gemeinde in Kurland)). This paper provides a more detailed analysis of two other word collections (both published in 1874 in issue 3 of XV volume of “Magazin”) of Zēvalds. They contained current lexis, including a lot of new terms. The first one is created as a successive excerpt of neologisms and lesser-known words (in Latvian-German comparison) from the weekly newspaper “Baltijas Vēstnesis” (using numbers 44th, 48th, 49th un 51st from 1872 and successive first 49 from 1873, excl. number 9th). There are 467 numbered entries or 495 words in total. Most of the words in Zēvalds’s collection are related to terminological lexis. They can be divided into four groups (indicating the serial number used in the original): (1) terms currently used in the same form or with minor changes of ending (7. greizsirdība, 29. pilnvare, 41. māksla, 33. cēlons, 69. veicināšana, 88. pirmvaloda, 237. izvilktne (= atvilktne), 275. viels); (2) terms which have a different correspondence in modern Latvian (32. valodas=iztirzāšana (= valodniecība), Sprachforschung; 49. lietuve (= lejkanna), Gieskanne; 54. rakstiens (=raksts, dokuments), Schriftstück; 183. atvēles=zīme (= atļauja), Erlaubnißschein; 187. jūras=pāržmauga (= jūrasšaurums), Meerenge); (3) words, that could still be considered as potential terms (11. tiesas=laulība, Zivilehe; 37. sauljumte, Sonnenschirm) and (4) those, which, from the moment of fixation, can be considered occasional words (43. spīdgans, Sternschnuppen, Meteor; 387. muldu=valsts, Reich der Träume; 409. tulpete (= runas=vieta), Katheder, Rednerbühne). Zēvalds’s collection is a unique material that allows identifying the perception of the interested reader about the lexical neologisms in one newspaper. Zēvalds’s second collection of words contains the technical expressions from legal country house purchase agreements. There are 83 numbered entries (in German-Latvian comparison) from the legal contract written in German with a lot of additional conditions and long pay-outs delay. This list (at least the part containing legal terms and terminological word-groups) can be regarded as the first term bulletin in Latvian. The possible addressee of this term list is the parish pastors to whom farmers sought advice on such matters. Publications of the teacher Pēteris Zēvalds is a small but interesting episode in the history of the Latvian language, which has not earned attention so far but provides researchers with interesting material about the lexical development in the 70s of XIX century.

Background:Comorbidities in rheumatic diseases (RDs) have been associated with increased morbidity and mortality. Evidence on prevalence of comorbidities in antiphospholipid syndrome (APS) and its difference from high comorbidity burden RDs is limited.Objectives:To compare the prevalence of common comorbidities between APS [primary (PAPS) and Systemic lupus erythematosus (SLE)-APS] and Rheumatoid arthritis (RA) patients.Methods:326 APS patients from the Greek registry (237 women, mean age 48.7±13.4 years, 161 PAPS) were matched 1:2 for age and sex with 652 RA patients from Greek RA Registry. Prevalence of cardiovascular (CV) risk factors, stroke, coronary artery disease (CAD), osteoporosis, diabetes mellitus (DM), Chronic obstructive pulmonary disease (COPD), depression and neoplasms were compared between APS and RA using logistic regression analysis.Results:Regarding CV burden, hyperlipidemia and obesity (ΒMI≥30) were comparable while hypertension, smoking, CAD and stroke were more prevalent in APS compared to RA patients (Table 1). Osteoporosis and depression were more frequent in APS while DM, COPD and neoplasms were comparable between two groups. Comparison of APS subgroups to 1:2 matched RA patients revealed that smoking and stroke were more prevalent in PAPS and SLE-APS vs RA. Hypertension, CAD and osteoporosis were more prevalent only in SLE-APS vs. RA while DM was less prevalent in PAPS vs. RA patients.Table 1.Comparison of comorbidities between Antiphospholipid syndrome (APS) vs. matched Rheumatoid Arthritis (RA) patients and between primary APS (PAPS) or Systemic Lupus Erythematosus-APS (SLE-APS) vs matched RA patientsAPSRAOR*PAPSRAORSLE-APSRAORn (%)326652161322165330Hypertension97 (29.8)136 (21)1.61 (1.19-2.18)40 (25)75 (23.3)1.09 (0.70-1.69)57 (34.6)61 (18.5)2.33 (1.52-3.56)Smoking175 (53.7)264 (40.5)1.70 (1.30-2.22)87 (54)142 (44)1.49 (1.02-2.18)88 (53.3)122 (37)1.95 (1.33-2.85)Hyperlipidemia79 (24.2)135 (20.7)1.23 (0.89-1.68)40 (24.8)62 (19.3)1.39 (0.88-2.18)39 (23.6)73 (22)1.09 (0.70-1.70)Obesity48 (20.5)105 (19.5)1.06 (0.73-1.56)20 (17)51 (19)0.86 (0.49-1.52)28 (24)54 (19.7)1.28 (0.76-2.15)Stroke±66 (20.3)9 (1.4)13.8 (6.5-29.1)36 (22.4)4 (1.2)19.9 (6.6-59.9)30 (18.2)5 (1.5)7.8 (2.7-22.6)Coronary disease±16 (4.9)13 (2)3.14 (1.17-8.45)2 (1.2)7 (2.2)0.46 (0.04-4.77)14 (8.5)6 (1.8)10.9 (2.7-44.3)Osteoporosis×66 (20.3)92 (14)1.45 (1.01-2.06)19 (11.8)42 (13)0.96 (0.54-1.73)47 (28.5)50 (15)1.91 (1.20-3.05)Diabetes×18 (5.5)58 (9)0.58 (0.33-1.01)5 (3)29 (9)0.34 (0.13-0.89)13 (8)29 (9)0.88 (0.44-1.79)COPD≠11 (3.4)14 (2.2)1.26 (0.56-2.84)3 (1.9)6 (2)0.96 (0.23-4.0)8 (5)8 (2.4)1.28 (0.44-3.72)Depression#53 (16.3)66 (10)1.70 (1.15-2.53)23 (14)30 (9.3)1.69 (0.93-3.05)30 (18.2)36 (10.9)1.65 (0.96-2.84)Neoplasms˅14 (4.3)27 (4.1)1.05 (0.54-2.06)5 (3)12 (3.7)0.84 (0.28-2.52)9 (5.5)15 (4.6)1.31 (0.55-3.1)*OR: Odds ratio, crude or adjusted for: ± age, sex, smoking, hypertension, hyperlipidemia, BMI, corticosteroid (Cs) duration × Cs duration ≠ smoking, Cs duration #sex, disease duration, Cs duration ˅ age, disease durationConclusion:Comorbidity burden in APS (PAPS and SLE-APS) is comparable or even higher to that in RA, entailing a high level of diligence for CV risk prevention, awareness for depression and corticosteroid exposure minimization.Disclosure of Interests:Stylianos Panopoulos: None declared, Konstantinos Thomas: None declared, Georgios Georgiopoulos: None declared, Dimitrios Boumpas Grant/research support from: Unrestricted grant support from various pharmaceutical companies, Christina Katsiari: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis, Alexandros Drosos: None declared, Kyriaki Boki: None declared, Theodoros Dimitroulas: None declared, Alexandros Garyfallos Grant/research support from: MSD, Aenorasis SA, Speakers bureau: MSD, Novartis, gsk, Charalambos Papagoras: None declared, PELAGIA KATSIMPRI: None declared, Apostolos Tziortziotis: None declared, Christina Adamichou: None declared, Evripidis Kaltsonoudis: None declared, Evangelia Argyriou: None declared, GEORGIOS VOSVOTEKAS Grant/research support from: MSD, Janssen, Consultant of: MSD, Novartis, Roche, UCB pharma, Bristol-Myers Squibb, AbbVie, Speakers bureau: UCB pharma, Menarini, Bristol-Myers Squibb, MSD, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Dimitrios Vassilopoulos: None declared, Maria Tektonidou Grant/research support from: AbbVie, MSD, Novartis and Pfizer, Consultant of: AbbVie, MSD, Novartis and Pfizer

Benign ethnic neutropenia (BEN) is defined as a neutrophil count of <1.5×109 cells/L in healthy individuals and is more common in populations of certain ethnicities, e.g. African or Middle Eastern ethnicity. Neutrophil values are commonly included in eligibility criteria for research participation, but little is known about the relationship between BEN, HIV acquisition, and the occurrence of adverse events during clinical trials. We investigated these relationships using data from an HIV vaccine efficacy trial of healthy adults from 5 South African sites. We analysed data from the double-blind, placebo-controlled, randomized trial HVTN 503, and its follow-on study HVTN 503-S to assess the prevalence of BEN, its association with HIV infection, and adverse event reporting. These data were then compared with a time- and age-matched, non-pregnant cohort from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007–2008 in the United States (US). The 739 South African participants had a median age of 22.0 years (interquartile range = 20–26) and 56% (n = 412) were male. Amongst the US cohort of 845 participants, the median age was 26 (IQR: 21–30) and the majority (54%, 457/745) were also male. BEN was present at enrolment in 7.0% (n = 52) of South African participants (6% in the placebo group versus 8% in the vaccine group); 81% (n = 42) of those with BEN were male. Pretoria North had the highest prevalence of BEN (11.6%, 5/43), while Cape Town had the lowest (0.7%, 1/152). Participants with BEN had a lower median neutrophil count (1.3 vs. 3.2x109 cells/L; p<0.001) and BMI (20.8 vs. 22.3 kg/m2; p<0.001) when compared to those without BEN. A greater proportion of Black South Africans had neutrophil counts <1.5×109 cells/L compared to US non-Hispanic Whites from the NHANES cohort (7% [52/739] vs. 0.6% [3/540]; p<0.001). BEN did not increase the odds for HIV infection (adjusted odds ratio [aOR]: 1.364, 95% confidence interval [95% CI]: 0.625–2.976; p = 0.4351). However, female gender (aOR: 1.947, 95% CI: 1.265–2.996; p = 0.0025) and cannabis use (aOR: 2.192, 95% CI: 1.126–4.266; p = 0.0209) increased the odds of HIV acquisition. The incidence rates of adverse events were similar between participants in the placebo group with BEN, and those without: 12.1 (95% CI: 7.3–20.1) vs. 16.5 (95% CI: 14.6–18.7; p = 0.06) events per 100 person-years (py) were noted in the infections and infestations system organ class, respectively. The vaccine group had an event incidence rate of 19.7 (95% CI: 13.3–29.2) vs. 14.8 (95% CI: 13.0–16.8; p = 0.07) events per 100py in the group with, and without BEN, respectively. BEN is more prevalent in Black South Africans compared to US Non-Hispanic Whites. Our data do not support excluding populations from HIV vaccine trials because of BEN. BEN was not associated with increased risk for HIV infection or Adverse events on a vaccine trial. Predictors of HIV infection risk were females and cannabis use, underlying the continued importance of prevention programmes in focusing on these populations.

