The role of tocilizumab therapy in critically ill patients with severe acute respiratory syndrome coronavirus 2

Abstract Context Tocilizumab (TCZ), an interleukin-6 (IL-6) receptor antagonist, has been approved for use in rheumatoid arthritis and cytokine storm syndrome (CSS) associated with chimeric antigen receptor T cells treatment. Although TCZ is currently utilized in the treatment of critically ill coronavirus 2019 (COVID-19) patients, data on survival impact is minimal. Objectives To assess the mortality rate of patients presenting with COVID-19 who received TCZ for suspected CSS. Methods This retrospective cohort study was conducted at Henry Ford Health System between March 10, 2020 and May 18, 2020. Data collection began in May 2020 and was completed in June 2020. Patients included in the study required hospital admission and had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction on nasopharyngeal swab. Eligibility criteria to receive TCZ, per hospital protocol, included any of the following: persistent fever, defined as 38.0 °C for at least 6 hours; a diagnosis of the acute respiratory distress syndrome (ARDS); serum ferritin ≥1,000 (ng/mL) or doubling within 24 hours; D-Dimer ≥ 5 (mg/L); serum lactate dehydrogenase ≥500 (IU/L); or interlukin-6 level ≥5 times the upper limit of normal. Dosing was initially determined by weight, then changed to a fixed 400 mg per hospital protocol. A comparator cohort was created from patients with COVID-19 and ARDS who did not receive TCZ. Patient survival was analyzed using the Kaplan–Meier method and compared by log rank test. A multivariable cox regression was applied to evaluate the association between TCZ and mortality. Results One hundred and thirty patients were evaluated in the study, 54 (41.5%) of whom received TCZ. Patients who received TCZ were younger (mean age, 63.8 vs. 69.4 years; p=0.0083) and had higher body mass indices (mean, 33.9 vs. 30.4; p=0.005). Of the comorbid conditions evaluated, heart disease was more common in the comparator group than the TCZ group (27 patients [35.5%] vs. 10 patients [18.5%]; p=0.034). A Kaplan–Meier survival curve demonstrated no difference in survival between TCZ and comparator patients (log rank p=0.495). In the multivariable Cox regression model for mortality at 30 days, treatment with TCZ was not associated with decreased mortality (hazard ratio, 1.1; 95% confidence interval, 0.53–2.3; p=0.77). Lower mean C-reactive protein (CRP) levels were demonstrated within 48 hours of disposition in the TCZ group (mean TCZ, 4.9 vs. mean comparator, 13.0; p=<0.0001). Conclusions In this cohort study, no difference in survival was observed in critically ill patients treated with TCZ.

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Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study

Annals of Intensive Care ◽

10.1186/s13613-020-00652-0 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Rene A. Posma ◽

Trine Frøslev ◽

Bente Jespersen ◽

Iwan C. C. van der Horst ◽

Daan J. Touw ◽

...

Keyword(s):

Cohort Study ◽

Mortality Rate ◽

Critically Ill ◽

Critically Ill Patients ◽

Cox Regression ◽

Lower Mortality ◽

Prognostic Impact ◽

Icu Admission ◽

Lactate Levels ◽

Restricted Cubic Splines

Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.

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Association of Low Alanine Aminotransferase Values with Extubation Failure in Adult Critically Ill Patients: A Retrospective Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10153282 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3282

Author(s):

Yoav Weber ◽

Danny Epstein ◽

Asaf Miller ◽

Gad Segal ◽

Gidon Berger

Keyword(s):

