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1

Mullins, Ewen. "Engineering for disease resistance: persistent obstacles clouding tangible opportunities." Pest Management Science 71, no. 5 (April 2, 2015): 645–51. http://dx.doi.org/10.1002/ps.3930.

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Skoglund, Kristofer, Annika Rosengren, Georgios Lappas, Maria Fedchenko, and Zacharias Mandalenakis. "Long-term survival in patients with isolated pulmonary valve stenosis: a not so benign disease?" Open Heart 8, no. 2 (September 2021): e001836. http://dx.doi.org/10.1136/openhrt-2021-001836.

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Background and objectivesDuring the last decades, the survival rates in patients with congenital heart disease have increased dramatically, particularly in patients with complex heart malformations. However, the survival in patients with simple defects is still unknown. We aimed to determine the characteristics and the risk of mortality in patients with isolated pulmonary valve stenosis (PS).MethodsSwedish inpatient, outpatient and cause of death registries were used to identify patients born between 1970 and 2017 with a diagnosis of PS, without any other concomitant congenital heart lesion. For each patient with PS, 10 control individuals without congenital heart disease were matched by birth year and sex from the total population registry. We used median-unbiased method and Kaplan-Meier survival analysis to examine the risk of mortality.ResultsWe included 3910 patients with PS and 38 770 matched controls. The median age of diagnosis of PS was 0.7 years (IQR 0.3–7.0). During a median follow-up of 13.5 years (IQR 6.5–23.5), 88 patients with PS and 192 controls died; 500 patients with PS (12%) underwent at least one transcatheter or surgical valve intervention. The overall mortality rate was significantly higher in patients with PS compared with matched controls (HR 4.67, 95% CI 3.61 to 5.99, p=0.001). Patients with an early diagnosis of PS (0–1 year) had the highest risk of mortality (HR 10.99, 95% CI 7.84 to 15.45).ConclusionsIn this nationwide, register-based cohort study, we found that the risk of mortality in patients with PS is almost five times higher compared with matched controls. Patients with an early diagnosis of PS appears to be the most vulnerable group and the regular follow-up in tertiary congenital heart units may be the key to prevention.
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3

Milik, Mariola. "Antropologia Thomasa Keatinga." Polonia Sacra 25, no. 1 (April 30, 2021): 99. http://dx.doi.org/10.15633/ps.3910.

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4

Zhang, Wanna, Long Ma, Feng Zhong, Yanan Wang, Yuyuan Guo, Yanhui Lu, and Gemei Liang. "Fitness costs of reproductive capacity and ovarian development in aBt-resistant strain of the cotton bollwormHelicoverpa armigera(Hübner) (Lepidoptera: Noctuidae)." Pest Management Science 71, no. 6 (October 1, 2014): 870–77. http://dx.doi.org/10.1002/ps.3900.

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5

Li, Jingjing, Xiaomin Li, Rune Bai, Yan Shi, Qingbo Tang, Shiheng An, Qisheng Song, and Fengming Yan. "RNA interference of the P450CYP6CM1gene has different efficacy in B and Q biotypes ofBemisia tabaci." Pest Management Science 71, no. 8 (October 8, 2014): 1175–81. http://dx.doi.org/10.1002/ps.3903.

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6

Gomez-Polo, Priscila, Oscar Alomar, Cristina Castañé, Jonathan G. Lundgren, Josep Piñol, and Nuria Agustí. "Molecular assessment of predation by hoverflies (Diptera: Syrphidae) in Mediterranean lettuce crops." Pest Management Science 71, no. 9 (October 27, 2014): 1219–27. http://dx.doi.org/10.1002/ps.3910.

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Tuan, Shu-Jen, Chung-Chieh Lee, and Hsin Chi. "Population and damage projection of Spodoptera litura (F.) on peanuts (Arachis hypogaea L.) under different conditions using the age-stage, two-sex life table." Pest Management Science 70, no. 12 (November 3, 2014): 1936. http://dx.doi.org/10.1002/ps.3920.

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Cocco, Arturo, Giuseppe Serra, Andrea Lentini, Salvatore Deliperi, and Gavino Delrio. "Spatial distribution and sequential sampling plans forTuta absoluta(Lepidoptera: Gelechiidae) in greenhouse tomato crops." Pest Management Science 71, no. 9 (December 1, 2014): 1311–23. http://dx.doi.org/10.1002/ps.3931.

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9

Nauen, Ralf, Peter Jeschke, Robert Velten, Michael E. Beck, Ulrich Ebbinghaus‐Kintscher, Wolfgang Thielert, Katharina Wölfel, Matthias Haas, Klaus Kunz, and Georg Raupach. "Flupyradifurone: a brief profile of a new butenolide insecticide." Pest Management Science 71, no. 6 (November 27, 2014): 850–62. http://dx.doi.org/10.1002/ps.3932.

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10

Perina, Fabiano J., Douglas C. Amaral, Rafael S. Fernandes, Claudia RG Labory, Glauco A. Teixeira, and Eduardo Alves. "Thymus vulgarisessential oil and thymol againstAlternaria alternata(Fr.) Keissler: effects on growth, viability, early infection and cellular mode of action." Pest Management Science 71, no. 10 (December 4, 2014): 1371–78. http://dx.doi.org/10.1002/ps.3933.

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11

Forster, W. Alison, and Mark O. Kimberley. "The contribution of spray formulation component variables to foliar uptake of agrichemicals." Pest Management Science 71, no. 9 (November 28, 2014): 1324–34. http://dx.doi.org/10.1002/ps.3934.

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12

Duke, Stephen O. "A Growth Year forPest Management Science." Pest Management Science 71, no. 1 (December 8, 2014): 1–2. http://dx.doi.org/10.1002/ps.3935.

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13

Afifi, Maha, Elizabeth Lee, Lewis Lukens, and Clarence Swanton. "Maize (Zea mays) seeds can detect above-ground weeds; thiamethoxam alters the view." Pest Management Science 71, no. 9 (December 12, 2014): 1335–45. http://dx.doi.org/10.1002/ps.3936.

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14

van Wijngaarden, René PA, Lorraine Maltby, and Theo CM Brock. "Acute tier-1 and tier-2 effect assessment approaches in the EFSA Aquatic Guidance Document: are they sufficiently protective for insecticides?" Pest Management Science 71, no. 8 (November 25, 2014): 1059–67. http://dx.doi.org/10.1002/ps.3937.

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15

Velasco-Hernández, María Concepción, Ricardo Ramirez-Romero, Carla Sánchez-Hernández, Antonio Biondi, Alejandro Muñoz-Urias, and Nicolas Desneux. "Foraging behaviour of the parasitoidEretmocerus eremicusunder intraguild predation risk byMacrolophus pygmaeus." Pest Management Science 71, no. 9 (December 1, 2014): 1346–53. http://dx.doi.org/10.1002/ps.3938.

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16

Huitu, Otso, and Toni Laaksonen. "Vertebrate pest management: diverse solutions for diverse problems." Pest Management Science 71, no. 2 (January 2, 2015): 165. http://dx.doi.org/10.1002/ps.3939.

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Sandi Ramadhan, Lutfi Afifah, Satriyo Restu Adhi, and Budi Irfan. "INTENSITAS PENYAKIT TANAMAN PADI (Oryza sativa L.) VARIETAS CIHERANG PADA APLIKASI BEBERAPA TEKNIK PENGENDALIAN." Jurnal Agrotech 13, no. 2 (December 31, 2023): 127–34. http://dx.doi.org/10.31970/agrotech.v13i2.148.

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Teknik pengendalian penyakit tanaman dapat memengaruhi intensitas penyakit. Penelitian ini bertujuan mendapatkan teknik pengendalian terbaik yang dapat menekan intensitas penyakit pada tanaman padi (Oryza sativa L.) varietas Ciherang. Metode penelitian yang digunakan adalah metode eksperimen, dengan rancangan acak kelompok (RAK) faktor tunggal, terdiri dari 4 perlakuan dan 6 ulangan. Perlakuan teknik pengendalian terdiri dari kontrol (K), pengendalian kombinasi (PK), pengendalian biointensif (PB) dan pengendalian sintetis (PS). Data hasil pengamatan dianalisis dengan sidik ragam dan apabila hasilnya berbeda nyata, maka diuji lanjut dengan uji beda nyata terkecil (BNT) pada taraf 5%. Hasil penelitian menunjukkan, terdapat pengaruh nyata pada intensitas penyakit blas (Pyricularia oryzae), hawar daun bakteri (Xanthomonas oryzae), dan hawar daun pelepah (Rhizoctonia solani). Perlakuan PS memberikan hasil terendah terhadap insidensi penyakit blas (39,3-37,6%), insidensi hawar daun bakteri (15,5-54,5%), insidensi hawar daun pelepah (0,3-60,6%), severitas penyakit blas (31,1-51,1%), severitas penyakit hawar daun bakteri (14,5-39,0%), dan severitas hawar daun pelepah (0,2-25,8%).
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18

Park, Kwon Moo, Sun-Don Kim, Jin Bong Park, Sung-Jong Hong, and Pan Dong Ryu. "Electrophysiological Properties of Ion Channels in Ascaris suum Tissue Incorporated into Planar Lipid Bilayers." Korean Journal of Parasitology 59, no. 4 (August 18, 2021): 329–39. http://dx.doi.org/10.3347/kjp.2021.59.4.329.

