Fusarium, Scedosporium and Other Rare Mold Invasive Infections: Over Twenty-Five-Year Experience of a European Tertiary-Care Center.

Invasive mold infections (IMD) are an emerging concern due to the growing prevalence of patients at risk, encompassing but not limited to allogeneic hematopoietic stem cell transplant recipients, hematological malignancies patients, solid organ transplant recipients and intensive care unit patients. In contrast with invasive aspergillosis and mucormycosis, other hyalohyphomycoses and phaeohyphomycoses remain poorly known. We conducted a retrospective analysis of the clinical, biological, microbiological and evolutive features of 92 IMD having occurred in patients in our tertiary-care center over more than 25 years. A quarter of these infections were due to multiple molds. Molds involved were Fusarium spp. (36.2% of IMD with a single agent, 43.5% of IMD with multiple agents), followed by Scedosporium spp. (respectively 14.5% and 26.1%) and Alternaria spp. (respectively 13.0% and 8.7%). Mortality at day 84 was higher for Fusarium spp., Scedosporium spp. or multiple pathogens IMD compared with Alternaria or other pathogens (51.7% vs. 17.6%, p < 0.05). Mortality at day 84 was also influenced by host factor: higher among hematology and alloHSCT patients than in other patients (30.6% vs. 20.9% at day 42 and 50.0% vs. 27.9% at day 84, p = 0.041). Better awareness, understanding and treatments are awaited to improve patient prognosis.

Staphylococcus epidermidis bloodstream infections are a cause of septic shock in intensive care unit patients.

OBJECTIVES: Staphylococcus epidermidis (SE) is a supposedly low-virulence agent, which may cause proven bloodstream infections (BSIs), with little-known consequences on intensive care unit (ICU) patients. We aimed at studying ICU patients diagnosed with BSIs caused by SE (SE-BSIs). METHODS: We constituted a retrospective cohort in two medical ICUs. SE-BSIs were defined by two or more independent SE-positive blood cultures of the same strain, within 48 hours, without concurrent infection. RESULTS: We included 59 patients; 58% were men (n = 34), with median age of 67 (interquartile range 60-74) years and a simplified acute physiology score II of 59 (36-74) points, and 56% were immunocompromised (n = 33). Among the 37 (63%) patients requiring norepinephrine initiation or increase at the onset of SE-BSI versus patients not requiring vasopressors (37%; n = 22), concomitant arterial lactate levels reached 2.8 (1.9-5.8) versus 1.5 (1.3-2.2) mmol/l (P <0.01), whereas the mean blood pressure was 49 (42-54) versus 61 (56-65) mm Hg (P = 0.01) and the mortality was 46% (n = 17) vs 14% (n = 3) at day 28 (P = 0.01), respectively. Regarding antibiotics, the susceptibility rates toward linezolid and vancomycin were 71% (n = 41/58) and 100% (n = 54/54), respectively. At the time of SE-BSI, all but one patient had a central venous access device. CONCLUSION: This work highlights SE-BSIs as a cause of septic shock, mostly in immunocompromised ICU patients, with increasing concerns about resistance to antibiotics and central line management.

Assessment of plasma Catestatin in COVID-19 reveals a hitherto unknown inflammatory activity with impact on morbidity-mortality.

Introduction: Neuroendocrine cells release Catestatin (CST) from Chromogranin A (CgA) to regulate stress responses. As regards COVID-19 patients (COVID+) requiring oxygen supply, to date nobody has studied CST as a potential mediator in the regulation of immunity. Patients & Methods: Admission plasma CST and CgA - its precursor - concentrations were measured (ELISA test) in 73 COVID+ and 27 controls. Relationships with demographics, comorbidities, disease severity and outcomes were analysed (Mann-Whitney, Spearman correlation tests, ROC curves). Results: Among COVID+, 49 required ICU-admission (COVID+ICU+) and 24 standard hospitalization (COVID+ICU-). Controls were either healthy staff (COVID-ICU-, n=11) or COVID-ICU+ patients (n=16). Median plasma CST were higher in COVID+ than in controls (1.6 [1.02; 3.79] vs 0.87 [0.59; 2.21] ng/mL, p<0.03), with no difference between COVID+ and COVID-ICU+. There was no difference between groups in either CgA or CST/CgA ratios, but these parameters were lower in healthy controls (p<0.01). CST did not correlate with either hypoxia- or usual inflammation-related parameters. In-hospital mortality was similar whether COVID+ or not, but COVID+ had longer oxygen support and more complications (p<0.03). CST concentrations and the CST/CgA ratio were associated with in-hospital mortality (p<0.01) in COVID+, whereas CgA was not. CgA correlated with care-related infections (p<0.001). Conclusion: Respiratory COVID patients release significant amounts of CST in the plasma making this protein widely available for the neural regulation of immunity. If confirmed prospectively, plasma CST will reliably help in predicting in-hospital mortality, whereas CgA will facilitate the detection of patients prone to care-related infections.

