The timing of death in burn patients.

Aim: When treating burn patients, some patients die in the chronic phase, even if they overcome the acute phase of the burn. To elucidate the timing of death and its underlying causes among burn patients. Methods: Patients evaluated were admitted to our burn center between January 2015, and December 2019. Patient information, time, and cause of death were retrospectively collected from their medical records. Results: Among 342 admitted patients, 49 died. The time of death was as follows: within 24 h (n = 9), within 3 days (n = 7), within 1 week (n = 5), within 2 weeks (n = 4), within 3 weeks (n = 3), within 30 days (n = 6), within 60 days (n = 5), and after 60 days (n = 9). The causes of death within 3 days were hypoxic encephalopathy, extensive burns (>80%), severe heat stroke, and acute coronary syndrome. The causes of death after 3 days were sepsis, pneumonia, intestinal ischemia, pancreatitis, and worsening of chronic diseases. The mortality rate was similar for patients ≥65 years of age and those with a burn area of ≥20%, with both groups showing a particularly poor prognosis. Conclusions: The timing of death in hospitalized burn patients showed a bimodal distribution as approximately 40% of patients who survived the resuscitation period died after 30 days. Elderly patients were at particularly high risk for mortality. In burn care, treatment planning should consider not only the short-term but also the long-term prognosis.

The Tri-Steps Model of Critical Conditions in Intensive Care: Introducing a New Paradigm for Chronic Critical Illness.

Background: The prevailing model for understanding chronic critical illness is a biphasic model, suggesting phases of acute and chronic critical conditions. A major challenge within this model is the difficulty in determining the timing of the process chronicity. It is likely that the triad of symptoms (inflammation, catabolism, and immunosuppression [ICIS]) could be associated with this particular point. We aimed to explore the impact of the symptom triad (inflammation, catabolism, immunosuppression) on the outcomes of patients hospitalized in intensive care units (ICUs). Methods: The eICU-CRD database with 200,859 ICU admissions was analyzed. Adult patients with the ICIS triad, identified by elevated CRP (>20 mg/L), reduced albumin (<30 g/L), and low lymphocyte counts (<0.8 × 109/L), were included. The cumulative risk of developing ICIS was assessed using the Nelson-Aalen estimator. Results: This retrospective cohort study included 894 patients (485 males, 54%), with 60 (6.7%) developing ICIS. The cumulative risk of ICIS by day 21 was 22.5%, with incidence peaks on days 2-3 and 10-12 after ICU admission. Patients with the ICIS triad had a 2.5-fold higher mortality risk (p = 0.009) and double the likelihood of using vasopressors (p = 0.008). The triad onset day did not significantly affect mortality (p = 0.104). Patients with ICIS also experienced extended hospital (p = 0.041) and ICU stays (p < 0.001). Conclusions: The symptom triad (inflammation, catabolism, immunosuppression) during hospitalization increases mortality risk by 2.5 times (p = 0.009) and reflects the chronicity of the critical condition. Identifying two incidence peaks allows the proposal of a new Tri-steps model of chronic critical illness with acute, extended, and chronic phases.

Systemic immune response of burns from the acute to chronic phase.

Immune responses that occur following burn injury comprise a series of reactions that are activated in response to damaged autologous tissues, followed by removal of damaged tissues and foreign pathogens such as invading bacteria, and tissue repair. These immune responses are considered to be programmed in living organisms. Developments of modern medicine have led to the saving of burned patients who could not be cured previously; however, the programmed response is no longer able to keep up, and various problems have arisen. This paper describes the mechanism of immune response specific to burn injury and the emerging concept of persistent inflammation, immunosuppression, and catabolism syndrome.

Urea to creatinine ratio as a predictor of persistent critical illness.

