Hyperoxaemia and hypoxaemia are associated with harm in patients with ARDS

Abstract Background Oxygen therapy is routinely administered to mechanically ventilated patients. However, there remains uncertainty about the optimal oxygen titration target in patients with the acute respiratory distress syndrome (ARDS). Methods Prospectively identified adult patients meeting the Berlin definition of ARDS between 1st January 2014 and 13th December 2016 were analyzed. Oxygen exposure variables were collected at 6-hourly intervals. The primary exposure was the average time-weighted partial pressure of arterial oxygen (PaO2) calculated over a maximum of 7 days from meeting ARDS criteria. The primary outcome was ICU mortality. Univariable and multivariable logistic regression analyses were performed to assess the impact of exposure variables on clinical outcomes. Results are presented as odds ratio [95% confidence interval]. Results 202 patients were included in the final analysis. Overall ICU mortality was 31%. The average time-weighted PaO2 during the first 7 days of ARDS was similar between non-survivors and survivors (11.3 kPa [10.2, 12.5] (84.8 mmHg [76.5, 93.8]) vs. 11.9 kPa [10.9, 12.6] (89.3 mmHg [81.8, 94.5]); p = 0.08). In univariable and multivariable analysis, average time-weighted PaO2 demonstrated a U-shaped relationship with ICU mortality. There was a similar relationship identified with hospital mortality. Conclusions In patients with ARDS, the predicted probability of both ICU and hospital mortality was lowest when the average time-weighted PaO2 was between 12.5 and 14 kPa (93.8–105.0 mmHg), suggesting this is a reasonable oxygenation target for clinicians to aim for.

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Making sense of non-randomized comparative treatment studies in times of Covid-19: A case study of tocilizumab

10.1101/2021.04.06.21254612 ◽

2021 ◽

Author(s):

Ruth R C Owen ◽

Nawab Qizilbash ◽

Sara Velazquez Diaz ◽

Jose Maria Castellano Vazquez ◽

Stuart J Pocock

Keyword(s):

Hospital Mortality ◽

Primary Outcome ◽

Multivariable Analysis ◽

Randomised Clinical Trial ◽

Control Group ◽

Making Sense ◽

Competing Risk Models ◽

Effectiveness Studies ◽

The Impact

BACKGROUND Tocilizumab (TCZ) is an interleukin-6 inhibitor and the second established effective drug for the treatment of hospitalized patients with Covid-19. In this study, we sought to validate the recent positive findings from the randomised clinical trial RECOVERY and to evaluate the challenges in the analysis and interpretation of non-randomized comparative effectiveness studies in Covid-19. METHODS We performed a retrospective cohort study using an openly available database of hospitalised Covid-19 patients in Spain. The primary outcome was all-cause in-hospital mortality at 28 days. We used multivariable Fine and Gray competing risk models which adjusted for both fixed and time-variant confounders to investigate the effect of TCZ on the primary outcome. RESULTS We analysed 2547 patients hospitalised with Covid-19 between 1st January and 28th June 2020. Patients in the TCZ group tended to have more severe Covid-19 at admission, as measured by biomarkers of disease severity including CRP, D-dimer and LDH. At 28 days, 91 out of 440 TCZ patients had died compared to 267 out of 2107 patients in the control group. In multivariable analysis, there was no evidence of an association between TCZ and the primary outcome (adjusted hazard ratio 1.20, 95% CI 0.86 to 1.64, P=0.26). CONCLUSIONS Our observational study failed to find a benefit of TCZ on all-cause in-hospital mortality in Covid-19 patients compared with randomized trials, highlighting the impact that unmeasured confounding and other sources of bias can have in a retrospective observational setting. For future observational studies, we recommend prospective data collection to ensure all variables have the necessary quality, completeness and timing for reliable treatment evaluation.

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Abstract 17492: Extent and Pattern of Late Gadolinium Enhancement Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy

Circulation ◽

10.1161/circ.132.suppl_3.17492 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Dong Geum Shin ◽

Hye-Jeong Lee ◽

Junbeom Park ◽

Young Jin Kim ◽

Jae-Sun Uhm ◽

...