Ключові слова: система укріплень, фортеця Тягин, археологічні дослідження, фортифікаційна лінія, Північне Причорномор’я. Анотація Історико-археологічне вивчення маловідомого періоду перебування українських земель у складі Великого князівства Литовського і Руського : розбудови фортець, організації транснаціональної торгівлі, матеріальної культури є актуальним завданням сучасного етапу наукових досліджень. Завдяки археологічним розкопкам останніх 2016-2021рр. зроблені видатні відкриття у галузі вивчення комплексу пам’яток Південної фортифікаційної лінії, які засвідчують наявність спільної історичної спадщини Литви і України у Північному Причорномор’ї. У статті показано, що дослідження 2016-2021 рр. довели надзвичайну важливість вивчення археологічних пам’яток українських земель доби середньовіччя у Північному Причорномор’ї. Знаковим відкриттям, визнаним українською та світовою спільнотою, постало створення доказової бази існування будівельних залишків фортеці Тягинь, архітектурно-археологічних об’єктів та ознак литовської присутності. Її розташування на крайньому Півдні території Великого князівства Литовського та Руського уособлювало важливий форпост захисту українських земель, важливого чинника створення передумов становлення нового суспільного стану козацтва та його використання у захисті батьківщини. Посилання Аrhiv, 1854 – Аrhiv sctoriko-yuridichnyh svedeniy, otnosyaschihsya do Rossii, izd.Nikolaem Kalachovym. M., 1854. kn. 2., 544 s [in Russian] Biliaieva, Fialko, Hulenko, 2017 – Biliaieva S.O., Fialko O.Ye. Hulenko K.S. Arkheolohichni doslidzhennia poselennia bilia s. Tiahynka u 2016 r. [Archaeological investigationsof the settlement andfortress tiagin: some resultsand problems] // Novi doslidzhennia pam’iatok kozatskoi doby v Ukraini. Vyp. 26. 2017. S. 495-502. [in Ukrainian] Vytkunas, Zabyla, 2017 – Vytkunas M., Zabyla H. Horodyshcha baltov: neyzvestnoe nasledye [Fortified settlements of the Balts: unknown heritage]. Vylnius: Lietuvos archeologijos draugija, 2017. 88 s. [in Russian] Hoshkevych, 1916 – Hoshkevych V.Y. Raskopky na ostrove protyv m. Tiahynky [Excavation on the island against Tyaginki] // Letopys muzeia za 1914 hod. Kherson, 1916. Vyp. 6. 48 s. [in Russian] Hutsul, 2011 – Hutsul V.M. Knightly military technology in the Kyiv-Russian and Polish-Lithuanian states in the XIII-XVI centuries: tools, concepts and practices of armed struggle [Knightly military technology in the Kyiv-Russian and Polish-Lithuanian states in the XIII-XVI centuries: tools, concepts and practices of armed struggle]: dis. cand. ist. science: 07.00.02; Nat. Kyiv-Mohyla University acad. Kyiv, 2011. 306 p. [in Ukrainian] Diachenko, 2004 – Diachenko S.A. Levoberezhe Nyzhneho Dnepra na karte Rychchy Zanony 1767 hoda [The left bank of the Lower Dnieper on the Ricci Zanoni map of 1767] // Naukovi Zapysky. Problemy arkheolohii, etnohrafii, literaturoznavstva, mystetstvoznavstva, muzeieznavstva, onomastyky, sotsiolohii. Kherson., Ailant. 2004. S. 54-71. [in Russian] Ehorov, 1985 – Ehorov V.L. Ystorycheskaia heohrafyia Zolotoi Ordу [Historical geography of the Golden Horde]. M., 1985. 246 s. [in Russian] Enhel, 2014 – Enhel Y.Kh. Istoriia Ukrainy ta ukrainskykh kozakiv [History of Ukraine and Ukrainian Cossacks]. Kharkov 2014. 640 s. [in Ukrainian] Yelnykov, 2006 – Yelnykov M. Do pytannia pro kilkist zolotoordynskykh horodyshch na Nyzhnomu Dnipri [On the question of the number of Golden Horde settlements on the Lower Dnieper] // Pivnichne Prychornomor’ia i Krym u dobu serednovichchia (XIV-XVI st.). Kirovohrad. 2006. S. 45-51. [in Ukrainian] Zharkykh, 2017 – Zharkykh . Natysk na pivden: Try roky polityky Vitovta (1397 – 1399 rr.) [The pressure on the south: Three years of Vytautas' policy (1397 - 1399)], 2017. URL: https://www.m-zharkikh.name/en/History/Monographs/Essays/SourceValueGenealogies/Structure.html [in Ukrainian] Ylynskyi, 2010 – Ylynskyi V.E. Horod Tiahyn-Semymaiak na Tavanskoi pereprave.(Ystorycheskaia spravka) [The city of Tyagin-Semimayak on the Tavan ferry. (Historical information)] // Zapovidna Khortytsia. Materialy IV mizhnarodnoi naukovo-praktychnoi konferentsii «Istoriia zaporozkoho kozatstva: v pam’iatkakh ta muzeinoi praktytsi. Spetsialnyi vypusk. Zbirka naukovykh prats. Zaporizhzhia. 2010. S. 308-313. [in Russian] Ivakin, 1996 – Ivakin H.Yu. Istorychnyi rozvytok Kyieva KhIII-KhV st.: istoryko-topohrafichni narysy [Historical development of Kyiv in the XIII-middle of the XVI century]. K. 1996. 271 s. [in Ukrainian] Kobaliia, 2018. – Kobaliia D. Krepost Tiahyn y ee sovremennoe sostoianye [Tyagin fortress and its current state] // Scriptorium nostrum. 2018. № 2 (11). s. 172-196. [in Russian] Krasnozhon, 2018 – Krasnozhon A.V. Fortetsi ta mista Pivnichno-Zakhidnoho Prychornomor’ia [Fortress and cities of the North-Western Black Sea coast]. Odesa: Vydavnytstvo Chornomor’ia. 2018. 311 s. [in Ukrainian] Na rozi, 2018 – Na rozi dvokh svitiv. Istorychna spadshchyna Ukrainy ta Lytvy na terytorii Khersonskoi oblasti [At the corner of two worlds. Historical heritage of Ukraine and Lithuania in the Kherson region] / Avt. kol.: S.O. Biliaieva, K.S. Hulenko, O.Ye. Fialko, M.M. Iievlev, O.V. Hrabovska, O.V. Manihda, O.V. Chubenko, O.V. Symonenko, O.S. Dzneladze, D.M. Sikoza. NAN Ukrainy. Instytut arkheolohii; KhMHO «Kulturnyi tsentr Ukraina-Lytva». Kyiv; Kherson: Hileia, 2018. 72 s. [in Ukrainian] Olenkovskaia, Olenkovskyi, 1978 – Olenkovskaia M.Y., Olenkovskyi N.P. Razvedky na terrytoryy Khersonskoi oblasty [Exploration in the territory of the Kherson region] // Arkheolohycheskye otkrыtyia 1977 hoda. M., 1978. S. 364. [in Russian] Petrashyna, 2011 – Petrashyna V. 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Bulavy y pernachi na terenakh Ukrainy: zbroia ta symvol vlady [Maces and feathers on the territory of Ukraine: weapons and symbols of power] // Istoriia davnoi zbroi. Doslidzhennia 2014: zb. nauk. pr. Instytut istorii Ukrainy NAN Ukrainy; Natsionalnyi viiskovo-istorychnyi muzei Ukrainy. Kyiv: In-t istorii Ukrainy NANU. 2014. S. 227-241. [in Ukrainian] Chernaia, 1998 – Chernaia E.D. Kollektsyia polyvnoi keramyky Khersonskoho kraevedcheskoho muzeia [Collection of glazed ceramics of the Kherson Museum of Local Lore] // Ystoryko-kulturnыe sviazy Prychernomoria y Sredyzemnomoria X-XVIII vv. Po materialam polyvnoi keramyky. Tezysы dokladov nauchnoi konferentsyy. Symferopol, 1998. S. 186-189. [in Russian] Shlapak, 2004 – Shlapak M. Belhorod-Dnestrovskaia krepost. Yssledovanye srednevekovoho oboronnoho zodchestva [Belgorod-Dnestrovskaya fortress. Study of medieval defense architecture]. Kyshynev, 2004. 237 s. [in Russian] Evarnickij, 1898 – Evarnickij D.I. Vol'nosti zaporozhskih kozakov [Liberties of the Zaporozhye Cossacks]. SPb., 1898. 427 s. [in Russian] Yavornytskyi, 1990 – Yavornytskyi D.I. Istoriia zaporozkykh kozakiv. U 3-kh t [History of the Zaporozhian Cossacks. In 3 volumes]. T. 1 / Peredmova V.A. Smoliia; Red. kol.: P.S. Sokhan (holova), V.A. Smolii (zast. holovy), V.H. Sarbei, H.Ya. Serhiienko, M.M. Shubravska (vidp. sekr.). AN Ukrainskoi RSR. Arkheohrafichna komisiia, Instytut istorii. K.: Naukova dumka, 1990. 596 s. [in Ukrainian] Urbanavićiene, 1995 – Urbanaviċiene S. Dictarų kapininas // Lietuvos archeologija. 1995. T. 11. S. 169-206. [In Lithuanian]

Abstract Background. The IPSS risk model provides survival projections for patients with de novo MDS managed with supportive measures alone. For patients receiving investigational treatment, a prognostic stratification model is needed that can be applied at intervals after diagnosis and that adjusts for the impact of prior therapy, secondary forms of disease, proliferative CMML, and adverse cytogenetic subsets (e.g. 3 abnormalities, chromosome 7 abnormalities). Aims. To develop a new MDS risk model that accounts for subsets not included in IPSS, that refines prognostic subsets, and that applies at any time during course of MDS. Study Group. We analyzed 1915 patients with MDS referred from 1993 to 2005 (including CMML, secondary MDS, MDS with prior therapy). Only 507 patients (26%) had primary MDS without prior therapy (i.e. categorizable by IPSS). Patients were randomly divided into a study group (n=958) and a test group (n=957). Results. A multivariate analysis of prognostic factors in the study group identified the following adverse independent factors as continuous and categorical values (p&lt;0.001), which were given weighted points based on coefficient (score point = coefficient: 0.15). This is shown in Table 1. Cutoffs for anemia, thrombocytopenia and blasts, and cytogenetic subsets, were different for IPSS. The new MDS prognostic model divided patients into four prognostic groups with significantly different outcomes, shown in Table 2. The model was validated in the test group with excellent segregation (Table 2). It was also highly prognostic in the 507 patients with newly diagnosed MDS (as per the original IPSS groups): median survivals 4.7, 3.0, 1.2, 0.75 years. Applying the prognostic score of the new model within the four IPSS risk groups, overall and in primary MDS without prior therapy, was highly prognostic in each. Applying IPSS within each of the 4 risk groups of the new MDS model was not prognostic. The model was also prognostic for multiple MDS subsets tested (Table 3). The new model accounts for duration of MDS and prior therapy. It is applicable to any patient with MDS at any time during the course of MDS. The new risk model was also tested in the 3 arm decitabine trial (n = 124); these patients were divided by the new model into 5 (4%) low risk, 21 (17%) Intermediate 1, 45 (30%) Intermediate 2, and 53 (43%) high risk. This indicates the worse prognosis in this study group (higher risk MDS 79%) The respective median survivals were: not reached (100% at 3 years), 42, 19, and 13 months, respectively (Table 3). This indicated the applicability of the model in a different MDS study group and suggested a better survival than expected (therapy effect?). To verify this, a cumulative score for the 124 patients was calculated and an average score deducted, which was associated with a predicted historical median survival of 13 months overall, 30 months for low-Intermediate 1 and 10 months for Intermediate 2-high risk, versus median survivals of 20 months overall, 44 months for low-Intermediate 1, and 15 months for Intermediate 2-high. Conclusions. A new prognostic model was developed and validated for MDS, which accounts for all MDS or CMML cases, regardless of prior therapy. The model has been validated in an independent test group and was shown to be superior to IPSS. It was also used to demonstrate an improved survival with decitabine compared with the expected (historical) survival by the new risk model. Further validations are needed in independent MDS populations. Table 1 Prognostic factor Coefficient Points Performance status ≥2 0.267 2 Age (in years) 60–64 0.179 1 ≥ 65 0.336 2 Platelets (× 109/L) &lt;30 0.418 3 30–49 0.270 2 50–199 0.184 1 Hemoglobin (g/dL) &lt;12.0 0.274 2 Marrow blast % 5–10 0.222 1 11–29 0.260 2 WBC (× 109/L) &gt;20 0.258 2 Karyotype Chromosome 7 abnormality or complex ≥ 3 abnormalities 0.479 3 Prior transfusion Yes 0.107 1 Table 2 Survival Study Group Test Group Risk Score No. Pts (%) Median (Mos) 3-year % No. Pts Median (Mos) 3-year % Low 0 – 4 157(16) 54 63 159 45 58 Intermediate 1 5 – 6 229(24) 25 34 228 23 35 Intermediate 2 7 –8 233(24) 14 16 244 13 15 High ≥ 9 341(36) 6 4 326 6 3 Table 3 Median Survival (Mo)/1-yr Survival % by new MDS Model Disease* Low Intermediate 1 Intermediate 2 High CMML (n=176) 33 19 12 8 MDS – prior therapy (n=702) 38 19 12 8 Secondary MDS (n=571) 43 19 16 6 Decitabine trial (3-arm – n=124) Not reached -100% at 3-yr 42 19 13 Post decitabine failure (n=59) (% 1 yr surv) 100% 54% 41% 18%