Cohort Study ◽

High Risk ◽

Critically Ill ◽

Critically Ill Patients ◽

Alanine Aminotransferase ◽

Cox Regression ◽

Independent Predictor ◽

Extubation Failure ◽

Increased Risk ◽

Ventilated Patients

Background: Liberation from mechanical ventilation is a cardinal landmark during hospitalization of ventilated patients. Decreased muscle mass and sarcopenia are associated with a high risk of extubation failure. A low level of alanine aminotransferase (ALT) is a known biomarker of sarcopenia. This study aimed to determine whether low levels of ALT are associated with increased risk of extubation failure among critically ill patients. Methods: This was a retrospective single-center cohort study of mechanically ventilated patients undergoing their first extubation. The study’s outcome was extubation failure within 48 h and 7 days. Multivariable logistic and Cox regression were performed to determine whether ALT was an independent predictor of these outcomes. Results: The study included 329 patients with a median age of 62.4 years (IQR 48.1–71.2); 210 (63.8%) patients were at high risk for extubation failure. 66 (20.1%) and 83 (25.2%) failed the extubation attempt after 48 h and 7 days, respectively. Low ALT values were more common among patients requiring reintubation (80.3–61.5% vs. 58.6–58.9%, p < 0.002). Multivariable logistic regression analysis identified ALT as an independent predictor of extubation failure at 48 h and 7 days. ALT ≤ 21 IU/L had an adjusted hazard ratio (HR) of 2.41 (95% CI 1.31–4.42, p < 0.001) for extubation failure at 48 h and ALT ≤ 16 IU/L had adjusted HR of 1.94 (95% CI 1.25–3.02, p < 0.001) for failure after 7 days. Conclusions: Low ALT, an established biomarker of sarcopenia and frailty, is an independent risk factor for extubation failure among hospitalized patients. This simple laboratory parameter can be used as an effective adjunct predictor, along with other weaning parameters, and thereby facilitate the identification of high-risk patients.

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Atrial fibrillation increased in-hospital and 4-year all-cause mortality in Critically ill patients with liver cirrhosis

10.21203/rs.3.rs-381056/v1 ◽

2021 ◽

Author(s):

Yanting Luo ◽

Bingyuan Wu ◽

Yuankai Wu ◽

Long Peng ◽

Zexiong Li ◽

...

Keyword(s):

Atrial Fibrillation ◽

Liver Cirrhosis ◽

Intensive Care ◽

Mortality Rate ◽

Critically Ill ◽

Clinical Data ◽

Critically Ill Patients ◽

Cox Regression ◽

Kaplan Meier ◽

All Cause Mortality

Abstract ObjectiveThe purpose of this study was to use a large database that contains information on patient intensive care unit (ICU) admissions to study critically ill patients with cirrhosis and the relation with atrial fibrillation and short-term and 4-year mortality. MethodsThe Monitoring in Intensive Care Database III database was used to identify patients with cirrhosis hospitalized in an ICU from 2001 to 2012. Demographic and clinical data were extracted from the database. Clinical data and demographic information were collected for each patient in our study. Kaplan-Meier analysis and multivariate Cox regression models were performed to examine the relation between atrial fibrillation and in-hospital and 4-year all-cause mortality. ResultsA total of 1,481 patients (mean age 58 years, 68% male) with liver cirrhosis treated in an ICU were included in the analysis, and the prevalence of atrial fibrillation was 14.2%. The in-hospital all-cause mortality rate was 26.60%, and patients who had a significantly higher rate of atrial fibrillation (21.57% vs. 11.50%, P < 0.001). Multivariate analysis indicated that atrial fibrillation was significantly associated with in-hospital all-cause mortality (hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.19 to 1.95; P < 0.001), and 4-year all-cause mortality (HR = 1.55, 95% CI: 1.12 to 2.13; P = 0.008). Kaplan-Meier survival analysis showed that patients with atrial fibrillation had a significantly higher in-hospital and 4-year all-cause mortality rate than patients without atrial fibrillation. ConclusionsCritically ill patients with liver cirrhosis have a significantly increased rate of atrial fibrillation, and the presence of atrial fibrillation is an independent risk for in-hospital and 4-year all-cause mortality.

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Thromboelastography Parameters as Predictors for Long-Term Survival in Critically Ill Patients

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029619876028 ◽

2019 ◽

Vol 25 ◽

pp. 107602961987602

Author(s):

Cuizhu Luo ◽

Bingjie Zhuang ◽

Zhongqing Chen

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Cox Regression ◽

Maximum Amplitude ◽

Curve Analysis ◽

Term Survival ◽

Survival Estimate ◽

Long Term Survival ◽

Kaplan Meier

Thromboelastography (TEG) is used for monitoring abnormal blood coagulation in critically ill patients. However, the correlation between TEG parameters and long-term survival in these patients is unknown. We aimed to quantify the effect of TEG on long-term survival of critically ill patients. Critically ill patients undergoing TEG were retrospectively examined. Baseline patient characteristics and coagulation function indexes were compared. Cox regression, receiver–operating characteristic curve analysis, and Kaplan-Meier survival estimate curve were performed. We included 167 critically ill patients. Clot formation speed (K) and reaction time (R) were higher, whereas maximum amplitude (MA) and angle were lower in the mortality group than in the survival group ( P < .01). All TEG parameters were risk factors for 2-year survival in critically ill patients ( P < .01). The area under the curve of MA for predicting 2-year survival was 0.756 (95% confidence interval: 0.670-0.841). The Kaplan-Meier survival estimate curve analysis showed that MA predicted 2-year survival of critically ill patients( P < .01). Maximum amplitude can effectively predict 2-year survival of critically ill patients, indicating the influence of the coagulation system on these patients.

