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Timmerman, Michelle, Misoo Chung, Randall B. Wilkening, Paul V. Fennessey, Frederick C. Battaglia, and Giacomo Meschia. "Relationship of fetal alanine uptake and placental alanine metabolism to maternal plasma alanine concentration." American Journal of Physiology-Endocrinology and Metabolism 275, no. 6 (December 1, 1998): E942—E950. http://dx.doi.org/10.1152/ajpendo.1998.275.6.e942.
Повний текст джерелаАнотація:
Uterine and umbilical uptakes of alanine (Ala) were measured in 10 ewes before (control) and during intravenous infusion of Ala, which increased maternal arterial Ala concentration from 115 ± 14 to 629 ± 78 μM ( P < 0.001). In 8 of these ewes, placental Ala fluxes were traced by constant intravenous infusion ofl-[3,3,3-2H3]Ala in the mother andl-[1-13C]Ala in the fetus. Rates are reported as micromoles per minute per kilogram fetus. Ala infusion increased uterine uptake (2.5 ± 0.6 to 15.6 ± 3.1, P < 0.001), umbilical uptake (3.1 ± 0.5 to 6.9 ± 0.8, P < 0.001), and net uteroplacental utilization (−0.7 ± 0.8 to 8.6 ± 2.7, P < 0.01) of Ala. Control Ala flux to fetus from mother ( R f,m) was much less than the Ala flux to fetus from placenta ( R f,p) (0.17 ± 0.04 vs. 5.0 ± 0.6). Two additional studies utilizingl-[U-13C]Ala as the maternal tracer confirmed the small relative contribution of R f,m to R f,p. During maternal Ala infusion, R f,m increased significantly ( P < 0.02) but remained a small fraction of R f,p (0.71 ± 0.2 vs. 7.3 ± 1.3). We conclude that maternal Ala entering the placenta is metabolized and exchanged for placental Ala, so that most of the Ala delivered to the fetus is produced within the placenta. An increase in maternal Ala concentration increases placental Ala utilization and the fetal uptake of both maternal and placental Ala.
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BONDAREV, V. Yu, V. I. KOZLOVSKY, A. B. KRYSA, J. S. ROBERTS, and Ya K. SKASYRSKY. "SCANNING E-BEAM LONGITUDINALLY PUMPED RT OPERABLE LASER BASED ON MOVPE-GROWN GaInP/AlGaInP MQW STRUCTURE." International Journal of Nanoscience 03, no. 01n02 (February 2004): 193–201. http://dx.doi.org/10.1142/s0219581x04001985.
Повний текст джерелаАнотація:
The 17- and 25-period Ga 0.5 In 0.5 P /( Al 0.7 Ga 0.3)0.5 In 0.5 P quantum well structures were grown by metalorganic vapor phase epitaxy on a GaAs substrate misoriented by 10° from (001) to (111)A. A microcavity with dielectric oxide mirrors was fabricated on the basis of each structure. Lasing at 619 nm (632 nm) with 0.7 W (6 W) output power was achieved under scanning electron beam longitudinal pumping at room temperature using the 17-period (25-period) structure. The threshold current density at a 40 keV electron energy was 8 A/cm 2. It is shown that low threshold and high power lasing requires the position of the QWs to coincide with the antinodes of the cavity mode, at the maximum of the gain spectrum due to the QW ground state.
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Volkamer, R., S. Baidar, T. L. Campos, S. Coburn, J. P. DiGangi, B. Dix, T. K. Koenig, et al. "Aircraft measurements of bromine monoxide, iodine monoxide, and glyoxal profiles in the tropics: comparison with ship-based and in situ measurements." Atmospheric Measurement Techniques Discussions 8, no. 1 (January 19, 2015): 623–87. http://dx.doi.org/10.5194/amtd-8-623-2015.
Повний текст джерелаАнотація:
Abstract. Tropospheric chemistry of halogens and organic carbon over tropical oceans modifies ozone and atmospheric aerosols, yet atmospheric models remain largely untested for lack of vertically resolved measurements of bromine monoxide (BrO), iodine monoxide (IO), and small oxygenated hydrocarbons like glyoxal (CHOCHO) in the tropical troposphere. BrO, IO, glyoxal, nitrogen dioxide (NO2), water vapor (H2O) and O2-O2 collision complexes (O4) were measured by the CU Airborne Multi AXis Differential Optical Absorption Spectroscopy (CU AMAX-DOAS) instrument, in situ aerosol size distributions by an Ultra High Sensitivity Aerosol Spectrometer (UHSAS), and in situ H2O by Vertical-Cavity Surface-Emitting Laser hygrometer (VCSEL). Data are presented from two research flights (RF12, RF17) aboard the NSF/NCAR GV aircraft over the tropical Eastern Pacific Ocean (tEPO) as part of the "Tropical Ocean tRoposphere Exchange of Reactive halogens and Oxygenated hydrocarbons" (TORERO) project. We assess the accuracy of O4 slant column density (SCD) measurements in the presence and absence of aerosols, and find O4-inferred aerosol extinction profiles at 477 nm agree within 5% with Mie calculations of extinction profiles constrained by UHSAS. CU AMAX-DOAS provides a flexible choice of geometry which we exploit to minimize the SCD in the reference spectrum (SCDREF, maximize signal-to-noise), and to test the robustness of BrO, IO, and glyoxal differential SCDs. The RF12 case study was conducted in pristine marine and free tropospheric air. The RF17 case study was conducted above the NOAA RV Ka'imimoana (TORERO cruise, KA-12-01), and provides independent validation data from ship-based in situ Cavity Enhanced- and MAX-DOAS. Inside the marine boundary layer (MBL) no BrO was detected (smaller than 0.5 pptv), and 0.2–0.55 pptv IO and 32–36 pptv glyoxal were observed. The near surface concentrations agree within 20% (IO) and 10% (glyoxal) between ship and aircraft. The BrO concentration strongly increased with altitude to 3.0 pptv at 14.5 km (RF12, 9.1 to 8.6° N; 101.2 to 97.4° W). At 14.5 km 5–10 pptv NO2 agree with model predictions, and demonstrate good control over separating tropospheric from stratospheric absorbers (NO2 and BrO). Our profile retrievals have 12–20 degrees of freedom (DoF), and up to 500 m vertical resolution. The tropospheric BrO VCD was 1.5 × 1013 molec cm−2 (RF12), and at least 0.5 × 1013 molec cm−2 (RF17, 0–10 km, lower limit). Tropospheric IO VCDs correspond to 2.1 × 1012 molec cm−2 (RF12) and 2.5 × 1012 molec cm−2 (RF17), and glyoxal VCDs of 2.6 × 1014 molec cm−2 (RF12) and 2.7 × 1014 molec cm−2 (RF17). Surprisingly, essentially all BrO, and the dominant IO and glyoxal VCD fraction was located above 2 km (IO: 58 ± 5%, 0.1–0.2 pptv; glyoxal: 52 ± 5%, 3–20 pptv). To our knowledge there are no previous vertically resolved measurements of BrO and glyoxal from aircraft in the tropical free troposphere.
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Pati, Nalini K., Frances Garvin, Vicki Antonenas, Ian Kerridge, Kenneth F. Bradstock, and David J. Gottlieb. "Best Approach for Harvesting Bone Marrow to Maximize TNC and CD34+ Cell Counts." Blood 112, no. 11 (November 16, 2008): 3468. http://dx.doi.org/10.1182/blood.v112.11.3468.3468.
Повний текст джерелаАнотація:
Abstract Background: Bone marrow (BM) has been utilized as a source of stem cells for transplantation for many years. Although the use of BM has decreased with the advent of mobilized stem cells, utilization is increasing once again due to the lower rate of chronic GVHD associated with BM as a stem cell source. There is no generally accepted technique for harvesting BM. Protocols vary both in relation to the volume of each aspirate, the number of aspirates performed at each puncture site and the total volume of harvests. Method: BM was collected from the posterior iliac crests (PIC) in 2 separate bags: 10ml aspirates from the left and 20 ml aspirates from the right. Samples taken at the start and after 100, 150, 200, 250, & 500 ml were analyzed for TNC, CD34+ and CD3+ cell counts. Results: The following table shows cell number (mean ± SEM ×106) for the parameters indicated. Aspirate Volume (mls) Parameter Start (n=4) 100mls (2) 150mls (2) 200mls (2) 250mls (4) 500mls (4) 10 TNC 555 ± 28 286 ± 38 257 ± 40 226 ± 8 199 ± 11 158.5±18.5 CD34 5.8 ± 0.05 1.8 ± 0.1 1.7 ± 0.2 1.3 ± 0.4 1.1 ± 0.2 0.8 ± 0.1 CD3 65.8 ± 12.0 35.8 ± 6.9 32.8 ± 8.0 29.9 ± 1.5 28.4 ± 5.1 29.8 ± 6.2 20 TNC 914 ± 52 627 ± 137 458 ± 44 429 ± 113 391 ± 81 264 ± 24 CD34 9.1 ± 0.5 3.8 ± 0.2 2.4 ±0.2 2.7 ± 0.1 2.3 ± 0.7 1.0 ± 0.2 CD3 106.9 ±22.1 64.6 ± 5.3 55.0±14.1 56.5±14.7 53.7±14.6 41.2 ± 9.6 There is a rapid fall in the yield of CD34+ cells obtained with increasing harvest volume (19 and 25% of the initial number after 250 ml for 10 and 20 ml aspirates respectively; 14 and 11% respectively after 500 ml). In contrast the CD3+ cell numbers fall more slowly (43 and 50% after 250 ml, 45 and 38% after 500 ml). By the time 500 ml has been aspirated, there is no difference in the total number of CD34+ cells obtained from a 10 ml versus a 20 ml aspirate of bone marrow. Conclusion: CD34+ cell yields fall rapidly when BM is harvested along the PIC. Using additional areas such as the anterior iliac crests may be preferable to a large volume PIC harvest for optimizing CD34+ stem cell collection. After 500 ml of BM has been harvested, 20 ml BM aspirates do not increase CD34+ cell numbers and 10 ml aspirates should be taken to minimize unnecessary blood loss and reduce T cell contamination.
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Ko, Byoung-goo, Ji-won Seo, Bong-ju Sung, Wook Song, Jun Hyun Bae, Byunggul Lim, and Parivash Jamrasi. "Prediction Equations of Physical Fitness Age for Korean Adults." Exercise Science 30, no. 3 (August 31, 2021): 352–60. http://dx.doi.org/10.15857/ksep.2021.30.3.352.
Повний текст джерелаАнотація:
PURPOSE: This study aimed to develop prediction equations for estimating the physical fitness age (PFA) of Korean adults in young (19-40 years), middle (41-64 years), and old (65-80 years) age groups.METHODS: Data from 122,842 individuals who participated in Korea National Physical Fitness Survey and National Fitness 100 from 2009 to 2014 were collected. Body composition, muscular strength, muscular endurance, flexibility, cardiorespiratory endurance, agility, power, balance, and coordination were measured. Pearson’s correlation and stepwise regression analyses were used to analyze the data.RESULTS: The equations were as follows: PFA for young males=22.321 −.088 (20-m PACER)+.317 (body mass index [BMI]); PFA for young females=24.486 −.143 (20-m PACER)+.304 (BMI); PFA for middle-aged males=66.644 −.044 (standing long jump) −.069 (20-m PACER) – .201 (weight) −.075 (modified sit-ups)+.269 (10-m shuttle run)+.320 (BMI); PFA for middle-aged females=66.814 −.098 (standing long jump) −.113 (modified sit-ups); PFA for older males=84.795+.093 (figure-of-8 walk) −.100 (chair standing) −.122 (weight) −.102 (relative grip strength) −.060 (sit-and-reach)+.147 (3-m up-and-go); and PFA for older females=80.577+.097 (figureof-8 walk)+.306 (3-m up-and-go) −.280 (weight) −.088 (relative grip strength) −.069 (sit-and-reach)+.393 (BMI) −.088 (chair standing) −.011 (2-min step-in-place).CONCLUSIONS: Our prediction equations for PFA can be used as a tool to prescribe sex- and age-appropriate exercise program and to verify the effect of the application of the exercise program by comparing pre -and post-PFA.
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Alexander, S. L., C. H. G. Irvine, J. H. Livesey та R. A. Donald. "Effect of isolation stress on concentrations of arginine vasopressin, α-melanocyte-stimulating hormone and ACTH in the pituitary venous effluent of the normal horse". Journal of Endocrinology 116, № 3 (березень 1988): 325–34. http://dx.doi.org/10.1677/joe.0.1160325.
Повний текст джерелаАнотація:
ABSTRACT A non-surgical, non-stressful technique was used for collection of pituitary venous blood from five conscious horses every minute for two 10-min periods before and during isolation from the herd, which caused a predictable, yet humane and physiological, emotional stress. Pituitary blood was also sampled every 5 min for two approximately 90-min periods before and after isolation, while jugular blood was sampled every 15 min throughout the experiment. During isolation, all horses became agitated, hyperventilating and sweating. Packed red cell volume increased, as did pituitary venous concentrations of adrenaline (mean ± s.e.m. concentration before isolation, 621·5±112·3 pmol/l; peak during isolation, 2665·4 ± 869·8 pmol/l; P <0·05) and noradrenaline (before, 871·8 ± 111·8 pmol/l; peak, 2726·1 ± 547·4 pmol/l; P<0·02). Concentrations of arginine vasopressin (AVP) were higher in pituitary venous but not in jugular blood during isolation than during the preceding 10-min period (P <0·05). Although AVP secretion increased in all horses, in three of the five it rose dramatically in the first minute of isolation to 25·7 (horse 1), 13·6 (horse 4) and 145·1 (horse 5) times the level in the last sample collected before isolation. Mean pituitary venous concentrations of ACTH and α-MSH increased during isolation in the three horses which had large increases in AVP secretion, but, overall, stress did not significantly affect ACTH or α-MSH secretion. Similarly, mean jugular cortisol levels were not significantly altered by isolation. However, the magnitudes of ACTH, AVP and α-MSH responses to isolation were negatively correlated with the jugular cortisol level before isolation. The changes in pituitary venous concentrations of ACTH and AVP were synchronous under resting conditions, whether samples were collected at intervals of 1 (P <0·01) or 5 (P <0·005) min; however, this synchrony was lost during isolation. The changes in pituitary venous concentrations of ACTH and α-MSH were synchronous both at rest (P <0·025 for 1-min sampling, P <0·01 for 5-min sampling) and during isolation (P<0·01). We conclude that isolation stress increases AVP secretion and may alter the temporal relationship between pituitary venous concentrations of AVP and ACTH. Furthermore, the magnitude of the responses of AVP, ACTH and α-MSH to isolation is significantly affected by the prevailing cortisol level. J. Endocr. (1988) 116, 325–334
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Касаткин, А. В., Р. Шкода, and Н. В. Чуканов. "On restudy of mineral specimens from museum collections. I. Cannonite and leguernite from Bukuka deposit, Transbaikalia." Новые данные о минералах, no. 2020(54) (August 10, 2020): 53–60. http://dx.doi.org/10.25993/fm.2020.54.2020.004.
Повний текст джерелаАнотація:
Редкие сульфаты висмута каннонит Bi2O(SO4)(OH)2 и легернит Bi12.67O14(SO4)5 установлены нами в результате переизучения образцов висмутина из вольфрамового месторождения Букука (В. Забайкалье), хранящихся в систематической коллекции Минералогического музея им. А.Е. Ферсмана РАН под номером 56077. Оба минерала тесно срастаются между собой в составе полиминеральных псевдоморфоз по грубообразованным кристаллам висмутина, образуя прожилки длиной до 4 см и мощностью до 0.5 см. Эмпирические формулы: каннонит Bi2.06S0.97O5(OH)2, легернит Bi12.67S5.00O34. Параметры моноклинных элементарных ячеек: у каннонита a = 7.691(1), b = 13.874(2), c = 5.6569(8) Å, β = 109.23(1)°, V = 569.90(9) ų и Z = 4; у легернита: a = 11.197(2), b = 5.714(1), c = 11.879(2) Å, β = 99.37(2)°, V = 749.9(2) ų и Z = 1. Сильные полосы в КР-спектрах: у каннонита 111, 121, 144, 184, 221, 318, 437, 450, 560, 619, 983, 1059, 3439 см–1, у легернита 150, 183, 216, 313, 474, 969 см–1. Оба минерала найдены впервые на территории Российской Федерации.
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Tascilar, K., D. Simon, G. Krönke, A. Kleyer, A. Ramming, R. Atreya, M. Tenbusch, et al. "POS1426 PATIENTS WITH IMMUNE MEDIATED INFLAMMATORY DISEASES ARE OVERREPRESENTED IN LOW- FREQUENCY VIRAL SYMPTOM CLUSTERS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 996.2–997. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1598.
Повний текст джерелаАнотація:
Background:Viral respiratory infections are common in the general population and result in a spectrum of outcomes ranging from effective viral clearance with no symptoms, to a maladaptive immune response that can result in severe symptomatic disease and death. Although patients with immune-mediated inflammatory diseases (IMID) are considered susceptible to poor outcomes from infectious syndromes, it is not known whether IMID patients are overall more prone to manifest common viral infection symptoms.Objectives:To explore frequency patterns of common viral infection symptoms in IMID patients.Methods:We previously recruited patients with IMIDs and individuals with no IMIDs for a seroprevalence study between February 1st and April 30th 2020 (1). Participants were questioned for the presence of eleven common viral disease symptoms. We clustered these data using an unsupervised binary data clustering algorithm (2) into 6 symptom clusters based on symptom frequency. Three major clusters (broadly symptomatic, intermediately symptomatic and oligo-/asymptomatic) and 2 sub-clusters (higher and lower frequency) for each major cluster. In addition, qualitative symptom clustering was done. We estimated standardized residuals to quantify the over/underrepresentation of IMID diagnosis frequencies in each subject cluster. We used Poisson regression to compare symptom counts by diagnosis.Results:We analyzed 1909 participants (757 with IMIDs; 1152 non-IMID controls; Table 1). Within each major subject cluster (Figure 1A), IMID patients showed the highest positive deviation from the expected frequencies in lower frequency sub-clusters while non IMID controls showed the highest positive deviations in the higher frequency sub-clusters (Figure 1B). Inflammatory bowel disease and psoriasis were remarkably overrepresented in the lower frequency sub-cluster of the broadly-symptomatic cluster while RA was overrepresented in the lower frequency sub-clusters of intermediate and oligo-/asymptomatic clusters. X axis of Figure 1A presents qualitative symptom clusters. Regression analysis shows that RA patients among other IMIDs reported overall less symptoms (RR= 0.69, 95%CI, 0.58 - 0.80) compared to non-IMID controls.Figure 1.A) distribution of common viral respiratory disease symptoms across patient and symptom clusters. B) Standardized residuals indicating deviation from expected frequencies of IMID diagnoses across patient clusters. sob: shortness of breath, mskpain: musculoskeletal painConclusion:This analysis shows that symptoms of common respiratory viral infections are less frequent in RA patients and to a lesser extent in other IMID patient. As major clusters in this analysis can also be considered to represent exposure categories, these data suggest that IMIDs or their treatments may mitigate common respiratory viral infection symptoms.References:[1]Simon D. et al. Nat Commun (2020) 11, 3774[2]Bhatia P. et al. J. Stat. Softw (2017) 76(9)Table 1.Participant characteristics and distribution of IMID diagnoses across subject clusters.ClustersBroad SymptomaticIntermediate SymptomaticOligo-AsymptomaticOverallHigherLowerHigherLowerHigherLowerN190910185412259283769Age, years, mean (SD)45.4(15.2)42.4(13.3)47.3 (15.2)42.4(12.9)50.4(15.5)41.8(14.9)46.8(15.9)Male1080 (56.6)42 (41.6)38 (44.7)196 (47.6)137 (52.9)178 (62.9)489 (63.6)Diagnosis, n(%)No-IMID1152 (60.3)72 (71.3)44 (51.8)280 (68.0)112 (43.2)207 (73.1)437 (56.8)RA226 (11.8)7 (6.9)5 (5.9)29 (7.0)56 (21.6)17 (6.0)112 (14.6)IBD178 (9.3)5 (5.0)15 (17.6)46 (11.2)29 (11.2)19 (6.7)64 (8.3)SpA142 (7.4)7 (6.9)5 (5.9)23 (5.6)25 (9.7)14 (4.9)68 (8.8)Psoriasis89 (4.7)4 (4.0)9 (10.6)14 (3.4)8 (3.1)13 (4.6)41 (5.3)Other122 (6.4)6 (5.9)7 (8.2)20 (4.9)29 (11.2)13 (4.6)47 (6.1)Symptom count/patient, mean (SD)1.2 (1.7)6.0 (1.3)3.9 (1.1)2.2 (1.0)1.5 (0.6)0.5 (0.5)0.0 (0.0)IBD, inflammatory bowel disease.Acknowledgements:This study was supported by the Deutsche Forschungsgemeinschaft (DFG- FOR2886 PANDORA and the CRC1181), the Bundesministerium für Bildung und Forschung (BMBF; project MASCARA), the H2020 GA 810316 - 4D-Nanoscope ERC Synergy Project, the IMI funded project RTCure, the Emerging Fields Initiative MIRACLE of the Friedrich-Alexander-Universität Erlangen-Nürnberg as well as the Schreiber Stiftung gemeinnützige Gesellschaft mbH.Disclosure of Interests:None declared
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Padala, Kalpana P., Prasad R. Padala, Shelly Y. Lensing, Richard A. Dennis, Melinda M. Bopp, Christopher M. Parkes, Mark K. Garrison, Patricia M. Dubbert, Paula K. Roberson, and Dennis H. Sullivan. "Efficacy of Wii-Fit on Static and Dynamic Balance in Community Dwelling Older Veterans: A Randomized Controlled Pilot Trial." Journal of Aging Research 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/4653635.