Background Multiple myeloma (MM), a malignant neoplasm of plasma cells in the bone marrow, accounts for up to 1.8% of all cancers in the U.S., most frequently affecting people 65-74 years old. A variety of therapies are available to manage MM, including stem cell transplantation (SCT), immunomodulatory drugs (IMiD), proteasome inhibitors (PI), monoclonal antibodies (mAB), and alkylating agents (alk). Given the heterogeneity of MM and the rapidly evolving therapeutic landscape, MM contemporaneous real-world treatment patterns are not well described. We examined the patient characteristics and first-line (LT1) treatment patterns in NDMM patients. Methods MM patients (≥18 years), diagnosed in April 30, 2015 - April 29, 2017 (early cohort) or in April 30, 2017 - April 30, 2019 (recent cohort), were followed retrospectively from MM diagnosis to last patient activity in the Flatiron Health database - a geographically-diverse, longitudinal electronic health record spanning over 280 community and academic cancer clinics in the U.S. LT1 regimens were described as: 1) containing an IMiD (thalidomide, lenalidomide [R], or pomalidomide), PI (bortezomib [V], carfilzomib, or ixazomib), alk (melphalan, cyclophosphamide [C], bendamustine), mAB (daratumumab, elotuzumab), or combinations of these; and 2) doublet/monotherapy (doublets-) vs. triplet or greater agent (triplets+) combinations. Treatment patterns were examined by SCT status and by cytogenetic risk (high: del17p, t(4;14) and/or t(14;16); standard: ≥1 cytogenetic tests without high cytogenetic risk) and age groups (<65, 65-74, ≥75). Duration of therapy (DOT) and time to next therapy (TTNT) were estimated using Kaplan-Meier methods in the early cohort with longer follow-up. Results Of 4,070 NDMM patients, 3,433 were non-SCT (nSCT: early cohort: n=1,736; recent cohort: n=1,697) and 637 had SCT (early cohort: n=407; recent cohort: n=230). In nSCT patients, mean age at diagnosis was 70 years (SD: 10); 46% were female; 36% had stage III (699/1916, among non-missing), and 15% (392/2574, among non-missing) had high risk MM (25% had unknown cytogenetics). SCT patients were younger at diagnosis (mean [SD]: 61 years [9]); 44% were female; 25% (117/470, in non-missing) had stage III, and 19% (102/547, in non-missing) had high risk MM (14% had unknown cytogenetics). Overall, proportions with known cytogenetic risk were similar within SCT status cohorts over time but were lower in the SCT group (nSCT early vs. recent cohort: 26% vs. 24% had unknown cytogenetics; and in SCT: 15% vs. 13%, respectively). In nSCT and SCT patients, respectively, most common regimens were VRd (d: dexamethasone; 44% and 58%), Rd (16% and 7%), Vd (13% and 1%), and VCd (12% and 4%). In nSCT patients, the use of VRd increased over time (37% [early cohort] to 51% [recent cohort]), while frontline therapy with Rd/Vd doublets (19% to 14%/16% to 9%) and with VCd (13% to 11%) decreased. In the nSCT recent cohort, VRd (51%) frontline therapy dominated, with a slightly higher proportion of patients in the high-risk group vs. standard and unknown risk receiving VRd (56% vs. 53% and 46%); use of doublet therapy with Rd/Vd was lower in the high risk (12%/5%) vs. standard risk group (14%/9%). Irrespective of age, VRd was the most common frontline regimen in the nSCT recent cohort, albeit its use was lower among patients 75+ years of age (43%) vs. younger patients (54% [<65 years] and 59% [65-74 years]); 75+ year old patients had a higher use of Rd/Vd doublets (19%/15%) vs. <65 (10%/5%) or 65-74 (10%/6%) years of age. Triplets+ were more commonly used than doublets- across all cohorts: 59% vs. 41% (nSCT early cohort); 74% vs. 26% (nSCT recent cohort); and 89% vs. 11% (SCT early cohort); 95% vs. 5% (SCT recent cohort). mAB use in the recent cohort was low: 1.4% nSCT and 2.2% SCT patients. In the nSCT early cohort, the median (95% CI) LT1 DOT was 10 months (9-11) and for TTNT was 14 months (13-16). Conclusions PI/IMiD treatment combinations were most commonly observed in both nSCT and SCT patients, with an increase in use from early (40%) to recent (56%) cohort in nSCT patients. Use of triplets, generally, is on the rise from early (60%) to recent cohorts (74%). LT1 TTNT was lower than has been shown in clinical trials. These findings indicate a notable change in treatment patterns over time in nSCT NDMM patients, highlighting the changing landscape of MM management. Disclosures Ailawadhi: Celgene: Consultancy; Takeda: Consultancy; Cellectar: Research Funding; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Research Funding. Romanus:Takeda: Employment. Cherepanov:Takeda: Employment. Yin:Takeda: Employment. Cheng:Takeda: Employment. Hari:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amgen: Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Cell Vault: Equity Ownership; AbbVie: Consultancy, Honoraria.

Abstract Abstract 1914 Novel therapeutic approaches are needed for women with metastatic breast cancer (BrCa). In our phase I clinical trial, infusions of anti-CD3 activated T cells (ATC) armed with anti-CD3 x anti-Her2/neu bispecific antibody (Her2Bi) induced specific cytotoxicity (SC) directed at SK-BR-3 breast cancer cells by fresh peripheral blood lymphocytes (PBL) and induced elevated serum levels of Th1 cytokines. In this study, we took advantage of armed ATC induced anti-tumor immune responses by infusing “immune” T cells collected by leukopheresis. We expanded “immune T cells” with anti-CD3 and IL-2, followed by a cryopreservation for multiple re-infusions of ATC after high dose chemotherapy (HDC) and autologous stem cell transplant (SCT). We asked whether this approach would transfer anti-tumor responses back into patients after HDC and SCT to accelerate the development of cellular and humoral anti-tumor responses. This strategy of “prime” with armed ATC and “boost” with ATC was performed in 5 evaluable patients. The “priming” portion involved 8 infusions of (2 infusions/week for 4 weeks) armed ATC given with daily low dose IL-2 (300,000 IU/m2/day) and twice weekly GM-CSF (250 μg/m2). Approximately 3 weeks after the armed ATC infusions, patients underwent a second leukopheresis for the collection and expansion of ATC. The expanded ATC from 6 patients at an effector:target ratio (E/T) of 25:1 exhibited specific cytotoxicity (SC) ranging from 3.7–25.8 (mean = 13.6%) directed at the SK-BR-3. Phenotyping of the ATC showed a mean of 50.2 % (25–74) CD4+ cells, 30.4 % (16.3-51.3) CD8+ cells, 11.6% (4.5-24.3) CD56+CD16+ cells, and 29.5% (10.4–41) CD4+CD25+ cells. A separate leukopheresis after G-CSF stimulation was performed to obtain CD34+ cells for the SCT. After HDC and PBSCT, 5 evaluable patients received multiple infusions with a mean total of 54×109 ATC (16–110 × 109) beginning day +1 after SCT. No G-CSF was given to accelerate engraftment. There were no dose-limiting side effects or delays in engraftment. One patient developed sepsis, multiple organ failure and recovered fully with supportive care and antibiotics. Phenotyping at 2 weeks after SCT showed the mean proportions of CD4+ and CD8+ cells to be 55.5 and 17.7%, respectively. Specific cytotoxicity (SC) directed at SK-BR-3 targets ranged from 4.7 to 70% at E/T of 25:1 up to 18 months post SCT but not against a negative control cell line-Daudi. Mean serum anti-SK-BR-3 antibody levels were 800 ng/ml preSCT and 1500, 1080 and 1360 ng/ml at 1, 2, and 3 months post SCT, respectively. In vitro anti-SK-BR-3 antibody synthesis was assessed using a new assay (Thakur et al, Cancer Immunol Immunother EPub, 2011) showed easily detectable levels of in vitro anti-SK-BR-3 antibody synthesis. The mean anti-SK-BR-3 antibody synthesis in the presence of CpG in pre-immunotherapy (Pre-IT), mid-IT, 1 months post-IT, pre-SCT and 1, 2, and 3 months post-SCT is summarized in the table. PBL produced anti-SK-BR-3 antibody pre-SCT and there was clear recovery of anti-SK-BR-3 antibody synthesis by PBL at 2 and 3 months after SCT. These data show infusions of immune ATC transferred cytotoxic T lymphocytes and humoral antibody activity directed at tumor antigens. These novel findings suggest that adaptive immunity was transferred into patients by ATC infusions and the stem cell product after myeloablation and SCT leading to rapid reconstitution of anti-tumor immunity.Time PointsCulture ConditionsMean±SD (n=3)Pre-ITCpG23±27Mid-ITCpG66±671M Post-ITCpG41±67Pre-SCTCpG92±101M Post-SCTCpG9±182M Post-SCTCpG45±273M Post-SCTCpG82±55 Disclosures: Lum: Transtarget Inc: Equity Ownership, Founder of Transtarget.

Abstract Abstract 1056 Poster Board I-78 Introduction: We previously showed that a prolonged myelosuppressive maintenance chemotherapy was superior to S-HAM as a postremission therapy in patients > 16 years of age with AML after a TAD-HAM double induction therapy and TAD consolidation chemotherapy with regard to relapse-free survival (RFS) and borderline significance of the overall survival (OS) in responding patients (Buchner et al., JCO 2003, 21:4496-4504). Here we present long-term follow-up data with a median follow-up of 7.9 years from diagnosis and 7.1 years from the date of complete remission. Patients and Methods: Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were upfront randomized in the AMLCG1992 study of the German AML Co-operative Group to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age ≥ 60 years] x 6 (HAM in patients ≥ 60 years only in case of blast persistence on day 16 of therapy) induction, TAD consolidation, and monthly maintenance with cycles of cytarabine combined with either daunorubicin (course 1), 6-thioguanine (course 2), cyclophosphamide (course 3), and again 6-thioguanine (course 4), and restarting with course 1 for 3 years, or to receive TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age ≥ 60 years) x 8 instead of maintenance. Results: A total of 576 patients (69.2%) achieved a complete remission (CR) those were 294 of 429 (68.5%) patients randomized to receive maintenance and 282 of 403 (70.0%) patients randomized to receive intensive consolidation S-HAM (p=n.s.). 190 patients received maintenance therapy as intended and 135 patients received an intensive consolidation therapy as intended. This prolonged follow-up analysis verified the superior relapse-free survival in all patients in the maintenance arm (10-year RFS 30.0 ± 5.6 versus 19.9 ± 6.1 %, p = 0.015). Stratified by age, the 10-year RFS was superior in younger patients < 60 years (36.9 ± 7.1 versus 25.2 ± 8.0 %, p = 0.038) and borderline significant in elderly patients (17.2 ± 4.5 versus 6.8 ± 6.2 %, p = 0.075). A subgroup analysis of known risk groups (lactate dehydrogenase (LDH) level < 700U/l versus ≥ 700U/l at diagnosis, cytogenetic risk profile, bone marrow blasts on day 16 after the start of the induction therapy) revealed a superior RFS in the subgroup of patients with LDH level > 700 U/l at diagnosis (33.5 ± 12.3 versus 18.2 ± 9.5 %, p = 0.043). This superior RFS also translated into a superior 10-year relapse-free interval (RFI) of all responding patients in the maintenance arm (35.7 ± 6.3 versus 27.6 ± 5.9 %, p = 0.015) with borderline significance in younger patients (42.9 ± 7.4 versus 35.0 ± 7.4 %, p = 0.053) and a significant difference in elderly patients (20.6 ± 10.0 versus 8.4 ± 7.5 %, p = 0.043). In this updated analysis, there was a trend, but no significant difference in the OS (maintenance arm: 10-year OS 24.3 ± 4.8, intensive consolidation arm: 19.7 ± 4.7 %, p = 0.148), and we verified a trend for a better OS in responding patients for the maintenance arm (10-year OS in responding patients 33.6 ± 7.5 versus 28.5 ± 6.2 %, p = 0.093). The event-free survival (EFS) also showed a trend towards better EFS in the maintenance arm (10-year EFS 20.7 ± 4.2 versus 14.8 ± 4.1 %, p = 0.082) which was significant in elderly patients (10-year EFS 10.5 ± 5.5 versus 3.9 ± 3.7 %, p = 0.044). Discussion: This updated analysis with a long-term follow-up of median 7.9 years from diagnosis and 7.1 years from CR verified the superior RFS and the trend for enhanced OS in responding patients. These results suggest the superiority of a prolonged monthly myelosuppressive maintenance therapy as compared to intensive consolidation S-HAM after TAD-HAM induction and TAD consolidation. Disclosures: No relevant conflicts of interest to declare.