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Ion channels are important targets of anthelmintic agents. In this study, we identified 3 types of ion channels in Ascaris suum tissue incorporated into planar lipid bilayers using an electrophysiological technique. The most frequent channel was a large-conductance cation channel (209 pS), which accounted for 64.5% of channels incorporated (n=60). Its open-state probability (Po) was ~0.3 in the voltage range of –60~+60 mV. A substate was observed at 55% of the main-state. The permeability ratio of Cl- to K+ (PCl/PK) was ~0.5 and PNa/PK was 0.81 in both states. Another type of cation channel was recorded in 7.5% of channels incorporated (n=7) and discriminated from the large-conductance cation channel by its smaller conductance (55.3 pS). Its Po was low at all voltages tested (~0.1). The third type was an anion channel recorded in 27.9% of channels incorporated (n=26). Its conductance was 39.0 pS and PCl/PK was 8.6±0.8. Po was ~1.0 at all tested potentials. In summary, we identified 2 types of cation and 1 type of anion channels in Ascaris suum. Gating of these channels did not much vary with voltage and their ionic selectivity is rather low. Their molecular nature, functions, and potentials as anthelmintic drug targets remain to be studied further.
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Paduano, Sergio, Roberto Rongo, Rosaria Bucci, Giuseppe Carvelli, and Iacopo Cioffi. "Impact of functional orthodontic treatment on facial attractiveness of children with Class II division 1 malocclusion." European Journal of Orthodontics 42, no. 2 (October 5, 2019): 144–50. http://dx.doi.org/10.1093/ejo/cjz076.

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Summary Background/objectives Whether orthodontic treatment with functional appliances improves facial aesthetics is still under debate. This study aimed to determine whether functional orthodontic treatment improves the facial attractiveness of patients with Class II division 1 malocclusion. Materials/method Extraoral lateral photographs of 20 children with Class I (CLI, 11.7 ± 0.8 years), and before (T1) and after treatment (T2) photographs of patients with Class II division 1 (CLII T1 and CLII T2; mean age ± SD = 11.1 ± 0.6 years) treated with functional appliances, were transformed into black silhouettes. Three panels of examiners including 30 orthodontists (39.0 ± 10.1 years), 30 dentists (40.0 ± 9.7) and 30 laypersons (39.0 ± 9.2) evaluated the attractiveness of patients’ silhouettes using a 100-mm visual analogue scale, and the sagittal position of patients’ upper lip, lower lip, and chin using a 3-point Likert scale. Two-way ANOVA and a chi-square test were used to test differences among groups. Statistically significance was set as P < 0.05. Results The silhouettes of CLII T2 individuals were more attractive than those of the other groups (all Ps < 0.001). The upper lip, lower lip, and the chin of these individuals were judged to be normally positioned in 69.5 per cent, 74.9 per cent, and 72.3 per cent of the assessments, respectively (all Ps < 0.05). Limitations This study did not account for the psychological profile of the examiners, which may have affected the ratings. Conclusions/implications Orthodontic treatment with functional appliances is associated with a superior facial profile attractiveness. Functional treatment should be considered as a treatment option to improve the facial appearance of children with Class II division 1 malocclusion.
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Chokshi, Rikki, Masayuki Matsushita, and J. Ashot Kozak. "Sensitivity of TRPM7 channels to Mg2+ characterized in cell-free patches of Jurkat T lymphocytes." American Journal of Physiology-Cell Physiology 302, no. 11 (June 1, 2012): C1642—C1651. http://dx.doi.org/10.1152/ajpcell.00037.2012.

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Transient receptor potential melastatin 7 (TRPM7) channels were originally identified electrophysiologically when depletion of cytosolic Mg2+ resulted in the gradual development of an outwardly rectifying cation current. Conversely, inclusion of millimolar Mg2+ in internal solutions prevented activation of these channels in whole cell patch clamp. We recently demonstrated that the Jurkat T-cell whole cell TRPM7 channels are inhibited by internal Mg2+ in a biphasic manner, displaying high [IC50(1) ≈ 10 μM] and low [IC50(2) ≈ 165 μM] affinity inhibitor sites. In that study, we had characterized the dependence of the maximum cell current density on intracellular Mg2+ concentration. To characterize Mg2+ inhibition in Jurkat T cells in more detail and compare it to whole cell results, we recorded single TRPM7 channels in cell-free membrane patches and investigated the dependence of their activity on Mg2+ added on the cytoplasmic side. We systematically varied free Mg2+ from 265 nM to 407 μM and evaluated the extent of channel inhibition in inside-out patch for 58 patches. We found that the TRPM7 channel shows two conductance levels of 39.0 pS (γ1) and 18.6 pS (γ2) and that both are reversibly inhibited by internal Mg2+. The 39.0-pS conductance is the dominant state of the channel, observed most frequently in this recording configuration. The dose-response relation in inside-out patches shows a steeper Mg2+ dependence than in whole cell, yielding IC50(1) of 25.1 μM and IC50(2) of 91.2 μM.. Single-channel analysis shows that the primary effect of Mg2+ in multichannel patches is a reversible reduction of the number of conducting channels (No). Additionally, at high Mg2+ concentrations, we observed a saturating 20% reduction in unitary conductance (γ1). Thus Mg2+ inhibition in whole cell can be explained by a drop in individual participating channels and a modest reduction in conductance. We also found that TRPM7 channels in some patches were not sensitive to this ion at submaximal Mg2+ concentrations. Interestingly, Mg2+ inhibition showed the property of use dependence: with repeated applications, Mg2+ effect became gradually more potent, which suggests that Mg2+ sensitivity of the channel is a dynamic characteristic that depends on other membrane factors.
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21

Bell, M. V., and J. R. Dick. "The appearance of rods in the eyes of herring and increased di-docosahexaenoyl molecular species of phospholipids." Journal of the Marine Biological Association of the United Kingdom 73, no. 3 (August 1993): 679–88. http://dx.doi.org/10.1017/s002531540003321x.

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The retina of larval herring (Clupea harengus L.) contains only cones, with rods recruited progressively from about eight weeks onwards. The molecular species composition of phospholipids from the eyes of herring of different ages was determined to find whether the appearance of di-docosahexaenoyl molecular species (di22:6n-3) of phospholipids, which are characteristic of rod outer segment membranes in higher vertebrates, coincided with the appearance of rods. In the eyes of larval herring (cone-only retina) di22:6n-3 molecular species comprised 25.9% of phosphatidylethanolamine (PE), 22.9% of phosphatidylserine (PS) and 4.2% of phosphatidylcholine (PC). In the eyes of adult herring (rod:cone ratio of about 20:1) the proportion of di22:6n-3 molecular species had increased to 49.5%, 39.0% and 16.8% in PE, PS and PC, respectively. Juvenile herring had intermediate values of di22:6n-3 phospholipids. The results confirm the hypothesis that the amounts of di22:6n-3 molecular species of phospholipids in retina increase during development as rods appear, and also show that cones contain smaller amounts of these unique lipids. Three other molecular species containing docosahexaenoic acid, 16:0/22:6n-3, 18:1/22:6n-3 and 18:0/22:6n-3 were also major components of eye phospholipids, emphasizing the important role of 22:6n-3 in vision.
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Anand, Maxima, and Manan Anand. "The study of mannose receptors status in HIV-1 discordant couples." International Journal of Advances in Medicine 4, no. 6 (November 22, 2017): 1578. http://dx.doi.org/10.18203/2349-3933.ijam20175170.

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Background: It is more than two decades the presence of HIV virus has created a pandemic in human community. The current study was designed to study the levels of mannose receptors on vaginal epithelial cells of female partners of seronegative couple and of seronegative wife of seropositive husband.Methods: It is a case control observational study.in the study,30 controls: seronegative couples- husband seronegative and wife seronegative and 30 cases (study group): serodiscordant couples-husband seropositive and wife seronegative were included. The gynecological examination of the female partner was carried out, both per speculum (PS) and per vaginal (PV). Any lesions or inflammation was noted. the area was cleaned, and smear was collected. The smear was immediately fixed with 1:1 ether alcohol. The gynecological examination of the female partner was carried out, both per speculum (PS) and per vaginal (PV). Any lesions or inflammation was noted. the area was cleaned, and smear was collected. The smear was immediately fixed with 1:1 ether alcohol.Results: Although sexual mode of transmission is highest in India, large numbers of couples are serodiscordant. In this study, the discordant couples were married for an average of 19.3 years. Their youngest child had a mean age of 8.34 years. The mother being seronegative, all children were seronegative. The Husband’s qualified for ART at the time of detection of HIV status depending on their CD4 value. It means that they were harboring the virus for more than 10 years. Despite unprotected sex, the virus was not transmitted to the wife. Search for alternate pathway of HIV entry through vaginal mucosa showed: The females in control group revealed >98% epithelial cells had mannose receptors in almost all the females. As against serodiscordant females had mannose receptors in < 10% vaginal epithelial cells. There is a significant difference (p<0.01) between the control group and study group. Thus, the absence of mannose receptors probably prevents the HIV transmission.Conclusions: This observation will be helpful in developing effective microbicide and will open new frontiers for drug development which will halt sexual transmission of HIV and will also help in vaccine development.
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Zhu, Meifang, Weidong Yan, Yan Lu, Yanmo Chen, Hans-Jürgen P. Adler, Petra Pötschke, and Jürgen Pionteck. "Modification of PP by blending with PS and reactive polymers." Macromolecular Symposia 164, no. 1 (February 2001): 369–76. http://dx.doi.org/10.1002/1521-3900(200102)164:1<369::aid-masy369>3.0.co;2-6.

