Autoimmune thrombotic thrombocytopenic purpura associated with disseminated sarcoidosis: A case report.

Sarcoidosis is an inflammatory disease known to be associated with multiple autoimmune disorders. There is a restricted number of descriptions of the association between sarcoidosis and autoimmune thrombotic thrombocytopenic purpura (aTTP). We present the case of a 63-year-old woman admitted to the hospital to investigate a possible sarcoidosis who had hemolytic anemia and thrombocytopenia, with low ADAMTS13 activity and anti-ADAMTS13 antibodies, leading to a diagnosis of aTTP. Sarcoidosis was later confirmed and the two conditions evolved separately after 6 months, questioning the link between them. Clinicians should be aware of this rare cause of thrombocytopenia in patients with sarcoidosis, as aTTP is a life-threatening condition.

Magnesium sulphate in patients with thrombotic thrombocytopenic purpura (MAGMAT): a randomised, double-blind, superiority trial.

PURPOSE: Studies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate supplementation on TTP recovery. METHODS: In this multicenter, randomised, double-blind, controlled, superiority study, we enrolled adults with a clinical diagnosis of TTP. Patients were randomly allocated to receive magnesium sulphate (6 g intravenously followed by a continuous infusion of 6 g/24 h for 3 days) or placebo, in addition to the standard treatment. The primary outcome was the median time to platelet normalisation (defined as a platelet count ≥ 150 G/L). Efficacy and safety were assessed by intention-to-treat. RESULTS: Overall, we enrolled 74 participants, including one who withdrew his/her consent. Seventy-three patients were further analyzed, 35 (48%) allocated to magnesium sulphate and 38 (52%) to placebo. The median time to platelet normalisation was 4 days (95% confidence interval [CI], 3-4) in the magnesium sulphate group and 4 days (95% CI 3-5) in the placebo group. The cause-specific hazard ratio of response was 0.93 (95% CI 0.58-1.48, p = 0.75). The number of patients with ≥ 1 serious adverse reactions was similar in the two groups. By day 90, four patients in the magnesium sulphate group and two patients in the placebo group had died (p = 0.42). The most frequent adverse event was low blood pressure occurring in 34% in the magnesium sulphate group and 29% in the placebo group (p = 0.80). CONCLUSION: Among patients with TTP, the addition of magnesium sulphate to the standard of care did not result in a significant improvement in time to platelet normalisation.

Predictors of acute ischemic cerebral lesions in immune-mediated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

BACKGROUND: The immune form of thrombotic thrombocytopenic purpura (iTTP) and the hemolytic and uremic syndrome (HUS) are two major forms of thrombotic microangiopathy (TMA). Their treatment has been recently greatly improved. In this new era, both the prevalence and predictors of cerebral lesions occurring during the acute phase of these severe conditions remain poorly known. AIM: The prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and Shiga toxin-producing Escherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study. METHODS: Univariate analysis was performed to report the main differences between patients with iTTP and those with HUS or between patients with acute cerebral lesions and the others. Multivariable logistic regression analysis was used to identify the potential predictors of these lesions. RESULTS: Among 73 TMA cases (mean age 46.9 ± 16 years (range 21-87 years) with iTTP (n = 57) or HUS (n = 16), one-third presented with acute ischemic cerebral lesions on magnetic resonance imagery (MRI); two individuals also had hemorrhagic lesions. One in ten patients had acute ischemic lesions without any neurological symptom. The neurological manifestations did not differ between iTTP and HUS. In multivariable analysis, three factors predicted the occurrence of acute ischemic lesions on cerebral MRI: (1) the presence of old infarcts on cerebral MRI, (2) the level of blood pulse pressure, (3) the diagnosis of iTTP. CONCLUSION: At the acute phase of iTTP or HUS, both symptomatic and covert ischemic lesions are detected in one third of cases on MRI. Diagnosis of iTTP and the presence of old infarcts on MRI are associated with the occurrence of such acute lesions as well as increased blood pulse pressure, that may represent a potential target to further improve the therapeutic management of these conditions.

Sepsis-associated coagulopathy in onco-hematology patients presenting with thrombocytopenia: a multicentric observational study.

