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Journal articles on the topic 'INS-1 Zellen'

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Published: 4 June 2021
Last updated: 2 February 2022

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1

Köhler, D., M. Hetzel, M. Klingner, T. Koch, S. Ewig, G. Becher, H. Lindemann, T. Voshaar, and U. Costabel. "Die Rolle der Luftschadstoffe für die Gesundheit." Pneumologie 73, no. 05 (April 16, 2019): 274–87. http://dx.doi.org/10.1055/a-0873-3574.

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ZusammenfassungIn Deutschland gibt es regionale Fahrverbote für ältere Dieselfahrzeuge ohne SCR-Katalysator bei Überschreitung der Grenzwerte für NO2. Dies hat zu einer intensiven Diskussion über die Rolle der Luftschadstoffe für die Gesundheit geführt. In der Replik wird dargestellt, dass die Daten zur Wirkung von Stickstoffdioxid (NO2) und Feinstaub (PM10 und PM2,5) nicht ausreichen, um die Fahrverbote zu begründen.Für NO2 gibt es passagere Reaktionen bei unbehandelten Asthmatikern ab 500 µg/m3. Die deutschen Grenzwerte (Jahresmittelwert 40 µg/m3) fußen im Wesentlichen auf einer Metaanalyse von 9 Studien aus Innenraumbelastungen wobei nur in 4 Studien NO2 gemessen wurde. In der großen europäischen Escape-Studie von 2014 wurde kein Einfluss von NO2 auf die Mortalität gefunden.Als Surrogatparameter für andere Schadstoffe ist NO2 ebenfalls nicht mehr geeignet, da seit Einführung der Partikelfilter bei Dieselautos (etwa ab 2000) der KFZ-Anteil am Feinstaub an der Straße unter 10 % liegt. Der Feinstaub besteht im Wesentlichen aus Aufwirbelung von mineralischen, organischen Bodensubstanzen sowie Reifenabrieb und wird am stärksten durch Wetterphänomene, vor allen Dingen durch Sonneneinstrahlung beeinflusst.Die Grenzwerte für NO2 und Feinstaub werden errechnet aus epidemiologischen Beobachtungsstudien. Es findet sich zumeist eine schwache Assoziation zwischen der Konzentra-tion und zahlreichen Erkrankung sowie der Mortalität. Epidemiologische Beobachtungsstudien erlauben nur die Bildung einer Hypothese. Permanente Wiederholungen der Beobachtungsstudien betätigen nur, dass manche gefundenen Phänomene nicht zufällig sind. Eine Kausalität kann daraus nicht abgeleitet werden, da es zahlreiche Erklärungsmodelle neben dem NO2 und Feinstaub gibt. Dazu wären Interventionsstudien im Niedrigdosisbereich sowie Tierexperimente erforderlich. Diese Daten fehlen nahezu komplett bzw. sind, soweit vorhanden, allesamt negativ.Nie diskutiert wird eine starke Widerlegung der Hypothese der Gefährdung von NO2 und Feinstaub im Grenzwertbereich durch das Inhalationsrauchen. Die Raucher stellen quasi einen inhalationstoxikologischen Großversuch dar. Der Zigarettenrauch enthält sehr hohe Feinstaub-, Stickstoffmonoxid- (NO) und NO2-Konzentrationen, die vom Organismus erstaunlich gut toleriert werden. Das hängt damit zusammen, dass NO ein Naturstoff ist, der in den Zellen oder auch in den Nasennebenhöhlen in z. T. sehr hohen Konzentrationen (über 30 000 µg/m3) vorkommt. Eines der Abbauprodukte von NO ist NO2, was im Wasser zu Nitrat und Nitrit disproportioniert wird. Ein Teil von NO2 wird zur Synthese von Fettsäuren verwendet.Zigaretten haben ein Kondensat von ca. 7 – 10 mg. Nimmt man als Vergleich eine lebenslange Dauerbelastung durch Feinstaub und NO2 in den Grenzwertkonzentrationen an, müssten alle Raucher nach wenigen Tagen bis Monaten zahlreiche Erkrankungen entwickeln, die dem Feinstaub und NOx angelastet werden. Auch die Mortalität müsste drastisch erhöht sein; nahezu alle Raucher müssten bereits nach 1 packyear verstorben sein. Der Unterschied wird noch größer, wenn man die nachgewiesene Toxizität und Kanzerogenität des Zigarettenrauchs im Vergleich zu dem i. d. R. deutlich weniger gefährlichen Feinstaub an der Straße ins Verhältnis setzt.
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2

Afrough, Aimaz, Samer A. Srour, Qaiser Bashir, Neeraj Saini, Chitra Hosing, Uday R. Popat, Partow Kebriaei, et al. "Prognostic Impact of Beta 2 Microglobulin in Patients with Immunoglobulin Light-Chain Amyloidosis Undergoing Autologous Hematopoietic Stem Cell Transplantation." Blood 136, Supplement 1 (November 5, 2020): 20–21. http://dx.doi.org/10.1182/blood-2020-141360.

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Background: Risk stratification for Immunoglobulin light chain amyloidosis (AL) has been refined with advances in the understanding of disease biology. Although nonspecific, beta 2 microglobulin (β2M) levels correlate with disease burden and are considered a prognostic marker in several hematologic malignancies. Recently, we and others have shown the association of β2M levels with survival in AL. In this study, we evaluated the role of β2M as a predictor of outcome for high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) in patients with AL. Methods: We identified 175 consecutive patients with AL who received auto-HCT between 2009 and 2019 at our institution. A β2M≥3.5 mg/L, regardless of renal function status was used as a cutoff value. Hematologic and organ responses were evaluated according to the Consensus Guidelines for AL. Revised Mayo staging system was utilized for Cardiac staging. Results: The median age at auto-HCT was 60 years (range, 27 to 77). Of 175 patients, 153 (87%) had a β2M value available, of whom 57 (37%) had a β2M ≥ 3.5 mg/L. There were no significant differences in baseline characteristics between the 2 groups, except for the higher level of LDH, worse renal function, and more patients with renal involvement in the β2M ≥ 3.5 group, and more patients with lambda light chain type in the β2M <3.5 group (Table 1). The median follow-up from auto-HCT was 38 months (range; 1 to 124). One-year non-relapse mortality (NRM) was 2%. The 1-year NRM was 5% (n=3) and 1% (n=1) in patients with β2M≥3.5, and β2M<3.5, respectively (p=0.115). Hematologic CR after auto-HCT was seen in 21 (37%), and 38 (40%) patients with β2M≥3.5 and β2M<3.5, respectively (p=0.864). Organ response (OR) after auto-HCT was seen in 36 (73%), and 65 (71%) patients with β2M≥3.5 and β2M<3.5, respectively (p=1.00). The 3-year progression-free survival (PFS) was 66%, and 74% in patients with β2M≥3.5, and β2M<3.5 (p=0.17) (Figure 1A).The 3-year overall survival (OS) was 73%, ad 89% in patients with β2M≥3.5, and β2M<3.5 (p=0.009) (Figure 1B). On Cox-regression multivariate analysis, cardiac involvement with AL (p=0.043), and β2M≥3.5 (p=0.029) were associated with a shorter OS. Conclusion: In this single-center retrospective analysis, we showed that high serum β2M is associated with shorter OS. β2M may be incorporated as a prognostic marker for AL if these findings are confirmed in larger studies. Disclosures Bashir: Acrotech: Research Funding; StemLine: Research Funding; Celgene: Research Funding; Takeda: Other: Advisory Board, Research Funding; KITE: Other: Advisory Board; Amgen: Other: Advisory Board; Purdue: Other: Advisory Board. Hosing:NKARTA Inc.: Consultancy. Popat:Bayer: Research Funding; Novartis: Research Funding. Kebriaei:Novartis: Other: Served on advisory board; Jazz: Consultancy; Ziopharm: Other: Research Support; Kite: Other: Served on advisory board; Pfizer: Other: Served on advisory board; Amgen: Other: Research Support. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Manasanch:Sanofi: Research Funding; Adaptive Biotechnologies: Honoraria; GSK: Honoraria; Sanofi: Honoraria; BMS: Honoraria; Takeda: Honoraria; Quest Diagnostics: Research Funding; Merck: Research Funding; JW Pharma: Research Funding; Novartis: Research Funding. Lee:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Regeneron: Research Funding; Genentech: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy. Kaufman:Janssen: Research Funding; Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding. Patel:Cellectis: Research Funding; Nektar: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Oncopeptides: Consultancy; Poseida: Research Funding. Thomas:BMS: Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; X4 Pharma: Research Funding; Genentech: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards. Orlowski:STATinMED Research: Consultancy; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding. Champlin:Genzyme: Speakers Bureau; Johnson and Johnson: Consultancy; Actinium: Consultancy; Cytonus: Consultancy; Omeros: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Takeda: Patents & Royalties. Qazilbash:Angiocrine: Research Funding; Bioline: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy; Janssen: Research Funding.
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Afrough, Aimaz, Leonard C. Alsfeld, Samer A. Srour, Qaiser Bashir, Neeraj Saini, Chitra Hosing, Uday R. Popat, et al. "Outcome of Patients with Immunoglobulin Light-Chain Amyloidosis with t(11;14) Undergoing Autologous Hematopoietic Stem Cell Transplantation." Blood 136, Supplement 1 (November 5, 2020): 18–19. http://dx.doi.org/10.1182/blood-2020-141307.