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Pötschke, Petra, Hauke Malz, and Jürgen Pionteck. "Influence of interfacial reaction on morphology in modified PP/PS blends." Macromolecular Symposia 149, no. 1 (January 2000): 231–36. http://dx.doi.org/10.1002/1521-3900(200001)149:1<231::aid-masy231>3.0.co;2-k.

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Müller, Alejandro J., Maria Luisa Arnal, and Francisco López-Carrasquero. "Nucleation and crystallization of PS-b-PEO-b-PCL triblock copolymers." Macromolecular Symposia 183, no. 1 (July 2002): 199–204. http://dx.doi.org/10.1002/1521-3900(200207)183:1<199::aid-masy199>3.0.co;2-s.

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Taylor, Anne G., and Julie P. Harmon. "The effect of dibutyl phthalate (DBP) plasticizer on the stability of optical properties of polystyrene (PS) after exposure to gamma radiation." Polymer Degradation and Stability 41, no. 1 (January 1993): 9–15. http://dx.doi.org/10.1016/0141-3910(93)90054-m.

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Lim, Jong Min, Iti Gupta, Hiroyuki Furuta, and Dongho Kim. "Comparative photophysics of sapphyrin derivatives: effects of confused and fused pyrrole rings." Journal of Porphyrins and Phthalocyanines 15, no. 09n10 (September 2011): 858–64. http://dx.doi.org/10.1142/s1088424611003719.

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We have investigated the photophysical properties of [22] π-conjugated pentapyrrolic systems, sapphyrin, N-confused and N-fused sapphyrins, with a particular focus on the effects of confused and fused pyrrole rings on their electronic structures using steady-state and time-resolved spectroscopic methods, two-photon absorption cross-section (σ(2)) measurements and quantum mechanical calculations. The absorption spectra of N-confused and N-fused sapphyrins exhibit relatively red-shifted features compared to sapphyrin. In parallel with these spectral features, the reduced HOMO–LUMO gaps were observed in going from sapphyrin to N-fused sapphyrin. In the analysis of the anisotropy of the induced current density (AICD), N-confused and N-fused sapphyrins show that extra π-electrons in confused and fused pyrrole rings contribute to the extension of their π-conjugation pathways. Slightly larger twophoton absorption cross-section values of N-confused and N-fused sapphyrins (3250 and 3900 GM) than that of sapphyrin (2900 GM) also reflect an enhanced π-conjugation effect due to bicyclic and endocyclic extensions in π-conjugation pathways, respectively. The excited singlet and triplet state lifetimes of N-confused sapphyrin were determined to be 60 ps and 1 μs, respectively, due to conformational change and acceleration of nonradiative decay processes, being in a sharp contrast with those of sapphyrin (2.4 ns and 13 μs, respectively). In the case of N-fused sapphyrin, very short singlet excited-state lifetime of 5 ps was detected probably due to the excited-state NH-tautomerization process which enhances nonradiative decay processes.
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Catarata, Maria Joana Pereira, Sandra Saleiro, and Vânia Sá Araújo. "Outcomes of Airway Stents in the Palliative Care of Patients With Cancer." American Journal of Hospice and Palliative Medicine® 38, no. 1 (May 26, 2020): 19–24. http://dx.doi.org/10.1177/1049909120926466.

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Introduction: A significant proportion of patients with advanced primary or metastatic intrathoracic malignancy will eventually develop central airway obstruction. The morbidity associated with malignant airway obstruction (MAO) is considerable and the management is difficult. Our aim was to evaluate the outcomes of tracheobronchial stenting in patients with MAO and its role in palliative care. Material and Methods: This retrospective study involved a consecutive case series of patients with advanced cancer with MAO who underwent tracheobronchial stenting between August 2014 and August 2019. The European Cooperative Oncology Group (ECOG) scale was used to evaluate patient functional status before and after tracheobronchial stenting. Univariate survival analysis included Kaplan-Meier curves with Log-Rank test, while Cox regression was used as a multivariate analysis. Results: We included 28 patients with median age of 55.0 years (interquartile range = 49.3-66.5) and 89.3% male. The most frequent primary tumour was the esophagus followed by lungs. The majority of the patients (75%) expressed immediate symptom relief after stenting and there was a significant improvement in the mean ECOG performance status (PS; P = .005). There was no intraprocedure mortality and complications were observed in 6 patients. The median survival after airway stenting was 39.0 days (95% CI = 32.2-45.8) with poorer PS after stent insertion associated with lower overall survival (hazard ratio = 2.3 [95% CI = 1.1-4.9], P = .030) on multivariate analysis. Conclusion: Airway stent is a safe and effective procedure that offers rapid palliation of symptoms with no major complications. Therefore, stent placement should be considered as part of the treatment of patients with terminal cancer.
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Schuette, Wolfgang, Sylke Nagel, Claus-Peter Schneider, Walburga Engel-Riedel, Christian Schumann, Martin Kohlhaeufl, Monika Serke, Gert Hoeffken, Cornelius Kortsik, and Martin Reck. "65 plus: A randomized phase III trial of pemetrexed and bevacizumab versus pemetrexed, bevacizumab, and carboplatin as first-line treatment for elderly patients with advanced nonsquamous, non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 8013. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.8013.

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8013 Background: Pemetrexed (P) and bevacizumab (B) are efficacious drugs for treatment of non-squamous NSCLC. In this trial the benefit of combining PB with carboplatin (C) was investigated in elderly patients (pts) ≥ 65 years with NSCLC. Methods: In this German multicenter (27 centers), open-label phase III trial pts with stage IIIb/IV non-squamous NSCLC were recruited. Pts were randomized 1:1 to P (500 mg/m2) + B (7.5 mg/kg) or P+B+C (AUC5) d1 q3 wks for 4 to 6 cycles followed by maintenance therapy with B or P+B. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), 1-year survival rate, overall response rate (ORR) as well as tolerability (AEs/SAEs). Results: 271 pts were enrolled from Sep 2009 to Jan 2012, the ITT population consists of 251 evaluable pts, less than 10 pts are still receiving maintenance therapy. Baseline characteristics were balanced between both treatment groups (PB 118 pts, PBC 133 pts). Median age was 71 years in PB and 72 in PBC. Median PFS time was 4.8 mo in PB and 6.8 mo in PBC. Treatment comparison for ECOG performance status (PS) 0-1 subgroup (PB 112 pts, PBC 126 pts): p=0.0426 (Wilcoxon test), hazard ratio (HR) = 1.31 (95% CI 0.99-1.73). ORR was 31.4% in PB vs. 44.4% in PBC (p=0.0343). Median OS time was 11.6 mo in PB vs. 15.2 mo in PBC. Treatment comparison ECOG PS 0-1: p=0.2050, HR = 1.20 (95% CI 0.85-1.70). 1-year survival rates were 48.2% and 58.8%, respectively. Compared to this the median OS time in the small group of pts with ECOG PS 2 was 11.5 mo in PB vs. 3.8 mo in PBC. AE grade 3/4 and SAE profiles were comparable in both treatment arms, 76 pts (64.4%) with AEs grade 3/4 in PB and 87 pts (65.4%) in PBC, 58 pts (49.2%) with SAEs in PB and 64 pts (48.1%) in PBC. 46 pts (39.0%) in PB vs. 69 pts (51.9%) in PBC received maintenance therapy. Conclusions: Combination of PBC demonstrates with a median OS of 15.2 mo a strong efficacy with acceptable toxicity profile for elderly patients. Addition of carboplatin is recommended for eligible patients. However, in patients with ECOG PS 2 the administration of carboplatin must be carefully reviewed. Clinical trial information: NCT00976456.
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Girard-Reydet, Emmanuel, Anne Sévignon, Jean-Pierre Pascault, Cristina E. Hoppe, María J. Galante, Patricia A. Oyanguren, and Roberto J. J. Williams. "Influence of the Addition of Polystyrene-block-poly(methyl methacrylate) Copolymer (PS-b-PMMA) on the Morphologies Generated by Reaction-Induced Phase Separation in PS/PMMA/Epoxy Blends." Macromolecular Chemistry and Physics 203, no. 7 (April 1, 2002): 947. http://dx.doi.org/10.1002/1521-3935(20020401)203:7<947::aid-macp947>3.0.co;2-8.

