Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis
Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care. To derive sepsis phenotypes from clinical data, determine their reproducibility and correlation with host-response biomarkers and clinical outcomes, and assess the pote...
Saved in:
| Published in: | JAMA : the journal of the American Medical Association Vol. 321; no. 20; p. 2003 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
28.05.2019
|
| Subjects: | |
| ISSN: | 1538-3598, 1538-3598 |
| Online Access: | Get more information |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care.
To derive sepsis phenotypes from clinical data, determine their reproducibility and correlation with host-response biomarkers and clinical outcomes, and assess the potential causal relationship with results from randomized clinical trials (RCTs).
Retrospective analysis of data sets using statistical, machine learning, and simulation tools. Phenotypes were derived among 20 189 total patients (16 552 unique patients) who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients and n = 31 160 unique patients), in a prospective cohort study of sepsis due to pneumonia (n = 583), and in 3 sepsis RCTs (n = 4737).
All clinical and laboratory variables in the electronic health record.
Derived phenotype (α, β, γ, and δ) frequency, host-response biomarkers, 28-day and 365-day mortality, and RCT simulation outputs.
The derivation cohort included 20 189 patients with sepsis (mean age, 64 [SD, 17] years; 10 022 [50%] male; mean maximum 24-hour Sequential Organ Failure Assessment [SOFA] score, 3.9 [SD, 2.4]). The validation cohort included 43 086 patients (mean age, 67 [SD, 17] years; 21 993 [51%] male; mean maximum 24-hour SOFA score, 3.6 [SD, 2.0]). Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the β phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. There were consistent differences in biomarker patterns by phenotype. In the derivation cohort, cumulative 28-day mortality was 287 deaths of 5691 unique patients (5%) for the α phenotype; 561 of 4420 (13%) for the β phenotype; 1031 of 4318 (24%) for the γ phenotype; and 897 of 2223 (40%) for the δ phenotype. Across all cohorts and trials, 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P < .001). In simulation models, the proportion of RCTs reporting benefit, harm, or no effect changed considerably (eg, varying the phenotype frequencies within an RCT of early goal-directed therapy changed the results from >33% chance of benefit to >60% chance of harm).
In this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects. Further research is needed to determine the utility of these phenotypes in clinical care and for informing trial design and interpretation. |
|---|---|
| AbstractList | Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care.ImportanceSepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care.To derive sepsis phenotypes from clinical data, determine their reproducibility and correlation with host-response biomarkers and clinical outcomes, and assess the potential causal relationship with results from randomized clinical trials (RCTs).ObjectiveTo derive sepsis phenotypes from clinical data, determine their reproducibility and correlation with host-response biomarkers and clinical outcomes, and assess the potential causal relationship with results from randomized clinical trials (RCTs).Retrospective analysis of data sets using statistical, machine learning, and simulation tools. Phenotypes were derived among 20 189 total patients (16 552 unique patients) who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients and n = 31 160 unique patients), in a prospective cohort study of sepsis due to pneumonia (n = 583), and in 3 sepsis RCTs (n = 4737).Design, Settings, and ParticipantsRetrospective analysis of data sets using statistical, machine learning, and simulation tools. Phenotypes were derived among 20 189 total patients (16 552 unique patients) who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients and n = 31 160 unique patients), in a prospective cohort study of sepsis due to pneumonia (n = 583), and in 3 sepsis RCTs (n = 4737).All clinical and laboratory variables in the electronic health record.ExposuresAll clinical and laboratory variables in the electronic health record.Derived phenotype (α, β, γ, and δ) frequency, host-response biomarkers, 28-day and 365-day mortality, and RCT simulation outputs.Main Outcomes and MeasuresDerived phenotype (α, β, γ, and δ) frequency, host-response biomarkers, 28-day and 365-day mortality, and RCT simulation outputs.The derivation cohort included 20 189 patients with sepsis (mean age, 64 [SD, 17] years; 10 022 [50%] male; mean maximum 24-hour Sequential Organ Failure Assessment [SOFA] score, 3.9 [SD, 2.4]). The validation cohort included 43 086 patients (mean age, 67 [SD, 17] years; 21 993 [51%] male; mean maximum 24-hour SOFA score, 3.6 [SD, 2.0]). Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the β phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. There were consistent differences in biomarker patterns by phenotype. In the derivation cohort, cumulative 28-day mortality was 287 deaths of 5691 unique patients (5%) for the α phenotype; 561 of 4420 (13%) for the β phenotype; 1031 of 4318 (24%) for the γ phenotype; and 897 of 2223 (40%) for the δ phenotype. Across all cohorts and trials, 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P < .001). In simulation models, the proportion of RCTs reporting benefit, harm, or no effect changed considerably (eg, varying the phenotype frequencies within an RCT of early goal-directed therapy changed the results from >33% chance of benefit to >60% chance of harm).ResultsThe derivation cohort included 20 189 patients with sepsis (mean age, 64 [SD, 17] years; 10 022 [50%] male; mean maximum 24-hour Sequential Organ Failure Assessment [SOFA] score, 3.9 [SD, 2.4]). The validation cohort included 43 086 patients (mean age, 67 [SD, 17] years; 21 993 [51%] male; mean maximum 24-hour SOFA score, 3.6 [SD, 2.0]). Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the β phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. There were consistent differences in biomarker patterns by phenotype. In the derivation cohort, cumulative 28-day mortality was 287 deaths of 5691 unique patients (5%) for the α phenotype; 561 of 4420 (13%) for the β phenotype; 1031 of 4318 (24%) for the γ phenotype; and 897 of 2223 (40%) for the δ phenotype. Across all cohorts and trials, 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P < .001). In simulation models, the proportion of RCTs reporting benefit, harm, or no effect changed considerably (eg, varying the phenotype frequencies within an RCT of early goal-directed therapy changed the results from >33% chance of benefit to >60% chance of harm).In this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects. Further research is needed to determine the utility of these phenotypes in clinical care and for informing trial design and interpretation.Conclusions and RelevanceIn this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects. Further research is needed to determine the utility of these phenotypes in clinical care and for informing trial design and interpretation. Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care. To derive sepsis phenotypes from clinical data, determine their reproducibility and correlation with host-response biomarkers and clinical outcomes, and assess the potential causal relationship with results from randomized clinical trials (RCTs). Retrospective analysis of data sets using statistical, machine learning, and simulation tools. Phenotypes were derived among 20 189 total patients (16 552 unique patients) who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients and n = 31 160 unique patients), in a prospective cohort study of sepsis due to pneumonia (n = 583), and in 3 sepsis RCTs (n = 4737). All clinical and laboratory variables in the electronic health record. Derived phenotype (α, β, γ, and δ) frequency, host-response biomarkers, 28-day and 365-day mortality, and RCT simulation outputs. The derivation cohort included 20 189 patients with sepsis (mean age, 64 [SD, 17] years; 10 022 [50%] male; mean maximum 24-hour Sequential Organ Failure Assessment [SOFA] score, 3.9 [SD, 2.4]). The validation cohort included 43 086 patients (mean age, 67 [SD, 17] years; 21 993 [51%] male; mean maximum 24-hour SOFA score, 3.6 [SD, 2.0]). Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the β phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. There were consistent differences in biomarker patterns by phenotype. In the derivation cohort, cumulative 28-day mortality was 287 deaths of 5691 unique patients (5%) for the α phenotype; 561 of 4420 (13%) for the β phenotype; 1031 of 4318 (24%) for the γ phenotype; and 897 of 2223 (40%) for the δ phenotype. Across all cohorts and trials, 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P < .001). In simulation models, the proportion of RCTs reporting benefit, harm, or no effect changed considerably (eg, varying the phenotype frequencies within an RCT of early goal-directed therapy changed the results from >33% chance of benefit to >60% chance of harm). In this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects. Further research is needed to determine the utility of these phenotypes in clinical care and for informing trial design and interpretation. |
| Author | Seymour, Christopher W Chang, Chung-Chou H Vodovotz, Yoram Cooper, Gregory Gomez, Hernando Elliott, Corrine F Berry, Scott Wang, Shu Kellum, John A Mi, Qi Huang, David T Clermont, Gilles Opal, Steven M Weiss, Jeremy C Visweswaran, Shyam Yende, Sachin Angus, Derek C Kennedy, Jason N van der Poll, Tom Talisa, Victor Yealy, Donald M Xu, Zhongying |
| Author_xml | – sequence: 1 givenname: Christopher W surname: Seymour fullname: Seymour, Christopher W organization: Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 2 givenname: Jason N surname: Kennedy fullname: Kennedy, Jason N organization: Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 3 givenname: Shu surname: Wang fullname: Wang, Shu organization: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 4 givenname: Chung-Chou H surname: Chang fullname: Chang, Chung-Chou H organization: Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 5 givenname: Corrine F surname: Elliott fullname: Elliott, Corrine F organization: Berry Consultants, Austin, Texas – sequence: 6 givenname: Zhongying surname: Xu fullname: Xu, Zhongying organization: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 7 givenname: Scott surname: Berry fullname: Berry, Scott organization: Berry Consultants, Austin, Texas – sequence: 8 givenname: Gilles surname: Clermont fullname: Clermont, Gilles organization: Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 9 givenname: Gregory surname: Cooper fullname: Cooper, Gregory organization: Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 10 givenname: Hernando surname: Gomez fullname: Gomez, Hernando organization: Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 11 givenname: David T surname: Huang fullname: Huang, David T organization: Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 12 givenname: John A surname: Kellum fullname: Kellum, John A organization: Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 13 givenname: Qi surname: Mi fullname: Mi, Qi organization: Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 14 givenname: Steven M surname: Opal fullname: Opal, Steven M organization: Department of Medicine, Infectious Disease Division, Rhode Island Hospital, Providence – sequence: 15 givenname: Victor surname: Talisa fullname: Talisa, Victor organization: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 16 givenname: Tom surname: van der Poll fullname: van der Poll, Tom organization: Center of Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands – sequence: 17 givenname: Shyam surname: Visweswaran fullname: Visweswaran, Shyam organization: Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 18 givenname: Yoram surname: Vodovotz fullname: Vodovotz, Yoram organization: Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 19 givenname: Jeremy C surname: Weiss fullname: Weiss, Jeremy C organization: Machine Learning Department, Carnegie Mellon University, Pittsburgh, Pennsylvania – sequence: 20 givenname: Donald M surname: Yealy fullname: Yealy, Donald M organization: Department of Emergency Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania – sequence: 21 givenname: Sachin surname: Yende fullname: Yende, Sachin organization: Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania – sequence: 22 givenname: Derek C surname: Angus fullname: Angus, Derek C organization: Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31104070$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkM1LAzEQxYNU7IdePUqOHtyaSZru5ij1q1C0YPW6ZDezmJJN1s220P_eRSv4LvPe8GMY3pgMfPBIyCWwKTAGt1td6ylnoKYyVXBCRiBFlgipssE_PyTjGLesF4j0jAwFAJuxlI2IucfW7nVng7-hH9pZc_TaG7oOHfrOakc3Lequ7gNd1o2z5Q8UaajoS9ijowtnfb91dP2JPnSHBiOtQkvfsIk2npPTSruIF8c5Ie-PD5vFc7J6fVou7laJlkx0SVYamclSKaErJYpsxgvDKyxMwaEELRjKuZIGgPe_V2UPqZThDLKC6WKukE_I9e_dpg1fO4xdXttYonPaY9jFnHPBWZpCmvXo1RHdFTWavGltrdtD_tcM_waluGg_ |