В статье рассматриваются вопросы тактики боя на нартах, в частности, известных по этнографическим описаниям корякских нарт. Очевидно, что с древнейших времен боевое использование колесниц и нарт было схожим: обстрел врага – разворот – опять стрельба. Так они действовали против нарт/колесниц противника и не столь подвижных пеших бойцов. Колесницы, как и нарты, действовали группами. Для нарт, как и колесниц, была необходима не слишком пересеченная местность, хотя нарты использовались в зимний период, а колесницы – в летний. Различие же между военным использованием колесниц и нарт наблюдается, скорее, социальное. Если ездовыми и/или беговыми нартами обладало практически все мужское население оленных чукчей и коряков, то в первобытных обществах колесницей, как считается, обладали лишь знатные/богатые члены племени. В целом можно отметить сходство боевого использования нарт и колесниц. Их владельцы, очевидно, обладали высоким социальным статусом. Библиографические ссылки Антропова В.В. 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Background:Golimumab showed trial efficacy in subjects with active rheumatoid arthritis (RA) previously treated with TNF-inhibitors (TNFi); no trial data are available for psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).Objectives:To assess the effectiveness of golimumab after TNFi failure in patients with RA, PsA, or axSpA in a real-world setting.Methods:GO-BEYOND-Italy is an ongoing, multicenter, prospective, observational study of RA, PsA, or axSpA patients starting golimumab after TNFi failure. Patients were enrolled between July 2017 and December 2019, and followed for 1 year, with evaluations at 3, 6, and 12 months. This interim analysis estimates the effectiveness after 3 months of golimumab therapy. Differences from baseline were tested by paired t-tests.Results:193 patients were enrolled: 38 (19.7%) with RA (median age 54 years; median disease duration 9.5 years), 91 (47.2%) with PsA (median age 53 years; median disease duration 9.0 years) and 64 (33.2%) with axSpA (median age 54 years; median disease duration 7.2 years). Majority of the RA (73.7%), PsA (51.6%) and axSpA (53.1%) were females. Previous TNFi treatment included etanercept (44.6% of patients), adalimumab (42.0%), infliximab (8.8%) and certolizumab (4.7%). The main reason for switching to golimumab was loss of efficacy of TNFi (78.9% in RA, 83.5% in PsA, 75% in axSpA). Comorbidities were highly prevalent (RA 65.8%, PsA 65.9%, axSpA 75%); hypertension (31.1%), dyslipidaemia (13.5%), fibromyalgia (10.4%) were the most common ones. DAS28-CRP significantly reduced in RA and PsA (p<0.01) after 3 months of treatment. In RA, rates of DAS28-CRP remission and low disease activity (LDA) were 29.6% and 22.2%, respectively, and 65.2% of patients achieved good/moderate EULAR response. As for PsA, good/moderate EULAR response was observed in 78.8% of patients and 28% of patients achieved minimal disease activity. In axSpA, ASDAS-CRP (p<0.01), BASDAI (p<0.01) and ASAS-HI (p=0.032) significantly reduced; rates of ASDAS-CRP inactive disease and LDA were 15.2% and 26.1%, respectively; 14% of patients had a ≥50% improvement in baseline BASDAI. After 3 months of golimumab treatment, there was a decrease in the prevalence of enthesitis (32.9% to 16.5%), nail (17.6% to 12.9%) and skin psoriasis (42.4% to 34.1%) in PsA patients; the frequency of extra articular manifestations tended to decrease also in axSpA patients.Conclusion:Preliminary results of the GO-BEYOND-Italy study showed a good short-term effectiveness of golimumab in RA, PsA and axSpA after TNFi failure.Table 1.Effectiveness of golimumab at 3 months in the GO-BEYOND-Italy studyRheumatoid arthritis (n=38)Psoriatic arthritis (n=91)Axial spondyloarthritis (n=64)DAS28-CRP, mean (SD)n=27DAS28-CRP, mean (SD)n=47ASDAS-CRP, mean (SD)n=44V0 / V14.05 (0.8) / 3.10* (1.0)V0 / V13.66 (1.0) / 2.79* (1.2)V0 / V12.86 (1.0) / 2.33* (1.0)V1: DAS28-CRP disease activity, n (%)n=27V1: EULAR response, n (%)n=33V1: ASDAS-CRP disease activity, n (%)n=46Remission8 (29.6)Good16 (48.5)Inactive disease7 (15.2)Low disease activity6 (22.2)Moderate10 (30.3)Low disease activity12 (26.1)Moderate disease activity13 (48.1)No response7 (21.2)High disease activity22 (47.8)Very high disease activity5 (10.9)V1: EULAR response, n (%)n=23V1: MDA, n (%)n=75Good7 (30.4)Yes21 (28.0)BASDAI, mean (SD)n=50Moderate8 (34.8)V0 / V15.99 (2.1) / 4.92 (2.3)*No response8 (34.8)V1: BASDAI50, n (%)7 (14.0)ASAS-HI, mean (SD)n=48V0 / V110.67 (3.8) / 9.68 (4.6)^*p value for the difference from V0 <0.01. ^ p for the difference from V0=0.032Abbreviations: ASDAS: Ankylosing Spondylitis Disease Activity Score; ASAS-HI: Assessment of SpondyloArthritis international society Health Index; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; CRP: C-reactive protein; DAS: disease activity score; EULAR: European League Against Rheumatism; MDA: Minimal Disease Activity; SD: standard deviation; V0: baseline; V1: 3 months evaluation.Disclosure of Interests:Salvatore D’Angelo Speakers bureau: AbbVie, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB, Enrico Tirri Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Angela Maria Giardino Employee of: MSD Italia, Marco Matucci-Cerinic Speakers bureau: BMS, Pfizer, Actelion, Consultant of: Eli-Lilly, Celgene, Chemomab, CSL Behring, Grant/research support from: BMS, Pfizer, Celgene, CSL Behring, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI, Leonardo Santo: None declared., francesco ciccia: None declared., Bruno Frediani: None declared., Marcello Govoni: None declared., Francesca Bobbio Pallavicini: None declared., Rosa Daniela Grembiale: None declared., Andrea Delle Sedie: None declared., Stefania Cercone Employee of: MSD Italia, RITA MULE’: None declared., Francesco Paolo Cantatore Speakers bureau: Pfizer, Sanofi Genzyme and Roche, Consultant of: Pfizer, Sanofi Genzyme and Roche outside this work., Rosario Foti: None declared., Elisa Gremese: None declared., Roberto Perricone: None declared., Fausto Salaffi: None declared., Ombretta Viapiana Speakers bureau: Novartis, UCB, Abbvie, MSD, Fresenius kabi, Gilead, Biogen, Consultant of: Novartis, Abbvie, Fresenius kabi, Gilead, Biogen, Alberto Cauli Speakers bureau: Abbvie, Alfa-Sigma, BMS, Celgene, Galapagos, Glaxo, MSD, Novartis, Janssen, Pfizer, Sanofi, UCB, Consultant of: Abbvie, Alfa-Sigma, BMS, Celgene, Galapagos, Glaxo, MSD, Novartis, Janssen, Pfizer, Sanofi, UCB, Rorberto Giacomelli: None declared., Luisa Arcarese: None declared., Giuliana Guggino Speakers bureau: Novartis, Celgene, Abbvie, Sandoz, Eli Lilly, Pfizer, Jansen, ROMUALDO RUSSO: None declared., Domenico Capocotta: None declared., Francesca Nacci: None declared., Maria Grazia Anelli: None declared., valentina picerno: None declared., Florenzo Iannone Speakers bureau: Pfizer, AbbVie, Janssen, Celgene, Novartis, MSD, BMS, UCB, Roche, Consultant of: Pfizer, AbbVie, Janssen, Celgene, Novartis, MSD, BMS, UCB, Roche outside this work.

Abstract Background: There has been major improvement in the survival of patients with multiple myeloma (MM), mostly due to the availability of more effective drugs and increased use of autologous hematopoietic progenitor cell transplantation (AHPCT). Access to AHPCT has been linked to demographic, geographic and socioeconomic parameters. We hypothesize that the distance between the patient county of residence and a transplant center is an adequate surrogate of access to advanced care (comprising not only AHPCT, but also experimental therapies) and may affect survival of MM patients. Methods: We conducted an analysis of patients diagnosed with MM between 2002 and 2011 reported to the Surveillance Epidemiology and End Results program (SEER-18). Cases reported from death certificate or autopsy only, and cases with missing race or county of residence were excluded (1% of total). Patients were classified according to the distance between county of residence and the nearest program accredited by the Foundation for the Accreditation of Cellular Therapy (FACT): Cohort A (<20 miles), B (20-70 miles), C (70-200 miles) and D (>200 miles). Results: We included 45,079 patients with median follow up of survivors of 30 months. There were substantial differences between the cohorts, particularly in race-ethnicity, income and education (Table 1). Median survival was 34, 37, 31 and 30 months for cohorts A, B, C and D respectively (Figure 1). Using Cox proportional hazards, we built two different survival models. Model 1 included demographic parameters and distance to transplant center. Compared to cohort A, risk of death was lower in cohort B and higher in cohorts C and D (Table 2). Model 2 included all parameters of model 1 plus median household income and proportion of adults in the county of residence with at least bachelor degree. Income and education were strongly associated with survival and displaced distance to transplant center from the model (Table 2). Other factors associated with worse survival were age, earlier year of diagnosis, male sex, presentation with plasma cell leukemia, and race-ethnicity. Conclusion: Distance to transplant center, a surrogate for access to advanced care, is associated with survival in patients with MM, likely reflecting underlying differences in demographics, income and education. Abstract 858. Table 1 –Characteristics of the patientsTotalABCDN=45,079N=19,476N=15,614N=8,262N=1,727PFemale20,419 (45.3%)8,967 (46.0%)7,036 (45.1%)3,654 (44.2%)762 (44.1%)0.02Age68.468.468.868.368.20.005Race-ethnicity<0.001AIAN211 (0.5%)39(0.2%)36 (0.2%)36 (0.4%)100 (5.8%)API2282 (5.1%)1381(7.1%)751 (4.8%)124 (1.5%)26 (1.5%)Hispanic4557 (10.1%)2504 (12.9%)1,129 (7.2%)470 (5.7%)454 (26.3%)NHB8615 (19.1%)4708 (24.2%)2,236 (14.3%)1,600 (19.4%)71 (4.1%)NHW29,414 (65.2%)10,844 (55.7%)11,462 (73.4%)6,032 (73.0%)1,076 (62.3%)Year of diagnosis0.022002-200621,076 (46.8%)9,185 (47.2%)7,185 (46.0%)3,854 (46.6%)852 (49.3%)2007-201124,003 (53.2%)10,291 (52.8%)8,429 (54%)4,408 (53.4%)875 (50.7%)Household income$59.157$60,254$66,540$45,237$46,633<0.001Adults with at least bachelor degree29.7%32.8%31.6%19.7%24.3%<0.001Disease0.46Multiple Myeloma44,749 (99.3%)19,327 (99.3%)15,498 (99.3%)8,212 (99.2%)1,712 (99.1%)Plasma Cell Leukemia330 (0.7%)149 (0.7%)116 (0.7%)60 (0.8%)15 (0.9%) Table 2 – Multivariate analysis of factors associated with survival in MM Factor Reference HR 95% C.I. P Model 1 Year of diagnosis Per year 0.963 0.959-0.968 <0.001 Age at diagnosis Per year 1.042 1.041-1.044 <0.001 Female Male 0.90 0.89-0.93 <0.001 Plasma Cell Leukemia Multiple Myeloma 2.94 2.60-3.31 <0.001 Race-ethnicity <0.001 AIAN NHW 1.04 0.87-1.26 0.65 API NHW 1.03 0.97-1.09 0.32 Hispanic NHW 1.14 1.09-1.19 <0.001 NHB NHW 1.11 1.07-1.15 <0.001 Distance to advanced care <0.001 20 - 70 miles <20 miles 0.96 0.93-0.99 0.005 70-200 miles <20 miles 1.10 1.06-1.14 <0.001 >200 miles <20 miles 1.10 1.03-1.17 0.004 Model 2 Year of diagnosis Per year 0.963 0.959-0.968 <0.001 Age at diagnosis Per year 1.042 1.041-1.044 <0.001 Female Male 0.91 0.89-0.93 <0.001 Plasma Cell Leukemia Multiple Myeloma 2.94 2.60-3.31 <0.001 Race-ethnicity <0.001 AIAN NHW 1.04 0.86-1.25 0.68 API NHW 1.06 1.00-1.12 0.04 Hispanic NHW 1.15 1.10-1.20 <0.001 NHB NHW 1.08 1.05-1.12 <0.001 Household income Per $10,000 0.98 0.96-0.99 0.001 % adults with bachelor degree Per % point 0.994 0.992-0.996 <0.001 Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Abstract Background: The need to repeat peripheral blood stem cell (PBSC) mobilization and collection arises infrequently in healthy donors, but may be required due to insufficient initial collection, graft failure, or relapse of the recipient’s disease. Currently no published data exists on the efficacy of remobilization of healthy PBSC donors. Studies of remobilization in patients undergoing autologous transplantation (ASCT) have largely focused on the use of alternative mobilization agents such as chemotherapy or plerixafor. Boeve et al (Bone Marrow Transplant, 2004) reported that remobilization with G-CSF in patients undergoing ASCT who failed initial mobilization with G-CSF, resulted in higher numbers of CD34+ cells collected than the initial collection, though this required a doubling of the dose of G-CSF. Patients/Methods: We performed retrospective chart review of 977 consecutive adult (>18 yrs) donors who underwent apheresis for PBSC donation at Washington University School of Medicine from 1995 through 2013. We identified 66 donors who had undergone more than one mobilization. Two cohorts of donors were identified for analysis: Group 1 included donors mobilized initially and again subsequently with G-CSF (10 ug/kg/day), or GM-CSF (5 ug/kg/day) + G-CSF (10 ug/kg/day). Group 2 consisted of donors mobilized with a CXCR4 antagonist, plerixafor (240-320 ug/kg) or POL6326 (1000-2500 ug/kg), and subsequently were remobilized with G-CSF (10 ug/kg/day). Statistical Analysis: Spearman correlations were performed to analyze the relationship between peak peripheral blood (PB) CD34+/uL level; the number of CD34+ cells collected per kg (recipient weight); and the number of CD34+ cells per L of apheresis collected during initial mobilization (MOB1) and remobilization (MOB2); and the interval (days) between MOB1 and MOB2. One-way ANOVA with repeated measures analyses were performed to determine the relationship of PB CD34+/uL, CD34+/kg and CD34+/L during MOB1 and MOB2. Results: Group 1 included 30 donors. The median age was 49 years (range 18-75) and 15 were male. The median number of days between MOB1 and MOB2 was 140 (range 26-2238). All 30 donors were remobilized due to graft failure or relapse of the recipient’s disease. PB CD34+/uL, CD34+/kg and CD34+/L all correlated between MOB1 and MOB2. The mean PB CD34/uL at MOB1 was 69 compared to 37 at MOB2 (p= 0.029); the mean CD34/kg collected at MOB1 was 5.6x106 compared to 3.3x106 at MOB2 (p= 0.002); and the mean CD34/L collected at MOB1 was 24.0x106 compared to 17.6x106at MOB2 (p= 0.023). The interval between MOB1 and MOB2 did not correlate with any of the MOB2 variables. Results from the analysis are summarized in Table 1. Group 2 included 32 donors. The median age was 51 years (range 21-67) and 18 were male. The median number of days between MOB1 and MOB2 was 20 (range 4-1123). 18 donors were remobilized due to mobilization failure, while 14 were remobilized due to graft failure or relapse of the recipient’s disease. The mean PB CD34/uL at MOB1 was 15 compared to 68 at MOB2 (p< 0.001); the mean CD34/kg collected at MOB1 was 2.5x106 compared to 7.1x106 at MOB2 (p< 0.001); and the mean CD34/L collected at MOB1 was 10.6x106 compared to 30.1x106at MOB2 (p< 0.001). The interval between MOB1 and MOB2 did not correlate with any of the MOB2 variables. Results from the analysis are summarized in Table 2. Conclusion: Remobilization with G-CSF or GM-CSF and G-CSF after initial successful mobilization with the same regimen results in poorer mobilization while remobilization with G-CSF after initial mobilization with a CXCR4 antagonist results in dramatically improved mobilization. The reason for this remains unclear, but in this study the interval between collections was not associated with successful remobilization. Abstract 850. Table 1 Group 1 MOB 1 MOB 2 One-way ANOVA Spearman Correlation PB CD34/ul 69 (13-417) 37 (1-115) F(1.0, 29.0) = 5.26, p= 0.029 r= 0.615, p< 0.001 CD34/kg (x106) 5.6 (0.8-13.8) 3.3 (0.3-10.6) F(1.0, 29.0) = 11.77, p= 0.002 r= 0.483, p= 0.007 CD34/L (x106) 24.0 (4.5-72.0) 17.6 (2.8-41.3) F(1.0, 29.0) = 5.74, p= 0.023 r= 0.566, p< 0.001 Abstract 850. Table 2 Group 2 MOB 1 MOB 2 One-way ANOVA Spearman Correlation PB CD34/ul 15 (2-54) 68 (14-358) F(1.0, 31.0) = 23.16, p< 0.001 r= 0.433, p= 0.013 CD34/kg (x106) 2.5 (0.2-19.7) 7.1 (1.7-42.4) F(1.0, 31.0) = 33.84, p< 0.001 r= 0.769, p< 0.001 CD34/L (x106) 10.6 (1.4-67.1) 30.1 (6.0-165.0) F(1.0, 31.0) = 34.70, p< 0.001 r= 0.774, p< 0.001 Disclosures No relevant conflicts of interest to declare.

