A nomogram for predicting hospital mortality of critical ill patients with sepsis and cancer: a retrospective cohort study based on MIMIC-IV and eICU-CRD.

OBJECTIVE: Sepsis remains a high cause of death, particularly in immunocompromised patients with cancer. The study was to develop a model to predict hospital mortality of septic patients with cancer in intensive care unit (ICU). DESIGN: Retrospective observational study. SETTING: Medical Information Mart for Intensive Care IV (MIMIC IV) and eICU Collaborative Research Database (eICU-CRD). PARTICIPANTS: A total of 3796 patients in MIMIC IV and 549 patients in eICU-CRD were included. PRIMARY OUTCOME MEASURES: The model was developed based on MIMIC IV. The internal validation and external validation were based on MIMIC IV and eICU-CRD, respectively. Candidate factors were processed with the least absolute shrinkage and selection operator regression and cross-validation. Hospital mortality was predicted by the multivariable logistical regression and visualised by the nomogram. The model was assessed by the area under the curve (AUC), calibration curve and decision curve analysis curve. RESULTS: The model exhibited favourable discrimination (AUC: 0.726 (95% CI: 0.709 to 0.744) and 0.756 (95% CI: 0.712 to 0.801)) in the internal and external validation sets, respectively, and better calibration capacity than Acute Physiology and Chronic Health Evaluation IV in external validation. CONCLUSIONS: Despite that the predicted model was based on a retrospective study, it may also be helpful to predict the hospital morality of patients with solid cancer and sepsis.

Short- and medium-term survival of critically ill patients with solid cancer admitted to the intensive care unit.

BACKGROUND: A great increase in the number of patients needs critical care to the intensive care unit (ICU) due to improvements in oncology. The aim of the study was to explore risk factors affecting survival of critically ill patients with solid cancers in ICU. METHODS: The study retrospectively reviewed patients between 2001 and 2012, which were collected by Medical Information Mart for Intensive Care III (MIMIC-III) from the Beth Israel Deaconess Medical Center in Boston, MA, USA. RESULTS: A total of 38,508 adult patients, who were admitted to ICUs and 8,308 (21.6%) were diagnosed as an underlying malignancy; 1,671 and 3,165 adult patients with sold cancer were admitted to surgical ICU (SICU) and medical ICU (MICU), respectively. Patients in SICU had a higher survival rate at the point of 28-, 90-day, and 1-, 3-year than patients in MICU (P<0.001 for all). Multivariate analysis demonstrated that age ≥70, emergency admission, the presence of metastases, Oxford Acute Severity of Illness Score (OASIS) ≥30 and sepsis were independent risk factors affecting 28-day survival in SICU. In MICU, emergency admission, metastatic disease, Sequential Organ Failure Assessment (SOFA) ≥3, Simplified Acute Physiology Score II (SAPS II) ≥39, Acute Physiology Score III (APS III) ≥40, Oxford Acute Severity of Illness Score (OASIS) ≥30, Elixhauser comorbidity index ≥9 and sepsis were independent risk factors for 28-day survival rate. The area under curve (AUC) of the OASIS for predicting ICU mortality was 0.824 [95% confidence interval (CI): 0.805-0.842], which was obviously higher than other scores in SICU. The AUC of the SAPS II for predicting ICU mortality was 0.820 (95% CI: 0.806-0.833), which was slightly higher than other scores in MICU. CONCLUSIONS: Patients with cancer in SICU have longer survival time than patients with cancer in MICU. The prediction of prognosis of critically ill cancer patients can guide treatment and optimize medical resources.

The effect of the underlying malignancy on short- and medium-term survival of critically ill patients admitted to the intensive care unit: a retrospective analysis based on propensity score matching.

BACKGROUND: Advances in oncology led to a substantial increase in the number of patients requiring admission to the ICU. It is significant to confirm which cancer critical patients can benefit from the ICU care like noncancer patients. METHODS: An observational retrospective cohort study using intensive care unit (ICU) admissions of Medical Information Mart for Intensive Care III from the Beth Israel Deaconess Medical Center in Boston, MA, USA between 2001 and 2012 was conducted. Propensity score matching was used to reduce the imbalance between two matched cohorts. ICU patients with cancer were compared with those without cancer in terms of patients' characteristics and survival. RESULTS: There were 38,508 adult patients admitted to ICUs during the period. The median age was 65 years (IQR, 52-77) and 8308 (21.6%) had an underlying malignancy diagnosis. The noncancer group had a significant survive advantage at the point of 28-day, 90-day, 365-day and 1095-day after ICU admission compared with cancer group (P < 0.001 for all) after PSM. Subgroup analysis showed that the diagnosis of malignancy didn't decrease 28-day and 90-day survive when patients' age ≥ 65-year, patients in surgical intensive care unit or cardiac surgery recovery unit or traumatic surgical intensive care unit, elective admissions, patients with renal replacement therapy or vasopressor support (P > 0.05 for all). CONCLUSIONS: Malignancy is a common diagnosis among ICU patients. Patients without cancer have a survive advantage compared with patients with cancer in the short- and medium-term. However, in selected groups, cancer critical patients can benefit from the ICU care service like noncancer patients in the short-term.