Повний текст джерелаАнотація:
Background/Objectives. Balance problems are well-established modifiable risk factors for falls, which are common in older adults. The objective of this study was to establish the efficacy of a Wii-Fit interactive video-game-led physical exercise program to improve balance in older Veterans. Methods. A prospective randomized controlled parallel-group trial was conducted at Veterans Affairs Medical Center. Thirty community dwelling Veterans aged 68 (±6.7) years were randomized to either the exercise or control groups. The exercise group performed Wii-Fit program while the control group performed a computer-based cognitive program for 45 minutes, three days per week for 8-weeks. The primary (Berg Balance Scale (BBS)) and secondary outcomes (fear of falling, physical activity enjoyment, and quality of life) were measured at baseline, 4 weeks, and 8 weeks. Results. Of 30 randomized subjects, 27 completed all aspects of the study protocol. There were no study-related adverse events. Intent-to-treat analysis showed a significantly greater improvement in BBS in the exercise group (6.0; 95% CI, 5.1–6.9) compared to the control group (0.5; 95% CI, −0.3–1.3) at 8 weeks (average intergroup difference (95% CI), 5.5 (4.3–6.7), p < 0.001) after adjusting for baseline. Conclusion. This study establishes that the Wii-Fit exercise program is efficacious in improving balance in community dwelling older Veterans. This trial is registered with ClinicalTrials.gov Identifier NCT02190045.
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Baker, Lindsay B., Kelly A. Barnes, Bridget C. Sopeña, Ryan P. Nuccio, Adam J. Reimel, and Corey T. Ungaro. "Sweat Sodium, Potassium, and Chloride Concentrations Analyzed Same Day as Collection Versus After 7 Days Storage in a Range of Temperatures." International Journal of Sport Nutrition and Exercise Metabolism 28, no. 3 (May 1, 2018): 238–45. http://dx.doi.org/10.1123/ijsnem.2017-0199.
Повний текст джерелаАнотація:
The purpose of this study was to determine the effect of storage temperature on sodium ([Na+]), potassium ([K+]), and chloride ([Cl−]) concentrations of sweat samples analyzed 7 days after collection. Using the absorbent patch technique, 845 sweat samples were collected from 39 subjects (32 ± 7 years, 72.9 ± 10.5 kg) during exercise. On the same day as collection (PRESTORAGE), 609 samples were analyzed for [Na+], [Cl−], and [K+] by ion chromatography (IC) and 236 samples were analyzed for [Na+] using a compact ion-selective electrode (ISE). Samples were stored at one of the four conditions: −20 °C (IC, n = 138; ISE, n = 60), 8 °C (IC, n = 144; ISE, n = 59), 23 °C (IC, n = 159; ISE, n = 59), or alternating between 8 °C and 23 °C (IC, n = 168; ISE, n = 58). After 7 days in storage (POSTSTORAGE), samples were reanalyzed using the same technique as PRESTORAGE. PRESTORAGE sweat electrolyte concentrations were highly related to that of POSTSTORAGE (intraclass correlation coefficient: .945–.989, p < .001). Mean differences (95% confidence intervals) between PRESTORAGE and POSTSTORAGE were statistically, but not practically, significant for most comparisons: IC [Na+]: −0.5(0.9) to −2.1(0.9) mmol/L; IC [K+]: −0.1(0.1) to −0.2(0.1) mmol/L; IC [Cl−]: −0.4(1.4) to −1.3(1.3) mmol/L; ISE [Na+]: −2.0(1.1) to 1.3(1.1) mmol/L. Based on typical error of measurement results, 95% of the time PRESTORAGE and POSTSTORAGE sweat [Na+], [K+], and [Cl−] by IC analysis fell within ±7–9, ±0.6–0.7, and ±9–13 mmol/L, respectively, while sweat [Na+] by ISE was ±6 mmol/L. All conditions produced high reliability and acceptable levels of agreement in electrolyte concentrations of sweat samples analyzed on the day of collection versus after 7 days in storage.
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Archer, JA, and GJ Judson. "Selenium concentrations in tissues of sheep given a subcutaneous injection of barium selenate or sodium selenate." Australian Journal of Experimental Agriculture 34, no. 5 (1994): 581. http://dx.doi.org/10.1071/ea9940581.
Повний текст джерелаАнотація:
Young sheep were allocated to 6 treatment groups, each of 8 ewes and 8 wethers. Treatments given were nil, 0.1, or 0.5 mg selenium (Se)/kg body weight as a subcutaneous injection of sodium selenate (Na2SeO4), and 0.8, 1.4, or 2.9 mg Se/kg body weight as a subcutaneous injection of barium selenate (BaSeO4). At 14, 28, 56, and 112 days after treatment, 2 ewes and 2 wethers from each group were slaughtered and samples of blood, liver, kidney, cardiac and skeletal muscle, lymph nodes, and faeces were collected for Se assay. On days 0, 1, 3, 7, 13, 27, and 55 blood and spot faecal samples were taken for Se assay from the 24 sheep selected for slaughter on day 112. In sheep given Na2Se04 there was a rapid but transient increase in the mean Se concentration in tissues, particularly the liver of sheep given the highest dose of Na2SeO4. In these sheep on days 14,28,56, and 112 the respective mean liver concentrations were 169, 62,25, and 6.9 �mol/kg DM: the mean value on day 14 was 15 times the mean value in untreated sheep. In sheep given BaSeO4 there was a gradual increase in mean Se concentration of tissues during the experiment. Faecal Se concentrations increased in sheep given the Se injections. The marked but transient increase in liver Se concentrations in sheep given Na2SeO4 suggests that this organ provides an important protective mechanism against toxicity by readily accumulating and excreting Se into the gut. Our results indicate that the BaSeO4 doses were unlikely to cause Se toxicity in young sheep or result in Se residues in tissues above those recommended for human consumption. The BaSeO4 should be administered subcutaneously in the neck or other sites of the body not sold for human consumption, since deposits of BaSeO4 remain at the site of injection for at least 112 days and may be dangerous if inadvertently consumed.
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Djamdjian, Laura, Thierry Naas, Didier Tandé, Gaelle Cuzon, Catherine Hanrotel-Saliou, and Patrice Nordmann. "CTX-M-93, a CTX-M Variant Lacking Penicillin Hydrolytic Activity." Antimicrobial Agents and Chemotherapy 55, no. 5 (February 22, 2011): 1861–66. http://dx.doi.org/10.1128/aac.01656-10.
Повний текст джерелаАнотація:
ABSTRACTExtended-spectrum β-lactamases (ESBLs) of the CTX-M type are increasingly being reported worldwide, with more than 90 known variants. ClinicalEscherichia coliisolate Bre-1 was isolated in 2009 and displayed an unusual ESBL phenotype, made of a synergy image between expanded cephalosporins and clavulanic acid discs and susceptibility to penicillins.E. coliBre-1 harbored a novel CTX-M-encoding gene, designatedblaCTX-M-93. CTX-M-93 differed from CTX-M-27 by only a single L169Q substitution. Compared to CTX-M-27, CTX-M-93 conferred higher MICs of ceftazidime forE. coli(MIC of 8 versus 1.5 μg/ml) and decreased MICs of other expanded-cephalosporins (MIC of cefotaxime of 1 versus 32 μg/ml) and penicillins (MIC of ticarcillin of 0.5 versus >256 μg/ml). A comparison of enzymatic properties revealed that the L169Q substitution led to a decreasedKmfor ceftazidime (25.5 versus 330 μM) but decreased hydrolytic activity against good substrates, such as cefotaxime (kcatof 0.6 versus 113 s−1), probably owing to the alteration of the omega loop positioning during the catalytic process. TheblaCTX-M-93gene was surrounded by the ISEcp1and IS903elements and inserted onto a 150-kb non-self-transferrable IncF-type plasmid.E. coliBre-1 belongs to phylogroup D and is of multilocus sequence type (MLST) 624, a sequence type found only in rare Spanish CTX-M-14-producingE. coliisolates. We have characterized a novel CTX-M variant, CTX-M-93, lacking significant penicillin hydrolysis but with increased ceftazidime hydrolysis.
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Geurts, Carla L. M., Gordon G. Sleivert, and Stephen S. Cheung. "Local cold acclimation during exercise and its effect on neuromuscular function of the hand." Applied Physiology, Nutrition, and Metabolism 31, no. 6 (December 2006): 717–25. http://dx.doi.org/10.1139/h06-076.
Повний текст джерелаАнотація:
Most acclimation research is performed on resting individuals, whereas in real life, cold exposure is often accompanied by physical activity. We examined the effects of 2 weeks of repeated cold exposure of the hand with or without an elevated core temperature from exercise on neuromuscular function of the first dorsal interosseus (FDI) muscle and manual performance of the hand. The experimental group (4 female, 6 male; age, 25.1 ± 6.9 y) cooled their hands in 8 °C water for 30 min daily while cycling (50% of heart rate reserve); the control group (4 female, 4 male; age, 25.1 ± 5.7 y) remained still. Manual function testing consisted of tactile sensitivity, grip strength, manual dexterity, and evoked twitch force in a custom-made myograph. Thermal sensation, skin temperature of index finger (Tif) and hand (Tfdi), as well as rectal temperature (Tre), were recorded daily. Tre increased significantly during bicycling, by 0.6 ± 0.2 °C. Minimal Tif and Tfdi of the groups combined increased significantly during exposure days from 8.7 ± 0.7 °C and 12.4 ± 2.8 °C to 10.1 ± 1.3 °C and 15.0 ± 3.0 °C, respectively (p = 0.04), with no significant difference between groups. Thermal ratings improved significantly on exposure days. Manual function was impaired with cooling, but with no significant difference between groups or across time. Deterioration of twitch characteristics with cooling did not change with repeated cold exposure. Although the increasing core temperature during cold water immersion changed the acute temperature response and thermal ratings, it had no effect on local cold acclimation or manual function.
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Krug, Annemarie, Corinne Cannavale, Naiman Khan, and Hannah Holscher. "Prebiotics Affect the Fecal Microbiota and Gastrointestinal Health of Adults Participating in a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 1570. http://dx.doi.org/10.1093/cdn/nzaa062_027.
Повний текст джерелаАнотація:
Abstract Objectives Prebiotics are defined as substrates that are selectively utilized by host microorganisms conferring a health benefit. We aimed to determine the effects of the prebiotics fructooligosaccharides (FOS) and galactooligosaccharides (GOS) on the fecal microbiota and gastrointestinal health in adults. Methods We conducted a randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 26) 25–45 years of age. Participants consumed two 4-week treatments in a randomized, counterbalanced order. The prebiotic beverage (PRE) was 8 oz low-fat lactose-free milk with 5 g FOS and 5 g GOS. The control beverage (CON) was 8 oz low-fat lactose-free milk without the added prebiotics. Each condition was separated by a 4-week washout. Fecal samples were collected at baseline and end of each condition. Fecal short-chain fatty acid (SCFA) concentrations were quantified using gas chromatography-mass spectrometry (GC-MS). Fecal pH was measured using a pH meter. Gastrointestinal health was assessed using the Bristol stool scale and a stool frequency and ease of passage log before the first and during the last week of each condition. SAS 9.4 was used to conduct general linear mixed modeling with treatment as a fixed effect and participant and period as random effects. Normality was assessed using the Shapiro-Wilk test and log and arcsine transformations were applied as needed. Results There was a 153% increase in fecal bifidobacteria relative abundances in the prebiotic group compared to control (CON: 2.8 ± 0.6, PRE: 6.9 ± 1.7; P = 0.002). No differences were detected between the groups in fecal acetate (CON: 278 ± 30.1, PRE: 231 ± 24.4; P = 0.2), butyrate (CON: 68.4 ± 10.1, PRE: 62.9 ± 12.2; P = 0.4), or propionate (CON: 76.5 ± 7.5, PRE: 76.7 ± 12.5; P = 0.4) concentrations, or fecal pH (CON: 6.86 ± 0.10, PRE: 6.91 ± 0.14; P = 0.5). Stool frequency (stool/day) increased by 26% in PRE compared to CON (CON: 1.0 ± 0.1, PRE: 1.3 ± 0.1; P = 0.01). Ease of stool passage tended to improve in PRE compared to CON (CON: 2.2 ± 0.1, PRE: 2.0 ± 0.1; P = 0.1). There was no difference in stool consistency (CON: 3.7 ± 0.3, PRE: 3.7 ± 0.2; P = 0.8). Conclusions These findings are suggestive of the beneficial health effects of consumption of the prebiotics FOS and GOS on gastrointestinal health in adults. Funding Sources USDA National Institute of Food and Agriculture, Hatch Project 1009249.
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Turner, Michael J., Toru Kawada, Shuji Shimizu, Masafumi Fukumitsu, and Masaru Sugimachi. "Differences in the dynamic baroreflex characteristics of unmyelinated and myelinated central pathways are less evident in spontaneously hypertensive rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 309, no. 11 (December 1, 2015): R1397—R1405. http://dx.doi.org/10.1152/ajpregu.00315.2015.
Повний текст джерелаАнотація:
The aim of the study was to identify the contribution of myelinated (A-fiber) and unmyelinated (C-fiber) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity (SNA) and arterial pressure (AP) in anesthetized Wistar-Kyoto (WKY; n = 8) and spontaneously hypertensive rats (SHR; n = 8). The left aortic depressor nerve (ADN) was electrically stimulated with two types of binary white noise signals designed to preferentially activate A-fibers (A-BRx protocol) or C-fibers (C-BRx protocol). In WKY, the central arc transfer function from ADN stimulation to SNA estimated by A-BRx showed strong derivative characteristics with the slope of dynamic gain between 0.1 and 1 Hz ( Gslope) of 14.63 ± 0.89 dB/decade. In contrast, the central arc transfer function estimated by C-BRx exhibited nonderivative characteristics with Gslope of 0.64 ± 1.13 dB/decade. This indicates that A-fibers are important for rapid baroreflex regulation, whereas C-fibers are likely important for more sustained regulation of SNA and AP. In SHR, the central arc transfer function estimated by A-BRx showed higher Gslope (18.46 ± 0.75 dB/decade, P < 0.01) and that estimated by C-BRx showed higher Gslope (8.62 ± 0.64 dB/decade, P < 0.001) with significantly lower dynamic gain at 0.01 Hz (6.29 ± 0.48 vs. 2.80 ± 0.36%/Hz, P < 0.001) compared with WKY. In conclusion, the dynamic characteristics of the A-fiber central pathway are enhanced in the high-modulation frequency range (0.1–1 Hz) and those of the C-fiber central pathway are attenuated in the low-modulation frequency range (0.01–0.1 Hz) in SHR.
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Reddy, M. M., and P. M. Quinton. "Localization of Cl- conductance in normal and Cl- impermeability in cystic fibrosis sweat duct epithelium." American Journal of Physiology-Cell Physiology 257, no. 4 (October 1, 1989): C727—C735. http://dx.doi.org/10.1152/ajpcell.1989.257.4.c727.
Повний текст джерелаАнотація:
We studied the Cl- permeability properties of apical and basolateral membranes of human reabsorptive sweat duct (RSD) from normal and cystic fibrosis (CF) subjects. In normal ducts, Cl- substitution by impermeant anion gluconate in the lumen increased the voltage divider ratio (VDR) from 4.8 +/- 0.9 to 7.0 +/- 1.1 (n = 8, P less than 0.05), whereas Cl- substitution in the contraluminal bath decreased the VDR from 3.2 +/- 0.7 to 1.9 +/- 0.4 (n = 7, P less than 0.05). These results are consistent with a significant Cl- permeability in both apical and basolateral membranes of normal ducts. Amiloride (10(-4) M) in the lumen of normal ducts resulted in a small increase in VDR from 4.2 +/- 0.6 to 5.0 +/- 0.8 (n = 10, P less than 0.05), whereas the current-induced basolateral membrane voltage deflections (delta Vb) increased from 6.9 +/- 1.3 to 7.7 +/- 1.2 mV, suggesting that inhibition of Na+ permeability decreased basolateral membrane Cl- permeability. In the absence of luminal Cl-, amiloride decreased delta Vb and induced much greater effect on VDR (from 5.2 +/- 1.1 to 10.8 +/- 2.3, n = 9, P less than 0.05) than in the presence of Cl-. Likewise, in the presence of amiloride, Cl- substitution in the lumen had greater effect on VDR (increased from 3.5 +/- 0.5 0.5 to 10.0 +/- 1.5, n = 15, P less than 0.05) than in the absence of amiloride. These results indicate that Na+ conductance in the apical membrane of the normal duct is significantly smaller than Cl- conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
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Park, Junghyun, and Marc Rodger. "Retrospective Cohort of Unprovoked Venous Thromboembolism Patients: What Proportion Have Potent Thrombophilias Necessitating Indefinite Anticoagulants?" Blood 126, no. 23 (December 3, 2015): 2318. http://dx.doi.org/10.1182/blood.v126.23.2318.2318.
