Development of a Prognostic Model for Hospital Mortality in Patients with Systemic Lupus Erythematosus Admitted to the Intensive Care Unit
Keywords:
clinical prognostic model, cox regression analysis, intensive care unit, mortality, systemic lupus erythematosus
Abstract
Objectives: This study aimed to develop a prognostic model to predict mortality among SLE patients in ICU.
Methods: In this retrospective cohort study, we extracted SLE patients from the MIMIC-IV database. Multivariate Cox regression based on the Akaike information criterion and P value was used to establish the prognostic model. Internal validation was performed by a bootstrap resampling approach with 100 replications. The discrimination and calibration of the model were evaluated by Harrell's concordance index and calibration plot. Decision curve analysis was performed to evaluate its clinical application.
Results: A total of 301 patients were finally included in the study. 276 (91.7%) patients were in the survivor group and 25 (8.3%) patients were in the non-survivor group. Multivariate Cox regression analysis included Peripheral vascular disease (adjusted HR 8.47 [2.57-27.98]，p<0.001), Peptic ulcer disease (adjusted HR 3.79 [1.01-14.14]，p=0.048), Metastatic solid tumor (adjusted HR 16.80 [3.95-71.90]，p<0.001), GCS motor upon ICU admission (adjusted HR 0.79 [0.65-0.98]，p=0.028), lowest SBP (adjusted HR 0.95 [0.93-0.97], p<0.001) and lowest AG (adjusted HR 1.18 [1.09-1.29]，p<0.001) to construct the model. The adjusted C-index was 0.805 and the calibration plot revealed that the predicted outcome was in agreement with the actual observations. The Kaplan–Meier survival curves revealed a significantly lower survival probability in the high-risk group than in the low-risk group (P < 0.0001). DCA showed that the model was clinically useful.
Conclusion: The prognostic model could help clinicians to stratify SLE patients and provide appropriate care.
References
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[22] Gayam, V., Mandal, A. K., Khalid, M., Kaler, J., Thapa, S., Garlapati, P., ... & Reddy, M. (2018). A Rare Case of Systemic Lupus Erythematosus with Gastric Ulcer and Acute Pancreatitis: A Case Report and Literature Review. Gastroenterology Research, 11(4), 321-325. https://doi.org/10.14740/gr1087w
[23] Ha, F. J., Weickhardt, A. J., Parakh, S., Vincent, A. D., Glassford, N. J., Warrillow, S., ... & Bellomo, R. (2017). Survival and functional outcomes of patients with metastatic solid organ cancer admitted to the intensive care unit of a tertiary centre. Critical Care and Resuscitation, 19(2), 159-166.
[24] Barth, C., Soares, M., Toffart, A. C., Timsit, J. F., Burghi, G., Irrazabal, C., ... & Azoulay, E. (2018). Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs). Annals of Intensive Care, 8(1), 80. https://doi.org/10.1186/s13613-018-0428-2
[25] Hsu, C.-Y., Lin, M.-S., Su, Y.-J., Cheng, T.-T., Lin, Y.-S., Chen, Y.-C., ... & Yu, C.-L. (2016). Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14 832 patients with systemic lupus erythematosus: a nested case–control study. Rheumatology. https://doi.org/10.1093/rheumatology/kew287
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[30] Bombardier, C., Gladman, D. D., Urowitz, M. B., Caron, D., & Chang, C. H. (1992). Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis and Rheumatism, 35(6), 630-640.
[31] Hay, E. M., Bacon, P. A., Gordon, C., Isenberg, D. A., Maddison, P., Snaith, M. L., ... & Zoma, A. (1993). The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. The Quarterly Journal of Medicine, 86(7), 447-458.