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Niino, H., J. Ihlemann, S. Ono, and A. Yabe. "Surface microstructure formation by ps- and fs-laser ablation of an elastomer composite." Macromolecular Symposia 160, no. 1 (October 2000): 159–66. http://dx.doi.org/10.1002/1521-3900(200010)160:1<159::aid-masy159>3.0.co;2-m.

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Vishnevskaya, I. A., A. E. Chalykh, V. K. Gerasimov, and L. I. Jarova. "Phase equilibria of PS with PMMA and poly(co-methyl methacrylate and styrene)mers." Macromolecular Symposia 175, no. 1 (October 2001): 259–64. http://dx.doi.org/10.1002/1521-3900(200110)175:1<259::aid-masy259>3.0.co;2-9.

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Burns, Karen E. A., Jeena Khan, Vorakamol Phoophiboon, Vatsal Trivedi, J. Carolina Gomez-Builes, Benedetta Giammarioli, Kimberley Lewis, Dipayan Chaudhuri, Kairavi Desai, and Jan O. Friedrich. "Spontaneous Breathing Trial Techniques for Extubating Adults and Children Who Are Critically Ill." JAMA Network Open 7, no. 2 (February 23, 2024): e2356794. http://dx.doi.org/10.1001/jamanetworkopen.2023.56794.

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ImportanceConsiderable controversy exists regarding the best spontaneous breathing trial (SBT) technique to use.ObjectiveTo summarize trials comparing alternative SBTs.Data SourcesSeveral databases (MEDLINE [from inception to February 2023], the Cochrane Central Register of Controlled Trials [in February 2023], and Embase [from inception to February 2023] and 5 conference proceedings (from January 1990 to April 2023) were searched in this systematic review and meta-analysis.Study SelectionRandomized trials directly comparing SBT techniques in critically ill adults or children and reporting at least 1 clinical outcome were selected.Data Extraction and SynthesisPaired reviewers independently screened citations, abstracted data, and assessed quality for the systematic review and meta-analysis using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA guidelines). Data were pooled using random-effects models.Main Outcomes and MeasuresPrimary outcomes included SBT success, extubation success, and reintubation.ResultsThe systematic review and meta-analysis identified 40 trials that included 6716 patients. Low-quality evidence (14 trials [n = 4459]) suggested that patients were not more likely to pass a pressure support (PS) compared with a T-piece SBT (risk ratio [RR], 1.04; 95% CI, 0.97-1.11; P = .31; I2 = 73%), unless 1 outlier trial accounting for all heterogeneity was excluded (RR, 1.09; 95% CI, 1.06-1.12; P &amp;lt; .001; I2 = 0% [13 trials; n = 3939]; moderate-quality evidence), but were significantly more likely to be successfully extubated (RR, 1.07; 95% CI, 1.04-1.10; P &amp;lt; .001; I2 = 0%; 16 trials [n = 4462]; moderate-quality evidence). Limited data (5 trials [n = 502]) revealed that patients who underwent automatic tube compensation/continuous positive airway pressure compared with PS SBTs had a significantly higher successful extubation rate (RR, 1.10; 95% CI, 1.00-1.21; P = .04; I2 = 0% [low-quality evidence]). Compared with T-piece SBTs, high-flow oxygen SBTs (3 trials [n = 386]) had significantly higher successful extubation (RR, 1.06; 95% CI, 1.00-1.11; P = .04; I2 = 0%) and lower reintubation (RR, 0.37; 95% CI, 0.21-0.65; P = &amp;lt;.001; I2 = 0% [both low-quality evidence]) rates. Credible subgroup effects were not found.Conclusions and RelevanceIn this systematic review and meta-analysis, the findings suggest that patients undergoing PS compared with T-piece SBTs were more likely to be extubated successfully and more likely to pass an SBT, after exclusion of an outlier trial. Pressure support SBTs were not associated with increased risk of reintubation. Future trials should compare SBT techniques that maximize differences in inspiratory support.
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Song, Rui, Jun Zhao, Juan Yang, Xin Linghu, and Qingrong Fan. "The Study of Stress-Yielding of Aged Atactic Polystyrene (a-PS) by Differential Scanning Calorimetry." Macromolecular Chemistry and Physics 202, no. 4 (February 1, 2001): 512–15. http://dx.doi.org/10.1002/1521-3935(20010201)202:4<512::aid-macp512>3.0.co;2-q.

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Li, Y., K. Gao, V. E. Villafañe, and E. W. Helbling. "Ocean acidification mediates photosynthetic response to UV radiation and temperature increase in the diatom <i>Phaeodactylum tricornutum</i>." Biogeosciences 9, no. 10 (October 12, 2012): 3931–42. http://dx.doi.org/10.5194/bg-9-3931-2012.

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Abstract. Increasing atmospheric CO2 concentration is responsible for progressive ocean acidification, ocean warming as well as decreased thickness of upper mixing layer (UML), thus exposing phytoplankton cells not only to lower pH and higher temperatures but also to higher levels of solar UV radiation. In order to evaluate the combined effects of ocean acidification, UV radiation and temperature, we used the diatom Phaeodactylum tricornutum as a model organism and examined its physiological performance after grown under two CO2 concentrations (390 and 1000 μatm) for more than 20 generations. Compared to the ambient CO2 level (390 μatm), growth at the elevated CO2 concentration increased non-photochemical quenching (NPQ) of cells and partially counteracted the harm to PS II (photosystem II) caused by UV-A and UV-B. Such an effect was less pronounced under increased temperature levels. The ratio of repair to UV-B induced damage decreased with increased NPQ, reflecting induction of NPQ when repair dropped behind the damage, and it was higher under the ocean acidification condition, showing that the increased pCO2 and lowered pH counteracted UV-B induced harm. As for photosynthetic carbon fixation rate which increased with increasing temperature from 15 to 25 °C, the elevated CO2 and temperature levels synergistically interacted to reduce the inhibition caused by UV-B and thus increase the carbon fixation.
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Wagner, Anna Dorothea, Manel Rakez, Benoist Chibaudel, Richard Adams, John Raymond Zalcberg, Leonard B. Saltz, Alan P. Venook, et al. "Sex differences in efficacy and toxicity of first-line treatment of metastatic colorectal cancer (CRC): An analysis of 18,399 patients in the ARCAD database." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 4029. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.4029.

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4029 Background: The clearance of 5-FU differs significantly between men (M) and women (W). Adjuvant chemotherapy (CT) for CRC has a higher toxicity in W. The impact of sex on efficacy and toxicity in first-line trials of metastatic CRC (mCRC) is unknown. Methods: We analyzed patient (pt) and tumor characteristics, toxicities (nausea (AE1), vomiting (AE2), diarrhea, neutropenia (AE3)) and efficacy (overall survival (OS), progression-free survival (PFS)) according to sex in the following treatment groups: A: CT alone, B: CT + bevacizumab, C: CT + EGFR-antibodies, with subgroup analyses in the CT alone group for single-agent, doublets and triplets, as well as irinotecan- and oxaliplatin-based regimens. Pts from trials with treatments still used today and all relevant data available were eligible. OS and PFS were assessed using Kaplan-Meier and Cox models adjusted for primary tumor location and performance status (PS). Results: We included 28 trials with 18.399 pts (11.352 M and 7.047 W). W were younger (61 vs. 63 years), had more often a PS of 1 (49 vs 45%), BRAF mutations (10 vs. 7%), right-sided tumors (42 vs. 35%) and less often rectal tumors (26 vs. 32%). Significant differences in toxicity are reported in table. Rates of diarrhea were similar. There was no sex disparity in OS in the predefined subgroups except for pts receiving triplets where OS was better in M (HRadj=1.39 (1.05 - 1.85)). Median (interquartile range) OS in months for M and W was 16.7 (9.2-27.4) and 16.2 (8.9-27.2) in group 1, 21.9 (12.7-37.5) and 22.3 (12.9 – 39.0) in group 2, and 26.8 (14.6-45.3) and 24.8 (12.3-49.2) in group 3. HRsadj (W vs M) (95% CI), p values for OS were 1.02 (0.96-1.09), .557, 0.92 (0.83-1.03), .142, 0.99 (0.85-1.14), .866. Conclusions: M and W with mCRC differ significantly regarding patient and tumor characteristics. The significant higher toxicity in W does not translate in a higher treatment efficacy. Apart from known sex differences in pharmacokinetics of 5-FU, differences in pharmacodynamics must be postulated. [Table: see text]
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Smolnikova, M. V., A. A. Barilo, M. A. Malinchik, and S. V. Smirnova. "Search for genetic markers of predisposition to psoriasis and psoriatic arthritis." Medical Immunology (Russia) 22, no. 5 (December 1, 2020): 925–32. http://dx.doi.org/10.15789/1563-0625-sfg-2050.