| CitedBy_id | crossref_primary_10_1186_s12879_022_07210_y crossref_primary_10_1371_journal_pone_0271667 crossref_primary_10_1016_j_ccc_2023_02_003 crossref_primary_10_1097_SHK_0000000000002506 crossref_primary_10_1002_rth2_12465 crossref_primary_10_3389_fmed_2021_617486 crossref_primary_10_1016_j_jcrc_2025_155262 crossref_primary_10_3390_medicina58121843 crossref_primary_10_1172_JCI158348 crossref_primary_10_1097_MCC_0000000000001280 crossref_primary_10_3390_diagnostics14242845 crossref_primary_10_1016_j_surg_2024_08_037 crossref_primary_10_1186_s13054_023_04690_5 crossref_primary_10_3390_diagnostics12102498 crossref_primary_10_1016_j_ccc_2019_08_002 crossref_primary_10_1016_j_cell_2022_01_012 crossref_primary_10_1016_j_thromres_2021_03_017 crossref_primary_10_3390_jcm14062113 crossref_primary_10_1097_PCC_0000000000003314 crossref_primary_10_1080_14737159_2020_1851199 crossref_primary_10_5005_jaypee_journals_10071_24933_139 crossref_primary_10_1016_j_jcrc_2025_155269 crossref_primary_10_1097_MCC_0000000000001297 crossref_primary_10_3390_cells13141172 crossref_primary_10_1016_j_ccc_2023_02_001 crossref_primary_10_1097_ALN_0000000000003600 crossref_primary_10_1002_ams2_944 crossref_primary_10_1080_17520363_2025_2521251 crossref_primary_10_1186_s13054_020_02917_3 crossref_primary_10_1186_s40560_024_00747_x crossref_primary_10_1007_s15010_025_02607_8 crossref_primary_10_1016_j_isci_2024_109325 crossref_primary_10_1186_s13054_021_03734_y crossref_primary_10_3389_fped_2021_743544 crossref_primary_10_1016_j_ajem_2023_10_045 crossref_primary_10_1016_j_resplu_2023_100435 crossref_primary_10_5492_wjccm_v11_i1_1 crossref_primary_10_1513_AnnalsATS_202211_946OC crossref_primary_10_1016_j_jss_2020_03_046 crossref_primary_10_1097_CCM_0000000000006621 crossref_primary_10_1177_10600280221096886 crossref_primary_10_1097_CCM_0000000000006862 crossref_primary_10_2147_JIR_S418697 crossref_primary_10_1213_ANE_0000000000007715 crossref_primary_10_1016_j_xgen_2025_100971 crossref_primary_10_1097_SHK_0000000000001864 crossref_primary_10_3390_geriatrics9020045 crossref_primary_10_1080_14787210_2021_1846522 crossref_primary_10_1097_CCM_0000000000004676 crossref_primary_10_1016_j_ejim_2019_07_008 crossref_primary_10_1097_CCE_0000000000001087 crossref_primary_10_1126_scitranslmed_abq4433 crossref_primary_10_1161_CIRCRESAHA_121_319969 crossref_primary_10_1016_j_ccc_2019_08_014 crossref_primary_10_1097_CCE_0000000000001085 crossref_primary_10_3389_fmed_2022_880896 crossref_primary_10_3390_jcm11185332 crossref_primary_10_1186_s13054_019_2655_7 crossref_primary_10_3389_fmed_2022_878337 crossref_primary_10_1097_CCM_0000000000004617 crossref_primary_10_1097_ACO_0000000000000964 crossref_primary_10_1097_CCM_0000000000004856 crossref_primary_10_1016_j_ccc_2023_03_002 crossref_primary_10_1159_000525548 crossref_primary_10_1016_j_ccc_2023_03_006 crossref_primary_10_1016_j_ccc_2023_03_005 crossref_primary_10_1136_thorax_2022_219016 crossref_primary_10_1016_j_semnephrol_2025_151665 crossref_primary_10_1186_s13054_022_04106_w crossref_primary_10_3389_fcimb_2020_00236 crossref_primary_10_1007_s41030_020_00110_z crossref_primary_10_1080_0886022X_2025_2459349 crossref_primary_10_3390_biomedicines13092315 crossref_primary_10_7759_cureus_72255 crossref_primary_10_3390_cells13110892 crossref_primary_10_1055_s_0044_1787992 crossref_primary_10_1055_s_0044_1787991 crossref_primary_10_1055_s_0044_1787990 crossref_primary_10_1186_s40635_023_00491_w crossref_primary_10_1001_jamainternmed_2020_0183 crossref_primary_10_1186_s13054_022_03907_3 crossref_primary_10_3389_fimmu_2024_1495260 crossref_primary_10_1186_s40635_020_00338_8 crossref_primary_10_1093_jamia_ocz211 crossref_primary_10_1038_s41746_024_01194_6 crossref_primary_10_14814_phy2_15048 crossref_primary_10_3390_biomedicines8110494 crossref_primary_10_1097_MCC_0000000000001066 crossref_primary_10_1136_emermed_2019_209239 crossref_primary_10_1016_j_jcrc_2024_154932 crossref_primary_10_4330_wjc_v15_i3_76 crossref_primary_10_1001_jama_2023_18591 crossref_primary_10_3390_jpm14020149 crossref_primary_10_1016_j_eclinm_2025_103173 crossref_primary_10_1186_s12967_021_03051_6 crossref_primary_10_1007_s00108_020_00862_5 crossref_primary_10_1186_s40001_025_02660_x crossref_primary_10_1186_s13054_024_04876_5 crossref_primary_10_1097_MCC_0000000000001078 crossref_primary_10_3389_fcvm_2023_1200441 crossref_primary_10_1001_jamanetworkopen_2024_34197 crossref_primary_10_1161_JAHA_122_028882 crossref_primary_10_1001_jama_2020_2278 crossref_primary_10_1186_s13613_021_00952_z crossref_primary_10_1093_burnst_tkaf001 crossref_primary_10_1002_alz_13419 crossref_primary_10_1007_s11908_024_00833_z crossref_primary_10_1097_PCC_0000000000002870 crossref_primary_10_3390_cells11182833 crossref_primary_10_1016_j_jscai_2024_102047 crossref_primary_10_1186_s13054_022_04013_0 crossref_primary_10_1186_s12874_024_02440_x crossref_primary_10_1186_s13613_023_01143_8 crossref_primary_10_1007_s00134_019_05662_6 crossref_primary_10_3390_jcm12041513 crossref_primary_10_1007_s11886_024_02149_9 crossref_primary_10_1159_000539081 crossref_primary_10_1097_JS9_0000000000002668 crossref_primary_10_1007_s10916_022_01825_z crossref_primary_10_3390_medicina60111740 crossref_primary_10_1097_PEC_0000000000003397 crossref_primary_10_1186_s40635_021_00400_z crossref_primary_10_1080_07853890_2023_2197290 crossref_primary_10_1038_s41598_020_67864_z crossref_primary_10_3389_fimmu_2024_1413560 crossref_primary_10_1016_j_accpm_2019_09_003 crossref_primary_10_1186_s12967_024_05975_1 crossref_primary_10_1097_SHK_0000000000001486 crossref_primary_10_1038_s41598_020_77319_0 crossref_primary_10_3389_fmed_2021_628302 crossref_primary_10_3390_antibiotics13010046 crossref_primary_10_1007_s12185_022_03337_5 crossref_primary_10_1080_0886022X_2024_2325640 crossref_primary_10_1097_PCC_0000000000003708 crossref_primary_10_1097_CCE_0000000000001228 crossref_primary_10_1186_s13049_020_00745_6 crossref_primary_10_1002_emp2_13149 crossref_primary_10_1016_j_jss_2025_03_052 crossref_primary_10_1016_j_kint_2020_02_013 crossref_primary_10_1186_s12967_022_03655_6 crossref_primary_10_3389_fmed_2022_915224 crossref_primary_10_1097_CCM_0000000000004842 crossref_primary_10_1155_2024_6699274 crossref_primary_10_1186_s43054_023_00240_4 crossref_primary_10_1186_s40635_025_00744_w crossref_primary_10_14789_jmj_JMJ23_0042_P crossref_primary_10_17816_psaic1873 crossref_primary_10_1097_SHK_0000000000002316 crossref_primary_10_1016_j_ebiom_2021_103697 crossref_primary_10_1515_dx_2020_0142 crossref_primary_10_1093_burnst_tkaf014 crossref_primary_10_3389_fimmu_2024_1445858 crossref_primary_10_3390_antiox12030561 crossref_primary_10_1038_s41746_025_01587_1 crossref_primary_10_1513_AnnalsATS_202105_547OC crossref_primary_10_1007_s00134_023_07156_y crossref_primary_10_1016_j_mpmed_2021_08_010 crossref_primary_10_1016_j_cmi_2020_02_003 crossref_primary_10_1016_j_amjms_2024_07_022 crossref_primary_10_3389_fimmu_2024_1434688 crossref_primary_10_7326_ANNALS_24_02426 crossref_primary_10_1001_jamainternmed_2023_0257 crossref_primary_10_1016_j_jcrc_2020_11_006 crossref_primary_10_7759_cureus_73508 crossref_primary_10_1016_j_intimp_2024_113246 