The association between mortality and time of admission to ICU has been extensively studied but remains controversial. We revaluate the impact of time of admission on ICU mortality by retrospectively ...investigating a recent (2006-2014) and large ICU cohort with on-site intensivist coverage.
All adults (≥ 18 years) admitted to a tertiary care medical ICU were included in the study. Patients' characteristics, medical management, and mortality were prospectively collected. Patients were classified according to their admission time: week working days on- and off-hours, and weekends. ICU mortality was the primary outcome and adjusted Hazard-ratios (HR) of death were analysed by multivariate Cox model.
2,428 patients were included: age 62±18 years; male: 1,515 (62%); and median SAPSII score: 38 (27-52). Overall ICU mortality rate was 13.7%. Admissions to ICU occurred during open-hours in 680 cases (28%), during night-time working days in 1,099 cases (45%) and during weekends in 649 cases (27%). Baseline characteristics of patients were similar between groups except that patients admitted during the second part of night (00:00 to 07:59) have a significantly higher SAPS II score than others. ICU mortality was comparable between patients admitted during different time periods but was significantly higher for those admitted during the second part of the night. Multivariate analysis showed however that admission during weeknights and weekends was not associated with an increased ICU mortality as compared with open-hours admissions.
Time of admission, especially weeknight and weekend (off-hour admissions), did not influence the prognosis of ICU patients. The higher illness severity of patients admitted during the second part of the night (00:00-07:59) may explain the observed increased mortality.
Usually responsible for soft tissue infections, Clostridioides species can also cause bacteremia, life-threatening infections often requiring intensive care unit (ICU) admission. We conducted a ...multicenter retrospective study to investigate Clostridioides bacteremia in ICUs to describe the clinical and biologic characteristics and outcomes in critically ill patients. We identified 135 patients with Clostridioides bacteremia, which occurred almost exclusively (96%) in patients with underlying conditions. Septic shock and digestive symptoms were the hallmarks of Clostridioides bacteremia in the ICU. We identified 16 different species of Clostridioides, among which C. perfringens accounted for 31% of cases. Despite the high sensitivity of Clostridioides to common antimicrobial drugs, mortality rates were high: 52% for ICU patients and 71% overall at 3 months. In multivariate analysis, the most important factor associated with increased risk for death was the presence of hemolysis. Clostridioides bacteremia often leads to multiple organ failures, which have high mortality rates.
The capability of urinary TIMP-2 (tissue inhibitor of metalloproteinase) and IGFBP7 (insulin-like growth factor binding protein)-NephroCheck Test (NC) = (TIMP-2 x IGFBP7) / 1000)-to predict renal ...recovery from acute kidney injury (AKI) has been poorly studied. The aim of this study was to assess the performance of measurements of (TIMP-2 x IGFBP7) / 1000) over 24 hours to differentiate transient from persistent AKI.
Of 460 consecutive adult patients admitted to the ICU, 101 were prospectively studied: 56 men, 62 (52-71) years old. A fresh urine sample was collected at H0, H4, H12 and H24 to determine (TIMP-2 x IGFBP7) / 1000) levels. Areas under the curves of Delta NC H4-Ho and H12-H4 and serum creatinine (sCr) for detection of AKI recovery were compared.
Forty-one (40.6%) patient were diagnosed with AKI: 27 transient and 14 persistent AKI. At admission (H0), AKI patients had a significantly higher NC score than patients without AKI (0.43 0.07-2.06 vs 0.15 0.07-0.35, p = 0.027). In AKI groups, transient AKI have a higher NC, at H0 and H4, than persistent AKI (0.87 0.09-2.82 vs 0.13 0.05-0.66 p = 0.035 and 0.13 0.07-0.61 vs 0.05 0.02-0.13 p = 0.013). Thereafter, NC level decreased in both AKI groups with a Delta NC score H4-H0 and H12-H4 significantly more important in transient AKI. Roc curves showed however that delta NC scores did not discriminate between transient and persistent AKI.
In our population, absolute urinary levels of NC score were higher at early hours after ICU admission (H0 and H4) in transient AKI as compared to persistent AKI patients. NC variations (Delta NC scores) over the first 12 hours may indicate the AKI's evolving nature with a more significant decrease in case of transient AKI but were not able to differentiate transient from persistent AKI.