Coagulation disorders increase mortality rate during septic shock, but the impact of concomitant hematological malignancies remains unknown. The study assessed coagulation disorders in onco-hematological patients with thrombocytopenia (<100 G/L) admitted to ICU for septic shock. Among 146 included patients, 50 patients had lymphoma and 49 patients had acute leukemia. ICU mortality rate was 43.8% (n = 64). Median increase in prothrombin time (PT) at day(d) 1 was 4.7 s (IQR 3.2-7.9) in ICU survivors vs. 6.4 s (IQR 4.5-13.7; p < 0.01) in non-survivors. Fibrinogen kinetics (increase in fibrinogen levels between d1 and d2) was +0.55 (-0.22-1.55) vs. +0.10 g/L (-0.40-0.50; p = 0.03) in surviving and non-surviving patients, respectively. PT increase ≥6 s at d1 (OR 5.5; 95% CI 1.1-6.0; p = 0.03) and mechanical ventilation (OR 7.4; 95% CI 3.3-17.7; p < 0.001) were independently associated with ICU mortality. This study provides information and new ways to identify hematological patients with high-risk mortality.

Immune-mediated thrombotic thrombocytopenic purpura prognosis is affected by blood pressure.

Background: The prevalence, prognostic role, and diagnostic value of blood pressure in immune-mediated thrombotic thrombocytopenic purpura (iTTP) and other thrombotic microangiopathies (TMAs) remain unclear. Methods: Using a national cohort of iTTP (n = 368), Shigatoxin-induced hemolytic uremic syndrome (n = 86), atypical hemolytic uremic syndrome (n = 84), and hypertension-related thrombotic microangiopathy (n = 25), we sought to compare the cohort's blood pressure profile to assess its impact on prognosis and diagnostic performances. Results: Patients with iTTP had lower blood pressure than patients with other TMAs, systolic (130 [interquartile range (IQR) 118-143] vs 161 [IQR 142-180] mmHg) and diastolic (76 [IQR 69-83] vs 92 [IQR 79-105] mmHg, both p < 0.001). The best threshold for iTTP diagnosis corresponded to a systolic blood pressure <150 mmHg. iTTP patients presenting with hypertension had a significantly poorer survival (hazard ratio 1.80, 95% confidence interval 1.07-3.04), and this effect remained significant after multivariable adjustment (hazard ratio = 1.14, 95% confidence interval 1.00-1.30). Addition of a blood pressure criterion modestly improved the French clinical score to predict a severe A disintegrin and metalloprotease with thrombospondin type 1 deficiency in patients with an intermediate score (i.e., either platelet count <30 × 109/L or serum creatinine <200 µM). Conclusions: Elevated blood pressure at admission affects the prognosis of iTTP patients and may help discriminate them from other TMA patients. Particular attention should be paid to blood pressure and its management in these patients.

Neurologic outcome of VZV encephalitis one year after ICU admission: a multicenter cohort study.

BACKGROUND: Varicella-zoster virus (VZV) is one of the main viruses responsible of acute encephalitis. However, data on the prognosis and neurologic outcome of critically ill patients with VZV encephalitis are limited. We aimed to describe the clinical features of VZV encephalitis in the ICU and to identify factors associated with a favorable neurologic outcome. We performed a multicenter cohort study of patients with VZV encephalitis admitted in 18 ICUs in France between 2000 and 2017. Factors associated with a favorable neurologic outcome, defined by a modified Rankin Score (mRS) of 0-2 1 year after ICU admission, were identified by multivariable regression analysis. RESULTS: Fifty-five patients (29 (53%) men, median age 53 (interquartile range 36-66)) were included, of whom 43 (78%) were immunocompromised. ICU admission occurred 1 (0-3) day after the onset of neurological symptoms. Median Glasgow Coma Score at ICU admission was 12 (7-14). Cerebrospinal fluid examination displayed a median leukocyte count of 68 (13-129)/mm3, and a median protein level of 1.37 (0.77-3.67) g/L. CT scan and MRI revealed brain lesions in 30% and 66% of the cases, respectively. Invasive mechanical ventilation was implemented in 46 (84%) patients for a median duration of 13 (3-30) days. Fourteen (25%) patients died in the ICU. One year after ICU admission, 20 (36%) patients had a favorable neurologic outcome (mRS 0-2), 12 (22%) had significant disability (mRS 3-5), and 18 (33%) were deceased (lost to follow-up n = 5, 9%). On multivariable analysis, age (OR 0.92 per year, (0.88-0.97), p = 0.01), and invasive mechanical ventilation (OR 0.09 CI 95% (0.01-0.84), p = 0.03) reduced the likelihood of favorable neurologic outcome. CONCLUSION: One in every three critically ill patients with VZV encephalitis had a favorable neurologic outcome 1 year after ICU admission. Older age and invasive mechanical ventilation were associated with a higher risk of disability and death.