Повний текст джерелаАнотація:
Introduction Thrombophilia testing in unprovoked venous thromboembolism patients (VTE) is controversial. Common thrombophilias such as Factor V Leiden or prothrombin gene variant appear to not importantly increase the risk of VTE recurrence, and thus are not considered in anticoagulation management decisions. However, patients with potent thrombophilias such as antiphospholipid antibodies (APLA), antithrombin deficiency, protein C and S deficiency, and homozygous genetic thrombophilias or combined defects are at higher risk of recurrence and it is recommended that they receive long-term anticoagulation. If the proportion of patients with "potent" thrombophilia is high then thrombophilia testing should be conducted. We sought to determine the proportion of unprovoked VTE patients with "potent" thrombophilia. Methods All patients with managed in our oral anticoagulation management system in the period from 1998 to 2015 were potentially eligible for the study. Inclusion criteria were: 1) symptomatic, objectively confirmed VTE unprovoked proximal deep vein thrombosis or pulmonary embolism. Exclusion criteria were: 1) cancer or myeloproliferative disease at the time of VTE diagnosis; 2) no cast, surgery, trauma or immobilization (>3 days in bed 90% of waking hours) in the 90 days prior to diagnosis. We selected unprovoked VTE patients diagnosed between 2002 and 2010, as thrombophilia testing was relatively universal and available in our electronic system in that time frame (N=1344). We then selected a convenience sample of N=1165. The primary outcome measure was the proportion of patients with "potent" thrombophilia (potent= homozygous Factor V Leiden, homozygous Prothrombin gene variant, APLA, protein C, protein S or anti-thrombin deficiency or combined deficiencies). Results In 1165 patients with unprovoked VTE, complete screening was done in 470 patients (40.34%) and 976 (83.78%) had at least one thrombophilia test. Complete thrombophilia testing was defined as a screen including testing for factor V Leiden, prothrombin gene defect, APLA, anti-thrombin deficiency, protein C, and protein S. Potent thrombophilias were demonstrated in 103/1165 patients (8.84%; 95% CI, 7.34 to 10.61) (Table 2) in the total study population, and 103/976 (10.55%; 95% CI, 9.62-14.47) in patients with at least one thrombophilia test. Conclusion The proportion of unprovoked VTE patients with "potent" thrombophilia is high. Given a high proportion of "potent' thrombophilia patients who likely benefit from indefinite anticoagulation, complete thrombophilia testing appears warranted in patients with unprovoked VTE in whom anticoagulants maybe discontinued. Thrombophilia testing is warranted for a selected group of patients to detect high-risk thrombophilias that could impact anticoagulation management. Table 1. Thrombophilia screening Complete screening 470 (40.3%) No screening 189 (16.2%) At least one thrombophilia test 976 (83.8%) Table 2. Thrombophilia All patients (n=1165) Tested for individual thrombophilia % 95% CI % 95% CI FVL Heterozygous 162/1165 (13.9%) 12.0-16.0% 162/883 (18.4%) 15.9-21.0% FVL Homozygous 4/1165 (0.3%) 0.1-0.9% 4/883 (0.5%) 0.2-1.2% Prothrombin Heterozygous 63/1165 (5.4%) 4.3-6.9% 63/831 (7.6%) 6.0-9.6% Prothrombin Homozygous 1/1165 (0.0%) 0.0-0.5% 1/831 (0.1%) 0.0-0.7% Antithrombin deficiency 10/1165 (0.9%) 0.5-1.6% 10/815 (1.2%) 0.7-2.2% Protein C deficiency 18/1165 (1.6%) 1.0-2.4% 18/639 (2.8%) 1.8-4.4% Protein S deficiency 13/1165 (1.1%) 0.7-1.9% 13/635 (2.1%) 1.2-3.5% Lupus anticoagulant 24/1165 (2.1%) 1.4-3.1% 24/849 (2.8%) 1.9-4.2% Anticardiolipin IgM 16/1165 (1.4%) 0.9-2.2% 16/886 (1.8%) 1.1-2.9% Anticardiolipin IgG 20/1165 (1.7%) 1.1-2.6% 20/885 (2.2%) 1.5-3.5% β-2 microglobulin IgM 10/1165 (0.9%) 0.5-1.6% 10/333 (3.0%) 1.6-5.4% β-2 microglobulin IgG 8/1165 (0.7%) 0.4-1.4% 8/333 (2.4%) 1.2-4.7% Homocysteine 50/1165 (5.7%) 4.3-7.4% 50/668 (7.5%) 5.7-9.7% Factor VIII elevated 11/1165 (0.9%) 0.5-1.7% 11/646 (1.7%) 1.0-3.0% At least one or more of the above 331/1165 (28.4%) 25.9-31.1% 331/976 (33.9%) 31.0-36.9% Potent thrombophilia 103/1165 (8.8%) 7.34-10.6% 103/976 (10.6%) 9.6-14.5% Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
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Borthakur, Gautam, Nitin Jain, Hagop Kantarjian, E. Lin, Farhad Ravandi, Sherry Pierce, and Elihu Estey. "Survival Is Poorer in Patients with Secondary Core Binding Factor Acute Myelogenous Leukemia Compared with De Novo Core Binding Factor Leukemia." Blood 110, no. 11 (November 16, 2007): 2856. http://dx.doi.org/10.1182/blood.v110.11.2856.2856.
Повний текст джерелаАнотація:
Abstract Translocation (8;21)(q22;q22) and inversion of chromosome 16 [inv(16) (p13q22)] are considered good-risk cytogenetic abnormalities in acute myeloid leukemia (AML) accounting for 15% of primary AML cases (Blood. 2002 Dec 15;100(13):4325–36) and are characterized at the molecular level by disruption of genes encoding subunits of core binding factor (CBF). Increasing age, increasing peripheral blast percentage and complex cytogenetics are associated with poor overall survival in these patients (Br J Haematol. 2006 Oct;135(2):165–73). Here we assess differences in patient characteristics and outcomes between the primary and secondary core binding factor AML. One hundred eighty nine CBF AML patients treated at our institution were studied; 18 (9.5%) had secondary AML. Patients with secondary CBF AML were older (p= 0.02, median ages 57 vs. 44 years) and had lower WBC counts (p=0.03) (Table1). Overall survival (OS) was worse in the secondary AML patients (94 weeks versus 621 weeks, p=0.0016) (Figure 1). Age, hemoglobin, platelet count, and bilirubin were significantly associated with OS in the univariate analysis. In the multivariate analysis, after adjusting for age, hemoglobin, WBC, and bilirubin, secondary CBF AML was marginally significantly associated with worse OS (hazard ratio 1.884, CI95% 0.979–3.625, p=0.058) but not worse PFS (p= 0.15) (Table 2). These data suggest that the secondary CBF AML has much poorer prognosis than the primary CBF AML, further indicating that “CBF AML” is not a homogeneous entity with a uniformly good prognosis. Table 1: Summary statistics of patients’ continuous characteristics by abnormality status Patient characteristics Total patients Primary AML (n=171, male=96) Secondary AML (n=18, male=8) p-value (primary vs secondary AML) Median (range) Median (range) Median (range) Age (years) 44 (16–88) 44 (16–88) 57 (31–75) 0.02 WBC (103/mm3) 14.7 (0.6–387) 16.4 (0.6–387) 6.6 (0.8–103.8) 0.03 Hemoglobin (g/dl) 8.1 (2.5–14.3) 8.2 (2.5–14.3) 7.8 (4.8–10.8) 0.33 Platelet count (103/mm3) 38 (5–350) 38 (5–350) 39 (9–139) 0.88 Bilirubin (mg/dl) 0.6 (0.0–15.3) 0.6 (0.0–5.0) 0.6 (0.1–15.3) 0.94 Creatinine (mg/dl) 0.9 (0.5–2.9) 0.9 (0.5–2.9) 0.9 (0.5–1.8) 0.66 Table 2: Multivariate Cox proportional hazards model in estimating the association between covariates and patients’ survival Variable Hazard ratio (95% CI) p-value Abnormality (secondary vs primary) 1.884 (0.979–3.625) 0.058 Age (1 year increase) 1.028 (1.012–1.044) 0.0004 Hemoglobin (1gm/dl increase) 0.864 (0.769–0.970) 0.014 WBC (103/mm3 increase) 1.003 (1.000–1.007) 0.061 Bilirubin (1 mg/dl increase) 1.179 (1.044–1.332) 0.008 Figure Figure
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Hagen, M., K. Tascilar, M. Reiser, L. Valor, J. Haschka, A. Kleyer, A. Hueber, et al. "OP0318 TREATMENT TAPERING AND WITHDRAWAL IN RHEUMATOID ARTHRITIS WITH STABLE REMISSION - FINAL ANALYSIS OF THE RETRO STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 194–95. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2174.
Повний текст джерелаАнотація:
Background:Due to better treatment strategies and higher remission rates the management of rheumatoid arthritis (RA) patients in sustained remission is of increasing interest (1). The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated the possibility to taper and stop disease modifying anti-rheumatic drugs (DMARDs).Objectives:To compare one-year remission and relapse rates in rheumatoid arthritis patients randomized to continued treatment, reduced treatment or gradual treatment withdrawal after stable remission under routine care.Methods:Primary data of the phase III, randomized, controlled RETRO trial in RA patients with stable conventional synthetic and/or biologic DMARD treatment in sustained (>6 months) DAS28-ESR remission (<2.6 units). Patients were randomized 1:1:1 into three strategy arms (continuation of 100% DMARD dose, CONT; tapering to 50% DMARD dose, TAP; 50% tapering followed by withdrawal of DMARDs, STOP). The primary endpoint was the proportion of patients in sustained DAS28-ESR remission after 1 year.Results:316 RA patients in sustained remission were included, 303 were randomized (CONT: N=100; TAP: N=102; STOP: N=101) and 282 (93%) had complete data sets after 1 year (CONT:N=93; TAP: N=93; STOP: N=96; Table 1). After 1 year, 81.2%, 58.6%, 43.3% of patients, maintained their remission state over 1 year in the CONT, TAP and STOP arms, respectively (p=0.0004 with log rank test for trend; Figure 1). Hazard ratios for flare were 3.02 (95%CI 1.69 to 5.40) and 4.34 (95%CI 2.48 to 7.60) for the TAP and STOP arms. RA patients who flared were more likely to be female, have longer disease duration, RF/ACPA positivity and higher baseline DAS-28 scores with standardized mean differences >0.2. Serious adverse events were reported in 10.8%, 7.5%, and 13.5% in the CONT, TAP and STOP arms, respectively.Table 1.Baseline CharacteristicsGroupControlReduceReduce/StopOverallN939396282Age, mean(SD)55.9 (12.7)56.9 (13.0)56.5 (13.3)56.5 (13.0)Female, n (%)53 (57.0)57 (62.0)57 (59.4)167 (59.4)RF, n (%)52 (55.9)58 (62.4)52 (54.2)162 (57.4)ACPA, n (%)53 (57.0)50 (54.9)55 (57.3)158 (56.4)Disease duration, years, mean(SD)7.6 (6.9)7.8 (6.9)6.8 (8.1)7.4 (7.3)Remission duration, months, mean(SD)20.6 (18.0)16.5 (15.9)22.7 (30.4)20.0 (22.6)Biologics, n (%)39 (41.9)44 (47.3)39 (40.6)122 (43.3)Methotrexate, n (%)71 (76.3)67 (72.0)75 (78.1)213 (75.5)Other DMARDs, n (%)24 (25.8)20 (21.5)16 (16.7)60 (21.3)Glucocorticoids, n (%)27 (29.0)23 (24.7)17 (17.7)67 (23.8)CRP, mg/L, mean(SD)0.3 (0.3)0.5 (0.5)0.5 (0.6)0.4 (0.5)ESR, mm/h, mean(SD)11.3 (8.4)12.2 (8.8)13.0 (10.0)12.2 (9.1)Tender joint count, mean(SD)0.2 (0.6)0.0 (0.2)0.1 (0.3)0.1 (0.4)Swollen joint count, mean(SD)0.1 (0.3)0.1 (0.3)0.1 (0.4)0.1 (0.3)Physician VAS,mm, mean(SD)1.8 (4.2)2.6 (4.4)2.0 (3.9)2.1 (4.2)Patient VAS,mm, mean(SD)6.4 (9.0)5.5 (8.3)4.5 (8.4)5.5 (8.6)HAQ, standard, mean(SD)0.2 (0.4)0.2 (0.3)0.2 (0.4)0.2 (0.4)HAQ, alternative, mean(SD)0.2 (0.4)0.1 (0.3)0.2 (0.3)0.2 (0.3)DAS-28, mean(SD)1.7 (0.7)1.7 (0.6)1.7 (0.6)1.7 (0.6)SDAI, mean(SD)1.4 (1.5)1.4 (1.5)1.3 (1.3)1.3 (1.4)DAS-28 remission, n (%)91 (97.8)93 (100.0)95 (99.0)279 (98.9)SDAI remission, n (%)79 (87.8)79 (84.9)88 (92.6)246 (88.5)Boolean remission, n (%)69 (75.8)71 (76.3)76 (79.2)216 (77.1)Conclusion:This randomized controlled study shows that half of RA patients in sustained remission relapse when tapering/stopping their DMARDs. Presence of autoantibodies, higher baseline DAS28-ESR and female sex are predictors for flares.References:[1]Schett G et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis. 2016 Aug;75(8):1428-37.Disclosure of Interests:Melanie Hagen Speakers bureau: advisory boards, Koray Tascilar Speakers bureau: advisory board, Michaela Reiser: None declared, Larissa Valor: None declared, Judith Haschka Speakers bureau: advisory board, Arnd Kleyer Speakers bureau: advisory board, Axel Hueber Speakers bureau: advisory boards, Bernhard Manger Speakers bureau: advisory boards, Jayme Cobra Speakers bureau: advisory boards, Camille Figuereido Speakers bureau: advisory boards, Stephanie Finzel Speakers bureau: advisory boards, Hans-Peter Tony Speakers bureau: advisory boards, Joerg Wendler Speakers bureau: advisory boards, Stefan Kleinert Speakers bureau: advisory boards, Florian Schuch Speakers bureau: advisory boards, Monika Ronneberger: None declared, Martin Feuchtenberger Speakers bureau: advisory boards, Martin Fleck Speakers bureau: advisory boards, Karin Manger: None declared, Wolfgang Ochs: None declared, Matthias Schmitt-Haendle: None declared, Hanns-Martin Lorenz Speakers bureau: advisory boards, Rieke Alten Speakers bureau: advisory boards, Jörg Henes Speakers bureau: advisory boards, Klaus Krueger Speakers bureau: advisory boards, Jürgen Rech Speakers bureau: advisory boards, Georg Schett Speakers bureau: advisory boards.
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Finney, M. R., L. R. Fanning, P. J. Vincent, D. G. Winter, M. A. Hoffman, K. J. Antepara, N. J. Greco, et al. "Umbilical Cord Blood CD133+ Stem Cells Exhibit Vasculogenic Capacity In Vitro and Augment Neovasculogenesis In Vivo in a Murine Model of Vascular Ischemia." Blood 108, no. 11 (November 16, 2006): 1790. http://dx.doi.org/10.1182/blood.v108.11.1790.1790.
Повний текст джерелаАнотація:
Abstract Recent reports have utilized a variety of cell types for cellular therapy in mediating therapeutic angiogenesis in response to ischemia. We sought to assess the vasculogeneic potential of selected CD133+ hematopoietic stem cells (HSC) from umbilical cord blood (UCB) utilizing in vitro functional assays and an in vivo murine hind-limb ischemia model. Methods & Results: Mononuclear cells (MNC) from UCB or bone marrow (BM) were incubated with CD133+ conjugated magnetic beads, followed by automated sorting through magnetic columns (Miltenyi). Routine yield of CD133+ cells was 0.5±0.2% of UCB MNC and 0.7±0.3% of BM MNC, with a purity of 79±2% (UCB, n=30) and 84±5% (BM, n=12). Surface expression in the UCB CD133+ population was 3.6±1.5% KDR(VEGFR2), 8.7± 3.8% CXCR4 and 22.7±2.8% CD105 compared to 9.2±1.8% KDR, 14.4±1.3% CXCR4 and 23.7±2.3% CD105 in the BM CD133+ population. We measured chemotactic migration of cells towards SDF-1 (100ng/mL) compared to control wells containing media alone. The fold increase over control was 4.9±2.9 UCB MNC, 1.8±0.7 UCB CD133+ and 8.3±1.7 BM CD133+ (n=3). Angiogenic protein assays of CD133+ cells demonstrated elevated levels of IL-8 production as compared to MNC (103+/−380 pg/mL greater in CD133+ than MNC from the same UCB unit) when cultured for 24h in basal media. NOD/SCID mice underwent ligation of the right femoral artery and were given cells or vehicle control via intracardiac injection immediately following injury. Mice were given 1 x 106 MNC or 0.5 x 106 CD133+ cells. Laser Doppler flow measurements were obtained from both limbs each week for 6 weeks and the ratio of perfusion in the ischemic/healthy limb was calculated. At 28 days, perfusion ratios were statistically higher in study groups receiving UCB CD133+ cells, 0.55±0.06 (n=9), BM CD133+ cells 0.47±0.07 (n=8), BM MNC 0.48±0.8 (n=6) compared to cytokine controls 0.37±0.03 (n=12, p<0.05). Mice receiving UCB MNC did not show statistically significant improvement in measured blood flow over control animals 0.42±0.05 (n=8, p=0.34). At sacrifice, bone marrow was harvested to assess engraftment of human cells by flow cytometric analysis. Mice injected with UCB CD133+ cells showed 19±4.9% positive huCD45 cells compared to 2.5±0.6% for UCB MNC, 1.6±0.4% for BM CD133+ cells and 2.3±0.3% for BM MNC (n=3). Histological studies from day 42 tissue samples of muscle distal to arterial ligation were evaluated for capillary density. Control animals had capillary density of 131±6.9 cells/mm2. Capillary density was statistically higher that controls in animals receiving UCB CD133+ (320±18; p<0.0001), BM CD133++ (183±9.3; p<0.0001), and UCB MNC (164±10.5; p=0.011). Mice treated with BM MNC (135±9.4) did not have a statistically significant increase in capillary density from controls (p=0.73). In addition, animals treated with either UCB or BM-derived CD133+ cells had statistically higher capillary density than unselected MNC (p=<0.0001 and p=0.0004, respectively). Conclusions: In vitro functional assays showed that UCB-derived CD133+ HSC demonstrate enhanced homing capability (migration) as well as the potential for cellular recruitment (via IL-8 production) for angiogenesis in response to ischemia. Furthermore, UCB derived CD133+ HSC mediate significantly improved blood flow in an in vivo murine hind-limb injury model of ischemia, indicating the greater vasculogenic potential of selected CD133+ cells from of this stem cell source.
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Cruz, Rogério Santos de Oliveira, Rafael Alves de Aguiar, Tiago Turnes, Felipe Domingos Lisbôa, João Antônio Gesser Raimundo, and Fabrizio Caputo. "Reliability of a laboratory-based long sprint cycling test: applications of the smallest worthwhile changes in performance for repeated measures designs." Brazilian Journal of Kinanthropometry and Human Performance 20, no. 2 (May 15, 2018): 201–10. http://dx.doi.org/10.5007/1980-0037.2018v20n2p201.
Повний текст джерелаАнотація:
The aims of the present study were to assess the reliability of long sprint cycling performance in a group of recreationally trained cyclists and to provide thresholds for changes in performance for this particular group of subjects in repeated measures designs through a scale of magnitudes. Repeatability of mean power output during a 1-min cycling time trial was assessed in a group of 15 recreationally trained cyclists (26 ± 5, years, 176 ± 5 cm, 78 ± 8 kg). They were tested on separate days, approximately one week apart. The test and retest values for the whole group of cyclists were 7.0 ± 0.5 W/kg and 6.9 ± 0.6 W/kg (systematic change and 90% confidence limits of -1.0% ± 1.1%). Our results indicated good test-retest reproducibility (typical error of 1.8%, 90% confidence limits of 1.4% to 2.6%; intraclass correlation coefficient of 0.96, confidence limits of 0.91 to 0.99), but suggested a reduction of mean power for the “slower” subjects on retest (-2.0%, 90% confidence limits of ±1.8%). If not monitored, this systematic decrease could interfere in results of studies utilizing groups with similar performance levels, particularly investigating strategies to improve performance in sprint cycling exercises around 1 min. The thresholds for moderate, large, very large and extremely large effects for mean power output on long sprint cycling performance are about 0.4%, 1.3%, 2.3%, 3.6%, and 5.8%, respectively.
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Wang, Jingbo, Xiaojun Huang, Ying Hu, Song Xue, Haoyu Cheng, Yuming Yin, Weijie Zhang, Jiangying Gu, Junbao He, and Fan Yang. "Successful Result of 113 Patients for Refractory/Recurrent Leukemia By Allogeneic Hematopoietic Cell Transplantation and Prophylactic Immunotherapy." Blood 128, no. 22 (December 2, 2016): 5856. http://dx.doi.org/10.1182/blood.v128.22.5856.5856.