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Psoriasis (PS) and psoriatic arthritis (PsA) are interrelated diseases that occur in approximately 30% of patients and are characterized by the presence of a systemic inflammatory reaction that occurs as a result of a violation of the functional state of the immune system. With the advent of new technologies, several new pro-inflammatory cytokines, such as IL-23, IL-31, and IL-33, which play an important role in the pathogenesis of the psoriatic process, have been discovered and characterized. It was determined that single nucleotide polymorphisms (SNPs) in the promoter regions of the IL23, IL31 and IL33 genes play an important role in controlling the expression of relevant cytokines involved in the immunopathogenesis of psoriatic disease. The purpose of the study: to analyze the distribution of genotypes and allelic variants of polymorphisms of the IL23A (rs2066808), IL23R (rs2201841), IL31 (rs7977932) and IL33 (rs7044343), in order to search for genetic markers of predisposition to psoriasis and psoriatic arthritis. Materials and methods. The genotyping of the patients was conducted: psoriasis (PS, n = 77), median age 31.0 years (27.0-43.0), psoriatic arthritis (PsA, n = 99), median age 49.0 years (39.0-56.0) and practically healthy residents of Krasnoyarsk (n = 103), a median age of 32.0 years (24.0-38.0). DNA was isolated from whole venous blood using a standard sorbent kit. Genotyping of single nucleotide polymorphisms IL23A (rs2066808), IL23R (rs2201841), IL31 (rs7977932), IL33 (rs7044343) was carried out using real-time PCR using specific oligonucleotide primers and fluorescentlylabeled probes. Results and discussion. The frequencies of allelic variants of the studied cytokine genes in the control group obtained during the study correspond to their distribution in Caucasoid populations – the alleles IL23A * T, IL23R * T, IL31 * C, IL33 * C prevail. When comparing the distribution frequency of allelic variants of the IL23A, IL23R, IL31, IL33 genes, we did not obtain statistically significant differences between patients and the control group. Conclusions. Despite the fact that when comparing the distribution frequency of allelic variants of the IL23A, IL23R, IL31, IL33 genes, we did not obtain statistically significant differences between the patients and the control group, there are results worthy of attention. So, in patients with PS, the frequency of the C * IL23A allelic variant (rs2066808) is lower than in the population sample, which may indicate its specific role in relation to the development of the disease. All this dictates the need to continue research with the assessment of other SNPs and increase the sample of patients in search of potential genetic markers of psoriatic disease.
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Sciamanna, Rosalba, Guillermo Arribas, Carmen Albano, Valentin Merola, and Cybelle Pacheco. "Settling the question of optimum concentration and methodology used for adding an antioxidant to PS/PP polyblend." Macromolecular Symposia 176, no. 1 (December 2001): 31–38. http://dx.doi.org/10.1002/1521-3900(200112)176:1<31::aid-masy31>3.0.co;2-8.

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Frielinghaus, H., K. Mortensen, and K. Almdal. "Differences of Interaction Parameter of a PS/PEO homopolymer blend and diblock copolymer in comparison to other systems." Macromolecular Symposia 149, no. 1 (January 2000): 63–68. http://dx.doi.org/10.1002/1521-3900(200001)149:1<63::aid-masy63>3.0.co;2-1.

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Ohba, Akihiro, Jun Hashimoto, Ken Kato, Yoshinori Ito, Nobukazu Hokamura, Chikatoshi Katada, Hiromichi Ishiyama, et al. "Phase II study of chemoradiotherapy with docetaxel for elderly patients with stage II/III esophageal carcinoma: An updated report." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 208. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.208.

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208 Background: Definitive chemoradiotherapy (CRT) is one of the curative options for resectable esophageal carcinoma (EC). However, there are limited data on CRT in elderly patients, and it is difficult for elderly patients to receive chemotherapy containing cisplatin. The aim of this prospective study was to clarify the efficacy and safety of definitive CRT with docetaxel (DTX) in elderly patients. Methods: The eligibility criteria for this study were as follows: clinical stage II-III (UICC 6th, non-T4) EC; performance status (PS) 0-1; age > 70; and no desire for surgical treatment. Chemotherapy consisted of 6 cycles of a 1-h infusion of DTX (10 mg/m2) repeated weekly. Radiation was concurrently applied at a dose of 60 Gy in 30 fractions. We calculated that with a sample size of 37 patients, assuming that the expected and threshold 2-year survival was 50% and 30% with one-sided alpha of 5% with 80% power. Results: Between July 2008 and January 2011, 16 patients were enrolled. The study was closed prematurely due to poor accrual. The median age was 77 years (range, 73-81); male/female: 14/2; PS 0/1: 4/12; clinical Stage IIA/IIB/III: 3/4/9. Of the 16 patients, 14 (88%) completed the CRT, 1 patient (6%) could not complete the treatment because of grade 3 esophagitis, and 1 (6%) refused to continue the treatment. The median follow-up time was 57.9 months. Six patients achieved complete response (CR), resulting in a 37.5% CR rate (95% confidence interval (CI): 15.2-64.6). The 2-year overall survival rate was 62.5% (95% CI: 39.0-86.0). The median survival time was 27.8months (95% CI: 23.7-31.9). Acute toxicities included grade 3/4 esophagitis (31%), anorexia (13%), leukopenia (6%), neutropenia (6%), thrombocytopenia (6%), mucositis (6%), and infection (6%). No treatment-related deaths were observed. Grade 3 or 4 esophagitis, pleural effusion, pericardial effusion, and pneumonitis developed as late adverse events in 13%, 13%, 6%, and 6% of patients, respectively. Conclusions: Although it is difficult to conclude about efficacy of CRT with DTX for elderly stage II-III EC patients, considering that this study was terminated prematurely, CRT with DTX seemed to have substantial clinical activity. Clinical trial information: 000001846.
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Zeichner, Simon B., Shannon Gleason, Ana G. Antun, Amelia Langston, Leonard T. Heffner, Vamsi K. Kota, Manila Gaddh, and Martha Arellano. "Survival of Patients Diagnosed with Primary Refractory and Relapsed Acute Myeloid Leukemia from 2008-2012: A Single Institution Experience." Blood 126, no. 23 (December 3, 2015): 4955. http://dx.doi.org/10.1182/blood.v126.23.4955.4955.

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Abstract Introduction: Acute myeloid leukemia (AML) is one of the most lethal types of adult cancer, with 10,460 deaths among 18,860 diagnoses in 2014. Although some patients are cured with induction and consolidation chemotherapy with or without stem cell transplantation (SCT), between 50-80% of patients will either fail to obtain a complete remission (CR; primary refractory AML) or will relapse. The median overall survival (OS) for relapsed and refractory AML patients is dismal, and there is no clear consensus on the management of relapsed/refractory AML. In this study, with extended follow-up, we set out to look at our own experience with primary refractory and relapsed AML patients in order to try to identify the best therapy and factors associated with improved outcomes. Methods: This retrospective study in AML patients seen at Emory University Hospital (EUH) was IRB approved. Descriptive statistics were used to characterize the demographic and clinical variables. Cytogenetic and molecular signatures were defined based upon the European Leukemia Network and Southwest Oncology group classifications (Döhner et al. 2010, Slovak et al. 2000). Response criteria were based upon the revised recommendations of the International Working Group (Cheson et al. 2003). The combined prognostic score was created using previously validated prognostic variables including age (< 60 vs. >/= 60), Eastern Cooperative Oncology Group Performance Status (ECOG PS; 0-1 vs. >/= 2), and cytogenetic and molecular signatures (favorable vs unfavorable). A score of 0 was termed "favorable" and a score of 1 or greater was termed "unfavorable." The Kaplan-Meier and Cox proportional hazard statistical methods were used to estimate OS. Results: Review of electronic medical records identified 67 consecutive patients between January 1st 2008 and December 31st 2012 diagnosed with primary refractory or relapsed AML. Median age was 56 (range 18-81). Cytogenetic/molecular signatures were favorable in 6%, intermediate in 60%, and unfavorable in 34%, and PS was 0-1 in 34% and 2 in 66%. The majority of patients had a combined prognostic score of unfavorable (n = 53, 79%). Among the 67 patients, 17 (25%) achieved CR with salvage therapy, with 13 (76%) of those able to undergo SCT. With an extended follow-up of approximately 5.6 years, the median OS of our refractory/relapsed AML cohort was 4 months (95% CI 2.2-5.8), with 8% of patients living at least 5 years from their date of relapse. Univariate analysis identified the following factors to be associated with a significantly worse median OS: Secondary AML at initial diagnosis (2.0 vs 5.0 months; p = 0.005), unfavorable cytogenetic/molecular signature at initial diagnosis (3.0 vs 6.0 months; p = 0.014), ECOG PS of 2 or greater at relapse (2.0 vs. 7.0 months; p< 0.001), an unfavorable combined prognostic score at relapse (3.0 vs 18.0 months; p < 0.001), lack of SCT after salvage (3.0 vs. 39.0 months; p < 0.001), lack of treatment in the refractory/relapsed setting with the combination of induction chemotherapy and hypomethylating agents (1.0 vs 8.0 months; p < 0.001), and lack of attainment of CR in the refractory/relapsed setting (3.0 vs. 40.0 months; p < 0.001). In the final multivariable model, only a favorable combined prognostic score at relapse (hazard ratio, HR 0.5; 95% CI 0-0.8; p = 0.02; Figure 1) and ECOG PS of 0-1 (HR 0.42; 95% CI 0.1-0.8; p=0.04) were associated with an improved OS, while the lack of attainment of a CR in the refractory/relapsed setting (HR 15.9; 95%CI 15.2-16.6; p < 0.001; Figure 2) was associated with a worse OS. Conclusion: In our cohort, the median OS among all patients diagnosed with primary refractory/relapsed AML was dismal. Despite the incorporation of novel agents and treatment approaches among this vulnerable patient population, there remains significant heterogeneity in patient outcomes within the first year, with only a small minority having a significantly longer OS. Similarly to patients with newly diagnosed AML, the most important prognostic variables among our refractory/relapsed AML cohort appears to be their combined prognostic score and their ability to achieve a CR in the salvage setting. It may be beneficial for future studies to focus on improving both, modifiable patient prognostic factors (i.e., PS) and treatment approaches in order to achieve CR in the refractory/relapsed setting. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Kota: Pfizer: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding.
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Zarrabi, Kevin K., Benjamin Miron, Xin Yin, Lisa Rosenblatt, Sarah B. Guttenplan, William John, Taavy A. Miller, et al. "Abstract 5095: Characteristics of patients with advanced renal cell carcinoma (aRCC) who received first-line (1L) nivolumab plus cabozantinib (NIVO+CABO), pembrolizumab plus lenvatinib (PEM+LEN), or nivolumab (NIVO) monotherapy in the real-world (RW) setting." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5095. http://dx.doi.org/10.1158/1538-7445.am2024-5095.