Clostridium haemolyticum Infection: A Cause of Hemolytic Anemia in a Patient with Bone Marrow Necrosis.

Clostridium haemolyticum is a sporulating Gram-positive anaerobic rod that is considered to be one of the most fastidious and oxygen-sensitive anaerobes. It is a well-known animal pathogen and the cause of bacillary hemoglobinuria primarily in cattle. To date, human infections caused by C. haemolyticum have been reported in three patients with malignant underlying diseases. We present herein the case of a 30-year-old obese woman with no significant past medical history who developed bacteremia caused by C. haemolyticum with massive intravascular hemolysis associated with bone marrow necrosis and acute renal failure. Because of subculture failure, the diagnosis was made on the basis of 16S rDNA sequencing and next-generation sequencing. The patient, who had been afebrile for 20 days after a 17-day-course of antibiotics, experienced a second bacteremic episode caused by C. haemolyticum. After having been successfully treated for 42 days with clindamycin and amoxicillin-clavulanic acid, the patient developed acute myeloid leukemia as a result of bone marrow regeneration. Although uncommon in humans, infections caused by C. haemolyticum are severe and should be considered in a febrile patient who has severe hemolytic anemia. This case also highlights the importance of using molecular techniques for the identification of this fastidious anaerobic organism.

Sinusoidal Obstruction Syndrome in Critically Ill Patients in the Era of Defibrotide: A Retrospective Multicenter Study.

Sinusoidal obstruction syndrome (SOS) is a life-threatening liver complication of high- dose chemotherapy. Defibrotide is the only available therapeutic option approved for SOS. The prognosis of SOS in patients requiring intensive care unit (ICU) admission remains unknown. The primary objective of this study was to assess the outcome of SOS patients in ICU. This retrospective study was conducted between 2007 and 2019 in 13 French ICUs. Seventy-one critically ill adult patients with SOS defined according to European Society for Blood and Marrow Transplantation criteria and treated with defibrotide were included. The main reasons for ICU admission were respiratory failure and acute kidney injury. Mechanical ventilation, vasopressors, and renal replacement therapy were required in 59%, 52%, and 49% of patients, respectively. Twenty-three percent of patients experienced a bleeding event during defibrotide treatment. Hospital mortality was 54%, mainly related to multiorgan failure. Older age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00 to 1.04), mechanical ventilation (HR, 1.99; 95% CI, 1.00 to 3.99), renal replacement therapy (HR, 2.55; 95% CI, 1.32 to 4.91) were independent predictors of hospital mortality. Defibrotide prophylaxis (HR, 0.35; 95% CI, 0.13 to 0.92) was associated with better outcomes. Critically ill patients with SOS have a high mortality rate in the ICU, especially if organ support is required. Additional studies assessing the impact of defibrotide prophylaxis are warranted.

A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP.

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.

Influence of deprivation on initial severity and prognosis of patients admitted to the ICU: the prospective, multicentre, observational IVOIRE cohort study.

BACKGROUND: The influence of socioeconomic status on patient outcomes is unclear. We assessed the impact of socioeconomic deprivation on severity of illness at intensive care unit (ICU) admission, and on the risk of death at 3 months after ICU admission. METHODS: The IVOIRE study was a prospective, observational, multicentre cohort study in the ICU of 8 participating hospitals in France, including patients aged ≥ 18 years admitted to the ICU and receiving at least one life support therapy for organ failure. The primary outcomes were severity at admission (assessed by SAPSII score), and mortality at 3 months. Socioeconomic data were obtained from interviews with patients or family. Deprivation was assessed using the EPICES score. RESULTS: Among 1294 patents included between 2013 and 2016, 629 (48.6%) were classed as deprived and differed significantly from non-deprived subjects in terms of sociodemographic characteristics and pre-existing conditions. The mean SAPS II score at admission was 50.1 ± 19.4 in deprived patients and 52.3 ± 17.3 in non-deprived patients, with no significant difference by multivariable analysis (ß = - 1.85 [95% CI - 3.86; + 0.16, p = 0.072]). The proportion of death was 31.1% at 3 months, without significant differences between deprived and non-deprived patients, even after adjustment for confounders. CONCLUSIONS: Deprivation is frequent in patients admitted to the ICU and is not associated with disease severity at admission, or with mortality at 3 months between deprived and non-deprived patients. Trial registration The IVOIRE cohort is registered with ClinicalTrials.gov under the identifier NCT01907581, registration date 17/7/2013.