Abstract Background: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma that usually presents as advanced-stage disease. Relapse is common, and management of relapsed/refractory MCL is difficult due to a limited number of approved agents and numerous comorbidities seen in this typically elderly patient population. We conducted a study of bendamustine plus rituximab (BR) in patients with relapsed/refractory MCL and presented preliminary results (Czuczman et al, ASH 2012, Abstract 3662). Final data are being analyzed in a multivariate analysis of baseline demographic and disease factors affecting outcomes for this study, and we present below the final data for individual subgroups for best overall response, DOR, and progression free survival (PFS). Patients and Methods: This multicenter, open-label, single-arm, phase 2 study was conducted to evaluate the efficacy, tolerability, and safety of BR in adults with relapsed or refractory CD20-positive B-cell MCL. Relapsed disease was defined as having achieved CR with a previous therapy but demonstrating recurrent disease >6 mo after the last dose. Refractory disease was defined as either a lack of CR while undergoing previous therapy or the loss of CR <6 mo after the last dose. Bendamustine 90 mg/m2 was administered on days 1 and 2; rituximab 375 mg/m2 was administered on day 1 of a 28-day cycle. The treatment period was 6 cycles, but patients without disease progression and without a documented CR could receive up to 8 cycles. Results of a univariate analysis will be conducted, and variables with a P value ≤0.1 will be included in a multivariate analysis. For the multivariate analysis, logistical regression will be used to examine the predictive value of baseline variables associated with response in categorical analyses. Results: Forty-five patients received ≥1 dose of BR. Median age was 70 years, 71% were male, and 82% had stage IV disease. Median treatment duration was 6 cycles. For the entire cohort, the overall response rate (ORR) was 82%. Results of a multivariate analysis, which is designed to identify baseline characteristics predictive of response to BR study treatment and to examine the association of response with survival in patients, will be presented. Final data among patients with relapsed (n=21) and refractory (n=24) MCL show overall response rates (ORRs) of 90% (n=19; CR 16 [76%], PR 3 [14%], 2 not calculable [NC]); and 75% (n=18; CR 5 [21%], PR 13 [54%], 1 NC), respectively. Median DOR (95% CI) was 19.7 mo (11.1, 38.8) and 15.3 mo (7.9, 35.3), and median PFS was 23.1 mo (13.2, 41.5) and 17.1 (8.3, 24.0), for relapsed and refractory patients, respectively. ORRs based on patients’ response to most recent prior rituximab treatment were CR, 95% (n=18; CR 15, PR 3); PR, 89% (n=8; CR 3, PR 5); stable disease (SD), 56% (n=5; CR 1, PR 4); progressive disease (PD), 71% (n=5; CR 1, PR 4); unknown, 100% (n=1; CR 1). DORs based on response to prior rituximab: CR, 17.0 mo (10.7, 38.8); PR, 17.9 mo (4.9, 35.9); SD, 35.3 mo (7.9, 35.3); PD, 14.3 mo (3.9, NC); unknown was NC. PFS results were: CR, 22.1 mo (13.2, 41.5); PR, 18.1 mo (4.7, 38.7); SD, 17.9 mo (2.4, 40.4); PD, 13.8 mo (5.4, NC); unknown was NC. In subgroups based on MIPI category, the ORR of patients in categories ≤3 was 92% (n=22; CR 14, PR 8); in 4–5 was 92% (n=11; CR 5, PR 6); in >5 was 44% (n=4; CR 2, PR 2). DORs based on risk category: ≤3, 20.6 mo (14.3, 35.5); 4–5, 11.1 mo (5.1, 21.3); >5, NC (5.1, NC). PFS results were: ≤3, 23.2 mo (16.2, 40.4); 4–5, 12.8 mo (8.3, 24.0); >5, 7.9 mo (2.0, NC). Main treatment-emergent grade 3/4 adverse events (>10%) were hematologic: neutropenia (n=15), lymphopenia (n=6), and leukopenia (n=5). Conclusion: The multivariate analysis is intended to indicate which patient characteristics are most closely associated with efficacy endpoints such as durability of response to BR. BR showed efficacy across a wide range of patient subgroups with relapsed/refractory MCL. In the subgroup of patients with relapsed MCL, CR was more common than PR, while patients with refractory MCL were more likely to achieve PR than CR. This information may be used to help guide treatment decisions when considering BR in heavily treated MCL patients. The BR regimen is generally well-tolerated and may serve as the backbone to which other active agents can be added in the study regimens to further improve anti-lymphoma activity. Support: Teva BPP R&D, Inc. Disclosures Czuczman: Teva: Consultancy. Off Label Use: Bendamustine is FDA-approved for adults with chronic lymphocytic leukemia or indolent B-cell non-Hodgkin's lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.. Goy:JNJ: Membership on an entity's Board of Directors or advisory committees, Research funding for clinical trials through institution, Research funding for clinical trials through institution Other, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research funding for clinical trials through institution, Research funding for clinical trials through institution Other; Millennium: Membership on an entity's Board of Directors or advisory committees, Research fundiing for clinical trials through institution, Research fundiing for clinical trials through institution Other, Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research funding for clinical trials through institution Other, Speakers Bureau. Munteanu:Teva: Employment, Equity Ownership. van der Jagt:Teva: Consultancy, Honoraria, Research Funding, Speakers Bureau; Lundbeck: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Настоящая работа является первым общим описанием на русском языке двух некрополей Кампокиаро (Кампобассо, Италия) – Виченне и Морионе, датируемых последней третью VII в. – началом VIII в. Культурное содержание некрополей показывает прочные связи с населением центральноазиатского происхождения. Важнейшим признаком некрополей являются захоронения с конем, соответствующие евразийскому кочевому погребальному обряду. Автор поддержал выводы европейских исследователей о том, что с большой долей вероятности некрополи оставлены булгарами дукса–гаштальда Алзеко, зафиксированными Павлом Диаконом в VIII в. на территориях Бояно, Сепино и Изернии. Аналогии некрополей Кампокиаро с погребениями Аварского каганата показывают присутствие в аварском обществе булгар со схожим погребальным обрядом. Из тысяч погребений с конем, оставленных аварским населением, булгарам могла принадлежать большая часть. Авары и булгары составляли основу и правящую верхушку каганата. 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Статья посвящена находкам предметов вооружения и конского снаряжения, выявленным на памятниках салтово-маяцкой культуры, расположенных в среднем течении р. Северский Донец. В верхнем ее течении (в пределах лесостепной зоны) эти предметы являются частой находкой и встречаются в основном в захоронениях катакомбных и кремационных некрополей. В степи они попадаются реже, что вызвало появление версий о слабом знакомстве проживавшего здесь населенияс военным делом. Анализ материалов, выявленных в среднем течении Северского Донца, показывает несостоятельность указанных точек зрения. На расположенных здесь памятниках предметы вооружения и конского снаряжения встречаются достаточно часто. Так, на крупном поселении у с. Маяки Славянского р-на количество предметов этой категории составляет около 20% от общего количества находок металлических изделий. Данный вывод вполне согласуется с наличием в рассматриваемом регионе группы укрепленных поселений (Донецких городищ), оборонять которые без значительного воинского контингента не представляется возможным. Вполне логично, что большая часть находок предметов вооружения сконцентрирована именно на этих памятниках. Библиографические ссылки Аксенов В.С. Комплексы конского снаряжения салтовского времени с начельниками (по материалам Верхнесалтовского катакомбного могильника) // Степи Европы в эпоху средневековья. Т 4. Хазарское время / Гл.ред. А.В. Евглевский. Донецк: ДонНУ, 2005. С. 245−260. Аксенов В.С. Новые поминальные комплексы воинов-всадников салтовского времени с территории Верхнего Подонечья // Степи Европы в эпоху средневековья. Т 4. Хазарское время / Гл.ред. А.В. Евглевский. Донецк: ДонНУ, 2005а. Т.4. С. 357−368. Аксенов В.С., Колода В.В. Богатый вещевой комплекс близ Старой Покровки на Харьковщине // Хазарский альманах. Т.15. / Гл. ред. О.Б. Бубенок. 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Objective: CeQur Simplicity™ (CeQur, Marlborough, MA) is a 3-day insulin delivery patch designed to meet mealtime insulin requirements. A recently reported 48-week, randomized, multicenter, interventional trial compared efficacy, safety and self-reported outcomes in 278 adults with type 2 diabetes (T2D) on basal insulin therapy who initiated and managed mealtime insulin therapy with a patch pump versus insulin pen. We assessed changes in key glycemic metrics among a subset of patients who wore a continuous glucose monitoring (CGM) device. Methods: Study participants (patch, n = 49; pen, n = 48) wore a CGM device in masked setting during the baseline period and prior to week 24. Glycemic control was assessed using international consensus guidelines for percentage of Time In Range (%TIR: >70% at 70-180 mg/dL), Time Below Range (%TBR: <4% at <70 mg/dL; <1% at <54 mg/dL), and Time Above Range (%TAR: <25% at >180 mg/dL; <5% at >250 mg/dL). Results: Both the patch and pen groups achieved recommended targets in %TIR (74.1% ± 18.7%, 75.2 ± 16.1%, respectively) and marked reductions in %TAR >180 mg/dL (21.1% ± 19.9%, 19.7% ± 17.5%, respectively) but with increased %TBR <70 mg/dL (4.7% ± 5.2%, 5.1 ± 5.8, respectively), all P < .0001. No significant between-group differences in glycemic improvements or adverse events were observed. Conclusions: CGM confirmed that the patch or pen can be used to safely initiate and optimize basal-bolus therapy using a simple insulin adjustment algorithm with SMBG. Preference data suggest that use of the patch vs pen may enhance treatment adherence.