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Abstract Background: Recent advances in immunotherapy have introduced new treatment modalities for aRCC. In absence of guideline recommendations, it is unclear what factors drive providers in selecting 1L treatments for aRCC. To address this gap, we described the baseline demographic and clinical characteristics of patients with aRCC who received 1L NIVO+CABO, PEM+LEN, or NIVO monotherapy in the RW setting. Methods: In this retrospective cohort study, treating oncologists from a US nationally representative network abstracted electronic health record data from patients with aRCC who initiated 1L NIVO+CABO or NIVO monotherapy (off-label in the US) between 2/1/2021 and 6/12/2023, or PEM+LEN between 9/1/2021 and 6/12/2023. Patient demographic and clinical characteristics were summarized descriptively. Results: Compared with patients who received NIVO+CABO (n = 200) or PEM+LEN (n = 100), patients who received NIVO (n = 147) were relatively older at 1L initiation (Table). Sex, race, and region of residence were comparable across cohorts. Patients who received NIVO were more likely to have an ECOG PS score of ≥ 2 (59.2%) compared with NIVO+CABO (14.5%) or PEM+LEN (20%) cohorts. The distribution of MSKCC or IMDC risk scores at 1L initiation was comparable across cohorts . Grade 3 or 4 tumors were reported among 56.5%, 41.0%, and 43.5% of those who received NIVO+CABO, PEM+LEN, and NIVO, respectively. Conclusions: This study suggests that 1L treatment for aRCC using IO monotherapy may be more likely to be considered than IO-TKI therapy for older patients and those with poorer ECOG PS, possibly reflecting perceived tolerability of TKI combinations in these patient populations. Further research is needed to understand the impact of these 1L treatment selection patterns on outcomes. Table: Key patient characteristics at 1L initiation. PEM+LEN NIVO+CABO NIVO n = 100 n = 200 n = 147 Mean age, year (standard deviation) 64.4 (7.9) 66.3 (7.4) 74.1 (9.6) Male, n (%) 93 (63.3) 122 (61.0) 93 (63.3) Race, n (%) White 61 (61.0) 127 (63.5) 91 (61.9) Non-white/unknown 39 (39.0) 73 (36.5) 56 (38.1) Region of residence, n (%) Northeast 23 (23.0) 44 (22.0) 37 (25.2) Midwest 22 (22.0) 53 (26.5) 27 (18.4) South 20 (20.0) 34 (17.0) 33 (22.4) West 35 (35.0) 69 (34.5) 50 (34.0) MSKCC or IMDC risk score, n (%) Favorable 13 (13.0) 28 (14.0) 22 (15.0) Intermediate 57 (57.0) 100 (50.0) 74 (50.3) Poor 28 (28.0) 68 (34.0) 41 (27.9) ECOG-PS, n (%) 0 or 1 80 (80.0) 171 (85.5) 60 (40.8) ≥2 20 (20.0) 29 (14.5) 87 (59.2) Grade of tumor differentiation, n (%) Grade 1 3 (3.0) 10 (5.0) 16 (10.9) Grade 2 56 (56.0) 77 (38.5) 67 (45.6) Grade 3 36 (36.0) 98 (49.0) 55 (37.4) Grade 4 5 (5.0) 15 (7.5) 9 (6.1) Citation Format: Kevin K. Zarrabi, Benjamin Miron, Xin Yin, Lisa Rosenblatt, Sarah B. Guttenplan, William John, Taavy A. Miller, Parisa Asgarisabet, Prathamesh Pathak, Monica Ahlquist, Yul Brian Gash, Daniel M. Geynisman. Characteristics of patients with advanced renal cell carcinoma (aRCC) who received first-line (1L) nivolumab plus cabozantinib (NIVO+CABO), pembrolizumab plus lenvatinib (PEM+LEN), or nivolumab (NIVO) monotherapy in the real-world (RW) setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5095.
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Schuette, W., S. Nagel, L. Fischer von Weikersthal, S. Pabst, C. Schumann, T. Salm, K. Roscher, and N. Dickgreber. "Docetaxel plus carboplatin with or without levofloxacin prophylaxis in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): The APRONTA trial." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 8047. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8047.

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8047 Background: Elderly pts receiving chemotherapy are more likely to have febrile neutropenia and infection than younger pts. Prophylactic fluoroquinolone during chemotherapy reduces the rate of infection and hospitalization vs placebo. The effect of prophylactic treatment with the fluoroquinolone, levofloxacin, on infection rates and survival during docetaxel plus carboplatin therapy was assessed in elderly pts with advanced NSCLC. Methods: In this randomized, double-blind, placebo-controlled Phase III study, eligible pts were aged ≥65 years with previously untreated, histologically/cytologically proven stage IIIB/IV NSCLC, and normal cardiac, renal, hepatic, and hematologic function. Active infection or antibiotics 72 hours before inclusion was not permitted. A planned sample size of 192 pts was considered sufficient for analysis. Pts were randomized to docetaxel (75 mg/m2 IV, Day 1) plus carboplatin (AUC 6 IV, Day 1) q3w, plus placebo or levofloxacin (500 mg po, once daily) on Days 5–11. Primary endpoint was grade 3/4 infection rate or systemic antibiotic therapy of grade 1/2 infection rate. Secondary endpoints were progression free-survival and overall survival. Between-group comparisons were performed using Fisher's exact test. Results: 192 pts (median age 70 years; ECOG PS 0/1/2 in 36%/55%/9%) were randomized to docetaxel plus carboplatin and levofloxacin (n=99) or placebo (n=93); 5 pts received no treatment and were excluded from the ITT population. Rate of grade 3/4 infection was 27.5% (95% CI: 19.3–39.0%) with levofloxacin vs 36.7% (95% CI: 27.1–48.0%) with placebo. Median progression-free survival (PFS) for patients in the levofloxacin arm was 165 days compared with 121 days in the placebo arm (p=0.22). Median overall survival was comparable between groups (307 vs 314 days, respectively; p=0.28). Conclusions: Levofloxacin prophylaxis reduces the rate of grade 3/4 infection compared with placebo. [Table: see text]
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Businelli, Laurent, Yves Gnanou, and Bernard Maillard. "Dependence of transfer reaction on solvent in the free radical polymerization of styrene: application to the synthesis of PS/PEO copolymers using PEO-based transfer agents." Macromolecular Chemistry and Physics 201, no. 18 (December 1, 2000): 2805–10. http://dx.doi.org/10.1002/1521-3935(20001201)201:18<2805::aid-macp2805>3.0.co;2-f.

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Shevelok, A. N. "Association Between Hyperaldosteronemia and Electrophysiological Myocardial Activity in Heart Failure with Preserved Ejection Fraction." Russian Archives of Internal Medicine 10, no. 5 (October 9, 2020): 382–89. http://dx.doi.org/10.20514/2226-6704-2020-10-5-382-389.