Keyword(s):

Late Gadolinium Enhancement ◽

Ventricular Arrhythmia ◽

Dilated Cardiomyopathy ◽

Cardiac Death ◽

Primary Outcome ◽

Multivariable Analysis ◽

Gadolinium Enhancement ◽

Nonischemic Dilated Cardiomyopathy ◽

The Impact

Background: Late gadolinium enhancement (LGE) by cardiac MR (CMR) has been related to adverse clinical outcomes in patients with nonischemic dilated cardiomyopathy (NIDC). But, a statistically significant association between LGE and arrhythmic risk in NIDC has not been demonstrated consistently. This study evaluated the impact of the presence, location and pattern of LGE on arrhythmic risk prediction in NICM. Methods: This study included 365 patients (54±15years) with NICM who underwent CMR. The extent, location and pattern of LGE were categorized. We analyzed for the primary outcome of ventricular arrhythmia (VA) including sustained or nonsustained ventricular tachycardia (VT), appropriate implantable cardioverter-defibrillator (ICD) intervention and ventricular fibrillation (VF). Cardiac death and hospitalization for heart failure (HF) were evaluated as secondary outcomes. Results: LGE was seen in 267 (73 %) patients. During median follow-up of 44±36 months, patients with LGE had higher incidence of cardiac death (15 % vs. 2 %, p<0.001), hospitalization for HF (40 % vs. 15 %, p<0.001) and VA (14% vs. 6%, p=0.03). In multivariable analysis, the presence of LGE (HR 2.78; 95% CI 1.10-7.02; p=0.03) was the independent predictor of arrhythmias. Patients with extensive LGE had higher VA (32% vs. 10%, p<0.001) with lower cumulative survival free of VA than those without extensive LGE (p=0.001). The frequent LGE location was as follows: LV septum 64%, LV-RV junction 42% and inferior 10%. VA was lower in patients with than without localized LGE limited to LV-RV junction (21% vs. 46%, p=0.005). Interestingly, while the incidence of ventricular arrhythmia was higher in patients with transmural LGE (29% vs. 10%, p=0.003), it was lower in those with patch LGE (2% vs. 16%, p=0.02) than the other patients. Conclusions: In patients with NICM, the LGE was an independent prognostic predictor of VA. Extensive LGE and specific location of LGE was related with the arrhythmic events.

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60. Evaluation of Outcomes Associated with Intermittent Versus Extended Infusion of Piperacillin/tazobactam in Acutely Ill Veterans

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.105 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S50-S51

Author(s):

Marianne Angeli Encarnacion ◽

Ariel Ma ◽

Scott T Johns

Keyword(s):

Mortality Rate ◽

Hospital Mortality ◽

Clinical Outcomes ◽

Final Analysis ◽

Hospital Length Of Stay ◽

Control Group ◽

Protocol Group ◽

Elevated Liver Enzymes ◽

The Impact ◽

Extended Infusion

Abstract Background Antibiotic dosing optimization is a key principle of antimicrobial stewardship. This study evaluated the impact of an extended infusion piperacillin/tazobactam dosing protocol on clinical outcomes in acutely ill veterans treated for infections at VA San Diego. Methods This retrospective cohort study looked at veterans admitted to the medical-surgical unit who were treated with piperacillin/tazobactam for at least 48 hours. The control group included patients who received treatment between 12/14/2017 to 7/22/2018, and the “protocol” or after protocol implementation group included patients who received treatment between 7/23/2018 to 2/28/2019. Excluded from the study were veterans with microbiological cultures showing intermediate sensitivity or resistance to piperacillin/tazobactam, those who experienced interruption in therapy, or those who required dialysis. Primary clinical outcomes included in-hospital mortality rate, 30-day mortality rate, hospital length of stay (LOS), and 30-day readmission rates. Rates of adverse effects such as elevated liver enzymes, thrombocytopenia, acute kidney impairment (AKI), and Clostridium difficile infection were also collected. χ 2, Fisher’s exact, and Mann-Whitney U tests were used for statistical analysis. Results 260 veterans were included in the final analysis: 96% male, mean age 65 years, mean BMI 29, 84 met SIRS criteria for sepsis, and 55% received at least 48 hours of concomitant vancomycin. Groups had similar outcomes for median LOS, in-hospital mortality, and 30-day mortality. The incidence of AKI was significantly lower in the protocol group (39.2% vs. 56.9%, p=0.004), in veterans on concomitant vancomycin (42.3% vs. 63.2%, p=0.011), and in veterans with obesity (36.4% vs. 70.8%, p=0.001). Rates of liver enzyme elevation, thrombocytopenia, and C. difficile infection were lower in the protocol group though these were not significant. Conclusion There was a significantly lower rate of AKI with EI dosing which supports enhanced patient safety. This may be the preferred method of administration for obese patients and/or those receiving vancomycin concurrently. This is the first study to demonstrate that EI piperacillin/tazobactam dosing significantly reduces rates of AKI in patients on concomitant vancomycin. Disclosures All Authors: No reported disclosures