Abstract Background Placebo can have a significant therapeutic effect in patients with hand osteoarthritis (OA). This aim of the study is to identify factors associated with a clinically meaningful placebo response in patients with hand OA. Methods This post-hoc analysis of two double-blind, placebo-controlled, randomized trials (RCTs) investigating the efficacy of GCSB-5 or diacerein as treatments for hand OA analyzed the efficacy of a placebo. Clinical and laboratory factors associated with a clinically meaningful response, defined as an improvement in the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score > 10 at 4 weeks relative to baseline, were identified. Results The mean improvement in the AUSCAN pain score was − 6.0 ± 20.3, with marked variation between 143 hand OA patients (range: − 76.4 to 33.2). A clinically meaningful improvement was observed in 54 (37.8%) patients. Placebo responders had worse AUSCAN pain scores (55.7 ± 19.7 vs. 43.6 ± 21.6, p = 0.001) and a worse AUSCAN stiffness (68.2 ± 20.5 vs. 57.5 ± 24.5, p = 0.008) at baseline than non-responders. Improvements in pain correlated with the baseline pain level (Pearson r = − 427, p < 0.001). Structural joint changes such as tender, swollen, enlarged, or deformed joint counts did not differ between placebo responders and non-responders. In a multivariable analysis, only baseline AUSCAN pain was associated with a clinically meaningful placebo response (OR: 1.054, 95% CI [1.019–1.089], p = 0.002). Conclusions High levels of pain at baseline are predictive of a clinically meaningful placebo response in patients with hand OA. Further studies are needed to optimize and utilize the benefit of placebo responses in patients with hand OA.

Abstract Background Osteonecrosis of the femoral head is a common complication in the treatment of developmental dysplasia of the hip (DDH). While functional outcomes of affected patients are good in childhood, it is not clear how they change during the transition to young adulthood. This study determined the relationship between osteonecrosis and hip function, physical function and health status in adolescents and young adults. Methods We performed a cross-sectional study of 169 patients with a mean age of 19.7 ± 3.8 years with and without osteonecrosis following an open or closed reduction (1995–2005). We also performed a separate longitudinal evaluation of an historical cohort of 54 patients with osteonecrosis, embedded in this sample. All completed patient-reported outcome measures in 2015/2016 to quantify hip function (maximum score 100); physical function (maximum score 100); and general health status (maximum score 1). We graded all radiographs for subtype of osteonecrosis (Bucholz-Ogden); acetabular dysplasia (centre-edge angle); subluxation (Shenton’s line); and osteoarthritis (Kellgren-Lawrence). Analyses were adjusted for the number of previous surgical procedures on the hip and for the severity of residual hip dysplasia. Results In 149 patients (186 hips) with and without osteonecrosis, the mean differences (95% confidence interval) in hip function, physical function and quality of life were − 4.7 (− 10.26, 0.81), − 1.03 (− 9.29, 7.23) and 0.10 (− 1.15, 1.18), respectively. Adjusted analyses stratified across types of osteonecrosis showed that only patients with Bucholz-Odgen grade III had reduced hip function (p < 0.01) and physical function (p < 0.05) but no difference in health-related quality of life when compared to no osteonecrosis. Conclusion Osteonecrosis secondary to DDH is a relatively benign disorder in adolescents and young adulthood. Affected patients demonstrated minimal physical disability, a normal quality of life but reduced hip function.

Background Endovascular coiling is usually the first line treatment modality for most ruptured intracranial aneurysms. However, there is still some debate as to whether microsurgical clipping or coiling is the treatment of choice for complex wide-necked ruptured middle cerebral artery (MCA) aneurysms. Our aim was to assess the efficacy, safety and longevity of simple endovascular coiling for ruptured MCA aneurysms Methods This was a single-centre 10 years retrospective study (2008–2019) of all endovascularly treated patients with ruptured MCA aneurysms ( n = 148). Patients were treated with simple coiling ( n = 111), balloon-assisted coiling ( n = 13), dual micro-catheter coiling ( n = 19), balloon-assisted and dual micro-catheter coiling ( n = 4) and woven endobridge (WEB) device ( n = 1). The standard follow-up protocol consisted of Magnetic Resonance angiography at 6, 12 and 24 months. Our primary endpoints were mortality at 2, 12 and 24 months and dependency at discharge. Secondary endpoints included aneurysm occlusion, complications, re-canalisation, rebleeding and retreatment rates. Results All-cause mortality at 2, 12 and 24 months was 4.7% ( n = 7), 8.1% ( n = 12) and 10.8% ( n = 16), respectively. 81.3% of patients remained independent in activities of daily livings (ADLs) at the point of discharge. Over a mean follow-up period of 19.7 months, we demonstrated re-bleeding and re-treatment rates of 2.7% ( n = 4) and 4.1% ( n = 6) respectively. Complete occlusion was achieved in 54% ( n = 79) of aneurysms, with recanalisation observed in 18.2% ( n = 27) of the patients. Conclusions Our results demonstrate that simple endovascular coiling techniques offer a safe and effective solution in the management of ruptured MCA aneurysms without the requirement for re-treatment either surgically or endovascularly using endoluminal stents or other devices.

Abstract Purpose We analyzed the association between bedtime smart device usage habits and accelerometer-measured sleep outcomes (total sleeping time, sleep efficiency, and wake after sleep onset) in Hong Kong children and adolescents aged 8–14. Methods A total of 467 students in Hong Kong participated in this study from 2016 to 2017. They self-reported their bedtime smart device usage habits. The primary caregiver of each participant was also invited to complete a self-administered questionnaire about the family’s social-economic status and bedtime smart device usage habits. An ActiGraph GT3X accelerometer was used to assess participants’ 7-day sleep outcomes. Results The mean age of the participants was 10.3 (SD 1.9), and 54% were girls. Among the participants, 27% (n = 139) used a smart device before sleep, and 33% (n = 170) kept the smart device on before sleep. In total, 27% (n = 128) placed the smart device within reach before sleep, 23% (n = 107) would wake up when notifications were received, and 25% (n = 117) immediately checked the device after being awakened by a notification. Multiple regression controlling for age, sex, socio-economic status, and other confounders showed that those who woke up after receiving a notification had a statistically longer sleeping time (19.7 min, 95% CI: 0.3, 39.1, p = 0.046), lower sleep efficiency (− 0.71%, 95% CI − 1.40, − 0.02, p = 0.04), and a longer wake after sleep onset (2.6 min, 95% CI: 0.1, 5.1, p = 0.045) than those who did not. Nonetheless, all primary caregivers’ bedtime smart device habits were insignificantly associated with all sleep outcomes of their children. Conclusion Those who woke up after receiving smart device notifications had lower sleep efficiency and longer wake after sleep onset than those who did not, and they compensated for their sleep loss by lengthening their total sleep time.

SUMMARY The Mabian fault zone, distanced ∼200 km to the east of the Xianshuihe-Xiaojiang fault system, is located in the western vicinity of the relatively stable South China Block. Since 1917, about 54 M &gt; 4.7 earthquakes, including the 1974 Ms = 7.1 Mabian event have occurred around this fault zone, suggesting that significant strain is localized within the Mabian fault zone. Here, we built a three-dimensional finite element model to investigate the main parameters that possibly control strain localization around the Mabian fault zone averaged over the active deformation timescale. In the model, the Xianshuihe-Xiaojiang fault system is specified as a discontinuous contact interface for its motion governed by a Coulomb-friction law, and the crustal rheology is simplified as a frictional upper crust underlain by a viscoelastic lower crust. In addition, Global Positioning System (GPS) data are used to mimic the horizontal tectonic loading, and the model base is supported by a hydrostatic pressure. Numerical results show that with the weak fault strength and the low viscosity contrast between the Tibetan plateau and the South China Block, strain rates from motion of the southeastern Tibetan plateau could be propagated across the Xianshuihe-Xiaojiang fault system more widely within the Mabian fault zone. Constrained by the estimates on slip rates of the faults and on rheological structures of the crust, our optimal model predicts the effective friction coefficient of the Xianshuihe-Xiaojiang fault of 0.05 - 0.1. Under this condition, relative motion across the Xianshuihe-Xiaojiang fault system is largely partitioned by the geometric bend near the center of the fault system, resulting in a relatively high strain rate of 2.1 - 3×10–8 yr–1 accumulating around the Mabian fault zone. Keeping the weak strength of the fault, numerical results also show that if the middle portion of the Xianshuihe-Xiaojiang fault system follows the Daliangshan fault, strain accumulation around the Mabian fault zone could be significantly reduced. It thus can be concluded that the strain partitioning from the weak strength and the special geometry of the Xianshuihe-Xiaojiang fault system must play a crucial role in active deformation around the Mabian area out of the Tibetan plateau deformation domain. This in turn means that in the Xianshuihe-Xiaojiang fault system, the Anninghe-Zemuhe fault is still the main boundary between the southeastern Tibetan plateau and the South China Block.