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Background. Sudden cardiac death, one of the most common types of cardiac death, is most often triggered by ventricular arrhythmia. Plasma aldosterone level has been shown to be an independent risk factor of life-threatening ventricular arrhythmia in patients with left ventricular systolic dysfunction following acute myocardial infarction. Whether either effect also occurs in patients with heart failure and preserved ejection fraction is currently unknown. Purpose. The study aims to investigate the relationship between plasma aldosterone level and ventricular arrhythmias in longterm heart failure with preserved ejection fraction. Methods. A cross-sectional study included 158 patients (58 men and 100 women, mean age 62.3±7.4 years) with heart failure with preserved ejection fraction (> 50%). Patients had no history of primary aldosteronism and did not use the mineralocorticoid receptor antagonists during the last 6 weeks. Aldosterone plasma level was measured and 24-hour electrocardiographic monitoring was performed. Results. According to laboratory results 99 patients (62.7%, 95% confidence interval 55.0-70.0%) had normal (40-160 pg/ml) aldosterone plasma level (nAld) and 59 patients (37.3%, 95% CI 30.0-45.0%) had high (> 160 pg/ml) aldosterone level (hAld). hAld patients more often had QTc prolongation (44.1% versus 18.2%) and ventricular arrhythmias (83.1% vs 61.6%) compared to nAld patients (all Ps <0.001). The number of ventricular premature complexes in 24 hours were higher in hAld group (median 214, range 64-758) compared to nAld (median 52, range 16-198, P < 0.003). hAld patients more often occurred bigemy, couple ventricular ectopy and nonsustained ventricular tachycardia (39.0% vs 19.0%, р=0.01). In Cox regression model’s high aldosterone plasma level was the independent risk factors of QTc prolongation (odds ratio 1.6, 95% confidence interval 1.1-5.7, p=0.034) and prognostically unfavorable ventricular arrhythmias (odds ratio 1.8, 95% confidence interval 1.2-6.8, p=0.024). Conclusion. In long-term HFpEF plasma aldosterone level is significantly related to QTc prolongation as well as ventricular arrhythmias.
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Schnitte, S., T. Funk, J. Henes, and S. Saur. "AB0041 THE PHENOTYPE OF PERIPHERAL BLOOD DENDRITIC CELLS OF PATIENTS WITH ADULT-ONSET STILL´S DISEASE COMPARED TO HEALTHY DONORS AND PATIENTS WITH PSORIATIC ARTHRITIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1155–56. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3900.

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BackgroundAdult-onset still´s disease (AOSD) is a rare autoinflammatory disease. A triad of high fever, arthritis and skin rash is described, but multiple forms of manifestation, as the lack of detectable biomarkers, aggravate making the diagnosis (1).Psoriatic arthritis (PsA), another autoimmune disease with jointal manifestation, affects approximately 30% of all patients with psoriasis (2).Dendritic cells (DCs) are potent antigen presenting cells linking adaptive and innate immunity. In various autoimmune diseases alterations of DCs were detected (4).ObjectivesThe etiology and effect of peripheral blood DCs on the arthritis in both diseases is not cleared yet (1,3). This project tried to examine alterations of DCs in AOSD patients compared to those with PsA and a healthy control group (HC).Methods13 patients with AOSD were analysed and compared.Leukocytes were separated with density gradient centrifugation and sorted with flow cytometry. The contingent of DC subsets in the peripheral blood (pDCs, CD1c+DCs, CD141+DCs) was compared between AOSD patients and the other two groups (n=12).Monocytes of the peripheral blood were incubated with IL-4 and GM-CSF to differentiate to DCs. The addition of lipopolysaccharides helped gaining immature (n=11) and mature (n=9) DCs. Their phenotype was characterized by CD1a, CD206, Osteoactivin (OA), CCR7, CD14, DC sign, CCR7, CD14, CD40, HLA-DR, CD80, CD83, CD86. The expression levels of the surface proteins were again compared.ResultsThe DC subset rates did not differ significantly between AOSD patients and both other groups.The surface markers showed a significant difference in expression of CD80 on mature DCs of AOSD patients and those with PsA. Immature DCs presented a significantly different level of OA on patients with AOSD and HCs. All other measured surface markers did not vary between the groups.ConclusionThe DC subsets analysis did not show significant differences. An arthritic manifestation in AOSD might not depend on the fraction of DCs in the peripheral blood.OA inhibits T cell responses strongly as coinhibitory molecule on antigen presenting cells. The lower expression of OA on DCs of patients with AOSD might represent a lower inhibition of T cells in comparison to HCs (5).The interaction of CD80 and CD86 with CD28 is necessary to produce IL-6. The pro-inflammatory effect is limited by CD80/ CD86 itself (6). CD80, in contrast to CD86, is expressed differently in patients with AOSD and PsA. As CD80 and CD86 function as cofactors, an alteration of both might have been expected.References[1]Efthimiou P, Kontzias A, Hur P, Rodha K, Ramakrishna GS, Nakasato P. Adult-onset Still’s disease in focus: Clinical manifestations, diagnosis, treatment, and unmet needs in the era of targeted therapies. Semin Arthritis Rheum. 2021;51(4):858-74.[2]Henes JC, Ziupa E, Eisfelder M, Adamczyk A, Knaudt B, Jacobs F, et al. High prevalence of psoriatic arthritis in dermatological patients with psoriasis: a cross-sectional study. Rheumatol Int. 2014;34(2):227-34.[3]Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet. 2018;391(10136):2273-84.[4]Takenaka MC, Quintana FJ. Tolerogenic dendritic cells. Semin Immunopathol. 2017;39(2):113-20.[5]Gutknecht M, Geiger J, Joas S, Dörfel D, Salih HR, Müller MR, et al. The transcription factor MITF is a critical regulator of GPNMB expression in dendritic cells. Cell Commun Signal. 2015;13:19.[6]Lanier LL, O’Fallon S, Somoza C, Phillips JH, Linsley PS, Okumura K, et al. CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL. J Immunol. 1995;154(1):97-105.Disclosure of InterestsSarah Schnitte Grant/research support from: The project was financially supported by Novartis., Tanja Funk: None declared, Jörg Henes: None declared, Sebastian Saur: None declared
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Saha, P., J. Dainty, A. Iftikhar Talib, T. Toyoda, A. Humberstone, A. Macgregor, and M. Yates. "POS0647 A COMPARISON OF 20 YEAR DISABILITY OUTCOMES IN VALIDATED CASES OF RHEUMATOID ARTHRITIS AND PSORIATIC ARTHRITIS IN THE NORFOLK ARTHRITIS REGISTER." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 600.2–601. http://dx.doi.org/10.1136/annrheumdis-2023-eular.3920.

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BackgroundRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are common inflammatory rheumatic diseases with distinct clinical phenotypes, that can both result in significant disability. Whilst some data in selected samples report no difference in Health Assessment Questionnaire scores (HAQ) between RA and PsA(1), there is a lack of definitive long term population based data.The Norfolk Arthritis Register (NOAR) is an inception cohort of early inflammatory arthritis established in 1989, with over 4,500 cases of new onset inflammatory arthritis. Cases were recruited in primary care or from hospital clinics, and inclusion criteria were age >16 years with 2 swollen joints lasting ≥4 weeks. Data was collated on demographics and disability through Health Assessment Questionnaires (HAQ) over variable years of follow up (0-20 years); HAQ scores values range from 0 to 3, and the higher the score the greater the disability [2].ObjectivesOur aim was to compare differences between both baseline and follow-up HAQ scores in RA and PsA, in cases selected from the same base population and followed continuously for over 20 years.MethodsCases included in this study were recruits into NOAR, who were followed at intervals of 1, 2, 3, 4, 5, 7, 8, 10, 12, 15, 18 and 20 years. Cases of RA were defined using American College of Rheumatology (ACR) criteria; cases of PsA were classified by retrospective clinical record review.Cases with RA were compared to cases with PsA, and data analysis was carried out in R. Independent samples t-tests were used to assess statistical significance of unadjusted HAQ scores.ResultsA total of 1,812 cases of RA (85.4%) and 308 cases of PsA (14.5%) were identified with complete data on sex and age within the NOAR cohort who had recorded HAQ scores. The mean age of onset for RA was 56.3 years (min 18.6 – max 88.6; SD 13.9), and 47.3 years for PsA (min 16 – max 79.9, SD 13.1).Baseline HAQMean baseline HAQ scores were higher for RA at 0.854 (SD 0.704) when compared with PsA at 0.706 (SD 0.688) (p<0.001).Females had higher baseline HAQ scores than males (0.915 vs 0.677) consistent across both disease types which was statistically significant (RA – 0.919 vs. 0.716, p <0.001: PsA – 0.885 vs. 0.533, p <0.001).Follow-up HAQCases were followed up to 20 years. 1,812 cases of RA were identified at baseline, decreasing to 1552 with 1-year follow up (85.6%) and 165 cases with 20-year follow up (9.1%). 308 PsA cases were identified at baseline, 248 followed up at 1-year (80.5%) and 21 cases for 20-years (6.8%).Figure 1 illustrates that cases with RA had higher mean HAQ scores than PsA throughout a follow up period of up to 20 years. Mean HAQ scores accumulated over the follow up period for RA, whilst there was a decrease in HAQ scores after 12 years of follow up for those with PsA before increasing after 18 years.Figure 1.A comparison of the mean Health Assessment Questionnaire scores between Rheumatoid Arthritis and Psoriatic arthritisConclusionThe NOAR cohort is unique in its long follow up period of up to 20 years, allowing for the assessment of HAQ longitudinally. The relationship between higher HAQ scores in RA than PsA holds for both baseline HAQ scores and follow-up HAQ scores throughout the follow-up period, supporting the association of RA with greater disability. We hypothesise that this may be due to the nature of joint damage and other comorbidities associated with RA. We also demonstrate from this data that females present with statistically higher baseline HAQ scores than males within both diseases.In conclusion, there are evident trends with higher HAQ scores in RA over PsA consistent over time.References[1]Sokoll KB, Helliwell PS. Comparison of disability and quality of life in rheumatoid and psoriatic arthritis. J Rheumatol. 2001 Aug;28(8):1842–6.[2]Uhlig T, Haavardsholm EA, Kvien TK. Comparison of the Health Assessment Questionnaire (HAQ) and the modified HAQ (MHAQ) in patients with rheumatoid arthritis. Rheumatology. 2006 Apr 1;45(4):454–8.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Sohn, Joohyuk, Kyong Hwa Park, Hee Kyung Ahn, Keun Seok Lee, Jee Hyun Kim, Sung-Bae Kim, Kyoung Eun Lee, et al. "Preliminary safety and efficacy of GX-I7, a long-acting interleukin-7, in combination with pembrolizumab in patients with refractory or recurrent metastatic triple negative breast cancer (mTNBC): Dose escalation period of Phase Ib/II study (KEYNOTE-899)." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 1072. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.1072.