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Comparison of D-dimer level measured on the third day of hospitalization with D-dimer level in predicting in-hospital mortality in COVID-19 patients

European Heart Journal ◽

10.1093/eurheartj/ehab724.1897 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

M Selcuk ◽

T Cinar ◽

N Gunay ◽

M Keskin ◽

V Cicek ◽

...

Keyword(s):

Hospital Mortality ◽

Primary Outcome ◽

Multivariable Analysis ◽

Hospital Death ◽

Funding Sources ◽

Auc Value ◽

Wbc Count ◽

D Dimer ◽

Higher Sensitivity ◽

The Ideal

Abstract Objective The present study aimed to compare the value of D-dimer measured on the 3rd day of hospitalization with admission D-dimer level in predicting in-hospital mortality in coronavirus disease 2019 (COVID-19) cases. Method In total, 231 patients with COVID-19 disease were included in the study. D-dimer levels were estimated using immunoturbidimetric assay with normal range of 0–500 μg/mL. In the current research, the primary outcome was the in-hospital mortality. Results In the present research, 39 (16.8%) COVID-19 cases died during the index hospitalization. In a multivariable analysis; age, D-dimer (3rd day) (OR: 1.00, 95% CI: 1.00–1.00, p<0.001), WBC count, and creatinine were independent predictors of the in-hospital death for COVID-19 cases. The ideal value of D-dimer level on the 3rd day of hospitalization was 774 μq/mL (area under curve (AUC): 0.903, 95% CI: 0.836–0.968; p<0.01) with sensitivity of 83.2% and specificity of 83.6%. It was noted that D-dimer level on the 3rd day of hospitalization had a higher sensitivity (83.2% vs 67.6%, respectively) and AUC value than that of D-dimer level on admission (0.903 vs 0.799, respectively). Conclusion The main finding in this investigation was that D-dimer elevation on the 3rd of hospitalization is more sensitive predictor of in-hospital mortality than D-dimer elevation on admission in COVID-19 patients. Even though further investigations are needed to forecast precise prognosis in patients with COVID-19 disease in terms of D-dimer levels, we believe that D-dimer levels on the 3rd day of hospitalization have an enhanced potential to be used as a prognostic marker in routine clinical practice. FUNDunding Acknowledgement Type of funding sources: None. Table 1 Figure 1

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Impact of non-cystic fibrosis bronchiectasis on critically ill patients in Korea: a retrospective observational study

Scientific Reports ◽

10.1038/s41598-021-95366-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Youngmok Park ◽

Seung Hyun Yong ◽

Ah Young Leem ◽

Song Yee Kim ◽

Sang Hoon Lee ◽

...

