Multicenter Retrospective Study of Invasive Fusariosis in Intensive Care Units, France.

Invasive fusariosis can be life-threatening, especially in immunocompromised patients who require intensive care unit (ICU) admission. We conducted a multicenter retrospective study to describe clinical and biologic characteristics, patient outcomes, and factors associated with death and response to antifungal therapy. We identified 55 patients with invasive fusariosis from 16 ICUs in France during 2002----2020. The mortality rate was high (56%). Fusariosis-related pneumonia occurred in 76% of patients, often leading to acute respiratory failure. Factors associated with death included elevated sequential organ failure assessment score at ICU admission or history of allogeneic hematopoietic stem cell transplantation or hematologic malignancies. Neither voriconazole treatment nor disseminated fusariosis were strongly associated with response to therapy. Invasive fusariosis can lead to multiorgan failure and is associated with high mortality rates in ICUs. Clinicians should closely monitor ICU patients with a history of hematologic malignancies or stem cell transplantation because of higher risk for death.

The combination of kidney function variables with cell cycle arrest biomarkers identifies distinct subphenotypes of sepsis-associated acute kidney injury: a post-hoc analysis (the PHENAKI study).

BACKGROUND: The severity and course of sepsis-associated acute kidney injury (SA-AKI) are correlated with the mortality rate. Early detection of SA-AKI subphenotypes might facilitate the rapid provision of individualized care. PATIENTS AND METHODS: In this post-hoc analysis of a multicenter prospective study, we combined conventional kidney function variables with serial measurements of urine (tissue inhibitor of metalloproteinase-2 [TIMP-2])* (insulin-like growth factor-binding protein [IGFBP7]) at 0, 6, 12, and 24 h) and then using an unsupervised hierarchical clustering of principal components (HCPC) approach to identify different phenotypes of SA-AKI. We then compared the subphenotypes with regard to a composite outcome of in-hospital death or the initiation of renal replacement therapy (RRT). RESULTS: We included 184 patients presenting SA-AKI within 6 h of the initiation of catecholamines. Three distinct subphenotypes were identified: subphenotype A (99 patients) was characterized by a normal urine output (UO), a low SCr and a low [TIMP-2]*[IGFBP7] level; subphenotype B (74 patients) was characterized by existing chronic kidney disease (CKD), a higher SCr, a low UO, and an intermediate [TIMP-2]*[IGFBP7] level; and subphenotype C was characterized by very low UO, a very high [TIMP-2]*[IGFBP7] level, and an intermediate SCr level. With subphenotype A as the reference, the adjusted hazard ratio (aHR) [95%CI] for the composite outcome was 3.77 [1.92-7.42] (p < 0.001) for subphenotype B and 4.80 [1.67-13.82] (p = 0.004) for subphenotype C. CONCLUSIONS: Combining conventional kidney function variables with urine measurements of [TIMP-2]*[IGFBP7] might help to identify distinct SA-AKI subphenotypes with different short-term courses and survival rates.

Neurological burden and outcomes of excessive ß-lactam serum concentrations of critically ill septic patients: a prospective cohort study.

BACKGROUND: Therapeutic drug monitoring (TDM) contributes to optimizing exposure to ß-lactam antibiotics. However, how excessive exposure to ß-lactams can increase the burden of care of critically ill patients is unclear. PATIENTS AND METHODS: In a prospective cohort study, we examined whether excessive ß-lactam serum concentrations contribute to neurological deterioration and the associated complications of adult septic patients without recent history of neurological disease treated with ß-lactams in a medical ICU. Excessive ß-lactam concentrations were defined as serum concentrations that exceeded the upper limit of the therapeutic range recommended by the French Societies of Pharmacology and Therapeutics (SFPT) and Anesthesia and Intensive Care Medicine (SFAR). Neurological deterioration was defined as an increase in the neurological Sequential Organ Failure Assessment score (nSOFA) of ≥1 between the day of starting treatment at admission and the day of TDM performed 2 days after treatment initiation. RESULTS: We included 119 patients [median age: 65 years; males: 78 (65.5%)] admitted for acute respiratory distress [59 (49.6%)] or septic shock [25 (21%)]. In adjusted logistic regression analysis, an excessive ß-lactam serum concentration was associated with neurological deterioration [OR (95% CI): 10.38 (3.23-33.35), P < 0.0001]. Furthermore, in adjusted linear regression analysis, an excessive ß-lactam serum concentration was associated with longer time to discharge alive (ß=0.346, P = 0.0007) and, among mechanically ventilated patients discharged alive, with longer time to extubation following the withdrawal of sedation (ß=0.248, P = 0.0030). CONCLUSIONS: These results suggest that excessive exposure to ß-lactams could complicate the management of septic patients in the ICU and confirm the clinical relevance of the upper concentration limits recommended for dose reduction.