crossref_primary_10_1097_MCC_0000000000000834 crossref_primary_10_1097_PCC_0000000000002422 crossref_primary_10_1038_s41598_021_87668_z crossref_primary_10_1002_ams2_740 crossref_primary_10_1513_AnnalsATS_202205_399ED crossref_primary_10_1038_s41598_022_23032_z crossref_primary_10_1097_CCE_0000000000000178 crossref_primary_10_1186_s13054_025_05588_0 crossref_primary_10_1097_CCE_0000000000000191 crossref_primary_10_1038_s41591_021_01614_0 crossref_primary_10_3389_fimmu_2022_829210 crossref_primary_10_3389_fsci_2025_1557323 crossref_primary_10_1016_j_pcl_2022_01_015 crossref_primary_10_1016_j_cpcardiol_2022_101337 crossref_primary_10_1007_s00380_020_01640_x crossref_primary_10_1097_PCC_0000000000003789 crossref_primary_10_1097_SHK_0000000000001675 crossref_primary_10_1016_S2213_2600_23_00237_0 crossref_primary_10_1007_s12028_023_01712_6 crossref_primary_10_1186_s13054_023_04717_x crossref_primary_10_1097_CCE_0000000000001274 crossref_primary_10_2147_IDR_S499643 crossref_primary_10_1016_j_ebiom_2023_104942 crossref_primary_10_1016_j_bja_2021_08_007 crossref_primary_10_1186_s40560_023_00672_5 crossref_primary_10_1097_CCM_0000000000003932 crossref_primary_10_2196_37928 crossref_primary_10_1164_rccm_202001_0003LE crossref_primary_10_1038_s41598_022_11061_7 crossref_primary_10_1002_ams2_760 crossref_primary_10_3389_fphar_2021_765435 crossref_primary_10_1016_S2213_2600_23_00468_X crossref_primary_10_1093_ndt_gfad142 crossref_primary_10_3390_microorganisms11051119 crossref_primary_10_1093_aje_kwad107 crossref_primary_10_1001_jama_2019_12591 crossref_primary_10_3389_fimmu_2023_1257572 crossref_primary_10_1038_s41598_021_99828_2 crossref_primary_10_1016_j_jaim_2020_11_010 crossref_primary_10_1016_j_resuscitation_2024_110196 crossref_primary_10_1007_s11739_025_03960_0 crossref_primary_10_1001_jama_2019_12587 crossref_primary_10_1039_D5BM00352K crossref_primary_10_1093_biostatistics_kxaf023 crossref_primary_10_1186_s40635_022_00433_y crossref_primary_10_3390_biomedicines10020198 crossref_primary_10_3390_ijms242417429 crossref_primary_10_1016_j_anclin_2025_05_005 crossref_primary_10_1002_cyto_b_22232 crossref_primary_10_1016_j_jcrc_2024_154793 crossref_primary_10_1186_s12871_024_02838_6 crossref_primary_10_2196_54621 crossref_primary_10_1371_journal_pgph_0004429 crossref_primary_10_1186_s13054_020_03393_5 crossref_primary_10_1186_s13054_023_04762_6 crossref_primary_10_1016_S2213_2600_23_00266_7 crossref_primary_10_1186_s13613_025_01532_1 crossref_primary_10_1038_s41598_023_42657_2 crossref_primary_10_1136_archdischild_2019_317789 crossref_primary_10_3389_fmed_2021_775511 crossref_primary_10_1186_s13054_024_05046_3 crossref_primary_10_1136_bmjhci_2021_100458 crossref_primary_10_1038_s41598_025_86664_x crossref_primary_10_3390_jcm14124026 crossref_primary_10_1186_s13054_022_03977_3 crossref_primary_10_1016_j_ecoenv_2024_117238 crossref_primary_10_1016_j_jss_2022_10_030 crossref_primary_10_1007_s00101_020_00849_9 crossref_primary_10_1007_s00134_021_06363_9 crossref_primary_10_1186_s13054_022_04020_1 crossref_primary_10_1016_j_clim_2020_108660 crossref_primary_10_1186_s13054_019_2528_0 crossref_primary_10_3390_jcm11020336 crossref_primary_10_1016_j_idc_2022_08_001 crossref_primary_10_2147_IDR_S390947 crossref_primary_10_1186_s13054_021_03586_6 crossref_primary_10_1097_SHK_0000000000002151 crossref_primary_10_1164_rccm_202407_1394OC crossref_primary_10_1186_s13054_024_04837_y crossref_primary_10_1186_s13023_022_02315_8 crossref_primary_10_4103_JTCCM_D_22_00016 crossref_primary_10_3390_jcm11216545 crossref_primary_10_4103_JTCCM_D_22_00015 crossref_primary_10_1097_CCE_0000000000000550 crossref_primary_10_1080_21548331_2020_1720215 crossref_primary_10_1093_ajhp_zxae139 crossref_primary_10_3389_fimmu_2022_867625 crossref_primary_10_1136_bmj_2023_076175 crossref_primary_10_1093_ajhp_zxae134 crossref_primary_10_1164_rccm_202006_2522OC crossref_primary_10_2196_46807 crossref_primary_10_1097_TA_0000000000003691 crossref_primary_10_1007_s00134_024_07593_3 crossref_primary_10_1097_CCM_0000000000005034 crossref_primary_10_1097_CCM_0000000000006362 crossref_primary_10_1186_s40779_022_00422_y crossref_primary_10_1038_s41598_024_70522_3 crossref_primary_10_1007_s00134_019_05898_2 crossref_primary_10_1001_jamanetworkopen_2020_37739 crossref_primary_10_1007_s11739_023_03223_w crossref_primary_10_1186_s40001_025_02903_x crossref_primary_10_3390_ijms22094933 crossref_primary_10_51867_ajernet_6_3_53 crossref_primary_10_3389_fgene_2024_1294381 crossref_primary_10_3390_cells13050439 crossref_primary_10_3389_fimmu_2021_622601 crossref_primary_10_1002_ped4_12405 crossref_primary_10_1007_s15010_025_02569_x crossref_primary_10_1164_rccm_202311_2086SO crossref_primary_10_1007_s11908_023_00815_7 crossref_primary_10_1016_j_hroo_2025_07_003 crossref_primary_10_1016_j_jtha_2024_02_006 crossref_primary_10_1164_rccm_202412_2377OC crossref_primary_10_1016_j_jad_2023_12_005 crossref_primary_10_1097_MCC_0000000000000772 crossref_primary_10_1016_j_biocel_2025_106823 crossref_primary_10_3389_fimmu_2021_792448 crossref_primary_10_3389_fmed_2020_598621 crossref_primary_10_5694_mja2_50338 crossref_primary_10_1097_CCM_0000000000005054 crossref_primary_10_1186_s13054_020_02866_x crossref_primary_10_1371_journal_pdig_0000334 crossref_primary_10_1097_01_CCN_0000654796_79252_dc crossref_primary_10_1007_s00068_023_02358_x crossref_primary_10_1542_peds_2023_062967 crossref_primary_10_1542_peds_2021_052565 crossref_primary_10_1016_j_respe_2023_102176 crossref_primary_10_1016_j_surg_2024_03_042 crossref_primary_10_1186_s13054_021_03682_7 crossref_primary_10_1038_s41746_022_00580_2 crossref_primary_10_1097_SHK_0000000000002598 crossref_primary_10_1097_SHK_0000000000002115 crossref_primary_10_1097_CCE_0000000000000116 crossref_primary_10_1186_s12014_025_09556_2 crossref_primary_10_3389_fphar_2025_1622754 crossref_primary_10_1097_CCM_0000000000005046 crossref_primary_10_1097_CCM_0000000000006135 crossref_primary_10_1186_s13054_024_05004_z crossref_primary_10_1001_jama_2019_12595 crossref_primary_10_1111_ijcp_14376 crossref_primary_10_6339_21_JDS996 crossref_primary_10_1080_17512433_2019_1643235 crossref_primary_10_3389_fphys_2022_1050849 crossref_primary_10_1007_s40262_024_01424_w crossref_primary_10_1016_j_heliyon_2023_e20714 crossref_primary_10_1007_s00134_021_06587_9 crossref_primary_10_1097_SHK_0000000000001935 crossref_primary_10_1097_ACO_0000000000001216 crossref_primary_10_1186_s12931_023_02476_5 crossref_primary_10_3389_fimmu_2021_795052 crossref_primary_10_61958_NMRV5643 crossref_primary_10_1186_s13054_020_2778_x crossref_primary_10_1016_j_coviro_2020_07_010 crossref_primary_10_3390_jcm14134450 crossref_primary_10_1016_j_ajem_2019_158460 crossref_primary_10_3390_life14101257 crossref_primary_10_1016_j_pharmthera_2020_107529 crossref_primary_10_4103_jpgm_jpgm_357_24 crossref_primary_10_1097_CCM_0000000000006560 