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An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections (Aspergillus, Mucorales, and Pneumocystis jirovecii) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis.

All neutrophil and lymphocyte counts during hospital admission were collected along with demographics, underlying HM, main laboratory values on ICU admission, vital organ support in ICU and hospital mortality. [...]while lymphopenia has been well documented in critically ill patients [3, 4], most studies focused on ICU admission values with little information on kinetics. [...]the median neutropenia duration was 6 days in our patients with a faster recovery in survivors.

The incidence of sepsis has been rising overall but updated data in cancer patients are lacking. After a cancer diagnosis, incidence of sepsis and overall mortality peak within the first year. However, how much sepsis contributes to mortality remains unclear. We used a multistate model approach to analyze the incidence, risk factors and associated mortality of sepsis within 1 year of cancer diagnosis in middle aged adults. Analysis of a large US health insurance claims database (Marketscan) between 2005 and 2014. Patients with a new diagnosis of cancer who received chemotherapy were included. Within a year of diagnosis, we assessed inpatient admissions for sepsis based on ICD-9 codes and survival using hospitalizations, outpatient visits and prescriptions filled. Competing risk and multistate models were used to assess the incidence of sepsis and transition probabilities between cancer, sepsis and death. 119,379 patients (38.9% males), aged 55 (50-60) years, were included; 2,560 developed isolated sepsis, 477 severe sepsis and 1331 septic shock within 1 year, with associated hospital mortality of 14.8%, 30% and 46% respectively. The probability of sepsis increased between 2005 and 2014; at 1 year, its cumulative incidence was 3.7% with a probability of mortality after sepsis of 35.5% (95% CI 21.6%-50.9%). Age, male gender, Charlson comorbidity index, hematological malignancies and metastases at diagnosis were associated with sepsis and mortality. Incidence and mortality of sepsis were 3.7% and 35.5% at 1 year after cancer diagnosis and were both associated with baseline patient and cancer characteristics.

Thrombotic thrombocytopenic purpura (TTP) is a diagnostic and therapeutic emergency. Therapeutic plasma exchange (TPE) combined with immunosuppression has been the cornerstone of the initial management. To produce optimal benefits, emerging treatments must be used against a background of best standard of care. Clarifying current uncertainties is therefore crucial. The objective of this study was to analyze a large high-quality database (Marketscan) of TTP patients managed between 2005 and 2014, in the pre-caplacizumab era, in order to assess the impact of time to first TPE and use of first-line rituximab on mortality, and whether mortality declines over time. Among the 1096 included patients (median age 46 [IQR 35-55], 70% female), 28.8% received TPE before day 2 in the ICU. Hospital mortality was 7.6% (83 deaths). Mortality was independently associated with older age (hazard ratio [HR], 1.024/year; 95% confidence interval [95%CI], [1.009-1.040]), diagnosis of sepsis (HR, 2.360; 95%CI [1.552-3.588]), and the need for mechanical ventilation (HR, 4.103; 95%CI, [2.749-6.126]). Factors independently associated with lower mortality were TPE at ICU admission (HR, 0.284; 95%CI, [0.112-0.717]), TPE within one day after ICU admission (HR, 0.449; 95%CI, [0.275-0.907]), and early rituximab therapy (HR, 0.229; 95% CI, [0.111-0.471]). Delayed TPE was associated with significantly higher costs. Immediate TPE and early rituximab are associated with improved survival in TTP patients. Improved treatments have led to a decline in mortality over time, and alternate outcome variables such as the use of hospital resources or longer term outcomes therefore need to be considered.

Patients with hematological malignancies (HM) often require ICU admission, and acute respiratory or renal failure are then independent risk factors for mortality. Data are scarce on acute liver dysfunction (ALD), despite HM patients cumulating risk factors. The objective of this retrospective cohort study was to assess the prevalence of ALD in critically ill HM patients and its impact on outcome. Data of all patients with HM admitted to the medical ICU between 2008 and 2018 were extracted from electronic medical records. ALD was defined by ALT > 165 U/L, AST > 230 U/L, or total bilirubin > 4 mg/dL. Univariate and multivariate logistic regressions were used to analyze hospital mortality. Charts of survivors with ALD were reviewed to assess impact of ALD on subsequent anti-cancer treatment. We included 971 patients (60% male), age 64 (54–72) years, of whom 196 (20%) developed ALD. ALD patients were younger, more frequently had liver cirrhosis or acute leukemia, and had increased severity of illness and vital organ support needs. ALD was associated with hospital mortality in univariate (OR 4.14, 95% CI 2.95–5.80, p < 0.001) and multivariate analysis (OR 1.86, 95% CI 1.07–3.24, p = 0.03). Hospital mortality was 46% in ALD patients; among 106 survivors, a third of patients requiring therapy received it as previously planned, and half of the patients were alive at 1 year. In summary, in a large population of critically ill patients with hematological malignancies, 20% developed ALD, which was an independent risk factor for hospital mortality and occasionally altered further anti-cancer treatment.