Respiratory effects of lung recruitment maneuvers depend on the recruitment-to-inflation ratio in patients with COVID-19-related acute respiratory distress syndrome.

BACKGROUND: In the context of acute respiratory distress syndrome (ARDS), the response to lung recruitment maneuvers (LRMs) varies considerably from one patient to another and so is difficult to predict. The aim of the study was to determine whether or not the recruitment-to-inflation (R/I) ratio could differentiate between patients according to the change in lung mechanics during the LRM. METHODS: We evaluated the changes in gas exchange and respiratory mechanics induced by a stepwise LRM at a constant driving pressure of 15 cmH2O during pressure-controlled ventilation. We assessed lung recruitability by measuring the R/I ratio. Patients were dichotomized with regard to the median R/I ratio. RESULTS: We included 30 patients with moderate-to-severe ARDS and a median [interquartile range] R/I ratio of 0.62 [0.42-0.83]. After the LRM, patients with high recruitability (R/I ratio ≥ 0.62) presented an improvement in the PaO2/FiO2 ratio, due to significant increase in respiratory system compliance (33 [27-42] vs. 42 [35-60] mL/cmH2O; p < 0.001). In low recruitability patients (R/I < 0.62), the increase in PaO2/FiO2 ratio was associated with a significant decrease in pulse pressure as a surrogate of cardiac output (70 [55-85] vs. 50 [51-67] mmHg; p = 0.01) but not with a significant change in respiratory system compliance (33 [24-47] vs. 35 [25-47] mL/cmH2O; p = 0.74). CONCLUSION: After the LRM, patients with high recruitability presented a significant increase in respiratory system compliance (indicating a gain in ventilated area), while those with low recruitability presented a decrease in pulse pressure suggesting a drop in cardiac output and therefore in intrapulmonary shunt.

Doppler Echocardiographic Indices Are Specific But Not Sensitive to Predict Pulmonary Artery Occlusion Pressure in Critically Ill Patients Under Mechanical Ventilation.

OBJECTIVES: The objective of this study was to prospectively evaluate the ability of transthoracic echocardiography to assess pulmonary artery occlusion pressure in mechanically ventilated critically ill patients. DESIGN: In a prospective observational study. SETTING: Amiens University Hospital Medical ICU. PATIENTS: Fifty-three mechanically ventilated patients in sinus rhythm admitted to our ICU. INTERVENTION: Transthoracic echocardiography was performed simultaneously to pulmonary artery catheter. MEASUREMENTS AND MAIN RESULTS: Transmitral early velocity wave recorded using pulsed wave Doppler (E), late transmitral velocity wave recorded using pulsed wave Doppler (A), and deceleration time of E wave were recorded using pulsed Doppler as well as early mitral annulus velocity wave recorded using tissue Doppler imaging (E'). Pulmonary artery occlusion pressure was measured simultaneously using pulmonary artery catheter. There was a significant correlation between pulmonary artery occlusion pressure and lateral ratio between E wave and E' (E/E' ratio) (r = 0.35; p < 0.01), ratio between E wave and A wave (E/A ratio) (r = 0.41; p < 0.002), and deceleration time of E wave (r = -0.34; p < 0.02). E/E' greater than 15 was predictive of pulmonary artery occlusion pressure greater than or equal to 18 mm Hg with a sensitivity of 25% and a specificity of 95%, whereas E/E' less than 7 was predictive of pulmonary artery occlusion pressure less than 18 mm Hg with a sensitivity of 32% and a specificity of 81%. E/A greater than 1.8 yielded a sensitivity of 44% and a specificity of 95% to predict pulmonary artery occlusion pressure greater than or equal to 18 mm Hg, whereas E/A less than 0.7 was predictive of pulmonary artery occlusion pressure less than 18 mm Hg with a sensitivity of 19% and a specificity of 94%. A similar predictive capacity was observed when the analysis was confined to patients with EF less than 50%. A large proportion of E/E' measurements 32 (60%) were situated between the two cut-off values obtained by the receiver operating characteristic curves: E/E' greater than 15 and E/E' less than 7. CONCLUSIONS: In mechanically ventilated critically ill patients, Doppler transthoracic echocardiography indices are highly specific but not sensitive to estimate pulmonary artery occlusion pressure.