A randomized controlled trial comparing the efficacy of tigecycline versus meropenem in the treatment of postoperative complicated intra-abdominal infections.

BACKGROUND: The efficacy and safety of tigecycline in the treatment of complicated intra-abdominal infections (cIAIs) is potentially controversial. Here we conducted the non-inferiority study to assess the efficacy and safety of tigecycline versus meropenem in the treatment of postoperative cIAIs. METHODS: Data of abdominal tumor surgery patients with postoperative cIAIs admitted to intensive care unit (ICU) between October 2017 and December 2019 were collected. A prospective, randomized controlled trial was conducted in which 56 eligible patients with cIAIs randomly received intravenous tigecycline or meropenem for 3 to 14 days. Patients and clinicians were not blinded to the group allocation. RESULTS: The total of 56 patients were enrolled, which were divided into 2 groups, one group included 30 patients receiving meropenem and another group included 26 receiving tigecycline therapy. The 2 groups were similar at demographic and baseline clinical characteristics. Microorganisms were isolated from 46 of 56 patients (82.14%), with a total of 107 pathogens were cultured in two groups. The two groups had similar distribution of infecting microorganisms. The primary end point was the clinical response at the end-oftherapy (EOT) visit and upon discharge visit and comprehensive efficacy. The clinical success rates were 83.33%, 76.67% for meropenem versus 76.92%, 88.46% for tigecycline at the EOT visit and upon discharge visit (P>0.05), respectively. Comprehensive efficacy did not significantly differ between two groups either. There were no significant differences in 30-day and 60-day all-cause mortality between two groups (P>0.05). The univariable analysis identified that serum albumin at admission ICU, colorectal cancer on oncology type, postoperative abdominal bleeding were the risk factors for 60-day all-cause mortality. The multivariable analysis showed that postoperative abdominal bleeding were independent predictors of 60-day all-cause mortality. Gastrointestinal disorders and antibacterials-induced Fungal Infection were the most frequently reported adverse events (AEs). The incidence of AEs was similar between meropenem and tigecycline groups (P>0.05). CONCLUSIONS: Taken together, the study demonstrated that tigecycline is as effective and safe as meropenem for postoperative cIAIs in abdominal tumors patients. Tigecycline is non-inferior to meropenem.

Long noncoding RNA LINC01194 enhances the malignancy of laryngeal squamous cell carcinoma by sponging miR-655 to increase SOX18 expression.

Long noncoding RNAs (lncRNAs) have undergone a comprehensive study for their involvements in tumor treatments. The purpose of our study was to explore the biological effects and regulatory mechanisms of lncRNA LINC01194 (LINC01194) in laryngeal squamous cell carcinoma (LSCC). The levels of LINC01194 in 105 LSCC patients were detected by RT-qPCR. The diagnostic and prognostic value of LINC01194 in LSCC patients were statistically analyzed. The potential functions of LINC01194 in proliferation, apoptosis, and metastasis of LSCC cells were evaluated. The interaction among LINC01194, miR-655 and SOX18 was explored by bioinformatics analysis, luciferase reporter assays and biotinylated RNA pull-down. We found that the expression levels of LINC01194 were highly expressed in LSCC, which was negatively correlated with the clinical outcome of LSCC patients. The area under the ROC curve for LINC01194 was up to 0.8388. Functional assays indicated that LINC01194 knockdown distinctly inhibited LSCC cells proliferation, induced apoptosis, and also attenuated LSCC cells migration and invasion in vitro. Furthermore, we elucidated that LINC01194 promoted SOX18 expression in LSCC cells via functioning as a molecular sponge for miR-655. Overall, based on our findings, LINC01194 served as a tumor promoter and potentially represents a novel prognostic indicator and therapeutic target in LSCC.

Neoadjuvant therapy does not adversely affect the short-term outcome of critically ill cancer patients who underwent surgery.