Keyword(s):

Hospital Mortality ◽

Odds Ratio ◽

Negative Impact ◽

Icu Mortality ◽

Chest Computed Tomography ◽

Lower Survival Rate ◽

All Cause Mortality ◽

Hospital Stays ◽

The Mean ◽

The Impact

AbstractThis study investigated the impact of bronchiectasis on patients admitted to the intensive care unit (ICU) at a hospital in Korea. Patients with bronchiectasis were diagnosed using results of chest computed tomography performed before ICU admission. The severity of bronchiectasis was based on the number of affected lobes, and patients with ≥ 3 bronchiectatic lobes were classified into the severe bronchiectasis group. Overall, 823 patients were enrolled. The mean age was 66.0 ± 13.9 years, and 63.4% were men. Bronchiectasis and severe bronchiectasis were present in 148 (18.0%) and 108 (13.1%) patients, respectively. The increase in the number of bronchiectatic lobes was related to the rise in ICU mortality (P for trend = 0.012) and in-hospital mortality (P for trend = 0.004). Patients with severe bronchiectasis had higher odds for 28-day mortality [odds ratio (OR) 1.122, 95% confidence interval (CI) 1.024–1.230], ICU mortality (OR 1.119, 95% CI 1.023–1.223), and in-hospital mortality (OR 1.208, 95% CI 1.092–1.337). The severe bronchiectasis group showed lower overall survival (log-rank P < 0.001), and the adjusted hazard ratio was 1.535 (95% CI 1.178–2.001). Severe bronchiectasis had a negative impact on all-cause mortality during ICU and hospital stays, resulting in a lower survival rate.

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A shorter symptom-onset to remdesivir treatment (SORT) interval is associated with a lower mortality in moderate-to-severe COVID-19: A real-world analysis

10.1101/2020.11.05.20226373 ◽

2020 ◽

Author(s):

Ravindra M Mehta ◽

Sameer Bansal ◽

Suhitha Bysani ◽

Hariprasad Kalpakam

Keyword(s):

Symptom Onset ◽

Severe Disease ◽

Tertiary Care ◽

Length Of Hospital Stay ◽

Final Analysis ◽

Drug Discontinuation ◽

Mechanically Ventilated ◽

Moderate Disease ◽

All Cause Mortality ◽

The Impact

AbstractBackgroundRemdesivir is the current recommended anti-viral treatment in moderate-to-severe COVID-19. However, data on several aspects of its use such as impact of timing of therapy, efficacy, and safety in this severity category are limited. The current study aimed to evaluate the impact of timing of remdesivir initiation (symptom-onset to remdesivir treatment [SORT] interval) on in-hospital all-cause mortality in patients with moderate-to-severe COVID-19.MethodsThis retrospective study was conducted between June 25, 2020 and October 3, 2020, at a tertiary care dedicated COVID center in India. Consecutive patients with moderate-to-severe COVID-19 (moderate: SpO2 <94%; severe: SpO2 <90%) were included. Data were collected from the health records of the hospital. Remdesivir was administered along with other standard medications as per protocol. The main outcome was the impact of SORT interval on in-hospital all-cause mortality. Subgroups were formed based on SORT interval. Other measures analyzed included overall in-hospital mortality, length of hospital stay, and safety.ResultsOf 350 patients treated with remdesivir, 346 were included for the final analysis (males: 270 [78.0%]; median [range] age: 60 [24-94] years). Overall, 243 (70.2%) patients had ≥1 comorbidity; 109 (31.5%) patients had moderate disease, 237 (68.5%) had severe disease, and 50 (14.5%) patients required mechanical ventilation. Of the 346 patients, 76 (22.0%) patients died (moderate: 3 [2.8%], severe: 73 [30.8%]). In the subset of mechanically ventilated patients, 43 (86.0%) died. All-cause mortality was significantly lower in patients with SORT interval ≤9 days (n = 260) compared with those with SORT interval >9 days (n = 86; 18.1% vs 33.7%; P = .004). The odds of death were significantly lower in patients with SORT interval ≤9 days vs >9 days (odds ratio = 0.44; 95% CI, 0.25-0.76; P = .004). Adverse events (transaminitis ≥5 times upper limit of normal or estimated glomerular filtration rate <30ml/min) leading to drug discontinuation were seen in 4 (1.1%) patients.ConclusionIn this large series of moderate-to-severe COVID-19, initiation of remdesivir ≤9 days from symptom-onset was associated with a significant mortality benefit. These findings indicate a treatment window and reinforce the need for earlier remdesivir initiation in moderate-to-severe COVID-19 infection.

