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Автор: Grafiati
Опубліковано: 30 травня 2022
Оновлено: 31 травня 2022

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1

Xi, Jing, Kathleen Harnden, Jingqin Luo, Greg S. Call, Elizabeth Mauer, Karyn Ronski, Cynthia X. Ma, and Neil Vasan. "Abstract P3-09-04: Genomic landscape of HER2-negative advanced or metastatic breast cancer with PIK3CA gain-of-function mutations." Cancer Research 82, no. 4_Supplement (February 15, 2022): P3–09–04—P3–09–04. http://dx.doi.org/10.1158/1538-7445.sabcs21-p3-09-04.

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Abstract Background: Alpelisib and fulvestrant are used as a combination treatment option for postmenopausal PIK3CA-mutated, hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced or metastatic breast cancer (a/mBC) patients. However, despite the presence of activating mutations in PIK3CA, the majority of patients do not derive benefit, or ultimately progress while on alpelisib therapy. Here, we investigate the genomic landscape of PIK3CA-mutated, HER2- a/mBC using next-generation sequencing (NGS) to provide insight into possible mechanisms of therapeutic resistance to alpelisib/fulvestrant and to identify potential targetable pathways. Methods: We utilized the Tempus LENS platform to retrospectively analyze de-identified NGS data from 2,918 a/mBC patients with formalin-fixed, paraffin-embedded tumor biopsies sequenced using the Tempus|xT solid tumor assay (DNA-seq of 595-648 genes at 500x coverage; full transcriptome RNA-seq). Mutations identified included germline and/or somatic single nucleotide variants, insertions/deletions and copy number variations (gains defined as ≥8 copies). We used curated clinical data to determine HER2 and hormone receptor (ER/PR) status. Results: Among 2,918 a/mBC patients, we identified somatic mutations in PIK3CA in 782 (26.8%). Within these tumors, 629 (80.4%) had one of the 11 mutations currently included in the alpelisib companion diagnostic, and we focused on this population (here defined as mut-PIK3CA). Of these 629, 546 (86.8%) were HER2-, with 176 (32.3%) and 370 (67.7%) derived from primary and metastatic tumors, respectively. Cases were further classified as HR+ (defined as ER+ or PR+) or triple negative (TNBC). While the majority of mutPIK3CA samples were identified in HR+ disease, 10% of the cases occurred in TNBC. Within the mutPIK3CA cohort, tumor mutational burden high (TMB-H; defined as ≥10 mutations/MB) was detected in 11.5% of samples, while microsatellite instability high (MSI-H) was detected in 0.5%. MSI-H was detected at a higher frequency in TNBC compared to HR+. Overall, the most commonly co-mutated genes among mutPIK3CA, HER2- samples were TP53 (34.6%), CDH1 (21.6%), ESR1 (12.3%), KMT2C (11%), MAP3K1 (9.5%), ARID1A (8.1%), PTEN (6.8%), GATA3 (6.6%), NF1 (5.9%), and TBX3 (5.9%) among others (Table 1); some of these genes have previously been implicated in resistance to endocrine therapy or PI3K inhibitor. In addition, in HR+ disease, metastatic samples had a higher frequency of mutations in genes implicated in endocrine resistance, such as ESR1 (18.7% vs 1.9%), ERBB2 (3.3% vs 2.6%), NF1 (6.8% vs 2.6%), compared to primary tumors. We also identified copy number gains (CNG) in several cell cycle genes, including: CCND1 (15.2%), CDK4 (2.7%), and AURKA (2.6%) (Table 1). Finally, further analyses at the transcript-level are the subject of on-going research. Conclusions: Our study highlights that there is substantial genomic heterogeneity among mutPIK3CA, HER2- a/mBCs. Across a series of comparisons between primary and metastatic samples, as well as HR+ and TNBC subtypes, we identified a number of co-mutations that occur alongside mutPIK3CA and which could be potentially exploited by targeted therapies. Future studies are needed to assess the prognostic/predictive role of these and other candidate gene alterations. Table 1. Genomic features of mutPIK3CA, HER2– a/mBCPrimaryMetastaticTotalAny PIK3CA Mutation1255527782mutPIK3CA2204425629HER2– (n=176)HER2– (n=370)546HR+ HER2– 154 (88%)TNBC 22 (12%)HR+ HER2– 337 (91%)TNBC 33 (9%)TMB-H16 (10.3%)2 (9.1%)41 (12%)4 (12%)63 (11.5%)MSI-H1 (0.6%)1 (4.5%)0 (0%)1 (3.0%)3 (0.5%)Co-mutations (mutPIK3CA): n (%)TP5347 (30.5%)14 (63.6%)101 (30%)27 (81.8%)189 (34.6%)CDH137 (24%)1 (4.5%)75 (22.3%)5 (15.2%)118 (21.6%)KMT2C17 (11%)1 (4.5%)40 (11.9%)2 (6.1%)60 (11%)MAP3K117 (11%)1 (4.5%)31 (9.2%)1 (3%)50 (9.2%)ARID1A15 (9.7%)0 (0%)26 (7.7%)2 (6.1%)43(7.9%)PTEN12 (7.8%)1 (4.5%)21 (6.2%)3 (9.1%)37 (6.8%)GATA311 (7.1%)0 (0%)23 (6.8%)2 (6.1%)35 (6.6%)TBX311 (7.1%)1 (4.5%)19 (5.6%)1 (3%)32 (5.9%)NCOR12 (1.3%)1 (4.5%)18 (5.3%)0 (0%)21 (3.8%)FOXA17 (4.5%)2 (9.1%)10 (3%)1 (3%)20 (3.7%)MAP2K41 (0.6%)1 (4.5%)12 (3.6%)1 (3%)15 (2.7%)ESR13 (1.9%)0 (0%)63 (18.7%)1 (3%)67 (12.3%)PIK3R13 (1.9%)0 (0%)4 (1.2%)0 (0%)7 (1.3%)AKT11 (0.6%)0 (0%)1 (0.6%)0 (0%)2 (0.4%)RB15 (3.2%)1 (4.5%)8 (2.4%)1 (3%)15 (2.7%)NF14 (2.6%)3 (13.6%)23 (6.8%)2 (6.1%)32 (5.9%)ERBB24 (2.6%)4 (18.2%)11 (3.3%)2 (6.1%)21 (3.8%)CCND1 CNG22 (14%)0 (0%)61 (18%)0 (0%)83 (15.2%)AURKA CNG3 (1.9%)0 (0%)11 (3.3%)0 (0%)14 (2.6%)CDK4 CNG5 (3.2%)1 (4.5%)7 (2.1%)1 (3.0%)14 (2.6%)1any somatic variant detected in PIK3CA2somatic PIK3CA mutations among the 11 currently included in the alpelisib companion diagnostic (C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, and H1047Y) Citation Format: Jing Xi, Kathleen Harnden, Jingqin Luo, Greg S. Call, Elizabeth Mauer, Karyn Ronski, Cynthia X. Ma, Neil Vasan. Genomic landscape of HER2-negative advanced or metastatic breast cancer with PIK3CA gain-of-function mutations [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-09-04.
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2

Guglielmelli, Paola, Giada Rotunno, Annalisa Pacilli, Elisa Rumi, Vittorio Rosti, Federica Delaini, Margherita Maffioli, et al. "Prognostic Impact of Bone Marrow Fibrosis in Primary Myelofibrosis: A Study of Agimm Group on 540 Patients." Blood 126, no. 23 (December 3, 2015): 351. http://dx.doi.org/10.1182/blood.v126.23.351.351.

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Abstract Background. The prognostic significance of bone marrow (BM) fibrosis grade in pts with primary myelofibrosis (PMF) is debated. A fibrosis grade greater than 1 was associated with a 2-fold higher risk of death compared with pts with early/prefibrotic MF (grade 0) [Thiele J, Ann Hematol 2006]. Recent data suggest that more accurate prediction of survival is achieved when fibrosis grade is added to IPSS [Verner C, Blood 2008; Giannelli U, Mod Pathol 2012]. Aim. To analyze the prognostic impact of fibrosis in diagnostic BM samples of 540 WHO-2008 diagnosed PMF pts with extensive clinical and molecular information collected in 6 Italian centers belonging to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative). Methods. The clinical variables assessed were those previously identified as prognostically relevant in the IPSS score. Published methods were used to screen mutations of JAK2, MPL, CALR, EZH2, ASXL1, IDH1/2 and SRSF2. European consensus scoring system was used to grade fibrosis (on a scale of MF-0 to MF-3). The prognostic value of fibrosis with regard to overall survival (OS) was estimated by Kaplan-Meier method and Cox regression. Results. Pts' median age was 61y; median follow-up 3.7y; median OS 10.5y; 184 pts (34.1%) died. IPSS risk category: low 33.7%, Int-1 27.7%, Int-2 19.1%, High-risk 19.5%. Mutational rate: JAK2 V617F 62.6%, CALR 20.7% (type-1/1-like 77.7%, type2/2-like-2 21.4%), MPL W515 5.9%; 62 (11.5%) were triple negative (TN). 171 pts (31.7%) were High-Molecular Risk (HMR) category (Vannucchi AM, Leukemia 2013); mutation rate: EZH2 7.2%, ASXL1 22.2%, IDH1-2 2.4%, SRSF2 8.3%. According to fibrosis grading, 50 pts were MF-0 (9.3%), 180 MF-1 (33.3%), 196 MF-2 (36.3%), 114 MF-3 (21.1%). Compared with both MF-0 and MF-1, MF-2 and MF-3 pts presented more frequently constitutional symptoms (P<.0001), larger splenomegaly (P<.0001), greater risk of developing anemia (P<.0001) or thrombocytopenia (P=.003). We found a significant association (P<.0001) between IPSS higher/Int-2 risk categories and MF-2 and -3 (20.5% and 37.8%, respectively, vs 14.8% and 6.0% for MF-0 and -1). There was no correlation between fibrosis grade and phenotypic driver mutations; in particular, TN pts were equally distributed among MF fibrosis grades (10%, 10.6%, 14.3% and 8.8% from MF-0 to -3, respectively). Conversely, the frequency of HMR pts increased progressively according to fibrosis grade: 8 pts MF-0 (16%), 46 MF-1 (25.6%), 66 MF-2 (33.7%) and 51 MF-3 (44.7%) (P<.0001). In particular, we found a significant association between fibrosis grade and ASXL1 (12%, 15%, 23.5% and 36% from MF-0 to -3; P<.0001) and EZH2 (2%, 3.9%, 8.2%, 13.2%; P=.01) mutations. Also, pts with 2 or more HMR mutated genes were preferentially MF-2 or -3 ( 0%, 4.4% 10.2% and 10.5% from MF-0 to -3; P=.001). Median OS was significantly shorter in pts with MF-2 (OS 6.7y, HR 7.3, IC95% 2.7-20.0; P<.0001) and MF-3 (OS 7.2y, HR 8.7, IC95% 3.1-24.2; P<.0001) compared with MF-1 (14.7y; HR 3.9, IC95% 1.4-10.9, P=.008) and MF-0 (P<.0001) used as reference group (OS not reached) (Figure). Excluding MF-0, MF-2 and -3 maintained negative prognostic impact with HR 1.9 (1.3-2.6; P=.001) and 2.2 (1.5-3.3; P<.0001) respectively vs MF-1. The impact of fibrosis on OS was maintained when analysis was restricted to younger (≤65y) pts. In multivariate analysis using the individual IPSS variables, grade MF-2 and -3 were independently predictive of survival (HR 3.9 (1.4-10.8), and HR 4.2 (1.5-12.0), respectively, P=.008 for both). The negative impact on survival of MF-2/-3 was maintained regardless of IPSS category, HMR status, number of HMR mutated genes and driver mutations, included as covariates (Table). In low, Int-1 and Int-2, but not high-risk IPSS categories, MF-2/-3 associated with reduced survival (P<.03). Conclusions. Overall, these results indicate that higher grades (MF-2 and MF-3) of fibrosis correlate with defined clinical and molecular variables and independently negatively impact on OS in PMF, suggesting the opportunity to explore its value in the setting of clinical and molecular prognostic scores for PMF. Table. Multivariate Analysis Variables HR 95% CI P value HMR status 2.4 1.5-3.7 <.0001 HMR≥2mutations 4.3 2.8-6.4 .009 IPSS scoring Int1 2.9 1.6-5.1 <.0001 Int2 10.0 5.6-17.7 <.0001 High 9.7 5.5-17.2 <.0001 Driver mutations CALR type2 3.4 1.3-8.6 .010 JAK2/MPL 2.4 1.4-4.3 .003 TN 4.5 2.3-8.8 <.0001 Fibrosis MF-2/MF-3 3.8 1.4-10.6 .010 Figure 1. Figure 1. Disclosures Passamonti: Novartis: Consultancy, Honoraria, Speakers Bureau. Barbui:Novartis: Speakers Bureau. Vannucchi:Shire: Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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3

Sorigue, Marc, Juan-Manuel Sancho, Santiago Mercadal, Ruben Fernández-Álvarez, Helena Pomares, Olga Garcia, Eva González-Barca, et al. "Prevalence, Predictive Factors Therapy and Outcome of Patients with Follicular Lymphoma Refractory to First Line Immunochemotherapy." Blood 126, no. 23 (December 3, 2015): 1510. http://dx.doi.org/10.1182/blood.v126.23.1510.1510.

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Abstract Background: Follicular lymphoma (FL) is the most frequent indolent lymphoma and is characterized by a high response to immunochemotherapy (ICT). However, patients refractory to first-line ICT have a worse prognosis. The objective of this study was to determine the prevalence of refractory FL, the factors that predict refractoriness as well as the salvage treatment and outcome. Patients and methods: This is a retrospective analysis including stage II-IV FL patients treated with first-line ICT in 3 Spanish institutions. The cohort was divided into ICT-refractory patients (less than partial response after induction or maintenance/consolidation therapy, as well as relapse or progression within 6 months of the last dose of therapy) and ICT-sensitive. Baseline features, therapy received and outcome were analyzed. Results: 283 patients were included, the median age was 58 years-old (range 28 to 85) and 53% were female. 200/231 (87%) had a good performance status (ECOG < 2), 260/295 (88%) presented with stages III and IV and 163/284 (57%) had bone marrow involvement. High-risk FLIPI score was seen in 108/256 (42%), high serum LDH in 78/263 (28%) and high serum B2-microglobulin in 138/253 (54%). RCHOP was administered to 226 (80%), RCVP to 36 (13%) and rituximab in combination with fludarabine or bendamustine-based therapy to 21 (7%). Seventeen patients received consolidation with radioimmunotherapy and 140 received maintenance with rituximab (n=137) or interferon (n=3). Sixteen patients received complementary radiotherapy. Forty-three (16%) patients were ICT-refractory (37 within 6 months of the completion of induction and 6 during or within 6 months of the completion of maintenance/consolidation therapy). On univariate analysis, high-risk FLIPI (OR 5.4, [95% CI 2.3-12.6]), high-risk FLIPI2 (5.4, [2.4-12.4]), B symptoms (3.2, [1.6-6.6]), ECOG ≥ 2 (4.6, [2-10.9]), involvement of > 4 nodal regions (2.3, [1.02-5.3]), hepatomegaly (7.5, [2.6-21.5]), splenomegaly (2.8, [1.4-5.9]), high B2-microglobulin (4, [1.7-9.5]), high serum LDH (3.9, [1.8-8]) and treatment with RCVP (compared with RCHOP, 2.8, [1.2-6.2]) were correlated with refractoriness. On multivariate analysis, high-risk FLIPI score (4.9, [2.1-11.7]) and treatment with RCVP (3.4, [1.2-9.4]) were the only variables associated with refractoriness. After exclusion of FLIPI, ECOG ≥ 2 (3, [1.1-8.4]) and high serum LDH (4.7, [2-11]) were correlated with refractoriness, in addition to RCVP therapy (4.5, [1.5-13.2]). Ten-year OS probabilities in ICT-sensitive and ICT-refractory patients were 83% (95% CI 76%-90%) and 33% (12%-54%), respectively (p<0.001) (Figure 1). ICT-refractory patients were more likely to be also refractory to second-line therapies than ICT-sensitive patients (21/31 [68%] vs 10/58 [17%], p<0.001). In addition, histological transformation was suspected by clinical or biological features or confirmed by tissue biopsy in 11/43 ICT-refractory and 8/240 ICT-sensitive (p<0.0001). Death among ICT-refractory patients was more frequently due to lymphoma than in ICT-sensitive patients (19/23 [83%] vs 14/28 [50%], p=0.033). Conclusions: In this series of FL treated with first-line ICT, the prevalence of refractoriness was low and occurred most frequently during or within 6 months of induction rather than maintenance/consolidation therapy. FLIPI score and RCVP treatment (compared to RCHOP) were predictive of refractoriness. The response rate of ICT-refractory FL patients to second-line therapy is low and the prognosis is poor. Supported in part by RD12/0036/0029 del RTICC, Instituto Carlos III. Figure 1. Overall survival in immunochemotherapy (ICT)-sensitive and ICT-refractory patients (p<001) Figure 1. Overall survival in immunochemotherapy (ICT)-sensitive and ICT-refractory patients (p<001) Disclosures Sancho: CELLTRION, Inc.: Research Funding. Sureda:Seattle Genetics Inc.: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau.
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4

Magnus, Dan, Santosh Bhatta, and Julie Mytton. "432 Establishing injury surveillance in emergency departments in Nepal: epidemiology and burden of paediatric injuries." Emergency Medicine Journal 37, no. 12 (November 23, 2020): 825.2–827. http://dx.doi.org/10.1136/emj-2020-rcemabstracts.7.