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Background- In patients with light chain amyloidosis (AL), t(11;14) detected by fluorescence in situ hybridization (FISH) is the most common cytogenetic aberration. Several studies have shown that t(11;14) is associated with inferior outcomes in newly diagnosed AL patients [1, 2]. In contrast, at least one study in patients with t(11;14) who underwent high-dose therapy and autologous hematopoietic stem cell transplantation (auto-HCT) showed improved complete response (CR) rate and prolonged hematologic event-free survival[3]. In this single-center, retrospective analysis, we evaluated the outcome of patients with AL and t(11;14) who underwent auto-HCT at our institution. Method- We identified 122 consecutive patients with AL with cardiac or renal involvement who received an auto-HCT between 2011 and 2019. Baseline FISH data were available for 92 patients, 15 (16 %) of whom had t(11;14). Seventy-seven (84%) patients without t(11;14) were included as control . Hematologic and organ responses were evaluated according to the Consensus Guidelines for AL [4]. Revised Mayo staging system was utilized for Cardiac staging [5]. Result- The median age at auto-HCT was 60 years (range, 27 to 77). There were no significant differences in baseline characteristics between the two groups (Table 1). The median follow-up from auto-HCT was 28 months (range, 1 to 100). Overall, 40%, and 42% of patients with or without t(11;14), respectively (p=0.573), received post-auto-HCT maintenance therapy. One-year non-relapse mortality (NRM) was 2%. The 1-year NRM was 0 and 2.6% (n=2) in patients with or without t(11;14) (p=0.366). Hematologic CR after auto-HCT was seen in 7 (47%) and 33 (42%) patients with or without t(11;14), respectively (p=0.78). Organ response (OR) after auto-HCT was seen in 10 (71%) and 50 (67%) patients with or without t(11;14), respectively (p=0.586). The 2-year hematologic disease-free survival (Heme DFS) was 93% and 87% with or without t(11;14), respectively (p=0.422). The 2-year progression-free survival (PFS) was 92%, and 87% in patients with or without t(11;14) (p=0.6) (Figure 1A).The 2-year overall survival was 100%, ad 87% in patients with or without t(11;14) (p=0.2) (Figure 1B). Cardiac involvement with AL was associated with a shorter OS (p=0.012). Conclusion- In this single-center retrospective analysis, we showed that auto-HCT is safe and feasible in selected patients with AL and t(11;14), and these patients have comparable outcomes to patients without t(11;14). Disclosures Bashir: Celgene: Research Funding; StemLine: Research Funding; Acrotech: Research Funding; Takeda: Other: Advisory Board, Research Funding; KITE: Other: Advisory Board; Purdue: Other: Advisory Board; Amgen: Other: Advisory Board. Hosing:NKARTA Inc.: Consultancy. Popat:Bayer: Research Funding; Novartis: Research Funding. Kebriaei:Amgen: Other: Research Support; Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Novartis: Other: Served on advisory board; Ziopharm: Other: Research Support; Jazz: Consultancy. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Manasanch:Adaptive Biotechnologies: Honoraria; Sanofi: Research Funding; Novartis: Research Funding; JW Pharma: Research Funding; Merck: Research Funding; Quest Diagnostics: Research Funding; Takeda: Honoraria; BMS: Honoraria; Sanofi: Honoraria; GSK: Honoraria. Lee:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Regeneron: Research Funding; Genentech: Consultancy. Kaufman:Janssen: Research Funding; Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding. Patel:Oncopeptides: Consultancy; Celgene: Consultancy, Research Funding; Cellectis: Research Funding; Janssen: Consultancy, Research Funding; Nektar: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Poseida: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Thomas:Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; X4 Pharma: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards; Genentech: Research Funding; BMS: Research Funding. Orlowski:STATinMED Research: Consultancy; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding. Champlin:Actinium: Consultancy; Omeros: Consultancy; Takeda: Patents & Royalties; Cytonus: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau; Johnson and Johnson: Consultancy. Qazilbash:Janssen: Research Funding; Bioline: Research Funding; Angiocrine: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy.
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Afrough, Aimaz, Leonard C. Alsfeld, Ruby Delgado, Uday R. Popat, Partow Kebriaei, Betul Oran, Neeraj Saini, et al. "Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma." Blood 136, Supplement 1 (November 5, 2020): 22. http://dx.doi.org/10.1182/blood-2020-141261.

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Background: Hematopoietic cell transplantation (HCT) is an integral part of the treatment of multiple myeloma (MM). While autologous stem cell transplantation (auto-HCT) is most commonly used, the duration of response is typically finite. Allogeneic HCT (allo-HCT) can provide prolonged survival in some patients, given the added benefit of the graft-versus-myeloma effect. However, long-term data is needed to show this improvement. Method: We retrospectively reviewed a cohort of 37 consecutive patients with newly diagnosed MM who received allo-HCT as part of consolidation therapy between 1994 to 2016. Results: The median age was 54 years (range, 32 to 68), and 54% were male. The Revised International Staging System (R-ISS) stages were I, II, III, and unknown in 27%, 38%, 11%, and 24% of patients, respectively. High-risk cytogenetics (IMWG definition) was identified in 22% of patients. The median time from diagnosis to allo-HCT was 8.8 months (range; 3.3 to 34.3). For induction treatment, fourteen patients (38%) received a combination of immunomodulatory drug (IMiD) plus proteasome inhibitor (PI), sixteen patients (43%) received either IMiD or PI in combination with other agents, and seven patients (19%) did not receive either an IMiD or PI. Twenty-seven (73%) patients received auto-HCT before allo-HCT. Thirty-four (92%) patients received allo-HCT as part of various clinical trials. Median time from auto-HCT to allo-HCT was 4 months (2.5 to 27.3). Prior to allo-HCT, 1 (3%) patient was in complete remission (CR), 18 (48.5%) were in very good partial remission (VGPR), and 18 (48.5%) were in partial remission (PR). Twenty-three (62%) patients received non-myeloablative (NMA) conditioning, 10 (27%) reduced-intensity (RIC), and 4 (11%) myeloablative conditioning (MAC). The graft source was matched unrelated (MUD) in 16% and matched sibling donor (MRD) in 84% of patients. Ten (27%) patients received maintenance therapy after allo-HCT, including bortezomib (n=2), thalidomide (n=2), ixazomib (n=2), and lenalidomide (n=4). The median days to neutrophil and platelet engraftment was 12 (ANC ≥500/µL_ range; 10 to 59) and 13 (platelet count ≥20K/µL _range; 9 to 70), respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) was 16% at 1-year and 19% at 3-years after allo-HCT. There was no difference in NRM between MAC or NMA/RIC conditioning. The overall response rate (PR or better) was 97%, with a 54% stringent CR+CR rate. The incidence of grade I-IV acute graft-versus-host disease (GVHD) was 35%, while chronic GVHD was seen in 62%. Causes of death were deemed to be disease-related in 8 patients, treatment-related in 11 patients, and 1 unknown. The median follow-up in surviving patients was 12.6 years (range; 2.8 to 15.8 years). The 3, 5, and 10-year actuarial overall survival (OS) rates were 70%, 56%, and 47%, respectively (Figure 1A). The 3, 5, and 10-year actuarial progression-free survival (PFS) rates were 66%, 50%, and 36%, respectively (Figure 1B). At the last follow up, 46% (n=17) of patients were alive in the entire cohort, 65% (n=11) of which survived for longer than 10-years from transplant. Sixteen percent (n=6) remained alive and in continued remission for more than 10 years from transplant, one-third of whom received maintenance treatment post allo-HCT. The longest ongoing remission was 15.8 years in this cohort. Conclusion: Allo-HCT may result in durable (>10 years) remission in a number of MM patients when performed early in the disease course. Larger studies would help identify the patients who would benefit the most, given the risk of graft-versus-host disease after allo-HCT. Disclosures Popat: Bayer: Research Funding; Novartis: Research Funding. Kebriaei:Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Amgen: Other: Research Support; Jazz: Consultancy; Novartis: Other: Served on advisory board; Ziopharm: Other: Research Support. Oran:Celgene: Consultancy; ASTEX: Research Funding; Arog Pharmaceuticals: Research Funding. Hosing:NKARTA Inc.: Consultancy. Manasanch:Adaptive Biotechnologies: Honoraria; GSK: Honoraria; Sanofi: Honoraria; BMS: Honoraria; Takeda: Honoraria; Quest Diagnostics: Research Funding; Merck: Research Funding; JW Pharma: Research Funding; Novartis: Research Funding; Sanofi: Research Funding. Lee:Amgen: Consultancy, Research Funding; Genentech: Consultancy; Regeneron: Research Funding; Daiichi Sankyo: Research Funding; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Kaufman:Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding; Janssen: Research Funding. Patel:Precision Biosciences: Research Funding; Takeda: Consultancy, Research Funding; Cellectis: Research Funding; Janssen: Consultancy, Research Funding; Poseida: Research Funding; Oncopeptides: Consultancy; Nektar: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Orlowski:Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; STATinMED Research: Consultancy; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees. Thomas:Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; X4 Pharma: Research Funding; Pharmacyclics: Other: Advisory Boards; Xencor: Research Funding; Genentech: Research Funding. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Champlin:Takeda: Patents & Royalties; Actinium: Consultancy; Johnson and Johnson: Consultancy; Omeros: Consultancy; Cytonus: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau. Qazilbash:Bioclinica: Consultancy; Amgen: Research Funding; Angiocrine: Research Funding; Bioline: Research Funding; Janssen: Research Funding. Bashir:Celgene: Research Funding; Amgen: Other: Advisory Board; Purdue: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; Acrotech: Research Funding; StemLine: Research Funding; KITE: Other: Advisory Board.
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Brook, Michael A. "Macromolecules Containing Metal and Metal-like Elements, Volume 4: Group IVA Polymers Edited by Alaa S. Abd-El-Aziz (University of Winnipeg), Charles E. Carraher, Jr. (Florida Atlantic University), Charles U. Pittman, Jr. (Mississippi State University) and Martel Zeldin (Hobart and William Smith Colleges). John Wiley & Sons, Inc.: Hoboken, NJ. 2005. xviii + 348 pp. $125.00. ISBN 0-471-68238-1." Journal of the American Chemical Society 127, no. 44 (November 2005): 15659. http://dx.doi.org/10.1021/ja059736s.