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Metabolic Syndrome and Mortality in Continuous Ambulatory Peritoneal Dialysis Patients: A 5-Year Prospective Cohort Study

Kidney & Blood Pressure Research ◽

10.1159/000502145 ◽

2019 ◽

Vol 44 (5) ◽

pp. 1026-1035

Author(s):

WenLong Gu ◽

Chunyan Yi ◽

Xueqing Yu ◽

Xiao Yang

Keyword(s):

Metabolic Syndrome ◽

Cohort Study ◽

Cardiovascular Mortality ◽

Cox Regression ◽

Rank Test ◽

Diabetic Patients ◽

Survival Functions ◽

Log Rank Test ◽

Kaplan Meier ◽

Technique Failure

Background/Aims: Metabolic syndrome (MS) has been widely proved as a predictor of cardiovascular disease, all-cause, and cardiovascular mortality in general population. But its effects on mortality and technique failure have not been well illustrated in peritoneal dialysis (PD) patients. We aimed to investigate the association of MS and clinical outcomes in Chinese continuous ambulatory PD (CAPD) patients. Methods: A single-center, prospective, observational cohort study was conducted in CAPD patients enrolled from September 1 to December 31, 2011, and followed up until December 31, 2016. Demographic, clinical, biochemical and anthropological data were collected. The relationships between MS and mortality and technique failure were assessed using Kaplan-Meier and Cox Regression Survival Functions. Results: A total of 511 patients were enrolled. The baseline mean age was 48.4 ± 14.4 years, 282 patients (55.2%) were male, and 130 patients (25.4%) were diabetic. In total, 213 patients (41.7%) met the diagnostic criterion of MS. During a median of 4.4 years (interquartile range 2.3–5.3 years) follow-up period, 114 patients died, of whom, 65 patients (48%) died in MS group versus 49 patients (30%) in non-MS group. Patients who died tended to be older, higher in inflammation markers and with poorer nutritional state. Kaplan-Meier Survival Functions found patients with MS had a significant rising of all-cause mortality (log-rank test = 12.811, p < 0.001) and cardiovascular mortality (log-rank test = 14.529, p < 0.001) in all patients, and a significant rising of cardiovascular mortality (log-rank test = 4.486, p = 0.034) in non-diabetic patients. After adjusting for confounders, Cox Regression showed that MS was significantly associated with higher cardiovascular mortality in all patients (hazard ratio [HR] 2.21, 95% CI 1.12–4.36, p = 0.022) and in non-diabetic patients (HR 2.60, 95% CI 1.07–6.35, p = 0.036), but it has no significant effect on technique failure. Conclusion: In CAPD patients, MS predicted mortality, especially cardiovascular mortality. No relationship was found between MS and technique survival.

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TIMP-2*IGFBP7 as an auxiliary identification of successful discontinuation CRRT and prediction of renal recovery in critically ill patients: a case control study

10.21203/rs.2.20260/v2 ◽

2020 ◽

Author(s):

yuanyuan xie ◽

Alexander Zarbock ◽

Alessandra Brendolan ◽

Francesca Martino ◽

Sara Samoni ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Cox Regression ◽

Kidney Injury ◽

Renal Recovery ◽

Cox Regression Analysis ◽

Cycle Arrest ◽

Kaplan Meier ◽

Icu Discharge ◽

The Moment

Abstract Background Cell cycle arrest biomarkers as TIMP-2*IGFBP7 are elevated in the Acute Kidney Stress and can predict the probability of developing Acute Kidney Injury (AKI). Approximately 25% of those patients with AKI deteriorate clinically and are unable to maintain adequate homeostasis, eventually requiring continuous renal replacement therapy. However, when clinical improvement occurs, the ideal mode of weaning patients from CRRT is an unmet medical need. Methods We performed a prospective single-center study of AKI patients treated with CRRT between October 2017 to April 2019 in a multidisciplinary ICU of an Italian hospital. All patients admitted to ICU requiring CRRT were enrolled. Urine samples for measuring urinary TIMP-2*IGFBP7 levels were collected immediately upon enrollment and at the moment when CRRT was discontinued. The primary endpoint was independence from RRT for at least 7 days after CRRT discontinuation. Renal recovery, which was defined as serum creatinine (SCr) level <1.5 times the baseline value at ICU discharge or day 28, was the secondary endpoint. Results 73 patients were enrolled of whom 45 patients effectively discontinued CRRT (61.6%). The patients with a TIMP-2*IGFBP7 concentration >2(ng/ml) 2 /1000 at enrollment were longer CRRT-dependent. The ROC-AUC values for the prediction of successful discontinuation with TIMP-2*IGFBP7 concentrations at enrollment, at discontinuation of CRRT and with the final model were 0.828, 0.814 and 0.882, respectively. The risk for CRRT discontinuation failure was nearly 5 times higher patients with a positive biomarker at CRRT discontinuation (OR 4.879, P=0.043), and 3.5 times higher in patients with a TIMP-2*IGFBP7 concentration >2(ng/ml) 2 /1000 at patient enrollment (OR 3.515, P=0.016). Multivariate Cox regression analysis showed a significant association between successful discontinuation of CRRT and TIMP-2*IGFBP7-negative patients at CRRT discontinuation (RR 0.436, 95% CI 0.202-0.939, P=0.034). Kaplan-Meier curves revealed that TIMP-2*IGFBP7 concentration <2 (ng/ml) 2 /1000 at enrollment and TIMP-2*IGFBP7 turning negative were positively related to high renal recovery rate. Conclusions Urinary TIMP-2*IGFBP7 can serve as a biomarker for identifying successful discontinuation CRRT and predicting renal recovery in critically ill patients.