Post-partum acute kidney injury: sorting placental and non-placental thrombotic microangiopathies using the trajectory of biomarkers.

BACKGROUND: Among the severe complications of preeclampsia (PE), acute kidney injury (AKI) is problematic if features of thrombotic microangiopathy (TMA) are present. Although a haemolysis enzyme liver low-platelets syndrome is considerably more frequent, it is vital to rule out a flare of atypical haemolytic and uraemic syndrome (aHUS). Our objective was to improve differential diagnosis procedures in post-partum AKI. METHODS: A total of 105 cases of post-partum AKI, admitted to nine different regional French intensive care units from 2011 to 2015, were analysed. Analysis included initial and final diagnosis, renal features, haemostasis and TMA parameters, with particular focus on the dynamics of each component within the first days following delivery. A classification and regression tree (CART) was used to construct a diagnostic algorithm. RESULTS: AKI was attributed to severe PE (n = 40), post-partum haemorrhage (n = 33, including 13 renal cortical necrosis) and 'primary' TMA (n = 14, including 10 aHUS and 4 thrombotic thrombocytopenic purpura). Congruence between initial and final diagnosis was low (63%). The dynamics of haemoglobin, haptoglobin and liver enzymes were poorly discriminant. In contrast, the dynamic pattern of platelets was statistically different between primary TMA-related AKI and other groups. CART analysis independently highlighted the usefulness of platelet trajectory in the diagnostic algorithm. Limitations of this study include that only the most severe cases were included in this retrospective study, and the circumstantial complexity is high. CONCLUSION: Trajectory of platelet count between admission and Day 3 helps to guide therapeutic decisions in cases of TMA-associated post-partum AKI. Our study also strongly suggests that during the post-partum period, there may be a risk of transient, slowly recovering TMA in cases of severe endothelial injury in women without a genetic mutation known to induce aHUS.

Direct admission to the intensive care unit from the emergency department and mortality in critically ill hematology patients.

BACKGROUND: The aim of this study was to assess the benefit of direct ICU admission from the emergency department (ED) compared to admission from wards, in patients with hematological malignancies requiring critical care. METHODS: Post hoc analysis derived from a prospective, multicenter cohort study of 1011 critically ill adult patients with hematologic malignancies admitted to 17 ICU in Belgium and France from January 2010 to May 2011. The variable of interest was a direct ICU admission from the ED and the outcome was in-hospital mortality. The association between the variable of interest and the outcome was assessed by multivariable logistic regression after multiple imputation of missing data. Several sensitivity analyses were performed: complete case analysis, propensity score matching and multivariable Cox proportional-hazards analysis of 90-day survival. RESULTS: Direct ICU admission from the ED occurred in 266 (26.4%) cases, 84 of whom (31.6%) died in the hospital versus 311/742 (41.9%) in those who did not. After adjustment, direct ICU admission from the ED was associated with a decreased in-hospital mortality (adjusted OR: 0.63; 95% CI 0.45-0.88). This was confirmed in the complete cases analysis (adjusted OR: 0.64; 95% CI 0.45-0.92) as well as in terms of hazard of death within the 90 days after admission (adjusted HR: 0.77; 95% CI 0.60-0.99). By contrast, in the propensity score-matched sample of 402 patients, direct admission was not associated with in-hospital mortality (adjusted OR: 0.92; 95% CI 0.84-1.01). CONCLUSIONS: In this study, patients with hematological malignancies admitted to the ICU were more likely to be alive at hospital discharge if they were directly admitted from the ED rather than from the wards. Assessment of early predictors of poor outcome in cancer patients admitted to the ED is crucial so as to allow early referral to the ICU and avoid delays in treatment initiation and mis-orientation.

Center effect in intubation risk in critically ill immunocompromised patients with acute hypoxemic respiratory failure.