INTRODUCTION: Persistent critical illness (PCI) is a syndrome in which the acute presenting problem has been stabilized, but the patient's clinical state does not allow ICU discharge. The burden associated with PCI is substantial. The most obvious marker of PCI is prolonged ICU length of stay (LOS), usually greater than 10 days. Urea to Creatinine ratio (UCr) has been suggested as an early marker of PCI development. METHODS: A single-center retrospective study. Data of patients admitted to a general mixed medical-surgical ICU during Jan 1st 2018 till Dec 31st 2022 was extracted, including demographic data, baseline characteristics, daily urea and creatinine results, renal replacement therapy (RRT) provided, and outcome measures - length of stay, and mortality (ICU, and 90 days). Patients were defined as PCI patients if their LOS was >10 days. We used Fisher exact test or Chi-square to compare PCI and non-PCI patients. The association between UCr with PCI development was assessed by repeated measures linear model. Multivariate Cox regression was used for 1 year mortality assessment. RESULTS: 2098 patients were included in the analysis. Patients who suffered from PCI were older, with higher admission prognostic scores. Their 90-day mortality was significantly higher than non-PCI patients (34.58% vs 12.18%, p < 0.0001). A significant difference in UCr was found only on the first admission day among all patients. This was not found when examining separately surgical, trauma, or transplantation patients. We did not find a difference in UCr in different KDIGO (Kidney Disease Improving Global Outcomes) stages. Elevated UCr and PCI were found to be significantly associated with 1 year mortality. CONCLUSION: In this single center retrospective cohort study, UCr was not found to be associated with PCI development.

Persistent inflammation, immunosuppression, and catabolism syndrome (PICS): a review of definitions, potential therapies, and research priorities.

Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) is a clinical endotype of chronic critical illness. PICS consists of a self-perpetuating cycle of ongoing organ dysfunction, inflammation, and catabolism resulting in sarcopenia, immunosuppression leading to recurrent infections, metabolic derangements, and changes in bone marrow function. There is heterogeneity regarding the definition of PICS. Currently, there are no licensed treatments specifically for PICS. However, findings can be extrapolated from studies in other conditions with similar features to repurpose drugs, and in animal models. Drugs that can restore immune homeostasis by stimulating lymphocyte production could have potential efficacy. Another treatment could be modifying myeloid-derived suppressor cell (MDSC) activation after day 14 when they are immunosuppressive. Drugs such as interleukin (IL)-1 and IL-6 receptor antagonists might reduce persistent inflammation, although they need to be given at specific time points to avoid adverse effects. Antioxidants could treat the oxidative stress caused by mitochondrial dysfunction in PICS. Possible anti-catabolic agents include testosterone, oxandrolone, IGF-1 (insulin-like growth factor-1), bortezomib, and MURF1 (muscle RING-finger protein-1) inhibitors. Nutritional support strategies that could slow PICS progression include ketogenic feeding and probiotics. The field would benefit from a consensus definition of PICS using biologically based cut-off values. Future research should focus on expanding knowledge on underlying pathophysiological mechanisms of PICS to identify and validate other potential endotypes of chronic critical illness and subsequent treatable traits. There is unlikely to be a universal treatment for PICS, and a multimodal, timely, and personalised therapeutic strategy will be needed to improve outcomes for this growing cohort of patients.

Influencing factors for persistent inflammation, immunosuppression, and catabolism syndrome in patients with severe acute pancreatitis and establishment of a predictive model / 临床肝胆病杂志