An elderly man of my acquaintance once told me that there was nothing much to recommend living beyond 90. Things have changed over the past two decades, however. These days all he'd need is a touch of Viagra, an attitude reorientation, a little bit of manifesting and he'd be feeling as fit as, as, well … as a man in his 60s. Had he been around now, as a knowledgeable nonagenarian, he need not have mourned the passing of the years. Instead, he could have concentrated on becoming daily younger. As Second Youth so blithely trumpets: "In your youth, your mind, body and spirit are capable of great recuperative powers but, as you get older, you believe that those powers diminish. Not true! As long as you have a will -- and a method -- to improve your life, you will find the power to make it happen." Lacking the method? Look no longer… Books entitled RealAge: Are You as Young as You Can Be? (Roizen 1999) appear at the top of the New York Times best seller list, arguing that some 70-year olds can have the health profile of average 44-year olds within three years of making the right choices. (www.RealAge.com) This is the book's manifesto: The whole point of RealAge is to promote old age. Healthy, vibrant and young old age. RealAge shows you how you can live at eighty with all the energy and vigor of a fifty-five year old, how you can be the ninety year old who still lives on your own, travels and forcefully expresses feisty opinions -- the person who leaves the 'kids' marveling, 'How does she do it?' Having respect for old age means wanting to end the suffering that so often goes along with it. No one wants to be bedridden, afflicted with heart disease, or undergoing cancer treatment. Everyone wants to be able to do all the things he or she has always done and more. [Italics, gendered language, original] (Roizen 1999, p. 10) This website-supported best seller is part of a burgeoning industry which includes Cassel and Vallasi (1999) The Practical Guide to Aging: What Everyone Needs to Know, and Perls and Silver (1999) Living to 100: Lessons in Living to Your Maximum Potential at Any Age. "‘People have gotten old before, but never this many people and never this many people with such a high level of education … [boomers] will become obsessed with health and prevention of all the infirmities that accompany aging’ predicts Russell." (Wetzstein 1999, citing Russell.) The hypothesis put forward by Russell, by Wetzstein (1999) and by others, is that this is an 'age and stage' issue. It represents a new generational perspective reflective of the mindset and the life experience of the post mid-1940s 'baby boomer'. This website-supported best seller is part of a burgeoning industry which includes Cassel and Vallasi (1999) The Practical Guide to Aging: What Everyone Needs to Know, and Perls and Silver (1999) Living to 100: Lessons in Living to Your Maximum Potential at Any Age. "‘People have gotten old before, but never this many people and never this many people with such a high level of education … [boomers] will become obsessed with health and prevention of all the infirmities that accompany aging’ predicts Russell." (Wetzstein 1999, citing Russell.) The hypothesis put forward by Russell, by Wetzstein (1999) and by others, is that this is an 'age and stage' issue. It represents a new generational perspective reflective of the mindset and the life experience of the post mid-1940s 'baby boomer'. Boomers refuse to see 40 as middle aged (Wetzstein 1999), and would perish the thought that the Rolling Stones would ever retire. They define 50s as ‘Second youth’. (Gabriel & Molli 1995) They continue to participate in adventure and encounter holidays and subscribe to complementary health care regimes and new age approaches to daily life. They sign up for www.lovinguniversity.net and marvel at how much younger 43-yr old founder Susan Bradley looks on her website than in a recent Who Weekly (2001, p. 71). This baby boomer refusal to age has manifested itself widely in general and specialist consumer magazines, in broadcast TV and radio shows concentrating on good health and super-fitness, and in other elements of popular culture. Even given the hype, however, this new perspective might have long-term beneficial health/medical effects. The aging of the boomer generation may not be accurately predictable from the data collected from other generations with other mindsets. The back cover of Second Youth proclaims: "Desperate and aging far too fast she staked everything on discovering a natural source of Young Women's Hormones. Now, her triumph gives you thirty extra years of Second Youth. Age moved backwards for this woman. Just as it can -- this very month -- for you". (Gabriel & Molli 1995, back cover) Did someone mention snake oil? Or Bluebeard? Coupled with an optimism that allows them to forecast health and happiness into double-digit decades, however, boomers have a demonstrable suspicion of conventional medical ‘authority’ and a willingness to do their own research on health topics of interest. According to Mycek (1999) "In 1998, the [US] bill for homeopathic remedies (chiropractic and massage therapy, vitamins, yoga, herbal remedies, hypnosis, acupuncture) exceeded the total gross domestic product of all [US] hospitals put together." For boomers, a greater emphasis on health is not going to mean more of the same health care products, delivered in the same way. It is going to mean doing things differently. But is this a healthy way for us to look at aging and (shall we mention the word) death? Is our desire/burning commitment to remain indefinitely young and healthy in some way 'sick'? It is eminently reasonable to hypothesise -- as many people approaching their 'middle years' do -- that baby boomers are aiming to reinvent the aging process. (Dychtwald, 1999) The past quarter century has seen the burgeoning growth of preventative/health promotion and complementary health promoting services including nutritionists, naturopaths, chiropractors, rebalancers, meditation teachers, physiotherapists, counsellors and life coaches. The oldest members of the richest, best informed, most numerous generation in history are turning 55. The boomers (born from 1946--1960) can't put off for any longer the fact that -- chronologically -- they are approaching middle age. But what does this mean to a generation with many members who would rather be dead than old? Does the denial of chronological age, and the espousal of 'physiological age' (the premise upon which the RealAge philosophy and empire is built) represent a sick fantasy to avoid accepting our mortality? Baby boomers are a specific, much researched, sociocultural phenomenon. Their aim is to move beyond actuarial projections to re-write expectations of aging. From the self-help movement to the success of the potency drug Viagra, there is ample evidence that boomers have plans and expectations for their own aging processes that differ radically from those adopted by their parents. People born into the prosperity and plenty of the early post-WWII years often police their health attitudes and behaviours in proactive ways. These patterns are likely to impact upon their health profiles in the future and to influence the creation of services tailored to meet different hopes, fears and expectations. Who says Cher can't look young forever? Most health care planning is based on actuarial data that examines past events and extrapolates from these events into the future. However, this is not likely to result in a valid prediction of the health and aging patterns of the boomer generation. Graham May is a futurologist. He suggests that (May 2000), in anticipating the future, we are attempting either to foresee it, to manage it, or to create it. The philosophical distinctions between these perspectives provide different rationales for those who wish to influence the future. Attempts to foresee, or predict, the future – for example by extrapolating trends – presuppose that in some very particular ways the future already exists and/or is closely related to the forces evident in the present and the past. Managing the present with the future in mind accepts that present actions and decisions influence the future, and suggests that the future does not exist and is capable of being influenced by our current choices. The creation of the future – through techniques such as ‘creative visioning’ – works on the basis that once situations that do not exist have been imagined they can be brought into existence. These three approaches, separately and in parallel, offer ways of negotiating the uncertainty and essential unpredictability of the future, and of longevity and fitness. The longevity and second youth approach combines the idea of managing the future and envisioning it: 'the manifestation' approach. Baby boomers have already created a different future for our society. They are credited with re-writing the institutions of marriage (via de factos, divorce, blended families, single parents, older pregnancies); marketing (psychodemographics rather than age, sex, socioeconomic status); religion (the decline of the Church and the rise of new age philosophies, faith healing, angels on demand); education (just-in-time learning, lifelong learning); work practices -- and health. The boomers are also rewriting what aging means for them, and to them. Using popular culture starting points, such as Second Youth and RealAge, it seems that a major boomer project of the next twenty years is working to defy/turn back the aging clock. This project is invested with the hopes, fears, dreams and expectations of millions of citizens in western societies. Boomers are practical, however, as well as ‘just in time’ and they know that a belief that they can do it is half the battle. Let's assume that although many boomers are already fitter and healthier than any generation before them at their age, others may be intending to ‘make a break’ for fitness as an early priority of their retirement. Boomers may also expect their retirement years to be years of health and plenty, and they seem to indicate that they're prepared actively to work with these goals in mind. However, not all will be successful in beating their biology. How do boomers expect to manage their own chronic ailments in the future: arthritis, failing hearing and sight, late onset diabetes, heart disease, incontinence, dementia etc? Will the stem cell implants solve all foreseeable problems? Excluding alternative and complementary medical strategies, the health care industry is one of the biggest sectors of the economy representing 8% GDP (and rising). As indicated by its growing place in popular culture, health is also a hobby, pastime and pleasure – and the contemporary obsession with health is … sick. Although the social advantage to be conferred by living as healthily as possible, and as well as possible, is self-evident, it may require a level of selfishness and self-absorption unparalleled in human history. More to the point, however, this approach to getting older brings problems of its own. Firstly, it is built on a fear of aging, and a wish to deny the aging process which may become more desperate as the years (and they will) take their toll. Far from increasing the pleasure and satisfaction of 'a good age' this dynamic, operating over the decades, is as likely to build frustration, depression and a sense of powerlessness. As a (breast) cancer patient once told me: 'It's bad enough having cancer without everyone else thinking it's my fault for not having a positive enough attitude!' Aging is going to happen -- will we go with the flow - or end up like King Canute, with wet feet, trying to turn back the tide? Secondly, this perspective is counter-productive in fetishising a numerical age. When we're so focused on chronological age, biological age and the celebrating of our first, second and third 'year younger' parties (with fruit and water, please) we're not coming to terms with what's real for us in our ecological niche. Humanity is comprised of sentient, vertebrate, mammals. Far better to know our life cycle, and plan our lives to fit within it, than to pretend it can be revered. Much better to accept that we can be a very fit seventy year old (or a very unfit seventy year old) than to persuade ourselves that 'That's just my chronology, my real age is 44.' I'm sure we'll all be able to tell the difference… If anyone seriously believed the hype of living 26 years younger, you'd have to feel more than sorry for them. You'd have to suspect that maybe, even if they were blissfully unaware of it, they're a little bit sick. I gather that there's a Centre for Positive Aging recently started up in Perth: that's something altogether healthier References Cassel, C. and Vallasi, G. The Practical Guide to Aging: What Everyone Needs to Know. New York: New York University Press, 1999. Dychtwald, K. 'Age power': how the new-old will transform medicine in the 21st century, Geriatrics, vol. 54, no. 12, 1999, 22—7. Gabriel, V. and Molli, J. Second Youth, Melbourne: Bookman Press, 1995. May, G. Worldviews, assumptions and typologies of the future, Journal of Future Studies, vol. 5, no. 2, November, 2000, 37—51 Mycek, S. We’re not in Kansas anymore, Trustee, vol. 52, no. 8, 1999, 20—4 Perls, T. and Silver, M. Living to 100: Lessons in Living to Your Maximum Potential at Any Age, New York: Basic Books, 1999. Roizen, M. RealAge: Are You as Young as You Can Be? London: Thorsons, 1999 Wetzstein, C. Boomers’ new quest: to be forever young, Insight on the News, vol. 15, no. 24, 28th June, 1999, 40 Who Weekly Love is in the air, no. 474, 2 April, 2001, 71