BACKGROUND: Acute respiratory failure is the leading reason for intensive care unit (ICU) admission in immunocompromised patients, and the need for invasive mechanical ventilation has become a major clinical endpoint in randomized controlled trials (RCTs). However, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. This study explores how this outcome varies across ICUs. METHODS: Hierarchical models and permutation procedures for testing multiple random effects were applied on both data from an observational cohort (the TRIAL-OH study: 703 patients, 17 ICUs) and a randomized controlled trial (the HIGH trial: 776 patients, 31 ICUs) to characterize ICU variation in intubation risk across centers. RESULTS: The crude intubation rate varied across ICUs from 29 to 80% in the observational cohort and from 0 to 86% in the RCT. This center effect on the mean ICU intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p value = 0.013, median OR 1.48 [1.30-1.72]; RCT: p value 0.004, median OR 1.51 [1.36-1.68]). Two ICU-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to ICU admission) and could partly explain this center effect. In the RCT that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation. CONCLUSION: Intubation rates varied considerably among ICUs, even after adjustment on individual characteristics.

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.

Long-term health-related quality of life of critically ill patients with haematological malignancies: a prospective observational multicenter study.

BACKGROUND: Although outcomes of critically ill patients with haematological malignancies (HMs) have been fully investigated in terms of organ failure and mortality, data are scarce on health-related quality of life (HRQOL) in this population. We aim to assess post-intensive care unit (ICU) burden and HRQOL of critically ill patients with HMs and to identify risk factors for quality-of-life (QOL) impairment. RESULTS: In total, 1011 patients with HMs who required ICU admission in 17 ICUs in France and Belgium were included in the study; 278 and 117 patients were evaluated for QOL at 3 months and 1 year, respectively, after ICU discharge. HRQOL was determined by applying the interview form of the Short Form 36 (SF-36) questionnaire. Psychological distress symptoms were evaluated using the Hospital Anxiety Depression Score (HADS) and the Impact of Event Scale (IES). In-hospital mortality rates at 3 months and 1 year were, respectively, 39.1, 50.7 and 57.2%, respectively. At 3 months, median [IQR] physical and mental component summary scores (PCS and MCS) (SF-36) were 37 [28-46] and 51 [45-58], respectively. PCS was lower in ICU patients with HMs when compared to general ICU septic patients (52 [5-13], p = 0.00001). The median combined HAD score was 8 [5-13], and the median IES score was 8 [3-16]. However, recovery during the first year after ICU discharge was not consistent in all dimensions of HRQOL. Three months after ICU discharge, the maximum daily Sequential Organ Failure Assessment score and status of the underlying malignancy at ICU admission were significantly associated with MCS impairment (- 0.54 points [95% CI - 0.99; - 0.1], p = 0.018 and - 4.83 points [95% CI - 8.44; - 1.22], p = 0.009, respectively). CONCLUSION: HRQOL is strongly impaired in critically ill patients with HMs at 3 months and 1 year after ICU discharge. Organ failure and disease status are strongly associated with QOL. The kinetic evaluation of QOL at 3 months and 1 year offers the opportunity to focus on QOL aspects that may be improved by therapeutic interventions during the first year after ICU discharge.

Granulocyte colony-stimulating factor and respiratory status of critically ill neutropenic patients with hematologic malignancies.

In patients with hematologic malignancies, respiratory status may deteriorate during neutropenia recovery. This multicenter, observational study aims to evaluate granulocyte colony-stimulating factor (G-CSF) impact on respiratory status in critically ill neutropenic patients. Among 1011 critically ill patients with hematologic malignancies, 288 were neutropenic and included in this study. 201 (70%) did not receive G-CSF at day 1 or 2. After propensity score matching for the probability of receiving G-CSF at day 1 or 2, there was no association between G-CSF and respiratory deterioration at day 14 (OR =1.19; 95%CI (0.57-2.51); p = .64). Additional sensitivity analysis in patients admitted for acute respiratory failure showed similar results (OR =1.34; 95%CI (0.5-3.59); p = .57). Among patients who recovered from neutropenia, 75% experienced respiratory deterioration during neutropenia recovery. This study confirms that neutropenia recovery is a situation at risk of respiratory deterioration. However, whether G-CSF is an aggravating factor cannot be supported by our results.

Clinical Significance of Upper Airway Virus Detection in Critically Ill Hematology Patients.

RATIONALE: Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients. OBJECTIVES: To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients. METHODS: This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified. MEASUREMENTS AND MAIN RESULTS: Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22-3.50). CONCLUSIONS: Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.