crossref_primary_10_51893_2022_1_OA3 crossref_primary_10_1177_1753425920980078 crossref_primary_10_1002_jpen_1945 crossref_primary_10_1038_s41420_023_01766_7 crossref_primary_10_1038_s41598_022_08032_3 crossref_primary_10_1016_j_jss_2022_10_096 crossref_primary_10_3389_fmed_2020_00117 crossref_primary_10_1186_s40001_024_01866_9 crossref_primary_10_1007_s11739_024_03836_9 crossref_primary_10_1186_s12929_024_01043_4 crossref_primary_10_1097_CCM_0000000000004132 crossref_primary_10_4274_balkanmedj_galenos_2023_2023_4_6 crossref_primary_10_1038_s41746_021_00481_w crossref_primary_10_1186_s13054_023_04437_2 crossref_primary_10_1007_s11596_024_2870_6 crossref_primary_10_1002_phar_2448 crossref_primary_10_1177_08850666231153393 crossref_primary_10_1016_j_eclinm_2025_103240 crossref_primary_10_1165_rcmb_2024_0561ED crossref_primary_10_1186_s12874_023_02138_6 crossref_primary_10_3390_ijms23158399 crossref_primary_10_1002_phar_2683 crossref_primary_10_1161_ATVBAHA_119_312754 crossref_primary_10_2217_fmb_2022_0170 crossref_primary_10_1080_14787210_2020_1812384 crossref_primary_10_31260_RepertMedCir_01217273_973 crossref_primary_10_1097_SHK_0000000000001906 crossref_primary_10_3390_pathogens13010089 crossref_primary_10_1016_j_compbiomed_2019_103488 crossref_primary_10_1097_MEJ_0000000000000893 crossref_primary_10_1016_j_medin_2024_02_006 crossref_primary_10_1136_thorax_2023_220538 crossref_primary_10_1097_CCM_0000000000005247 crossref_primary_10_1007_s00134_023_07171_z crossref_primary_10_1038_s41390_021_01673_6 crossref_primary_10_1016_j_ajem_2023_03_022 crossref_primary_10_1097_CCE_0000000000000955 crossref_primary_10_3389_fmed_2020_598652 crossref_primary_10_1016_j_biopha_2023_115719 crossref_primary_10_3389_fped_2023_1035576 crossref_primary_10_1177_10760296211047231 crossref_primary_10_1007_s00464_024_10756_4 crossref_primary_10_1007_s11606_020_05653_0 crossref_primary_10_1161_JAHA_120_020085 crossref_primary_10_36290_aim_2020_059 crossref_primary_10_1080_13543784_2022_2102477 crossref_primary_10_1093_jleuko_qiae107 crossref_primary_10_1111_exsy_12806 crossref_primary_10_1016_j_bja_2021_10_050 crossref_primary_10_1097_QCO_0000000000000583 crossref_primary_10_1097_CCM_0000000000005675 crossref_primary_10_3389_fcell_2023_1330433 crossref_primary_10_1007_s00134_025_07924_y crossref_primary_10_1002_emp2_12660 crossref_primary_10_3390_biomedicines10092260 crossref_primary_10_1097_pq9_0000000000000483 crossref_primary_10_1186_s13054_022_03915_3 crossref_primary_10_1038_s41366_025_01805_6 crossref_primary_10_3389_fsci_2024_1469417 crossref_primary_10_12998_wjcc_v8_i18_3920 crossref_primary_10_1007_s00134_024_07586_2 crossref_primary_10_1097_CCM_0000000000004568 crossref_primary_10_1055_a_1105_0572 crossref_primary_10_3389_fgene_2022_884762 crossref_primary_10_1007_s11908_021_00747_0 crossref_primary_10_1097_CCE_0000000000000974 crossref_primary_10_3389_fimmu_2024_1441838 crossref_primary_10_1164_rccm_201912_2441OC crossref_primary_10_1038_s41598_020_74906_z crossref_primary_10_1186_s12879_023_08147_6 crossref_primary_10_1007_s12325_022_02280_5 crossref_primary_10_1186_s13054_023_04533_3 crossref_primary_10_1183_13993003_02011_2024 crossref_primary_10_1016_j_cca_2023_117738 crossref_primary_10_3389_fimmu_2021_592303 crossref_primary_10_1016_j_jcrc_2020_09_002 crossref_primary_10_1111_bjh_18835 crossref_primary_10_1007_s11306_024_02089_z crossref_primary_10_1038_s41598_021_84860_z crossref_primary_10_1093_cid_ciaf187 crossref_primary_10_1017_S0950268824000645 crossref_primary_10_1016_j_bspc_2023_105146 crossref_primary_10_1016_j_ccc_2021_07_003 crossref_primary_10_1016_j_medine_2024_02_006 crossref_primary_10_1097_CCM_0000000000005203 crossref_primary_10_1016_j_heliyon_2024_e28520 crossref_primary_10_1111_jth_14812 crossref_primary_10_1016_j_immuni_2021_10_012 crossref_primary_10_1038_s41598_021_88970_6 crossref_primary_10_2196_16912 crossref_primary_10_1007_s00134_020_05934_6 crossref_primary_10_1016_j_jbi_2021_103789 crossref_primary_10_1038_s41598_025_94483_3 crossref_primary_10_3389_fmed_2025_1575237 crossref_primary_10_3389_fimmu_2020_558898 crossref_primary_10_1164_rccm_202312_2265ED crossref_primary_10_1016_j_medine_2025_502172 crossref_primary_10_1007_s00134_020_06000_x crossref_primary_10_1155_2020_8032806 crossref_primary_10_1038_s41598_024_55667_5 crossref_primary_10_1097_CCE_0000000000000083 crossref_primary_10_3389_fimmu_2024_1391395 crossref_primary_10_1097_CCE_0000000000001176 crossref_primary_10_1097_TA_0000000000002613 crossref_primary_10_1371_journal_pone_0246332 crossref_primary_10_1007_s12519_023_00689_8 crossref_primary_10_1001_jamanetworkopen_2020_16209 crossref_primary_10_1016_j_artmed_2024_102905 crossref_primary_10_1186_s13054_019_2521_7 crossref_primary_10_1371_journal_pone_0232175 crossref_primary_10_3389_fphar_2024_1475414 crossref_primary_10_1186_s13054_025_05639_6 crossref_primary_10_18621_eurj_1333071 crossref_primary_10_1186_s13005_025_00492_y crossref_primary_10_1016_j_jtha_2022_11_013 crossref_primary_10_1097_CCE_0000000000001183 crossref_primary_10_1016_j_chest_2024_04_035 crossref_primary_10_1016_j_jbi_2021_103762 crossref_primary_10_1080_10903127_2024_2386445 crossref_primary_10_1186_s13054_025_05256_3 crossref_primary_10_1016_j_chest_2024_04_018 crossref_primary_10_1155_2022_5351137 crossref_primary_10_2196_58779 crossref_primary_10_1186_s13054_024_05061_4 crossref_primary_10_1097_CCM_0000000000005406 crossref_primary_10_1097_CCM_0000000000004320 crossref_primary_10_3390_jcm12041499 crossref_primary_10_1093_cei_uxae019 crossref_primary_10_1213_ANE_0000000000006753 crossref_primary_10_1227_neu_0000000000003249 crossref_primary_10_1055_a_1200_4662 crossref_primary_10_1097_SHK_0000000000001980 crossref_primary_10_1097_CCM_0000000000004305 crossref_primary_10_1002_ccd_30103 crossref_primary_10_1016_j_atherosclerosis_2019_12_009 crossref_primary_10_1177_0310057X231195098 crossref_primary_10_1007_s40121_022_00684_y crossref_primary_10_3390_cells9010120 crossref_primary_10_1007_s11739_023_03512_4 crossref_primary_10_1002_ams2_843 crossref_primary_10_1016_j_intimp_2020_107143 crossref_primary_10_1186_s13054_023_04571_x crossref_primary_10_3390_nu13072366 crossref_primary_10_1093_burnst_tkae073 crossref_primary_10_3389_fphys_2022_1094199 crossref_primary_10_1016_j_mib_2020_02_005 crossref_primary_10_1097_AS9_0000000000000429 crossref_primary_10_1097_PCC_0000000000003244 crossref_primary_10_1111_cts_13088 crossref_primary_10_7554_eLife_58142 crossref_primary_10_1038_s44161_023_00391_y crossref_primary_10_1093_ckj_sfab207 crossref_primary_10_9778_cmajo_20220193 crossref_primary_10_1038_s41598_021_99581_6 crossref_primary_10_1111_sdi_12915 crossref_primary_10_1038_s41590_023_01660_5 crossref_primary_10_1097_MCO_0000000000000628 crossref_primary_10_3390_ijms25020962 crossref_primary_10_2147_JIR_S492902 