Objective To investigate the influencing factors for persistent inflammation, immunosuppression, and catabolism syndrome (PICS) in patients with severe acute pancreatitis(SAP), and to establish a predictive model. Methods A retrospective analysis was performed for the clinical data of 163 patients who were admitted to the intensive care unit and the emergency intensive care unit due to SAP in The First Affiliated Hospital of Guangxi Medical University from May 2012 to May 2022, and according to the diagnostic criteria for PICS, these patients were divided into PICS group (65 SAP patients with PICS) and non-PICS group (98 SAP patients without PICS). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Variance inflation factor and correlation matrix heatmap were used to evaluate multicollinearity between variables, and Lasso regression and multivariate logistic regression were used to identify independent risk factors and establish a nomogram predictive model. The receiver operating characteristic (ROC) curve, the calibration curve, and the Hosmer-Lemeshow goodness-of-fit test were used for the internal validation of the model, and the decision curve was used to evaluate the clinical practicability of the model. Results The univariate analysis showed that there were significant differences between the PICS group and the non-PICS group in mean arterial pressure, hemoglobin, hematocrit (HCT), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), blood urea nitrogen, creatinine, Glasgow coma score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation, acute respiratory distress syndrome, acute kidney injury (AKI), acute liver injury, hypovolemic shock, sepsis, intra-abdominal hypertension, intra-abdominal hemorrhage, and multiple organ dysfunction syndrome (all P < 0.05). The Lasso regression analysis showed that related predictive variables included PLR, HCT, APACHE Ⅱ, SOFA, mechanical ventilation, AKI, hypovolemic shock, and intra-abdominal hypertension, and the multivariate logistic regression analysis showed that PLR (odds ratio [ OR ]=1.006, P < 0.05), mechanical ventilation ( OR =4.324, P < 0.05), AKI ( OR =3.432, P < 0.05), and hypovolemic shock ( OR = 6.910, P < 0.05) were independent risk factors for PICS in patients with SAP. Model fitting was performed for the above factors, and bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.874 (95% confidence interval: 0.822-0.925); the calibration curve of the model was close to the reference curve, and the Hosmer-Lemeshow goodness-of-fit test showed that the model was well fitted ( χ 2 =8.895, P =0.351). The decision curve analysis showed that the predictive model had good clinical practicability. Conclusion PLR, mechanical ventilation, AKI, and hypovolemic shock are independent risk factors for PICS in patients with SAP, and the nomogram model established has good discriminatory ability, calibration, and clinical practicability.

Lymphocyte trajectories are associated with prognosis in critically ill patients: A convenient way to monitor immune status.

Background: Immunosuppression is a risk factor for poor prognosis of critically ill patients, but current monitoring of the immune status in clinical practice is still inadequate. Absolute lymphocyte count (ALC) is not only a convenient biomarker for immune status monitoring but is also suitable for clinical application. In this study, we aimed to explore different trajectories of ALC, and evaluate their relationship with prognosis in critically ill patients. Methods: We retrospectively enrolled 10,619 critically ill patients admitted to a general intensive care unit (ICU) with 56 beds from February 2016 to May 2020. Dynamic ALC was defined as continuous ALC from before ICU admission to 5 days after ICU admission. Initial ALC was defined as the minimum ALC within 48 h after ICU admission. Group-based trajectory modeling (GBTM) was used to group critically ill patients according to dynamic ALC. Multivariate cox regression model was used to determine the independent association of trajectory endotypes with death and persistent inflammation, immunosuppression, catabolism syndrome (PICS). Results: A total of 2022 critically ill patients were unsupervisedly divided into four endotypes based on dynamic ALC, including persistent lymphopenia endotype (n = 1,211; 58.5%), slowly rising endotype (n = 443; 22.6%), rapidly decreasing endotype (n = 281; 14.5%) and normal fluctuation endotype (n = 87; 4.4%). Among the four trajectory endotypes, the persistent lymphopenia endotype had the highest incidence of PICS (24.9%), hospital mortality (14.5%) and 28-day mortality (10.8%). In multivariate cox regression model, persistent lymphopenia was associated with increased risk of 28-day mortality (HR: 1.54; 95% CI: 1.06-2.23), hospital mortality (HR: 1.66; 95% CI: 1.20-2.29) and PICS (HR: 1.79; 95% CI: 1.09-2.94), respectively. Sensitivity analysis further confirmed that the ALC trajectory model of non-infected patients and non-elderly patients can accurately distinguished 91 and 90% of critically ill patients into the same endotypes as the original model, respectively. Conclusion: The ALC trajectory model is helpful for grouping critically ill patients, and early persistent lymphopenia is associated with poor prognosis. Notably, persistent lymphopenia may be a robust signal of immunosuppression in critically ill patients.