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Анотація:
Aims/Objectives/BackgroundGlobally, injuries cause more than 5 million deaths annually. Children and young people are a particularly vulnerable group and injuries are the leading cause of death in people aged 5–24 years globally and a leading cause of disability.In most low and middle-income countries where the majority of global child injury burden occurs, systems for routinely collecting injury data are limited. There is a continuing need for better data on childhood injuries and for injury surveillance.The aim of our study was to introduce a hospital-based injury surveillance tool – the first of its kind in Nepal and explore its feasibility. We undertook prospective collection of data on all injuries/trauma presenting to 2 hospital emergency departments to describe the epidemiology of paediatric hospital injury presentations and associated risk factors.Methods/DesignA new injury surveillance system for use in emergency departments in Nepal was designed and used to collect data on patients presenting with injuries. Data were collected prospectively in two hospitals 24 h a day over 12 months (April 2019 - March 2020) by trained data collectors using tablet computers.Abstract 432 Table 1Socio-demographic profile and characteristics of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020 (N=2696)CharacteristicsFrequencyGender Male 1778 Female 918 Age groups 0–4 years 653 5–9 years 866 10–14 years 680 15–17 years 497 Median year (IRQ) 8 (5 – 13) Ethnicity/caste Janajati 1384 Brahmin/Chhetri 892 Dalit 148 Madhesi 146 Muslim 74 Others 50 Unknown 2 Place where injury occurred Home/Compound 1576 Highway/road/street 636 School 233 Recreational area 138 Workplace 76 Other 37 Activities at the time injury occurred Leisure/Play 1889 Travelling (other than to/from school/work) 296 Work 202 Travelling (to/from school/work) 184 Education 42 Organised sports 11 Other 52 Unknown 20 Intent of injury Unintentional 2560 Intentional (self-harm) 61 Intentional (assault) 75 Unintentional (n=2560) Fall 912 Animal or insect related 728 Road traffic injury 356 Injured by a blunt force 201 Stabbed, cut or pierced 176 Fire, burn or scald 65 Poisoning 52 Suffocation/choking 36 Electrocution 12 Drowning and submersion 7 Other 13 Unknown 2 Self-harm (n=61) Poisoning 38 Hanging, strangulation, suffocation 12 Stabbed, cut or pierced 6 Injured by blunt object 4 Other 1 Assault (n=75) Bodily force (physical violence) 43 Injured by blunt object 18 Stabbed, cut or pierced 8 Pushing from a high place 2 Poisoning 2 Sexual assault 1 Other 1 Nature of injury (one most severe) Cuts, bites or open wound 1378 Bruise or superficial injury 383 Fracture 299 Sprain, strain or dislocation 243 Internal injury 124 Head Injury/Concussion 83 Burns 67 Other 115 Unknown 2 Not recorded 2 Severity of injury No apparent injury 125 Minor 1645 Moderate 813 Severe 111 Not recorded 2 Disposition Discharged 2317 Admitted to hospital 164 Transferred to another hospital 179 Died 21 Leave Against Medical Advice (LAMA) 11 Unknown 2 Not recorded 2 Note:Not recorded = missing cases95% CI calculated using one proportion test and normal approximation method in Minitab.Abstract 432 Table 2Distribution of injuries by age-group, sex and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups & Sex0 - 4 years5 - 9 years10–14 years15–17 yearsMaleFemaleTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 239 (26.2) 328 (36.0) 249 (27.3) 96 (10.5) 636 (69.7) 276 (30.3) 912 (100) Animal or insect related 175 (24.0) 260 (35.7) 190 (26.1) 103 (14.1) 470 (64.6) 258 (35.4) 728 (100) Road traffic injury 49 (13.8) 108 (30.3) 86 (24.2) 113 (31.7) 223 (62.6) 133 (37.4) 356 (100) Injured by a blunt force 54 (26.9) 74 (36.8) 49 (24.4) 24 (11.9) 150 (74.6) 51 (25.4) 201 (100) Stabbed, cut or pierced 20 (11.4) 56 (31.8) 49 (27.8) 51 (29.0) 127 (72.2) 49 (27.8) 176 (100) Fire, burn or scald 42 (64.6) 10 (15.4) 9 (13.8) 4 (6.2) 27 (41.5) 38 (58.5) 65 (100) Poisoning 33 (63.5) 6 (11.5) 5 (9.6) 8 (15.4) 26 (50.0) 26 (50.0) 52 (100) Suffocation/choking 24 (66.7) 5 (13.9) 2 (5.6) 5 (13.9) 20 (55.6) 16 (44.4) 36 (100) Electrocution 2 (15.7) 0 (0.0) 3 (25.0) 7 (58.3) 10 (83.3) 2 (16.7) 12 (100) Drowning and submersion 1 (14.3) 1 (14.3) 3 (42.9) 2 (28.6) 3 (42.9) 4 (57.1) 7 (100) Other 6 (46.2) 4 (30.8) 3 (23.1) 0 (0.0) 10 (76.9) 3 (23.1) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) 2 (100) Total 647 (25.3) 852 (33.3) 648 (25.3) 413 (16.1) 1702 (66.5) 858 (33.5) 2560 (100) Self-harm Poisoning 0 (0.0) 0 (0.0) 6 (15.8) 32 (84.2) 7 (18.4) 31 (81.6) 38 (100) Hanging 0 (0.0) 0 (0.0) 3 (25.0) 9 (75.0) 4 (33.3) 8 (66.7) 12 (100) Stabbed, cut or pierced 0 (0.0) 0 (0.0) 2 (33.3) 4 (66.7) 1 (16.7) 5 (83.3) 6 (100) Injured by blunt object 0 (0.0) 2 (50.0) 2 (50.0) 0 (0.0) 4 (100) 0 (0.0) 4 (100) Other 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) 0 (0.0) 1 (100) Total 0 (0.0) 2 (3.3) 13 (21.3) 46 (75.4) 17 (27.9) 44 (72.1) 61 (100) Assault Bodily force (physical violence) 3 (7.0) 1 (2.3) 11 (25.6) 28 (65.1) 37 (86.0) 6 (14.0) 43 (100) Injured by blunt object 2 (11.1) 8 (44.4) 4 (22.2) 4 (22.2) 13 (72.2) 5 (27.8) 18 (100) Stabbed, cut or pierced 1 (12.5) 0 (0.0) 2 (25.0) 5 (62.5) 7 (87.5) 1 (12.5) 8 (100) Pushing from a high place 0 (0.0) 1 (50.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 2 (100) Poisoning 0 (0.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 1 (50.0) 2 (100) Sexual assault 0 (0.0) 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Other 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Total 6 (8.0) 12 (16.0) 19 (25.3) 38 (50.7) 59 (78.7) 16 (21.3) 75 (100) Abstract 432 Table 3Association of injury location, nature and severity with age among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups0 – 4 years5 – 9 years10–14 years15–17 yearsTotalChi-SquareInjury characteristicsn (%)n (%)n (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 537 (34.1) 504 (32.0) 319 (20.2) 216 (13.7) 1576 (100) <0.001 Highway/road/street 85 (13.4) 196 (30.8) 190 (29.9) 165 (25.9) 636 (100) School 15 (6.4) 107 (45.9) 85 (36.5) 26 (11.2) 233 (100) Recreational area 9 (6.5) 44 (31.9) 55 (39.9) 30 (21.7) 138 (100) Workplace 1 (1.3) 4 (5.3) 19 (25.0) 52 (68.4) 76 (100) Other 6 (16.2) 11 (29.7) 12 (32.4) 8 (21.6) 37 (100) Total 653 (24.2) 866 (32.1) 680 (25.2) 497 (18.4) 2696 (100) Nature of injury Cuts, bites or open wound 328 (23.8) 506 (36.7) 314 (22.8) 230 (16.7) 1378 (100) <0.001 Bruise or superficial injury 81 (21.1) 99 (25.8) 118 (30.8) 85 (22.2) 383 (100) Fracture 48 (16.1) 101 (33.8) 112 (37.5) 38 (12.7) 299 (100) Sprain, strain or dislocation 48 (19.8) 78 (32.1) 72 (29.6) 45 (18.5) 243 (100) Internal injury 44 (35.5) 8 (6.5) 18 (14.5) 54 (43.5) 124 (100) Head Injury/Concussion 18 (21.7) 26 (31.3) 18 (21.7) 21 (25.3) 83 (100) Burns 42 (62.7) 9 (13.4) 10 (14.9) 6 (9.0) 67 (100) Other 41 (35.7) 38 (33.0) 18 (15.7) 18 (15.7) 115 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Severity of injury No apparent injury 39 (31.2) 45 (36.0) 26 (20.8) 15 (12.0) 125 (100) <0.001 Minor 419 (25.5) 535 (32.5) 406 (24.7) 285 (17.3) 1645 (100) Moderate 171 (21.0) 262 (32.2) 225 (27.7) 155 (19.1) 813 (100) Severe 23 (20.7) 23 (20.7) 23 (20.7) 42 (37.8) 111 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Abstract 432 Table 4Association of injury location, nature and severity with sex among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020SexMaleFemaleTotalChi-SquareInjury characteristicsn (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 979 (62.1) 597 (37.9) 1576 (100) <0.001 Highway/road/street 421 (66.2) 215 (33.8) 636 (100) School 176 (75.5) 57 (24.5) 233 (100) Recreational area 111 (80.4) 27 (19.6) 138 (100) Workplace 62 (81.6) 14 (18.4) 76 (100) Other 29 (78.4) 8 (21.6) 37 (100) Total 1778 (65.9) 918 (34.1) 2696 (100) Nature of injury Cuts, bites or open wound 959 (69.6) 419 (30.4) 1378 (100) <0.001 Bruise or superficial injury 246 (64.2) 137 (35.8) 383 (100) Fracture 200 (66.9) 99 (33.1) 299 (100) Sprain, strain or dislocation 154 (63.4) 89 (36.6) 243 (100) Internal injury 50 (40.3) 74 (59.7) 124 (100) Head Injury/Concussion 59 (71.1) 24 (28.9) 83 (100) Burns 27 (40.3) 40 (59.7) 67 (100) Other 79 (68.7) 36 (31.3) 115 (100) Unknown 2 (100) 0 (0.0) 2 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Severity of injury No apparent injury 81 (64.8) 44 (35.2) 125 (100) 0.048 Minor 1102 (67.0) 543 (33.0) 1645 (100) Moderate 533 (65.6) 280 (34.4) 813 (100) Severe 60 (54.1) 51 (45.9) 111 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Abstract 432 Table 5Distribution of injuries by outcome and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Outcome of injuryDischargedAdmittedTransferredDiedLAMAUnknownTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 787 (86.5) 65 (7.1) 53 (5.8) 0 (0.0) 4 (0.4) 1 (0.1) 910 (100) Animal/insect bite/sting 704 (96.7) 3 (0.4) 19 (2.6) 0 (0.0) 1 (0.1) 1 (0.1) 728 (100) Road traffic injury 260 (73.0) 47 (13.2) 44 (12.4) 5 (1.4) 0 (0.0) 0 (0.0) 356 (100) Injured by a blunt force 190 (94.5) 4 (2.0) 6 (3.0) 0 (0.0) 1 (0.5) 0 (0.0) 201 (100) Stabbed, cut or pierced 165 (93.8) 8 (4.5) 3 (1.7) 0 (0.0) 0 (0.0) 0 (0.0) 176 (100) Fire, burn or scald 52 (80.0) 12 (18.5) 1 (1.5) 0 (0.0) 0 (0.0) 0 (0.0) 65 (100) Poisoning 30 (57.7) 4 (7.7) 16 (30.8) 1 (1.9) 1 (1.9) 0 (0.0) 52 (100) Suffocation/choking/asphyxia 24 (66.7) 4 (11.1) 6 (16.7) 1 (2.8) 1 (2.8) 0 (0.0) 36 (100) Electrocution 7 (58.3) 2 (16.7) 2 (16.7) 1 (8.3) 0 (0.0) 0 (0.0) 12 (100) Drowning and submersion 4 (57.1) 0 (0.0) 0 (0.0) 3 (42.9) 0 (0.0) 0 (0.0) 7 (100) Other 12 (92.3) 1 (7.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 2237 (87.5) 150 (5.9) 150 (5.9) 11 (0.4) 8 (0.3) 2 (0.1) 2558 (100) Self-harm Poisoning 5 (13.2) 8 (21.1) 23 (60.5) 0 (0.0) 2 (5.3) 0 (0.0) 38 (100) Hanging 1 (8.3) 0 (0.0) 1 (8.3) 10 (83.3) 0 (0.0) 0 (0.0) 12 (100) Stabbed, cut or pierced 6 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 6 (100) Injured by blunt object 4 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 17 (27.9) 8 (13.1) 24 (39.3) 10 (16.4) 2 (3.3) 0 (0.0) 61 (100) Assault Bodily force (physical violence) 34 (79.1) 5 (11.6) 3 (7.0) 0 (0.0) 1 (2.3) 0 (0.0) 43 (100) Injured by blunt object 18 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 18 (100) Stabbed, cut or pierced 6 (75.0) 1 (12.5) 1 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 8 (100) Pushing from a high place 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Poisoning 1 (50) 0 (0.0) 1 (50.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Sexual assault 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 63 (84.0) 6 (8.0) 5 (6.7) 0 (0.0) 1 (1.3) 0 (0.0) 75 (100) Abstract 432 Figure 1Seasonal variation of injuries identified by the injury surveillance system over a year among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Results/ConclusionsThe total number of ED patients with injury in the study was 10,154.2,696 were patients aged <18 years. Most injuries in children were unintentional and over half of children presenting with injuries were <10 years of age. Falls, animal bites/stings and road traffic injuries accounted for nearly 75% of all injuries with some (drowning, poisonings and burns) under-represented. Over half of injuries were cuts, bites and open wounds. The next most common injury types were superficial injuries (14.2%); fractures (11.1%); sprains/dislocations (9.0%). Child mortality was 1%.This is the biggest prospective injury surveillance study in a low or middle country in recent years and supports the use of injury surveillance in Nepal for reducing child morbidity and mortality through improved data.CHILD PAPER: RESULTS SECTIONTotal number of ED patients: 33046Total number of ED patient with injury: 10154 (adult=7458 & children=2696)8.2% (n=2696) patients with injury were children aged <18 yearsHetauda hospital: 2274 (84.3%)Chure hill hospital: 422 (15.7%)
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5

Rivera Teran, V., D. Alpizar-Rodriguez, S. Sicsik, F. Irazoque-Palazuelos, D. Miranda, D. Vega-Morales, J. C. Casasola, et al. "FRI0546 GENDER DIFFERENCES OF RHEUMATIC DISEASES IN MEXICAN POPULATION: DATA FROM THE MEXICAN BIOLOGICS REGISTRY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 874–75. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6091.