crossref_primary_10_1111_eci_14159 crossref_primary_10_1186_s40560_020_0435_8 crossref_primary_10_3389_fimmu_2020_624279 crossref_primary_10_1186_s13054_022_03972_8 crossref_primary_10_1016_S2213_2600_20_30124_7 crossref_primary_10_1186_s13613_025_01474_8 crossref_primary_10_1097_CCM_0000000000005816 crossref_primary_10_3389_fimmu_2025_1593342 crossref_primary_10_1038_s41598_023_42081_6 crossref_primary_10_3390_metabo14100521 crossref_primary_10_3389_fpubh_2024_1330606 crossref_primary_10_3390_electronics11091507 crossref_primary_10_1016_j_mpaic_2024_06_010 crossref_primary_10_1056_NEJMra2403213 crossref_primary_10_1186_s13054_024_04877_4 crossref_primary_10_1111_jgh_16038 crossref_primary_10_3390_jcm10081693 crossref_primary_10_1097_PCC_0000000000003263 crossref_primary_10_1186_s12967_022_03469_6 crossref_primary_10_1186_s13054_022_04118_6 crossref_primary_10_3390_microorganisms11092165 crossref_primary_10_1016_j_jcrc_2022_154221 crossref_primary_10_1186_s13054_022_04071_4 crossref_primary_10_1016_j_chest_2024_03_006 crossref_primary_10_1038_s41581_019_0199_3 crossref_primary_10_1097_MCC_0000000000001186 crossref_primary_10_1186_s12931_020_01337_9 crossref_primary_10_1097_QCO_0000000000000767 crossref_primary_10_1111_liv_15141 crossref_primary_10_1016_j_bbrc_2025_152116 crossref_primary_10_1186_s40635_019_0286_6 crossref_primary_10_1007_s00595_021_02380_9 crossref_primary_10_3390_life15081317 crossref_primary_10_1016_j_ebiom_2021_103776 crossref_primary_10_1513_AnnalsATS_202102_209ST crossref_primary_10_1038_s41598_025_00830_9 crossref_primary_10_1097_01_NPR_0000884868_44595_f6 crossref_primary_10_3389_fphys_2021_678540 crossref_primary_10_1016_j_bbe_2021_06_009 crossref_primary_10_1093_jamia_ocz106 crossref_primary_10_1186_s13054_024_05030_x crossref_primary_10_1016_j_ijmedinf_2023_105286 crossref_primary_10_1001_jamanetworkopen_2020_9271 crossref_primary_10_3389_fendo_2024_1452993 crossref_primary_10_1016_j_ijbiomac_2024_136578 crossref_primary_10_1186_s40635_020_00304_4 crossref_primary_10_1007_s15010_025_02628_3 crossref_primary_10_1016_j_compbiomed_2020_104182 crossref_primary_10_1093_burnst_tkae080 crossref_primary_10_1016_j_jcrc_2024_154848 crossref_primary_10_1016_j_annemergmed_2021_03_003 crossref_primary_10_1016_j_ebiom_2020_103081 crossref_primary_10_4103_jisppd_jisppd_478_20 crossref_primary_10_1007_s00134_022_06928_2 crossref_primary_10_1038_s41581_021_00489_1 crossref_primary_10_36290_aim_2019_074 crossref_primary_10_1002_advs_202500457 crossref_primary_10_1016_j_semnephrol_2022_10_011 crossref_primary_10_1371_journal_pdig_0000110 crossref_primary_10_1016_j_imed_2021_09_001 crossref_primary_10_1055_s_0040_1715827 crossref_primary_10_1186_s12245_025_00889_1 crossref_primary_10_1371_journal_pone_0256790 crossref_primary_10_1371_journal_pone_0268547 crossref_primary_10_1038_s44321_023_00004_y crossref_primary_10_26508_lsa_202101091 crossref_primary_10_3389_fmed_2021_762198 crossref_primary_10_1111_sdi_12963 crossref_primary_10_1186_s13054_020_03351_1 crossref_primary_10_1097_NNR_0000000000000521 crossref_primary_10_1097_CCE_0000000000000251 crossref_primary_10_36290_vnl_2019_082 crossref_primary_10_1002_emp2_13264 crossref_primary_10_1016_j_jbi_2021_103949 crossref_primary_10_1038_s41591_020_0752_4 crossref_primary_10_1016_j_jbi_2024_104615 crossref_primary_10_1161_CIR_0000000000001219 crossref_primary_10_1542_peds_2021_052888P crossref_primary_10_1177_08850666241301689 crossref_primary_10_1097_SLA_0000000000004360 crossref_primary_10_1097_PCC_0000000000002532 crossref_primary_10_1182_blood_2020009774 crossref_primary_10_3389_fimmu_2022_966329 crossref_primary_10_1164_rccm_202007_2728ED crossref_primary_10_1542_peds_2021_052888D crossref_primary_10_1038_s41467_025_62848_x crossref_primary_10_7759_cureus_15531 crossref_primary_10_1016_j_csbj_2020_11_009 crossref_primary_10_1513_AnnalsATS_202305_497IP crossref_primary_10_1186_s12871_021_01552_x crossref_primary_10_2196_45614 crossref_primary_10_15252_emmm_201810128 crossref_primary_10_3390_antibiotics13020187 crossref_primary_10_1038_s41598_021_95431_7 crossref_primary_10_1097_CCM_0000000000004948 crossref_primary_10_1080_17476348_2025_2518282 crossref_primary_10_1371_journal_pone_0265052 crossref_primary_10_1016_j_cmpb_2023_107772 crossref_primary_10_1016_j_ajem_2020_09_013 crossref_primary_10_1002_alz_14624 crossref_primary_10_1016_j_chest_2021_04_038 crossref_primary_10_3389_fimmu_2020_589304 crossref_primary_10_1186_s12890_025_03648_3 crossref_primary_10_1089_sur_2021_007 crossref_primary_10_1186_s13062_025_00657_4 crossref_primary_10_1017_ice_2019_354 crossref_primary_10_1097_MLR_0000000000001997 crossref_primary_10_3389_fpubh_2025_1610220 crossref_primary_10_1186_s40635_023_00592_6 crossref_primary_10_1016_j_jbi_2024_104671 crossref_primary_10_1186_s12967_020_02620_5 crossref_primary_10_1080_13102818_2024_2349587 crossref_primary_10_1038_s41598_024_59047_x crossref_primary_10_1038_s41598_025_10665_z crossref_primary_10_1177_10760296231218711 crossref_primary_10_1016_j_ebiom_2020_103044 crossref_primary_10_1097_SHK_0000000000002413 crossref_primary_10_1155_2023_2081588 crossref_primary_10_1002_bcp_70185 crossref_primary_10_1186_s13054_023_04507_5 crossref_primary_10_1016_j_ajem_2025_01_054 crossref_primary_10_1136_tsaco_2020_000462 crossref_primary_10_1016_j_isci_2025_112083 crossref_primary_10_1097_SHK_0000000000002653 crossref_primary_10_1007_s00134_022_06908_6 crossref_primary_10_1093_ofid_ofaa596 crossref_primary_10_3389_fimmu_2023_1325020 crossref_primary_10_1038_s41591_022_01843_x crossref_primary_10_3389_fimmu_2025_1431066 crossref_primary_10_1038_s41467_023_39269_9 crossref_primary_10_1097_SHK_0000000000002402 crossref_primary_10_1097_EA9_0000000000000014 crossref_primary_10_3389_fimmu_2024_1341752 crossref_primary_10_1007_s00068_021_01750_9 crossref_primary_10_1039_D4FO00350K crossref_primary_10_1007_s00134_025_07873_6 crossref_primary_10_1097_CCE_0000000000001153 crossref_primary_10_1053_j_ajkd_2023_01_449 crossref_primary_10_1016_S1473_3099_21_00019_0 crossref_primary_10_1038_s41598_025_93961_y crossref_primary_10_1186_s13054_022_04003_2 crossref_primary_10_3389_fmed_2023_1174429 crossref_primary_10_1186_s12967_023_04002_z crossref_primary_10_1097_PCC_0000000000002560 crossref_primary_10_1186_s13054_022_04103_z crossref_primary_10_1097_MCP_0000000000000669 crossref_primary_10_1016_j_bjane_2024_844480 crossref_primary_10_1016_j_chest_2024_01_028 crossref_primary_10_3390_jpm14030225 crossref_primary_10_1093_jamia_ocad228 crossref_primary_10_1016_j_ebiom_2022_104335 crossref_primary_10_3389_fmed_2022_1043589 crossref_primary_10_3390_jcm12103493 crossref_primary_10_1016_S2213_2600_23_00330_2 crossref_primary_10_1089_tmj_2024_0281 crossref_primary_10_1038_s41598_021_84003_4 crossref_primary_10_1016_j_clim_2024_110301 