Comparison of Short- and Long-Term Mortality in Patients with or without Cancer Admitted to the ICU for Septic Shock: A Retrospective Observational Study.

Introduction: Cancer patients are at high risk of developing septic shock (SSh) and are increasingly admitted to ICU given their improved long-term prognosis. We, therefore, compared the prognosis of cancer and non-cancer patients with SSh. Methods: We conducted a monocentric, retrospective cohort study (2013−2019) on patients admitted to ICU for SSh. We compared the clinical characteristics and management and studied short- and long-term mortality with ICU and in-hospital mortality and 1-year survival according to cancer status. Results: We analyzed 239 ICU stays in 210 patients, 59.5% of whom were men (n = 125), with a median age of 66.5 (IQR 56.3−77.0). Of the 121 cancer patients (57.6% of all patients), 70 had solid tumors (33.3%), and 51 had hematological malignancies (24.3%). When comparing ICU stays of patients with versus without cancer (n = 148 vs. n = 91 stays, respectively), mortality reached 30.4% (n = 45) vs. 30.0% (n = 27) in the ICU (p = 0.95), and 41.6% (n = 59) vs. 35.6% (n = 32) in hospital (p = 0.36), respectively. ICU length of stay (LOS) was 5.0 (2.0−11.3) vs. 6.0 (3.0−15.0) days (p = 0.27), whereas in-hospital LOS was 25.5 (13.8−42.0) vs. 19.5 (10.8−41.0) days (p = 0.33). Upon multivariate analysis, renal replacement therapy (OR = 2.29, CI95%: 1.06−4.93, p = 0.03), disseminated intravascular coagulation (OR = 5.89, CI95%: 2.49−13.92, p < 0.01), and mechanical ventilation (OR = 7.85, CI95%: 2.90−21.20, p < 0.01) were associated with ICU mortality, whereas malignancy, hematological, or solid tumors were not (OR = 1.41, CI95%: 0.65−3.04; p = 0.38). Similarly, overall cancer status was not associated with in-hospital mortality (OR = 1.99, CI95%: 0.98−4.03, p = 0.06); however, solid cancers were associated with increased in-hospital mortality (OR = 2.52, CI95%: 1.12−5.67, p = 0.03). Lastly, mortality was not significantly different at 365-day follow-up between patients with and without cancer. Conclusions: In-hospital and ICU mortality, as well as LOS, were not different in SSh patients with and without cancer, suggesting that malignancies should no longer be considered a barrier to ICU admission.

Combining predictive markers for severe COVID-19: Torquetenovirus DNA load and SARS-CoV-2 RNAemia.

RATIONALE/OBJECTIVES: SARS-CoV-2 is the cause of worldwide COVID-19, which severity has been linked to the immune and inflammatory response. Here, we investigate Torquetenovirus (TTV) DNA load - a marker reflecting the intensity of the overall immune response - as well as SARS-CoV-2 RNAemia and IgM/IgG antibodies in COVID-19-positive patients. METHODS: Two hundred and fifteen COVID-19-positive patients were enrolled, including 87 severe cases and 128 mild-moderate cases. SARS-CoV-2 RNAemia and IgM/IgG antibodies, as well as TTV DNA loads, were measured on longitudinal plasma samples. RESULTS: The rate of severe cases was higher in patients with low TTV DNA load in plasma considering a threshold of 700 copies/mL. In severe patients, SARS-CoV-2 RNAemia positivity rates were higher than those in mild-moderate cases at any timepoint. When combined, TTV DNA load and SARS-CoV-2 RNAemia allowed to predict the outcome of COVID-19 infection, with a higher risk (HR=12.4) of ICU admission in patients with low TTV DNA load and positive SARS-CoV-2 RNAemia. CONCLUSIONS: TTV DNA load and SARS-CoV-2 RNAemia may be effective, non-invasive markers reflecting disease severity and poor outcome that could be conveniently measured in a clinical laboratory setting, as soon as COVID-19 diagnosis is made.

Immunosuppression in patients with grade 3 acute-on-chronic liver failure at transplantation: A practice analysis study.