Abnormal laboratory findings and plasma concentration monitoring of lopinavir and ritonavir in COVID-19.

It is not known whether the adverse events (AEs) associated with the administration of lopinavir and ritonavir (LPV/r) in the treatment of COVID-19 are concentration-dependent. In a retrospective study of 65 patients treated with LPV/r and therapeutic drug monitoring (TDM) for severe forms of COVID-19 (median age: 67; males: 41 [63.1%]), 33 (50.8%) displayed a grade ≥2 increase in plasma levels of hepatobiliary markers, lipase and/or triglycerides. A causal relationship between LPV/r and the AE was suspected in 9 of the 65 patients (13.8%). At 400 mg b.i.d., the plasma trough concentrations of LPV/r were high and showed marked interindividual variability (median [interquartile range]: 16,600 [11,430-20,842] ng/ml for lopinavir and 501 [247-891] ng/ml for ritonavir). The trough lopinavir concentration was negatively correlated with body mass index, while the trough ritonavir concentration was positively correlated with age and negatively correlated with prothrombin activity. However, the occurrence of abnormal laboratory values was not associated with higher trough plasma concentrations of LPV/r. Further studies will be needed to determine the value of TDM in LPV/r-treated patients with COVID-19.

Estimation of Pulmonary Artery Occlusion Pressure Using Doppler Echocardiography in Mechanically Ventilated Patients.

OBJECTIVES: Evaluation of left atrial pressure is frequently required for mechanically ventilated critically ill patients. The objective of the present study was to evaluate the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines for assessment of the pulmonary artery occlusion pressure (a frequent surrogate of left atrial pressure) in this population. DESIGN: A pooled analysis of three prospective cohorts of patients simultaneously assessed with a pulmonary artery catheter and echocardiography. SETTINGS: Medical-surgical intensive care department of two university hospitals in France. PATIENTS: Mechanically ventilated critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 98 included patients (males: 67%; mean ± SD age: 59 ± 16; and mean Simplified Acute Physiology Score 2: 54 ± 20), 53 (54%) experienced septic shock. Using the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, the predicted pulmonary artery occlusion pressure was indeterminate in 48 of the 98 patients (49%). Of the 24 patients with an elevated predicted left atrial pressure (grade II/III diastolic dysfunction), only 17 (71%) had a pulmonary artery occlusion pressure greater than or equal to 18 mm Hg. Similarly, 20 of the 26 patients (77%) with a normal predicted left atrial pressure (grade I diastolic dysfunction) had a measured pulmonary artery occlusion pressure less than 18 mm Hg. The sensitivity and specificity of American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines for predicting elevated pulmonary artery occlusion pressure were both 74%. The agreement between echocardiography and the pulmonary artery catheter was moderate (Cohen's Kappa, 0.48; 95% CI, 0.39-0.70). In a proposed alternative algorithm, the best echocardiographic predictors of a normal pulmonary artery occlusion pressure were a lateral e'-wave greater than 8 (for a left ventricular ejection fraction ≥ 45%) or an E/A ratio less than or equal to 1.5 (for a left ventricular ejection fraction < 45%). CONCLUSIONS: The American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines do not accurately assess pulmonary artery occlusion pressure in ventilated critically ill patients. Simple Doppler measurements gave a similar level of diagnostic performance with less uncertainly.

Thyroid Storm in the ICU: A Retrospective Multicenter Study.