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Convalescent plasma is of limited clinical benefit in critically ill patients with coronavirus disease-2019: a cohort study

Journal of Translational Medicine ◽

10.1186/s12967-021-03028-5 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Li Huang ◽

Che Zhang ◽

Xihui Zhou ◽

Zhou Zhao ◽

Weiping Wang ◽

...

Keyword(s):

Cohort Study ◽

Critically Ill ◽

Critically Ill Patients ◽

Clinical Benefit ◽

Clinical Characteristics ◽

Clinical Evidence ◽

Control Group ◽

Cumulative Mortality ◽

Kaplan Meier ◽

Significant Difference

Abstract Background Recently, convalescent plasma (CP) transfusion was employed for severe or critically ill patients with coronavirus disease-2019. However, the benefits of CP for patients with different conditions are still in debate. To contribute clinical evidence of CP on critically ill patients, we analyze the characteristics and outcomes of patients with or without CP transfusion. Methods In this cohort study, 14 patients received CP transfusion based on the standard treatments, whereas the other 10 patients received standard treatments as control. Clinical characteristics and outcomes were analyzed. The cumulative survival rate was calculated by Kaplan–Meier survival analysis. Results Data analysis was performed on 24 patients (male/female: 15/9) with a median age of 64.0 (44.5–74.5) years. Transient fever was reported in one patient. The cumulative mortality was 21% (3/14) in patients receiving CP transfusion during a 28-day observation, whereas one dead case (1/10) was reported in the control group. No significant difference was detected between groups in 28-day mortality (P = 0.615) and radiological alleviation of lung lesions (P = 0.085). Conclusion In our current study, CP transfusion was clinically safe based on the safety profile; however, the clinical benefit was not significant in critically ill patients with more comorbidities at the late stage of disease during a 28-day observation. Graphic abstract

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TIMP-2*IGFBP7 as an auxiliary identification of successful discontinuation CRRT and prediction of renal recovery in critically ill patients: a case control study

10.21203/rs.2.20260/v1 ◽

2020 ◽

Author(s):

yuanyuan xie ◽

Alexander Zarbock ◽

Alessandra Brendolan ◽

Francesca Martino ◽

Sara Samoni ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Cox Regression ◽

Renal Recovery ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Icu Discharge ◽

Successful Weaning ◽

The Moment ◽

Patient Enrollment

Abstract Background Predicting the successful discontinuation of continues renal replacement therapy (CRRT) may decrease under- and-overtreatment of critically ill patients and subsequently improve patients’ outcome and utilization of health care resources. The aim of this study was to investigate whether TIMP-2*IGFBP7 in addition to renal and non-renal parameters can predict the successful weaning from CRRT. Methods All patients admitted to ICU requiring CRRT were enrolled. Urine samples for measuring urinary TIMP-2*IGFBP7 levels were collected immediately upon enrollment and at the moment when CRRT was discontinued. The primary endpoint was the independence from RRT for at least 7 days after CRRT discontinuation. Persistent renal dysfunction, which was defined as a SCr level >1.5 times the baseline value at ICU discharge or day 28, was the secondary endpoint. Results 73 patients were enrolled of whom 45 patients effectively discontinued CRRT (61.6%). The patients with a TIMP-2*IGFBP7 concentration >2(ng/ml)2/1000 at enrollment were longer CRRT-dependent. The ROC-AUC values for the prediction of successful discontinuation with TIMP-2*IGFBP7 concentrations at enrollment, at discontinuation of CRRT and with the final model were 0.828, 0.814 and 0.882, respectively. The risk for CRRT discontinuation failure was nearly 5 times higher patients with a positive biomarker at CRRT discontinuation (OR 4.879, P=0.043), and 3.5 times higher in patients with a TIMP-2*IGFBP7 concentration >2(ng/ml)2/1000 at patient enrollment (OR 3.515, P=0.016). Multivariate Cox regression analysis showed a significant association between successful discontinuation of CRRT and TIMP-2*IGFBP7-negative patients at CRRT discontinuation (RR 0.436, 95% CI 0.202-0.939, P=0.034). Kaplan-Meier curves revealed that TIMP-2*IGFBP7 concentration <2 (ng/ml)2/1000 at enrollment and TIMP-2*IGFBP7 turning negative were positively related to high renal recovery rate. Conclusions Urinary TIMP-2*IGFBP7 can serve as a biomarker for identifying successful discontinuation CRRT and predicting renal recovery in critically ill patients.