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1072 Background: Pembrolizumab monotherapy did not significantly improve OS as 2nd and 3rd-lines treatment for mTNBC compared to standard chemotherapy in phase III study (KEYNOTE-119) leading to high unmet needs of effective treatment. Recent studies showed that higher lymphocyte count is an independent factor which correlates with better response to checkpoint blockade in cancer patients. GX-I7, a long-acting interleukin-7, could potentially provide synergistic anti-tumor efficacy with pembrolizumab by increasing number of T cells both in tumor microenvironment (TME) and peripheral blood (PB). Methods: This is an open-label, phase Ib/II study in patients with refractory or recurrent TNBC who failed from standard chemotherapy in the metastatic setting, with ≤3rd-lines of previous chemotherapy. The dose escalation phase adopted the 3+3 design. The GX-I7 doses were administered IM q9w or q12w, with or without cyclophosphamide pre-conditioning depending on the allocation, and in combination with pembrolizumab 200 mg IV q3w. The objectives were dose limiting toxicities (DLTs), safety, pharmacodynamic markers including lymphocyte increase and RP2D. Results: As of January 30, 2020, GX-I7 and pembrolizumab were exposed to 24 patients (median age 46.0 years [29-75], ECOG PS 1 [58.3%], median cycle no. 3 [1-9]). Treatment was discontinued in 13 (54.2%), majority due to PD and 11 patients are ongoing. No DLTs were reported in all dose groups. Treatment related AEs occurred in 91.7% of patients with grade 1-2 and 9.1% with grade 3 (no grade 4). Common AEs were injection site reaction (39.0%) and fever (13.0%), which were easily managed. Grade 3 toxicity were AST/ALT elevation and infusion related reaction, reported from 1 patient each (4.2%). GX-I7 induced dose-dependent lymphocyte proliferation in PB, with approximately 4-folds increase in high doses. 17 patients were evaluable; confirmed objective responses from ongoing patients included one partial response (5.9%), 2 stable disease (11.8%) and 1 durable unconfirmed PD (5.9%). Conclusions: GX-I7 in combination with pembrolizumab was well tolerated, with no DLTs reported. There was no apparent increase of immune-related AEs with the addition of GX-I7. Pharmacodynamics data support proof of mechanism and it warrants further clinical studies. Clinical trial information: NCT03752723 .
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Geng, Tingting, Kai Zhu, Qi Lu, Zhenzhen Wan, Xue Chen, Liegang Liu, An Pan, and Gang Liu. "Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: A cohort study." PLOS Medicine 20, no. 1 (January 10, 2023): e1004135. http://dx.doi.org/10.1371/journal.pmed.1004135.

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Background The influence of overall lifestyle behaviors on diabetic microvascular complications remains unknown. In addition, the potential mediating biomarkers underlying the association is unclear. This study aimed to examine the associations of the combined lifestyle factors with risks of total and individual microvascular complications among patients with type 2 diabetes (T2D) and to explore the potential mediation effects of metabolic biomarkers. Methods and findings This retrospective cohort study included 15,104 patients with T2D free of macro- and microvascular complications at baseline (2006 to 2010) from the UK Biobank. Healthy lifestyle behaviors included noncurrent smoking, recommended waist circumference, regular physical activity, healthy diet, and moderate alcohol drinking. Outcomes were ascertained using electronic health records. Over a median of 8.1 years of follow-up, 1,296 cases of the composite microvascular complications occurred, including 558 diabetic retinopathy, 625 diabetic kidney disease, and 315 diabetic neuropathy, with some patients having 2 or 3 microvascular complications simultaneously. After multivariable adjustment for sociodemographic characteristics, history of hypertension, glycemic control, and medication histories, the hazard ratios (95% confidence intervals (CIs)) for the participants adhering 4 to 5 low-risk lifestyle behaviors versus 0 to 1 were 0.65 (0.46, 0.91) for diabetic retinopathy, 0.43 (0.30, 0.61) for diabetic kidney disease, 0.46 (0.29, 0.74) for diabetic neuropathy, and 0.54 (0.43, 0.68) for the composite outcome (all Ps-trend ≤0.01). Further, the population-attributable fraction (95% CIs) of diabetic microvascular complications for poor adherence to the overall healthy lifestyle (<4 low-risk factors) ranged from 25.3% (10.0%, 39.4%) to 39.0% (17.7%, 56.8%). In addition, albumin, HDL-C, triglycerides, apolipoprotein A, C-reactive protein, and HbA1c collectively explained 23.20% (12.70%, 38.50%) of the associations between overall lifestyle behaviors and total diabetic microvascular complications. The key limitation of the current analysis was the potential underreporting of microvascular complications because the cases were identified via electronic health records. Conclusions Adherence to overall healthy lifestyle behaviors was associated with a significantly lower risk of microvascular complications in patients with T2D, and the favorable associations were partially mediated through improving biomarkers of glycemic control, systemic inflammation, liver function, and lipid profile.
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Grohé, Christian, Thomas Wehler, Tobias Dechow, Sven Henschke, Wolfgang Schuette, Ina Dittrich, Stefan Hammerschmidt, et al. "Second-line nintedanib plus docetaxel for patients with lung adenocarcinoma after failure on first-line immune checkpoint inhibitor combination therapy: Initial efficacy and safety results from VARGADO Cohort C." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 9033. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.9033.

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9033 Background: The treatment landscape in advanced non-small cell lung cancer (NSCLC) has undergone significant changes, with immune checkpoint inhibitor (ICI) +/- chemotherapy now the preferred first-line (1L) regimen for metastatic, non-mutated NSCLC. However, only limited clinical data are available to guide subsequent treatment selection. Nintedanib (Vargatef), an oral triple angiokinase inhibitor targeting the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) pathways, is approved in the EU and other countries in combination with docetaxel for the treatment of advanced adenocarcinoma NSCLC after failure on 1L chemotherapy. Methods: This analysis is part of the ongoing, prospective, non-interventional VARGADO study (NCT02392455) of nintedanib + docetaxel. Here, we present initial efficacy and safety results from 100 patients (pts) with adenocarcinoma NSCLC in Cohort C, who received second-line (2L) nintedanib + docetaxel after failure on prior 1L ICI in combination with chemotherapy. Results: In Cohort C, the median age was 63 years (range: 43–84); 58 pts (58.0%) were men, and 71 pts (71.0%) had ECOG PS 0/1. Ninety-five pts (95.0%) had received prior 1L pembrolizumab-based combination therapy. Thirty-nine pts (39.0%) had progressed within 6 months after the start of 1L therapy, and 66 pts (66.0%) had progressed within 9 months. Objective response rate with 2L nintedanib + docetaxel was 37.3% (22/59 pts), disease control rate was 67.8% (40/59 pts), and median progression-free survival (PFS) was 4.4 months (95% confidence interval [CI]: 2.6–6.6). Among pts who had experienced disease progression < 9 months after the start of 1L therapy (n = 66), median PFS from the start of 2L nintedanib + docetaxel was 4.1 months (95% CI: 2.5–6.6). Among pts with disease progression ≥9 months after the start of 1L therapy (n = 34), median PFS from the start of 2L nintedanib + docetaxel was 8.5 months (95% CI: 2.4–not estimable). Grade ≥3 treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation were observed in 47 pts (47.0%), 37 pts (37.0%) and 28 pts (28.0%), respectively. Conclusions: Initial data from VARGADO Cohort C provide the first evidence that 2L nintedanib + docetaxel has encouraging and clinically meaningful efficacy, and a manageable safety profile in pts with advanced adenocarcinoma NSCLC following progression on 1L ICI in combination with chemotherapy. Clinical trial information: NCT02392455.
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