OBJECTIVES: Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission. DESIGN: Retrospective, multicenter, national study over an 18-year period (2000-2017). SETTING: Thirty-one French ICUs. PATIENTS: The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were "definite thyroid storm," as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure. MEASUREMENTS AND MAIN RESULTS: Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves' disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients [26%]) and antithyroid-drug discontinuation (13 patients [14%]) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03-1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77-50.12; p = 0.008) as being independently associated with in-ICU mortality. CONCLUSIONS: Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.

Neurotoxic Concentration of Piperacillin during Continuous Infusion in Critically Ill Patients.

This retrospective cohort study included 53 patients admitted to the intensive care unit (ICU), with an average age of 69 years, without neurologic disorder before initiation of a continuous piperacillin infusion at the standard dose and who underwent piperacillin serum concentration monitoring. Among them, 23 developed a neurologic disorder for which the piperacillin causality was chronologically and semiologically suggestive. A concentration threshold of 157.2 mg/liter independently predicted neurotoxicity with 96.7% specificity and 52.2% sensitivity and may constitute a limitation when targeting less susceptible pathogens.

Urgent Chemotherapy for Life-Threatening Complications Related to Solid Neoplasms.

OBJECTIVES: Solid neoplasms can be directly responsible for organ failures at the time of diagnosis or relapse. The management of such specific complications relies on urgent chemotherapy and eventual instrumental or surgical procedures, combined with advanced life support. We conducted a multicenter study to address the prognosis of this condition. DESIGN: A multicenter retrospective (2001-2015) chart review. SETTING: Medical and respiratory ICUs. PATIENTS: Adult patients who received urgent chemotherapy in the ICU for organ failure related to solid neoplasms were included. The modalities of chemotherapy, requirements of adjuvant instrumental or surgical procedures, and organ supports were collected. Endpoints were short- and long-term survival rates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-six patients were included. Lung cancer was the most common malignancy distributed into small cell lung cancer (n = 57) and non-small cell lung cancer (n = 33). The main reason for ICU admission was acute respiratory failure in 111 patients (81.6%), of whom 89 required invasive mechanical ventilation. Compression and tissue infiltration by tumor cells were the leading mechanisms resulting in organ involvement in 78 (57.4%) and 47 (34.6%) patients. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 37%, 58%, 74%, and 88%, respectively. Small cell lung cancer was identified as an independent predictor of hospital survival. However, this gain in survival was not sustained since the 1-year survival rates of small cell lung cancer, non-small cell lung cancer, and non-lung cancer patients all dropped below 20%. CONCLUSIONS: Urgent chemotherapy along with aggressive management of organ failures in the ICU can be lifesaving in very selected cancer patients, most especially with small cell lung cancer, although the long-term survival is hardly sustainable.

Life threatening rickettsiosis and the role of hemophagocytic lymphohistiocytosis syndrome (HLH): Case report of a 21-year-old woman.

Hemophagocytic lymphohistiocytosis (HLH) syndrome is an uncontrolled activation of macrophages, causing multiorgan dysfunction. The prognosis depends on the cause and the delay of diagnosis and treatment. Several infections can cause HLH, including rickettsia, a gram-negative bacterium. The diagnosis of rickettsia is based on clinical signs, including fever, headache, rash and sometimes tick bite site. The importance of an early diagnosis of rickettsia is the key. We present a case of rickettsia infection complicated with severe HLH occurring in a 21-year-old woman. The diagnosis was confirmed by serology 4 weeks after admission. She was treated with immunoglobulin, corticosteroids, and doxycycline with a favorable outcome.

Modes of administration of nitric oxide devices and ventilators flow-by impact the delivery of pre-determined concentrations.