Повний текст джерелаАнотація:
Abstract Objective: To retrospectively evaluate the results of allogeneic hematopoietic stem cell transplantation for Refractory/Recurrent leukemia. Methods: From July 2012 to May 2016, total 113 patients with Refractory/Recurrent leukemia were enrolled, including 31 cases of ALL, 73 cases of AML and 8 cases of CML-BP, 1 case of Prolymphocytic leukemia. The average leukemia burden was 51% (10-99) in bone marrow before conditioning. Myeloablative conditioning regimens consisted of 13 cases of BuCy, 47 cases of TBI/FLAG, 28 cases of TBI/Cy, and 16 cases of FLAG that followed by reduced-intensified BUCY, 9 cases of CLAG/BuCy. Transplant types included sibling HLA-identical allo-HSCT (n=22) and relative HLA-haploidentical HSCT (n=91). All patients received cyclosporine A, MMF and methotrexate for GVHD prophylaxis. Analyzed outcomes were hematological engraftment, incidence of acute and chronic GVHD, incidence of CMV/EBV infecton, incidence of relapse, and nonrelapse mortality (NRM), Overall survival (OS) and Disease-free survival (DFS). Results: The median mononuclear cells and CD34+ for transfusion were 8.83 (7.02-11.64) ×108/Kg and 2.91 (0.8-8.32) ×106/Kg. 111 patients achieved stable engraftment, 2 patients died of infection before engraftment. The median time of ANC≥0.5×109/L was 16 days(8-29) and the median time of platelet ≥20×109/L was 22 days (8-150). On day 28postallogeneic transplant, 110 patients were in complete remission of bone marrow, 1 patient was in hematologic relapse. Immunity residue were negative in 107 patients and positive in 4 patients. 62 patients developed acute GVHD, the accumulative incidence of aGVHD was (57.6±4.8)%, the accumulative incidence of II-IV grade aGVHD was (47.2±4.8)%, and the accumulative incidence of III-IV grade aGVHD was (25.2±4.1)%. 62 patients developed cGVHD (43 patients extensive, 19 patients limited), the accumulative incidence of cGVHD was (70.2±6.6)% and for extensive type, the accumulative incidence was (43.6±5.2)%. The accumulative incidence of CMV infection was (42.3±4.7)%, and the accumulative incidence of EBV infection was (4.5±2)%. 10 patients developed virus cystitis, and the accumulative incidence was (9.1±2.1)%. The median follow-up time post transplantation was 10 months (1-46), 35 patients occurred hematologic relapsed and the accumulative incidence of relapse was (39.7±5.9)%. For AML, ALL and CML-BP patients, the accumulative incidence of relapse were (33.8±6.9)%, (56.6±11.7)% and (25±15.3)%respectively (p>0.05). On median follow up (10 months), 49 patients died and 64 patients survived. The cause of death included relapse (28 cases), infection (6 cases), GVHD (11 cases) diffuse alveolar hemorrhage (2cases), radiation enteritis (1 case), and TMA (1 case).Among 64 survirors, two-year accumulative incidences of OS were (49.3±5.7)%, and two-year accumulative incidences of LFS were (45.1±5.4). The two-year accumulative incidences of OS for AML, ALL and CML-BP patients were ( 52.4±7.1)%, (28.1±9.7)%,and (87.5±11.7)%respectively (p>0.05). The two-year accumulative incidence of LFS for AML, ALL and CML-BP patients were (49.8±6.5)%, (24.7±9.1)%, and (70±18.2)%respectively (p>0.05). Incidence of relapse, OS and LFS were similar in different conditioning cohorts (p>0.05). There was no significant difference in the incidence of relapse, OS and LFS over two years among patients with C-Kit, FLT3, MLL and without such genes(p>0.05). There is significant difference in incidence of relapse, OS and LFS among patients with different leukemia burdens(p<0.01). Patients with leukemia burden at 10-19% has lower relapse rate but higher OS and LFS compared to patients with leukemia burden at 80%. Incidence of relapse, OS and LFS for the prophylactic immunotherapy cohort were 32.9%, 61.1% and 57.6% respectively, compared to 45.2%, 35.8% and 35% for non prophylactic immunotherapy cohort (p<0.01). Incidence of relapse , OS and LFS for the cGVHD cohort were 12.9%, 68.4% and 66.2% respectively, compared to 78.7%, 13.9% and 12.8% for non cGVHD(p<0.01). Incidence of relapse , OS and LFS for extensive cGVHD cohort were 12.3%, 62.1% and 61.8% respectively, compared to 58.8%, 31.4% and 31.2% for non extensive cGVHD(p<0.01) Conclusion: Our clinical results have shown that the salvaged HSCT is a promising modality for treatment of Refractory/Recurrent leukemia. Especially for Refractory/Recurrent AML and CML-BP. Disclosures No relevant conflicts of interest to declare.
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Kano, Hideyuki, Douglas Kondziolka, Oscar Zorro, Javier Lobato-Polo, John C. Flickinger, and L. Dade Lunsford. "The results of resection after stereotactic radiosurgery for brain metastases." Journal of Neurosurgery 111, no. 4 (October 2009): 825–31. http://dx.doi.org/10.3171/2009.4.jns09246.
Повний текст джерелаАнотація:
Object Radiosurgery for brain metastasis fails in some patients, who require further surgical care. In this paper the authors' goal was to evaluate prognostic factors that correlate with the survival of patients who require a resection of a brain metastasis after stereotactic radiosurgery (SRS). Methods During the last 14 years when surgical navigation systems were routinely available, the authors identified 58 patients who required resection for various brain metastases after SRS. The median patient age was 54 years. Prior adjuvant treatment included whole-brain radiation therapy alone (17 patients), chemotherapy alone (9 patients), both radiotherapy and chemotherapy (10 patients), and prior resection before SRS (8 patients). The median target volumes at the time of SRS and resection were 7.7 cm3 (range 0.5–24.9 cm3) and 15.5 cm3 (range 1.3–81.2 cm3), respectively. Results At a median follow-up of 7.6 months, 8 patients (14%) were living and 50 patients (86%) had died. The survival after surgical removal was 65, 30, and 16% at 6, 12, and 24 months, respectively (median survival after resection 7.7 months). The local tumor control rate after resection was 71, 62, and 43% at 6, 12, and 24 months, respectively. A univariate analysis revealed that patient preoperative recursive partitioning analysis classification, Karnofsky Performance Scale status, systemic disease status, and the interval between SRS and resection were factors associated with patient survival. The mortality and morbidity rates of resection were 1.7 and 6.9%, respectively. Conclusions In patients with symptomatic mass effect after radiosurgery, resection may be warranted. Patients who had delayed local progression after SRS (> 3 months) had the best outcomes after resection.
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Diaz, Miguel A., Marta Gonzalez-Vicent, Manuel Ramirez, Antonio Perez, Javier Garcia-Castro, Julian Sevila, and Luis Madero. "Early “Mini” Donor Lymphocyte Infusions after Reduced-Intensity Conditioning in Allogeneic Transplant of Highly Purified CD34+ Cells from HLA-Identical Donors in Pediatric Leukemia Patients." Blood 106, no. 11 (November 16, 2005): 5387. http://dx.doi.org/10.1182/blood.v106.11.5387.5387.
Повний текст джерелаАнотація:
Abstract To maximize graft-versus-leukemia (GvL) effect while minimizing transplant-related morbidity and mortality (TRM), we designed a study of allogeneic CD34+ selected PBSC transplantation followed by donor lymphocyte infusion (DLI). PBSC CD34+ selection was performed with the CliniMACS device. Between June 2004 and July 2005, fifteen consecutive patients (5 females and 10 males) aged between 1–16 years (median 5 years) diagnosed of AML (6) and ALL (9) were conditioned with fludarabine 30 mg/m2/day x 5 days and melphalan 140 mg/m2/day x 1 day. Status at transplantation was 1st CR 10, 2nd CR 4 and 3th CR 1. GvHD prophylaxis consisted of CsA + short Mtx in 13 cases and CsA in 2. Patients were grafted with a median number of 6.9 x 106/Kg CD34+ cells (range: 1.5–30.9 x 106/Kg) and 15.6 x 103 CD3+ cells (range: 2–59.2 x 103/Kg). All patients engrafted. Median time to neutrophil and platelet engraftment was 12 days (range: 9–15 days) and 13 days (range: 9–42 days), respectively. DLI of 0.5 x 105/Kg CD3+ cells were scheduled on day +15, +30 and +60. A total of 40 DLI were performed. One patient had acute GvHD grade I after the 2nd DLI that resolved with topical steroid treatment and another one developed graft hypoplasia after first DLI resolved after G-CSF treatment. One patient died of a sepsis on day +15 (TRM 6% ± 5%). Two patients relapsed, one with an isolated CNS relapse (6 months postransplant) and the other with a medullar relapse (3 months). With a median follow-up of 6 months (range: 3–13 months) the disease free survival was 75% ± 13% and overall survival 87% ± 8%. The preliminary results of our transplantation strategy are encouraging. A large prospective study is needed to substantiate these results.
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Kim, Choo-Won, Alla Godelman, Vineet R. Jain, Avraham Merav, and Linda B. Haramati. "Postlobectomy Chest Radiographic Changes: A Quantitative Analysis." Canadian Association of Radiologists Journal 62, no. 4 (November 2011): 280–87. http://dx.doi.org/10.1016/j.carj.2010.12.005.
Повний текст джерелаАнотація:
Purpose To provide a quantative analysis of postlobectomy chest radiographic changes and to evaluate whether the scarring from prior sternotomy affects the size of the hemithorax and the duration of air leak in patients with subsequent lobectomy. Methods In this retrospective case-controlled series, 10 consecutive patients who had a lobectomy after a prior sternotomy and 30 controls, 3 for each case, matched for lobectomy site were identified. Pre- and postoperative chest radiographs were quantitatively analysed for diaphragmic elevation, size of each hemithorax, mediastinal shift, and the presence of pneumothorax. Charts were reviewed for air-leak duration, surgical complications, and duration of hospitalization. Results There was no difference between patients with lobectomy and with and without prior sternotomy for the following variables expressed as mean (SD): hemidiaphragm elevation (1.5 ± 2.5 vs 0.5 ± 2.0 cm; P = .2), change of hemithorax size (mean transverse, 0.99 ± 0.05 vs 0.97 ± 0.07; P = .5; craniocaudal, 0.93 ± 0.08 vs 0.91 ± 0.08; P = .4) and mediastinal shift (upper, 1.2 ± 0.4 vs 1.3 ± 0.6; P = .5; lower, 1.2 ± 0.4 vs 1.2 ± 0.3; P = .8), the latter 2 were expressed as the ratio of post- to preoperative measurements. These postlobectomy radiographic findings varied, depending on the resected lobe, and became progressively more pronounced during the first 12 months after surgery. There was no difference in pneumothorax duration (mean [SD]) (9.5 ± 21 days vs 6.4 ± 7.5 days; P = .5), air leak duration (mean [SD]) (0.7 ± 0.8 days vs 1.3 ± 3.9 days; P = .6), complication rate (20% vs 30%; P = .5), or hospital stay (mean [SD]) (6.0 ± 1.7 days vs 6.9 ± 4.7 days; P = .6). Conclusion There are specific patterns of volume loss, mediastinal shift, and hemidiaphragm displacement that can be quantified on postlobectomy chest radiographs. Prior sternotomy did not affect postlobectomy radiographic changes or patient outcome.
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Iwamuro, Masaya, Koji Miyahara, Chihiro Sakaguchi, Ryuta Takenaka, Sayo Kobayashi, Hirokazu Mouri, Shigetomi Tanaka, et al. "Diagnostic Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in Gastric Mesenchymal Tumors." Journal of Clinical Medicine 9, no. 5 (May 1, 2020): 1301. http://dx.doi.org/10.3390/jcm9051301.
Повний текст джерелаАнотація:
There have been no comparative studies investigating the results of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients with gastric mesenchymal tumors, including leiomyomas, leiomyosarcomas, schwannomas, and gastrointestinal stromal tumors (GISTs). We retrospectively reviewed the data of 142 patients with pathologically diagnosed gastric mesenchymal tumors treated at 11 institutions. We analyzed the correlation between the maximum standardized uptake value (SUVmax) evaluated using fluorodeoxyglucose-positron emission tomography (FDG-PET) and the tumor size. The correlation between the SUVmax and mitotic index was also investigated in GISTs. The SUVmax (mean ± standard deviation) was 0.5 ± 0.6 in very low-risk GISTs (n = 42), 2.1 ± 0.7 in low-risk GISTs (n = 26), 4.9 ± 0.8 in intermediate-risk GISTs (n = 22), 12.3 ± 0.8 in high-risk GISTs (n = 20), 1.0 ± 1.0 in leiomyomas (n = 15), 6.9 ± 1.2 in schwannomas (n = 10), and 3.5 in a leiomyosarcoma (n = 1). The SUVmax of GISTs with an undetermined risk classification was 4.2 ± 1.3 (n = 8). Linear associations were observed between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax of GISTs with a high mitotic index was significantly higher than that of GISTs with a low mitotic index (9.6 ± 7.6 vs. 2.4 ± 4.2). In conclusion, we observed positive correlations between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax also positively correlated with the mitotic index and risk grade in GISTs. Schwannomas showed a higher FDG uptake than GISTs and leiomyomas.
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Jian, Wang. "Symptomatic Cervical Vertebral Hemangioma Treated by Percutaneous Vertebroplasty." Pain Physician 4;16, no. 4;7 (July 14, 2013): E419—E425. http://dx.doi.org/10.36076/ppj.2013/16/e419.
Повний текст джерелаАнотація:
Background: Vertebral hemangioma (VH) is considered to be a benign lesion of bone with a rich vasculature. Most incidentally discovered hemangiomas are asymptomatic. Percutaneous vertebroplasty (PVP) has demonstrated efficacy in the treatment of symptomatic thoracic and lumbar VHs. To our knowledge, the reports concerning PVP on symptomatic cervical VHs are quite rare. Objective: Our intent was to assess PVP as treatment for symptomatic cervical hemangiomas. Study Design: Prospective evaluation. Setting: An inteventional pain management practice, single medical center. Methods: Eight patients with symptomatic cervical VHs were enrolled between December 2008 and February 2012, all of whom underwent magnetic resonance imaging (MRI) of the cervical spine. The patients with 8 vertebral bodies of VHs were treated by using PVP. The clinical and radiological data were collected and analyzed. Postoperative outcomes were determined using a visual analog scale. Results: Surgical levels include C3 (2 patients), C4 (3 patients), C5 (2 patients), and C6 (one patient). The average follow-up period was 27.4 months, with a minimum of 12 months. Mean operative time and x-ray exposure time were respectively 35 ± 7.1 minutes and 25 ± 7.7 seconds. The visual analogue scale for neck pain decreased significantly from 6.9 ± 0.6 preoperatively to 1.3 ± 0.5 (P < 0.01) on the second day after surgery, with a final score of 1.2 ± 0.5 (P < 0.01). Cement distribution was always diffuse and homogeneous. No cement leakage was observed in all cases except for 2 patients. There were no other major complications at the time of last follow-up evaluation. Limitations: An observational clinical trial with a relatively small sample size. Conclusion: Short-term results indicate that PVP appears to be an effective and safe treatment for symptomatic cervical VHs. Key words: Percutaneous vertebroplasty, symptomatic, cervical vertebral, hemangiomas
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Budäus, Lars, Jonas Schiffmann, Pierre Tennstedt, Dirk Bottke, Hans Heinzer, Markus Graefen, Lutz Moser, Detlef Bartkowiak, and Thomas Wiegel. "Redefining postprostatectomy biochemical progression: The significance of a PSA cutoff below 0.2 ng/ml—Results from two retrospective series with and without salvage radiotherapy." Journal of Clinical Oncology 33, no. 7_suppl (March 1, 2015): 153. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.153.
Повний текст джерелаАнотація:
153 Background: Biochemical recurrence (BCR) after radical prostatectomy (RP) is usually defined at a PSA >0.2 ng/ml. BCR may precede clinical progression by years. Though salvage radiotherapy (SRT) is recommend to be initiated at PSA <0.5 ng/ml, its efficiency at PSA <0.2 ng/ml is not well documented. Methods: We relied on two independent post-RP cohorts. Cohort 1 (n=311, Hamburg) comprised men whose post-RP PSA levels had risen to 0.1-0.2 ng/ml. Further biochemical and clinical progression were recorded during follow-up. Cohort 2 (n=198, Berlin) were patients with BCR who received SRT (66/72 Gy) at a PSA <0.5 ng/ml. The median follow-up was 6.9 years. Post-SRT progression and overall survival were addressed by Kaplan-Meier analysis and Cox regression modelling. Results: In cohort 1, 299 (96%) men experienced further PSA progression (>0.2 ng/ml) within a median time of 7 months. Subsequent PSA rise to >0.3, >0.4, and >0.6 ng/ml was recorded in 174 (58%), 123 (41%), and 24 (8%) men, respectively. Twenty-four (8%) men developed metastases. In cohort 2, 112 men received SRT at PSA between 0.03 and 0.2 ng/ml, and 86 at 0.2-0.499 ng/ml. The latter group, had a poorer 10-years BCR-free Kaplan-Meier rate, 43% vs. 66% (p=0.051). Together with pT<3, Gleason Score <7, and post-RP PSA <0.03 ng/ml, SRT at PSA <0.2 ng/ml was an independent favorable predictor of freedom from BCR (OR=0.60, p<0.05). Ultimately, 14 patients died. However, overall survival did not significantly correlate with the pre-SRT PSA. Conclusions: The vast majority of patients with a PSA >0.1 ng/ml after RP will subsequently progress to PSA >0.2 ng/ml. Improved progression free survival can be achieved, if SRT is administered at a PSA <0.2 ng/ml. Therefore the contemporary PSA threshold for defining BCR after RP needs to be reconsidered and early sRT should be contemplated on a individual basis for optimizing oncological outcomes.
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Murthy, Ravi, Rahul Sheth, Alda Tam, Sanjay Gupta, Vivek Subbiah, Filip Janku, Timothy Yap, et al. "397 Intra-tumor immunotherapy injections utilizing image guidance in interventional radiology: clinical trial experience at a tertiary care cancer center." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A422. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0397.
Повний текст джерелаАнотація:
BackgroundImage guided intra-tumor administration of investigational immunotherapeutic agents represents an expanding field of interest. We present a retrospective review of the safety, feasibility & technical nuances of real-time image guidance for injection & biopsy across a spectrum of extracranial solid malignancies utilizing the discipline of Interventional Radiology.MethodsPatients who were enrolled in image guided intratumoral immunotherapy injection (ITITI) clinical trials over a 6 year period (2013–19) at a single tertiary care cancer center were included in this analysis. Malignancy, location, imaging guidance utilized for ITITI & biopsy for injected (adscopal) & non-injected (abscopal) lesions were determined and categorized. Peri-procedural adverse events were noted.Results262 pts (146 female, 61 yrs median) participating in 29 immunotherapeutic clinical trials (TLR & STING agonists, gene therapy, anti CD-40, viral/bacterial/metabolic oncolytics) met study criteria. Malignancies included melanoma 88, sarcoma 32, colorectal 29, breast 23, lung 17, head & neck 15, ovarian 8, neuroendocrine 7, pancreatic adenocarcinoma 6, 3 each (cholangioCA, endometrial, bladder, GI tract), 2 each (RCC, thymicCA, lymphoma, merkel cell, prostate) & others 1 each (CUP, GIST, dermatofibrosarcoma, DSRT, neuroblastoma, thyroid). All 169 & 93 patients received the intended 1371 ITITI in parietal (abdominal/chest wall, extremity, neck, pelvis) or visceral (liver, lung, peritoneum, adrenal) locations respectively; 83 patients received lymph node injections within either location. Imaging guidance was US in 68% of the cohort (US 161, CT+US 19); CT was used in 30% (81) & MRI in 1 patient. Median diameter of the ITITI lesion was 32 mm (8–230 mm). Median volume of the ITITI therapeutic material/session was 2 ml (1–6.9 ml). Lesions were accessed using a coaxial technique. ITITI delivery needles used at operator preference & tailored to lesion characteristics were either a 21G/22G Chiba, 21G Profusion (Cook Medical), 22G Morrison (AprioMed), 25G hypodermic (BD) & 18G Quadrafuse (Rex Medical). 2840 core biopsies (>18G Tru-cut core, Mission, Bard Medical) were performed in 237 patients during 690 procedures; biopsy sessions were often concurrent & of the ITITI site. 137 patients also underwent biopsy of a non-ITITI site (89 parietal location). Dimensions of the non-ITITI lesion were median 10 mm (7–113 mm); US image guidance was used in 97 patients (72%) to obtain a total of 1257, >18G Tru-core samples. 1.3% of injections resulted in SAE (NCI CTC AE >3) and 0.5% of 4097 biopsies developed major complications (SIR Criteria); both categories were manageable.ConclusionsUtilizing real time image guidance, ITITI to the administration of a myriad of investigational immunotherapeutic agents with concomitant biopsy procedures to date are associated with a high technical success rate & favorable safety profile.AcknowledgementsJoshua Hein, Mara Castaneda, Jyotsna Pera, Yunfang Jiang,Shuang Liu, Holly Liu and Anna LuiTrial RegistrationN/AEthics ApprovalThe study was approved by Institution’s Ethics Board, approval number 2020-0536: A retrospective study to determine the safety, feasibility and technical challenges of real-time image guidance for intra-tumor injection and biopsy across multiple solid tumors.Consent2020-0536 Waiver of Informed ConsentReferenceSheth RA, Murthy R, Hong DS, et al. Assessment of image-guided intratumoral delivery of immunotherapeutics in patients with cancer. JAMA Netw Open 2020;3(7):e207911. doi:10.1001/jamanetworkopen.2020.7911
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Salykova, V. S., and L. V. Shtil’. "The content of biologically active substances in fruits of golden currant accessions breeding of research institute of horticulture of Siberia." Pomiculture and small fruits culture in Russia 61 (August 3, 2020): 95–102. http://dx.doi.org/10.31676/2073-4948-2020-61-95-102.