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6

Srour, Samer A., Yago Nieto, Swaminathan P. Iyer, Roberto N. Miranda, Farzaneh Maadani, Gabriela Rondon, Neeraj Saini, et al. "Autologous Stem Cell Transplantation for Angioimmunoblastic T-Cell Lymphoma." Blood 136, Supplement 1 (November 5, 2020): 40–41. http://dx.doi.org/10.1182/blood-2020-142889.

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Introduction: Peripheral T-cell lymphoma (PTCL) comprises a heterogeneous group of rare neoplasms, the majority characterized by an aggressive course and short survival. Angioimmunoblastic T-cell lymphoma (AITL) is the second most common subtype (19%) of PTCLs, with generally poor long-term prognosis. The outcomes for most reported cases of AITL are derived from cohorts which include other PTCL subtypes. There is limited data for the role of autologous stem cell transplantation (ASCT) in AITL, and the associated predictive factors for prognosis. We present the largest single center cohort of AITL patients who underwent ASCT either upfront or at time of relapse. Methods: We included consecutive patients with AITL who had confirmed diagnosis and underwent ASCT at our institution from May 2000 to November 2019. Primary endpoints: progression free survival (PFS) and overall survival (OS). Secondary endpoints were cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and to identify prognostic factors associated with PFS and OS. Kaplan-Meier method was used to estimate OS and PFS. CIR and NRM were determined using the competing risks method. Cox regression analyses were used to determine prognostic factors. Results: The study included 54 patients with a median age of 63 (range, 37-77) years and male predominance (57%). All patients had advanced stage III/IV at diagnosis. Additional patient and disease characteristics are outlined in Table 1. Carmustine, etoposide, cytarabine, and melphalan (BEAM) with (30%) or without (57%) rituximab (R; used at the discretion of treating physician for EBER-positive AITL) were the most commonly used preparative regimens. With a median follow-up of 47.4 (range, 7.1-142.2) months, the median PFS and OS of all study patients were 41 and 108 months, respectively. The 2- and 4-year PFS/OS were 58%/83% and 46%/65%, respectively. CIR of relapse at 1, 2, and 4 years were 30%, 34%, and 44%, respectively. NRM at 1, 2, and 4 years were 7.5%, 7.5%, and 10%, respectively. All variables listed in Table 1 were assessed for their prognostic impact in univariate analysis (UVA) for PFS and OS. Of those, transplant for relapsed AITL (HR 3.716 95% CI: 1.728-7.991; p=0.0008) and high LDH at transplant (HR 2.139, 95% CI: 1.023-4.471; p=0.0433) were significantly associated with worse PFS (Figure 1A, C). There was a tendency for improved PFS for women (HR 0.56, 95% CI: 0.259-1.209; p=0.1398) and patients who received R-BEAM conditioning (HR for BEAM 1.99, 95% CI: 0.808-4.899; p=0.1344). Similar UVA results were noted for OS, where transplant for relapsed AITL (HR 2.943, 95% CI: 1.173-7.382; p=0.0214) and high LDH at transplant (HR 2.771, 95% CI: 1.076-7.138; p=0.0348) were significantly associated with worse OS (Figure 1B, D). On multivariable analysis (MVA), transplant at relapse (HR 3.716 95% CI: 1.728-7.991; p=0.0008) was associated with inferior PFS (HR 3.038, 95% CI: 1.386-6.659; p=0.0055) and OS (HR 2.291, 95% CI: 1.054-4.979; p=0.0364). High LDH at transplant was associated with worse PFS (HR 2.291, 95% CI: 1.054-4.979; p=0.0364), and with a trend for inferior OS (HR 2.259, 95% CI: 0.838-6.093; p=0.1073). Only 10 (19%) patients were transplanted with active disease at transplant; disease status at transplant didn't have a significant impact on outcomes in UVA and MVA. A subset analysis subgrouping patients by 1 (n=33) vs 2 (n=16) vs >2 (n=5) prior lines of therapy showed no significant difference in outcomes between 2 vs >2 prior lines of therapy. Conclusions: Upfront ASCT is associated with significantly improved and durable survival in patients with AITL. Receiving more than one prior line of therapy (transplant for relapsed AITL) and elevated LDH at transplant are associated with very poor prognosis, for which allogeneic transplant and alternative novel therapies should be further explored. Disclosures Nieto: Secura Bio: Other: Grant Support; Astra Zeneca: Other: Grant Support; Novartis: Other: Grant Support; Affimed: Consultancy, Other: Grant Support. Popat:Bayer: Research Funding; Novartis: Research Funding. Qazilbash:Angiocrine: Research Funding; Janssen: Research Funding; Bioline: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy. Shpall:Takeda: Other: Licensing Agreement; Novartis: Membership on an entity's Board of Directors or advisory committees; Magenta: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Flowers:Cancer Prevention and Research Institute of Texas: Research Funding; Karyopharm: Consultancy; Pharmacyclics/Janssen: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; National Cancer Institute: Research Funding; V Foundation: Research Funding; Kite: Research Funding; Bayer: Consultancy; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; BeiGene: Consultancy; AbbVie: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; OptumRx: Consultancy. Champlin:Johnson and Johnson: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau; Cytonus: Consultancy; Omeros: Consultancy; Takeda: Patents & Royalties; Actinium: Consultancy. Hosing:NKARTA Inc.: Consultancy. Khouri:Bristol Myers Squibb: Research Funding; Pfizer: Research Funding.
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Nieto, Yago, Stephen K. Gruschkus, Roy B. Jones, Benigno C. Valdez, Melissa Timmons, Chitra Hosing, Paolo Anderlini, et al. "Factors Associated with the Improvement of Outcomes of High-Risk Relapsed Hodgkin Lymphoma (HL) Patients Receiving High-Dose Chemotherapy (HDC) and Autologous Stem-Cell Transplantation (ASCT): The MD Anderson Cancer Center Experience." Blood 136, Supplement 1 (November 5, 2020): 17–18. http://dx.doi.org/10.1182/blood-2020-139880.