Early risk factors for persistent inflammation immunosuppression and catabolism syndrome in patients with severe polytrauma / 中华急诊医学杂志

Objective:To retrospectively assess early risk factor of persistent inflammation, immunosuppression and catabolism syndrome (PICS) in patients with severe polytrauma, in order to deepen the understanding of the pathological changes of chronic critical illness (CCI) after severe polytrauma.Methods:A total of 276 patients with severe polytrauma admitted to Department of Trauma Surgery of Tongji Hospital from March 2019 to December 2020 were enrolled. Inclusion criteria included patients who suffered severe polytrauma, and injury severity score (ISS) ≥27, age ≥18 years old, and had length of hospital stay >15 days. Exclusion criteria included previous medical history of malignancy, or immunological, consumptive, and metabolic diseases. The patient’s clinical characteristics, ISS scores, Glasgow coma scale (GCS), sequential organ failure assessment, APACHEⅡ scores, and nutrition and immune indexes on day 3 after injury were collected. The difference between the PICS group and N-PICS group were performed by Student’s t test, χ2 test or Mann-Whitney U test. The early risk factors were assessed in patients with PICS after severe polytrauma by logistic regression analysis. Results:According to the diagnostic criteria of PICS, all enrolled patients were divided into two groups: PICS group ( n=102) and N-PICS group (without PICS, n=174). Compared with the N-PICS group, patients in the PICS group were older and associated with more brain and chest injuries. On the third day after injury, serum levels of IL-6 and IL-10, and the ratio of Treg cells were significantly higher, the number and ratio of NK cells subset, and the ratio of activated T lymphocyte were significantly lower in the PICS group than in the N-PICS group ( P<0.05). Logistic regression analysis showed that the age>65 years old ( OR=2.375, 95% CI: 1.442-4.531), GCS ≤8 scores ( OR=3.431, 95% CI: 1.843-8.512), IL-10 >10 pg/mL ( OR=2.173, 95% CI: 1.751-5.614), the ratio of Treg cells >7% ( OR=3.871, 95% CI: 1.723-6.312), and the occurrence of traumatic brain and chest injuries ( OR=2.846, 95% CI: 1.522-5.361) were the early risk factors in patients with PICS after severe polytrauma. Conclusions:Age>65 years old, GCS score, IL-10, the ratio of Treg cells, and the occurrence of traumatic brain and chest injuries could be used as the early risk factors in patients with PICS after severe polytrauma. The discovery of early risk factors will help identify patients at high risk of PICS after severe polytrauma, and create the possibility for early intervention.

A prospective study of clinical characteristics and prognosis in patients with persistent inflammation, immunosuppression and catabolism syndrome after polytrauma / 中华急诊医学杂志

Objective:To prospectively assess clinical characteristics, potential causes and prognosis in patients with persistent inflammation, immunosuppression and catabolism syndrome (PICS) after polytrauma.Methods:Totally 1 083 patients with polytrauma admitted to Department of Traumatic Surgery of Tongji Hospital from Janury 2019 to July 2020 were enrolled. Exclusion criteria included age<18 years old, length of hospital stay<15 days, previous medical history of malignancy, or immunological, consumptive, and metabolic diseases. According to the diagnostic criteria of PICS, all enrolled patients were divided into two groups: PICS group and N-PICS group (without PICS). The patient’s clinical characteristics, ISS score, GCS score, SOFA score, and prognosis were collected. The χ2 test or Student’s t test was uesd to compare the difference between the PICS group and N-PICS group. Results:The incidence of PICS in patients with polytrauma was 11.7% (127/1 083). The majority of PICS patients were middle-aged and elderly men, 68.5% with traumatic brain injury and 59% with thoracic injury. GCS score was significantly lower, while ISS, APACHE II and SOFA scores were significantly higher in the PICS group than in the N-PICS group ( P<0.01, P<0.05). Among PICS patients, 79.5% were treated with mechanical ventilation and 76.3% were associated with pulmonary infection, with a 28-day mortality of 5.5% and a 180-day mortality of 16.5%, which were siginifcantly different from those without PICS. Conclusions:PICS has a high incidence after polytrauma and is commonly seen in middle-aged and elderly male patients with severe polytrauma, especially accompanied by traumatic brain injury or/and thoracic injury. Patients with PICS after polytrauma have poor long-term prognosis, so early identification and intervention should be strengthened in clinical practice.