Transplantation for patients with acute-on-chronic liver failure grade 3 (ACLF3) has encouraging results with 1-year-survival of 80-90%. These patients with multiple organ failure meet the conditions for serious alterations of drug metabolism and increased toxicity. The goal of this study was to identify immunosuppression-dependent factors that affect survival. This retrospective monocentric study was conducted in patients with ACLF3 consecutively transplanted between 2007 and 2019. The primary endpoint was 1-year survival. Secondary endpoints were overall survival, treated rejection, and surgical complications. Immunosuppression was evaluated as to type of immunosuppression, post-transplant introduction timing, trough levels, and trough level intra-patient variability (IPV). One hundred patients were included. Tacrolimus IPV < 40% (P = .019), absence of early tacrolimus overdose (P = .033), use of anti-IL2-receptor antibodies (P = .034), and early mycophenolic acid introduction (P = .038) predicted 1-year survival. Treated rejection was an independent predictor of survival (P = .001; HR 4.2 (CI 95%: 1.13-15.6)). Early everolimus introduction was neither associated with higher rejection rates nor with more surgical complications. Management of immunosuppression in ACLF3 critically ill patients undergoing liver transplantation is challenging. Occurrence and treatment of rejection impacts on survival. Early introduction of mTOR inhibitor seems safe and efficient in this situation.

Pretransplant Intensive Care Unit Management and Selection of Grade 3 Acute-on-Chronic Liver Failure Transplant Candidates.

The aim of this study is to report on the liver transplantation (LT) activity and posttransplant outcome, over time, of patients with grade 3 acute-on-chronic liver failure (ACLF-3) in a single transplant center performing a large number of LTs for patients with ACLF-3. It aims at showing how pre-LT intensive care unit (ICU) management impacts post-LT outcomes, in particular through monitoring the transplantation for ACLF-3 model (TAM) score. A total of 100 patients who had ACLF-3 at the time of LT between 2007 and 2019 were included retrospectively. The cohort was divided in 2 periods, with 50 patients in each period. There was an increase in the number of patients with ACLF-3 who received an LT during the course of the study period and significantly higher 1-year post-LT survival rates in the second period compared with the first period (86% versus 66%, respectively; P = 0.02). Interestingly, patients during both periods had similar severity profiles and scores apart from a significantly lower number of patients with TAM scores >2 at the time of LT in the second period compared with the first period (1 [2%] versus 11 [22%], respectively; P ≤ 0.01). In addition, patients whose clinical condition improved in the ICU (with a TAM score downstaged between admission and LT) had significantly higher post-LT survival rates than those whose TAM score stayed the same or increased: 88% versus 70%, respectively (P = 0.04). This study shows a learning curve in LT for patients with ACLF-3, with optimized ICU management and patient selection leading to increased numbers of LTs for patients with ACLF-3 and improved post-LT outcomes. It also delineates how the TAM score can be used to identify the optimal transplantability window for patients with ACLF-3.

Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic.

BACKGROUND: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. METHODS: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. RESULTS: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11. CONCLUSION: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).

Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study.

OBJECTIVES: To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality. PATIENTS AND METHODS: We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis. RESULTS: Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8-43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2-4.4)), other haematological malignancies (OR 2.1 (1.2-3.8)), other underlying diseases (OR 4.3 (1.4-13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2-3.0)), fever (OR 2.4 (1.5-4.1)), tracheal intubation (OR 2.6 (1.5-4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1-6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3-3.7) and OR 2.2 (1.2-4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1-1.9), p < 0.01). CONCLUSIONS: Coinfections are frequent in IA patients and are associated with higher mortality.

Higher anticoagulation targets and risk of thrombotic events in severe COVID-19 patients: bi-center cohort study.