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HDC/ASCT is standard treatment of chemosensitive relapsed HL, with worse results for high-risk relapses (HRR) than for low-risk relapses. Aiming to improve the results of BEAM, we have studied newer HDC regimens seeking synergistic inhibition of DNA damage repair: gemcitabine/busulfan/melphalan (GBM) (Nieto, 2012) and vorinostat + GBM (SAHA/GBM) (Nieto, 2015). We wished to describe the evolution of results in HRR HL over the last 15 years and identify prognostic features. Methods We retrospectively analyzed all pts with HRR HL treated at MDACC with HDC/ASCT between 1/1/2005-12/31/2019. HRR HL was defined by ≥1 of the modified AETHERA criteria: primary refractory disease, relapse within 1 year of completing initial therapy, extranodal extension at relapse, B symptoms at relapse, or requiring > 1 salvage therapy line. All pts underwent similar pre-SCT evaluation and met eligibility criteria as per our institutional guidelines. HDC regimens included BEAM, busulfan/melphalan (BuMel), GBM and SAHA/GBM. Post-ASCT consolidative radiotherapy (RT) was considered for bulky relapses and/or PET+ lesions at ASCT. We evaluated age, gender, ASCT year, primary refractory disease, prior disease-free interval (DFI), prior radiotherapy (RT), relapse within prior RT field, extranodal extension at relapse, B symptoms at relapse, bulky relapse (largest lesion >5 cm), No. prior relapses, No. prior lines of therapy, prior brentuximab vedotin (BV), prior anti-PD1, PET results at ASCT, post-ASCT maintenance BV and post-ASCT RT. Differences by regimen cohort were tested with Kruskal Wallis or chi-square tests. Outcomes were compared with the log-rank test. Univariable and multivariable Cox regression analyses evaluated factors associated with progression-free survival (PFS) and overall survival (OS). Results A total of 501 pts, treated with BEAM (N=146), BuMel (N=38), GBM (N=189) and SAHA/GBM (N=128), were analyzed (Table 1). The GBM and SAHA/GBM cohorts had significantly more high-risk criteria (P=0.0006), with more pts with primary refractory disease (P=0.001) and bulky relapse (P<0.0001), as well as more pts with PET+ disease at ASCT (P=0.0002), and were slightly younger (P=0.04). Patient- and tumor-related variables did not change over time but there was a significant increase in prior BV (P<0.0001) and anti-PD1 (P<0.0001), a decrease in PET+ disease at ASCT (P=0.0008), and an increase in post-SCT BV (P<0.0001). BEAM and BuMel predominated earlier, GBM and BEAM in middle years, and SAHA/GBM and BEAM in later years (P<0.0001). Consequently, the SAHA/GBM cohort received more prior BV (P<0.0001) and anti-PD1 (P= 0.0001), and more post-ASCT BV (P<0.0001). At a median follow-up of 50 months (6-186), 205 pts (40.9%) experienced relapse and 129 pts (25.8%) died. There were 2 ASCT-related deaths (both after BEAM) and 11 cases of t-MDS/AML (2 BuMel, 5 BEAM, 3 GBM and 1 SAHA/GBM). Outcomes improved significantly over time, with 2-year PFS/OS of 58%/82% (2004-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016-2019) (P<0.0001) (Fig. 1 and 2). Multivariable analyses of PFS identified as independent favorable predictors: Prior BV (HR 0.61, P=0.03) and SAHA/GBM (GBM HR 1.24 compared to SAHA/GBM, BuMel HR 2.24, BEAM HR 2.26) (P=0.0003) (Fig. 3). The following were independent adverse PFS predictors: Primary refractory disease (HR 1.46, P=0.02), >2 prior lines (HR 1.51, P=0.04), bulky relapse (HR 1.45, P=0.01), B symptoms (HR 1.58, P=0.009), and PET+ at ASCT (HR 2.54, P<0.0001). Regarding OS, prior BV (HR 0.48, P=0.03) and SAHA/GBM (GBM: HR 1.55, BuMel: HR 5.08, BEAM: HR 5.31) (P<0.0001) (Fig. 4) were independent favorable predictors, whereas age >35 (HR 1.84, P=0.001), >2 prior lines (HR 1.89, P=0.01), B symptoms (HR 1.63, P=0.02), and PET+ (HR 2.24, P<0.0004) were adverse predictors. Post-SCT maintenance BV correlated with better PFS in univariate analyses (P=0.01) but did not retain significance in MVA (P=0.1). The 5-yr PFS/OS rates were: S/GBM: 72/87%, GBM: 55/75%, BEAM: 45/61% and BuMel: 39/57%. These differences persisted both within the PET-negative (P=0.0002 / P<0.0001) and PET+ subgroups (P=0.002 / P<0.0001). Conclusions Outcomes of HRR HL pts have improved over the last 15 years. Incorporation of newer agents (BV and anti-PD1) to salvage therapy, resulting in more PET-negative CRs at ASCT, and the use of more active HDC regimens (especially, SAHA/GBM) were associated with these improved results. Disclosures Nieto: Novartis: Other: Grant Support; Affimed: Consultancy, Other: Grant Support; Secura Bio: Other: Grant Support; Astra Zeneca: Other: Grant Support. Hosing:NKARTA Inc.: Consultancy. Kebriaei:Amgen: Other: Research Support; Jazz: Consultancy; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Pfizer: Other: Served on advisory board. Popat:Bayer: Research Funding; Novartis: Research Funding. Qazilbash:Janssen: Research Funding; Bioline: Research Funding; Angiocrine: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy. Alousi:Therakos: Research Funding; Alexion: Honoraria; Incyte: Honoraria, Research Funding. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Rezvani:GemoAb: Membership on an entity's Board of Directors or advisory committees; Formula Pharma: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Other: Educational grant; Affimed: Other: Educational grant; Takeda: Other: Licensing agreement; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; Virogen: Membership on an entity's Board of Directors or advisory committees. Khouri:Pfizer: Research Funding; Bristol Myers Squibb: Research Funding. Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Champlin:Genzyme: Speakers Bureau; DKMS America: Membership on an entity's Board of Directors or advisory committees; Cytonus: Consultancy; Actinium: Consultancy; Takeda: Patents & Royalties; Omeros: Consultancy; Johnson and Johnson: Consultancy. OffLabel Disclosure: Vorinostat and busulfan were used as part of conditioning regimens for ASCT for Hodgkin lymphoma.
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8

Jäkle, Frieder. "Macromolecules Containing Metal and Metal-Like Elements, Volume 1: A Half-Century of Metal- and Metalloid-Containing Polymers By Alaa S. Abd-El-Aziz (University of Winnipeg), Charles E. Carraher, Jr. (Florida Atlantic University), Charles U. Pittman, Jr. (Mississippi State University), John E. Sheats (Rider University), and Martel Zeldin (Hobart and William Smith Colleges). John Wiley & Sons, Inc.: Hoboken. 2003. x + 268 pp. $125.00. ISBN 0-471-45832-5." Journal of the American Chemical Society 126, no. 11 (March 2004): 3669–70. http://dx.doi.org/10.1021/ja033623w.

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9

Strati, Paolo, Haleigh Mistry, Brittany Pulsifer, Luis Fayad, Sairah Ahmed, Hun Ju Lee, Swami P. Iyer, et al. "Prognostic Value of Delta Lymphocyte Index (DLIx) in Patients with Large B-Cell Lymphoma (LBCL) Treated with Chimeric Antigen Receptor (CAR) T-Cell Therapy." Blood 136, Supplement 1 (November 5, 2020): 23–24. http://dx.doi.org/10.1182/blood-2020-135846.