Effect of High-Flow Nasal Oxygen vs Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure: The HIGH Randomized Clinical Trial.

Importance: High-flow nasal oxygen therapy is increasingly used for acute hypoxemic respiratory failure (AHRF). Objective: To determine whether high-flow oxygen therapy decreases mortality among immunocompromised patients with AHRF compared with standard oxygen therapy. Design, Setting, and Participants: The HIGH randomized clinical trial enrolled 776 adult immunocompromised patients with AHRF (Pao2 <60 mm Hg or Spo2 <90% on room air, or tachypnea >30/min or labored breathing or respiratory distress, and need for oxygen ≥6 L/min) at 32 intensive care units (ICUs) in France between May 19, 2016, and December 31, 2017. Interventions: Patients were randomized 1:1 to continuous high-flow oxygen therapy (n = 388) or to standard oxygen therapy (n = 388). Main Outcomes and Measures: The primary outcome was day-28 mortality. Secondary outcomes included intubation and mechanical ventilation by day 28, Pao2:Fio2 ratio over the 3 days after intubation, respiratory rate, ICU and hospital lengths of stay, ICU-acquired infections, and patient comfort and dyspnea. Results: Of 778 randomized patients (median age, 64 [IQR, 54-71] years; 259 [33.3%] women), 776 (99.7%) completed the trial. At randomization, median respiratory rate was 33/min (IQR, 28-39) vs 32 (IQR, 27-38) and Pao2:Fio2 was 136 (IQR, 96-187) vs 128 (IQR, 92-164) in the intervention and control groups, respectively. Median SOFA score was 6 (IQR, 4-8) in both groups. Mortality on day 28 was not significantly different between groups (35.6% vs 36.1%; difference, -0.5% [95% CI, -7.3% to +6.3%]; hazard ratio, 0.98 [95% CI, 0.77 to 1.24]; P = .94). Intubation rate was not significantly different between groups (38.7% vs 43.8%; difference, -5.1% [95% CI, -12.3% to +2.0%]). Compared with controls, patients randomized to high-flow oxygen therapy had a higher Pao2:Fio2 (150 vs 119; difference, 19.5 [95% CI, 4.4 to 34.6]) and lower respiratory rate after 6 hours (25/min vs 26/min; difference, -1.8/min [95% CI, -3.2 to -0.2]). No significant difference was observed in ICU length of stay (8 vs 6 days; difference, 0.6 [95% CI, -1.0 to +2.2]), ICU-acquired infections (10.0% vs 10.6%; difference, -0.6% [95% CI, -4.6 to +4.1]), hospital length of stay (24 vs 27 days; difference, -2 days [95% CI, -7.3 to +3.3]), or patient comfort and dyspnea scores. Conclusions and Relevance: Among critically ill immunocompromised patients with acute respiratory failure, high-flow oxygen therapy did not significantly decrease day-28 mortality compared with standard oxygen therapy. Trial Registration: clinicaltrials.gov Identifier: NCT02739451.

Oxygenation/non-invasive ventilation strategy and risk for intubation in immunocompromised patients with hypoxemic acute respiratory failure.

We investigated how the initial ventilation/oxygenation management may influence the need for intubation on the coming day in a cohort of immunocompromised patients with acute hypoxemic respiratory failure (ARF). Data from 847 immunocompromised patients with ARF were used to estimate the probability of intubation at day+1 within the first 3 days of ICU admission, according to oxygenation management. First, noninvasive ventilation (NIV) was compared to oxygen therapy whatever the administration device; then standard oxygen was compared to High Flow Nasal Cannula therapy alone (HFNC), NIV alone or NIV+HFNC. To take into account the oxygenation regimens over time and to handle confounders, propensity score weighting models were used. In the original sample, the probability of intubation at day+1 was higher in the NIV group vs oxygenation therapy (OR = 1.64, 95CI, 1.09-2.48) or vs the standard oxygen group (OR = 2.05, 95CI: 1.29-3.29); it was also increased in the HFNC group compared to standard oxygen (OR = 2.85, 95CI: 1.37-5.67). However, all these differences disappeared by handling confounding-by-indication in the weighted samples, as well as in the pooled model. Note that adjusted OR for day-28 mortality increased with the day of intubation. In this large cohort of immunocompromised patients, ventilation/oxygenation management had no impact on the probability of intubation on the coming day.