BACKGROUND: Thromboprophylaxis of COVID-19 patients is a highly debated issue. We aimed to compare the occurrence of thrombotic/ischemic events in COVID-19 patients with acute respiratory distress syndrome (ARDS) treated with either prophylactic or therapeutic dosage of heparin. All patients referred for COVID-19 ARDS in two intensive care units (ICUs) from two centers of a French tertiary hospital were included in our cohort study. Patients were compared according to their anticoagulant treatment to evaluate the risk/benefit of prophylactic anticoagulation versus therapeutic anticoagulation. Medical history, symptoms, biological data and imaging were prospectively collected. RESULTS: One hundred and seventy-nine patients (73% men) were analyzed: 108 in prophylactic group and 71 in therapeutic group. Median age and SAPS II were 62 [IQR 51; 70] years and 47 [IQR 37; 63] points. ICU mortality rate was 17.3%. Fifty-seven patients developed clinically relevant thrombotic complications during their ICU stay, less frequently in therapeutic group (adjusted OR 0.38 [0.14-0.94], p = 0.04). The occurrences of pulmonary embolism (PE), deep vein thrombosis (DVT) and ischemic stroke were significantly lower in the therapeutic group (respective adjusted OR for PE: 0.19 [0.03-0.81]; DVT: 0.13 [0.01-0.89], stroke: 0.06 [0-0.68], all p < 0.05). The occurrence of bleeding complications was not significantly different between groups, neither were ICU length of stay or mortality rate. D-dimer levels were significantly lower during ICU stay, and aPTT ratio was more prolonged in the therapeutic group (p < 0.05). CONCLUSION: Increasing the anticoagulation of severe COVID-19 patients to a therapeutic level might decrease thrombotic complications without increasing their bleeding risk.

Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients.

BACKGROUND: Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients. METHODS: We conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms. RESULTS: The 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2. CONCLUSIONS AND RELEVANCE: Delirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources. TRIAL REGISTRATION: NA.

Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases.

OBJECTIVES: The predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease. METHODS: To characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5-; n = 190/201) based on selected variables, collected retrospectively, without any missing data. RESULTS: Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; p < 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia; 82.6%; p < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; p < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; p < 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5- patients with myositis. CONCLUSION: Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.

PURPOSE: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection. METHODS: All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients. RESULTS: 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups. CONCLUSION: Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.

Adrenal gland-released vasostatin-I is a myocardial depressant factor.

Pheochromocytoma crisis is an exceptional consequence of the release of storage vesicles of the adrenal medulla. It is complicated by fulminant adrenergic myocarditis. It offers a unique opportunity to detect inotropic negative factors from neuroendocrine origin. Our objectives were (a) to describe a pheochromocytoma crisis, (b) to investigate in vivo myocardial depressant activities for the N-terminal 1-76 Chromogranin A-derived peptide, vasostatin-I (VS-I). A patient with a pheochromocytoma crisis was treated, including extracorporeal membrane oxygenation, until mass resection. Plasma concentrations of VS-I were time-dependently assessed with a specific immunoassay; correlations with invasive cardiovascular parameters were investigated. Increased VS-I concentrations were observed over 7 days until tumour resection. VS-I concentrations correlated positively with Chromogranin A levels, negatively with cardiac output and left ventricular stroke work index, but not with heart rate. This case illustrates the pharmacokinetics of VS-I in a pheochromocytoma crisis. It highlights myocardial depressant activity for this peptide at high concentrations.

Critically ill elderly patients (≥ 90 years): Clinical characteristics, outcome and financial implications.

BACKGROUND: Patients aged over 90 are being admitted to intensive care units (ICUs) with increasing frequency. The appropriateness of such decisions still remains controversial due to questionable outcome, limited resources and costs. Our objective was to determine the clinical characteristics and outcome in elderly patients (≥ 90 years) admitted in a medical ICU, with an additional focus on medico-economic implications. METHODS: We reviewed the charts of all patients (≥ 90 years) admitted to our ICU. We compared them with all other ICU patients (< 90 years), sought to identify ICU mortality predictors and also performed a long-term survival follow-up. RESULTS: In the study group of 317 stays: median age was 92 years (IQR: 91-94 years); most patients were female (71.3%.). Acute respiratory failure (52.4%) was the main admission diagnosis; mean SAPS II was 55.6±21.3; half the stays (49.2%) required mechanical ventilation (duration: 7.2±8.8 days); withholding and withdrawing decisions were made for 33.4% of all stays. ICU and hospital mortality rates were 35.7% and 42.6% respectively. Mechanical ventilation (OR = 4.83, CI95%: 1.59-15.82) was an independent predictor of ICU mortality whereas age was not (OR = 0.88, CI95%: 0.72-1.08). Social security reimbursement was significantly lower in the study group compared with all other ICU stays, both per stay (13,160 vs 22,092 Euros, p< 0.01) and per day of stay (p = 0.03). CONCLUSION: Among critically ill elderly patients (≥ 90 years), chronological age was not an independent factor of ICU mortality. ICU care-related costs in this population should not be considered as a limiting factor for ICU admission.

Liver transplantation in critically ill patients: Preoperative predictive factors of post-transplant mortality to avoid futility.