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Background:Most autoimmune diseases are more prevalent in women. Symptom severity, disease progression, response to therapy and overall survival differ between males and females with rheumatic diseases.Objectives:To identify the characteristics of autoimmune diseases presentation and treatment between male and female population using information from the Mexican Adverse Events Registry (BIOBADAMEX).Methods:BIOBADAMEX is a Mexican ongoing cohort that collects the information of patients using biologic and biosimilar drugs since 2016. For this study we included all patients enrolled in the registry and compared baseline clinical and disease characteristics, treatment and presence of adverse events between genders. We used logistic regression to analyze univariable associations.Results:A total of 655 participants were analysed, of which 82% were female (Table 1). We found women were older with a median of 53 years compared to 46 years in men (OR 1.02, CI 1.0-1.1). Smoking was higher in men (16%) compared to women (5%), (OR 0.3, CI 0.2-0.6). Women had longer disease duration, 9 years compared to 7 years in men (OR 1, CI 1.0-1.1). Rheumatoid arthritis (RA) was more prevalent in women (OR 2.7, CI 1-6.9), while ankylosing spondylitis (AS) and psoriatic arthritis (PsA) were more prevalent in men (OR 0.2, CI 0.1-0.4, and OR 0.3, CI 0.1-0.9 respectively). Women had more comorbidities than men (OR 1.8, CI 1.1-2.8) and used steroids more frequently (OR 1.7, CI 1.1-2.7). Differences in disease activity were not found, however we noticed high activity scores among participants.Table 1.Baseline characteristics in the cohort by sexWomenn=532 (82%)Menn=123 (18%)UnivariableaOR(95%CI)Age, median (IQR)53 (44-60)47 (34-55)1.02 (1.0-1.1)*Body Mass Index, median (IQR)27 (23-31)26 (23-30)1.0 (0.9-1.1)Smoking, n(%)28 (5)18 (16)0.3 (0.2- 0.6)*Disease duration, median (IQR)9 (4-16)7 (2-13)1.0 (1.0-1.1)*Diagnosis, n(%): RA414 (78)37 (30)2.4 (1.0-5.7)* AIJ12 (2)5 (4)0.5 (0.1-1.9) AS37 (7)56 (46)0.1 (0.1-0.4)* PsA19 (4)15 (12)0.3 (0.1-0.8)* SLE17 (3)3 (2)1.2 (0.3-5.2) Others33 (6)7 (6)1Disease Activity indexes, median (IQR) DAS28a4.9 (3.6-5.9)4.9 (3.0-5.9)1.1 (0.9-1.3) BASDAIb4.8 (2.9-8)5.3 (2.8-7.5)0.9 (0.8- 1.1) ASDASc3.2 (1.9-4.5)3.9 (2.5-4.7)0.8 (0.6-1.2) SLEDAId14.5 (5.0-19.5)25 (25.0-31.0)0.6 (0.4-1.1)High blood pressure, n(%)77 (15)14 (12)1.3 (0.7-2.4)Diabetes mellitus, n(%)46 (9)7 (6)1.5 (0.7-3.5)High cholesterol, n(%)41 (8)8 (7)1.2 (0.4-2.6)Other comorbidities, n(%):173 (33)26 (21)1.8 (1.1 -2.8)*Use of previous biologic, n(%):216 (40)44 (36)1.2 (0.8- 1.8)Use of steroids, n(%):215 (42)34 (29)1.7 (1.1 -2.7)*Use of DMARD, n(%):418 (79)89 (72)1.4 (0.9-2.2)Adverse eventsb, n(%):69 (13)14 (11)1.2 (0.7-2.1) Severeb, n(%):12 (17)3 (21)0.8 (0.2-3.1)Univariable logistic regression analysis. *p<0.05.an=469,bn=99,cn=71,dn=19,Table 1.Analysis of association between change (Δ) in FMD and relevant parameters by univariate and multivariate linear regression analysis.UnivariateRho (p)MultivariateBeta (p)Δ FMD (%)(r2=0.30)ChangeADMA (µmol/l)-0.63 (<0.001)-0.25 (0.01)MDA (nmol/ml)-0.58 (<0.001)-0.18 (0.02)SOD (U/ml)0.48 (<0.001)NSGSH (U/ml)0.02 (0.75)NSHOMA-0.21 (0.001)NSeGFR (ml/min/ 1.73 m2)-0.03 (0.62)NShsCRP (mg/l)-0.45 (<0.001)NSPTX3 (ng/ml)-0.49 (<0.001)-0.21 (0.01)SBP (mmHg)-0.26 (<0.001)NSDBP (mmHg)-0.11 (0.12)NSHemoglobin (g/dl)0.07 (0.32)NSTotal Cholesterol (mg/dl)-0.05 (0.49)NSTriglyceride (mg/dl)-0.11 (0.12)NSLDL (mg/dl)-0.12 (0.07)NSHDL (mg/dl)0.02 (0.82)NSHbA1c (%)-0.26 (<0.001)NSFigure 1.Scatter-plot graphs between FMD and ADMA, MDA, CuZn-SOD, PTX-3.Conclusion:In our study we found sex differences regarding age and disease duration, being higher in women. As expected, the prevalence of RA was higher in women and AS and PsA in men. Overall, women used more steroids than men. An interesting finding was that patients had high disease activity. Future longitudinal analyses will allow us to analyse sex differences in disease progression and treatment response.References:[1] Ortona E et al. Ann Ist Super Sanita 2016;52(2):205-12[2] Ngo ST et al. Front Neuroendocrinol 2014;3(3):347-69Disclosure of Interests:Vijaya Rivera Teran: None declared, Deshire Alpizar-Rodriguez: None declared, Sandra Sicsik: None declared, Fedra Irazoque-Palazuelos Consultant of: Bristol-Myers Squibb, Janssen, Pfizer Inc, Roche and UCB, Dafhne Miranda: None declared, David Vega-Morales: None declared, Julio Cesar Casasola: None declared, Sandra Carrilo: None declared, angel castillo: None declared, Sergio Duran Barragan: None declared, Omar Muñoz: None declared, Aleni Paz: None declared, Angélica Peña: None declared, Alfonso Torres: None declared, Daniel Xavier Xibille Friedmann Consultant of: Lilly, Abbvie, Speakers bureau: Lilly, Abbvie, Azucena Ramos: None declared, José Francisco Moctezuma: None declared, Francisco Aceves: None declared, Estefania Torres: None declared, Natalia Santana: None declared, Miguel Vazquez: None declared, Erick Zamora: None declared, Francisco Guerrero: None declared, Claudia Zepeda: None declared, Melanea Rivera: None declared, Kitzia Alvarado: None declared, Cesar Francisco Pacheco Tena: None declared
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6

Sherrod, Amanda M., Nancy L. Wells, Mary S. Dietrich, and Barbara A. Murphy. "Examining caregiver perceptions and distress related to patient pain." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e20555-e20555. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e20555.

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e20555 Background: We conducted a randomized trial comparing a brief baseline pain educational intervention with the addition of either a hot line for pain related issues or weekly calls from health providers to assess pain and medication use. Results of this trial have been previously reported (J Pain Symptom Manage. 2003 Apr;25(4):344-56). Caregiver beliefs may impact patient compliance with pain treatment so caregivers also received pain education. As a secondary endpoint we investigated caregiver beliefs related to: 1) known barriers to compliance with pain medication (feasibility of pain control, addiction concerns, fears of overdose and toxicity), 2) perceptions regarding patient pain level, 3) distress related to patient pain, and 4) efficacy in helping control patient pain. Methods: 28 informal caregivers completed the Family Pain Questionnaire (part 1: 8 items related to beliefs, part 2: 6 items related to pain perceptions). All items were scored using a 10cm visual analogue scale. Questionnaires were completed at baseline, immediately and 1 month post-education. Results: Caregiver characteristics: 64% married, 54% ≤ high school education. The caregiver pain belief subscale mean score was 4.9 (SD 1.7) at baseline, 5.6 (SD 1.4) post-education and 5.9 (SD 0.9) at 1 month indicating improved beliefs over time (p=.001). Caregivers consistently rated pain higher than patients (baseline: M=6.7 (SD=2.6) vs. M=4.1 (SD=2.3), p<0.001, 1-Month: M=5.1 (SD=3.2) vs. M=3.4 (SD=2.7), p=0.003). They also reported more distress related to pain than patients . Distress among caregivers due to patient pain was high at baseline (median=8.4, IQR: 5.6-9.5), and remained high at 1 month (median=7.7, IQR: 4.7-9.3). While not statistically significant, caregiver perception of ability to relieve pain improved from baseline (median=4.6, IQR: 0.8-8.3) to 1 month (median=2.4, IQR: 1.2-4.5, p=0.115). Conclusions: Despite improvements in caregiver beliefs regarding barriers to good pain control, decrease in levels of patient pain, and improved self-efficacy in assisting with pain control, caregiver distress related to patient pain remained high. Future research should be focused on further characterizing the factors that contribute to caregiver distress.
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Petrov, A. V., Y. O. Shevnina, A. S. Gaffarova, and A. A. Petrov. "Dynamic of radiographic and ultrasonographic indices of hip joints in patients with ankylosing spondylitis under treatment with tumor necrotic factor ― alpha inhibitors." Medical alphabet 2, no. 37 (January 20, 2020): 54–58. http://dx.doi.org/10.33667/2078-5631-2019-2-37(412)-54-58.

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Background. Inflammation of the hip joints in ankylosing spondylitis (AS) is a frequent and severe manifestation of the disease, which in 7–8 % of patients is accompanied by the requirements of hip joints prosthesis. In the treatment of hip arthritis associated with AS non-steroidal anti-inflammatory drugs (NSAIDs), sulfasalazine (SSZ) and tumor necrosis factor-alpha blockers were used. However, the influence of these treatment on the dynamics of structural changes in hip joints is not studied.Purpose. To evaluate the dynamics of clinical, radiologic and ultrasonographic indices of hip joints in patients with AS who take different treatment methods for 12 months: NSAIDs, SSZ and adalimumab (ADA).Materials and methods. Dynamic monitoring of 78 patients with AS (corresponding to the New York modified criteria of 1984), who also had clinical, ultrasonographic and radiographic signs of inflammation of hip joints. The patients were divided into three groups: patients of the group 1 (n = 25) were been receiving NSAIDs; patients of group 2 (n = 26) had started to take SSZ (2–3 grams per day) on background of NSAIDs; patients of group 3 (n = 27) were started to take ADA (subcutaneously, 40 mg once every 2 weeks) on the background of NSAID. In addition to the generally accepted clinical and laboratory studies, all patients were being underwent by X-ray examination with an evaluation of the BASRI-Hip index and ultrasonography of hip joints during 12 months of follow-up.Results and discussion. In patients of group 2 treatment with SSZ during 12 months had been resulted in a decrease in the severity of pain from the visual analogue scale (VAS) at hip joint motion (26.1 [13.9, 42.7] vs 69.3 [56.8, 79, 3]), CRP (4.4 [1.5, 6.9] mg/L vs 15.2 [8.3, 21.8] mg/L) and a decrease in the thickness of the hip synovial membrane (6.7 [5.8, 8.5] mm vs 9.6 [7.9, 11.8] mm) compared with the initial data. In patients of the group 3 treatment with ADA had been lead to decreasing of pain VAS (14.2 [5.2, 26.7], vs. 72.1 [65.3, 89.1], BASDAI and ASDASCRP (1.7 [1.1, 3.1] and 1.4 [1.1, 2.2] vs. 7.5 [5.9, 8.6] and 3.1 [2.6, 3.9]), CRP (2.7 [0.2, 5.8] mg/L vs. 24.3 [17.4, 35.9]) and decrease in the thickness of hip synovial membrane (6.3 [5.0, 7.7] mm vs. 9.9 [8.1, 12.6] mm) and an increase of the thickness of the hyaline cartilage covering the head of the femur in comparison with group 1 (0.15 [0.09; 0.22] mm vs. —0.08 [–0.12, —0.04] mm). The effect of both drugs on the dynamics of the radiographic index BASRI-Hip and the formation of new osteophytes in hip joints was not noted.Conclusion. Inclusion of SSZ and ADA in a complex of treatment of patients with hip arthritis associated with AS leads to a decrease of synovitis of hip joints. Usage of ADA is accompanies by ultrasonographic signs of the restoration of hip joints cartilage.
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Swic, Sebastian J., Alexander G. T. MacPhail, Chinmay B. Dalal, Steven J. T. Huang, Alina S. Gerrie, Thomas J. Nevill, Heather J. Sutherland, et al. "Prognostic Factors and Outcomes in Allogeneic Hematopoietic Stem Cell Transplant Vs. Non-Transplant Chronic Lymphocytic Leukemia (CLL) Patients: A Comparative Analysis with the Leukemia/BMT Program of British Columbia (BC) and the BC Provincial CLL Database." Blood 124, no. 21 (December 6, 2014): 2549. http://dx.doi.org/10.1182/blood.v124.21.2549.2549.

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Abstract Background: Chronic Lymphocytic Leukemia (CLL) patients (pts) have significant (sig) heterogeneity; survival ranges from decades to <5 years (yrs). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is promising treatment (tx) for high-risk pts. Ideally, predictive (pred) tools would allow clinicians to recognize such pts early, permitting transplant performance to maximize benefit and minimize procedure associated risk. Factors with significant (sig) pred capacity are not, however, entirely clarified. Moreover, limited studies compare CLL pts who have/have not received HSCT in terms of differences (diff) in characteristics (char) at diagnosis (dx), population (pop) composition and outcomes. This study evaluates pred factors for outcomes post allo-HSCT, and compares dx char between (bn) tx CLL pts who did /did not receive HSCT by evaluating a large pop-based CLL cohort (n= 1044) from the BC Provincial CLL Database (BCPCD). Methods: 102 CLL pts (71M, 31F) had consecutive allo-HSCT (01-91 to 03-13, L/BMT Program of BC). Median (med) age (range) at dx:HSCT was 50 (26-65):57 (32-68) yrs; med interval dx to HSCT 5.8 yrs (0.5 to 29). Most pts (78, 76%) received non-ablative therapy; (n=61 [60%] reduced-intensity fludarabine /busulfan [flu/bu] based [RIC], n=17 [17%] non-myeloablative flu-cyclophosphamide based [NMA]); 24 pts had myeloablative (MA) conditioning (CON). Donor status was 50% unrelated (UD) (51UD:51RD); 73M, 28 F. Results: With median (med) follow up (FU) (range) post allo-HSCT of 2 yrs (0.5-18); post dx of 9 yrs (1-38), 67 (50%) pts survive. 70 (69%) achieved CR post-HSCT a med of 187 (28-1274) days (d). 27 had CLL PROG a med of 339 (25-4367) d; 18 of 27 (67%) survive a med of 3 (0.5-18) yrs post HSCT. Factors pred OS post HSCT (KM p=; UVA HR=) (p<0.05) were: pre-HSCT FISH deletion 17p (del 17p) (0.005; 2.9), Dohner rank (0.02), HSCT specific comorbidity index (CoI) >3 vs. 0-2 (0.04; 2.5), HLA mismatched (MM) donor (0.03;2.3), pre-HSCT tx with alemtuzumab (alem) (0.005;3.0), CON (MA vs NMA or RIC) (0.046; 3.0), acute (A) graft vs host disease (GVHD) grade (g) 3-4 vs 0-2. (<0.001; 4.5), dn chim <90% (0.001; 5.2), abn FISH not clear post-HSCT (0.009; 2.6), yr of HSCT (pre- vs post-2010) (0.03; 3.13) and lack of CR post HSCT (<0.001; 10.5).The following sig pred for (OR; p=): >90% dn chim: no B symptoms at dx (2.5; 0.004), CON (RIC vs. NMA, (2.6; 0.006); clear FISH abn post-HSCT: CR post-HSCT (4.6; 0.004); CR post-HSCT: B symptoms at dx (0.4; 0.02), <=1 FISH abn (1.7; 0.045), rituximab (R) pre-HSCT (2.5; 0.001), clear FISH abn (2.5; 0.01), flu sensitivity (S) pre-HSCT (1.8; 0.03), S to last tx pre-HSCT (1.7; 0.03), CON (MA vs. RIC or NMA) (3.2; <0.001); PROG: Richter’s transformation ( Rich trans) pre-HSCT (3.5; 0.008), graft failure (3.3; 0.008), CoI >3 vs. 0-2 (6.9; 0.006), no R pre-HSCT (6.7; 0.01), CON (MA vs. NMA or RIC), (0.2; 0.03); NRM: pre-HSCT alem (2.7; 0.03), CoI >3 vs. 0-2 (2.7; 0.049), HLA MM (2.8; 0.01), CON (MA vs. rest) (3.0; 0.007), AGVHD g 3-4 vs. 0-2 (5.9; <0.001), FISH abn not clear (2.6; 0.04), and no CR (6.5; <0.001). Comparison bn allo-HSCT and BCPCD CLL pts showed sig diff at dx for Dohner FISH rank: more del 17p (23% vs.11%) and 11q (23% vs. 9%) in allo-HSCT pts (n=84 with pre-HSCT FISH); less +12 (13% vs. 17%), del 13q (24% vs.41%) or normal (22% vs 18%), p<0.001 than non-HSCT pts (n=952); Age at dx (med, range) was lower in HSCT (50, 26-65) vs non (62, 25-96), p<0.001; lymphocyte (lymph) count higher (14, 1-300 vs.11, 1-662, p=0.03), tx-free survival (TFS) from dx to 1st tx shorter at 0.75 (0-9.3) vs. 2.86 (0-20.6) yrs. Rich trans was more frequent in HSCT pts (8%) vs. non (3%), p=0.015.OS was sig better for HSCT pts (n=103) (med 17.6, SE 4.5, CI 95% 8.8-26) compared to non (n=494) (med 14.4, SE 1.1, CI 95% 12.1-16.6) (p=0.03). Conclusion: CLL allo-HSCT pts have sig diff than non including higher lymph at dx, shorter time to 1st tx, and higher risk FISH abn. 17p del remains high-risk with allo-HSCT. Pre-HSCT R increased post HSCT CR. Strategies to optimize post-HSCT CR and dn chim are important; these milestones are crucial to best outcome. PROG post-HSCT does not confer worse OS; rescue strategies are successful and deserve further study. Comparison of this large allo HSCT and pop-based BPCDB cohort indicate improved OS for allo-HSCT tx CLL pts vs. other, with a survival plateau. This data indicates early recognition of high-risk CLL patients for HSCT is likely to yield best long-term outcome. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
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Bassan, Renato, Arianna Masciulli, Tamara Intermesoli, Ernesta Audisio, Chiara Cattaneo, Enrico Maria Pogliani, Vincenzo Cassibba, et al. "Phase II Randomized Trial Of Radiation-Free Central Nervous System (CNS) Prophylaxis Comparing Intrathecal Triple Therapy With Liposomal Cytarabine (DepoCyte®) In Adult Acute Lymphoblastic Leukemia (ALL)." Blood 122, no. 21 (November 15, 2013): 3901. http://dx.doi.org/10.1182/blood.v122.21.3901.3901.