BACKGROUND: Nitric oxide (NO) is a strong vasodilator, selectively directed on pulmonary circulation through inhaled administration. In adult intensive care units (ICU), it is mainly used for refractory hypoxemia in mechanically ventilated patients. Several medical delivery devices have been developed to deliver inhaled nitric oxide (iNO). The main purpose of those devices is to guarantee an accurate inspiratory NO concentration, whatever the ventilator used, with NO2 concentrations lower than 0.3 ppm. We hypothesized that the performances of the different available iNO delivery systems could depend on their working principle and could be influenced by the ventilator settings. The objective of this study was to assess the accuracy of seven different iNO-devices combined with different ICU ventilators' flow-by to reach inspiratory NO concentration targets and to evaluate their potential risk of toxicity. METHODS: We tested seven iNO-devices on a test-lung connected to distinct ICU ventilators offering four different levels of flow-by. We measured the flow in the inspiratory limb of the patient circuit and the airway pressure. The nitric oxide/nitrogen (NO/N2) flow was measured on the administration line of the iNO-devices. NO and NO2 concentrations were measured in the test-lung using an electrochemical analyzer. RESULTS: We identified three iNO-device generations based on the way they deliver NO flow: "Continuous", "Sequential to inspiratory phase" (I-Sequential) and "Proportional to inspiratory and expiratory ventilator flow" (Proportional). Median accuracy of iNO concentration measured in the test lung was 2% (interquartile range, IQR -19; 36), -23% (IQR -29; -17) and 0% (IQR -2; 0) with Continuous, I-Sequential and Proportional devices, respectively. Increased ventilator flow-by resulted in decreased iNO concentration in the test-lung with Continuous and I-Sequential devices, but not with Proportional ones. NO2 formation measured to assess potential risks of toxicity never exceeded the predefined safety target of 0.5 ppm. However, NO2 concentrations higher than or equal to 0.3 ppm, a concentration that can cause bronchoconstriction, were observed in 19% of the different configurations. CONCLUSION: We identified three different generations of iNO-devices, based on their gas administration modalities, that were associated with highly variable iNO concentrations' accuracy. Ventilator's flow by significantly impacted iNO concentration. Only the Proportional devices permitted to accurately deliver iNO whatever the conditions and the ventilators tested.

Host transcriptomics and machine learning for secondary bacterial infections in patients with COVID-19: a prospective, observational cohort study.

BACKGROUND: Viral respiratory tract infections are frequently complicated by secondary bacterial infections. This study aimed to use machine learning to predict the risk of bacterial superinfection in SARS-CoV-2-positive individuals. METHODS: In this prospective, multicentre, observational cohort study done in nine centres in six countries (Australia, Indonesia, Singapore, Italy, Czechia, and France) blood samples and RNA sequencing were used to develop a robust model of predicting secondary bacterial infections in the respiratory tract of patients with COVID-19. Eligible participants were older than 18 years, had known or suspected COVID-19, and symptoms of a recent respiratory infection. A control cohort of participants without COVID-19 who were older than 18 years and with no infection symptoms was also recruited from one Australian centre. In the pre-analysis phase, data were filtered to include only individuals with complete blood transcriptomics and patient data (ie, age, sex, location, and WHO severity score at the time of sample collection). The dataset was then divided randomly (4:1) into a training set (80%) and a test set (20%). Gene expression data in the training set and control cohort were used for differential expression analysis. Differentially expressed genes, along with WHO severity score, location, age, and sex, were used for feature selection with least absolute shrinkage and selection operator (LASSO) in the training set. For LASSO analysis, samples were excluded if gene expression data were not obtained at study admission, no longitudinal clinical information was available, a bacterial infection at the time of study admission was present, or a fungal infection in the absence of a bacterial infection was detected. LASSO regression was performed using three subsets of predictor variables: patient data alone, gene expression data alone, or a combination of patient data and gene expression data. The accuracy of the resultant models was tested on data from the test set. FINDINGS: Between March, 2020, and October, 2021, we recruited 536 SARS-CoV-2-positive individuals and between June, 2013, and January, 2020, we recruited 74 participants into the control cohort. After prefiltering analysis and other exclusions, samples from 158 individuals were analysed in the training set and 47 in the test set. The expression of seven host genes (DAPP1, CST3, FGL2, GCH1, CIITA, UPP1, and RN7SL1) in the blood at the time of study admission was identified by LASSO as predictive of the risk of developing a secondary bacterial infection of the respiratory tract more than 24 h after study admission. Specifically, the expression of these genes in combination with a patient's WHO severity score at the time of study enrolment resulted in an area under the curve of 0·98 (95% CI 0·89-1·00), a true positive rate (sensitivity) of 1·00 (95% CI 1·00-1·00), and a true negative rate (specificity) of 0·94 (95% CI 0·89-1·00) in the test cohort. The combination of patient data and host transcriptomics at hospital admission identified all seven individuals in the training and test sets who developed a bacterial infection of the respiratory tract 5-9 days after hospital admission. INTERPRETATION: These data raise the possibility that host transcriptomics at the time of clinical presentation, together with machine learning, can forward predict the risk of secondary bacterial infections and allow for the more targeted use of antibiotics in viral infection. FUNDING: Snow Medical Research Foundation, the National Health and Medical Research Council, the Jack Ma Foundation, the Helmholtz-Association, the A2 Milk Company, National Institute of Allergy and Infectious Disease, and the Fondazione AIRC Associazione Italiana per la Ricerca contro il Cancro.

