Machine Learning Model Development and Validation for Predicting Outcome in Stage 4 Solid Cancer Patients with Septic Shock Visiting the Emergency Department: A Multi-Center, Prospective Cohort Study.

A reliable prognostic score for minimizing futile treatments in advanced cancer patients with septic shock is rare. A machine learning (ML) model to classify the risk of advanced cancer patients with septic shock is proposed and compared with the existing scoring systems. A multi-center, retrospective, observational study of the septic shock registry in patients with stage 4 cancer was divided into a training set and a test set in a 7:3 ratio. The primary outcome was 28-day mortality. The best ML model was determined using a stratified 10-fold cross-validation in the training set. A total of 897 patients were included, and the 28-day mortality was 26.4%. The best ML model in the training set was balanced random forest (BRF), with an area under the curve (AUC) of 0.821 to predict 28-day mortality. The AUC of the BRF to predict the 28-day mortality in the test set was 0.859. The AUC of the BRF was significantly higher than those of the Sequential Organ Failure Assessment score and the Acute Physiology and Chronic Health Evaluation II score (both p < 0.001). The ML model outperformed the existing scores for predicting 28-day mortality in stage 4 cancer patients with septic shock. However, further studies are needed to improve the prediction algorithm and to validate it in various countries. This model might support clinicians in real-time to adopt appropriate levels of care.

The feasibility of extracorporeal cardiopulmonary resuscitation for patients with active cancer who undergo in-hospital cardiac arrest.

Indications of extracorporeal cardiopulmonary resuscitation (ECPR) are still debatable, particularly in patients with cancer. Prediction of the prognosis of in-hospital cardiac arrest (IHCA) in patients with cancer receiving ECPR is important given the increasing prevalence and survival rate of cancer. We compared the neurologic outcomes and survival rates of IHCA patients with and without cancer receiving ECPR. Data from the extracorporeal membrane oxygenation registry between 2015 and 2019 were used in a retrospective manner. The primary outcome was 6-month good neurologic outcome, defined as a Cerebral performance category score of 1 or 2. The secondary outcomes were 1- and 3-month good neurologic outcome, and 6-month survival. Among 247 IHCA patients with ECPR, 43 had active cancer. The 6-month good neurologic outcome rate was 27.9% and 32.4% in patients with and without active cancer, respectively (P > 0.05). Good neurologic outcomes at 1-month (30.2% vs. 20.6%) and 3-month (30.2% vs. 28.4%), and the survival rate at 6-month (39.5% vs. 36.5%) were not significantly different (all P > 0.05) Active cancer was not associated with 6-month good neurologic outcome by logistic regression analyses. Therefore, patients with IHCA should not be excluded from ECPR solely for the presence of cancer itself.

Biomarker Analysis for Combination Therapy of Vitamin C and Thiamine in Septic Shock: A Post-Hoc Study of the ATESS Trial.

INTRODUCTION: We evaluated the effects of vitamin C and thiamine administration on biomarkers in patients with septic shock. METHODS: This was a post-hoc analysis of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial, a multicenter, double-blind, randomized controlled trial. Patients were randomized to either a treatment group (intravenous vitamin C and thiamine for 48 h) or a control group. Interleukin (IL)-6, IL-10, angiopoietin-II (AP2), and S100ß were assessed at baseline and at 72 h. The primary outcomes were the biomarker levels at 72 h, and the secondary outcome was reduction rate. RESULTS: Forty-five patients were assigned to the treatment group and 52 were assigned to the control group. Baseline biomarker levels and at 72 h were not significantly different between the treatment and the placebo groups. The reduction rates were not significantly different between the two groups. These outcome variables showed fair diagnostic accuracy for predicting 28-day mortality according to the area under the receiver operating characteristic curve. CONCLUSION: Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100ß. TRIAL REGISTRATION: NCT, ClinicalTrials.gov NCT03756220, ATESS. Registered 28 November 2018, https://clinicaltrials.gov/ct2/show/NCT03756220.

Prognostic factors for late death in septic shock survivors: a multi-center, prospective, registry-based observational study.

Septic shock patients who survive past the acute period are associated with an increased risk of long-term mortality. However, factors for predicting late death remain unclear. We aimed to investigate the prognostic factors associated with late mortality in septic shock patients with 28-day survival after admission. This retrospective observational study used a prospective, multi-center registry of septic shock patients between October 2015 and December 2019 involving 12 emergency departments (EDs) from the Korean Shock Society. Adult septic shock patients visiting the ED with 28-day survival after admission were included. Among 4624 septic shock patients, 3588 (77.6%) who survived past day 28 were analyzed. The 90-day mortality rate was 14.2%. Non-survivors were older (66.8 vs. 68.9 years; p = 0.032) and had higher lactate levels (3.7 vs. 4.0 mmol/L; p = 0.028) than survivors. Pulmonary and hepatobiliary infections and a history of malignancy (27.7 vs. 57.5%; p < 0.001) were more frequent in the non-survivor group than in the survivor group. Independent risk factors for late death on multivariate regression analysis were age; malignancy; and hemoglobin, blood urea nitrogen, and albumin levels. The length of intensive care unit stay and Sequential Organ Failure Assessment score were independently associated with late death. Approximately, one-seventh of septic shock patients who survived past day 28 of admission died by day 90. Physicians must pay attention to survivors with these risk factors during the post-acute period as they have an increased mortality risk.