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Abstract:
Introduction. The efficacy of CAR T-cell therapy in relapsed/refractory (r/r) LBCL has been associated with peak CAR T-cell expansion post-infusion. One of the critical factors that drives CAR T-cell expansion is the availability of homeostatic cytokines, such as IL-15, at the time of infusion. Consistent with this hypothesis, serum IL-15 levels have been associated with CAR T-cell therapy expansion and efficacy, higher levels favoring improved outcomes. Since induction of lymphodepleting conditioning (LDC) therapy results in decreased consumption of homeostatic cytokines and thereby increases their serum levels, we aimed to determine whether the magnitude of change in absolute lymphocyte count (ALC) pre- and post-conditioning, referred to as delta lymphocyte index (DLIx), impacts outcomes after CAR T-cell therapy in r/r LBCL. Methods. This is a retrospective study of all patients with r/r LBCL treated with standard of care (SOC) axicabtagene ciloleucel (axi-cel) at MD Anderson Cancer Center between 01/2018 and 04/2020 (data cut-off 06/30/2020). DLIx was defined as the difference in ALC between day of initiation of LDC and day of axi-cel infusion. All patients received LDC therapy with cyclophosphamide and fludarabine. CRS and ICANS were prospectively graded according to CARTOX criteria from 01/2018 to 04/2019, and ASTCT criteria from 05/2019 onward. Response to treatment and progression were defined according to 2014 Lugano criteria. Results. All 171 LBCL patients treated with SOC axi-cel were included in the analysis. At time of initiation of LDC, median age was 59 years (range, 18-85 years), 120 (70%) were male, 151 (88%) had an ECOG performance status of 0-1; 96 (56%) had an IPI > 3, median number of prior systemic therapies was 4 (range, 2-15), 45 (26%) had received an autologous SCT, 3 (2%) an allogeneic SCT; 86 (50%) patients received bridging therapy, including chemotherapy in 52 (30%), radiotherapy in 21 (12%), and biological therapy or corticosteroids in 13 (8%). Median ALC at time of LDC was 0.6 X 109/L (range, 0-2.8 X 109/L) and < lower limit of normal (LLN) in 131 (77%) patient; at time of axi-cel infusion it was 0.03 X109/L (range, 0-1.9 X109/L), and median DLIx was 0.5 X 109/L (range, 0.01-2.75 X 109/L). Ten (6%) patients experienced a delay between LDC and axi-cel infusion, with a median time of 13 days (range, 7-19 days), but no association between delay and DLIx was observed (p=0.79). On univariate analysis, the baseline characteristics associated with low DLIx were ALC < LLN (p<0.001), platelet count < LLN (p=0.003) and use of bridging therapy (p=0.02). On MVA, only the association between low DLIx and use of bridging therapy was maintained (Odds Ratio 0.4, 95% 0.2-0.8, p=0.007)(Figure), whereas the association with ALC < LLN was not maintained. Overall, 13 (8%) patients had grade (Gr) 3-4 CRS, and 61 (36%) had Gr 3-4 ICANS. There was no association between DLIx and incidence of Gr 3-4 CRS (p=0.28) or Gr 3-4 ICANS (0.43). Of 164 patients evaluable for response, complete responses (CR) was achieved in 89 (54%) patients, and DLIx was significantly higher in patients who achieved CR vs. non-CR (p=0.04)(Figure). After a median follow-up of 9 months (95% CI, 7-11 months), 94 patients progressed and/or died, and median progression-free survival (PFS) was 6 months (95% CI, 4-8 months). Median PFS was significantly shorter in patients with low DLIx (Q1 vs. Q2-4): 3 months vs 9 months (p=0.002). The association was maintained also after adjusting for bridging therapy use (Hazard Ratio (HR) 0.6, 95% CI 0.4-0.9; p=0.02)(Figure). At data cut-off, 56 (33%) patients died and median OS was not reached. Median OS was significantly shorter among patients with low DLIx (Q1 vs Q2-4) (7 months vs not reached, p<0.001). The association was maintained after adjusting for bridging therapy use (HR 0.4, 95% CI 0.2-0.7; p=0.001) (Figure). Discussion. DLIx has prognostic value in patients with r/r LBCL treated with axi-cel, with low DLIx independently associating with worse outcome. Additional studies are planned and will be presented to determine whether the pharmacokinetics of cyclophosphamide and fludarabine or other host factors impact DLIx, and whether levels of homeostatic cytokines correlate with DLIx. Such studies could lead to optimization of conditioning therapy and development of future combination strategies, aimed at improving CAR T-cell efficacy in these patients. Figure 1 Disclosures Lee: Takeda: Research Funding; Celgene: Research Funding; Guidepoint Blogal: Consultancy; Oncternal Therapeutics: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Aptitude Health: Speakers Bureau; Seattle Genetics: Research Funding. Iyer:Legend Biotech: Consultancy; Daiichi Sankyo: Consultancy; Seattle Genetics, Inc.: Research Funding; Merck: Research Funding; Afffimed: Research Funding; Trillium: Research Funding; Curio Biosciences: Honoraria; CRISPR: Research Funding; Spectrum: Research Funding; Rhizen: Research Funding; Target Oncology: Honoraria. Nastoupil:Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Merck: Research Funding; Karus Therapeutics: Research Funding; TG Therapeutics: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Gilead/KITE: Honoraria; Gamida Cell: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Bayer: Honoraria. Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Wang:Juno: Consultancy, Research Funding; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Pulse Biosciences: Consultancy; OMI: Honoraria, Other: Travel, accommodation, expenses; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Dava Oncology: Honoraria; InnoCare: Consultancy; Oncternal: Consultancy, Research Funding; Nobel Insights: Consultancy; Guidepoint Global: Consultancy; Targeted Oncology: Honoraria; Molecular Templates: Research Funding; OncLive: Honoraria; VelosBio: Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; BioInvent: Research Funding; Beijing Medical Award Foundation: Honoraria; Lu Daopei Medical Group: Honoraria; MoreHealth: Consultancy; Acerta Pharma: Research Funding; Verastem: Research Funding; Loxo Oncology: Consultancy, Research Funding. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Kebriaei:Pfizer: Other: Served on advisory board; Ziopharm: Other: Research Support; Amgen: Other: Research Support; Jazz: Consultancy; Novartis: Other: Served on advisory board; Kite: Other: Served on advisory board. Westin:Genentech: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Curis: Consultancy; 47 Inc: Consultancy; Kite: Consultancy; Juno: Consultancy; MorphoSys: Consultancy; Unum: Consultancy. Neelapu:N/A: Other; Takeda Pharmaceuticals: Patents & Royalties; Karus Therapeutics: Research Funding; Pfizer: Other: personal fees; Novartis: Other: personal fees; Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Precision Biosciences: Other: personal fees, Research Funding; Legend Biotech: Other; Unum Therapeutics: Other, Research Funding; Acerta: Research Funding; Adicet Bio: Other; Allogene Therapeutics: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Incyte: Other: personal fees; Poseida: Research Funding; Cellectis: Research Funding; Calibr: Other; Celgene: Other: personal fees, Research Funding.
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Greenbaum, Uri, Paolo Strati, Rima M. Saliba, Janet Torres, Gabriela Rondon, Yago Nieto, Chitra Hosing, et al. "The Easix (Endothelial Activation and Stress Index) Score Predicts for CAR T Related Toxicity in Patients Receiving Axicabtagene Ciloleucel (axi-cel) for Non-Hodgkin Lymphoma (NHL)." Blood 136, Supplement 1 (November 5, 2020): 17–18. http://dx.doi.org/10.1182/blood-2020-141388.