[32] Isenberg, D. A., Rahman, A., Allen, E., Farewell, V., Akil, M., Bruce, I. N., ... & Yee, C. S. (2005). BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group's disease activity index for patients with systemic lupus erythematosus. Rheumatology (Oxford, England), 44(7), 902-906. https://doi.org/10.1093/rheumatology/keh588
[2] Arnaud, L., & Tektonidou, M. G. (2020). Long-term outcomes in systemic lupus erythematosus: trends over time and major contributors. Rheumatology (Oxford, England), 59(Suppl 5), v29-v38. https://doi.org/10.1093/rheumatology/keaa265
[3] Ocampo-Piraquive, V., Nieto-Aristizábal, I., Cañas, C. A., & Tobón, G. J. (2018). Mortality in systemic lupus erythematosus: causes, predictors and interventions. Expert Review of Clinical Immunology, 14(12), 1043-1053. https://doi.org/10.1080/1744666X.2018.1541300
[4] Quintero, O. L., Rojas-Villarraga, A., Mantilla, R. D., & Anaya, J. M. (2013). Autoimmune diseases in the intensive care unit. An update. Autoimmunity Reviews, 12(3), 380-395. https://doi.org/10.1016/j.autrev.2012.08.006
[5] Gasparotto, M., Gatto, M., Binda, V., Doria, A., & Moroni, G. (2020). Lupus nephritis: clinical presentations and outcomes in the 21st century. Rheumatology (Oxford, England), 59(Suppl 5), v39-v51. https://doi.org/10.1093/rheumatology/keaa263
[6] Suárez-Avellaneda, A., Quintana, J. H., Aragón, C. C., Gallego, L. M., Gallego, C.-N., Bolaños, J. D., ... & Iglesias-Gamarra, A. (2020). Systemic lupus erythematosus in the intensive care unit: a systematic review. Lupus, 29(11), 1364-1376. https://doi.org/10.1177/0961203320944061
[7] Knaus, W. A., Draper, E. A., Wagner, D. P., & Zimmerman, J. E. (1985). APACHE II: a severity of disease classification system. Critical Care Medicine, 13(10), 818-829.
[8] Le Gall, J. R., Lemeshow, S., & Saulnier, F. (1993). A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA, 270(24), 2957-2963.
[9] Fatemi, A., Shamsaee, S., Raeisi, A., Sayedbonakdar, Z., & Smiley, A. (2017). Prognostic factors of mortality in Iranian patients with systemic lupus erythematosus admitted to intensive care unit. Clinical Rheumatology, 36(11), 2471-2477. https://doi.org/10.1007/s10067-017-3783-6
[10] Zamir, G., Haviv-Yadid, Y., Sharif, K., Bragazzi, N. L., Watad, A., Dagan, A., ... & Amital, H. (2018). Mortality of patients with systemic lupus erythematosus admitted to the intensive care unit - A retrospective single-center study. Best Practice & Research Clinical Rheumatology, 32(5), 701-709. https://doi.org/10.1016/j.berh.2019.01.002
[11] Hochberg, M. C. (1997). Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis and Rheumatism, 40(9), 1725.
[12] Jiang, D., Bian, T., Shen, Y., & Huang, Z. (2023). Association between admission systemic immune-inflammation index and mortality in critically ill patients with sepsis: a retrospective cohort study based on MIMIC-IV database. Clinical and Experimental Medicine, 1-10. https://doi.org/10.1007/s10238-023-01188-4
[13] Moons, K. G., Altman, D. G., Reitsma, J. B., Ioannidis, J. P., Macaskill, P., Steyerberg, E. W., ... & Collins, G. S. (2015). Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration. Annals of Internal Medicine, 162(1), W1-W73. https://doi.org/10.7326/M14-0697
[14] Wolff, R. F., Moons, K. G., Riley, R. D., Whiting, P. F., Westwood, M., Collins, G. S., ... & Reitsma, J. B. (2019). PROBAST: A Tool to Assess the Risk of Bias and Applicability of Prediction Model Studies. Annals of Internal Medicine, 170(1), 51-58. https://doi.org/10.7326/M18-1376
[15] Siripaitoon, B., Lertwises, S., Uea-Areewongsa, P., & Khwannimit, B. (2015). A study of Thai patients with systemic lupus erythematosus in the medical intensive care unit: epidemiology and predictors of mortality. Lupus, 24(1), 98-106. https://doi.org/10.1177/0961203314549320
[16] Su, B., & Li, H. (2023). Development and validation of models for risk of death in patients with systemic lupus erythematosus admitted to the intensive care unit: a retrospective study. Clinical Rheumatology. 2023;42(11):2987-99.