Повний текст джерелаАнотація:
Berries of golden currant have a nutritional value and a high content of biologically active substances (BAS). Variability and a high level of manifestation of accession parameters indicate the possibility of breeding for improving the biochemical composition of berries. The purpose of the work is to evaluate and select of golden currant accessions according to its high content of carotenoids, pectin and sum of pectin substances in fruits. The work was carried out at the Research Institute of Horticulture of Siberia, Department of Federal Altai Scientific Center of Agro-Biotechnologies, in 2016- 2018. Weather conditions of 2016, 2017 were characterized as quite warm and quite moist, 2018 was dry and cool. Biochemical analysis was carried out in the laboratory of industrial technologies during the period of full ripeness of berries. Pectin substances were determined by the titrometric method (GOST 29059-91), carotenoids – according to I. K. Murray (GOST 8756.22-80 ST SEV 6519-88). The objects of the research were the varieties and selected forms of golden currant breeding of the Research Institute of Horticulture of Siberia. The control variety was Levushka. As a result of the work, varieties and selected forms were evaluated by the content of biologically active substances (carotenoids, pectin, pectin substances), promising forms with maximum biochemical parameters were identified. The content of carotenoids in the accessions varied widely 0.5 – 11.9 mg/100 g, on the average 3.5 mg/100 g. Levushka varieties (11.9 mg/100 g) as well as Podarok to Ariadne (7.7 mg/100 g), Ida (6.5 mg/100 g), selected forms 4198-06-9 (6.9 mg/100 g) and 4197-06-1 (5.5 mg/100 g were noted with high values. Varieties Valentina and Otrada showed stability over the years, the coefficient of variation was 5.8 and 12.0 %, respectively. The pectin content in berries varied from 0.5 to 1.5 %, on the average 1.0 %, in the accessions Valentina, Ida, Otrada, 4190-06-13 – 1.3%, in 4268-07-1 – 1.4 %, 4197-06-1 – 1.5 %. The total amount of pectin substances in berries amounted to 0.9 – 1.6 % on the average – 1.3 %, with an increased value Ida variety, forms 4190-06-13, 4197-06- 1, 4198-06-9, 4268-07-1 were highlighted. Over the years of the research, the stability in the content of the sum of pectin substances was shown by accessions 4197-06-1 (V = 8, 7 %), 4268-07-1 (V = 10.7 %), 4190-06-13 (V = 1.7 %)
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Simonneau, Gerald. "Nadroparin 0.3 mL Versus Enoxaparin 40 mg in the Prevention of Venous Thromboembolism in Abdominal Surgery for Colorectal Cancer: A Randomized Double-Blind Comparative Study." Blood 106, no. 11 (November 16, 2005): 552. http://dx.doi.org/10.1182/blood.v106.11.552.552.
Повний текст джерелаАнотація:
Abstract Background: The relative benefit-to-risk ratio of various LMWH in the setting of colorectal cancer surgery has never been directly compared. Objective: We performed a multicenter, randomized, double-blind study to compare the efficacy and safety of enoxaparin 40 mg (4000 anti-Xa IU) and nadroparin 0.3 mL (2850 anti-Xa IU) in the prevention of venous thromboembolism (VTE) after colorectal cancer surgery. Methods: Patients undergoing elective colorectal adenocarcinoma resection under general anesthesia were recruited. They were randomized to receive once daily either nadroparin 0.3 mL or enoxaparin 40 mg subcutaneously for 9±2 days, starting 2 to 4 hours preoperatively. The primary efficacy outcome was the composite of deep-vein thrombosis (DVT) detected by bilateral venography or documented symptomatic DVT or pulmonary embolism (PE) up to Day 12. The main safety outcomes were major bleeding and all-cause death. A blinded independent committee adjudicated all outcomes. Results: A total of 1288 patients (median age: 69, range: 26–97 years; men: 61.4%) were randomized either to nadroparin (n=653) or to enoxaparin (n=635). Efficacy was evaluable in 950 (73.8%) patients who underwent contrast venography or had a symptomatic thromboembolic event. The rate of VTE at Day 12 was 15.9% for nadroparin and 12.6% for enoxaparin (relative risk reduction 21.3% [95% CI: −7.75; 42.5]). This difference was not statistically significant (p=0.13, Chi-squared test). In contrast, there were more symptomatic VTE, including symptomatic PE, in the enoxaparin group than in the nadroparin group (Table). Furthermore, the rate of major bleeding was significantly lower in nadroparin-treated patients than in enoxaparin-treated patients (Table). By Day 12, there were three (0.5%) deaths related to VTE or major bleeding in enoxaparin patients compared with none in nadroparin patients. By Day 60, 23 (3.5%) patients receiving nadroparin and 23 (3.5%) patients receiving enoxaparin had died. Conclusion: Enoxaparin 40 mg was not more effective than nadroparin 0.3 mL in the prevention of total VTE in patients undergoing colorectal cancer surgery. The non-significant difference between the two groups was mainly due to a lower rate of asymptomatic distal DVT in the enoxaparin group than in the nadroparin group. However, nadroparin was more effective than enoxaparin for reducing symptomatic VTE, including PE, and was associated with significantly less major bleeding. Efficacy and safety results at Day 12 Nadroparin 0.3 mL, n/N (%) Enoxaparin 40 mg, n/N (%) p *Chi-squared test Total VTE 74/464 (15.9) 61/486 (12.7) 0.13* Asymptomatic proximal DVT 15/503 (3.0) 14/515 (2.7) 0.81 Asymptomatic distal DVT 58/503 (11.5) 42/515 (8.2) 0.07 Symptomatic VTE 1/643 (0.2) 9/628 (1.4) 0.01 Symptomatic proximal DVT 1/643 (0.2) 4/628 (0.6) 0.22 Symptomatic PE 0/643 (0.0) 5/628 (0.8) 0.03 Major bleeding 47/643 (7.3) 72/628 (11.5) 0.01 All-cause death 2/643 (0.3) 8/628 (1.3) 0.06
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Ivanyuk, Gregory Yu, Victor N. Yakovenchuk, Taras L. Panikorovskii, Nataliya Konoplyova, Yakov A. Pakhomovsky, Ayya V. Bazai, Vladimir N. Bocharov та Sergey V. Krivovichev. "Hydroxynatropyrochlore, (Na,Сa,Ce)2Nb2O6(OH), a new member of the pyrochlore group from the Kovdor phoscorite–carbonatite pipe, Kola Peninsula, Russia". Mineralogical Magazine 83, № 1 (15 травня 2018): 107–13. http://dx.doi.org/10.1180/minmag.2017.081.102.
Повний текст джерелаАнотація:
AbstractHydroxynatropyrochlore, (Na,Сa,Ce)2Nb2O6(OH), is a new Na–Nb–OH-dominant member of the pyrochlore supergroup from the Kovdor phoscorite–carbonatite pipe, Kola Peninsula, Russia. It is cubic, Fd$\bar{3}$m, a = 10.3211(3) Å, V = 1099.46(8) Å3 and Z = 8 (from powder diffraction data) or a = 10.3276(5) Å, V = 1101.5(2) Å3 and Z = 8 (from single-crystal diffraction data). Hydroxynatropyrochlore is a characteristic accessory mineral of the low-carbonate phoscorite in the contact zone of the phoscorite–carbonatite pipe with host foidolite as well as in the carbonate-rich phoscorite and carbonatite of the pipe axial zone. It usually forms zonal cubic or cubooctahedral crystals (up to 0.5 mm in diameter) with irregularly shaped relics of amorphous U–Ta-rich hydroxykenopyrochlore inside. Characteristic associated minerals include rock-forming calcite, dolomite, forsterite, hydroxylapatite, magnetite and phlogopite, accessory baddeleyite, baryte, barytocalcite, chalcopyrite, chamosite–clinochlore, galena, gladiusite, juonniite, ilmenite, magnesite, pyrite, pyrrhotite, quintinite, spinel, strontianite, valleriite and zirconolite. Hydroxynatropyrochlore is pale brown, with an adamantine to greasy lustre and a white streak. The cleavage is average on {111} and the fracture is conchoidal. Mohs hardness is ~5. In transmitted light, the mineral is light brown, isotropic and n = 2.10(5) (λ = 589 nm). The calculated and measured densities are 4.77 and 4.60(5) g cm−3, respectively. The mean chemical composition determined by electron microprobe is: F 0.05, Na2O 7.97, CaO 10.38, TiO2 4.71, FeO 0.42, Nb2O5 56.44, Ce2O3 3.56, Ta2O5 4.73, ThO2 5.73, UO2 3.66, total 97.65 wt.%. The empirical formula calculated on the basis of Nb + Ta + Ti = 2 apfu is (Na1.02Ca0.73Ce0.09Th0.09 U0.05${\rm Fe}_{{\rm 0}{\rm. 02}}^{2 +} $)Σ2.00(Nb1.68Ti0.23Ta0.09)Σ2.00O6.03(OH1.04F0.01)Σ1.05. The simplified formula is (Na,Ca,Ce)2Nb2O6(OH). The mineral dissolves slowly in hot HCl. The strongest X-ray powder-diffraction lines [listed as (d in Å)(I)(hkl)] are as follows: 5.96(47)(111), 3.110(30)(311), 2.580(100)(222), 2.368(19)(400), 1.9875(6)(333), 1.8257(25)(440) and 1.5561(14)(622). The crystal structure of hydroxynatropyrochlore was refined to R1 = 0.026 on the basis of 80 unique observed reflections. The mineral belongs to the pyrochlore structure type A2B2O6Y1 with octahedral framework of corner-sharing BO6 octahedra with A cations and OH groups in the interstices. The Raman spectrum of hydroxynatropyrochlore contains characteristic bands of the lattice, BO6, B–O and O–H vibrations and no characteristic bands of the H2O vibrations. Within the Kovdor phoscorite–carbonatite pipe, hydroxynatropyrochlore is the latest hydrothermal mineral of the pyrochlore supergroup, which forms external rims around grains of earlier U-rich hydroxykenopyrochlore and separated crystals in voids of dolomite carbonatite veins. The mineral is named in accordance with the pyrochlore supergroup nomenclature.
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Sesin, C., G. Gallo, A. Gellett, A. Kronbergs, A. T. Sprabery, W. Xu, H. Patel, A. Deodhar, B. Combe, and G. R. Burmester. "POS1033 SAFETY OF IXEKIZUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS: AN INTEGRATED ANALYSIS OF 4 CLINICAL TRIALS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 789.1–789. http://dx.doi.org/10.1136/annrheumdis-2021-eular.567.
Повний текст джерелаАнотація:
Background:Patients with psoriatic arthritis (PsA) require long-term treatment, which may lead to adverse events (AEs). Ixekizumab, an interleukin-17A antagonist, is approved for the treatment of adults with active PsA.Objectives:We report a summary of safety outcomes for patients enrolled in 4 PsA studies with up to 3 years of exposure to ixekizumab.Methods:This integrated safety analysis included all patients with PsA who received at least 1 dose of ixekizumab (80 mg every 2 or 4 weeks) in 4 clinical trials (NCT01695239, NCT02349295, NCT02584855, NCT03151551). Safety outcomes included treatment-emergent adverse events (TEAEs), serious AEs (SAEs), discontinuations due to AEs, deaths, and AEs of special interest.Results:A total of 1401 patients were included in this safety analysis (51.5% female; mean age 49 years), with 2247.6 patient-years of exposure (Table 1). In all, 1131 patients (80.7%) reported ≥1 TEAE (exposure-adjusted incidence rate per 100 patient-years [IR] 50.3, 95% CI 47.5–53.3), mostly mild (32.9%) or moderate (39.7%) in severity. The most common TEAEs were nasopharyngitis (n=202, IR 9.0), upper respiratory infections (n=186, IR 8.3), and injection site reaction (n=156, IR 6.9). SAEs were reported by 134 patients (IR 6.0, 95% CI 5.0–7.1). 115 (8.2%) patients discontinued due to AEs (IR 5.1, 95% CI 4.3–6.1). Six deaths were reported (IR 0.3, 95% CI 0.1–0.6). Allergic reactions/hypersensitivity were reported in 102 patients (IR 4.5, 95% CI 3.7–5.5). Three cases were adjudicated as de novo inflammatory bowel disease (IR 0.13, 95% CI 0.04–0.41); 1 was ulcerative colitis (IR 0.04, 95% CI 0.01–0.32), 2 were Crohn’s disease (IR 0.09, 95% CI 0.02–0.36). Major adverse cardiac events occurred in 12 patients (IR 0.5) and malignancies in 15 (IR 0.7), 9 of which were non-melanoma skin cancer. Opportunistic infections occurred in 40 (2.9%) patients (IR 1.8, 95% CI 1.3–2.4). Candidiasis occurred in 24 patients (oral: IR 0.7, 95% CI 0.4–1.2; oral fungal infection: IR 0.3, 95% CI 0.1–0.6; esophageal infection: IR 0.1, 95% CI 0.0–0.4). No active or reactive cases of tuberculosis were reported. Other opportunistic infections included hepatitis B (IR 0.0, 95% CI 0.0–0.3), herpes simplex (IR 1.8, 95% CI 1.3–2.5), and herpes zoster (IR 0.7, 95% CI 0.4–1.2).Conclusion:The safety profile of ixekizumab across 4 clinical trials and up to 3 years of continuous treatment in patients with active PsA was consistent with the known safety profile reported in previous studies for psoriasis and PsA. No new safety events were found in this analysis.Pooled Ixekizumab(N=1401; Total Patient-Years=2247.6)n (IR)95% CIYear 0–1(n=1401)n (IR)95% CIYear 1–2(n=946)n (IR)95% CIYear 2–3(n=510)n (IR)95% CIYear ≥3(n=89)n (IR)95% CITotal Patient-Years2247.71207.3689.8347.72.9Patients with ≥1 TEAE1131 (50.3)1050 (87.0)496 (71.9)234 (67.3)6 (206.2)47.5–53.381.9–92.465.9–78.559.2–76.592.6–458.9SAEs134 (6.0)72 (6.0)53 (7.7)19 (5.5)1 (34.4)5.0–7.14.7–7.55.9–10.13.5–8.64.8–243.9Discontinuations due to AEs115 (5.1)61 (5.1)37 (5.4)17 (4.9)0 (0)4.3–6.13.9–6.53.9–7.43.0–7.90.0–274.7Hepatic reactions112 (5.0)80 (6.6)32 (4.6)14 (4.0)0 (0)4.1–6.05.3–8.33.3–6.62.4–6.80.0–274.7Allergic reaction/hypersensitivity102 (4.5)83 (6.9)23 (3.3)5 (1.4)0 (0)3.7–5.55.5–8.52.2–5.00.6–3.50.0–274.7Serious infection28 (1.2)18 (1.5)9 (1.3)3 (0.9)0 (0)0.9–1.80.9–2.40.7–2.50.3–2.70.0–274.7Malignancies15 (0.7)4 (0.3)8 (1.2)4 (1.2)0 (0)0.4–1.10.1–0.90.6–2.30.4–3.10.0–274.7Major adverse cardiac events12 (0.5)3 (0.2)8 (1.2)1 (0.3)0 (0)0.3–0.90.1–0.80.6–2.30.0–2.00.0–274.7Inflammatory bowel disease3 (0.1)3 (0.2)1 (0.1)0 (0.0)0 (0.0)0.0–0.40.1–0.80.0–1.00.0–2.30.0–274.7 Ulcerative colitis1 (0.0)1 (0.1)1 (0.1)0 (0.0)0 (0.0)0.0–0.30.0–0.60.0–1.00.0–2.30.0–274.7 Crohn’s disease2 (0.1)2 (0.2)0 (0.0)0 (0.0)0 (0.0)0.0–0.40.0–0.70.0–1.20.0–2.30.0–274.7AE, adverse event; CI, confidence interval; IR, exposure-adjusted incidence rate per 100 patient-years; SAE, serious adverse event; TEAE, treatment-emergent adverse event.Disclosure of Interests:Carlos Sesin Speakers bureau: Amgen, AbbVie, Sanofi, Radius, Pfizer, Eli Lilly and Company, Novartis, Gaia Gallo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Amanda Gellett Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Andris Kronbergs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Aubrey Trevelin Sprabery Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Wen Xu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Himanshu Patel Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Atul Deodhar Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly and Company, Glaxo Smith & Kline, Novartis, Pfizer, UCB, Bernard Combe Speakers bureau: AbbVie, BMS, Gilead-Galapagos, Eli Lilly and Company, MSD, Pfizer, Roche Chugai, Consultant of: AbbVie, Bayer, Gilead-Galapagos, Janssen, Eli Lilly and Company, Novartis, Roche Chugai, Grant/research support from: AbbVie, Eli Lilly and Company, Pfizer, Roche Chugai, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Janssen, Novartis, Eli Lilly and Company, MSD, Pfizer, Consultant of: AbbVie, Janssen, Novartis, Eli Lilly and Company, MSD, Pfizer.
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Zheng, Haotian, Siyi Cai, Shuxiao Wang, Bin Zhao, Xing Chang, and Jiming Hao. "Development of a unit-based industrial emission inventory in the Beijing–Tianjin–Hebei region and resulting improvement in air quality modeling." Atmospheric Chemistry and Physics 19, no. 6 (March 19, 2019): 3447–62. http://dx.doi.org/10.5194/acp-19-3447-2019.
Повний текст джерелаАнотація:
Abstract. The Beijing–Tianjin–Hebei (BTH) region is a metropolitan area with the most severe fine particle (PM2.5) pollution in China. An accurate emission inventory plays an important role in air pollution control policy making. In this study, we develop a unit-based emission inventory for industrial sectors in the BTH region, including power plants, industrial boilers, steel, non-ferrous metal smelting, coking plants, cement, glass, brick, lime, ceramics, refineries, and chemical industries, based on detailed information for each enterprise, such as location, annual production, production technology/processes, and air pollution control facilities. In the BTH region, the emissions of sulfur dioxide (SO2), nitrogen oxide (NOx), particulate matter with diameter less than 10 µm (PM10), PM2.5, black carbon (BC), organic carbon (OC), and non-methane volatile organic compounds (NMVOCs) from industrial sectors were 869, 1164, 910, 622, 71, 63, and 1390 kt in 2014, respectively, accounting for a respective 61 %, 55 %, 62 %, 56 %, 58 %, 22 %, and 36 % of the total emissions. Compared with the traditional proxy-based emission inventory, much less emissions in the high-resolution unit-based inventory are allocated to the urban centers due to the accurate positioning of industrial enterprises. We apply the Community Multi-scale Air Quality (CMAQ; version 5.0.2) model simulation to evaluate the unit-based inventory. The simulation results show that the unit-based emission inventory shows better performance with respect to both PM2.5 and gaseous pollutants than the proxy-based emission inventory. The normalized mean biases (NMBs) are 81 %, 21 %, 1 %, and −7 % for the concentrations of SO2, NO2, ozone (O3), and PM2.5, respectively, with the unit-based inventory, in contrast to 124 %, 39 %, −8 %, and 9 % with the proxy-based inventory; furthermore, the concentration gradients of PM2.5, which are defined as the ratio of the urban concentration to the suburban concentration, are 1.6, 2.1, and 1.5 in January and 1.3, 1.5, and 1.3 in July, for simulations with the unit-based inventory, simulations with the proxy-based inventory, and observations, respectively, in Beijing. For O3, the corresponding gradients are 0.7, 0.5, and 0.9 in January and 0.9, 0.8, and 1.1 in July, implying that the unit-based emission inventory better reproduces the distributions of pollutant emissions between the urban and suburban areas.