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Abstract Introduction Since the landmark study of Omura et al. (Blood 1980;55:199), validating cranial irradiation as an adjunct to intrathecal (IT) methotrexate, no other randomized trial of CNS prophylaxis was performed in adult ALL. Although the risk of CNS relapse is now only 1-4%, irradiation contributes to cumulative CNS toxicity together with high-dose methotrexate/cytarabine (HD-M/A), or is logistically difficult, so that developing an effective radiation-free CNS prophylaxis remains an important clinical task. IT DepoCyte® (ITD) might be advantageous, the slow release of liposome-associated cytarabine allowing therapeutic concentrations in the cerebrospinal fluid for 14+ days. An open trial reported prohibitive CNS toxicity from ITD in 6/31 patients (Jabbour et al. Blood 2007;109:3214), but ITD to ITD and HD-M/A to ITD intervals were short (14 and 10 days, respectively) and no patient suffered from CNS relapse. Methods In a phase II randomized trial (ClinicalTrials.gov NCT-00795756) we evaluated toxicity and feasibility (as primary study endpoint) of ITD 50 mg in comparison with IT triple therapy (ITT: methotrexate 12,5 mg, cytarabine 50 mg, prednisone 40 mg). Stratification was by cell lineage and risk class. ITT was given on d1 of courses 1,2,4,6,8; d15 of courses 1,2,8; and d1 of maintenance cycles 2-5 (12x). ITD was given on d1 of courses 1,2,4,6,8; d15 of courses 1,8 (T-ALL only); and d1 of maintenance cycle 2 (6-8x). The shortest ITD to ITD interval was 14 days in T-ALL (courses 1-2 [3x] and 8 [2x]), otherwise it was 21 days between ITD and any prior/subsequent ITD and HD course. ALL therapy consisted of eight induction-consolidation courses followed by risk/minimal residual disease-oriented maintenance or stem cell transplantation (SCT). In HD courses 3,7 (M/A) and 5 (M/Asparaginase) M dosage was 2.5 g/m2 (Ph- B-ALL) and 5 g/m2 (T-ALL) up to 55 years, and A 2 g/m2. Imatinib was used with de-intensified chemotherapy in Ph+ ALL; selected high-risk subsets received early SCT. Results Between 2007-12 201 total patients were enrolled and 141 randomized to ITT (n=73) or ITD (n=68). Median age was 42 years (range 18-68) and risk subsets (ITT/ITD) were SR-B 27.4%/29.4%; HR-B Ph- 26%/25%, Ph+ 23.3%/22.1%, SR-T 5.5%/5.9%, HR-T 17.8%/17.7%. Complete remission was 89% (n=65)/89.7% (n=61). Rates of actual v planned IT injections during induction-consolidation cycles 1-8, after removal of study losses (resistance, early death, SCT, toxicity and relapse), were ITT 374/415 (90.1%) v ITD 219/245 (89.3%) (P=0.76). Although toxicity/medical reasons caused 5 ITD patients to discontinue permanently the study v none in ITT arm (P=0.02), toxicity-driven omissions of IT therapy were marginally increased in ITD arm (29/415 [6.9%] v 24/245 [9.8%]; P=0.20). Neurologic toxicity occurred in 20 (27.4%) ITT v 36 (53%) ITD patients, respectively (P=0.002). According to NCI CTC grading (G), neurotoxicity episodes were GI 7 v 10 (P=0.36), GII 13 v 32 (P=0.003), GIII 4 v 12 (P=0.04), GIV 1 v 5 (P=0.12). GIII-IV neurotoxicity developed in 5/73 (6.8%) ITT patients v 10/52 (19.2%) and 5/16 (31.2%) B- and T-ALL ITD patients, respectively (P= 0.01), correlating in T-ALL with the second/third q14d ITD at courses 1,2,8 (4/5 patients, 5/6 episodes). Apart from reversible headache/radicular pain, the most serious toxicity occurred in 3 (4.1%) ITT patients (seizures 1; leukoencephalopathy 1; loss of consciousness 1) v 5 (7.3%) ITD patients (loss of consciousness 4, 1 with seizures; cerebral oedema/pseudotumor cerebri 1) (P=0.48). Four-year overall and disease-free survival were 54% and 52.2% v 58.9% and 47.7% in ITT and ITD arms, respectively, and relapse rate was 32.3% v 24.6% (all P=NS). In ITT arm there were 2 (3%) CNS and 2 (3%) combined CNS/marrow relapses. In ITD arm only one poorly compliant subject not given any HD course had an isolated CNS relapse (1.6%); no other patient had a CNS recurrence. Conclusion A radiation-free CNS prophylaxis with six spaced ITD in conjunction with HD-M/A may be feasible and at least as effective as other regimens. Excluding reversible headache/radiculitis, serious CNS toxicity was not significantly increased compared with ITT regimen, although some patients were forced to discontinue IT prophylaxis. The occasionally severe CNS toxicity prompts the investigation of a lower ITD dosage (25 mg), also to limit GI-II side effects, and the tighter schedule used in T-ALL should be abandoned because too toxic. Disclosures: Bassan: Mundipharma Oncology; Sigma-Tau; Amgen: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Off Label Use: Liposome-encapsulated cytarabine (DepoCyte®) used in a prospective phase II randomized trial of CNS prophylaxis in ALL. Masciulli:Novartis: Research Funding; Ospedali Riuniti di Bergamo: Research Funding; AIFA (Italian Regulatory Agency): Research Funding; AMGEN S.p.A.: Research Funding; Genzyme Olanda: Research Funding; Gruppo Italiano Trapianti di Midollo Osseo (GITMO): Research Funding; Pierre Fabre Italia S.p.A.: Research Funding; Università Cattolica del Sacro Cuore, Roma: Research Funding; Università degli Studi di Firenze: Research Funding; Sigma-Tau: Research Funding; Myeloproliferative disorder Research Consortium: Research Funding; Celgene: Research Funding; Associazione Italiana Linfomi (AIL): Research Funding; Fondazione Italiana Linfomi (FIL): Research Funding; LaRoche: Research Funding. Gallamini:Millenium: Consultancy. Marfisi:Novartis: Research Funding; Ospedali Riuniti di Bergamo: Research Funding; AIFA (Italian Regulatory Agency: Research Funding; AMGEN S.p.A.: Research Funding; Genzyme Olanda: Research Funding; Gruppo Italiano Trapianti di Midollo (GITMO): Research Funding; Pierre Fabre Italia S.p.A.: Research Funding; Università Cattolica del Sacro Cuore-Roma: Research Funding; Università degli Studi di Firenze: Research Funding; Sigma-Tau: Research Funding; Myeloproliferative disorder Research Consortium: Research Funding; Celgene: Research Funding; Associazione Italiana Linfomi (AIL): Research Funding; Fondazione Italiana Linfomi (FIL): Research Funding; LaRoche: Research Funding. Marchioli:Associazione Italiana Linfomi (AIL): Research Funding; Celgene: Research Funding; Myeloproliferative disorder Research Consortium: Research Funding; Sigma-Tau: Research Funding; Università Cattolica del Sacro Cuore, Roma: Research Funding; Pierre Fabre Italia S.p.A.: Research Funding; Gruppo Italiano Trapianti di Midollo (GITMO): Research Funding; Genzyme Olanda: Research Funding; AMGEN S.p.A.: Research Funding; AIFA (Italian Regulatory Agency): Research Funding; Ospedali Riuniti di Bergamo: Research Funding; Novartis: Research Funding; Fondazione Italiana Linfomi (FIL): Research Funding; LaRoche: Research Funding; Università degli Studi di Firenze: Research Funding. Rambaldi:Italfarmaco: Honoraria; Sanofi: Honoraria; Novartis: Honoraria.
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10

Strati, Paolo, Kari Chaffee, Sara Achenbach, Susan M. Schwager, Timothy G. Call, Neil E. Kay, James Cerhan, Susan L. Slager, and Tait D. Shanafelt. "Disease Progression and Complications Are the Main Cause of Death in Patients with Chronic Lymphocytic Leukemia (CLL) Independent of Age and Comorbidities at Diagnosis." Blood 126, no. 23 (December 3, 2015): 5265. http://dx.doi.org/10.1182/blood.v126.23.5265.5265.

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Abstract Introduction. CLL primarily affects elderly individuals who frequently have comorbid health conditions. It is typically assumed non-CLL-related etiologies will be the ultimate cause of death for most CLL patients, particularly those with comorbid conditions at diagnosis. Methods. Between 9/2002 and 11/2014, 1174 patients with newly diagnosed CLL were enrolled in a prospective cohort study evaluating the natural history of CLL. Comorbidities were prospectively recorded at the time of diagnosis. Comorbidities arising during the course of disease were not considered for this analysis. Standardized longitudinal follow-up was performed in all patients every 6 months for the first 3 years after diagnosis and annually thereafter through 04/2015. Internal and external medical records, death certificates, and information from next of kin were centrally reviewed to determine cause of death, using a standardized protocol. Categorical and continuous variables were evaluated using the c2 or Fisher exact tests and the Mann-Whitney test, as appropriate. Results. Baseline characteristics at time of CLL diagnosis are shown in the Table. Over 80% of patients had 2 or more comorbidities at diagnosis (median 3, range 0-11). After a median follow up of 5 years, 224 (19%) patients have died. The cause of death could be accurately determined in 183 (82%) of these patients. The cause of death was due to CLL in 135 (74%), including 84 (46%) CLL progressions, 14 (8%) infections, and 37 (20%) other cancers. Death was due to non-CLL-related causes (such as congestive heart failure, stroke or chronic obstructive pulmonary disease) in the remaining 48 (26%) patients. On univariable analysis, age and number of comorbid health conditions were not related to whether or not the cause of death was related/unrelated to CLL. The only specific co-morbid condition at diagnosis that predicted for non-CLL related death was stroke (8% vs 1%, p=0.04). Unmutated IGHV was the only prognostic factor thatpredicted greater likelihood of CLL-related death (70% vs 50%, p=0.03). Conclusions. The majority of patients with CLL have multiple comorbidities at time of diagnosis. Despite this fact, CLL progression and/or CLL-related complications are the primary cause of death. The number and type of comorbidities at diagnosis have minimal relationship to whether or not the ultimate cause of death was CLL-related. In contrast, the CLL-specific characteristic IGHV status (but interestingly not FISH defects) correlates with cause of death. Collectively, these findings illustrate the need for more effective CLL therapy, particularly treatments that can be tolerated by patients with comorbid health conditions. It is hoped the signaling inhibitors may help address this unmet need. Table. Number (%), median [range] N=1174 Age (years) 63 [23-89] Males Females 791 (67) 383 (33) Creatinine-Clearance > (mL/min) 86 [10-252] B2M (mg/dL) 2.3 [1.1-13.2] Rai stage 0 I-II III-IV 604 (52) 512 (38) 54 (10) CD49d positive negative 277 (30) 638 (70) CD38 positive negative 332 (30) 780 (70) ZAP70 positive negative 380 (37) 650 (63) IGHV unmutated mutated 394 (44) 506 (56) FISH del13q negative +12 del11q del17p 395 (40) 175 (18) 276 (28) 90 (9) 50 (5) Comorbid health conditions Other cancers 237 (20) Stroke 38 (3) Cardiac disease 326 (28) Hypertension 472 (40) Respiratory 210 (18) Endocrinologic 165 (14) Diabetes 118 (10) Hyperlipidemia 485 (41) Rheumatologic 489 (42) Gastrointestinal 384 (33) Genitourinary 412 (35) Psychiatric 197 (17) DVT/PE 33 (3) Substance abuse 58 (5) Sexually transmitted disease 35 (3) Obesity 376 (32) # of Comorbidities 0 1 2 3 4 > 4 66 (6) 148 (13) 203 (17) 220 (19) 206 (17) 331 (28) Disclosures Kay: Hospira: Research Funding; Genentech: Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Tolero Pharma: Research Funding. Cerhan:Kite Pharma: Research Funding.
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Roberts, Lara N., Raj K. Patel, Lynda Bonner, and Roopen Arya. "Outcomes From Root Cause Analysis of Hospital-Associated Thrombosis Over Twelve Months: A Single Centre Experience." Blood 118, no. 21 (November 18, 2011): 675. http://dx.doi.org/10.1182/blood.v118.21.675.675.

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Abstract Abstract 675 The national Venous Thromboembolism (VTE) Prevention Programme in England incorporates standardised guidance on risk assessment (RA) and thromboprophylaxis (TP) with a requirement for root cause analysis of all episodes of hospital associated thrombosis (HAT), defined as any VTE occurring whilst an inpatient or within 90 days of discharge. We report findings from audit of root cause analysis of HAT over 12 months at King's, a major London tertiary centre with 900 beds and an estimated 53 000 admissions per annum. 239 episodes of HAT were identified associated with surgical, medical and obstetric admission accounting for 101 (42.3%), 133 (55.6%) and 5 (2.1%) cases respectively. The estimated incidence of HAT is 4.5 per 1000 admissions. The mean age of patients with HAT was 62.7 (+/− 16.8) years, with males accounting for 53.6% of the cohort. HAT manifested as deep vein thrombosis in 121 (50.6%) and pulmonary embolism in 128 (49.6%). The median time to diagnosis of HAT following admission was 16 days (IQR 7–30). 171 (67.4%) of HAT occurred prior to discharge. Of the 78 (31.7%) events occurring post discharge, 60 (76.9%) required readmission for management of HAT and 2 (2.6%) represented with fatal events. HAT was associated with mortality in 51 cases (21.3%), with death directly attributable to PE in 16 (6.7%). The estimated incidence of HAT associated with fatal PE is 0.3 per 1000 admissions. Of note, autopsy was undertaken in 12/51 with PE identified as the primary cause of death in 11/12 (2/12 had known/suspected VTE prior to death). The five remaining patients with PE as the primary cause of death had the diagnosis made on clinical suspicion alone in four cases and radiological imaging in one case. The remaining deaths were attributed to other causes in 25, with 15 having unknown cause of death as certification occurred in the community (10 with known advanced malignancy at discharge). Root cause analysis has been completed for 149 (62.3%) of HAT episodes. Of these, 43.9% had RA undertaken on admission to hospital. Retrospective RA revealed 91.0% of patients were at high risk for VTE with 33.1% also at high risk of bleeding. 72% were prescribed anticoagulant TP. Anticoagulant prophylaxis was prescribed for 30/49 (61.2%) medical, 33/36 (91.7%) surgical and 3/4 (75%) obstetric HAT cases with a high VTE risk and low bleeding risk. Of those with a high bleeding risk, 8/23 (34.8%) and 15/27 (55.6%) medical and surgical patients respectively received anticoagulant TP for part of their admission. Mechanical TP was prescribed for 41/63 (65.1%) surgical, all obstetric (4) HAT cases and 5/15 (33.3%) medical patients in whom mechanical TP was indicated and appropriate. HAT was attributed to inadequate TP in 51 (32.5%), contraindication to chemical TP in 23 (14.6%), contraindication to all TP in 11 (7.0), TP failure in 43 (27.4%), line associated in 20 (12.7%), and was considered unexpected in 9 (5.7%) patients without any risk factors for VTE. Inadequate TP resulted from failure to prescribe in 17 (33.3%), unexplained delay in initiation in 8 (15.7%), unexplained missed doses in 7 (13.7%), inadequate duration of TP in 5 (9.8%) or inferior agent or dose in 9 (17.6%) cases with a combination of the above in 5 (9.8%) cases. Mortality associated with inadequate TP was 21.6% with death directly attributable to PE of 5.9%. TP remains underused in cases of HAT, with lowest rates associated with medical admission. At our centre, improved RA and TP could reduce the annual incidence of HAT by an estimated 21%. Further research is required to improve risk assessment and thromboprophylactic strategies to address unexpected events and those arising despite optimal TP. Disclosures: No relevant conflicts of interest to declare.
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12

Shah, Nina, Qaiser Bashir, Simrit Parmar, Yvonne T. Dinh, Sofia Qureshi, Gabriela Rondon, Uday R. Popat, et al. "Increased Bone Marrow Plasma Cell Infiltration Pre-Transplant Is Associated with Worse Outcomes in Patients Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation for Multiple Myeloma,." Blood 118, no. 21 (November 18, 2011): 4135. http://dx.doi.org/10.1182/blood.v118.21.4135.4135.