[17] Hsu, C. L., Chen, K. Y., Yeh, P. S., Hsu, Y. L., Chang, H. T., Shau, W. Y., ... & Tsai, S. H. (2005). Outcome and prognostic factors in critically ill patients with systemic lupus erythematosus: a retrospective study. Critical Care, 9(3), R177-R183. https://doi.org/10.1186/cc3461
[18] Lee, J., Dhillon, N., & Pope, J. (2013). All-cause hospitalizations in systemic lupus erythematosus from a large Canadian referral centre. Rheumatology (Oxford, England), 52(5), 905-909. https://doi.org/10.1093/rheumatology/kes376
[19] Mageau, A., Sacré, K., Perozziello, A., Ruckly, S., Dupuis, C., Bouadma, L., ... & Pène, F. (2019). Septic shock among patients with systemic lupus erythematosus: Short and long-term outcome. Analysis of a French nationwide database. The Journal of Infection, 78(6), 432-438. https://doi.org/10.1016/j.jinf.2019.03.012
[20] Gustafsson, J. T., & Svenungsson, E. (2014). Definitions of and contributions to cardiovascular disease in systemic lupus erythematosus. Autoimmunity, 47(2), 67-76. https://doi.org/10.3109/08916934.2013.847134
[21] Sagheer, S., Deka, P., Pathak, D., Khan, U., Zaidi, S. H., Akhlaq, A., ... & Dhillon, S. S. (2022). Clinical Outcomes of Acute Myocardial Infarction Hospitalizations With Systemic Lupus Erythematosus: An Analysis of Nationwide Readmissions Database. Current Problems in Cardiology, 47(11), 101086. https://doi.org/10.1016/j.cpcardiol.2022.101086
[22] Gayam, V., Mandal, A. K., Khalid, M., Kaler, J., Thapa, S., Garlapati, P., ... & Reddy, M. (2018). A Rare Case of Systemic Lupus Erythematosus with Gastric Ulcer and Acute Pancreatitis: A Case Report and Literature Review. Gastroenterology Research, 11(4), 321-325. https://doi.org/10.14740/gr1087w
[23] Ha, F. J., Weickhardt, A. J., Parakh, S., Vincent, A. D., Glassford, N. J., Warrillow, S., ... & Bellomo, R. (2017). Survival and functional outcomes of patients with metastatic solid organ cancer admitted to the intensive care unit of a tertiary centre. Critical Care and Resuscitation, 19(2), 159-166.
[24] Barth, C., Soares, M., Toffart, A. C., Timsit, J. F., Burghi, G., Irrazabal, C., ... & Azoulay, E. (2018). Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs). Annals of Intensive Care, 8(1), 80. https://doi.org/10.1186/s13613-018-0428-2
[25] Hsu, C.-Y., Lin, M.-S., Su, Y.-J., Cheng, T.-T., Lin, Y.-S., Chen, Y.-C., ... & Yu, C.-L. (2016). Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14 832 patients with systemic lupus erythematosus: a nested case–control study. Rheumatology. https://doi.org/10.1093/rheumatology/kew287
[26] Scheurer, M., Cao, L., Tong, H., Xu, G., Liu, P., Meng, H., ... & Huang, C. (2015). Systemic Lupus Erythematosus and Malignancy Risk: A Meta-Analysis. PLoS ONE, 10(4), e0123683. https://doi.org/10.1371/journal.pone.0123683
[27] Peng, J. C., Gong, W. W., Wu, Y., Yan, T. Y., & Jiang, X. Y. (2022). Development and validation of a prognostic nomogram among patients with acute exacerbation of chronic obstructive pulmonary disease in intensive care unit. BMC Pulmonary Medicine, 22(1), 306. https://doi.org/10.1186/s12890-022-02116-4
[28] Rishu, A. H., Khan, R., Al-Dorzi, H. M., Tamim, H. M., Al-Qahtani, S., Al-Ghamdi, G., ... & Arabi, Y. M. (2013). Even mild hyperlactatemia is associated with increased mortality in critically ill patients. Critical Care, 17(5), R197. https://doi.org/10.1186/cc12892
[29] Zhang, X., Yang, R., Tan, Y., Zhou, Y., Lu, B., Ji, X., ... & Zhang, Z. (2022). An improved prognostic model for predicting the mortality of critically ill patients: a retrospective cohort study. Scientific Reports, 12(1), 21450. https://doi.org/10.1038/s41598-022-25807-6
[30] Bombardier, C., Gladman, D. D., Urowitz, M. B., Caron, D., & Chang, C. H. (1992). Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis and Rheumatism, 35(6), 630-640.
[31] Hay, E. M., Bacon, P. A., Gordon, C., Isenberg, D. A., Maddison, P., Snaith, M. L., ... & Zoma, A. (1993). The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. The Quarterly Journal of Medicine, 86(7), 447-458.
[32] Isenberg, D. A., Rahman, A., Allen, E., Farewell, V., Akil, M., Bruce, I. N., ... & Yee, C. S. (2005). BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group's disease activity index for patients with systemic lupus erythematosus. Rheumatology (Oxford, England), 44(7), 902-906. https://doi.org/10.1093/rheumatology/keh588
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