IntroductionIn the year 2000, a group of likeminded individuals got together and convened the first annual World Barista Championship in Monte Carlo. With twelve competitors from around the globe, each competitor was judged by seven judges: one head judge who oversaw the process, two technical judges who assessed technical skills, and four sensory judges who evaluated the taste and appearance of the espresso drinks. Competitors had fifteen minutes to serve four espresso coffees, four cappuccino coffees, and four “signature” drinks that they had devised using one shot of espresso and other ingredients of their choice, but no alcohol. The competitors were also assessed on their overall barista skills, their creativity, and their ability to perform under pressure and impress the judges with their knowledge of coffee. This competition has grown to the extent that eleven years later, in 2011, 54 countries held national barista championships with the winner from each country competing for the highly coveted position of World Barista Champion. That year, Alejandro Mendez from El Salvador became the first world champion from a coffee producing nation. Champion baristas are more likely to come from coffee consuming countries than they are from coffee producing countries as countries that produce coffee seldom have a culture of espresso coffee consumption. While Ireland is not a coffee-producing nation, the Irish are the highest per capita consumers of tea in the world (Mac Con Iomaire, “Ireland”). Despite this, in 2008, Stephen Morrissey from Ireland overcame 50 other national champions to become the 2008 World Barista Champion (see, http://vimeo.com/2254130). Another Irish national champion, Colin Harmon, came fourth in this competition in both 2009 and 2010. This paper discusses the history and development of coffee and coffee houses in Dublin from the 17th century, charting how coffee culture in Dublin appeared, evolved, and stagnated before re-emerging at the beginning of the 21st century, with a remarkable win in the World Barista Championships. The historical links between coffeehouses and media—ranging from print media to electronic and social media—are discussed. In this, the coffee house acts as an informal public gathering space, what urban sociologist Ray Oldenburg calls a “third place,” neither work nor home. These “third places” provide anchors for community life and facilitate and foster broader, more creative interaction (Oldenburg). This paper will also show how competition from other “third places” such as clubs, hotels, restaurants, and bars have affected the vibrancy of coffee houses. Early Coffee Houses The first coffee house was established in Constantinople in 1554 (Tannahill 252; Huetz de Lemps 387). The first English coffee houses opened in Oxford in 1650 and in London in 1652. Coffee houses multiplied thereafter but, in 1676, when some London coffee houses became hotbeds for political protest, the city prosecutor decided to close them. The ban was soon lifted and between 1680 and 1730 Londoners discovered the pleasure of drinking coffee (Huetz de Lemps 388), although these coffee houses sold a number of hot drinks including tea and chocolate as well as coffee.The first French coffee houses opened in Marseille in 1671 and in Paris the following year. Coffee houses proliferated during the 18th century: by 1720 there were 380 public cafés in Paris and by the end of the century there were 600 (Huetz de Lemps 387). Café Procope opened in Paris in 1674 and, in the 18th century, became a literary salon with regular patrons: Voltaire, Rousseau, Diderot and Condorcet (Huetz de Lemps 387; Pitte 472). In England, coffee houses developed into exclusive clubs such as Crockford’s and the Reform, whilst elsewhere in Europe they evolved into what we identify as cafés, similar to the tea shops that would open in England in the late 19th century (Tannahill 252-53). Tea quickly displaced coffee in popularity in British coffee houses (Taylor 142). Pettigrew suggests two reasons why Great Britain became a tea-drinking nation while most of the rest of Europe took to coffee (48). The first was the power of the East India Company, chartered by Elizabeth I in 1600, which controlled the world’s biggest tea monopoly and promoted the beverage enthusiastically. The second was the difficulty England had in securing coffee from the Levant while at war with France at the end of the seventeenth century and again during the War of the Spanish Succession (1702-13). Tea also became the dominant beverage in Ireland and over a period of time became the staple beverage of the whole country. In 1835, Samuel Bewley and his son Charles dared to break the monopoly of The East India Company by importing over 2,000 chests of tea directly from Canton, China, to Ireland. His family would later become synonymous with the importation of coffee and with opening cafés in Ireland (see, Farmar for full history of the Bewley's and their activities). Ireland remains the highest per-capita consumer of tea in the world. Coffee houses have long been linked with social and political change (Kennedy, Politicks; Pincus). The notion that these new non-alcoholic drinks were responsible for the Enlightenment because people could now gather socially without getting drunk is rejected by Wheaton as frivolous, since there had always been alternatives to strong drink, and European civilisation had achieved much in the previous centuries (91). She comments additionally that cafés, as gathering places for dissenters, took over the role that taverns had long played. Pennell and Vickery support this argument adding that by offering a choice of drinks, and often sweets, at a fixed price and in a more civilized setting than most taverns provided, coffee houses and cafés were part of the rise of the modern restaurant. It is believed that, by 1700, the commercial provision of food and drink constituted the second largest occupational sector in London. Travellers’ accounts are full of descriptions of London taverns, pie shops, coffee, bun and chop houses, breakfast huts, and food hawkers (Pennell; Vickery). Dublin Coffee Houses and Later incarnations The earliest reference to coffee houses in Dublin is to the Cock Coffee House in Cook Street during the reign of Charles II (1660-85). Public dining or drinking establishments listed in the 1738 Dublin Directory include taverns, eating houses, chop houses, coffee houses, and one chocolate house in Fownes Court run by Peter Bardin (Hardiman and Kennedy 157). During the second half of the 17th century, Dublin’s merchant classes transferred allegiance from taverns to the newly fashionable coffee houses as places to conduct business. By 1698, the fashion had spread to country towns with coffee houses found in Cork, Limerick, Kilkenny, Clonmel, Wexford, and Galway, and slightly later in Belfast and Waterford in the 18th century. Maxwell lists some of Dublin’s leading coffee houses and taverns, noting their clientele: There were Lucas’s Coffee House, on Cork Hill (the scene of many duels), frequented by fashionable young men; the Phoenix, in Werburgh Street, where political dinners were held; Dick’s Coffee House, in Skinner’s Row, much patronized by literary men, for it was over a bookseller’s; the Eagle, in Eustace Street, where meetings of the Volunteers were held; the Old Sot’s Hole, near Essex Bridge, famous for its beefsteaks and ale; the Eagle Tavern, on Cork Hill, which was demolished at the same time as Lucas’s to make room for the Royal Exchange; and many others. (76) Many of the early taverns were situated around the Winetavern Street, Cook Street, and Fishamble Street area. (see Fig. 1) Taverns, and later coffee houses, became meeting places for gentlemen and centres for debate and the exchange of ideas. In 1706, Francis Dickson published the Flying Post newspaper at the Four Courts coffee house in Winetavern Street. The Bear Tavern (1725) and the Black Lyon (1735), where a Masonic Lodge assembled every Wednesday, were also located on this street (Gilbert v.1 160). Dick’s Coffee house was established in the late 17th century by bookseller and newspaper proprietor Richard Pue, and remained open until 1780 when the building was demolished. In 1740, Dick’s customers were described thus: Ye citizens, gentlemen, lawyers and squires,who summer and winter surround our great fires,ye quidnuncs! who frequently come into Pue’s,To live upon politicks, coffee, and news. (Gilbert v.1 174) There has long been an association between coffeehouses and publishing books, pamphlets and particularly newspapers. Other Dublin publishers and newspapermen who owned coffee houses included Richard Norris and Thomas Bacon. Until the 1850s, newspapers were burdened with a number of taxes: on the newsprint, a stamp duty, and on each advertisement. By 1865, these taxes had virtually disappeared, resulting in the appearance of 30 new newspapers in Ireland, 24 of them in Dublin. Most people read from copies which were available free of charge in taverns, clubs, and coffee houses (MacGiolla Phadraig). Coffee houses also kept copies of international newspapers. On 4 May 1706, Francis Dickson notes in the Dublin Intelligence that he held the Paris and London Gazettes, Leyden Gazette and Slip, the Paris and Hague Lettres à la Main, Daily Courant, Post-man, Flying Post, Post-script and Manuscripts in his coffeehouse in Winetavern Street (Kennedy, “Dublin”). Henry Berry’s analysis of shop signs in Dublin identifies 24 different coffee houses in Dublin, with the main clusters in Essex Street near the Custom’s House (Cocoa Tree, Bacon’s, Dempster’s, Dublin, Merchant’s, Norris’s, and Walsh’s) Cork Hill (Lucas’s, St Lawrence’s, and Solyman’s) Skinners’ Row (Bow’s’, Darby’s, and Dick’s) Christ Church Yard (Four Courts, and London) College Green (Jack’s, and Parliament) and Crampton Court (Exchange, and Little Dublin). (see Figure 1, below, for these clusters and the locations of other Dublin coffee houses.) The earliest to be referenced is the Cock Coffee House in Cook Street during the reign of Charles II (1660-85), with Solyman’s (1691), Bow’s (1692), and Patt’s on High Street (1699), all mentioned in print before the 18th century. The name of one, the Cocoa Tree, suggests that chocolate was also served in this coffee house. More evidence of the variety of beverages sold in coffee houses comes from Gilbert who notes that in 1730, one Dublin poet wrote of George Carterwright’s wife at The Custom House Coffee House on Essex Street: Her coffee’s fresh and fresh her tea,Sweet her cream, ptizan, and whea,her drams, of ev’ry sort, we findboth good and pleasant, in their kind. (v. 2 161) Figure 1: Map of Dublin indicating Coffee House clusters 1 = Sackville St.; 2 = Winetavern St.; 3 = Essex St.; 4 = Cork Hill; 5 = Skinner's Row; 6 = College Green.; 7 = Christ Church Yard; 8 = Crampton Court.; 9 = Cook St.; 10 = High St.; 11 = Eustace St.; 12 = Werburgh St.; 13 = Fishamble St.; 14 = Westmorland St.; 15 = South Great George's St.; 16 = Grafton St.; 17 = Kildare St.; 18 = Dame St.; 19 = Anglesea Row; 20 = Foster Place; 21 = Poolbeg St.; 22 = Fleet St.; 23 = Burgh Quay.A = Cafe de Paris, Lincoln Place; B = Red Bank Restaurant, D'Olier St.; C = Morrison's Hotel, Nassau St.; D = Shelbourne Hotel, St. Stephen's Green; E = Jury's Hotel, Dame St. Some coffee houses transformed into the gentlemen’s clubs that appeared in London, Paris and Dublin in the 17th century. These clubs originally met in coffee houses, then taverns, until later proprietary clubs became fashionable. Dublin anticipated London in club fashions with members of the Kildare Street Club (1782) and the Sackville Street Club (1794) owning the premises of their clubhouse, thus dispensing with the proprietor. The first London club to be owned by the members seems to be Arthur’s, founded in 1811 (McDowell 4) and this practice became widespread throughout the 19th century in both London and Dublin. The origin of one of Dublin’s most famous clubs, Daly’s Club, was a chocolate house opened by Patrick Daly in c.1762–65 in premises at 2–3 Dame Street (Brooke). It prospered sufficiently to commission its own granite-faced building on College Green between Anglesea Street and Foster Place which opened in 1789 (Liddy 51). Daly’s Club, “where half the land of Ireland has changed hands”, was renowned for the gambling that took place there (Montgomery 39). Daly’s sumptuous palace catered very well (and discreetly) for honourable Members of Parliament and rich “bucks” alike (Craig 222). The changing political and social landscape following the Act of Union led to Daly’s slow demise and its eventual closure in 1823 (Liddy 51). Coincidentally, the first Starbucks in Ireland opened in 2005 in the same location. Once gentlemen’s clubs had designated buildings where members could eat, drink, socialise, and stay overnight, taverns and coffee houses faced competition from the best Dublin hotels which also had coffee rooms “in which gentlemen could read papers, write letters, take coffee and wine in the evening—an exiguous substitute for a club” (McDowell 17). There were at least 15 establishments in Dublin city claiming to be hotels by 1789 (Corr 1) and their numbers grew in the 19th century, an expansion which was particularly influenced by the growth of railways. By 1790, Dublin’s public houses (“pubs”) outnumbered its coffee houses with Dublin boasting 1,300 (Rooney 132). Names like the Goose and Gridiron, Harp and Crown, Horseshoe and Magpie, and Hen and Chickens—fashionable during the 17th and 18th centuries in Ireland—hung on decorative signs for those who could not read. Throughout the 20th century, the public house provided the dominant “third place” in Irish society, and the drink of choice for itd predominantly male customers was a frothy pint of Guinness. Newspapers were available in public houses and many newspapermen had their own favourite hostelries such as Mulligan’s of Poolbeg Street; The Pearl, and The Palace on Fleet Street; and The White Horse Inn on Burgh Quay. Any coffee served in these establishments prior to the arrival of the new coffee culture in the 21st century was, however, of the powdered instant variety. Hotels / Restaurants with Coffee Rooms From the mid-19th century, the public dining landscape of Dublin changed in line with London and other large cities in the United Kingdom. Restaurants did appear gradually in the United Kingdom and research suggests that one possible reason for this growth from the 1860s onwards was the Refreshment Houses and Wine Licences Act (1860). The object of this act was to “reunite the business of eating and drinking”, thereby encouraging public sobriety (Mac Con Iomaire, “Emergence” v.2 95). Advertisements for Dublin restaurants appeared in The Irish Times from the 1860s. Thom’s Directory includes listings for Dining Rooms from the 1870s and Refreshment Rooms are listed from the 1880s. This pattern continued until 1909, when Thom’s Directory first includes a listing for “Restaurants and Tea Rooms”. Some of the establishments that advertised separate coffee rooms include Dublin’s first French restaurant, the Café de Paris, The Red Bank Restaurant, Morrison’s Hotel, Shelbourne Hotel, and Jury’s Hotel (see Fig. 1). The pattern of separate ladies’ coffee rooms emerged in Dublin and London during the latter half of the 19th century and mixed sex dining only became popular around the last decade of the 19th century, partly infuenced by Cesar Ritz and Auguste Escoffier (Mac Con Iomaire, “Public Dining”). Irish Cafés: From Bewley’s to Starbucks A number of cafés appeared at the beginning of the 20th century, most notably Robert Roberts and Bewley’s, both of which were owned by Quaker families. Ernest Bewley took over the running of the Bewley’s importation business in the 1890s and opened a number of Oriental Cafés; South Great Georges Street (1894), Westmoreland Street (1896), and what became the landmark Bewley’s Oriental Café in Grafton Street (1927). Drawing influence from the grand cafés of Paris and Vienna, oriental tearooms, and Egyptian architecture (inspired by the discovery in 1922 of Tutankhamen’s Tomb), the Grafton Street business brought a touch of the exotic into the newly formed Irish Free State. Bewley’s cafés became the haunt of many of Ireland’s leading literary figures, including Samuel Becket, Sean O’Casey, and James Joyce who mentioned the café in his book, Dubliners. A full history of Bewley’s is available (Farmar). It is important to note, however, that pots of tea were sold in equal measure to mugs of coffee in Bewley’s. The cafés changed over time from waitress- to self-service and a failure to adapt to changing fashions led to the business being sold, with only the flagship café in Grafton Street remaining open in a revised capacity. It was not until the beginning of the 21st century that a new wave of coffee house culture swept Ireland. This was based around speciality coffee beverages such as espressos, cappuccinos, lattés, macchiatos, and frappuccinnos. This new phenomenon coincided with the unprecedented growth in the Irish economy, during which Ireland became known as the “Celtic Tiger” (Murphy 3). One aspect of this period was a building boom and a subsequent growth in apartment living in the Dublin city centre. The American sitcom Friends and its fictional coffee house, “Central Perk,” may also have helped popularise the use of coffee houses as “third spaces” (Oldenberg) among young apartment dwellers in Dublin. This was also the era of the “dotcom boom” when many young entrepreneurs, software designers, webmasters, and stock market investors were using coffee houses as meeting places for business and also as ad hoc office spaces. This trend is very similar to the situation in the 17th and early 18th centuries where coffeehouses became known as sites for business dealings. Various theories explaining the growth of the new café culture have circulated, with reasons ranging from a growth in Eastern European migrants, anti-smoking legislation, returning sophisticated Irish emigrants, and increased affluence (Fenton). Dublin pubs, facing competition from the new coffee culture, began installing espresso coffee machines made by companies such as Gaggia to attract customers more interested in a good latté than a lager and it is within this context that Irish baristas gained such success in the World Barista competition. In 2001 the Georges Street branch of Bewley’s was taken over by a chain called Café, Bar, Deli specialising in serving good food at reasonable prices. Many ex-Bewley’s staff members subsequently opened their own businesses, roasting coffee and running cafés. Irish-owned coffee chains such as Java Republic, Insomnia, and O’Brien’s Sandwich Bars continued to thrive despite the competition from coffee chains Starbucks and Costa Café. Indeed, so successful was the handmade Irish sandwich and coffee business that, before the economic downturn affected its business, Irish franchise O’Brien’s operated in over 18 countries. The Café, Bar, Deli group had also begun to franchise its operations in 2008 when it too became a victim of the global economic downturn. With the growth of the Internet, many newspapers have experienced falling sales of their printed format and rising uptake of their electronic versions. Most Dublin coffee houses today provide wireless Internet connections so their customers can read not only the local newspapers online, but also others from all over the globe, similar to Francis Dickenson’s coffee house in Winetavern Street in the early 18th century. Dublin has become Europe’s Silicon Valley, housing the European headquarters for companies such as Google, Yahoo, Ebay, Paypal, and Facebook. There are currently plans to provide free wireless connectivity throughout Dublin’s city centre in order to promote e-commerce, however, some coffee houses shut off the wireless Internet in their establishments at certain times of the week in order to promote more social interaction to ensure that these “third places” remain “great good places” at the heart of the community (Oldenburg). Conclusion Ireland is not a country that is normally associated with a coffee culture but coffee houses have been part of the fabric of that country since they emerged in Dublin in the 17th century. These Dublin coffee houses prospered in the 18th century, and survived strong competition from clubs and hotels in the 19th century, and from restaurant and public houses into the 20th century. In 2008, when Stephen Morrissey won the coveted title of World Barista Champion, Ireland’s place as a coffee consuming country was re-established. 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