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Introduction. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common adverse effects of chimeric antigen receptor (CAR) T-cell therapy. Elevated biomarkers, such as ferritin and LDH, have been shown to correlate with more severe toxicity. The endothelial activation and stress index (EASIX) is a surrogate of endothelial activation, and correlates to other biomarkers of endothelial dysfunction. In allogeneic hematopoietic cell transplantation (HCT), it is predictive of toxicity such as fluid overload, which is correlative with endothelial dysfunction, as well as sinusoidal obstruction syndrome, non relapse mortality and overall survival (Luft et al, BMT 2019, Varma et al, BBMT, 2020, Jiang et al, Haematologica, 2020). In this study we describe the correlation of EASIX to CAR T cell related CRS and ICANS. Methods. Retrospective data from consecutive patients treated with standard of care axi-cel for non-Hodgkin's lymphoma at MD Anderson Cancer Center between January 2018 and April 2020 were included in the study. CRS and ICANS were graded according to CARTOX criteria (Neelapu et al, Nat Rev Clin Oncol, 2018), and after 5/2019, according to the ASTCT criteria (Lee et al, BBMT, 2019). EASIX parameters were recorded prior to lymphodepletion (the latest value on days -12 to -6) and were available for all 171 patients. The score was defined as lactate dehydrogenase (U/L) × creatinine (mg/dL)/ thrombocytes (10^9 cells per L), with LDH adjusted to the upper limit of normal. Predictors of toxicity were evaluated using Fine and Grey regression analysis considering death before grade 2-4 toxicity as a competing risk. Results. 171 consecutive patients treated with commercial axi-cel for diffuse large B cell lymphoma (n=133), transformed follicular lymphoma (n=28) and primary mediastinal lymphoma (n=10) were included in the study. Median age was 59 years (range, 18-85), and 120 (70%) were male. 151 patients had an ECOG performance status ≤1, 45 patients (26%) had a previous autologous HCT, and 3 (1.8%) had a previous allogeneic HCT. Prior to lymphodepletion, 96 (56%) patients had a high IPI score (≥3) and 134 (78%) were refractory to the previous line of treatment. With a median follow-up of 259 days (range: 25-800) since infusion, ICANS of any grade was noted in 109 (64%) patients, with 84 (49%) having grades 2-4. CRS of any grade was observed in 160 (93%) patients, with 81 (47%) having grades 2-4 CRS. A total of 56 (33%) patients were diagnosed with grade 2-4 ICANS and CRS. The median EASIX score for the entire cohort was 2.1 (range: 0.3-283; inter-quartiles: 1.1 and 4.6). On univariate analysis, EASIX levels above the median were associated with higher cumulative incidence (CI) of grade 2-4 ICANS (% CI: 61 vs 31%; HR=2.4, p<0.001); and levels above the upper quartile were associated with grade 2-4 CRS (% CI: 71 vs 38%; HR=2.2, p=0.02), (Figure 1,2). Additional predictors of grade 2-4 toxicity included IPI score ≥3 (HR=1.6, p=0.03) and female gender (HR=1.7, p=0.05) for ICANS; and IPI score ≥ 3 (HR=1.6, p=0.04) and lack of prior autologous transplant (HR=2, p=0.02) for CRS. Multivariate analysis showed EASIX score to be an independent predictor of grade 2-4 ICANS (HR=2.3, p=0.001) or CRS (HR=2.3, p=0.001); female gender of ICANS (HR=1.7, p=0.03) and lack of prior autologous transplant of CRS (HR=1.9, p=0.02). The impact of IPI did not reach statistical significance for either ICANS (HR=1.3, p=0.3) or CRS (HR=1.2, p=0.4). Further multivariate analysis for other biomarkers and their incorporation into a revised biomarker score will be presented at the meeting. Conclusions. Our results suggest that the EASIX score prior to lymphodepletion predicts higher grade CRS and ICANS in patients receiving axi-cel. These results of routinely available clinical variables require further prospective studies for validation, however our study shows that this score may better stratify patient risk of toxicity, and possibly inform clinical decisions and prevention strategies for patients at higher risk. Disclosures Nieto: Secura Bio: Other: Grant Support; Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support; Affimed: Consultancy, Other: Grant Support. Hosing:NKARTA Inc.: Consultancy. Westin:47: Research Funding; Amgen: Consultancy; Morphosys: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Lee:Celgene: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Guidepoint Blogal: Consultancy; Aptitude Health: Speakers Bureau; Oncternal Therapeutics: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding. Nastoupil:Celgene: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Bayer: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Gamida Cell: Honoraria; Gilead/KITE: Honoraria; Novartis: Honoraria, Research Funding; Merck: Research Funding; TG Therapeutics: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Wang:Guidepoint Global: Consultancy; Dava Oncology: Honoraria; Verastem: Research Funding; Molecular Templates: Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; Nobel Insights: Consultancy; Lu Daopei Medical Group: Honoraria; Beijing Medical Award Foundation: Honoraria; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Oncternal: Consultancy, Research Funding; OncLive: Honoraria; InnoCare: Consultancy; Targeted Oncology: Honoraria; Loxo Oncology: Consultancy, Research Funding; Pulse Biosciences: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Juno: Consultancy, Research Funding; BioInvent: Research Funding; VelosBio: Research Funding; Acerta Pharma: Research Funding. Flowers:AbbVie: Consultancy, Research Funding; Kite: Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; V Foundation: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Bayer: Consultancy; National Cancer Institute: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; BeiGene: Consultancy. Hawkins:Kite: Membership on an entity's Board of Directors or advisory committees. Rezvani:GemoAb: Membership on an entity's Board of Directors or advisory committees; Affimed: Other: Educational grant; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Other: Educational grant; Virogen: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing agreement; Formula Pharma: Membership on an entity's Board of Directors or advisory committees. Champlin:Takeda: Patents & Royalties; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau; Actinium: Consultancy; Johnson and Johnson: Consultancy; Omeros: Consultancy; Cytonus: Consultancy. Shpall:Magenta: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing Agreement; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees. Neelapu:Novartis: Other: personal fees; Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Celgene: Other: personal fees, Research Funding; Pfizer: Other: personal fees; Allogene Therapeutics: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Incyte: Other: personal fees; Precision Biosciences: Other: personal fees, Research Funding; Legend Biotech: Other; Adicet Bio: Other; Calibr: Other; Unum Therapeutics: Other, Research Funding; Poseida: Research Funding; Cellectis: Research Funding; Karus Therapeutics: Research Funding; Acerta: Research Funding; Takeda Pharmaceuticals: Patents & Royalties; N/A: Other. Kebriaei:Jazz: Consultancy; Novartis: Other: Served on advisory board; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Pfizer: Other: Served on advisory board; Amgen: Other: Research Support.
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11

Saini, Neeraj, Chia-Chi Chang, Paolo Strati, Loretta J. Nastoupil, Jason Westin, Ranjit Nair, Luis Fayad, et al. "Gut Bacterial Diversity Associates with Efficacy of Anti-CD19 CAR T-Cell Therapy in Patients with Large B-Cell Lymphoma." Blood 136, Supplement 1 (November 5, 2020): 34–35. http://dx.doi.org/10.1182/blood-2020-136756.