BACKGROUND: There were conflicting data regarding the effects of neoadjuvant therapy (NT) on the short-term outcomes of critically ill cancer patients. The aim of this study was to investigate whether NT adversely affect the short-term outcomes of critically ill cancer patients who underwent surgery. METHODS: This was a retrospective study which enrolled all critically ill cancer patients who admitted to intensive care unit (ICU) of Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College between September 2017 and September 2018. Patients were divided into two groups: NT group and no NT (nNT) group. The primary outcome was ICU mortality rate. Propensity score analysis and Logistic regression analysis were used to investigate risk factors of ICU death. RESULTS: Hundred and twenty-eight patients received NT and 737 patients did not. The ICU mortality was higher in NT group than that in nNT group (3.9% vs. 1.4%, P=0.041) before propensity score matching analysis. After matching, there were no significant difference in ICU mortality between NT group and nNT group. Univariable logistic analysis demonstrated that a history of coronary heart disease (P=0.008), NT (P=0.041), unplanned admission to ICU (P<0.001), simplified acute physiology score (SAPS) 3 on ICU admission (P<0.001), sequential organ failure assessment (SOFA) on ICU admission (P<0.001), acute kidney injury (P<0.001), and mechanical ventilation (P<0.001) were predictive of ICU death in all 865 patients. Multivariable logistic regression analysis demonstrated that history of coronary heart disease (P=0.010; OR =9.614; 95% CI, 1.731-53.405), SAPS 3 on ICU admission (P=0.026; OR =1.070; 95% CI, 1.008-1.135) and SOFA on ICU admission (P=0.031; OR =1.289; 95% CI, 1.024-1.622) were independent risk factors of ICU death, while NT was not predictive of ICU death (P=0.118). CONCLUSIONS: NT was not a risk factor for ICU death in critically ill cancer patients who underwent surgery.

The 28-day survive for critically ill cancer patients undergoing continuous renal replacement with postoperative acute kidney injure: a retrospective study of 86 cases.

BACKGROUND: Advances in oncology led to a substantial increase in the number of patients requiring admission to the intensive care unit (ICU). It remains controversial to start continuous renal replacement therapy (CRRT) for acute kidney injure (AKI) in critically ill patients with cancer because of the poor outcome and high costs. METHODS: In this retrospective study, we collected data from patients with cancer with postoperative AKI-stage 3 [Kidney Disease: Improving Global Outcomes (KDIGO), 2012] undergoing CRRT in the ICU of Cancer Hospital, Chinese Academy of Medical Sciences from January 2010 to January 2019. Patients were followed up until the time of death or the point of 28-day after ICU admission. Univariate and multivariate analysis was performed to identify risk factors for 28-day survive. RESULTS: Of 8,030 cancer patients after surgical operation admitted by ICU, a total of 86 (1.1%) patients developed postoperative AKI: male/female: 62/24, median age 61 [27-82] years. The number of digestive tract/lung/other types of cancer was 59, 10 and 17, respectively. The median Simplified Acute Physiology Score III (SAPS III) was 65 [49-109] and the median Sequential Organ Failure Assessment (SOFA) score was 6 [1-19]. There were 35 deaths eventually and all the deaths occur within 28 days after ICU admission. Twenty-eight-day survive rate was 57.1%±5.8%. In multivariate cox regression analysis, two risk factors independently affected 28-day survive: SAPS III score ≥65 [hazard ratio (HR): 3.451 (1.272-9.365), P=0.015], the presence of shock at the start of CRRT [HR: 10.262 (2.210-47.660), P=0.003]. The cancer status (P=0.076), cancer types (P>0.05 for both) and neoadjuvant therapy associated with cancer (P=0.949) showed no effects on 28-day survive. CONCLUSIONS: For cancer patients, postoperative AKI-stage 3 is a serious complication with a low 28-day survive rate. Patients with the presence shock at the start of CRRT or SAPS III ≥65 will have a poor 28-day survive. It should be emphasized that the cancer characteristics (status, types or treatment) don't affect 28-day survive.

A mouse model for studying the clearance of hepatitis B virus in vivo using a luciferase reporter.

Hepatitis B virus(HBV) infection remains a global problem, despite the effectiveness of the Hepatitis B vaccine in preventing infection. The resolution of Hepatitis B virus infection has been believed to be attributable to virus-specific immunity. In vivo direct evaluation of anti-HBV immunity in the liver is currently not possible. We have developed a new assay system that detects HBV clearance in the liver after the hydrodynamic transfer of a reporter gene and over-length, linear HBV DNA into hepatocytes, followed by bioluminescence imaging of the reporter gene (Fluc). We employed bioluminescence detection of luciferase expression in HBV-infected hepatocytes to measure the Hepatitis B core antigen (HBcAg)-specific immune responses directed against these infected hepatocytes. Only HBcAg-immunized, but not mock-treated, animals decreased the amounts of luciferase expression, HBsAg and viral DNA from the liver at day 28 after hydrodynamic infection with over-length HBV DNA, indicating that control of luciferase expression correlates with viral clearance from infected hepatocytes.