Tubular injury is the main cause of acute kidney injury (AKI) in critically ill COVID-19 patients. Proximal tubular dysfunction (PTD) and changes in urinary biomarkers, such as NGAL, TIMP-2, and ...IGFBP7 product (TIMP-2•IGFBP7), could precede AKI. We conducted a prospective cohort study from 2020/03/09 to 2020/05/03, which consecutively included all COVID-19 patients who had at least one urinalysis, to assess the incidence of PTD and AKI, and the effectiveness of PTD, NGAL, and TIMP-2•IGFBP7 in AKI and persistent AKI prediction using the area under the receiver operating characteristic curves (AUCs), Kaplan-Meier methodology (log-rank tests), and Cox models. Among the 60 patients admitted to the ICU with proven COVID-19 (median age: 63-year-old (interquartile range: IQR, 55-74), 45 males (75%), median simplified acute physiology score (SAPS) II: 34 (IQR, 22-47) and median BMI: 25.7 kg/m
(IQR, 23.3-30.8)) analyzed, PTD was diagnosed in 29 patients (48%), AKI in 33 (55%) and persistent AKI in 20 (33%). Urinary NGAL had the highest AUC for AKI prediction: 0.635 (95%CI: 0.491-0.779) and persistent AKI prediction: 0.681 (95%CI: 0.535-0.826), as compared to PTD and TIMP-2•IGFBP7 (AUCs <0.6). AKI was independently associated with higher SAPSII (HR = 1.04, 95%CI: 1.01-1.06,
= 0.005) and BMI (HR = 1.07, 95%CI: 1.00-1.14,
= 0.04) and persistent AKI with higher SAPSII (HR = 1.03, 95%CI: 1.00-1.06,
= 0.048) and nephrotoxic drug use (HR = 3.88, 95%CI: 1.20-12.5,
= 0.02). In conclusion, in critically ill COVID-19 patients, the incidence of PTD and AKI was relatively high. NGAL was the best urinary biomarker for predicting AKI, but only clinical severity was independently associated with its occurrence.
Background
In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin ...lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020.
Results
Median time from ibrutinib initiation was 6.6 3–18 months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 5–11 vs. 4 3–7, p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 1–2 vs. 0 0–2; p < 0.001) and higher rates of fungal 21% vs. 8%, p = 0.001 and viral 17% vs. 5%, p = 0.027 infections in patients receiving ibrutinib, ICU (27% vs. 38%, p = 0.254) and day-90 mortality (52% vs. 48%, p = 0.785) were similar between the two groups.
Conclusion
In ibrutinib-treated patients, severe infections requiring ICU admission were associated with a dismal prognosis, mostly impacted by initial organ failures. Opportunistic agents should be systematically screened by ICU clinicians in this immunocompromised population.
CD19-directed CAR T-cells have been remarkably successful in treating patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and transformed follicular lymphoma (t-FL). In this ...cohort study, we treated 60 patients with axicabtagene ciloleucel or tisagenlecleucel. Complete and partial metabolic responses (CMR/PMR) were obtained in 40% and 23% of patients, respectively. After 6.9 months of median follow-up, median progression-free survival (mPFS) and overall survival (mOS) were estimated at 3.1 and 12.3 months, respectively. Statistical analyses revealed that CMR, PFS, and OS were all significantly associated with age-adjusted international prognostic index (aaIPI, p < 0.05). T-cell subset phenotypes in the apheresis product tended to correlate with PFS. Within the final product, increased percentages of both CD4 and CD8 CAR+ effector memory cells (p = 0.02 and 0.01) were significantly associated with CMR. Furthermore, higher CMR/PMR rates were observed in patients with a higher maximal in vivo expansion of CAR T-cells (p = 0.05) and lower expression of the LAG3 and Tim3 markers of exhaustion phenotype (p = 0.01 and p = 0.04). Thus, we find that aaIPI at the time of infusion, phenotype of the CAR T product, in vivo CAR T-cell expansion, and low levels of LAG3/Tim3 are associated with the efficacy of CAR T-cell therapy in DLBCL patients.
Comprehensive data on emerging invasive fungal infections (EIFIs) in the critically ill are scarce. We conducted a case-control study to characterize EIFIs in patients admitted to a French medical ...ICU teaching hospital from 2006 to 2019. Among 6900 patients, 26 (4 per 1000) had an EIFI:
accounted for half, and other isolates were mainly
,
and
. EIFIs occurred mostly in patients with immunosuppression and severe critical illness. Antifungal treatments (mainly amphotericin B) were administered to almost all patients, whereas only 19% had surgery. In-ICU, mortality was high (77%) and associated with previous conditions such as hematological malignancy or cancer, malnutrition, chronic kidney disease and occurrence of acute respiratory distress syndrome and/or hepatic dysfunction. Day-90 survival rates, calculated by the Kaplan-Meier method, were similar between patients with EIFIs and a control group of patients with aspergillosis: 20%, 95% CI (9- 45) versus 18%, 95% CI (8- 45) (log-rank:
> 0.99). ICU management of such patients should be assessed on the basis of underlying conditions, reversibility and acute event severity rather than the mold species.