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Introduction: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has improved survival outcomes in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). However, many patients experience systemic toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) and about 60% relapse. Recent studies indicate that the gut microbiome can modulate tumor response and also influence toxicities associated with immune checkpoint inhibitor therapy. However, the influence of gut microbiome has not been well-studied in patients receiving CAR T-cell therapy. Here, we analyzed the association between gut microbiome composition and diversity metrics with survival outcomes and toxicities in r/r LBCL patients treated with anti-CD19 CAR T-cell therapy. Methods: Baseline stool samples were collected from r/r LBCL patients within 3 days of CAR T-cell infusion (days -3 to +3). Taxonomic profiling was performed on all samples using targeted ribosomal 16S RNA gene sequencing of the V4 region. The anti-tumor response was assessed as per Lugano 2014 criteria. Bacterial community alpha diversity was calculated using the inverse Simpson Index (ISI). Results were correlated with toxicity outcomes, including CRS and ICANS, as well as efficacy outcomes, including response, progression-free (PFS), and overall survival (OS). Results: We analyzed baseline stool samples from 33 r/r LBCL patients (24 DLBCL, 7 transformed follicular lymphoma, and 2 double-hit lymphomas) treated with standard of care axicabtagene ciloleucel (n =30) or tisagenlecleucel (n=3). The median age of the cohort (23 males, 10 females) was 54 (range 28 - 84) years. The number of patients with ECOG performance status (PS) 0-1, Ann-Arbor stage ≥3, and International Prognostic Index (IPI) of ≥3 at the time of apheresis were 29 (88%), 33 (100%), and 15 (46%), respectively. The median number of prior lines of therapy was 3 (range 2-6). The median follow-up from CAR-T infusion was 7.3 (range 0.8 -13.6) months. The best overall and complete response (CR) rates were 82% (27/33) and 58% (19/33), respectively. All patients were evaluable for toxicity assessment and 29 were evaluable for response assessment at 3 months (3 patients died of toxicity before 3 months and 1 was lost to follow-up). Since ongoing response at 3 months was previously shown to be associated with long-term durability (Locke et al, Lancet Oncol 2019), we analyzed differences in baseline gut microbiome markers in patients with or without ongoing CR at 3 months post-CAR-T infusion. ISI was significantly higher in patients with ongoing CR at 3 months (N=13) compared to those without ongoing CR (NoCR) group (N=16) (Fig.1A, p=0.045). However, beta diversity using weighted UniFrac distances by principal coordinate analysis was not significantly different. ISI did not correlate with age, sex, IPI score, ECOG PS, serum LDH, number of lines of therapy or disease status (primary refractory vs. relapsed). We found an increased relative abundance of several bacterial families in patients with ongoing CR vs. NoCR group. We also analyzed the impact of gut microbial diversity on PFS and OS by stratifying the patients according to the tertile of ISI. The PFS of patients in the highest tertile of ISI values (n=11, median PFS not reached) was significantly higher compared to those with intermediate (n=11, median PFS = 2.82 months, HR 12.7, 95% CI 3.61 to 44.77, log-rank, p=0.001) or low (n=11, median PFS = 2.43 months, HR 12.9, 95% CI 3.68 to 45.75, log-rank, p=0.001) ISI values (Fig. 1B). High ISI values also correlated positively and significantly with OS (Fig. 1C). We did not observe any significant association between microbial diversity, either alpha or beta, and toxicities including CRS [(grade 0-1 (N=22) vs ≥2 (N=11)] and ICANS [(grade 0-2 (N=23) vs ≥3 (N=10)]. Additional details including impact of microbial composition will be presented at the meeting. Conclusion: Our results suggest that the baseline gut bacterial diversity may serve as a predictive biomarker for efficacy of anti-CD19 CAR T-cell therapy in r/r LBCL patients, with high diversity favoring improved outcomes. If confirmed in larger studies, future investigations should explore if the microbiome could be a modulator of CAR T-cell response in order to determine whether developing therapeutic interventional strategies to favorably alter the microbiome are warranted. Disclosures Nastoupil: TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Merck: Research Funding; Celgene: Honoraria, Research Funding; Gamida Cell: Honoraria; Gilead/KITE: Honoraria; Bayer: Honoraria; Pfizer: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Karus Therapeutics: Research Funding. Westin:Janssen: Consultancy, Research Funding; Amgen: Consultancy; Kite: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; BMS: Consultancy, Research Funding; 47: Research Funding; Morphosys: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding. Lee:Guidepoint Blogal: Consultancy; Celgene: Research Funding; Seattle Genetics: Research Funding; Oncternal Therapeutics: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Aptitude Health: Speakers Bureau; Takeda: Research Funding. Kebriaei:Kite: Other: Served on advisory board; Novartis: Other: Served on advisory board; Ziopharm: Other: Research Support; Amgen: Other: Research Support; Pfizer: Other: Served on advisory board; Jazz: Consultancy. Shpall:Takeda: Other: Licensing Agreement; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Jain:Cellectis: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Research Funding; Aprea Therapeutics: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Pfizer: Research Funding; ADC Therapeutics: Research Funding; Incyte: Research Funding; TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Green:KDAc Therapeutics: Current equity holder in private company. Flowers:Kite: Research Funding; Pharmacyclics/Janssen: Consultancy; Spectrum: Consultancy; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; AbbVie: Consultancy, Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; Acerta: Research Funding; Karyopharm: Consultancy; V Foundation: Research Funding; National Cancer Institute: Research Funding; Bayer: Consultancy; Denovo Biopharma: Consultancy; Cancer Prevention and Research Institute of Texas: Research Funding; Millennium/Takeda: Consultancy, Research Funding; BeiGene: Consultancy; OptumRx: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding. Champlin:Genzyme: Speakers Bureau; DKMS America: Membership on an entity's Board of Directors or advisory committees; Cytonus: Consultancy; Omeros: Consultancy; Johnson and Johnson: Consultancy; Actinium: Consultancy; Takeda: Patents & Royalties. Wargo:Imedex, Dava Oncology, Omniprex, Illumina, gilead, PeerView, PET, MedImmune and Bristol-Myers Squibb: Honoraria, Speakers Bureau; Merck: Consultancy; Microbiome DX: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Roche/Genentech: Consultancy, Research Funding; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Astrazeneca: Consultancy; Biothera Pharmaceuticals: Consultancy. Neelapu:Celgene: Other: personal fees, Research Funding; Pfizer: Other: personal fees; Allogene Therapeutics: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Novartis: Other: personal fees; N/A: Other; Precision Biosciences: Other: personal fees, Research Funding; Incyte: Other: personal fees; Bristol-Myers Squibb: Other: personal fees, Research Funding; Acerta: Research Funding; Takeda Pharmaceuticals: Patents & Royalties; Poseida: Research Funding; Cellectis: Research Funding; Karus Therapeutics: Research Funding; Calibr: Other; Legend Biotech: Other; Adicet Bio: Other; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Unum Therapeutics: Other, Research Funding.
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Mehta, Rohtesh S., Roland Bassett, Julianne Chen, Benigno C. Valdez, Jitesh Kawedia, Amin M. Alousi, Gheath Alatrash, et al. "Myeloablative Fractionated Busulfan with Fludarabine in Older Patients: Long Term Outcomes of Prospective Phase II Clinical Trial." Blood 136, Supplement 1 (November 5, 2020): 10–11. http://dx.doi.org/10.1182/blood-2020-139325.

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Background: We started a randomized phase II trial [NCT01572662] that compared the safety of two myeloablative fractionated ("timed-sequential") busulfan with fludarabine (Bu-Flu) conditioning regimens: one with a lower dose of busulfan (area under the curve [AUC] of 16 000 μmol.min; 16K arm) and one with a higher dose (AUC of 20 000 μmol.min; 20K arm). After 49 patients were treated on the 16K group and 48 patients on the 20K group, the randomization was stopped as the higher dose arm was found to be as safe as the lower dose arm. The outcomes of those patients were previously reported, with the primary endpoint of interest being day 100 non-relapse mortality (NRM). The trial then continued enrolment as a single-arm study with increased accrual onto the higher dose arm. The current paper reports long-term outcomes of a total of 150 patients treated on the higher dose arm with an extended median follow-up of over 3.5 years. Methods: Patients with hematological malignancies up to 75 years of age were included. Bu dosing was determined on the basis of pharmacokinetic (PK) analyses conducted after day -13 and day -6 dose to achieve target AUC 20 000 ± 12% μmol.min (20K arm). On days −13 and −12, patients received 80 mg/m2 Bu IV daily as outpatient. Then, Flu 40 mg/m2 and Bu IV once daily were given as inpatient from day −6 though −3. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus from day −2 and methotrexate on days 1, 3, 6, and 11. Results: The median age was 61 years (interquartile range, 55-67); most were males (91; 61%) had an unrelated donor (n=93, 62%) and received peripheral blood graft (n=110, 73.3%). The most common diagnoses were acute myeloid leukemia (AML) and myelodysplastic syndrome (n = 88, 58.7%). Among AML, 41% (n=24) were in CR, 44% (n=26) had primary induction failure and 15% (n=9) had relapsed disease without attaining CR before HCT. Over half had HCT-Specific Comorbidity Index (HCT-CI) >3 (n=79, 52.7%). Estimated relapse, NRM, and overall survival (OS) were 40% (95% confidence interval (CI), 32.1%-47.9%), 22% (95% CI, 15.3%-28.7%), and 49.1% (95% CI, 41.7%-57.8%) at 3 years [Table]. The highest relapse rate at 3 years was noted in patients with myeloma (70.6%), followed by MDS (51.7%), and lymphoma (46.2%), while it was the lowest in myelofibrosis (13.6%). Among AML patients not in CR, the rate of relapse was not higher than those who were in CR (37.1% and 41.7%, respectively at 3 years). NRM at 3 years ranged from 7.7% (lymphoma) to 37.1% (AML, not in CR). Lymphoma patients had the lowest NRM (7.7%) and the best OS (69.2%) at 3 years, while AML patients not in CR had the highest NRM (37.1%) and the lowest OS (31.4%) [Figure]. Patients with HCT-CI 0-2 had lower NRM (14.1%; 95% CI, 5.9%-22.3%) and better OS (57.2%; 95% CI, 46.7%-70.1%) than those with HCT-CI > 3 (NRM: 29.1%; 95% CI, 19%-39.2% & OS: 41.7%; 95% CI, 32.2%-54.2%). Day 100 cumulative incidence of grade II-V acute GVHD was 38% (95% CI, 30.2%-45.8%), grade III-IV was 11.3% (95% CI, 6.2%- 16.4%). At 3 years, cumulative incidence of extensive chronic GVHD was 27% (95% CI, 20%-34%), bronchiolitis obliterans was 4.7% (95% CI, 1.3%-8.1%), and secondary malignancies was 8.7% (95% CI, 4.1%-13.2%). Conclusion: The fractionated myeloablative Bu-Flu conditioning regimen is well tolerated and leads to acceptable risk of NRM, relapse and long term survival in older patients, those with high risk disease and high comorbidities. Acknowledging the high risk study population, the long term outcomes, although acceptable, provide a framework to further improve upon. Modifications of this fractionated Bu-Flu regimen to further enhance its efficacy (with the addition of other chemotherapy agents) while reducing the toxicity and risk of NRM (with an inclusion of novel GVHD prophylaxis regimens) are currently being investigated. Disclosures Mehta: Incyte: Research Funding; Kadmon: Research Funding; CSL Behring: Research Funding. Alousi:Therakos: Research Funding; Alexion: Honoraria; Incyte: Honoraria, Research Funding. Bashir:Celgene: Research Funding; Amgen: Other: Advisory Board; KITE: Other: Advisory Board; Purdue: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; Acrotech: Research Funding; StemLine: Research Funding. Hosing:NKARTA Inc.: Consultancy. Kebriaei:Novartis: Other: Served on advisory board; Amgen: Other: Research Support; Jazz: Consultancy; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Pfizer: Other: Served on advisory board. Oran:Celgene: Consultancy; Arog Pharmaceuticals: Research Funding; ASTEX: Research Funding. Qazilbash:Angiocrine: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy; Bioline: Research Funding; Janssen: Research Funding. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Champlin:Takeda: Patents & Royalties; Johnson and Johnson: Consultancy; Actinium: Consultancy; Cytonus: Consultancy; Omeros: Consultancy; Genzyme: Speakers Bureau; DKMS America: Membership on an entity's Board of Directors or advisory committees. Popat:Bayer: Research Funding; Novartis: Research Funding.
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13

Ullrich, S., F. Ranta, D. Avram, M. Düfer, G. Drews, F. Lang, and HU Häring. "Die Hemmung von Calcineurin verhindert apoptotischen Zelltod insulinsezernierender INS-1-Zellen." Diabetologie und Stoffwechsel 2, S 1 (2007). http://dx.doi.org/10.1055/s-2007-982229.