Inpatients With 'Unexplained' Leukocytosis.

BACKGROUND: Unexplained or persistent leukocytosis is an increasing common cause of consultation to infectious disease physicians. Patients appear to be in a state of continued inflammation recently described as the persistent inflammation-immunosuppression and catabolism syndrome (PICS). Hospital course of such patients is frequently prolonged and associated with extensive use of empiric broad-spectrum antibiotics. We wished to determine the associated clinical features and outcome of such patients in anticipation of future specific diagnostic and therapeutic approaches to this syndrome. METHODS: We reviewed all infectious disease consultations from July 1, 2017, to March 31, 2018, for reason for consultation. Of those whose primary reason was "leukocytosis" or "bandemia," each chart was assessed for demographics, reason for admission, hospital day of consultation, peak white blood cell count, infections and possible microbiological colonization, antibiotic use, and outcome. RESULTS: A total of 29 patients were identified, constituting 4.5% of consults during the study period. Cause of admission was sepsis in 7, major trauma 6, cerebrovascular accident 5, major elective surgery 4, ischemic leg 3, and 1 each lung mass, acute myocardial infarction, interstitial lung disease, and angioblastic lymphoma. Peak total leukocyte count (WBC) was 26.4K ± 8.8 on mean day 9.6 ± 5.5 days of hospitalization. Mean duration of leukocytosis greater than 11K was 14.5 ± 10.6 days. Peak percentage early myelocytic ("band") leukocytes was 18.4 ± 13.8 and was of higher than 5% for a duration of 4.5 ± 5.6 days. Total eosinophilia count >500 was observed in 15 patients (range 500-2800) median hospital day 12. All patients received multiple and prolonged courses of broad-spectrum combination empiric antibiotics without apparent benefit either in terms of leukocytosis, signs of sepsis if present, or change in cultures, although those 7 with confirmed sepsis at admission tended to have shorter duration of leukocytosis and hospital course, whereas patients with trauma manifested greatest "bandemia." Most patients became colonized with resistant opportunistic organisms, the most significant being Clostridium difficile enteritis in 6 patients. Hospitalization was prolonged, and most common disposition was to nursing home or rehabilitation (11 patients, mean day of discharge 21.6 ± 16.8) and home (8 patients, day 16.0 ± 9.3). Three patients died at mean hospital day 35.7 ± 29.7. CONCLUSIONS: Except for 1 person with pelvic abscess post-cystectomy, patients appeared to have extensive tissue damage rather than active infection driving the leukocytosis. Patients appeared to meet clinical criteria for PICS that was substantiated by development of eosinophilia. Future studies should include direct measurements of the CD33CD11b+ myeloid suppressor cells, and the relative contribution of damage-associated molecular patterns (DAMPS) compared with pathogen-associated molecular patterns (PAMPS) such as endotoxin and other microbial products. More prudent and effective use of antibiotics could be possible.

[Advances in the research of severe burn-related corticosteroid insufficiency].

Despite considerable advances in diagnosis and treatment of the critical illness-related corticosteroid insufficiency (CIRCI), it is still not clear that whether it is common in severe burn patients or not, and how clinical diagnosis, treatment, and research progress. Severe burn is a systemic disease involving the damage of multiple organs of the whole body. The course of the disease is relatively long, and there often exists persistent inflammation, immunosuppression, and catabolism. On the basis of CIRCI study, the epidemiological evidence, possible mechanism, suspicious clinical manifestations, diagnosis and treatment of severe burn-related corticosteroid insufficiency (SBRCI) were briefly reviewed in this article in order to help clinical diagnosis and treatment of SBRCI.

[Nutritional support therapy during treatment of chronic critical illness].