BACKGROUND: The allocation of liver transplants to patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) with multi-organ failure who are admitted in ICU remains controversial due to their high post-transplant mortality rate and the absence of identified mortality risk factors. METHODS: We performed a single-center retrospective cohort study to determine the post-transplant mortality rate of patients with ALF and ACLF requiring ICU care prior to liver transplant (LT) and identified pretransplant factors of post-transplant mortality. RESULTS: Eighty-four patients (29 with ALF and 55 with ACLF) received a liver transplant while they were hospitalized at the ICU. Their mean model for end-stage liver disease (MELD) score was 41, and their mean sequential organ failure assessment (SOFA) was 15 the day before transplant. The overall 1-year survival rate was 66%. In multivariate analysis, pretransplant lactate level and acute respiratory distress syndrome (ARDS) were the only two independent factors associated with post-transplant mortality. The absence of ARDS and a pretransplant lactate level< 5 mmol/L led to the identification of a subgroup of ICU patients with a good 1-year post-transplant survival (>80%). CONCLUSIONS: Low lactatemia lactate level and the absence of ARDS could be useful criteria in selecting those patients in ICU who could be eligible for liver transplant.

Clinical features and outcomes in patients with disseminated toxoplasmosis admitted to intensive care: a multicenter study.

BACKGROUND: Characteristics and outcomes of adult patients with disseminated toxoplasmosis admitted to the intensive care unit (ICU) have rarely been described. METHODS: We performed a retrospective study on consecutive adult patients with disseminated toxoplasmosis who were admitted from January 2002 through December 2012 to the ICUs of 14 university-affiliated hospitals in France. Disseminated toxoplasmosis was defined as microbiological or histological evidence of disease affecting >1 organ in immunosuppressed patients. Isolated cases of cerebral toxoplasmosis were excluded. Clinical data on admission and risk factors for 60-day mortality were collected. RESULTS: Thirty-eight patients were identified during the study period. Twenty-two (58%) had received an allogeneic hematopoietic stem cell transplant (median, 61 [interquartile range {IQR}, 43-175] days before ICU admission), 4 (10%) were solid organ transplant recipients, and 10 (27%) were infected with human immunodeficiency virus (median CD4 cell count, 14 [IQR, 6-33] cells/µL). The main indications for ICU admission were acute respiratory failure (89%) and shock (53%). The 60-day mortality rate was 82%. Allogeneic hematopoietic stem cell transplant (hazard ratio [HR] = 2.28; 95% confidence interval [CI], 1.05-5.35; P = .04) and systolic cardiac dysfunction (HR = 3.54; 95% CI, 1.60-8.10; P < .01) within 48 hours of ICU admission were associated with mortality. CONCLUSIONS: Severe disseminated toxoplasmosis leading to ICU admission has a poor prognosis. Recipients of allogeneic hematopoietic stem cell transplant appear to have the highest risk of mortality. We identified systolic cardiac dysfunction as a major determinant of outcome. Strategies aimed at preventing this fatal opportunistic infection may improve outcomes.

Profile of the risk of death after septic shock in the present era: an epidemiologic study.

OBJECTIVES: To investigate mortality of ICU patients over a 3-month period after an initial episode of septic shock and to identify factors associated with mortality. DESIGN: Prospective multicenter observational cohort study. SETTING: Fourteen ICUs from 10 French nonacademic and university teaching hospitals. PATIENTS: All consecutive adult patients with septic shock admitted between October 2009 and September 2011 were eligible. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Multivariable analyses were performed using a Cox proportional hazard model and a flexible extension of the Cox model. In total, 1,495 of 10,941 patients (13.7%) had septic shock and 1,488 patients (99.5%) were included. Median age was 68 years (range, 58-78 yr). The majority of admissions (84%) were medical. Median (interquartile range) Simplified Acute Physiological Score II and Sequential Organ Failure Assessment were, respectively, 56 (45-70) and 11 (9-14). ICU and hospital mortality were, respectively, 39.4% and 48.6%. At 3 months, 776 patients (52.2%) had died. Factors significantly associated with increased risk of death in the multivariable Cox model were older age, male sex, comorbidities (immune deficiency, cirrhosis), Knaus C/D score, and high Sequential Organ Failure Assessment score. Flexible analyses indicated that the impact of Sequential Organ Failure Assessment score was greatest early after septic shock, while the onset of the effect of age, nosocomial infection, and cirrhosis was later. CONCLUSIONS: This is the most recent large-scale epidemiological study to investigate medium-term mortality in nonselected patients hospitalized in the ICU for septic shock. Advances in early management have improved survival at the initial phase, but risk of death persists in the medium term. Flexible modeling techniques yield insights into the profile of the risk of death in the first 3 months.