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Avram, D., F. Ranta, AM Hennige, F. Lang, HU Häring, and S. Ullrich. "Hemmung der Dexamethason-induzierten Apoptose durch PI3-Kinase-unabhängige Signalwege in insulinsezernierenden INS-1 Zellen." Diabetologie und Stoffwechsel 2, S 1 (2007). http://dx.doi.org/10.1055/s-2007-982149.

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15

Schinner, S., C. Papewalis, F. Kocaoglu, M. Schott, A. Vidal-Puig, S. Bornstein, and W. Scherbaum. "Sekretionsprodukte von Adipozyten induzieren die Proliferation von Ins-1 β-Zellen über den Wnt-Signalweg." Diabetologie und Stoffwechsel 1, S 1 (2006). http://dx.doi.org/10.1055/s-2006-944012.

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Tews, D., S. Lehr, S. Hartwig, A. Osmers, W. Paßlack, and J. Eckel. "Vergleichende Proteomanalyse isolierter Mitochondrien aus INS-1 Zellen: Rolle von Exendin-4 auf die Zytokin-induzierte Apoptose." Diabetologie und Stoffwechsel 2, S 1 (2007). http://dx.doi.org/10.1055/s-2007-982165.

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17

Oppermann, Katrin, Andrea Harrer, Georg Pilz, Peter Wipfler, Shahrzad Afazel, Elisabeth Haschke-Becher, Johann Sellner, Florian Deisenhammer, Eugen Trinka, and Jörg Kraus. "Routine-taugliche durchflusszytometrische Methode zur Identifikation von Multiple Sklerose PatientInnen mit einer nicht ausreichenden Therapieeffizienz unter einer Natalizumab-Therapie." LaboratoriumsMedizin 38, no. 1 (January 1, 2014). http://dx.doi.org/10.1515/labmed-2013-0026.

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ZusammenfassungNeutralisierende Antikörper gegen Natalizumab (NAB) kommen in 9% der mit Natalizumab behandelten Multiple Sklerose (MS) PatientInnen vor. Dies ist assoziiert mit einer verminderten Wirksamkeit von Natalizumab und in der Folge muss bei PatientInnen mit persistierenden NAB die Behandlung mit Natalizumab beendet werden.Da hohe Titer an NAB stark mit persistierenden NAB assoziiert sind, haben wir untersucht, ob die durchflusszytometrische Bestimmung der Sättigung des Alpha-4-Integrins mit Natalizumab das Potenzial hat, PatientInnen mit NAB früher zu identifizieren.Zellgebundenes Natalizumab und Natalizumab-Sättigung des Alpha-4 Integrins auf T-Zellen wurden mittels Durchflusszytometrie unter Verwendung eines monoklonalen anti-human IgG4 Antikörpers nachgewiesen. Mononukleäre Zellen wurden aus venösem Blut angereichert und bei PatientInnen mit NAB (n=4) 9 Monate lang alle 4 Wochen unmittelbar vor der nächsten Infusion und bei PatientInnen ohne NAB vor Beginn der Therapie und nach 1 (n=15), 2 (n=14), 3 (n=9), 6 (n=7) und 9 Monate (n=3) auf gebundenes Natalizumab untersucht. Der Natalizumab-Sättigungsgrad (in%) der T-Zellen wurde durch das ins Verhältnis Setzen von der mittleren Fluoreszenzintensität (MFI) von in vivo gebundenem Natalizumab mit der MFI von mit in vitro mit Natalizumab gesättigten Immunzellen bestimmt. Die Bestimmung der NAB aus dem Serum wurde mittels ELISA durchgeführt.Bei PatientInnen ohne NAB betrug die mittlere Natalizumab-Sättigung von T-Zellen über einen Zeitraum von 9 Monaten durchschnittlich 75% (95%iges Konfidenzintervall: 72–78%). Bei 2 der 4 PatientInnen mit NAB erreichte die Natalizumab-Sättigung der T-Zellen nach der ersten Infusion ca. 50% und fiel auf die Höhe des Ausgangsniveaus (Natalizumab-Sättigung vor Beginn der Therapie) nach der zweiten Infusion zurück. Im ELISA wurden niedrige NAB-Titer nach der ersten Infusion gemessen und die anschließende Entwicklung von anhaltend hoch titrigen NAB führte nach ca. 6 Monaten zum Abbruch der Therapie mit Natalizumab. Bei den zwei anderen PatientInnen betrug der Natalizumab-Sättigungsgrad der T-Zellen 74% und 68% nach der ersten Infusion, und ging danach vorübergehend auf das Ausgangsniveau zurück. Bei beiden PatintInnen erholten sich die Natalizumab-Sättigungen nach ca. 6 Monaten wieder. NAB wurden nach 2 bzw. 3 Monaten nachgewiesen und waren nach ca. 5 bis 6 Monaten wieder verschwunden.Die Überwachung der Natalizumab-Sättigung auf T-Zellen ist eine schnelle und zuverlässige Methode, um PatientInnen zu identifizieren, bei denen aufgrund von NAB Natalizumab nur vermindert wirken kann. Beides, hoch- und niedrig titrige NAB, reduzieren gleichermaßen effektiv die zelluläre Natalizumab-Sättigung. Interessanterweise zeigte die mittels Durchflusszytometrie gemessene Natalizumab-Sättigung, dass dieses Verfahren sehr empfindlich ist, da die NAB anscheinend länger wirksam sind, als die Nachweisgrenze des ELISA vermuten lässt.
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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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Chao Xu, Junbo Wang, Deyong Chen, Jian Chen, Bowen Liu, Wenjie Qi, XichenZheng, Hua Wei, Guoqing Zhang. The Electrochemical Seismometer Based on a Novel Designed.Sensing Electrode for Undersea Exploration. 20th International Conference on Solid-State Sensors, Actuators and Microsystems &Eurosensors XXXIII (TRANSDUCERS &EUROSENSORS XXXIII). IEEE, 2019. DOI: 10.1109/TRANSDUCERS.2019.8808450. VIII. Chebotareva, I. Ya. New algorithms of emission tomography for passive seismic monitoring of a producing hydrocarbon deposit: Part I. Algorithms of processing and numerical simulation [Novyye algoritmyemissionnoyto mografiidlyapassivnogoseysmicheskogomonitoringarazrabatyvayemykhmestorozhdeniyuglevodorodov. Chast’ I: Algoritmyobrabotki I chislennoyemodelirovaniye]. FizikaZemli. 2010; 46(3):187-98. DOI: 10.1134/S106935131003002X IX. Danilov, A. V. and Konechnaya, Ya. V. 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. URL: https://www.gubkin.ru/faculty/geology_and_geophysics/chairs_and_departments/exploration_geophysics_and_computers_systems/files/2013_SPb_Frolov.pdf. (Date of access September 2, 2019). XII. Gibbons, S. J., Asming, V., Fedorov, A., Fyen, J., Kero, J., Kozlovskaya, E., Kværna, T., Liszka, L., Näsholm, S.P., Raita, T., Roth, M., Tiira, T., Vinogradov, Yu. The European Arctic: A laboratory for seismoacoustic studies. Seism. Res. Letters. 2015; 86 (3): 917–928. XIII. GOST 8.395-80. State system for ensuring the uniformity of measurements. Reference conditions of measurements while calibrating. General requirements [Gosudarstvennayasistemaobespecheniyaedinstvaizmereniy. Normal’nyyeusloviyaizmereniypripoverke. Obshchiyetrebovaniya]. Moscow: Standartinform, 2008. URL: http://gostrf.com/normadata/1/4294821/4294821960.pdf (Date of access September 2, 2019). XIV. Guralp 6TD. Operators’ Guide. Document Number: MAN-T60-0002, Issue J: April, 2017. Guralp Systems Limited. 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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, no. 1 (June 28, 2020). http://dx.doi.org/10.26782/jmcms.spl.10/2020.06.00048.

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