Chronic critical illness (CCI) refers to a group of critically ill patients who survive the acute phase of intensive care, but with persistent organ dysfunction, thus entering a chronic period of continuous dependence on life support system, and still need to stay in intensive care unit (ICU) for a long time. Persistent inflammatory response-immunosuppression-catabolic syndrome (PICS) is the main pathophysiological feature of CCI. Three factors interact to form a vicious circle, leading to poor prognosis. Nutritional support therapy is a key link in the comprehensive treatment of CCI. Enteral nutrition (EN) should be started as soon as possible if conditions permit. If EN can not be implemented, temporary or transitional parenteral nutrition (PN) should be used, and EN should be added gradually in time. At the same time, the amount of PN should be gradually reduced. When EN meets more than 60% of patients' energy and protein requirements, PN can be considered to be discontinued. The main strategies and functions of CCI nutritional support therapy are as follows: strengthening high protein supply to correct negative nitrogen balance and inhibit catabolism, selecting branched chain amino acids (BCAA) to promote anabolism, using immunomodulators (arginine, ω3 polyunsaturated fatty acids) to improve immune suppression and inflammatory response, supplementing micronutrients (vitamins and trace elements) to counteract the decrease in intake and the increase in consumption, and adding probiotics to maintain the intestinal microecological balance, and so on. Reasonable nutritional support therapy not only improve malnutrition of CCI patients, but also help to reduce complications, thus speeding up rehabilitation, improving prognosis, shortening ICU hospitalization time, and even reducing mortality.

Late immune consequences of combat trauma: a review of trauma-related immune dysfunction and potential therapies.

With improvements in personnel and vehicular body armor, robust casualty evacuation capabilities, and damage control resuscitation strategies, more combat casualties are surviving to reach higher levels of care throughout the casualty evacuation system. As such, medical centers are becoming more accustomed to managing the deleterious late consequences of combat trauma related to the dysregulation of the immune system. In this review, we aim to highlight these late consequences and identify areas for future research and therapeutic strategies. Trauma leads to the dysregulation of both the innate and adaptive immune responses, which places the injured at risk for several late consequences, including delayed wound healing, late onset sepsis and infection, multi-organ dysfunction syndrome, and acute respiratory distress syndrome, which are significant for their association with the increased morbidity and mortality of wounded personnel. The mechanisms by which these consequences develop are complex but include an imbalance of the immune system leading to robust inflammatory responses, triggered by the presence of damage-associated molecules and other immune-modifying agents following trauma. Treatment strategies to improve outcomes have been difficult to develop as the immunophenotype of injured personnel following trauma is variable, fluid and difficult to determine. As more information regarding the triggers that lead to immune dysfunction following trauma is elucidated, it may be possible to identify the immunophenotype of injured personnel and provide targeted treatments to reduce the late consequences of trauma, which are known to lead to significant morbidity and mortality.

Advances in the research of severe burn-related corticosteroid insufficiency / 中华烧伤杂志

Despite considerable advances in diagnosis and treatment of the critical illness-related corticosteroid insufficiency (CIRCI), it is still not clear that whether it is common in severe burn patients or not, and how clinical diagnosis, treatment, and research progress. Severe burn is a systemic disease involving the damage of multiple organs of the whole body. The course of the disease is relatively long, and there often exists persistent inflammation, immunosuppression, and catabolism. On the basis of CIRCI study, the epidemiological evidence, possible mechanism, suspicious clinical manifestations, diagnosis and treatment of severe burn-related corticosteroid insufficiency (SBRCI) were briefly reviewed in this article in order to help clinical diagnosis and treatment of SBRCI.