crossref_primary_10_1097_SHK_0000000000002067 crossref_primary_10_1097_SHK_0000000000002068 crossref_primary_10_1111_joim_13220 crossref_primary_10_1007_s11908_023_00818_4 crossref_primary_10_3389_fcell_2021_756340 crossref_primary_10_1186_s13063_023_07644_y crossref_primary_10_1001_jama_2025_3046 crossref_primary_10_3389_fcimb_2023_1274842 crossref_primary_10_1111_anae_15369 crossref_primary_10_15252_emmm_202114436 crossref_primary_10_1097_CCE_0000000000000881 crossref_primary_10_1186_s12879_024_09203_5 crossref_primary_10_3389_fdgth_2023_1142822 crossref_primary_10_1007_s00134_021_06595_9 crossref_primary_10_1001_jama_2024_0179 crossref_primary_10_1016_S2213_2600_20_30404_5 crossref_primary_10_1186_s13054_021_03541_5 crossref_primary_10_1186_s13054_021_03750_y crossref_primary_10_3389_fimmu_2021_733537 crossref_primary_10_1186_s40635_022_00445_8 crossref_primary_10_1038_s41598_024_69185_x crossref_primary_10_1002_advs_202303090 crossref_primary_10_1097_SHK_0000000000002047 crossref_primary_10_1186_s12911_021_01460_7 crossref_primary_10_2478_jccm_2023_0022 crossref_primary_10_1186_s13054_025_05532_2 crossref_primary_10_1016_j_ajem_2024_07_030 crossref_primary_10_1183_23120541_00121_2024 crossref_primary_10_1016_j_pharmthera_2024_108684 crossref_primary_10_1016_j_arth_2020_06_063 crossref_primary_10_3389_fmed_2023_1252021 crossref_primary_10_3390_antibiotics12050925 crossref_primary_10_3389_fimmu_2020_01391 crossref_primary_10_1007_s10877_021_00664_6 crossref_primary_10_3389_fmed_2021_627830 crossref_primary_10_1213_ANE_0000000000007170 crossref_primary_10_1016_j_bspc_2025_107827 crossref_primary_10_3389_fimmu_2025_1589959 crossref_primary_10_1097_CCE_0000000000000672 crossref_primary_10_1093_ofid_ofac381 crossref_primary_10_1213_ANE_0000000000006247 crossref_primary_10_1007_s40123_025_01174_3 crossref_primary_10_1007_s41666_024_00184_3 crossref_primary_10_1097_SHK_0000000000002264 crossref_primary_10_1055_a_1813_2057 crossref_primary_10_3892_etm_2024_12689 crossref_primary_10_1002_ams2_477 crossref_primary_10_1016_j_scitotenv_2025_179018 crossref_primary_10_1371_journal_pone_0252793 crossref_primary_10_1097_MNH_0000000000000604 crossref_primary_10_1007_s10875_022_01386_3 crossref_primary_10_1164_rccm_202108_1908ST crossref_primary_10_1007_s00134_019_05909_2 crossref_primary_10_1186_s13054_022_04121_x crossref_primary_10_3389_fmed_2021_681336 crossref_primary_10_1002_mdr2_70024 crossref_primary_10_1016_j_chest_2021_04_062 crossref_primary_10_1016_j_ebiom_2022_104387 crossref_primary_10_3389_fimmu_2023_1277033 crossref_primary_10_1016_j_ccc_2021_11_013 crossref_primary_10_1007_s00134_022_06868_x crossref_primary_10_3390_jcm12031185 crossref_primary_10_1186_s13054_025_05423_6 crossref_primary_10_1097_CCE_0000000000001308 crossref_primary_10_1002_alz_70017 crossref_primary_10_1007_s00134_020_06109_z crossref_primary_10_1097_CCM_0000000000004053 crossref_primary_10_1186_s40560_025_00790_2 crossref_primary_10_2217_fmb_2022_0044 crossref_primary_10_1186_s13613_021_00977_4 crossref_primary_10_3389_fcimb_2025_1673959 crossref_primary_10_1007_s00101_023_01366_1 crossref_primary_10_1097_SHK_0000000000002482 crossref_primary_10_1186_s13613_020_00740_1 crossref_primary_10_1097_MCC_0000000000000641 crossref_primary_10_1111_tri_13818 crossref_primary_10_1186_s13613_025_01524_1 crossref_primary_10_4187_respcare_07405 crossref_primary_10_2147_JIR_S369703 crossref_primary_10_1016_j_otsr_2025_104422 crossref_primary_10_1111_apt_18274 crossref_primary_10_1186_s12931_024_03018_3 crossref_primary_10_1002_jpen_2539 crossref_primary_10_5492_wjccm_v11_i5_311 crossref_primary_10_1164_rccm_202106_1350OC crossref_primary_10_1007_s00134_020_05960_4 crossref_primary_10_1186_s40560_025_00802_1 crossref_primary_10_1126_scitranslmed_adh0185 crossref_primary_10_3390_ijms26051894 crossref_primary_10_1016_j_annemergmed_2020_04_042 crossref_primary_10_1007_s11739_025_04008_z crossref_primary_10_3389_fmed_2024_1431791 crossref_primary_10_3390_ijms26104825 crossref_primary_10_1016_S2352_4642_24_00017_8 crossref_primary_10_1093_bmb_ldac001 crossref_primary_10_1097_MS9_0000000000002773 crossref_primary_10_1007_s00134_024_07572_8 crossref_primary_10_1016_j_surg_2025_109535 crossref_primary_10_1186_s13054_024_04871_w crossref_primary_10_1097_CCM_0000000000004018 crossref_primary_10_1016_j_eclinm_2025_103341 crossref_primary_10_1096_fj_202500530RR crossref_primary_10_1007_s12028_021_01260_x crossref_primary_10_1164_rccm_201908_1595WS crossref_primary_10_1371_journal_pone_0265818 crossref_primary_10_3390_jcm8111869 crossref_primary_10_1097_CCE_0000000000000800 crossref_primary_10_1186_s12879_024_10415_y crossref_primary_10_1513_AnnalsATS_202011_1372OC crossref_primary_10_1007_s00134_023_07226_1 crossref_primary_10_1371_journal_pone_0240753 crossref_primary_10_3390_jcm14092983 crossref_primary_10_1097_PEC_0000000000002865 crossref_primary_10_3389_fimmu_2022_882774 crossref_primary_10_1186_s12871_023_02265_z crossref_primary_10_1513_AnnalsATS_202004_399OC crossref_primary_10_1007_s00134_021_06479_y crossref_primary_10_1186_s40560_022_00602_x crossref_primary_10_1002_ncp_11194 crossref_primary_10_1186_s13049_025_01350_1 crossref_primary_10_3389_fimmu_2025_1577105 crossref_primary_10_3389_fmed_2021_770343 crossref_primary_10_1002_jhm_13078 crossref_primary_10_1186_s13054_021_03487_8 crossref_primary_10_1111_jgs_16194 crossref_primary_10_3390_biomedicines12122892 crossref_primary_10_1186_s12879_025_11064_5 crossref_primary_10_3390_jcm13206044 crossref_primary_10_1016_j_jss_2022_04_052 crossref_primary_10_1097_CCM_0000000000006463 crossref_primary_10_2147_JIR_S513678 crossref_primary_10_3389_fimmu_2024_1500734 crossref_primary_10_1089_ars_2020_8062 crossref_primary_10_1038_s41746_025_01863_0 crossref_primary_10_1016_j_ebiom_2022_104394 crossref_primary_10_3389_fimmu_2025_1546474 crossref_primary_10_1007_s00134_025_08052_3 crossref_primary_10_1097_PCC_0000000000003292 crossref_primary_10_3390_microorganisms11092231 crossref_primary_10_1007_s00134_023_07239_w crossref_primary_10_1016_j_jacadv_2022_100126 crossref_primary_10_1007_s10238_024_01545_3 crossref_primary_10_1148_radiol_212830 crossref_primary_10_3389_fneur_2024_1366307 crossref_primary_10_1007_s00134_020_06038_x crossref_primary_10_1016_j_jacadv_2022_100120 crossref_primary_10_1002_hsr2_70288 crossref_primary_10_1055_a_2114_8333 crossref_primary_10_1016_j_cmpb_2022_106655 crossref_primary_10_1186_s40635_023_00531_5 crossref_primary_10_1186_s12982_024_00216_8 crossref_primary_10_1186_s40635_023_00555_x crossref_primary_10_1055_a_2657_6380 crossref_primary_10_1186_s13054_021_03578_6 crossref_primary_10_1055_s_0044_1785504 crossref_primary_10_1097_PCC_0000000000003070 crossref_primary_10_3389_fmed_2025_1502628 crossref_primary_10_1016_j_eclinm_2024_103013 crossref_primary_10_1016_j_jchf_2023_06_024 crossref_primary_10_1097_CCM_0000000000004451 