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Abstract Abstract 4135 Multiple myeloma (MM) is the second most common adult hematologic malignancy. High dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) have become the standard of care for eligible patients. Though the impact of bone marrow (BM) plasma cell (PC) percentage has been explored in the post-SCT setting, its role before SCT is not yet known We performed a retrospective review of 1826 MM pts who underwent HDC and auto-SCT at our institution from 7/8/98 – 12/31/2010. We further identified patients who had post-induction, pre-SCT BM biopsy information available. Patients were divided into 2 groups: those with <10% PC infiltration (“PC low”) and those with ≥10% plasma cell infiltration (“PC high”). Additional data, such as demographics, time of diagnosis, response, time to progression and time of death were also collected. Progression-free (PFS) and overall (OS) survivals were estimated by the Kaplan-Meier method. Log-rank test was performed to test the difference in survival between groups. 1489 pts were studied, 605 female and 884 male. Patient characteristics are detailed in Table 1. Median time from diagnosis to auto-SCT was 247 days (range 45–7895). 1299 (87%) patients underwent auto-SCT after 2000. Nearly all patients received melphalan-based conditioning. 1174 patients had <10% involvement of BM by PCs and 315 had > 10% involvement. The details of best responses before and after auto-SCT are also listed in Table 1. For patients in the PC low group, 32% had a CR, 20% had a VGPR, 31% had a PR, 13% had <PR and 3% had progressive disease after auto-SCT. For patients in the PC high group, 11% had a CR, 14% had a VGPR, 48% had a PR, 21% had <PR and 5% had progressive disease (PD) after auto-SCT. Median PFS was significantly shorter for the PC high group versus the PC low group (24.8 vs 29.5 months, p=0.05), as was median OS (52.5 vs 79.4 months respectively, p<0.001). When only those patients who had a PR to induction were examined, there was again a significant difference in both PFS (24.4 vs 33.2 months, p=0.04) and OS (58.3 vs 81.2 months, p =0.002) for those patients in the PC high versus PC low groups, respectively. Finally, when looking at those patients who underwent auto-SCT in the era of novel therapeutics (after 2000), the differences between the PC high and PC low groups were maintained for both PFS (24.4 vs 29.5 months respectively (p=0.029)) and OS (54.8 vs 88.4 months respectively, p<0.001). Table 1. Patient characteristics and responses All patients (n=1489) PC <10% (n=1174) PC ≥ 10% (n=315) Male 884 (59%) 718 (61%) 166 (53%) Female 605 (41%) 456 (39%) 149 (47%) Race 988 (66%) 784 (67%) 204 (65%) Caucasian 230 (15%) 181 (15%) 49 (16%) African American 33 (2%) 24 (2%) 9 (3%) Asian Unknown/other 238 (16%) 185 (16%) 53 (17%) Durie-Salmon Stage (1440 pts) I 218 (15%) 179 (16%) 39 (13%) II 597 (41%) 486 (43%) 111 (37%) III 626 (43%) 472 (42%) 154 (51%) Cytogenetics (1265) Normal 943(75%) 782 (79%) 161 (58%) Abnormal 322 (25%) 207 (21%) 115 (42%) Response prior to auto-SCT CR 66 (4%) 66 (6%) 0 (0%) VGPR 255 (17%) 244 (21%) 11(3%) PR 817 (55%) 655 (56%) 162 (51%) <PR 232 (16%) 144 (12%) 88 (28%) PD 93 (6%) 45 (4%) 48(15%) unknown 26 (2%) 20 (2%) 6 (2%) Median time to SCT (range) 247 days (45–7895) 239 days (45–7895) 259 days (74–5580) SCT after 2000 1299 (87%) 1037 (88%) 262 (83%) Best response after SCT CR 384 (26%) 350 (32%) 34 (11%) VGPR 298 (20%) 253 (20%) 45 (14%) PR 510 (34%) 359 (31%) 151 (48%) <PR 223 (15%) 157 (13%) 66 (21%) PD 45 (3%) 30 (3%) 15 (5%) Not evaluable 29 (2%) 9 (1%) 4 (1%) PFS from SCT (months) 29.5 24.8 P=0.05 OS from SCT (months) 79.4 52.5 P<0.001 PR-PFS from SCT (months) 33.2 24.4 P = 0.04 PR- OS from SCT (months) 81.2 58.3 P = 0.002 Post-2000 SCT PFS from SCT (months) 29.5 24.4 P = 0.029 Post-2000 SCT OS from SCT (months) 88.4 54.8 P<0.001 Extensive BM infiltration by PCs before auto-SCT is associated with a worse outcome in patients treated with HDC and auto-SCT. This finding persists when looking specifically at patients with a PR before auto-SCT. Thus, BM disease burden may further assist us in stratifying patients with a PR and may warrant further disease reduction before stem cell collection. Additionally, the differences between PC high and PC low groups are maintained in the modern era, despite the availability of several new salvage agents over the last 10 years. Further prospective study is warranted to determine the true impact of PC infiltration in the BM. Disclosures: No relevant conflicts of interest to declare.
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Barge, Luani, Steven Tran, Glen A. Kennedy, David Ritchie, David Gottlieb, Sam Milliken, Andrew Spencer, et al. "Improvement in Non-Relapse Mortality Following Allogeneic Transplantation for Chronic Lymphocytic Leukaemia in Australia and New Zealand: An Australasian Bone Marrow Transplant Recipient Registry Study." Blood 136, Supplement 1 (November 5, 2020): 25–26. http://dx.doi.org/10.1182/blood-2020-136574.

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Background The treatment landscape for chronic lymphocytic leukaemia (CLL) has significantly changed over the past decade with the advent of targeted therapies. Subsequent improvement in remission rates has been seen in all patient groups, however patients with high-risk genetic features (del17p, TP53 mutation) continue to have poorer outcomes. In such patients, and in multiply relapsed/refractory standard risk patients, allogeneic stem cell transplantation remains a viable management option despite the associated morbidity and mortality. The aim of this study was to examine trends in allogeneic stem cell transplantation for CLL in Australia and New Zealand over the past decade, and to identify predictive factors for overall survival (OS) and progression free survival (PFS). Methods Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients receiving a first allogeneic stem cell transplantation for CLL, in the absence of Richter's transformation, between January 2009 and December 2018. Transplant outcomes were compared between 2 time periods, 2009-2013 and 2014-2018 using log rank test for survival and Gray's test for cumulative incidence curves. Cox regression analysis was performed to identify factors predictive of survival. Medians are reported with ranges, hazard ratios (HR) and cumulative incidence with 95% confidence intervals (CI). Results A total of 153 patients (75% males) were included. Median age at transplantation was 55 years (range 23-69) with a median time from diagnosis to transplantation of 5.7 years (range 100days - 24.7years). Most patients received reduced intensity or non-myeloablative conditioning (84.3%, n=129) and did not receive T cell depleting therapy (73%, n=94). The median follow up was 5.9 years (range 0.8-11years). Median time to neutrophil engraftment was 16 days (range 6-49) and median time to platelet engraftment was 18 days (range 1-69). At 100 days following transplantation the cumulative incidence of graft failure was 3.9%, CMV reactivation 41% (95% CI 31-50%) and CMV disease 3.2% (95% CI 1-8%). Acute graft versus host disease (aGVHD) grade II-IV occurred in 39% (95% CI 29-49%) of patients and grade III-IV in 17% (95% CI 9-25%). The cumulative incidence of chronic GVHD (cGVHD) was 65% (95% CI 53-76%) at 5 years; extensive cGVHD occurred in 77% of patients with cGVHD. Median OS was 4.3 years (95% CI 3.6-not reached) and PFS was 2.6 years (95% CI 1.7-3.9). The most common contributors to mortality were infection (43%), GVHD (40%) and persistent disease or relapse (24%). In a multivariate analysis active disease at time of transplantation was associated with a worse OS (HR 2.16, 1.01-4.63), however, age, matched sibling donor, myeloablative conditioning and the use of T cell depleting therapies did not have a significant impact. The use of myeloablative conditioning was associated with improved PFS (HR 1.85, 1.1-3.1) in a univariate analysis but lost significance in multivariate analysis. Ninety-seven patients underwent transplantation between 2009-2013 and 56 patients between 2014-2018. There was no statistical difference in patient age, performance status, donor or disease status at transplantation between the groups. Myeloablative conditioning was used in 18.6% and 8.9% (p=0.197), and T cell depleting therapy in 25% and 31% (p=0.58), for the 2009-2013 and 2014-2018 periods respectively. There was a significant improvement in 5-year non-relapse mortality (NRM) from 41.5% (31-52%) to 23.4% (13-29%; p=0.04). Five year OS (46% vs 56%), PFS (36% vs 46%) and relapse rates (21% vs 31%) were not statistically different. Cumulative incidence of both acute and chronic GVHD was reduced in the later cohort; aGVHD 51% (95% CI 34-65%) vs 29% (95% CI 16-43%; p=0.03), cGVHD 76% (95% CI 57-88%) vs 53% (36-66%; p=0.02). Kaplan-meier and cumulative incidence curves for these outcomes are presented in figure 1. Conclusion The number of allogeneic stem cell transplantations performed for CLL has reduced over the past decade in Australasia. There has been an improvement in NRM and incidence of GVHD, however OS and PFS have not significantly changed. This may reflect improved GVHD prophylaxis and management, or advances in supportive care. Further analysis of impact of high-risk genetic factors at transplantation is pending at the time of abstract submission. Figure Disclosures Spencer: Celgene, Janssen and Takeda: Speakers Bureau; AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding; AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria. Greenwood:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tam:AbbVie: Honoraria, Research Funding; BeiGene: Honoraria; Janssen: Honoraria, Research Funding. Di Ciaccio:Jansen: Honoraria, Other: travel and accomodation grant. Hamad:Novartis: Honoraria; Abbvie: Honoraria.
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Hens, Luc, Nguyen An Thinh, Tran Hong Hanh, Ngo Sy Cuong, Tran Dinh Lan, Nguyen Van Thanh, and Dang Thanh Le. "Sea-level rise and resilience in Vietnam and the Asia-Pacific: A synthesis." VIETNAM JOURNAL OF EARTH SCIENCES 40, no. 2 (January 19, 2018): 127–53. http://dx.doi.org/10.15625/0866-7187/40/2/11107.

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Climate change induced sea-level rise (SLR) is on its increase globally. Regionally the lowlands of China, Vietnam, Bangladesh, and islands of the Malaysian, Indonesian and Philippine archipelagos are among the world’s most threatened regions. Sea-level rise has major impacts on the ecosystems and society. It threatens coastal populations, economic activities, and fragile ecosystems as mangroves, coastal salt-marches and wetlands. This paper provides a summary of the current state of knowledge of sea level-rise and its effects on both human and natural ecosystems. The focus is on coastal urban areas and low lying deltas in South-East Asia and Vietnam, as one of the most threatened areas in the world. About 3 mm per year reflects the growing consensus on the average SLR worldwide. The trend speeds up during recent decades. The figures are subject to local, temporal and methodological variation. In Vietnam the average values of 3.3 mm per year during the 1993-2014 period are above the worldwide average. Although a basic conceptual understanding exists that the increasing global frequency of the strongest tropical cyclones is related with the increasing temperature and SLR, this relationship is insufficiently understood. Moreover the precise, complex environmental, economic, social, and health impacts are currently unclear. SLR, storms and changing precipitation patterns increase flood risks, in particular in urban areas. Part of the current scientific debate is on how urban agglomeration can be made more resilient to flood risks. Where originally mainly technical interventions dominated this discussion, it becomes increasingly clear that proactive special planning, flood defense, flood risk mitigation, flood preparation, and flood recovery are important, but costly instruments. Next to the main focus on SLR and its effects on resilience, the paper reviews main SLR associated impacts: Floods and inundation, salinization, shoreline change, and effects on mangroves and wetlands. The hazards of SLR related floods increase fastest in urban areas. This is related with both the increasing surface major cities are expected to occupy during the decades to come and the increasing coastal population. In particular Asia and its megacities in the southern part of the continent are increasingly at risk. The discussion points to complexity, inter-disciplinarity, and the related uncertainty, as core characteristics. An integrated combination of mitigation, adaptation and resilience measures is currently considered as the most indicated way to resist SLR today and in the near future.References Aerts J.C.J.H., Hassan A., Savenije H.H.G., Khan M.F., 2000. Using GIS tools and rapid assessment techniques for determining salt intrusion: Stream a river basin management instrument. 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Resilience and shifts in agro-ecosystems facing increasing sea-level rise and salinity intrusion in Ben Tre province, Mekong Delta. Climatic Change, 133, 69-84. Doi: 10.1007/s10584-014-1113-4. Serra P., Pons X., Sauri D., 2008. Land cover and land use in a Mediterranean landscape. Applied Geography, 28, 189-209. Shearman P., Bryan J., Walsh J.P., 2013.Trends in deltaic change over three decades in the Asia-Pacific Region. Journal of Coastal Research, 29, 1169-1183. Doi: 10.2112/JCOASTRES-D-12-00120.1. SIWRR-Southern Institute of Water Resources Research, 2016. Annual Report. Ministry of Agriculture and Rural Development, Ho Chi Minh City, 1-19. Slangen A.B.A., Katsman C.A., Van de Wal R.S.W., Vermeersen L.L.A., Riva R.E.M., 2012. Towards regional projections of twenty-first century sea-level change based on IPCC RES scenarios. Climate Dynamics, 38, 1191-1209. Doi: 10.1007/s00382-011-1057-6. Spencer T., Schuerch M., Nicholls R.J., Hinkel J., Lincke D., Vafeidis A.T., Reef R., McFadden L., Brown S., 2016. Global coastal wetland change under sea-level rise and related stresses: The DIVA wetland change model. Global and Planetary Change, 139, 15-30. Doi:10.1016/j.gloplacha.2015.12.018. Stammer D., Cazenave A., Ponte R.M., Tamisiea M.E., 2013. Causes of contemporary regional sea level changes. Annual Review of Marine Science, 5, 21-46. Doi: 10.1146/annurev-marine-121211-172406. Tett P., Mee L., 2015. Scenarios explored with Delphi. In: Coastal zones ecosystems services. Eds., Springer, Berlin, Germany, 127-144. Tran Hong Hanh, 2017. Land use dynamics, its drivers and consequences in the Ca Mau province, Mekong delta, Vietnam. PhD dissertation, 191p. VUBPRESS Brussels University Press, ISBN 9789057186226, Brussels, Belgium. Tran Thuc, Nguyen Van Thang, Huynh Thi Lan Huong, Mai Van Khiem, Nguyen Xuan Hien, Doan Ha Phong, 2016. Climate change and sea level rise scenarios for Vietnam. Ministry of Natural resources and Environment. Hanoi, Vietnam. Tran Hong Hanh, Tran Thuc, Kervyn M., 2015. Dynamics of land cover/land use changes in the Mekong Delta, 1973-2011: A remote sensing analysis of the Tran Van Thoi District, Ca Mau province, Vietnam. Remote Sensing, 7, 2899-2925. Doi: 10.1007/s00254-007-0951-z Van Lavieren H., Spalding M., Alongi D., Kainuma M., Clüsener-Godt M., Adeel Z., 2012. Securing the future of Mangroves. The United Nations University, Okinawa, Japan, 53, 1-56. Water Resources Directorate. Ministry of Agriculture and Rural Development, 2016. Available online: http://www.tongcucthuyloi.gov.vn/Tin-tuc-Su-kien/Tin-tuc-su-kien-tong-hop/catid/12/item/2670/xam-nhap-man-vung-dong-bang-song-cuu-long--2015---2016---han-han-o-mien-trung--tay-nguyen-va-giai-phap-khac-phuc. Last accessed on: 30/9/2016. Webster P.J., Holland G.J., Curry J.A., Chang H.-R., 2005. Changes in tropical cyclone number, duration, and intensity in a warming environment. Science, 309, 1844-1846. Doi: 10.1126/science.1116448. Were K.O., Dick O.B., Singh B.R., 2013. Remotely sensing the spatial and temporal land cover changes in Eastern Mau forest reserve and Lake Nakuru drainage Basin, Kenya. Applied Geography, 41, 75-86. Williams G.A., Helmuth B., Russel B.D., Dong W.-Y., Thiyagarajan V., Seuront L., 2016. Meeting the climate change challenge: Pressing issues in southern China an SE Asian coastal ecosystems. Regional Studies in Marine Science, 8, 373-381. Doi: 10.1016/j.rsma.2016.07.002. Woodroffe C.D., Rogers K., McKee K.L., Lovdelock C.E., Mendelssohn I.A., Saintilan N., 2016. Mangrove sedimentation and response to relative sea-level rise. Annual Review of Marine Science, 8, 243-266. Doi: 10.1146/annurev-marine-122414-034025.
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Paulus, Michael G., Kathrin Renner, Steffen Pabel, Gabriela Pietrzyk, Andreas Luchner, Lars S. Maier, Christoph M. Birner, Katrin Streckfuß-Bömeke, Samuel T. Sossalla, and Alexander Dietl. "Abstract 16339: Mitochondrial Function in Animal and Novel Human Disease Models of Tachycardiomyopathy." Circulation 142, Suppl_3 (November 17, 2020). http://dx.doi.org/10.1161/circ.142.suppl_3.16339.

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Introduction: Clinical significance of tachycardiomyopathy (TCM) increased with trials on catheter ablation therapy. Myocardial biopsies from patients show disturbed mitochondrial architecture. Hypothesis: TCM involves mitochondrial dysfunction. Methods: First, TCM was investigated in an animal model: pacemaker implantation in 7 rabbits was followed by tachypacing for 30 days (TCM), 7 animals served as sham-operated controls (SHAM). Second, results of the animal study were evaluated for their translational perspective for human disease using a novel model of induced pluripotent stem cell-derived cardiomyocytes (iPS-CM), derived from 4 healthy donors. IPS-CM were paced with 120 bpm (TACH) or 60 bpm (CTRL) for 7 days in vitro. Targeted transcriptomics, high-resolution respirometry and flow cytometry (MitoSOX Red) were performed. To account for variations between cell differentiations, experiments on iPS-CM were carried out in a paired design. Results: TCM showed LV dilatation and dysfunction (ΔLVEDD +5.3±0.2mm; ΔFS -19±8%; TCM-SHAM; p<0.001). Histological findings resembled human disease entailing cardiomyocyte hypertrophy (CSA 519±32μm 2 vs. 413±21μm 2 , p<0.01) without fibrosis (hydroxyproline content, p=0.52). Mitochondrial transcriptome of TCM was characterized by downregulation of 10 antioxidative enzymes (e.g. GPX3, fold change (FC) 0.4; TCM/SHAM; p<0.05) as well as mitochondrial carriers, including ADP/ATP- and NADH-shuttling (SLC25A4, FC 0.7; SLC25A12, FC 0.8; p<0.01). As transcriptomics implied impaired substrate import, respirometry was performed in whole tissue. In support of our findings on the transcriptome level, mitochondrial oxidative phosphorylation capacity decreased in TCM (133±13 vs. 170±16 pmol·O 2 ·s -1 ·mg -1 ·tissue, p<0.05). Similarly, oxidative phosphorylation was reduced in iPS-CM (995±738 vs. 1838±901 pmolO 2 ·s -1 ·IU -1 citrate synthase activity, TACH vs. CTRL, p<0.01). Concurrently, tachypacing increased mitochondrial superoxide emission in iPS-CM (MFI 491±206 vs. 301±119, p<0.05). Conclusions: Persistent tachycardia alters two mitochondrial key functions in an animal and a novel human ex vivo model: oxidative phosphorylation capacity is reduced, while superoxide emission increases.
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Paramsothy, Pathmaja, Jaekyoung Hong, Daniel Isquith, Elizabeth Hulphers, Hua Bai, Pey Shadzi, Moni Neradilek, Edward A. Gill, and Xue-Qiao Zhao. "Abstract 366: Gender Differences Exist in Carotid Arterial Plaque Composition Among Men and Women with Carotid or Coronary Artery Disease and Elevated ApoB Levels." Arteriosclerosis, Thrombosis, and Vascular Biology 35, suppl_1 (May 2015). http://dx.doi.org/10.1161/atvb.35.suppl_1.366.