Nutritional support therapy during treatment of chronic critical illness / 中华胃肠外科杂志

Chronic critical illness (CCI) refers to a group of critically ill patients who survive the acute phase of intensive care, but with persistent organ dysfunction, thus entering a chronic period of continuous dependence on life support system, and still need to stay in intensive care unit (ICU) for a long time. Persistent inflammatory response-immunosuppression-catabolic syndrome (PICS) is the main pathophysiological feature of CCI. Three factors interact to form a vicious circle, leading to poor prognosis. Nutritional support therapy is a key link in the comprehensive treatment of CCI. Enteral nutrition (EN) should be started as soon as possible if conditions permit. If EN can not be implemented, temporary or transitional parenteral nutrition (PN) should be used, and EN should be added gradually in time. At the same time, the amount of PN should be gradually reduced. When EN meets more than 60% of patients’ energy and protein requirements, PN can be considered to be discontinued. The main strategies and functions of CCI nutritional support therapy are as follows: strengthening high protein supply to correct negative nitrogen balance and inhibit catabolism, selecting branched chain amino acids (BCAA) to promote anabolism, using immunomodulators (arginine, ω3 polyunsaturated fatty acids) to improve immune suppression and inflammatory response, supplementing micronutrients (vitamins and trace elements) to counteract the decrease in intake and the increase in consumption, and adding probiotics to maintain the intestinal microecological balance, and so on. Reasonable nutritional support therapy not only improve malnutrition of CCI patients, but also help to reduce complications, thus speeding up rehabilitation, improving prognosis, shortening ICU hospitalization time, and even reducing mortality.

Innate Immunity in the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome and Its Implications for Therapy.

Clinical and technological advances promoting early hemorrhage control and physiologic resuscitation as well as early diagnosis and optimal treatment of sepsis have significantly decreased in-hospital mortality for many critically ill patient populations. However, a substantial proportion of severe trauma and sepsis survivors will develop protracted organ dysfunction termed chronic critical illness (CCI), defined as ≥14 days requiring intensive care unit (ICU) resources with ongoing organ dysfunction. A subset of CCI patients will develop the persistent inflammation, immunosuppression, and catabolism syndrome (PICS), and these individuals are predisposed to a poor quality of life and indolent death. We propose that CCI and PICS after trauma or sepsis are the result of an inappropriate bone marrow response characterized by the generation of dysfunctional myeloid populations at the expense of lympho- and erythropoiesis. This review describes similarities among CCI/PICS phenotypes in sepsis, cancer, and aging and reviews the role of aberrant myelopoiesis in the pathophysiology of CCI and PICS. In addition, we characterize pathogen recognition, the interface between innate and adaptive immune systems, and therapeutic approaches including immune modulators, gut microbiota support, and nutritional and exercise therapy. Finally, we discuss the future of diagnostic and prognostic approaches guided by machine and deep-learning models trained and validated on big data to identify patients for whom these approaches will yield the greatest benefits. A deeper understanding of the pathophysiology of CCI and PICS and continued investigation into novel therapies harbor the potential to improve the current dismal long-term outcomes for critically ill post-injury and post-infection patients.

The long-term quality of life in patients with persistent inflammation-immunosuppression and catabolism syndrome after severe acute pancreatitis: A retrospective cohort study.

PURPOSE: To explore clinical characteristics and long-term quality of life (QOL) in severe acute pancreatitis (SAP) patients with persistent inflammation-immunosuppression and catabolism syndrome (PICS). MATERIALS AND METHODS: SAP patients admitted to ICU were eligible for the retrospective cohort study if they needed prolonged intensive care (>14days). Post-ICU QOL was assessed by a questionnaire, including 36-item Short Form Health Survey (SF-36) and record of re-work in a long-term follow-up. RESULTS: 214 SAP patients were enrolled, in which 149 (69.6%) patients met the criteria of PICS. PICS patients had more complications and ICU days compared to non-PICS patients (P<0.001), and their post-ICU mortality was higher (P=0.046). When adjusted for confounders, PICS was independently associated with higher post-ICU mortality (hazard ratio 4.5; 95% CI, 1.2 to 16.3; P=0.024). The 36-item Short Form Health Survey (SF-36) score was lower for PICS group in six subscales (P<0.001). Only 28.8% patients in the PICS group returned to work compared to 60% patients in the non-PICS group (P=0.001) CONCLUSIONS: SAP patients with prolonged ICU stay had a high morbidity of PICS, which was a risk factor for the post-ICU mortality and poor long-term QOL.