Mitral annular plane systolic excursion for assessing left ventricular systolic dysfunction in patients with septic shock.

Background: Using easy-to-determine bedside measurements, we developed an echocardiographic algorithm for predicting left ventricular ejection fraction (LVEF) and longitudinal strain (LVLS) in patients with septic shock. Methods: We measured septal and lateral mitral annular plane systolic excursion (MAPSE), septal and lateral mitral S-wave velocity, and the left ventricular longitudinal wall fractional shortening in patients with septic shock. We used a conditional inference tree method to build a stratification algorithm. The left ventricular systolic dysfunction was defined as an LVEF <50%, an LVLS greater than -17%, or both. Results: We included 71 patients (males: 61%; mean [standard deviation] age: 61 [15] yr). Septal MAPSE (cut-off: 1.2 cm) was the best predictor of left ventricular systolic dysfunction. The level of agreement between the septal MAPSE and the left ventricular systolic dysfunction was 0.525 [0.299-0.751]. A septal MAPSE ≥1.2 cm predicted normal LVEF in 17/18 patients, or 94%. In contrast, a septal MAPSE <1.2 cm predicted left ventricular systolic dysfunction with impaired LVLS in 46/53 patients (87%), although 32/53 (60%) patients had a preserved LVEF. Conclusions: Septal MAPSE is easily measured at the bedside and might help clinicians to detect left ventricular systolic dysfunction early-especially when myocardial strain measurements are not feasible.

Rare manifestations of cryoglobulinemic vasculitis: a case report.

Introduction: Cryoglobulinemic vasculitis is a type of small vessel vasculitis diseases that can cause dysfunction in multiple organs. It is characterized by general symptoms, often accompanied by nonspecific cutaneous, articular, neurological, and renal manifestations. Diagnosing cryoglobulinemia through biological testing can be time-consuming and sometimes yields negative results, making diagnosis challenging. There are also other potentially life-threatening complications that can significantly impact prognosis and delay urgent treatment, including digestive manifestations and heart failure. Case presentation: We report the case of a 60-year-old male patient with a medical history of rheumatoid arthritis. He was admitted to the Nephrology Department for investigation of necrotic vascular purpura, acute kidney injury, and pancytopenia. Laboratory tests revealed consumption of the C3 and C4 complement fractions and the presence of mixed-type III cryoglobulinemia. Despite the initiation of the treatment, the patient rapidly developed multiple severe organ failures, including renal, cardiac, respiratory, and finally digestive complications. Acute colic ischemia led to emergency surgery and the patient was transferred to the Intensive Care Unit. Despite surgical intervention and hemodynamic support, the patient experienced multi-visceral organ failure and died two hours after admission. Discussion: Mixed cryoglobulinemia vasculitis may result in rare cases of acute and life-threatening organ damage, such as cardiac or respiratory failure with pulmonary hemorrhage, gastrointestinal ischemia, and neurological disorders. These severe manifestations are associated with a poor prognosis and it is crucial to promptly initiate an aggressive therapeutic strategy.

Annexin-V positive extracellular vesicles level is increased in severe COVID-19 disease.