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Yoshidaya, Fumi, Naoki Hayashi, Atsushi Yoshida, Hiroshi Yagata, Hiroko Tsunoda, Koyu Suzuki, Seigo Nakamura, and Hideko Yamauchi. "Clinicopathologic features of multiple phyllodes tumors of the breast." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 1126. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.1126.
Повний текст джерелаАнотація:
1126 Background: Phyllodes tumor of the breast is one of the rare neoplasm accounting for 0.3-0.5% of all breast tumors. It is difficult to diagnose the histological type of phyllodes tumors preoperatively by radiological and even pathological findings. The aim of this study is to clarify the clinicopathological features of phyllodes tumors. Methods: We retrospectively reviewed records from 116 patients with phyllodes tumors who underwent surgery between 2003 and 2011. We determined the clinicopathological characteristics, including the presense of multiple lesions and the type of surgical procedure, of each histological type of phyllodes tumors which were classified as benign, borderline, and malignant. Results: The median follow-up time was 23.3 months. Benign phyllodes tumors were presented in 91 patients (78.4 %), borderline were in 17 patients (14.6 %), and malignant were in 8 patients (6.9 %). Ten patients (8.6 %) had multiple phyllodes tumors; 9 for ipsilateral and one for bilateral breasts. One hundred two patients underwent lumpetcomy and 14 patients underwent mastectomy. No patients received chemotherapy or radiation therapy. Noteworthy, all multiple tumors were diagnosed histologically benign. The median age at operation were 41 years (range, 12-72 years) for benign tumors, 44 years (26-67 years) for borderline, and 47 years (39-60 years) for malignant. The size of malignant tumors was significantly large (a median, 11.3 cm; range, 6-27 cm) compared to benign (a median, 4.4 cm; range 1-21 cm) and borderline (a median, 4.7cm; range 1-16 cm) (p = 0.001, and 0.03, respectively). Local recurrence developed in 14 of the 91 patients (15.4 %) with benign, 2 of the 17 patients (11.8 %) with borderline, and 2 of the 8 patients (25 %) with malignant tumors. Four patients (50 %) with malignant tumors but none with benign and borderline developed distant metastasis. Of the 4 patients, 3 had undergone mastectomy and one had lumpetcomy for initial treatment. No benign and borderline tumor had malignant change when tumors recurred. Conclusions: Our new findings indicated that multiple phyllodes tumors may be histologically benign. Furthermore, patients with benign or borderline phyllodes tumors had good prognosis regardless of surgical procedure.
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Nute, Drew W., Nicholas Kusnezov, and Brian R. Waterman. "Functional Outcomes and Complications Following Pectoralis Major Tendon Allograft Reconstruction in a Military Population." Orthopaedic Journal of Sports Medicine 7, no. 10 (October 1, 2019): 232596711987870. http://dx.doi.org/10.1177/2325967119878709.
Повний текст джерелаАнотація:
Background: There are limited data available regarding outcomes following pectoralis major tendon (PMT) reconstruction with allograft. Purpose: To evaluate the functional outcomes and complication profile following PMT reconstruction with allograft in a military population. Study Design: Case series; Level of evidence, 4. Methods: All active duty military personnel who underwent PMT allograft reconstruction between 2008 and 2013 were identified. Demographics, injury characteristics, and surgical technique were recorded from the electronic medical record. Self-reported pain scores and manual strength were evaluated pre- and postoperatively, as recorded in physician electronic medical record notes, in addition to the ability and degree to which each patient was able to return to function. Standardized outcome measures included the Bak criteria; visual analog scale for pain; Disabilities of the Arm, Shoulder and Hand (DASH) score; American Shoulder and Elbow Surgeons (ASES) score; and 36-Item Short Form Health Survey (SF-36). Complications, including rerupture and reoperation, were additionally recorded. Results: Nine male patients (mean ± SD age, 35.7 ± 5.8 years) underwent allograft PMT reconstruction. Mean improvement in self-reported pain score at a mean 53.5 months (range, 31.1-110.9 months) was 2.1 ± 1.3 points ( P = .08). Improvements in manual strength during forward flexion (0.5 ± 0.7; P = .03), adduction (0.6 ± 0.6; P = .01), and internal rotation (0.5 ± 0.7; P = .03) were significant. Seven patients (78%) returned to full preinjury level of occupational function, and 88% returned to performing the bench press, although maximum weight decreased by a self-reported mean of 141.3 lb. According to the Bak criteria, 5 (56%) patients had excellent outcomes, 2 (22%) had fair outcomes, and 2 (22%) had poor outcomes. Mean visual analog scale for pain (1.9 ± 2.8), DASH (10.8 ± 17.4), ASES (88.1 ± 20.3), and SF-36 scores (96.3% ± 6.9%) were obtained for the 8 patients available at final follow-up. Complications included 2 cases (22%) of persistent shoulder pain leading to military separation, 1 rerupture (11%), and 1 (11%) surgical scar revision. Conclusion: While allograft reconstruction is a reliable option to decrease pain and improve function in patients with tears not amenable to primary repair, patients should be educated about the risk profile and fitness limitations after surgery.
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Martin Lopez, M., B. Joven-Ibáñez, and J. L. Pablos. "SAT0428 IMPACT OF DOSE ESCALATION OF SECUKINUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS IN REAL-WORLD SETTING." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1168.2–1169. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6579.
Повний текст джерелаАнотація:
Background:Secukinumab (SEC) has provided efficacy in clinical trials in patients with psoriatic arthritis (PsA). In PsA patients, a gain in response has been suggested by dose escalation from 150 to 300 mg in the open phase of the FUTURE study1.Objectives:To analyze the usefulness of dose escalation of SEC from 150 to 300 in patients with non-responding PsA to 150 mg in real-world setting.Methods:Multicentric observational, longitudinal, retrospective study conducted in a tertiary hospital between January 2016 and December 2019. Patients with PsA (CASPAR criteria) receiving at least one dose of SEC were included. Medical records were reviewed to collect demographic and clinical data related to PsA (including activity assessment and treatment). Descriptive statistics and a comparative analysis of the efficacy of SCK by the Studentttest in the different dose groups and by the ANOVA test to compare the response between the three dose groups were performed.Results:98 patients with PsA treated with SEC, of which 69(70%) female were included. Mean age was 54 y.o (SD12) and average duration of the disease was 9 (SD 7) years. Three groups were made according to the dose received, SEC150, SEC300 and SEC150-300 (non-responders after SEC150 onset increasing to 300 mg). The SEC150 group includes 58(59%) patients of whom 32(55%) had received at least one biological (16 one biological, 8 two biological and 10 three or more). The survival of SEC was 1.3 (SD1) years and was suspended in 24(41%) patients, due to primary failure in 9, secondary failure 10, adverse events 4 and allergy to latex 1. The SEC300 group includes 12 (12%) patients of whom 10 (83%) had received at least one biological (1 one biological, 3 two and 6 three or more). The survival of the SEC was 1.6 SD (1.3) years and was suspended in 8 (67%) patients, due to primary failure in 2, secondary failure 5 and remission 1. Finally, the SEC150-300 group includes 28 (29%) patients of whom 17 (61%) had received at least one biologic (7 one biologic, 2 two and 8 three or more). The survival of the SEC was 1.6 (SD0.9) years and was suspended in 13 (46%) patients, all due to secondary failure. 54%, therefore, maintains the SCK after responding to the dose increase. The average time of dose increase to 300 mg was 9(SD6) months. In the three treatment groups, a significant decrease in the values of CRP, ASDAS-CRP and DAPSA was observed at 6 months of SEC (Table 1). However, when comparing the difference of means obtained during follow-up (ΔCRP, ΔASDAS and ΔDAPSA) between the 3 dose groups, no significant differences were found (p=0.76 for CRP, p=0.86 for ASDAS and p=0.35 for DAPSA).Table 1.Disease activity assessment at 6 months of SEC therapy.Baseline6 months after SECMean differencep valueCRP300 (mg/L)9±8,34,7±3,7-4,3 (IC95% -8,9 a 0,2)p=0,06CRP150 (mg/L)7,3±9,14,0±4,7-2,9 (IC95% -4,7 a -1,3)p=0,0009CRP150-300(mg/L)9,9±116,0±7,4-3,9 (IC95% -6,9 a -8,5)p=0,0142ASDAS-CRP3002,3±0,71,6±0,6-0,6 (IC95% -0,9 a -0,3)p=0,0014ASDAS-CRP1502,3±0,61,6±0,7-0,7 (IC95% -0,8 a -0,5)p<0,0001ASDAS-CRP150-3002,2±0,61,6±0,7-0,6 (IC95% -0,8 a -0,4)p<0,0001DAPSA30033,7±19,316,9±10,6-16,8 (IC95% -29,6 a -3,9)p=0,01DAPSA15027,4±11,415,4±10,4-11 (IC95% -14,4 a -7,6)p<0,0001DAPSA150-30028±9,915,8±8,7-12,2 (IC95% -15,3 a -9,1)p<0,0001CRP300: C-reactive protein in patients with SCK 300 mg, CRP150: in patients with SCK 150, CRP150-300: in patients with dose escalation from 150 to 300 (same for ASDAS-CRP and DAPSA), SEC: secukinumabConclusion:There are no significant differences in the response evaluated by CRP, ASDAS-CRP and DAPSA between the dose of 150 and 300 mg of SEC. However, both doses of treatment provided efficacy in clinical practice with significant reduction of activity parameters. In the case of patients not responding to SEC150 mg and prior failure to TNFi, increasing the dose to 300 mg could be an effective option.References:[1]Mease PJ, et al. ACR Open Rheum.2020 Jan;2(1):18-25.Disclosure of Interests:MARIA MARTIN LOPEZ: None declared, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, José Luis Pablos: None declared
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Xi, Jing, Kathleen Harnden, Jingqin Luo, Greg S. Call, Elizabeth Mauer, Karyn Ronski, Cynthia X. Ma, and Neil Vasan. "Abstract P3-09-04: Genomic landscape of HER2-negative advanced or metastatic breast cancer with PIK3CA gain-of-function mutations." Cancer Research 82, no. 4_Supplement (February 15, 2022): P3–09–04—P3–09–04. http://dx.doi.org/10.1158/1538-7445.sabcs21-p3-09-04.
Повний текст джерелаАнотація:
Abstract Background: Alpelisib and fulvestrant are used as a combination treatment option for postmenopausal PIK3CA-mutated, hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced or metastatic breast cancer (a/mBC) patients. However, despite the presence of activating mutations in PIK3CA, the majority of patients do not derive benefit, or ultimately progress while on alpelisib therapy. Here, we investigate the genomic landscape of PIK3CA-mutated, HER2- a/mBC using next-generation sequencing (NGS) to provide insight into possible mechanisms of therapeutic resistance to alpelisib/fulvestrant and to identify potential targetable pathways. Methods: We utilized the Tempus LENS platform to retrospectively analyze de-identified NGS data from 2,918 a/mBC patients with formalin-fixed, paraffin-embedded tumor biopsies sequenced using the Tempus|xT solid tumor assay (DNA-seq of 595-648 genes at 500x coverage; full transcriptome RNA-seq). Mutations identified included germline and/or somatic single nucleotide variants, insertions/deletions and copy number variations (gains defined as ≥8 copies). We used curated clinical data to determine HER2 and hormone receptor (ER/PR) status. Results: Among 2,918 a/mBC patients, we identified somatic mutations in PIK3CA in 782 (26.8%). Within these tumors, 629 (80.4%) had one of the 11 mutations currently included in the alpelisib companion diagnostic, and we focused on this population (here defined as mut-PIK3CA). Of these 629, 546 (86.8%) were HER2-, with 176 (32.3%) and 370 (67.7%) derived from primary and metastatic tumors, respectively. Cases were further classified as HR+ (defined as ER+ or PR+) or triple negative (TNBC). While the majority of mutPIK3CA samples were identified in HR+ disease, 10% of the cases occurred in TNBC. Within the mutPIK3CA cohort, tumor mutational burden high (TMB-H; defined as ≥10 mutations/MB) was detected in 11.5% of samples, while microsatellite instability high (MSI-H) was detected in 0.5%. MSI-H was detected at a higher frequency in TNBC compared to HR+. Overall, the most commonly co-mutated genes among mutPIK3CA, HER2- samples were TP53 (34.6%), CDH1 (21.6%), ESR1 (12.3%), KMT2C (11%), MAP3K1 (9.5%), ARID1A (8.1%), PTEN (6.8%), GATA3 (6.6%), NF1 (5.9%), and TBX3 (5.9%) among others (Table 1); some of these genes have previously been implicated in resistance to endocrine therapy or PI3K inhibitor. In addition, in HR+ disease, metastatic samples had a higher frequency of mutations in genes implicated in endocrine resistance, such as ESR1 (18.7% vs 1.9%), ERBB2 (3.3% vs 2.6%), NF1 (6.8% vs 2.6%), compared to primary tumors. We also identified copy number gains (CNG) in several cell cycle genes, including: CCND1 (15.2%), CDK4 (2.7%), and AURKA (2.6%) (Table 1). Finally, further analyses at the transcript-level are the subject of on-going research. Conclusions: Our study highlights that there is substantial genomic heterogeneity among mutPIK3CA, HER2- a/mBCs. Across a series of comparisons between primary and metastatic samples, as well as HR+ and TNBC subtypes, we identified a number of co-mutations that occur alongside mutPIK3CA and which could be potentially exploited by targeted therapies. Future studies are needed to assess the prognostic/predictive role of these and other candidate gene alterations. Table 1. Genomic features of mutPIK3CA, HER2– a/mBCPrimaryMetastaticTotalAny PIK3CA Mutation1255527782mutPIK3CA2204425629HER2– (n=176)HER2– (n=370)546HR+ HER2– 154 (88%)TNBC 22 (12%)HR+ HER2– 337 (91%)TNBC 33 (9%)TMB-H16 (10.3%)2 (9.1%)41 (12%)4 (12%)63 (11.5%)MSI-H1 (0.6%)1 (4.5%)0 (0%)1 (3.0%)3 (0.5%)Co-mutations (mutPIK3CA): n (%)TP5347 (30.5%)14 (63.6%)101 (30%)27 (81.8%)189 (34.6%)CDH137 (24%)1 (4.5%)75 (22.3%)5 (15.2%)118 (21.6%)KMT2C17 (11%)1 (4.5%)40 (11.9%)2 (6.1%)60 (11%)MAP3K117 (11%)1 (4.5%)31 (9.2%)1 (3%)50 (9.2%)ARID1A15 (9.7%)0 (0%)26 (7.7%)2 (6.1%)43(7.9%)PTEN12 (7.8%)1 (4.5%)21 (6.2%)3 (9.1%)37 (6.8%)GATA311 (7.1%)0 (0%)23 (6.8%)2 (6.1%)35 (6.6%)TBX311 (7.1%)1 (4.5%)19 (5.6%)1 (3%)32 (5.9%)NCOR12 (1.3%)1 (4.5%)18 (5.3%)0 (0%)21 (3.8%)FOXA17 (4.5%)2 (9.1%)10 (3%)1 (3%)20 (3.7%)MAP2K41 (0.6%)1 (4.5%)12 (3.6%)1 (3%)15 (2.7%)ESR13 (1.9%)0 (0%)63 (18.7%)1 (3%)67 (12.3%)PIK3R13 (1.9%)0 (0%)4 (1.2%)0 (0%)7 (1.3%)AKT11 (0.6%)0 (0%)1 (0.6%)0 (0%)2 (0.4%)RB15 (3.2%)1 (4.5%)8 (2.4%)1 (3%)15 (2.7%)NF14 (2.6%)3 (13.6%)23 (6.8%)2 (6.1%)32 (5.9%)ERBB24 (2.6%)4 (18.2%)11 (3.3%)2 (6.1%)21 (3.8%)CCND1 CNG22 (14%)0 (0%)61 (18%)0 (0%)83 (15.2%)AURKA CNG3 (1.9%)0 (0%)11 (3.3%)0 (0%)14 (2.6%)CDK4 CNG5 (3.2%)1 (4.5%)7 (2.1%)1 (3.0%)14 (2.6%)1any somatic variant detected in PIK3CA2somatic PIK3CA mutations among the 11 currently included in the alpelisib companion diagnostic (C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, and H1047Y) Citation Format: Jing Xi, Kathleen Harnden, Jingqin Luo, Greg S. Call, Elizabeth Mauer, Karyn Ronski, Cynthia X. Ma, Neil Vasan. Genomic landscape of HER2-negative advanced or metastatic breast cancer with PIK3CA gain-of-function mutations [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-09-04.
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Ahlkvist, L., K. Brown, and B. Ahrén. "Upregulated insulin secretion in insulin-resistant mice: evidence of increased islet GLP1 receptor levels and GPR119-activated GLP1 secretion." Endocrine Connections 2, no. 2 (June 2013): 69–78. http://dx.doi.org/10.1530/ec-12-0079.
Повний текст джерелаАнотація:
We previously demonstrated that the overall incretin effect and the β-cell responsiveness to glucagon-like peptide-1 (GLP1) are increased in insulin-resistant mice and may contribute to the upregulated β-cell function. Now we examined whether this could, first, be explained by increased islet GLP1 receptor (GLP1R) protein levels and, secondly, be leveraged by G-protein-coupled receptor 119 (GPR119) activation, which stimulates GLP1 secretion. Female C57BL/6J mice, fed a control (CD, 10% fat) or high-fat (HFD, 60% fat) diet for 8 weeks, were anesthetized and orally given a GPR119 receptor agonist (GSK706A; 10 mg/kg) or vehicle, followed after 10 min with gavage with a liquid mixed meal (0.285 kcal). Blood was sampled for determination of glucose, insulin, intact GLP1, and glucagon, and islets were isolated for studies on insulin and glucagon secretion and GLP1R protein levels. In HFD vs CD mice, GPR119 activation augmented the meal-induced increase in the release of both GLP1 (AUCGLP1 81±9.6 vs 37±6.9 pM×min, P=0.002) and insulin (AUCINS 253±29 vs 112±19 nM×min, P<0.001). GPR119 activation also significantly increased glucagon levels in both groups (P<0.01) with, however, no difference between the groups. By contrast, GPR119 activation did not affect islet hormone secretion from isolated islets. Glucose elimination after meal ingestion was significantly increased by GPR119 activation in HFD mice (0.57±0.04 vs 0.43±0.03% per min, P=0.014) but not in control mice. Islet GLP1R protein levels was higher in HFD vs CD mice (0.8±0.1 vs 0.5±0.1, P=0.035). In conclusion, insulin-resistant mice display increased islet GLP1R protein levels and augmented meal-induced GLP1 and insulin responses to GPR119 activation, which results in increased glucose elimination. We suggest that the increased islet GLP1R protein levels together with the increased GLP1 release may contribute to the upregulated β-cell function in insulin resistance.
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Hinsenveld, Wouter H., Inger R. de Ridder, Robert J. van Oostenbrugge, Jan A. Vos, Adrien E. Groot, Jonathan M. Coutinho, Geert J. Lycklama à Nijeholt, et al. "Workflow Intervals of Endovascular Acute Stroke Therapy During On- Versus Off-Hours." Stroke 50, no. 10 (October 2019): 2842–50. http://dx.doi.org/10.1161/strokeaha.119.025381.