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Introduction: Postmortem coronary artery histopathology and post-surgical carotid endarterectomy studies demonstrate that women have less calcification and inflammatory cells, but more smooth muscle cells than men. Gender differences in atherosclerotic plaque composition are not well known. Yet, the age-adjusted incidence of stroke and myocardial infarction are higher in men than women. Hypothesis: We hypothesized that gender differences exist in carotid plaque composition (CPC), % lipid rich necrotic core (LRNC) and % wall volume (PWV), comparing living women and men. Methods: The CPC study is a prospective, randomized study evaluating the effect of 1) atorvastatin + placebo + placebo vs 2) atorvastatin + niacin ER + placebo 3) atorvastatin + niacin ER + colsevelam on CPC. Participants had coronary or carotid artery disease and ApoB levels ≥120 mg/dL. CPC was evaluated using MRI. Baseline PWV [(wall volume/total vessel volume) х 100%], a measure of plaque burden that adjusts for variation in artery size, and % LRNC volume (among slices with LRNC present) were evaluated. Statistical analysis used Wilcoxon rank sum test, chi-square, and multivariate linear regression. Results: There were 82 women and 118 men. Women vs. men were older, mean±SD age 58±8 vs. 55±8 yrs. (p=0.008), had higher HDL-C, 48±13 vs. 40±10 mg/dL (p<0.001), higher ApoA1 147±24 vs. 126±19 mg/dL (p<0.001), higher ApoE 5.5±3.4 vs. 4.5±1.6 mg/dL (p=0.04), lower % of prior myocardial infarction 22% vs. 52% (p=0.02) and higher % of metabolic syndrome 48% vs. 46% (p=0.01). There were no significant differences in ApoB levels, 123±32 vs. 120±29 (p=0.4). After adjusting for age, HDL-C (strongly correlated with ApoA1, r=0.89), ApoE, prevalence of myocardial infarction and metabolic syndrome, the men-women difference in PWV was small and statistically non-significant ([[Unable to Display Character: &#8710;]] 0.0%, 95% CI -2.5 to 2.6%, p=1.0). However, among participants with LRNC, men had more % LRNC than women ([[Unable to Display Character: &#8710;]] 5.9%, 95% CI 1.4 to 10.3%, p=0.01) after the same adjustments. Conclusions: Gender differences exist in CPC in that there is a higher volume of LRNC in men compared to women. Further studies are needed which delineate the mechanisms underlying the differences in prevalence of LRNC comparing men to women.
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Ding, WY, JM Rivera-Caravaca, F. Marin, C. Torp-Pedersen, V. Roldan, and GYH Lip. "Novel tool for predicting residual stroke risk in atrial fibrillation: mCARS." EP Europace 23, Supplement_3 (May 1, 2021). http://dx.doi.org/10.1093/europace/euab116.158.

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Abstract Funding Acknowledgements Type of funding sources: None. Background Recently, CARS was proposed to predict 1-year absolute stroke risk in non-anticoagulated patients with atrial fibrillation (AF). We aimed to determine whether a modified CARS (mCARS) may be used to assess the residual stroke risk in anticoagulated AF patients. Methods We studied patient-level data of anticoagulated AF patients from the real-world Murcia AF Project and AMADEUS clinical trial. Individual mCARS was estimated for each patient using an estimated 64% risk reduction with anticoagulation. Results 3,503 patients were included (2,205 [62.9%] clinical trial and 1,298 [37.1%] real-world). In the clinical trial cohort, the median age was 71 (IQR 65-77) and CHA2DS2-VASc score 3 (IQR 2-4). In the real-world cohort, the median age was 76 (IQR 70-81) and CHA2DS2-VASc score 4 (IQR 3-5). At 1-year, there were 40 and 31 stroke events in the clinical trial and real-world cohorts, respectively. Average predicted residual stroke risk by mCARS was identical to actual stroke risk (1.8 [±1.8%] vs. 1.8% [95% CI, 1.3-2.4]) in the clinical trial, and broadly similar in the real-world (2.1 [±1.9%] vs. 2.4% [95% CI, 1.6-3.4]). Additionally, these values were comparable across the subgroups stratified by CHA2DS2-VASc score in both cohorts. AUCs of mCARS for prediction of stroke events in the clinical trial and real-world were 0.678 (95% CI, 0.598-0.758) and 0.712 (95% CI, 0.618-0.805), respectively. In an exploratory analysis, we found that mCARS was able to refine stroke risk estimation for each point of the CHA2DS2-VASc score in both cohorts. Conclusion Personalised residual 1-year absolute stroke risk in anticoagulated AF patients may be estimated using mCARS. Such patients with high residual stroke risk may benefit from more aggressive interventions and follow-up. Absolute 1-year stroke risk Clinical Trial Real-World Median (IQR) Range Median (IQR) Range CHA2DS2-VASc score 0 NA 0.9 (0.6 - 1.3) 0.2 - 1.4 CHA2DS2-VASc score 1 1.1 (0.7 - 1.4) 0.2 - 2.0 1.4 (0.9 - 1.7) 0.2 - 13.0 CHA2DS2-VASc score 2 2.0 (1.5 - 2.4) 0.3 - 10.8 2.1 (1.5 - 2.6) 0.3 - 10.8 CHA2DS2-VASc score 3 2.6 (2.1 - 3.4) 0.4 - 13.3 2.8 (2.5 - 3.4) 0.9 - 13.3 CHA2DS2-VASc score 4 3.6 (2.8 - 5.6) 0.3 - 18.1 3.9 (3.3 - 5.0) 1.1 - 21.0 CHA2DS2-VASc score 5 6.7 (3.6 - 14.0) 1.9 - 20.9 4.8 (3.9 - 12.2) 1.2 - 21.0 CHA2DS2-VASc score 6 13.6 (5.5 - 15.8) 2.4 - 21.8 12.8 (4.8 - 16.7) 2.2 - 21.8 CHA2DS2-VASc score 7 15.7 (14.5 - 17.4) 4.5 - 21.9 15.6 (5.9 - 17.5) 4.1 - 23.5 CHA2DS2-VASc score 8 16.5 (14.0 - 18.5) 13.1 - 20.3 16.9 (15.7 - 19.5) 13.6 - 21.0 IQR, interquartile range; NA, not applicable.
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18