Objectives: To evaluate extracellular vesicles levels in a cohort of SARS-CoV-2's patients hospitalized in an intensive care unit with and without COVID-19 associated thromboembolic events. Methods: In this study, we aim to assess endothelial and platelet membrane-derived extracellular vesicles levels in a cohort of SARS-CoV-2 patients with and without COVID-19-associated thromboembolic events who were hospitalized in an intensive care unit. Annexin-V positive extracellular vesicles levels were prospectively assessed by flow cytometry in one hundred twenty-three critically ill adults diagnosed with acute respiratory distress syndrome associated with a SARS-CoV-2 infection, ten adults diagnosed for moderate SARS-CoV-2 infection and 25 healthy volunteers. Results: On our critically ill patients, thirty-four patients (27.6%) had a thromboembolic event, Fifty-three (43%) died. Endothelial and platelet membrane-derived extracellular vesicles were drastically increased in SARS-CoV-2 patients hospitalized in the ICU compared to healthy volunteers. Moreover a slighty higher small/large ratio for platelets membrane-derived extracellular vesicles in patients was linked to thrombo-embolic events. Conclusion: A comparison between total annexin-V positive extracellular vesicles levels in severe and moderate SARS-CoV-2 infection and healthy controls showed a significant increase in patients with severe infection and their sizes could be considered as biomarkers of SARS-CoV-2 associated thrombo-embolic events.

Relationship between immunosuppression and intensive care unit-acquired colonization and infection related to multidrug-resistant bacteria: a prospective multicenter cohort study.

PURPOSE: The impact of immunosuppression on intensive care unit (ICU)-acquired colonization and infection related to multidrug-resistant (MDR) bacteria (ICU-MDR-col and ICU-MDR-inf, respectively) is unknown. METHODS: We carried out an observational prospective cohort study in 8 ICUs in France (all with single-bed rooms and similar organizational characteristics). All consecutive patients with an ICU stay > 48 h were included, regardless of immune status, and followed for 28 days. Patients underwent systematic screening for colonization with MDR bacteria upon admission and every week subsequently. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, solid-organ transplant, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic. The primary endpoint was the incidence rate of a composite outcome including ICU-MDR-col and/or ICU-MDR-inf. RESULTS: 750 patients (65.9% males, median age 65 years) were included, among whom 264 (35.2%) were immunocompromised. Reasons for ICU admission, severity scores and exposure to invasive devices and antibiotics during ICU stay were comparable between groups. After adjustment for center and pre-specified baseline confounders, immunocompromised patients had a lower incidence rate of ICU-MDR-col and/or ICU-MDR-inf (adjusted incidence ratio 0.68, 95% CI 0.52-0.91). When considered separately, the difference was significant for ICU-MDR-col, but not for ICU-MDR-inf. The distribution of MDR bacteria was comparable between groups, with a majority of Enterobacteriacae resistant to third-generation cephalosporins (~ 74%). CONCLUSION: Immunocompromised patients had a significantly lower incidence rate of a composite outcome including ICU-MDR-col and/or ICU-MDR-inf. This finding points to the role of contact precautions and isolation measures, and could have important implications on antibiotic stewardship in this population.

Post-traumatic stress disorder and quality of life alterations in survivors of immune-mediated thrombotic thrombocytopenic purpura and atypical hemolytic and uremic syndrome.

Thrombotic thrombocytopenic purpura (iTTP) and atypical hemolytic-uremic syndrome (aHUS), once in remission, may cause long-term symptoms, among which mental-health impairments may be difficult to detect. We conducted telephone interviews 72 [48-84] months after ICU discharge to assess symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) and the 36-item Short Form questionnaire (SF-36). Of 103 included patients, 52 had iTTP and 51 aHUS; 74% were female, median age was 39 y (31-54), and 39 (38%) patients were still taking treatment. Symptoms of anxiety, PTSD and depression were present in 50%, 27% and 14% of patients, respectively, with no significant difference between the iTTP and aHUS groups. Patients with PTSD symptoms had significantly greater weight gain and significantly worse perceived physical and/or emotional wellbeing, anxiety symptoms, and depression symptoms. The SF-36 physical and mental components indicated significantly greater quality-of-life impairments in patients with vs. without PTSD symptoms and in those with aHUS and PTSD vs. iTTP with or without PTSD. In the aHUS group, quality of life was significantly better in patients with vs. without eculizumab treatment. Factors independently associated with PTSD symptoms were male sex (odds ratio [OR], 0.11; 95%CI, 0.02-0.53), platelet count ≤20 G/L at acute-episode presentation (OR, 2.68; 1.01-7.38), and current treatment (OR, 2.69; 95%CI, 1.01-7.36). Mental-health screening should be routine in patients with iTTP and aHUS to ensure appropriate care.