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Cystatin C predicts long term mortality better than creatinine in a nationwide study of intensive care patients

Scientific Reports ◽

10.1038/s41598-021-85370-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Johanna Helmersson-Karlqvist ◽

Miklos Lipcsey ◽

Johan Ärnlöv ◽

Max Bell ◽

Bo Ravn ◽

...

Keyword(s):

Intensive Care ◽

Critically Ill ◽

Risk Prediction ◽

Cystatin C ◽

Mortality Risk ◽

Critically Ill Patients ◽

Cox Regression ◽

Sample Tube ◽

Long Term Mortality

AbstractDecreased glomerular filtration rate (GFR) is linked to poor survival. The predictive value of creatinine estimated GFR (eGFR) and cystatin C eGFR in critically ill patients may differ substantially, but has been less studied. This study compares long-term mortality risk prediction by eGFR using a creatinine equation (CKD-EPI), a cystatin C equation (CAPA) and a combined creatinine/cystatin C equation (CKD-EPI), in 22,488 patients treated in intensive care at three University Hospitals in Sweden, between 2004 and 2015. Patients were analysed for both creatinine and cystatin C on the same blood sample tube at admission, using accredited laboratory methods. During follow-up (median 5.1 years) 8401 (37%) patients died. Reduced eGFR was significantly associated with death by all eGFR-equations in Cox regression models. However, patients reclassified to a lower GFR-category by using the cystatin C-based equation, as compared to the creatinine-based equation, had significantly higher mortality risk compared to the referent patients not reclassified. The cystatin C equation increased C-statistics for death prediction (p < 0.001 vs. creatinine, p = 0.013 vs. combined equation). In conclusion, this data favours the sole cystatin C equation rather than the creatinine or combined equations when estimating GFR for risk prediction purposes in critically ill patients.

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Cohort study of the overall survival of patients with pancreatic cancer in a hospital of specialties of Quito-Ecuador in the period 2007–2017

Innovative Surgical Sciences ◽

10.1515/iss-2020-0030 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Andrés Moreno Roca ◽

Luciana Armijos Acurio ◽

Ruth Jimbo Sotomayor ◽

Carlos Céspedes Rivadeneira ◽

Carlos Rosero Reyes ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cohort Study ◽

Survival Time ◽

Univariate Analysis ◽

Rank Test ◽

Kaplan Meier ◽

Significant Difference ◽

Icd 10 ◽

The Difference ◽

Clinical Records

Abstract Objectives Pancreatic cancers in most patients in Ecuador are diagnosed at an advanced stage of the disease, which is associated with lower survival. To determine the characteristics and global survival of pancreatic cancer patients in a social security hospital in Ecuador between 2007 and 2017. Methods A retrospective cohort study and a survival analysis were performed using all the available data in the electronic clinical records of patients with a diagnosis of pancreatic cancer in a Hospital of Specialties of Quito-Ecuador between 2007 and 2017. The included patients were those coded according to the ICD 10 between C25.0 and C25.9. Our univariate analysis calculated frequencies, measures of central tendency and dispersion. Through the Kaplan-Meier method we estimated the median time of survival and analyzed the difference in survival time among the different categories of our included variables. These differences were shown through the log rank test. Results A total of 357 patients diagnosed with pancreatic cancer between 2007 and 2017 were included in the study. More than two-thirds (69.9%) of the patients were diagnosed in late stages of the disease. The median survival time for all patients was of 4 months (P25: 2, P75: 8). Conclusions The statistically significant difference of survival time between types of treatment is the most relevant finding in this study, when comparing to all other types of treatments.

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