Background It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. Methods Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. Results Influenza infection status was categorized into four groups: patients with influenza alone ( n  = 95, 5.8%), patients with influenza plus pulmonary co-infection ( n  = 58, 3.6%), patients with non-influenza pulmonary infection ( n  = 820, 50.9%), and patients without pulmonary infection ( n  = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU ( P  < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality ( P  < 0.001) but not hospital mortality ( P  = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90–1.13, P  = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. Conclusions Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.

Introduction. Diquat is an herbicide that can lead to rapid multiorgan system failure upon toxic ingestion. Although Diquat shares a similar chemical structure with paraquat, diquat is still readily available to the general population, and in contrast to paraquat, it is not regulated. We present a case of an intentional diquat poisoning which emphasizes the necessity of the early recognition due to atypical symptoms within the first 24 hours and certainly enhanced regulatory restrictions on this very toxic compound. Case. A 60-year-old male with a history of severe depression presented to the emergency department after intentional ingestion of a commercial herbicide containing diquat dibromide 2.30%. The earliest manifestations of this acute diquat intoxication comprised a glomerulonephritis and proximal tubular dysfunction. Progressive multiorgan system failure then developed with a significant delay (24–38 hours) including acute renal, liver failure, and then respiratory failure with refractory hypoxemia. Despite maximal supportive care, the end organ failure was lethal. Discussion. Diquat intoxication should be suspected in patient presenting an acute glomerulonephritis with coma. Diquat should undergo the same regulatory restrictions as paraquat-containing compounds.

Background Baroreflex allows to reduce sudden rises or falls of arterial pressure through parallel RR interval fluctuations induced by autonomic nervous system. During spontaneous breathing, the application of positive end-expiratory pressure (PEEP) may affect the autonomic nervous system, as suggested by changes in baroreflex efficiency and RR variability. During mechanical ventilation, some patients have stable cardiorespiratory phase difference and high-frequency amplitude of RR variability (HF-RR amplitude) over time and others do not. Our first hypothesis was that a steady pattern could be associated with reduced baroreflex sensitivity and HF-RR amplitude, reflecting a blunted autonomic nervous function. Our second hypothesis was that PEEP, widely used in critical care patients, could affect their autonomic function, promoting both steady pattern and reduced baroreflex sensitivity. Methods We tested the effect of increasing PEEP from 5 to 10 cm H2O on the breathing variability of arterial pressure and RR intervals, and on the baroreflex. Invasive arterial pressure, ECG and ventilatory flow were recorded in 23 mechanically ventilated patients during 15 minutes for both PEEP levels. HF amplitude of RR and systolic blood pressure (SBP) time series and HF phase differences between RR, SBP and ventilatory signals were continuously computed by complex demodulation. Cross-spectral analysis was used to assess the coherence and gain functions between RR and SBP, yielding baroreflex-sensitivity indices. Results At PEEP 10, the 12 patients with a stable pattern had lower baroreflex gain and HF-RR amplitude of variability than the 11 other patients. Increasing PEEP was generally associated with a decreased baroreflex gain and a greater stability of HF-RR amplitude and cardiorespiratory phase difference. Four patients who exhibited a variable pattern at PEEP 5 became stable at PEEP 10. At PEEP 10, a stable pattern was associated with higher organ failure score and catecholamine dosage. Conclusions During mechanical ventilation, stable HF-RR amplitude and cardiorespiratory phase difference over time reflect a blunted autonomic nervous function which might worsen as PEEP increases.

Therapeutic plasma exchange (TPE) is a therapeutic intervention that separates plasma from blood cells to remove pathological factors or to replenish deficient factors. The use of TPE is increasing over the last decades. However, despite a good theoretical rationale and biological plausibility for TPE as a therapy for numerous diseases or syndromes associated with critical illness, TPE in the intensive care unit (ICU) setting has not been studied extensively. A group of eighteen experts around the globe from different clinical backgrounds used a modified Delphi method to phrase key research questions related to “TPE in the critically ill patient”. These questions focused on: (1) the pathophysiological role of the removal and replacement process, (2) optimal timing of treatment, (3) dosing and treatment regimes, (4) risk–benefit assumptions and (5) novel indications in need of exploration. For all five topics, the current understanding as well as gaps in knowledge and future directions were assessed. The content should stimulate future research in the field and novel clinical applications.