crossref_primary_10_3389_fimmu_2025_1616794 crossref_primary_10_1186_s12916_021_01940_7 crossref_primary_10_3389_fgene_2023_1100352 crossref_primary_10_1038_s41467_024_48713_3 crossref_primary_10_3389_fimmu_2024_1287415 crossref_primary_10_1097_MD_0000000000028219 crossref_primary_10_1136_bmjopen_2020_042921 crossref_primary_10_1007_s00134_022_06890_z crossref_primary_10_1007_s12028_021_01199_z crossref_primary_10_3389_fmed_2022_794423 crossref_primary_10_3389_frai_2022_842306 crossref_primary_10_1097_MEJ_0000000000000705 crossref_primary_10_1515_biol_2022_0999 crossref_primary_10_1038_s41419_024_07072_z crossref_primary_10_1186_s40635_025_00801_4 crossref_primary_10_1099_jmm_0_001986 crossref_primary_10_1016_j_phymed_2024_155710 crossref_primary_10_1016_j_bbe_2022_12_008 crossref_primary_10_1016_j_ccc_2022_09_013 crossref_primary_10_1136_annrheumdis_2019_215959 crossref_primary_10_1186_s12879_025_11471_8 crossref_primary_10_1136_bmjopen_2023_078763 crossref_primary_10_1097_SHK_0000000000002081 crossref_primary_10_3389_fmed_2024_1510792 crossref_primary_10_1016_j_jinf_2024_106156 crossref_primary_10_1111_apt_16014 crossref_primary_10_1097_CCE_0000000000000865 crossref_primary_10_1093_jleuko_qiad163 crossref_primary_10_3390_antibiotics10080930 crossref_primary_10_1038_s41598_021_93635_5 crossref_primary_10_1186_s13054_022_04163_1 crossref_primary_10_1038_s41467_025_58527_6 crossref_primary_10_1016_j_jchf_2023_05_007 crossref_primary_10_1097_CCM_0000000000004229 crossref_primary_10_1186_s13054_024_04929_9 crossref_primary_10_1002_adbi_202300673 crossref_primary_10_1136_bmjpo_2024_003100 crossref_primary_10_1186_s13054_025_05371_1 crossref_primary_10_3389_fimmu_2024_1345321 crossref_primary_10_1002_lrh2_10315 crossref_primary_10_1111_acem_14265 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1001/jama.2019.5791 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1538-3598 |
| ExternalDocumentID | 31104070 |
| Genre | Validation Study Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NIGMS NIH HHS grantid: R34 GM102696 – fundername: NIGMS NIH HHS grantid: R01 GM107231 – fundername: NIGMS NIH HHS grantid: P50 GM076659 – fundername: NIGMS NIH HHS grantid: K08 GM117310 – fundername: NIGMS NIH HHS grantid: R35 GM119519 – fundername: NIGMS NIH HHS grantid: R01 GM061992 – fundername: NIGMS NIH HHS grantid: R01 GM105728 – fundername: NIGMS NIH HHS grantid: R01 GM101197 – fundername: NLM NIH HHS grantid: R01 LM012095 |
| GroupedDBID | --- -ET -~X .55 .XZ 0R~ 0WA 186 18M 29J 2CT 2FS 2KS 2WC 354 39C 4.4 53G 5GY 5RE 6TJ 85S AAIKC AAMNW AAQOH AAQQT AAWTL ABBLC ABCQX ABEHJ ABIVO ABOCM ABPMR ABPPZ ABRSH ABWJO ACGFS ACNCT ACPRK ADBBV ADUKH AFCHL AFFNX AFRAH AGFXO AGHSJ AHMBA ALMA_UNASSIGNED_HOLDINGS AMJDE ANMPU BKOMP BRYMA C45 CGR CJ0 CS3 CUY CVF EAM EBD EBS ECM EIF EJD EMOBN EX3 F5P GX1 H13 HF~ KOO KQ8 L7B MVM N4W N9A NEJ NPM NYF OBH OCB OGEVE OHH OK1 OMK OVD P2P PKN PQQKQ QJJ RAJ RNS SJN SV3 TEORI TN5 UHB UIG UKR UPT VVN WH7 WOW X7M XHN XSW XZL YCJ YFH YIF YIN YOC YPV YQT YQY YR2 YR5 YSK YYM YZZ ZCA ~H1 7X8 ACAHW ADXHL AETEA ARBJA |
| ID | FETCH-LOGICAL-a503t-8cd585c993af93b842bd2febdb21c1a30e5695d112407fcaf9970e418b0ab69e2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 909 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000469297300022&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1538-3598 |
| IngestDate | Thu Oct 02 05:55:20 EDT 2025 Wed Feb 19 02:24:42 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 20 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-a503t-8cd585c993af93b842bd2febdb21c1a30e5695d112407fcaf9970e418b0ab69e2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 |
| OpenAccessLink | https://jamanetwork.com/journals/jama/articlepdf/2733996/jama_seymour_2019_oi_190047.pdf |
| PMID | 31104070 |
| PQID | 2232077178 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2232077178 pubmed_primary_31104070 |
| PublicationCentury | 2000 |
| PublicationDate | 2019-05-28 |
| PublicationDateYYYYMMDD | 2019-05-28 |
| PublicationDate_xml | – month: 05 year: 2019 text: 2019-05-28 day: 28 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | JAMA : the journal of the American Medical Association |
| PublicationTitleAlternate | JAMA |
| PublicationYear | 2019 |
| References | 31104067 - JAMA. 2019 May 28;321(20):1981-1982 31593266 - JAMA. 2019 Oct 8;322(14):1416-1417 31656636 - J Thorac Dis. 2019 Sep;11(9):3672-3675 31593265 - JAMA. 2019 Oct 8;322(14):1416 36470827 - EBioMedicine. 2022 Dec;86:104335 |
| References_xml | – reference: 31656636 - J Thorac Dis. 2019 Sep;11(9):3672-3675 – reference: 36470827 - EBioMedicine. 2022 Dec;86:104335 – reference: 31593266 - JAMA. 2019 Oct 8;322(14):1416-1417 – reference: 31593265 - JAMA. 2019 Oct 8;322(14):1416 – reference: 31104067 - JAMA. 2019 May 28;321(20):1981-1982 |
| SSID | ssj0000137 |
| Score | 2.7219024 |
| Snippet | Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care.
To derive sepsis phenotypes... Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care.ImportanceSepsis is a... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 2003 |
| SubjectTerms | Algorithms Biomarkers - blood Cluster Analysis Datasets as Topic Hospital Mortality Humans Machine Learning Organ Dysfunction Scores Phenotype Reproducibility of Results Retrospective Studies Sepsis - classification Sepsis - mortality Sepsis - therapy |
| Title | Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/31104070 https://www.proquest.com/docview/2232077178 |
| Volume | 321 |
| WOSCitedRecordID | wos000469297300022&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1bS8MwFA7qRHzxfpk3IvhoNU3aJXkSUYeCKwOn7G00NxyMdtq53-9Jl-FeBMGXkoeGhpxzku9c-h2ELkwuY2qMiVoyVlHSUkmUp8RGxDhOGeeWuPpH4WeeZaLfl90QcKtCWeX8TKwPalNqHyO_hmuMEg7Oh7gZf0S-a5TProYWGsuowQDKeK3mfbFAH1VzZtZG7Znq5qSNP6xDsbxKa37O3-Blfc20N_-7wC20EQAmvp1pxDZassUOWuuEFPouMvegc7M47CV-AxRuwjgvDO6WE189BPN78wJ0_LRQc45Lh7Nyakc48ImOcPfdFqUP5FYY8C9-seNqWO2h1_ZD7-4xCq0WvGTYJBLagN-gAazkTjIlEqoMdVYZRWMd54zYtCVTA-AMHECn4SXJiU1ioUiuWtLSfbRSlIU9RJhrJlLKbc40uJpg4ZYQo4R0jjKtddpE5_P9G4Aq-_xEXtjyqxr87GATHcyEMBjPODcGDGAKfJoc_WH2MVr3kvU5fipOUMOBIdtTtKqnk2H1eVbrCDyzbucbvELHxQ |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Derivation%2C+Validation%2C+and+Potential+Treatment+Implications+of+Novel+Clinical+Phenotypes+for+Sepsis&rft.jtitle=JAMA+%3A+the+journal+of+the+American+Medical+Association&rft.au=Seymour%2C+Christopher+W&rft.au=Kennedy%2C+Jason+N&rft.au=Wang%2C+Shu&rft.au=Chang%2C+Chung-Chou+H&rft.date=2019-05-28&rft.issn=1538-3598&rft.eissn=1538-3598&rft.volume=321&rft.issue=20&rft.spage=2003&rft_id=info:doi/10.1001%2Fjama.2019.5791&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1538-3598&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1538-3598&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1538-3598&client=summon |