Chavdarov, Anatoliy V. "Special Issue No. – 10, June, 2020 Journal > Special Issue > Special Issue No. – 10, June, 2020 > Page 5 “Quantative Methods in Modern Science” organized by Academic Paper Ltd, Russia MORPHOLOGICAL AND ANATOMICAL FEATURES OF THE GENUS GAGEA SALISB., GROWING IN THE EAST KAZAKHSTAN REGION Authors: Zhamal T. Igissinova,Almash A. Kitapbayeva,Anargul S. Sharipkhanova,Alexander L. Vorobyev,Svetlana F. Kolosova,Zhanat K. Idrisheva, DOI: https://doi.org/10.26782/jmcms.spl.10/2020.06.00041 Abstract: Due to ecological preferences among species of the genus GageaSalisb, many plants are qualified as rare and/or endangered. Therefore, the problem of rational use of natural resources, in particular protection of early spring plant species is very important. However, literary sources analysis only reveals data on the biology of species of this genus. The present research,conducted in the spring of 2017-2019, focuses on anatomical and morphological features of two Altai species: Gagealutea and Gagea minima; these features were studied, clarified and confirmed by drawings and photographs. The anatomical structure of the stem and leaf blade was studied in detail. The obtained research results will prove useful for studies of medicinal raw materials and honey plants. The aforementioned species are similar in morphological features, yet G. minima issmaller in size, and its shoots appear earlier than those of other species Keywords: Flora,gageas,Altai species,vegetative organs., Refference: I. Atlas of areas and resources of medicinal plants of Kazakhstan.Almaty, 2008. II. Baitenov M.S. Flora of Kazakhstan.Almaty: Ġylym, 2001. III. DanilevichV. G. ThegenusGageaSalisb. of WesternTienShan. PhD Thesis, St. Petersburg,1996. IV. EgeubaevaR.A., GemedzhievaN.G. The current state of stocks of medicinal plants in some mountain ecosystems of Kazakhstan.Proceedings of the international scientific conference ‘”Results and prospects for the development of botanical science in Kazakhstan’, 2002. V. Kotukhov Yu.A. New species of the genus Gagea (Liliaceae) from Southern Altai. Bot. Journal.1989;74(11). VI. KotukhovYu.A. ListofvascularplantsofKazakhstanAltai. Botan. Researches ofSiberiaandKazakhstan.2005;11. VII. KotukhovYu. The current state of populations of rare and endangered plants in Eastern Kazakhstan. Almaty: AST, 2009. VIII. Kotukhov Yu.A., DanilovaA.N., AnufrievaO.A. Synopsisoftheonions (AlliumL.) oftheKazakhstanAltai, Sauro-ManrakandtheZaisandepression. BotanicalstudiesofSiberiaandKazakhstan. 2011;17: 3-33. IX. Kotukhov, Yu.A., Baytulin, I.O. Rareandendangered, endemicandrelictelementsofthefloraofKazakhstanAltai. MaterialsoftheIntern. scientific-practical. conf. ‘Sustainablemanagementofprotectedareas’.Almaty: Ridder, 2010. X. Krasnoborov I.M. et al. The determinant of plants of the Republic of Altai. Novosibirsk: SB RAS, 2012. XI. Levichev I.G. On the species status of Gagea Rubicunda. Botanical Journal.1997;6:71-76. XII. Levichev I.G. A new species of the genus Gagea (Liliaceae). Botanical Journal. 2000;7: 186-189. XIII. Levichev I.G., Jangb Chang-gee, Seung Hwan Ohc, Lazkovd G.A.A new species of genus GageaSalisb.(Liliaceae) from Kyrgyz Republic (Western Tian Shan, Chatkal Range, Sary-Chelek Nature Reserve). Journal of Asia-Pacific Biodiversity.2019; 12: 341-343. XIV. Peterson A., Levichev I.G., Peterson J. Systematics of Gagea and Lloydia (Liliaceae) and infrageneric classification of Gagea based on molecular and morphological data. Molecular Phylogenetics and Evolution.2008; 46. XV. Peruzzi L., Peterson A., Tison J.-M., Peterson J. Phylogenetic relationships of GageaSalisb.(Liliaceae) in Italy, inferred from molecular and morphological data matrices. Plant Systematics and Evolution; 2008: 276. XVI. Rib R.D. Honey plants of Kazakhstan. Advertising Digest, 2013. XVII. Scherbakova L.I., Shirshikova N.A. Flora of medicinal plants in the vicinity of Ust-Kamenogorsk. Collection of materials of the scientific-practical conference ‘Unity of Education, Science and Innovation’. Ust-Kamenogorsk: EKSU, 2011. XVIII. syganovA.P. PrimrosesofEastKazakhstan. Ust-Kamenogorsk: EKSU, 2001. XIX. Tsyganov A.P. Flora and vegetation of the South Altai Tarbagatay. Berlin: LAP LAMBERT,2014. XX. Utyasheva, T.R., Berezovikov, N.N., Zinchenko, Yu.K. ProceedingsoftheMarkakolskStateNatureReserve. Ust-Kamenogorsk, 2009. XXI. Xinqi C, Turland NJ. Gagea. Flora of China.2000;24: 117-121. XXII. Zarrei M., Zarre S., Wilkin P., Rix E.M. Systematic revision of the genus GageaSalisb. (Liliaceae) in Iran.BotJourn Linn Soc.2007;154. XXIII. Zarrei M., Wilkin P., Ingroille M.J., Chase M.W. A revised infrageneric classification for GageaSalisb. (Tulipeae; Liliaceae): insights from DNA sequence and morphological data.Phytotaxa.2011:5. View | Download INFLUENCE OF SUCCESSION CROPPING ON ECONOMIC EFFICIENCY OF NO-TILL CROP ROTATIONS Authors: Victor K. Dridiger,Roman S. Stukalov,Rasul G. Gadzhiumarov,Anastasiya A. Voropaeva,Viktoriay A. Kolomytseva, DOI: https://doi.org/10.26782/jmcms.spl.10/2020.06.00042 Abstract: This study was aimed at examining the influence of succession cropping on the economic efficiency of no-till field crop rotations on the black earth in the zone of unstable moistening of the Stavropol krai. A long-term stationary experiment was conducted to examine for the purpose nine field crop rotation patterns different in the number of fields (four to six), set of crops, and their succession in crop rotation. The respective shares of legumes, oilseeds, and cereals in the cropping pattern were 17 to 33, 17 to 40, and 50 to 67 %. It has been established that in case of no-till field crop cultivation the economic efficiency of plant production depends on the set of crops and their succession in rotation. The most economically efficient type of crop rotation is the soya-winter wheat-peas-winter wheat-sunflower-corn six-field rotation with two fields of legumes: in this rotation 1 ha of crop rotation area yields 3 850 grain units per ha at a grain unit prime cost of 5.46 roubles; the plant production output return and profitability were 20,888 roubles per ha and 113 %, respectively. The high production profitabilities provided by the soya-winter wheat-sunflower four-field and the soya-winter-wheat-sunflower-corn-winter wheat five-field crop rotation are 108.7 and 106.2 %, respectively. The inclusion of winter wheat in crop rotation for two years in a row reduces the second winter wheat crop yield by 80 to 100 %, which means a certain reduction in the grain unit harvesting rate to 3.48-3.57 thousands per ha of rotation area and cuts the production profitability down to 84.4-92.3 %. This is why, no-till cropping should not include winter wheat for a second time Keywords: No-till technology,crop rotation,predecessor,yield,return,profitability, Refference: I Badakhova G. Kh. and Knutas A. V., Stavropol Krai: Modern Climate Conditions [Stavropol’skiykray: sovremennyyeklimaticheskiyeusloviya]. Stavropol: SUE Krai Communication Networks, 2007. II Cherkasov G. N. and Akimenko A. S. Scientific Basis of Modernization of Crop Rotations and Formation of Their Systems according to the Specializations of Farms in the Central Chernozem Region [Osnovy moderniz atsiisevooborotoviformirovaniyaikh sistem v sootvetstvii so spetsi-alizatsiyeykhozyaystvTsentral’nogoChernozem’ya]. Zemledelie. 2017; 4: 3-5. III Decree 330 of July 6, 2017 the Ministry of Agriculture of Russia “On Approving Coefficients of Converting to Agricultural Crops to Grain Units [Ob utverzhdeniikoeffitsiyentovperevoda v zernovyyee dinitsysel’s kokhozyaystvennykhkul’tur]. IV Dridiger V. K., About Methods of Research of No-Till Technology [O metodikeissledovaniytekhnologii No-till]//Achievements of Science and Technology of AIC (Dostizheniyanaukiitekhniki APK). 2016; 30 (4): 30-32. V Dridiger V. K. and Gadzhiumarov R. G. Growth, Development, and Productivity of Soya Beans Cultivated On No-Till Technology in the Zone of Unstable Moistening of Stavropol Region [Rost, razvitiyeiproduktivnost’ soiprivozdelyvaniipotekhnologii No-till v zone ne-ustoychivog ouvlazhneniyaStavropol’skogokraya]//Oil Crops RTBVNIIMK (Maslichnyyekul’turyNTBVNIIMK). 2018; 3 (175): 52–57. VI Dridiger V. K., Godunova E. I., Eroshenko F. V., Stukalov R. S., Gadzhiumarov, R. G., Effekt of No-till Technology on erosion resistance, the population of earthworms and humus content in soil (Vliyaniyetekhnologii No-till naprotivoerozionnuyuustoychivost’, populyatsiyudozhdevykhcherveyisoderzhaniyegumusa v pochve)//Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2018; 9 (2): 766-770. VII Karabutov A. P., Solovichenko V. D., Nikitin V. V. et al., Reproduction of Soil Fertility, Productivity and Energy Efficiency of Crop Rotations [Vosproizvodstvoplodorodiyapochv, produktivnost’ ienergeticheskayaeffektivnost’ sevooborotov]. Zemledelie. 2019; 2: 3-7. VIII Kulintsev V. V., Dridiger V. K., Godunova E. I., Kovtun V. I., Zhukova M. P., Effekt of No-till Technology on The Available Moisture Content and Soil Density in The Crop Rotation [Vliyaniyetekhnologii No-till nasoderzhaniyedostupnoyvlagiiplotnost’ pochvy v sevoob-orote]// Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2017; 8 (6): 795-99. IX Kulintsev V. V., Godunova E. I., Zhelnakova L. I. et al., Next-Gen Agriculture System for Stavropol Krai: Monograph [SistemazemledeliyanovogopokoleniyaStavropol’skogokraya: Monogtafiya]. Stavropol: AGRUS Publishers, Stavropol State Agrarian University, 2013. X Lessiter Frank, 29 reasons why many growers are harvesting higher no-till yields in their fields than some university scientists find in research plots//No-till Farmer. 2015; 44 (2): 8. XI Rodionova O. A. Reproduction and Exchange-Distributive Relations in Farming Entities [Vosproizvodstvoiobmenno-raspredelitel’nyyeotnosheniya v sel’skokhozyaystvennykhorganizatsiyakh]//Economy, Labour, and Control in Agriculture (Ekonomika, trud, upravleniye v sel’skomkhozyaystve). 2010; 1 (2): 24-27. XII Sandu I. S., Svobodin V. A., Nechaev V. I., Kosolapova M. V., and Fedorenko V. F., Agricultural Production Efficiency: Recommended Practices [Effektivnost’ sel’skokhozyaystvennogoproizvodstva (metodicheskiyerekomendatsii)]. Moscow: Rosinforagrotech, 2013. XIII Sotchenko V. S. Modern Corn Cultivation Technologies [Sovremennayatekhnologiyavozdelyvaniya]. Moscow: Rosagrokhim, 2009. View | Download DEVELOPMENT AND TESTING OF AUTONOMOUS PORTABLE SEISMOMETER DESIGNED FOR USE AT ULTRALOW TEMPERATURES IN ARCTIC ENVIRONMENT Authors: Mikhail A. Abaturov,Yuriy V. Sirotinskiy, DOI: https://doi.org/10.26782/jmcms.spl.10/2020.06.00043 Abstract: This paper is concerned with solving one of the issues of the general problem of designing geophysical equipment for the natural climatic environment of the Arctic. The relevance of the topic has to do with an increased global interest in this region. The paper is aimed at considering the basic principles of developing and the procedure of testing seismic instruments for use at ultralow climatic temperatures. In this paper the indicated issue is considered through the example of a seismic module designed for petroleum and gas exploration by passive seismoacoustic methods. The seismic module is a direct-burial portable unit of around 5 kg in weight, designed to continuously measure and record microseismic triaxial orthogonal (ZNE) noise in a range from 0.1 to 45 Hz during several days in autonomous mode. The functional chart of designing the seismic module was considered, and concrete conclusions were made for choosing the necessary components to meet the ultralow-temperature operational requirements. The conclusions made served for developing appropriate seismic module. In this case, the components and tools used included a SAFT MP 176065 xc low-temperature lithium cell, industrial-spec electronic component parts, a Zhaofeng Geophysical ZF-4.5 Chinese primary electrodynamic seismic sensor, housing seal parts made of frost-resistant silicone materials, and finely dispersed silica gel used as water-retaining sorbent to avoid condensation in the housing. The paper also describes a procedure of low-temperature collation tests at the lab using a New Brunswick Scientific freezing plant. The test results proved the operability of the developed equipment at ultralow temperatures down to -55°C. In addition, tests were conducted at low microseismic noises in the actual Arctic environment. The possibility to detect signals in a range from 1 to 10 Hz at the level close to the NLNM limit (the Peterson model) has been confirmed, which allows monitoring and exploring petroleum and gas deposits by passive methods. As revealed by this study, the suggested approaches are efficient in developing high-precision mobile seismic instruments for use at ultralow climatic temperatures. The solution of the considered instrumentation and methodical issues is of great practical significance as a constituent of the generic problem of Arctic exploration. Keywords: Seismic instrumentation,microseismic monitoring,Peterson model,geological exploration,temperature ratings,cooling test, Refference: I. AD797: Ultralow Distortion, Ultralow Noise Op Amp, Analog Devices, Inc., Data Sheet (Rev. K). Analog Devices, Inc. URL: https://www.analog.com/media/en/technical-documentation/data-sheets/AD797.pdf(Date of access September 2, 2019). II. Agafonov, V. M., Egorov, I. V., and Shabalina, A. S. Operating Principles and Technical Characteristics of a Small-Sized Molecular–Electronic Seismic Sensor with Negative Feedback [Printsipyraboty I tekhnicheskiyekharakteristikimalogabaritnogomolekulyarno-elektronnogoseysmodatchika s otritsatel’noyobratnoysvyaz’yu]. SeysmicheskiyePribory (Seismic Instruments). 2014; 50 (1): 1–8. DOI: 10.3103/S0747923914010022. III. Antonovskaya, G., Konechnaya, Ya.,Kremenetskaya, E., Asming, V., Kvaema, T., Schweitzer, J., Ringdal, F. Enhanced Earthquake Monitoring in the European Arctic. Polar Science. 2015; 1 (9): 158-167. 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Analytical comparison of seismic instruments for stationary surveys in the Arctic [Sravnitel’nyyanalizseysmicheskoyapparaturydlyastatsionarnykhnablyudeniy v Arktike]. DSYS. URL: https://dsys.ru/upload/id254_docPDF_FranzJosefLand.pdf(Date of access September 2, 2019). X. Dew point temperature calculator. Maple Tech. International LLC. URL: https://www.calculator.net/dew-point-calculator.html?airtemperature=20&airtemperatureunit=celsius&humidity=0.34&dewpoint=&dewpointunit=celsius&x=51&y=14(Date of access September 2, 2019). XI. Frolov, A. S. Matching of wave fields recorded by different geophysical receivers [Soglasovaniyevolnovykhpoley, poluchennykh s primeneniyemrazlichnoyregistriruyushcheyapparatury]. Abstracts IX International scientific and technical conference competition of young specialists “Geophysics-2013”. Saint-Petersburg: Gubkin University, 2013. 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F., Chirkin, I. A., Rizanov, E. G., LeRoy, S. D., Koligaev, S. O. Long-term monitoring of microseismic emissions: Earth tides, fracture distribution, and fluid content. SEG, APPG Interpretation. 2016: 4 (2): T191–T204. XIX. Laverov, N. P., Bogoyavlenskiy, V. I., Bogoyavlenskiy, I. V. Fundamental Aspects of Rational Management of the Petroleum and Gas Resources of the Arctic and the Russian Continental Shelf: Strategy, Prospects, and Problems [Fundamental’nyyeaspektyratsional’nogoosvoyeniyaresursovneftiigazaArktiki I shel’faRossii: strategiya, perspektivyi problem].Arktika: ekologiya I ekonomika [Arctic: Ecology and Economy]. 2016; 2 (22): 4-13. XX. Lee, P. Low Noise Amplifier Selection Guide for Optimal Noise Performance, Analog Devices, Inc., AN-940 Application Note. Analog Devices, Inc. URL: https://www.analog.com/media/en/technical-documentation/application-notes/AN-940.pdf(Date of access September 2, 2019). XXI. Markatis, N., Polychronopoulou, K., Tselentis, Ak. Passive seismic tomography: A passive concept actively evolving. First Break. 2012; 30 (7): 83-90. XXII. Matveev, I. V. and Matveeva, N. V. Portable seismic recorder “SEISAR-5” with very low energy consumption for autonomous work in harsh climatic conditions [Portativnyyseysmicheskiyregistrator «Seysar-5» s ochen’ nizkimenergopotrebleniyemdlyaavtonomnoyraboty v slozhnykhklimatic heskikhusloviyakh]. Nauka I tekhnologicheskierazrabotki (Science and Technological Developments). 2017; 96 (3): 33-40. [Special Issue “Applied Geophysics: New Developments and Results. Part 1. Seismology and Seismic Exploration]. DOI: 10.21455/std2017.3-3. XXIII. Mishra, R. The Temperature Ratings of Electronic Parts.Electronics Cooling magazine. URL: http://www.electronics-cooling.com/2004/02/the-temperature-ratings-of-electronic-parts(Date of access September 2, 2019). XXIV. Moore, Sue E.; Stabeno, Phyllis J.; Van Pelt, Thomas I. The Synthesis of Arctic Research (SOAR) project. 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View | Download COMPARATIVE ANALYSIS OF RESULTS OF TREATMENT OF PATIENTS WITH FOOT PATHOLOGY WHO UNDERWENT WEIL OPEN OSTEOTOMY BY CLASSICAL METHOD AND WITHOUT STEOSYNTHESIS Authors: Yuriy V. Lartsev,Dmitrii A. Rasputin,Sergey D. Zuev-Ratnikov,Pavel V.Ryzhov,Dmitry S. Kudashev,Anton A. Bogdanov, DOI: https://doi.org/10.26782/jmcms.spl.10/2020.06.00044 Abstract: The article considers the problem of surgical correction of the second metatarsal bone length. The article analyzes the results of treatment of patients with excess length of the second metatarsal bones that underwent osteotomy with and without osteosynthesis. The results of treatment of patients who underwent metatarsal shortening due to classical Weil-osteotomy with and without osteosynthesis were analyzed. The first group consisted of 34 patients. They underwent classical Weil osteotomy. The second group included 44 patients in whomosteotomy of the second metatarsal bone were not by the screw. When studying the results of the treatment in the immediate postoperative period, weeks 6, 12, slightly better results were observed in patients of the first group, while one year after surgical treatment the results in both groups were comparable. One year after surgical treatment, there were 2.9% (1 patient) of unsatisfactory results in the first group and 4.5% (2 patients) in the second group. Considering the comparability of the results of treatment in remote postoperative period, the choice of concrete method remains with the operating surgeon. Keywords: Flat feet,hallux valgus,corrective osteotomy,metatarsal bones, Refference: I. A novel modification of the Stainsby procedure: surgical technique and clinical outcome [Text] / E. Concannon, R. MacNiocaill, R. Flavin [et al.] // Foot Ankle Surg. – 2014. – Dec., Vol. 20(4). – P. 262–267. II. Accurate determination of relative metatarsal protrusion with a small intermetatarsal angle: a novel simplified method [Text] / L. Osher, M.M. Blazer, S. Buck [et al.] // J. Foot Ankle Surg. – 2014. – Sep.-Oct., Vol. 53(5). – P. 548–556. III. Argerakis, N.G. The radiographic effects of the scarf bunionectomy on rearfoot alignment [Text] / N.G. Argerakis, L.Jr. Weil, L.S. Sr. Weil // Foot Ankle Spec. – 2015. – Apr., Vol. 8(2). – P. 89–94. IV. Bauer, T. Percutaneous forefoot surgery [Text] / T. Bauer // Orthop. Traumatol. Surg. Res. – 2014. – Feb., Vol. 100(1 Suppl.). – P. S191–S204. V. Biomechanical Evaluation of Custom Foot Orthoses for Hallux Valgus Deformity [Text] // J. Foot Ankle Surg. – 2015. – Sep.-Oct., Vol.54(5). – P. 852–855. VI. Chopra, S. Characterization of gait in female patients with moderate to severe hallux valgus deformity [Text] / S. Chopra, K. Moerenhout, X. Crevoisier // Clin. Biomech. (Bristol, Avon). – 2015. – Jul., Vol. 30(6). – P. 629–635. VII. Computer assisted planning and custom-made surgical guide for malunited pronation deformity after first metatarsophalangeal joint arthrodesis in rheumatoid arthritis: a case report [Text] / M. Hirao, S. Ikemoto, H. Tsuboi [et al.] // Comput. Aided Surg. – 2014. – Vol. 19(1-3). – P. 13–19. VIII. Correlation between static radiographic measurements and intersegmental angular measurements during gait using a multisegment foot model [Text] / D.Y. Lee, S.G. Seo, E.J. Kim [et al.] // Foot Ankle Int. – 2015. – Jan., Vol.36(1). – P. 1–10. IX. Correlative study between length of first metatarsal and transfer metatarsalgia after osteotomy of first metatarsal [Text]: [Article in Chinese] / F.Q. Zhang, B.Y. Pei, S.T. Wei [et al.] // Zhonghua Yi XueZaZhi. – 2013. – Nov. 19, Vol. 93(43). – P. 3441–3444. X. Dave, M.H. Forefoot Deformity in Rheumatoid Arthritis: A Comparison of Shod and Unshod Populations [Text] / M.H. Dave, L.W. Mason, K. Hariharan // Foot Ankle Spec. – 2015. – Oct., Vol. 8(5). – P. 378–383. XI. Does arthrodesis of the first metatarsophalangeal joint correct the intermetatarsal M1M2 angle? Analysis of a continuous series of 208 arthrodeses fixed with plates [Text] / F. Dalat, F. Cottalorda, M.H. Fessy [et al.] // Orthop. Traumatol. Surg. Res. – 2015. – Oct., Vol. 101(6). – P. 709–714. XII. Dynamic plantar pressure distribution after percutaneous hallux valgus correction using the Reverdin-Isham osteotomy [Text]: [Article in Spanish] / G. Rodríguez-Reyes, E. López-Gavito, A.I. Pérez-Sanpablo [et al.] // Rev. Invest. Clin. – 2014. – Jul., Vol. 66, Suppl. 