Повний текст джерелаАнотація:
Background and Purpose— Endovascular treatment (EVT) of patients with acute ischemic stroke because of large vessel occlusion involves complicated logistics, which may cause a delay in treatment initiation during off-hours. This might lead to a worse functional outcome. We compared workflow intervals between endovascular treatment–treated patients presenting during off- and on-hours. Methods— We retrospectively analyzed data from the MR CLEAN Registry, a prospective, multicenter, observational study in the Netherlands and included patients with an anterior circulation large vessel occlusion who presented between March 2014 and June 2016. Off-hours were defined as presentation on Monday to Friday between 17:00 and 08:00 hours, weekends (Friday 17:00 to Monday 8:00) and national holidays. Primary end point was first door to groin time. Secondary end points were functional outcome at 90 days (modified Rankin Scale) and workflow time intervals. We stratified for transfer status, adjusted for prognostic factors, and used linear and ordinal regression models. Results— We included 1488 patients of which 936 (62.9%) presented during off-hours. Median first door to groin time was 140 minutes (95% CI, 110–182) during off-hours and 121 minutes (95% CI, 85–157) during on-hours. Adjusted first door to groin time was 14.6 minutes (95% CI, 9.3–20.0) longer during off-hours. Door to needle times for intravenous therapy were slightly longer (3.5 minutes, 95% CI, 0.7–6.3) during off-hours. Groin puncture to reperfusion times did not differ between groups. For transferred patients, the delay within the intervention center was 5.0 minutes (95% CI, 0.5–9.6) longer. There was no significant difference in functional outcome between patients presenting during off- and on-hours (adjusted odds ratio, 0.92; 95% CI, 0.74–1.14). Reperfusion rates and complication rates were similar. Conclusions— Presentation during off-hours is associated with a slight delay in start of endovascular treatment in patients with acute ischemic stroke. This treatment delay did not translate into worse functional outcome or increased complication rates.
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Burkhart, Scott O., Christine Ellis, and Troy M. Smurawa. "VESTIBULAR AND OCULAR MOTOR FINDINGS IN ACUTELY INJURED 8-12-YEAR-OLD PATIENTS FOLLOWING CONCUSSION." Orthopaedic Journal of Sports Medicine 7, no. 3_suppl (March 1, 2019): 2325967119S0000. http://dx.doi.org/10.1177/2325967119s00005.
Повний текст джерелаАнотація:
Background: Vestibular and ocular motor deficits have been recognized as a key marker of the pathophysiology consistent with the diagnosis of concussion (Grady, 2010). Previous studies have been performed detailing the validity and clinical benefit of vestibular and ocular motor assessments (Corwin et al., 2015; Mucha et al., 2014). Recent guidelines and position statements have started recommending the use of vestibular and ocular motor assessment for pediatric patients (Matuszak et al., 2016), the most recent consensus statement recommending vestibular and ocular motor assessment by all practitioners within acute concussion settings (McCrory et al., 2017). Unfortunately, very little data exists with respect to vestibular and ocular motor performance in concussion patients between 8-12 years of age. The current study included a standardized administration of the Vestibular Ocular Motor Screening (VOMS) and the King-Devick Test (KD) in a sample of patients diagnosed with concussion and evaluated in an outpatient concussion clinic within 7 days of their initial date of injury. This study intended to evaluate performance on the VOMS and KD in an injured sample of patients 8-12 years of age. Methods: Pediatric patients diagnosed with concussion (n = 45) presenting to an outpatient concussion clinic within 7 days from their initial date of injury were administered a standardized version of the VOMS and KD. Patients were administered the VOMS and KD by certified athletic trainers educated and trained on administration. The VOMS consists of nine measures and was validated by the University of Pittsburgh (Mucha et al., 2014) as a symptom provocation measure with a symptom rating of 0-10 with convergence measured in centimeters, and scores of 6 cm or greater being indicative of abnormal. The KD is an ocular motor performance measure and has previously demonstrated reliability, sensitivity and specificity with respect to concussion diagnosis (Hecimovich et al., 2018). Demographic, acute injury, and baseline values were summarized using descriptive statistics. Point estimates and 95% confidence intervals were calculated for all end points. Pearson correlations were calculated based numerical values from the VOMS and KD data. Results: The total sample consisted of 14 females and 31 males, with a mean age of 10.6 + 1.4 years. 20% of the subjects (n = 9) reported a prior history of concussion with a total of 17 previous concussions reported. 13.3% of the sample (n = 6) reported a history of migraine and 4.4% (n = 2) reported a history of psychiatric diagnosis. Acute self-reported injury data based on signs and symptom markers were calculated including; dizziness (66.6%, n = 30), headache (82.2%, n = 37), vision problems (42.2%, n = 19), amnesia (35.5%, n = 16), and loss of consciousness (22.2%, n = 10). Descriptive statistics for baseline VOMS symptoms were recorded; headache (mean = 3.2 + 2.7, CI = 2.8-3.6), dizziness (mean = 1.3 + 1.7, CI = 1.1 -1.5) nausea (mean = 0.7 + 1.6, CI = 0.5-0.9), and fogginess (mean = 1.1 + 2.0, CI = 0.8 -1.4). VOMS convergence in centimeters across trials; T1 (mean = 5.1 + 5.2, CI = 4.6-5.9), T2 (mean = 6.2 + 5.8, CI = 5.3-7.1), and T3 (mean = 7.1 + 6.9, CI = 6.1-8.1). KD time in seconds; card 1 (mean = 22.4 + 9.5, CI = 21-23.8), card 2 (mean = 23.1 + 9.5, CI = 21.7-24.5), card 3 (mean = 27.2 + 9.3, CI = 25.8-28.6), and total (mean = 72.8 + 27.3, CI = 68.7-76.9). Pearson correlations revealed strong correlations across VOMS symptoms; headache (r = 0.89-0.99), dizziness (r = 0.78-0.98), nausea (r = 0.88-0.98), and fogginess (r = 0.89-0.98). Moderate correlations between KD time and convergence distance were observed; KD card 1 (convergence T1, r = 0.61, convergence T2, r = 0.58, convergence T3, r = 0.49), KD card 2 (convergence T1, r = 0.62, convergence T2, r = 0.58, convergence T3, r = 0.48), and KD total time (convergence T1, r = 0.59, convergence T2, r = 0.54, convergence T3, r = 0.46). Conclusion: To the best knowledge of the authors involved, this study is the first of its kind to explore the performance on the VOMS and KD in a sample of acutely injured (< 7 days) 8-12-year-old patients diagnosed with concussion. Several notable findings were observed. Headache was the most predominant symptom reported during VOMS administration and remained significantly higher than the other symptoms of dizziness, nausea, and fogginess. This finding may be the byproduct of increased difficulty in symptom description between the ages of 8-12. Further, correlations within symptoms were strong suggesting throughout VOMS administration symptoms remain relatively stable. Lastly, moderate relationships were noted between convergence on the VOMS and KD time scores. This is likely a result of both measures addressing ocular motor functioning but differing based on data medium (centimeters versus seconds). The current study was limited based on sample size and further data is necessary to draw larger conclusions based on 8-12-year-old injured VOMS and KD performance.
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Falchook, Gerald, Hui Gan, Siqing Fu, Meredith McKean, Arun Azad, David Sommerhalder, Judy Wang, et al. "481 Phase 1/2 study of THOR-707 (SAR444245), a pegylated recombinant non-alpha IL-2, as monotherapy and in combination with pembrolizumab or cetuximab in patients (pts) with advanced solid tumors." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A511. http://dx.doi.org/10.1136/jitc-2021-sitc2021.481.
Повний текст джерелаАнотація:
BackgroundTHOR-707 (SAR444245) is a recombinant human IL-2 molecule irreversibly bound to a PEG chain to block alpha-binding while retaining near-native affinity for beta/gamma IL-2 receptor subunits. We report updated results from the ongoing HAMMER phase 1/2 trial.MethodsSAR444245 was given via IV infusion as monotherapy Q2W [A] or Q3W [B], with pembrolizumab 200mg IV Q3W [C], or Q3W with cetuximab 400mg/m2 IV on D1 then 250mg/m2 IV QW [D] after pre-medication and peri-infusion hydration. A 3+3 design was used to identify the MTD/RP2D in pts with advanced solid tumors. Key objectives included assessments of safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD).Results68 pts, median age 61.5 (37–78) yrs with median 3 (1–10) prior therapies enrolled. Most common tumors: melanoma (n=10), colorectal (n=11). Doses tested by cohort: [A]: 8–16 µg/kg (n=9); [B]: 8–40 µg/kg (n=29); [C]: 8–32 µg/kg (n=20); [D]: 16–24 µg/kg (n=10). The most common (>30%) AEs included pyrexia (52.5%), nausea (50.0%), flu-like symptoms (44.1%), vomiting (36.8%), chills (32.4%), fatigue (32.4%), AST elevation (30.9%). AEs generally resolved promptly with supportive care. Grade(G) 3/4 (>5%) related AEs included ALT/AST elevation (5.9%), and decreased lymphocyte count (26.5% within first 24 hrs, recovering by 48–72 hrs, this lymphocyte migration is mechanistically consistent with immune cell margination). G3/4 CRS was observed in 2 pts. Two DLTs occurred: G3 infusion reaction (32 µg/kg [B]) and G3 AST/ALT/G2 bilirubin elevation with G2 CRS (24 µg/kg [C]). No vascular leak syndrome, QTc prolongation, cardiac, or end organ toxicity was observed. Half-life was ~10 h. Sustained increases in CD8 T and NK cells were observed (fold relative to baseline): monotherapy (1–9.4x and 2–43.3x); with pembrolizumab (0.5–5.78x and 1.5–26.9x); with cetuximab (1.3–7.57x and 3.6–45.4x). Max CD4 and eosinophils increased to 136 cell/µL and 1078 cell/µL. No IL-5 elevation or ADAs were observed. Transient IL-6 increases in 4 pts (500, 627, 1000, 1100 pg/mL) were not associated with AEs. Four pts had confirmed PRs (1 PD1-treated SCC, unknown primary [B]; 2 PD1-naïve BCC and 1 PD1-treated HNSCC [C]); 3 pts had minor responses -- prostate (-24%) and PD1-treated melanoma (-17%) [B]; PD1-treated NSCLC (¬-29%) [C] -- after ≥2 scans. 23 pts completed ≥5 cycles.ConclusionsSAR444245 was well tolerated and demonstrated antitumor activity in heavily pretreated patients, including prior checkpoint inhibitor therapy. Clinical safety, efficacy and PD suggest a wide therapeutic window. Combination with pembrolizumab and cetuximab leveraged SAR44245’s effects on CD8 T and NK cells.Trial RegistrationNCT04009681Ethics ApprovalThe clinical trial was approved by each institutions ethics’ and review board prior to beginning study enrollment.
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Méndez-Calderón, C. E., C. R. Lazzarotto, L. H. Aguiar, F. L. Ongaratto, K. C. S. Tavares, M. S. Alves, S. Gaudencio-Neto, et al. "157 EFFECT OF FSH STARVATION (COASTING) FOLLOWING SUPEROVULATION ON OOCYTE COMPETENCE AND CLONING EFFICIENCY IN GOATS." Reproduction, Fertility and Development 29, no. 1 (2017): 187. http://dx.doi.org/10.1071/rdv29n1ab157.
Повний текст джерелаАнотація:
Oocyte competence plays a key role in the overall efficiency of reproductive biotechnologies. In cattle, FSH starvation following superovulation (coasting) improves oocyte competence, blastocyst yield and pregnancy outcome when used in ovum pickup-in vitro production programs. The aim of this study was to compare the effect of coasting after exogenous FSH stimulation on goat oocyte quality and competence to support in vitro maturation and in vivo embryo development following cloning procedures in goats. Donor and recipient preparation, cumulus-oocyte complex (COC) retrieval and selection, IVM, cloning by somatic cell nuclear transfer, embryo transfer, and pregnancy diagnosis (Days 23–26) were performed according to our established procedures [Martins et al. 2016 doi: 10.1089/cell.2015.0082]. Cumulus-oocyte complexes were obtained in vivo from 71 cycling FSH-stimulated mature Nubian-crossed goats, combined or not with FSH starvation (coasting period). Donor females were oestrous synchronized with a progesterone intravaginal insert (Day 0). On Day 10, a 0.75-mg D-cloprostenol dose was given IM, with the onset of the superovulation treatment, composed of five 20-mg FSH doses (Folltropin®, Bioniche Animal Health, Pullman, WA, USA), via IM at 12-h intervals. Donors were subjected to laparoscopic ovum pickup either 9 h (control group, n = 36) or 21 h (coasting group, n = 35) after the last FSH dose, respectively. Skin fibroblast cell cultures from a male neonate were co-transfected with a mammary gland expression vector with the human lactoferrin (hLF) coding sequence and with CRISPR/Cas9 system either for the PRNP prion gene or the Rosa26 locus. A bi-allelic hLF-PRNP and a mono-allelic hLF-Rosa26 cell colony were used for cloning. Data were compared by ANOVA or the χ2 test (P < 0.05). No differences were observed between control and coasting for number of follicles (18.7 ± 1.4 v. 21.2 ± 1.7), and retrieved (17.3 ± 1.2 v. 20.7 ± 1.9), viable (15.9 ± 1.1 v. 19.6 ± 1.8), Grade I (1.5 ± 0.3 v. 2.5 ± 0.5), and Grades III+IV (6.0 ± 0.6 v. 5.7 ± 0.7) COC, as well as for COC retrieval (92.4%, 574/621 v. 94.5%, 685/725) and fusion (62.8%, 273/435 v. 61.3%, 311/507) rates, respectively, irrespective of the cell lines. However, the coasting group rendered higher number of Grade II COC (11.3 ± 1.2 v. 8.4 ± 0.7), number and proportion of Grades I+II COC (13.9 ± 1.5 v. 9.9 ± 0.9, 70.8% v. 62.4%), and maturation rate (70.9% v. 65.4%) than the control group, respectively, for a lower proportion of Grades III+IV (29.2% v. 37.6%, respectively). A total of 213 and 233 Day-1 cloned embryos from the control and the coasting groups were transferred to 18 (96/9 hLF-PRNP and 117/9 hLF-Rosa26 cells) and 19 (128/11 hLF-PRNP and 105/8 hLF-Rosa26 cells) female recipients, respectively, resulting in 1/9 (11.1%) and 4/11 (36.4%) pregnancies from the hLF-PRNP cells, and 3/9 (33.3%) and 3/8 (37.5%) from the hLF-Rosa26 cells, for the control (4/18, 22.2%) and coasting (7/19, 36.8%) groups, respectively, for an overall pregnancy rate of 29.7% (11/37). In conclusion, the use of coasting improved oocyte quality and in vitro maturation rate, also appearing to increase pregnancy outcome after goat cloning.
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Sader, Helio S., Mariana Castanheira, Cecilia G. Carvalhaes, Timothy B. Doyle, and Rodrigo E. Mendes. "1261. Antimicrobial Activity of Aztreonam-Avibactam against Gram-negative Bacteria Isolated from Patients Hospitalized with Pneumonia in Europe, Latin America, and Asia in 2019." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S647. http://dx.doi.org/10.1093/ofid/ofaa439.1445.
Повний текст джерелаАнотація:
Abstract Background Aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBL). Avibactam (AVI) is a non-β-lactam β-lactamase inhibitor that inhibits serine carbapenemases (CPEs), such as ESBLs, KPCs, AmpC, and some OXAs. ATM-AVI is under clinical development for treatment of serious infections caused by Gram-negative bacteria (GNB), including MBL-producers. Methods 2,582 GNB (1,630 Enterobacterales [ENT] and 952 nonfermentative-GNB) were consecutively collected (1/patient) from 56 medical centers located in Western Europe (W-EU; 22 centers in 10 nations), Eastern Europe (E-EU; 12 centers in 9 nations), Latin America (LATAM; 10 centers 6 nations), and the Asia-Pacific region (APAC; 12 centers in 8 nations) in 2019 and susceptibility (S) tested against ATM-AVI and comparators at a central laboratory by reference broth microdilution methods. Results Overall, 99.9% of ENT (MIC50/90, 0.06/0.25 mg/L), including 99.1% of carbapenem-resistant ENT (CRE; MIC50/90, 0.25/0.5 mg/L), were inhibited at an ATM-AVI MIC of ≤ 8 mg/L (Table). CRE rates were 1.4%, 23.7%, 6.3%, and 9.6% in W-EU, E-EU, LATAM, and APAC, respectively (6.9% overall). A CPE was identified in 95 of 113 CRE isolates (84.1%). These CPEs included NDM-like (31.0% of CRE), KPC-like (26.5%), OXA-48-like (24.8%), and VIM-like (7.1%). Six isolates produced 2 CPEs. The highest ATM-AVI MIC value among MBL-producers (n=43; MIC50/90, 0.12/0.5 mg/L) was 4 mg/L. Among P. aeruginosa, 75.1% were inhibited at ≤ 8 mg/L of ATM-AVI; S to meropenem (MEM), piperacillin-tazobactam, and ceftazidime were 69.4%, 72.5%, and 75.7%, respectively, and ranged from 64.3% in E-EU to 82.0% in W-EU. MEM non-S P. aeruginosa varied from 22.2% in W-EU to 54.8% in E-EU. ATM-AVI was highly active against S. maltophilia, inhibiting 95.0%, 100.0%, 100.0%, and 90.0% of isolates from W-EU, E-EU, LATAM, and APAC, respectively, at ≤8 mg/L. S. maltophilia S to cotrimoxazole were 90.0%, 97.7%, 85.7%, and 100.0% in W-EU, E-EU, LATAM, and APAC, respectively. ATM-AVI also was very active against Burkholderia spp. (highest MIC, 8 mg/L). Conclusion Our results support clinical development of ATM-AVI to treat pneumonia caused by ENT (including MBL-producers), P. aeruginosa, S. maltophilia, and Burkholderia spp. Table 1 Disclosures Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)
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Robson, Stephen C., Lyn S. Chitty, Stephen Morris, Talitha Verhoef, Gareth Ambler, Diana G. Wellesley, Ruth Graham, Claire Leader, Jane Fisher, and John A. Crolla. "Evaluation of Array Comparative genomic Hybridisation in prenatal diagnosis of fetal anomalies: a multicentre cohort study with cost analysis and assessment of patient, health professional and commissioner preferences for array comparative genomic hybridisation." Efficacy and Mechanism Evaluation 4, no. 1 (February 2017): 1–104. http://dx.doi.org/10.3310/eme04010.