Background
Ventilator-associated pneumonia (VAP) is a care-related event that could be promoted by immune suppression caused by critical diseases, malignancies and cancer treatments. Low dose of ...hydrocortisone was proposed for modulation of immune response in the critically ill population.
Methods
In this monocentric observational study, all cancer patients mechanically ventilated for more than 48 h were included. Effect of low-dose hydrocortisone administered during the first 48 h of mechanical ventilation was evaluated applying inverse probability weighting analysis after propensity score assessment. VAP impact on 1-year mortality, ICU length of stay and mechanical ventilation duration was secondarily determined.
Results
Within this cohort, 190 cancer patients were followed. VAP was confirmed in 22.1% of cases in the early hydrocortisone group and confirmed in 42.6% of cases in the no or late hydrocortisone group. Early hydrocortisone exhibited a protective effect on the risk of VAP (OR 0.23; 95% CI 0.12–0.44;
P
< 0.0001). VAP was associated with 1-year mortality (HR 1.60; 95% CI 1.10–2.34;
P
= 0.017) and increased ICU length of stay (mean extra length of stay: 4.2 days; 95% CI 0.6–7.8).
Conclusions
Immune modulation with low-dose hydrocortisone administered in the first days of mechanical ventilation could protect from VAP occurrence in cancer patients.
•To treat bacteria with MIC ≤ 2 mg/L, the optimal pharmacokinetic/pharmacodynamic (PK/PD) target of meropenem corresponds to plasma trough (Cmin) or steady-state concentration (Css) ≥ 10 mg/L ...(100%ƒT>5xMIC).•97% of septic intensive care unit (ICU) patients treated with continuous infusion of meropenem had Cmin or Css ≥ 10 mg/L.•64% of septic ICU patients treated with extended intermittent infusion of meropenem had Cmin or Css ≥ 10 mg/L.•Continuous and extended intermittent infusion of meropenem achieved median plasma concentration at 34 mg/L (IQR 27, 49) and 16 mg/L (IQR 8, 23), respectively.•Continuous infusion of 40–70 mg/kg/day of meropenem appears to be the better dosing regimen to achieve the PK/PD target.•The use of continuous infusion did not appear to be mandatory in patients with a lower estimated glomerular filtration rate.
The use of extended intermittent infusion (EII) or continuous infusion (CI) of meropenem is recommended in intensive care unit (ICU) patients, but few data comparing these two options are available. This retrospective cohort study was conducted between 1 January 2019 and 31 March 2020 in a teaching hospital ICU. It aimed to determine the meropenem plasma concentrations achieved with CI and EII.
The study included septic patients treated with meropenem who had one or more meropenem plasma trough (Cmin) or steady-state concentration (Css) measurement(s), as appropriate. It then assessed the factors independently associated with attainment of the target concentration (Cmin or Css ≥ 10 mg/L) and the toxicity threshold (Cmin or Css ≥ 50 mg/L) using logistic regression models.
Among the 70 patients analysed, the characteristics of those treated with EII (n = 33) and CI (n = 37) were balanced with the exception of estimates glomerular filtration rate (eGFR): median 30 mL/min/m2 (IQR 30, 84) vs. 79 mL/min/m2 (IQR 30, 124). Of the patients treated with EII, 21 (64%) achieved the target concentration, whereas 31 (97%) of those treated with CI achieved it (P < 0.001). Factors associated with target attainment were: CI (OR 16.28, 95% CI 2.05–407.5), daily dose ≥ 40 mg/kg (OR 12.23, 95% CI 1.76–197.0; P = 0.03) and eGFR (OR 0.98, 95% CI 0.97–0.99; P = 0.02). Attainment of toxicity threshold was associated with daily dose > 70 mg/kg (OR 35.5, 95% CI 5.61–410.3; P < 0.001).
The results suggest the use of meropenem CI at 40–70 mg/kg/day, particularly in septic ICU patients with normal or augmented renal clearance.
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