1. – P. S79-S84. XIII. Efficacy of Bilateral Simultaneous Hallux Valgus Correction Compared to Unilateral [Text] / A.V. Boychenko, L.N. Solomin, S.G. Parfeyev [et al.] // Foot Ankle Int. – 2015. – Nov., Vol. 36(11). – P. 1339–1343. XIV. Endolog technique for correction of hallux valgus: a prospective study of 30 patients with 4-year follow-up [Text] / C. Biz, M. Corradin, I. Petretta [et al.] // J. OrthopSurg Res. – 2015. – Jul. 2, № 10. – P. 102. XV. First metatarsal proximal opening wedge osteotomy for correction of hallux valgus deformity: comparison of straight versus oblique osteotomy [Text] / S.H. Han, E.H. Park, J. Jo [et al.] // Yonsei Med. J. – 2015. – May, Vol. 56(3). – P. 744–752. XVI. Long-term outcome of joint-preserving surgery by combination metatarsal osteotomies for shortening for forefoot deformity in patients with rheumatoid arthritis [Text] / H. Niki, T. Hirano, Y. Akiyama [et al.] // Mod. Rheumatol. – 2015. – Sep., Vol. 25(5). – P. 683–638. XVII. Maceira, E. Transfer metatarsalgia post hallux valgus surgery [Text] / E. Maceira, M. Monteagudo // Foot Ankle Clin. – 2014. – Jun., Vol. 19(2). – P.285–307. XVIII. Nielson, D.L. Absorbable fixation in forefoot surgery: a viable alternative to metallic hardware [Text] / D.L. Nielson, N.J. Young, C.M. Zelen // Clin. Podiatr. Med. Surg. – 2013. – Jul., Vol. 30(3). – P. 283–293 XIX. Patient’s satisfaction after outpatient forefoot surgery: Study of 619 cases [Text] / A. Mouton, V. Le Strat, D. Medevielle [et al.] // Orthop. Traumatol. Surg. Res. – 2015. – Oct., Vol. 101(6 Suppl.). – P. S217–S220. XX. Preference of surgical procedure for the forefoot deformity in the rheumatoid arthritis patients–A prospective, randomized, internal controlled study [Text] / M. Tada, T. Koike, T. Okano [et al.] // Mod. Rheumatol. – 2015. – May., Vol. 25(3). – P.362–366. XXI. Redfern, D. Percutaneous Surgery of the Forefoot [Text] / D. Redfern, J. Vernois, B.P. Legré // Clin. Podiatr. Med. Surg. – 2015. – Jul., Vol. 32(3). – P. 291–332. XXII. Singh, D. Bullous pemphigoid after bilateral forefoot surgery [Text] / D. Singh, A. Swann // Foot Ankle Spec. – 2015. – Feb., Vol. 8(1). – P. 68–72. XXIII. Treatment of moderate hallux valgus by percutaneous, extra-articular reverse-L Chevron (PERC) osteotomy [Text] / J. Lucas y Hernandez, P. Golanó, S. Roshan-Zamir [et al.] // Bone Joint J. – 2016. – Mar., Vol. 98-B(3). – P. 365–373. XXIV. Weil, L.Jr. Scarf osteotomy for correction of hallux abducto valgus deformity [Text] / L.Jr. Weil, M. Bowen // Clin. Podiatr. Med. Surg. – 2014. – Apr., Vol.31(2). – P. 233–246. View | Download QUANTITATIVE ULTRASONOGRAPHY OF THE STOMACH AND SMALL INTESTINE IN HEALTHYDOGS Authors: Roman A. Tcygansky,Irina I. Nekrasova,Angelina N. Shulunova,Alexander I.Sidelnikov, DOI: https://doi.org/10.26782/jmcms.spl.10/2020.06.00045 Abstract: Purpose.To determine the quantitative echogenicity indicators (and their ratio) of the layers of stomach and small intestine wall in healthy dogs. Methods. A prospective 3-year study of 86 healthy dogs (aged 1-7 yrs) of different breeds and of both sexes. Echo homogeneity and echogenicity of the stomach and intestines wall were determined by the method of Silina, T.L., et al. (2010) in absolute values ​​of average brightness levels of ultrasound image pixels using the 8-bit scale with 256 shades of gray. Results. Quantitative echogenicity indicators of the stomach and the small intestine wall in dogs were determined. Based on the numerical values ​​characterizing echogenicity distribution in each layer of a separate structure of the digestive system, the coefficient of gastric echogenicity is determined as 1:2.4:1.1 (mucosa/submucosa/muscle layers, respectively), the coefficient of duodenum and jejunum echogenicity is determined as 1:3.5:2 and that of ileum is 1:1.8:1. Clinical significance. The echogenicity coefficient of the wall of the digestive system allows an objective assessment of the stomach and intestines wall and can serve as the basis for a quantitative assessment of echogenicity changes for various pathologies of the digestive system Keywords: Ultrasound (US),echogenicity,echogenicity coefficient,digestive system,dogs,stomach,intestines, Refference: I. Agut, A. Ultrasound examination of the small intestine in small animals // Veterinary focus. 2009.Vol. 19. No. 1. P. 20-29. II. Bull. 4.RF patent 2398513, IPC51A61B8 / 00 A61B8 / 14 (2006.01) A method for determining the homoechogeneity and the degree of echogenicity of an ultrasound image / T. Silina, S. S. Golubkov. – No. 2008149311/14; declared 12/16/2008; publ. 09/10/2010 III. Choi, M., Seo, M., Jung, J., Lee, K., Yoon, J., Chang, D., Park, RD. Evaluation of canine gastric motility with ultrasonography // J. of Veterinary Medical Science. – 2002. Vol. 64. – № 1. – P. 17-21. IV. Delaney, F., O’Brien, R.T., Waller, K.Ultrasound evaluation of small bowel thickness compared to weight in normal dogs // Veterinary Radiology and Ultrasound. 2003 Vol. 44, № 5. Р 577-580. V. Diana, A., Specchi, S., Toaldo, M.B., Chiocchetti, R., Laghi, A., Cipone, M. Contrast-enhanced ultrasonography of the small bowel in healthy cats // Veterinary Radiology and Ultrasound. – 2011. – Vol. 52, № 5. – Р. 555-559. VI. Garcia, D.A.A., Froes, T.R. Errors in abdominal ultrasonography in dogs and cats // J. of Small Animal Practice. – 2012. Vol. 53. – № 9. – P. 514-519. VII. Garcia, D.A.A., Froes, T.R. Importance of fasting in preparing dogs for abdominal ultrasound examination of specific organs // J. of Small Animal Practice. – 2014. Vol. 55. – № 12. – P. 630-634. VIII. Gaschen, L., Granger, L.A., Oubre, O., Shannon, D., Kearney, M., Gaschen, F. The effects of food intake and its fat composition on intestinal echogenicity in healthy dogs // Veterinary Radiology and Ultrasound. 2016. Vol. 57. № 5. P. 546-550 IX. Gaschen, L., Kircher, P., Stussi, A., Allenspach, K., Gaschen, F., Doherr, M., Grone, A. Comparison of ultrasonographic findings with clinical activity index (CIBDAI) and diagnosis in dogs with chronic enteropathies // Veterinary radiology and ultrasound. – 2008. – Vol. 49. – № 1. – Р. 56-64. X. Gil, E.M.U. Garcia, D.A.A. Froes, T.R. In utero development of the fetal intestine: Sonographic evaluation and correlation with gestational age and fetal maturity in dogs // Theriogenology. 2015. Vol. 84, №5. Р. 681-686. XI. Gladwin, N.E. Penninck, D.G., Webster, C.R.L. Ultrasonographic evaluation of the thickness of the wall layers in the intestinal tract of dogs // American Journal of Veterinary Research. 2014. Vol. 75, №4. Р. 349-353. XII. Gory, G., Rault, D.N., Gatel, L, Dally, C., Belli, P., Couturier, L., Cauvin, E. Ultrasonographic characteristics of the abdominal esophagus and cardia in dogs // Veterinary Radiology and Ultrasound. 2014. Vol. 55, № 5. P. 552-560. XIII. Günther, C.S. Lautenschläger, I.E., Scholz, V.B. Assessment of the inter- and intraobserver variability for sonographical measurement of intestinal wall thickness in dogs without gastrointestinal diseases | [Inter-und Intraobserver-Variabilitätbei der sonographischenBestimmung der Darmwanddicke von HundenohnegastrointestinaleErkrankungen] // Tierarztliche Praxis Ausgabe K: Kleintiere – Heimtiere. 2014. Vol. 42 №2. Р. 71-78. XIV. Hanazono, K., Fukumoto, S., Hirayama, K., Takashima, K., Yamane, Y., Natsuhori, M., Kadosawa, T., Uchide, T. Predicting Metastatic Potential of gastrointestinal stromal tumors in dog by ultrasonography // J. of Veterinary Medical Science. – 2012. Vol. 74. – № 11. – P. 1477-1482. XV. Heng, H.G., Lim, Ch.K., Miller, M.A., Broman, M.M.Prevalence and significance of an ultrasonographic colonic muscularishyperechoic band paralleling the serosal layer in dogs // Veterinary Radiology and Ultrasound. 2015. Vol. 56 № 6. P. 666-669. XVI. Ivančić, M., Mai, W. Qualitative and quantitative comparison of renal vs. hepatic ultrasonographic intensity in healthy dogs // Veterinary Radiology and Ultrasound. 2008. Vol. 49. № 4. Р. 368-373. XVII. Lamb, C.R., Mantis, P. Ultrasonographic features of intestinal intussusception in 10 dogs // J. of Small Animal Practice. – 2008. Vol. 39. – № 9. – P. 437-441. XVIII. Le Roux, A. B., Granger, L.A., Wakamatsu, N, Kearney, M.T., Gaschen, L.Ex vivo correlation of ultrasonographic small intestinal wall layering with histology in dogs // Veterinary Radiology and Ultrasound.2016. Vol. 57. № 5. P. 534-545. XIX. Nielsen, T. High-frequency ultrasound of Peyer’s patches in the small intestine of young cats / T. Nielsen [et al.] // Journal of Feline Medicine and Surgery. – 2015. – Vol. 18, № 4. – Р. 303-309. XX. PenninckD.G. Gastrointestinal tract. In Nyland T.G., Mattoon J.S. (eds): Small Animal Diagnostic Ultrasound. Philadelphia: WB Saunders. 2002, 2nd ed. Р. 207-230. XXI. PenninckD.G. Gastrointestinal tract. In: PenninckD.G.,d´Anjou M.A. Atlas of Small Animal Ultrasonography. Blackwell Publishing, Iowa. 2008. Р. 281-318. XXII. Penninck, D.G., Nyland, T.G., Kerr, L.Y., Fisher, P.E. Ultrasonographic evaluation of gastrointestinal diseases in small animals // Veterinary Radiology. 1990. Vol. 31. №3. P. 134-141. XXIII. Penninck, D.G.,Webster, C.R.L.,Keating, J.H. The sonographic appearance of intestinal mucosal fibrosis in cats // Veterinary Radiology and Ultrasound. – 2010. – Vol. 51, № 4. – Р. 458-461. XXIV. Pollard, R.E.,Johnson, E.G., Pesavento, P.A., Baker, T.W., Cannon, A.B., Kass, P.H., Marks, S.L. Effects of corn oil administered orally on conspicuity of ultrasonographic small intestinal lesions in dogs with lymphangiectasia // Veterinary Radiology and Ultrasound. 2013. Vol. 54. № 4. P. 390-397. XXV. Rault, D.N., Besso, J.G., Boulouha, L., Begon, D., Ruel, Y. Significance of a common extended mucosal interface observed in transverse small intestine sonograms // Veterinary Radiology and Ultrasound. 2004. Vol. 45. №2. Р. 177-179. XXVI. Sutherland-Smith, J., Penninck, D.G., Keating, J.H., Webster, C.R.L. Ultrasonographic intestinal hyperechoic mucosal striations in dogs are associated with lacteal dilation // Veterinary Radiology and Ultrasound. – 2007. Vol. 48. – № 1. – P. 51-57. View | Download EVALUATION OF ADAPTIVE POTENTIAL IN MEDICAL STUDENTS IN THE CONTEXT OF SEASONAL DYNAMICS Authors: Larisa A. Merdenova,Elena A. Takoeva,Marina I. Nartikoeva,Victoria A. Belyayeva,Fatima S. Datieva,Larisa R. Datieva, DOI: https://doi.org/10.26782/jmcms.spl.10/2020.06.00046 Abstract: The aim of this work was to assess the functional reserves of the body to quantify individual health; adaptation, psychophysiological characteristics of the health quality of medical students in different seasons of the year. When studying the temporal organization of physiological functions, the rhythm parameters of physiological functions were determined, followed by processing the results using the Cosinor Analysis program, which reveals rhythms with an unknown period for unequal observations, evaluates 5 parameters of sinusoidal rhythms (mesor, amplitude, acrophase, period, reliability). The essence of desynchronization is the mismatch of circadian rhythms among themselves or destruction of the rhythms architectonics (instability of acrophases or their disappearance). Desynchronization with respect to the rhythmic structure of the body is of a disregulatory nature, most pronounced in pathological desynchronization. High neurotism, increased anxiety reinforces the tendency to internal desynchronization, which increases with stress. During examination stress, students experience a decrease in the stability of the temporary organization of the biosystem and the tension of adaptive mechanisms develops, which affects attention, mental performance and the quality of adaptation to the educational process. Time is shortened and the amplitude of the “initial minute” decreases, personal and situational anxiety develops, and the level of psychophysiological adaptation decreases. The results of the work are priority because they can be used in assessing quality and level of health. Keywords: Desynchronosis,biorhythms,psycho-emotional stress,mesor,acrophase,amplitude,individual minute, Refference: I. Arendt, J., Middleton, B. Human seasonal and circadian studies in Antarctica (Halley, 75_S) – General and Comparative Endocrinology. 2017: 250-259. (http://dx.doi.org/10.1016/j.ygcen.2017.05.010). II. BalandinYu.P. A brief methodological guide on the use of the agro-industrial complex “Health Sources” / Yu.P. Balandin, V.S. Generalov, V.F. Shishlov. Ryazan, 2007. III. Buslovskaya L.K. Adaptation reactions in students at exam stress/ L.K. Buslovskaya, Yu.P. Ryzhkova. Scientific bulletin of Belgorod State University. Series: Natural Sciences. 2011;17(21):46-52. IV. Chutko L. S. Sindromjemocionalnogovygoranija – Klinicheskie I psihologicheskieaspekty./ L.S Chutko. Moscow: MEDpress-inform, 2013. V. Eroshina K., Paul Wilkinson, Martin Mackey. The role of environmental and social factors in the occurrence of diseases of the respiratory tract in children of primary school age in Moscow. Medicine. 2013:57-71. VI. Fagrell B. “Microcirculation of the Skin”. The physiology and pharmacology of the microcirculation. 2013:423. VII. Gurova O.A. Change in blood microcirculation in students throughout the day. New research. 2013; 2 (35):66-71. VIII. Khetagurova L.G. – Stress/Ed. L.G. Khetagurov. Vladikavkaz: Project-Press Publishing House, 2010. IX. Khetagurova L.G., Urumova L.T. et al. Stress (chronomedical aspects). International Journal of Experimental Education 2010; 12: 30-31. X. Khetagurova L.G., Salbiev K.D., Belyaev S.D., Datieva F.S., Kataeva M.R., Tagaeva I.R. Chronopathology (experimental and clinical aspects/ Ed. L.G. Khetagurov, K.D. Salbiev, S.D.Belyaev, F.S. Datiev, M.R. Kataev, I.R. Tagaev. Moscow: Science, 2004. XI. KlassinaS.Ya. Self-regulatory reactions in the microvasculature of the nail bed of fingers in person with psycho-emotional stress. Bulletin of new medical technologies, 2013; 2 (XX):408-412. XII. Kovtun O.P., Anufrieva E.V., Polushina L.G. Gender-age characteristics of the component composition of the body in overweight and obese schoolchildren. Medical Science and Education of the Urals. 2019; 3:139-145. XIII. Kuchieva M.B., Chaplygina E.V., Vartanova O.T., Aksenova O.A., Evtushenko A.V., Nor-Arevyan K.A., Elizarova E.S., Efremova E.N. A comparative analysis of the constitutional features of various generations of healthy young men and women in the Rostov Region. Modern problems of science and education. 2017; 5:50-59. XIV. Mathias Adamsson1, ThorbjörnLaike, Takeshi Morita – Annual variation in daily light expo-sure and circadian change of melatonin and cortisol consent rations at a northern latitude with large seasonal differences in photoperiod length – Journal of Physiological Anthropology. 2017; 36: 6 – 15. XV. Merdenova L.A., Tagaeva I.R., Takoeva E.A. Features of the study of biological rhythms in children. The results of fundamental and applied research in the field of natural and technical sciences. Materials of the International Scientific and Practical Conference. Belgorod, 2017, pp. 119-123. XVI. Ogarysheva N.V. The dynamics of mental performance as a criterion for adapting to the teaching load. Bulletin of the Samara Scientific Center of the Russian Academy of Sciences. 2014;16:5 (1): S.636-638. XVII. Pekmezovi T. Gene-environment interaction: A genetic-epidemiological approach. Journal of Medical Biochemistry. 2010;29:131-134. XVIII. Rapoport S.I., Chibisov S.M. Chronobiology and chronomedicine: history and prospects/Ed. S.M. Chibisov, S.I. Rapoport ,, M.L. Blagonravova. Chronobiology and Chronomedicine: Peoples’ Friendship University of Russia (RUDN) Press. Moscow, 2018. XIX. Roustit M., Cracowski J.L. “Non-invasive assessment of skin microvascular function in humans: an insight into methods” – Microcirculation 2012; 19 (1): 47-64. XX. Rud V.O., FisunYu.O. – References of the circadian desinchronosis in students. Ukrainian Bulletin of Psychoneurology. 2010; 18(2) (63): 74-77. XXI. Takoeva Z. A., Medoeva N. O., Berezova D. T., Merdenova L. A. et al. Long-term analysis of the results of chronomonitoring of the health of the population of North Ossetia; Vladikavkaz Medical and Biological Bulletin. 2011; 12(12,19): 32-38. XXII. Urumova L.T., Tagaeva I.R., Takoeva E.A., Datieva L.R. – The study of some health indicators of medical students in different periods of the year. Health and education in the XXI century. 2016; 18(4): 94-97. XXIII. Westman J. – Complex diseases. In: Medical genetics for the modern clinician. USA: Lippincott Williams & Wilkins, 2006. XXIV. Yadrischenskaya T.V. Circadian biorhythms of students and their importance in educational activities. Problems of higher education. Pacific State University Press. 2016; 2:176-178. View | Download TRIADIC COMPARATIVE ANALYSIS Authors: Stanislav A.Kudzh,Victor Ya. Tsvetkov, DOI: https://doi.org/10.26782/jmcms.spl.10/2020.06.00047 Abstract: The present study of comparison methods based on the triadic model introduces the following concepts: the relation of comparability and the relation of comparison, and object comparison and attributive comparison. The difference between active and passive qualitative comparison is shown, two triadic models of passive and active comparison and models for comparing two and three objects are described. Triadic comparison models are proposed as an alternative to dyadic comparison models. Comparison allows finding the common and the different; this approach is proposed for the analysis of the nomothetic and ideographic method of obtaining knowledge. The nomothetic method identifies and evaluates the general, while the ideographic method searches for unique in parameters and in combinations of parameters. Triadic comparison is used in systems and methods of argumentation, as well as in the analysis of consistency/inconsistency. Keywords: Comparative analysis,dyad,triad,triadic model,comparability relation,object comparison,attributive comparison,nomothetic method,ideographic method, Refference: I. AltafS., Aslam.M.Paired comparison analysis of the van Baarenmodel using Bayesian approach with noninformativeprior.Pakistan Journal of Statistics and Operation Research 8(2) (2012) 259{270. II. AmooreJ. E., VenstromD Correlations between stereochemical assessments and organoleptic analysis of odorous compounds. Olfaction and Taste (2016) 3{17. III. BarnesJ., KlingerR. Embedding projection for targeted cross-lingual sentiment: model comparisons and a real-world study. Journal of Artificial Intelligence Research 66 (2019) 691{742. doi.org/10.1613/jair.1.11561 IV. Castro-SchiloL., FerrerE.Comparison of nomothetic versus idiographic-oriented methods for making predictions about distal outcomes from time series data. Multivariate Behavioral Research 48(2) (2013) 175{207. V. De BonaG.et al. Classifying inconsistency measures using graphs. Journal of Artificial Intelligence Research 66 (2019) 937{987. VI. FideliR. La comparazione. Milano: Angeli, 1998. VII. GordonT. F., PrakkenH., WaltonD. The Carneades model of argument and burden of proof. Artificial Intelligence 10(15) (2007) 875{896. VIII. GrenzS.J. The social god and the relational self: A Triad theology of the imago Dei. Westminster: John Knox Press, 2001. IX. HermansH.J. M.On the integration of nomothetic and idiographic research methods in the study of personal meaning.Journal of Personality 56(4) (1988) 785{812. X. JamiesonK. G., NowakR. Active ranking using pairwise comparisons.Advances in Neural Information Processing Systems (2011) 2240{2248. XI. JongsmaC.Poythress’s triad logic: a review essay. Pro Rege 42(4) (2014) 6{15. XII. KärkkäinenV.M. Trinity and Religious Pluralism: The Doctrine of the Trinity in Christian Theology of Religions. London: Routledge, 2017. XIII. KudzhS. A., TsvetkovV.Ya. Triadic systems. Russian Technology Magazine 7(6) (2019) 74{882. XIV. NelsonK.E.Some observations from the perspective of the rare event cognitive comparison theory of language acquisition.Children’s Language 6 (1987) 289{331. XV. NiskanenA., WallnerJ., JärvisaloM.Synthesizing argumentation frameworks from examples. Journal of Artificial Intelligence Research 66 (2019) 503{554. XVI. PührerJ.Realizability of three-valued semantics for abstract dialectical frameworks.Artificial Intelligence 278 (2020) 103{198. XVII. SwansonG.Frameworks for comparative research: structural anthropology and the theory of action. In: Vallier, Ivan (Ed.). Comparative methods in sociology: essays on trends and applications.Berkeley: University of California Press, 1971 141{202. XVIII. TsvetkovV.Ya.Worldview model as the result of education.World Applied Sciences Journal 31(2) (2014) 211{215. XIX. TsvetkovV. Ya. Logical analysis and variable scales. Slavic Forum 4(22) (2018) 103{109. XX. Wang S. et al. Transit traffic analysis zone delineating method based on Thiessen polygon. Sustainability 6(4) (2014) 1821{1832. View | Download DEVELOPING TECHNOLOGY OF CREATING WEAR-RESISTANT CERAMIC COATING FOR ICE CYLINDER". JOURNAL OF MECHANICS OF CONTINUA AND MATHEMATICAL SCIENCES spl10, № 1 (28 червня 2020). http://dx.doi.org/10.26782/jmcms.spl.10/2020.06.00048.

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