Повний текст джерелаАнотація:
BackgroundCurrent pathways for testing fetuses at increased risk of a chromosomal anomaly because of an ultrasound anomaly involve karyotyping after rapid aneuploidy exclusion. Chromosomal microarray (CMA) may detect more clinically significant chromosomal imbalances than karyotyping but evidence to guide UK health service providers on whether or not CMA should replace karyotyping is limited.Objectives(1) To compare detection rates of copy number variants (CNVs) and laboratory turnaround times (TATs) by karyotyping and CMA in fetuses with ultrasound anomalies, (2) to calculate test costs and the cost per additional pathogenic CNV detected by CMA relative to karyotyping and (3) to determine what factors influence parents’ and health professionals’ choice and decision-making about CMA.DesignA multicentre experimental research cohort study with an additional cost analysis.SettingA total of 20 fetal medicine units and nine cytogenetic laboratories across England and Wales.ParticipantsWomen with a fetus undergoing quantitative fluorescent polymerase chain reaction (QF-PCR) and karyotyping for clinical indications with (1) one or more structural anomalies identified on ultrasound or (2) an isolated nuchal translucency (NT) of ≥ 3.5 mm.InterventionsKaryotyping and CMA after exclusion of major chromosomal anomalies by QF-PCR. The array design consisted of 8-plex 60,000 60-mer oligonucleotides with a backbone resolution of ≈75 kb.Main outcome measuresRates of abnormal karyotypes and pathogenic CNVs and variants of unknown significance on CMA. Laboratory TATs for karyotyping and CMA. Costs of karyotyping and CMA and cost per additional pathogenic CNV detected by CMA. Parent and health professional attitudes to CMA.ResultsOut of the 1718 probands recruited, 1123 cases with normal QF-PCR and both karyotype and CMA were available for analysis. In the group with structural anomalies (n = 629), CMA detected more CNVs [6.8%, 95% confidence interval (CI) 4.4% to 9.3%] and more pathogenic CNVs (3.5%, 95% CI 1.5% to 5.5%) than karyotyping. In the increased NT group (n = 494), CMA detected more CNVs (4.5%, 95% CI 1.8% to 7.1%) than karyotyping but not more pathogenic CNVs. Compared with karyotyping, median TAT was 3 days [interquartile range (IQR) 0–13 days] longer with CMA but when actual set-up to reporting times were compared, CMA was 5 days (IQR 2–8 days) quicker. Cost calculations of the respective pathways indicated that, per patient, CMA is on average £113 more costly than karyotyping. The incremental cost per extra pathogenic CNV detected by CMA was greater in the increased NT than the structural anomaly group (£9439 vs. £3635). Qualitative evaluation suggested that parents find CMA acceptable, despite the uncertainties it may introduce, and that in the main it is acceptable to health professionals and commissioners.ConclusionsCMA is a robust, acceptable and probably cost-effective method to detect more clinically significant chromosomal imbalances in the anomalous fetus. The results suggest that CMA should replace karyotyping in these care pathways.Future workThe application of CMA (and exome sequencing) on cell-free DNA in maternal plasma.Trial registrationCurrent Controlled Trials ISRCTN01058191.FundingThis project was funded by the Efficacy and Mechanism Evaluation programme, a MRC and NIHR partnership. The funder had no role in the identification, design and conduct of the study and the reporting of the analysis. The funder did recommend the inclusion of the cell-free DNA aspects of the EACH study. Funding was also received from the Great Ormond Street Biomedical Research Centre.
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Shojania, A. Majid. "Improvement of Myelodysplasia and Partial Correction of panhypogammaglobulinemia after IV IgG Infusions and Splenectomy." Blood 112, no. 11 (November 16, 2008): 5105. http://dx.doi.org/10.1182/blood.v112.11.5105.5105.
Повний текст джерелаАнотація:
Abstract A man born in 1951 underwent a bone marrow examination, on May 10, 1991, for investigation of his pancytopenia. The bone marrow slides were sent to me for interpretation. I made the diagnosis of myelodysplasia (refractory anemia without excess blast). The patient was subsequently referred to a hematologist in another hospital for further investigation and management. A repeat bone marrow aspiration and biopsy on May 30, 1991 again demonstrated myelodysplasia. Bone marrow biopsy, flow cytometry and cytogenetic studies were normal. His Hgb was 124 G/L, WBC 2.2 and platelet (Plt) 151 × 10e9/L. CT scan of the chest and abdomen showed mediastinal and retroperitoneal lymphadenopathy and marked splenomegaly suggestive of lymphoma. There was no symptoms suggestive of lymphoma. The patient was followed without any therapy. In March 2002 he was referred to an immunologist because of frequent episodes of pneumonias. He was found to have panhypogammaglobulinemia. The immunologist recommended monthly I V immunoglobulin(IgG). Initially the patient refused this treatment; but subsequently he agreed and he was sent to me on November 3, 2003 for consideration of monthly IV IgG infusion. Hgb 125 g/L, WBC 2.5 and Plt 112 ×10e9/L.IgG 2.31, IgA <0.07 and IgM 0.1 g/L, IgD<0.01 G/L and IgE <2 KU/L. Repeat bone marrow aspriration and biopsy in February 2002 was unchanged compared to those 1991 and cytogenetics and immunophenotyping were again normal. He was started on IV IgG 40 G Q 4-weeks. The dose was reduced to 30 G Q 4-weeks on April 30, 2004 and then reduced to 25 G Q 4-weeks on April 8, 2005. On March 12,2004 because the pancytopenia was getting worse and CT scan had shown increasing size of the spleen and nodes, repeat bone marrow examination was performed. The marrow aspirate showed normal morphology and no evidence of myelodysplasia, Bone marrow biopsy showed normocellular marrow with occasional granuloma but no evidence of lymphoma. On June 4,2004, he underwent splenctomy. The spleen, and hilar splenic nodes showed non-caseating granulomas consistent with sarcoidosis, but no evidence of lymphoma. Post splenctomy hematological parameters became normal. After September 30, 2005 no more IV IgG was infused. His IgG and IgM remained persistently above pretreatment level. The result of Immunoglobulin levels and CBC before and after therapy are shown in the Table below. Unfortunately in February 2007 he died suddenly from overwhelming pneumococcal infection, despite the fact that he was given pneumovax prior to splenectomy. Conclusion: Repeated IV IgG infusion in this case, caused partial improvement of IgG and IgM, and was possibly responsible for recovery from myelodysplasia. Date IgG (G/L) IgA (G/L) IgM (G/L) Hgb (G/L) WBC X10e9/L Plt ×10e9/L 20/12/01 2.7 <0.1 0.3 132 1.4 118 12/3/2002 2.7 0.1 0.3 5/11/2003 2.31 <0.07 0.1 125 2.5 112 25/11/05 5.91 <0.07 0.5 159 9.3 380 20/01/06 5.92 <0.07 0.76 156 10.3 359 31/03/06 5.59 0.11 0.54 155 10.1 414 5/1/2007 6.19 <0.07 0.5 155 12.7 626
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Kantarjian, Hagop M., Richard A. Larson, Francois Guilhot, Stephen G. O’Brien, and Brian J. Druker. "Declining Rates of Adverse Events (AEs), Rare Occurrence of Serious AEs (SAEs), and No Unexpected Long-Term Side Effects at 5 Years in Patients with Newly Diagnosed Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) Initially Treated with Imatinib (IM) in the International Randomized Study of Interferon vs STI571 (IRIS)." Blood 108, no. 11 (November 1, 2006): 2136. http://dx.doi.org/10.1182/blood.v108.11.2136.2136.
Повний текст джерелаАнотація:
Abstract The IRIS trial compared interferon alfa + cytarabine (IFN+Ara-C) and imatinib (IM) in patients (pts) with newly diagnosed CML-CP. Among 553 pts randomized to receive 400 mg IM, 157 (28%) discontinued for reasons which included AEs or deaths unrelated to CML and treatment (6%) and unsatisfactory therapeutic effect (11%). Only 2.4% discontinued due to drug-related AEs. The average daily dose was 389±71 mg, suggesting that no major dose modifications were required due to toxicity. In pts still on IM, the average doses was 382±50 mg. Average duration of exposure is 50 mos (median 60 mos). Table 1 summarizes the most frequently reported non-hematologic AEs (regardless of relationship to study drug) in pts who started IM therapy and those who were still on IM at 2 and 4 years (n=456 and 409 respectively). Table 1. AEs (≥ 20%) on First-Line Imatinib Therapy AE All grades N= 551 (%) All grades, after 2 yrs N = 456 (%) All grades, after 4 yrs N = 409 (%) Grades 3/4 N= 551 (%) Fluid retention 61.7 20.2 5.6 2.5 – Superficial edema 59.9 18.2 5.1 1.5 – Other fluid retention events 6.9 2.4 0.7 1.3 Nausea 49.5 15.4 3.4 1.3 Muscle cramps 49.2 22.8 7.3 2.2 Musculoskeletal pain 47.0 20.8 6.1 5.4 Diarrhea 45.4 23.0 5.1 3.3 Rash and related terms 40.1 13.8 2.4 2.9 Fatigue 38.8 11.4 2.9 1.8 Headache 37.0 12.1 3.4 0.5 Abdominal pain 36.5 15.4 3.4 4.2 Joint pain 31.4 9.2 2.0 2.5 Nasopharyngitis 30.5 14.3 3.7 0 Hemorrhage 28.9 14.3 5.1 1.8 Myalgia 24.1 4.6 1.5 1.5 Vomiting 22.5 9.2 3.7 2.0 Upper respiratory tract infection 21.2 11.2 2.7 0.2 Cough 20.0 7.7 3.4 0.2 Hematologic toxicities were the most frequently occurring grade 3/4 AEs (Table 2). Table 2. Grade 3/4 laboratory abnormalities on First-line Imatinib Overall N = 551 (%) After 2 years N= 456 (%) After 4 years N= 409 (%) Hematologic – Neutropenia 16.7 7 1.0 – Thrombocytopenia 8.9 1.5 0.2 – Anemia 4.4 1.8 0.5 Biochemical – ↑ SGOT/SGPT 5.3 0.4 0 – ↑Total bilirubin 1.1 0.4 0.2 The most frequent reported AEs as well as grade 3/4 hematological and biochemical toxicities were observed at decreasing frequencies throughout therapy. After 4 years, 8% of pts experienced an SAE, compared with 14%, 12%, 7.5%, and 9% during year one through four of therapy. Overall, only 6% of pts had SAEs considered related to study drug (1.5% pts after 4 years of IM). Congestive heart failure/cardiac dysfunction (incl. pulmonary edemas) were reported for 3% of pts (<1% grade 3/4) and pleural effusion in 1% (<1% grade 3/4). Despite much shorter average exposure (12 mos), similar % of these AEs were noted for IFN+Ara-C. Although it should be considered that pts more likely to experience grade 3/4 events may have discontinued from the study prematurely, the 5-year data with IM in pts with newly diagnosed CML-CP show declining frequencies of AEs and SAEs over time. Occurrence of SAEs and laboratory abnormalities with long-term follow-up was rare. No unexpected long-term side effects were noted. These results confirm the IM tolerability and safety profile for durations exceeding 4 years.
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Baker, J., J. Curtis, D. Chernoff, and M. George. "FRI0572 LEPTIN-ADJUSTMENT OF THE MULTI-BIOMARKER DISEASE ACTIVITY (MBDA) SCORE REDUCES THE INFLUENCE OF ADIPOSITY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 888–89. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2221.
Повний текст джерелаАнотація:
Background:Obesity and excess adiposity influence inflammatory markers and bias disease activity assessment, especially among women. A multi-biomarker disease activity (aMBDA) score has been developed to account for the effects of age, sex and adiposity (leptin) and improves prediction of radiographic damage progression.1Objectives:1) Determine if the adjusted measure demonstrates a reduced association with adiposity.2) Assess the impact of the leptin-adjustment on the score over the range of adiposity.3) Assess relationships between MBDA scores and clinical disease activity.Methods:Patients with rheumatoid arthritis (RA), ages 18-75 years, completed whole-body dual-energy x-ray absorptiometry to quantify fat mass indices (FMI, kg/m2). Age-, sex-, and race-specific Z-Scores were calculated based on the distributions in a healthy reference population. Disease activity was assessed with the CDAI and swollen joint count (SJC). Baseline van der Heijde-Sharpe (vdHS) scores were determined by a radiologist. MBDA assays were performed on stored serum samples. Descriptive statistics described relationships between the FMI Z-Score and the MBDA and the aMBDA. Clinical disease activity, SJC, and radiographic damage were also compared across MBDA score categories.Results:Of 104 participants (50% female), the mean (SD) age was 56.1 (12.5) and mean BMI was 28.8 (6.9) (Table 1). The unadjusted MBDA score was strongly associated with BMI among women (Women: Rho=0.46 [p< 0.001]; Men: Rho=-0.12), while the aMBDA was not associated with BMI in women and was inversely correlated in men (Women: Rho=0.17; Men: Rho=-0.32 [p=0.02]). The unadjusted MBDA score was also strongly associated with FMI Z-Score among women (Figure; Women: Rho=0.42 [p=0.002]; Men: Rho=-0.10; p=0.01). The aMBDA was not significantly associated with FMI Z-Score (Female: Rho= 0.17; Male: Rho=-0.26). Leptin-adjustment reduced the MBDA score in the highest quartile of FMI in women but not men, and increased the MBDA score in the lowest FMI quartiles in both women and men; these patients in the lowest FMI quartile had the highest median SJC (p=0.05 for men, p=0.78 for women; Figure). The aMBDA reclassified 4 women (8%) and 9 men (17%) into higher disease activity categories and 2 women (4%) and 2 men (4%) into lower categories. CDAI, SJC, and radiographic scores were similar across activity categories for the unadjusted MBDA score and aMBDA (Table 2).Table 1.Baseline Characteristics.MenWomenN5252Age (yrs)59.1 (11.5)53.0 (12.8)Black, N (%)13 (25%)19 (36%)BMI27.3 (5.4)30.3 (8.0)FMI Z-Score-0.28 (1.3)0.05 (1.1)DAS28(CRP)3.09 (1.13)3.21 (1.24)Disease Duration11.4 (10.9)11.6 (11.9)CRP, mg/dL0.8 (0.5, 1.2)0.8 (0.5, 1.4)CCP Positive, N (%)45 (87%)40 (78%)vdHS (N=93)13 (4, 73)10.5 (2, 47)HAQ0.71 (0.59)0.83, (0.67)MBDA40.0 (13.8)42.1 (16.6)aMBDA43.6 (13.4)42.1 (15.3)Leptin, ng/mL15.1 (21.5)48.9 (41.5)Table 2.Clinical assessments across MBDA score categories.CDAISJCvdHSMBDAaMBDAMBDAaMBDAMBDAaMBDAMBDA CategoryLow14.6 (10.9)13.9 (9.9)2 (1, 5)2 (1, 5)9 (1, 33.5)9 (3, 32)Moderate13.2 (10.0)14.4 (11.4)2 (0, 5)3 (0, 6)10 (4, 49)10 (2, 53)High18.4 (12.3)17.7 (11.8)4 (1, 8)5 (2, 7)20.5 (5, 70.5)18 (4, 73)Conclusion:Leptin-adjustment of the MBDA score reduced bias related to excess adiposity in women with RA. Adjustment results in lower MBDA scores in women with greater adiposity, and higher MBDA scores in women and men with lesser adiposity. The aMBDA may reduce misclassification due to excess adiposity and improve identification of active disease among patients with lower adiposity. High aMBDA scores among men with low adiposity may reflect severe disease or excess comorbidity in this group.References:[1] Curtis et al.Rheumatology (Oxford) 2018. PMID: 30590790Figure.Impact of Adjustment on MBDA Score by FMI Z-Score Quartile.Disclosure of Interests:Joshua Baker Grant/research support from: Myriad RBM, Consultant of: Bristol-Myers Squib, Burns-White LLC, Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, David Chernoff Employee of: Myriad, Michael George Grant/research support from: Bristol Myers Squibb, Consultant of: AbbVie
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Santos-García, D., T. de Deus Fonticoba, E. Suárez Castro, A. Aneiros Díaz, and D. McAfee. "5-2-1 Criteria: A Simple Screening Tool for Identifying Advanced PD Patients Who Need an Optimization of Parkinson’s Treatment." Parkinson's Disease 2020 (March 24, 2020): 1–6. http://dx.doi.org/10.1155/2020/7537924.
Повний текст джерелаАнотація:
Objective. 5- (5 times oral levodopa tablet taken/day) 2- (2 hours of OFF time/day) 1- (1 hour/day of troublesome dyskinesia) criteria have been proposed by a Delphi expert consensus panel for diagnosing advanced Parkinson’s disease (PD). The aim of the present study is to compare quality of life (QoL) in PD patients with “5-2-1 positive criteria” vs QoL in PD patients without “5-2-1 positive criteria” (defined as meeting ≥1 of the criteria). Methods. This is a cross-sectional, observational, monocenter study. Three different instruments were used to assess QoL: the 39-Item Parkinson’s Disease Quality of Life Questionnaire Summary Index Score (PDQ-39SI); a subjective rating of perceived QoL (PQ-10); and the EUROHIS-QOL 8-Item Index (EUROHIS-QOL8). Results. From a cohort of 102 PD patients (65.4 ± 8.2 years old, 53.9% males; disease duration 4.7 ± 4.5 years), 20 (19.6%) presented positive 5-2-1 criteria: 6.9% for 5, 17.6% for 2, and 4.9% for 1. 37.5% (12/32) and 25% (5/20) of patients with motor complications and dyskinesia, respectively, presented 5-2-1 negative criteria. Both health-related (PDQ-39SI, 25.6 ± 14 vs 12.1 ± 9.2; p<0.0001) and global QoL (PQ-10, 6.1 ± 2 vs 7.1 ± 1.3; p=0.007; EUROHIS-QOL8, 3.5 ± 0.5 vs 3.7 ± 0.4; p=0.034) were worse in patients with 5-2-1 positive criteria. Moreover, nonmotor symptoms burden (Non-Motor Symptoms Scale total score, 64.8 ± 44.8 vs 39.4 ± 35.1; p<0.0001) and autonomy for activities of daily living (ADLS scale, 73.5 ± 13.1 vs 89.2 ± 9.3; p<0.0001) were worse in patients with 5-2-1 positive criteria. Patient’s principal caregiver’s strain (Caregiver Stain Index, 4.3 ± 3 vs 1.5 ± 1.6; p<0.0001), burden (Zarit Caregiver Burden Inventory, 28.4 ± 12.5 vs 10.9 ± 9.8; p<0.0001), and mood (Beck Depression Inventory II, 12.2 ± 7.2 vs 6.2 ± 6.1; p<0.0001) were worse in patients with 5-2-1 positive criteria as well. Conclusions. QoL is worse in patients meeting ≥1 of the 5-2-1 criteria. This group of patients and their caregivers are more affected as a whole. These criteria could be useful for identifying patients in which it is necessary to optimize Parkinson’s treatment.
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Blum, D., J. Hess, A. Omlin, G. Jurt, and F. Strasser ABHPM. "Comprehensive cancer cachexia staging and its impact in the outpatient oncology setting: A phase II study." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e20530-e20530. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e20530.
Повний текст джерелаАнотація:
e20530 Background: Symptom management in advanced cancer is based on appropriate and feasible syndrome staging. To test whether 1. various factors predict involuntary weight loss [WL], 2. patients [pts] attending a cachexia clinic [CC] improve nutritional intake [NI], and 3. eating-related distress [ERD] is a consequence of cachexia or psychological issues. Methods: The multidisciplinary CC (nurse, nutritionist, psycho-oncologist, palliative cancer care physician) applies standardized assessments (Symptom Visual Analogue Scales [VAS, 0=none, 10=severe], 2-day NI diary [% of calculated needs: calories, protein], secondary causes for impaired NI, weight history (2 months WL), Body Mass Index [BMI], C-reactive Protein [mg/dl, normal 8), ERD-VAS, Hospital Anxiety Depression Scale, spirituality [FICA]). Interventions include nutritional counseling, palliative cancer care and psychosocial supportive measures. Descriptive analysis, Spearman‘s Rank correlation and Factor analysis (Eigenvalue >1) were performed. Results: 58 pts (age 65 years [mean; range: 38, 85]; 28F/30M; cancer types: 24 GI, 13 GU, 12 lung/ENT, 9 other; survival 151 days [7, 776]) had 6.9% WL (-6, 22; 21%<2%), 21 kg/m2 BMI (15, 26), 52 CRP (1, 272; 32% normal), 5.6 anorexia, 1.6 anxiety, 6 HADS-A, 1.3 depression, 9 HADS-D, 68% of NI needs (1466kcal [400, 2700], 47g protein [15, 108]). WL correlated with NI kcal (r=-.29, p=.038) and protein (-.3,.035), not anorexia (.16), BMI (.032) or CRP (-.08); a 2 factor model (NI/anorexia/WL [.83/.79/.70], CRP/BMI [.86/.75] explains 67% variability. At second visit (21 days; 13, 64) 15/19 pts increased kcal (400kcal) and 15/16 protein (32g) NI, 6/17 weight. ERD correlated with anorexia (r=.56, p=.001) and depression (.48,.002), not anxiety (.23), WL (.038) or survival (-.15). A 3 factor model (ERD/anxiety/depression [.71/.85/.92], anorexia/survival [.82/.65], WL [.84]) explains 75% variability. Conclusions: A combination of clinical variables seems needed to characterize patients with involuntary WL. Most patients attending 2 consecutive cachexia clinic visits respond to multidimensional interventions. ERD seems to be associated both with loss of appetite and depression, not by WL or survival. Further testing of this intervention seems justified. [Table: see text]