Development and validation of the VitaL CLASS score to predict mortality in stage IV solid cancer patients with septic shock in the emergency department: a multi-center, prospective cohort study.

BACKGROUND: Clinical decision-making of invasive high-intensity care for critically ill stage IV cancer patients in the emergency department (ED) is challenging. A reliable and clinically available prognostic score for advanced cancer patients with septic shock presented at ED is essential to improve the quality of intensive care unit care. This study aimed to develop a new prognostic score for advanced solid cancer patients with septic shock available early in the ED and to compare the performance to the previous severity scores. METHODS: This multi-center, prospective cohort study included consecutive adult septic shock patients with stage IV solid cancer. A new scoring system for 28-day mortality was developed and validated using the data of development (January 2016 to December 2017; n = 469) and validation sets (January 2018 to June 2019; n = 428). The developed score's performance was compared to that of the previous severity scores. RESULTS: New scoring system for 28-day mortality was based on six variables (score range, 0-8): vital signs at ED presentation (respiratory rate, body temperature, and altered mentation), lung cancer type, and two laboratory values (lactate and albumin) in septic shock (VitaL CLASS). The C-statistic of the VitaL CLASS score was 0.808 in the development set and 0.736 in the validation set, that is superior to that of the Sequential Organ Failure Assessment score (0.656, p = 0.01) and similar to that of the Acute Physiology and Chronic Health Evaluation II score (0.682, p = 0.08). This score could identify 41% of patients with a low-risk group (observed 28-day mortality, 10.3%) and 7% of patients with a high-risk group (observed 28-day mortality, 73.3%). CONCLUSIONS: The VitaL CLASS score could be used for both risk stratification and as part of a shared clinical decision-making strategy for stage IV solid cancer patients with septic shock admitting at ED within several hours.

Cancer patients with neutropenic septic shock: etiology and antimicrobial resistance.

BACKGROUND/AIMS: Among patients with febrile neutropenia that developed after chemotherapy, high-risk patients, such as those having clinical instability or Multinational Association of Supportive Care in Cancer score of < 21, require hospitalization for intravenous empiric antibiotic therapy. Monotherapy with an anti-pseudomonal ß-lactam agent is recommended. Although many studies reported the microbial etiology of infections and resistant patterns of febrile neutropenia, the patients were not well characterized as having neutropenic septic shock. Therefore, this study aimed to determine the microbial spectrum of infections and resistance patterns of their isolates in patients with chemotherapy-induced neutropenic septic shock. METHODS: Data of adult patients diagnosed with neutropenic septic shock in the emergency department between June 2012 and December 2016 were extracted from a prospectively compiled septic shock registry at a single academic medical center. Thereafter, microbiological studies and antimicrobial susceptibility tests were conducted. RESULTS: In total, 109 bacteria were found in patients with neutropenic septic shock. Gram-negative bacteria were the predominant causative organisms (84, 77.1%). Moreover, 33 microorganisms (30.3%) were multidrug-resistant (MDR) bacteria with extended-spectrum ß-lactamase-producing Escherichia coli (17, 50%) being the commonest. The most commonly affected sites in patients with MDR bacterial infections were the gastrointestinal tract (45%) and unknown (43.5%). Approximately 48.5% of MDR bacteria were resistant to cefepime but not to piperacillin-tazobactam or carbapenem. CONCLUSION: MDR bacteria were prevalent in patients with chemotherapy-induced neutropenic septic shock. Therefore, piperacillin-tazobactam or carbapenem may be considered as empiric antibiotics if MDR bacteria are suspected to be causative agents.

The usefulness of C-reactive protein and procalcitonin to predict prognosis in septic shock patients: A multicenter prospective registry-based observational study.

The objective of this study was to evaluate the prognostic value of C-reactive protein (CRP), procalcitonin (PCT), and their combination for mortality in patients with septic shock. This multicenter, prospective, observational study was conducted between November 2015 and December 2017. A total of 1,772 septic shock patients were included, and the overall 28-day mortality was 20.7%. Although both CRP and PCT were elevated in the non-survivor group, only CRP had statistical significance (11.9 mg/dL vs. 14.7 mg/dL, p = 0.003, 6.4 ng/mL vs. 8.2 ng/mL, p = 0.508). Multivariate analysis showed that CRP and PCT were not independent prognostic markers. In the subgroup analysis of the CRP and PCT combination matrix using their optimal cut-off values (CRP 14.0 mg/dL, PCT 17.0 ng/dL), both CRP and PCT elevated showed significantly higher mortality (Odds ratio 1.552 [95% Confidence intervals 1.184-2.035]) than both CRP and PCT not elevated (p = 0.001) and only PCT elevated (p = 0.007). However, both CRP and PCT elevated was also not an independent predictor in multivariate analysis. Initial levels of CRP and PCT alone and their combinations in septic shock patients had a limitation to predict 28-day mortality. Future research is needed to determine new biomarkers for early prognostication in patients with septic shock.

Risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae infection causing septic shock in cancer patients with chemotherapy-induced febrile neutropenia.

Patients with chemotherapy-induced febrile neutropenia (FN) are vulnerable to extended-spectrum b-lactamase-producing Enterobacteriaceae (ESBL-PE) infection. Early identification of patients suspected to have ESBL-PE infection for empirical carbapenem administration is crucial; nevertheless, risk factors for ESBL-PE causing septic shock remain unclear. We identify factors to predict ESBL-PE in septic shock patients with chemotherapy-induced FN. In this observational, prospectively collected registry-based study, consecutive adult chemotherapy-induced FN patients with septic shock who were admitted to the emergency department between June 2012 and June 2018 were enrolled. Clinical and laboratory data extracted from the septic shock registry were assessed to identify risk factors for ESBL-PE. Of 179 chemotherapy-induced FN septic shock patients, ESBL-PE is isolated in 23 (12.8%). ESBL-PE infection is frequently seen in patients with hepatobiliary cancer (17.4% vs. 4.5%, P = 0.037), leukemia (13.0% vs. 2.6%, P = 0.046), and those with profound neutropenia (defined as absolute neutrophil count < 100) (73.9% vs. 43.6%, P = 0.007) in contrast to those with lung cancer (0% vs. 14.7%, P = 0.048) and other solid cancer (0% vs. 19.2%, P = 0.016). Multivariate logistic regression reveals that profound neutropenia (adjusted OR 3.67; 95% CI 1.372-9.799; P = 0.010) is an independent risk factor for ESBL-PE infection after adjusting age, the presence of solid tumor, and the parameters of sepsis severity scores. ESBL-PE is rare (12.9%) in chemotherapy-induced FN patients with septic shock. Early empirical carbapenem therapy might be considered in chemotherapy-induced FN patients with profound neutropenia.

Factors Predicting Bacterial Infection in Out-of-Hospital Cardiac Arrest Patients Undergoing Targeted Temperature Management.

The objective of this study was to determine a risk factor for predicting bacterial infection in patients, who survived out-of-hospital cardiac arrest (OHCA), during targeted temperature management (TTM). This prospective registry-based retrospective observational study was conducted from November 2010 to October 2017. We measured several biomarkers such as whole blood cell counts, and levels of C-reactive protein and procalcitonin daily during TTM. The primary outcome was bacterial growth in initial blood or sputum cultures. A total of 116 patients were analyzed in this study. The bacterial growth rate was 32.8% and the procalcitonin levels measured at 24 h from cardiac arrest was significantly higher in the culture-positive group than the culture-negative group (10.6 vs. 2.5 ng/mL, p = 0.017). Area under the receiver operating characteristic curve for procalcitonin obtained after 24 h was 0.727 and the cutoff value was 6.5 ng/mL (odds ratio 9.58 [95% confidential interval, CI 2.21-41.55], p = 0.003). Sensitivity was 71.4% [95% CI 41.9-91.6] and specificity was 79.3% [95% CI 60.3-92.0]. Procalcitonin measured at 24 h from cardiac arrest was associated with bacterial infection in OHCA patients undergoing TTM. Further prospective interventional studies are needed to validate these results.

Role of blood gas analysis during cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients.

To determine the relationship between acid-base findings, such as pH, pCO2, and serum lactate levels, obtained immediately after starting cardiopulmonary resuscitation and the return of spontaneous circulation (ROSC).A prospective observational study of adult, nontraumatic out-of-hospital cardiac arrest (OHCA) patients was conducted at an urban academic teaching institution between April 1, 2013 and March 31, 2015. Arterial blood sample for acid-base data was taken from all OHCA patients on arrival to the emergency department. Of 224 OHCA patients, 88 patients with unavailable blood samples or delayed blood sampling or ROSC within 4 minutes were excluded, leaving 136 patients for analysis.The pH in the ROSC group was significantly higher than in the non-ROSC group (6.96 vs. 6.85; P = 0.009). pCO2 and lactate levels in the ROSC group were significantly lower than those in the non-ROSC group (74.0 vs. 89.5 mmHg, P < 0.009; 11.6 vs. 13.6 mmol/L, P = 0.044, respectively). In a multivariate regression analysis, pCO2 was the only independent biochemical predictor for sustained ROSC (OR 0.979; 95% CI 0.960-0.997; P = 0.025) and pCO2 of <75 mmHg was 3.3 times more likely to achieve ROSC (OR 0.302; 95% CI 0.146-0.627; P = 0.001).pCO2 levels obtained during cardiopulmonary resuscitation on ER arrival was associated with ROSC in OHCA patients. It might be a potentially marker for reflecting the status of the ischemic insult. These preliminary results need to be confirmed in a larger population.