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Rapid Muscle Loss Negatively Impacts Survival in Critically Ill Patients With Cirrhosis

Journal of Intensive Care Medicine ◽

10.1177/0885066618775706 ◽

2018 ◽

Vol 35 (7) ◽

pp. 663-671 ◽

Cited By ~ 3

Author(s):

Sunmi Ju ◽

Sun Mi Choi ◽

Young Sik Park ◽

Chang-Hoon Lee ◽

Sang-Min Lee ◽

...

Keyword(s):

Hospital Mortality ◽

Critically Ill ◽

Muscle Mass ◽

Critically Ill Patients ◽

Mass Change ◽

Apache Ii Score ◽

Muscle Loss ◽

Icu Mortality ◽

Skeletal Muscle Index ◽

The Impact

Purpose: To assess the impact of rapid muscle loss before admission to intensive care unit (ICU) in critically ill patients with cirrhosis. Materials and Methods: Patients with cirrhosis who had undergone 2 or more recent computed tomography scans before admission to the medical ICU were included. Muscle cross-sectional area at the level of the third lumbar vertebra was quantified using OsiriX software. The rate of muscle mass change and skeletal muscle index (SMI) were also calculated. Multivariable Cox proportional hazards regression was used to evaluate the association between muscle loss and mortality. Results: Among 125 patients, 113 (90.4%) patients were classified as having sarcopenia. The mean body mass index was 22.6 (3.9) kg/m2. Thirty-nine (31.2%) patients were within the normal range for muscle mass change, while 86 (68.8%) patients demonstrated rapid decline in muscle mass before admission to the ICU. Patients with rapid muscle loss showed high ICU mortality (59.3%) and in-hospital mortality (77.9%). Multivariate Cox analysis showed that ICU mortality and in-hospital mortality were independently associated with malignancy, Acute Physiology and Chronic Health Evaluation (APACHE) II score, SMI, and rapid muscle loss. Conclusion: Rapid muscle decline is correlated with increased ICU mortality and in-hospital mortality in critically ill patients with cirrhosis.

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Paradox of trimethylamine-N-oxide, the impact of malnutrition on microbiota-derived metabolites and septic patients

Journal of Intensive Care ◽

10.1186/s40560-021-00581-5 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Ruey-Hsing Chou ◽

Po-Shan Wu ◽

Shen-Chih Wang ◽

Cheng-Hsueh Wu ◽

Shu-Fen Lu ◽

...

Keyword(s):

Primary Outcome ◽

Vascular Inflammation ◽

Nutrition Status ◽

Hospital Death ◽

Lower Plasma ◽

Mechanically Ventilated ◽

Icu Admission ◽

Daily Energy ◽

The Impact ◽

Antibiotic Courses

Abstract Background Trimethylamine N-oxide (TMAO) is a microbiota-derived metabolite, which is linked to vascular inflammation and atherosclerosis in cardiovascular (CV) diseases. But its effect in infectious diseases remains unclear. We conducted a single-center prospective study to investigate association of TMAO with in-hospital mortality in septic patients admitted to an intensive care unit (ICU). Methods Totally 95 septic, mechanically ventilated patients were enrolled. Blood samples were obtained within 24 h after ICU admission, and plasma TMAO concentrations were determined. Septic patients were grouped into tertiles according to TMAO concentration. The primary outcome was in-hospital death, which further classified as CV and non-CV death. Besides, we also compared the TMAO concentrations of septic patients with 129 non-septic patients who were admitted for elective coronary angiography (CAG). Results Septic patients had significantly lower plasma TMAO levels than did subjects admitted for CAG (1.0 vs. 3.0 μmol/L, p < 0.001). Septic patients in the lowest TMAO tertile (< 0.4 μmol/L) had poorer nutrition status and were given longer antibiotic courses before ICU admission. Circulating TMAO levels correlated positively with daily energy intake, the albumin and prealbumin concentration. Compared with those in the highest TMAO tertile, septic patients in the lowest TMAO tertile were at greater risk of non-CV death (hazard ratio 2.51, 95% confidence interval 1.21–5.24, p = 0.014). However, TMAO concentration was no longer an independent predictor for non-CV death after adjustment for disease severity and nutritional status. Conclusion Plasma TMAO concentration was inversely associated with non-CV death among extremely ill septic patients, which could be characterized as TMAO paradox. For septic patients, the impact of malnutrition reflected by circulating TMAO levels was greater than its pro-inflammatory nature.

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Clinical Validity of the diagnostic criteria for metabolic-associated fatty liver disease: a real-world experience

10.1101/2020.08.20.20176214 ◽

2020 ◽

Author(s):

Yasser Fouad ◽

Zeinab Saad ◽

Ehab Abdel Raheem ◽

Yasser Abel gany ◽

Hend Moness ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Multivariable Analysis ◽

Metabolic Dysfunction ◽

Alcoholic Fatty Liver ◽

Clinical Criteria ◽

Nafld Fibrosis Score ◽

Definition Of ◽

The Impact

Background and Aims: To eliminate the anti-definition of non-alcoholic fatty liver disease (NAFLD), positive clinical criteria for metabolic associated fatty liver disease are recently proposed. In this study, we examine the validation and utilization of these criteria. METHODS: Two cohorts of 316 consecutive patients were recruited, including 242 patients previously diagnosed to have NAFLD and 74 patients with concomitant NAFLD and chronic hepatitis C (CHC) The validity of the proposed criteria for MAFLD, namely presence of hepatic steatosis with one of three criteria, overweight/obesity, diabetes or evidence of metabolic dysregulation was assessed. Fibrosis was assessed using, fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS). The impact of MAFLD on the clinical outcomes in CHC patients was also investigated. Results: The clinical criteria captured 240 patients (99.2%). 215 (88.8%) met either overweight or diabetes and 25 (10.3%) met the presence of 2 criteria of metabolic dysfunction. In patients, with dual etiologies, in the multivariable analysis adjusting for age, sex, BMI, ALT, AST and diabetes, the presence of MAFLD were significantly associated with increase high FIB-4 score of fibrosis (Odds ratio [95% confidence interval], 3.77 [1.49-9.48], P < 0.005) when compared to those with MAFLD only. CONCLUSION: The proposed criteria for diagnosis of MAFLD is well validated and easily applicable to the entire spectrum of disease including non-obese subjects. Patients with lean MAFLD have favorable metabolic and fibrosis characteristics compared to their obese counterpart, while patients with concomitant MAFLD and CHC had severe metabolic and fibrosis characteristics compared to patients with MAFLD alone.

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Role of Postoperative Complications in Overall Survival after Radical Resection for Gastric Cancer: A Retrospective Single-Center Analysis of 1107 Patients

Cancers ◽

10.3390/cancers11121890 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1890 ◽

Cited By ~ 2

Author(s):

Christian Galata ◽

Susanne Blank ◽

Christel Weiss ◽

Ulrich Ronellenfitsch ◽

Christoph Reissfelder ◽

...

Keyword(s):

Risk Factors ◽

Gastric Cancer ◽

Overall Survival ◽

Postoperative Complications ◽

Hospital Mortality ◽

Surgical Complications ◽

Multivariable Analysis ◽

Radical Resection ◽

Entire Cohort ◽

The Impact

Background: The aim of this study was to investigate the impact of postoperative complications on overall survival (OS) after radical resection for gastric cancer. Methods: A retrospective analysis of our institutional database for surgical patients with gastroesophageal malignancies was performed. All consecutive patients who underwent R0 resection for M0 gastric cancer between October 1972 and February 2014 were included. The impact of postoperative complications on OS was evaluated in the entire cohort and in a subgroup after exclusion of 30 day and in-hospital mortality. Results: A total of 1107 patients were included. In the entire cohort, both overall complications (p < 0.001) and major surgical complications (p = 0.003) were significant risk factors for decreased OS in univariable analysis. In multivariable analysis, overall complications were an independent risk factor for decreased OS (p < 0.001). After exclusion of patients with complication-related 30 day and in-hospital mortality, neither major surgical (p = 0.832) nor overall complications (p = 0.198) were significantly associated with decreased OS. Conclusion: In this study, postoperative complications influenced OS due to complication-related early postoperative deaths. In patients successfully rescued from early postoperative complications, neither overall complications nor major surgical complications were risk factors for decreased survival.

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