Élie Azoulay

A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.

Background To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis. Methodology/Principal Findings Prospective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1) no AKI, 2) mild AKI (grouping stage 1 and 2 of AKIN score) and 3) severe AKI (stage 3 of AKIN score). Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs) to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF), IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock) were classified from AKIN score as no AKI (nu200a=u200a43), mild AKI (nu200a=u200a74) or severe AKI (nu200a=u200a59). The VDI did not differ between groups of AKI. After adjustment, mild and severe AKI were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], pu200a=u200a0.048 and HR 1.99 95%CI[1.30-3.03], pu200a=u200a0.001 respectively). Severe AKI had higher levels of plasma IL-10, MIF and IL-6 compared to “no AKI” and mild AKI (p<0.05 for each), with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (pu200a=u200a0.004). Conclusions AKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center

Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin‐I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value.

Are platelet transfusions harmful in acquired thrombotic thrombocytopenic purpura at the acute phase? experience of the French thrombotic microangiopathies reference center

enzyme inhibitors or angiotensin receptor blockers highlights the need for close BP monitoring, and dose adjustments in the peri-ASCT setting. A retrospective, non-validated study of 163 patients, without a multivariate analysis, found inferior progression-free survival and overall survival with the use of angiotensinconverting-enzyme inhibitors [7]. Although the current study includes a heterogeneous group of MM patients, there was no significant difference in progression-free survival for those who had early ASCT (more than half of whom were on maintenance therapy), with the use of angiotensin-converting-enyzme inhibitors or angiotensin receptor blockers or in the presence of hypotension. Eighteen patients met criteria for hypotension based on discontinuation of antiHTNs. Perhaps if these medications had not been discontinued, more adverse events would have occurred. The 43% incidence of hypotension associated with high-dose chemotherapy has significant implications for BP monitoring and anti-HTN adjustment, in a patient population that is often fatigued/deconditioned, hypovolemic, febrile, and thrombocytopenic and therefore at a high fall risk without early intervention.

Minimally Invasive Diagnostic Strategy in Immunocompromised Patients with Pulmonary Infiltrates

Acute respiratory failure (ARF) is the main reason for ICU admission in patients with haematological malignancies. High mortality rates of up to 50% are reported in this situation, and mortality is highest when mechanical ventilation is needed. Rapid and accurate diagnostic methods are needed in these vulnerable patients to ensure the prompt initiation of effective treatment. However, the broad array of possible cause of ARF raises diagnostic challenges. In this review, we discuss the DIRECT strategy, which identifies the most plausible diagnosis in each patient based on the type of immune deficiency and clinical presentation. We will focus on non-invasive laboratory tests developed in recent years, discussing their sensitivity and specificity. We also discuss the usefulness in cancer patients with specific organ dysfunctions of biomarkers introduced over the past few years.

Time trends in the reporting of conflicts of interest, funding and affiliation with industry in intensive care research: a systematic review

PurposeConflict of interest (COI) may compromise, or have the appearance of compromising, a researcher’s judgment or integrity in conducting or reporting research. We sought to assess time trends of COI and funding statement reporting in the critical care literature.MethodsPubMed was searched by using Medical Subject Headings and the appropriate corresponding keywords: “INTENSIVE CARE UNIT” or “ICU” as a major topic. Fourxa0years in a 15-year time period (2001–2016) were arbitrarily chosen and one study month was randomly selected for each study period. Studies published during the selected months were included in the analysis.ResultsThree hundred and seventy-four studies were evaluated, including five reviews (1.3%) and ten randomized clinical trials (RCTs) (2.7%). COI statements were available in 65% of the studies and 8% had declared COI. COI statement rate, declared COI and funding statements increased over time, while the number of authors affiliated with industry and the discordance between the lack of COI statement and affiliation with industry decreased. Declared COI were more frequent in 2011–2016 as compared to 2001–2010 (OR 4.06; 95% CI 1.15–25.79) and in the higher quartile of a journal’s impact factor (OR of 16.73; 95% CI 3.28–306.20). Surprisingly, focus of the study, country of the first author and/or endorsement of the study by a trial group were not associated with COI statements.ConclusionOur study suggests COI reporting to have been unintuitive to most investigators and unreliable before ICMJE statements, and that strong incentives are needed to implement adequate reporting of COI.

Hairy Cell Leukemia with Pulmonary Infiltrates

We report a case of acute respiratory failure and cutaneous rash in a 44-year-old woman treated for hairy cell leukemia. She was admitted to the ICU at the time of neutropenia recovery. She was at high risk for infection, most notably with intracellular pathogens (i.e., Legionella, Mycoplasma, Chlamydia, tuberculosis, and invasive fungal infections), but no pathogen was recovered. Her skin rash was a hypersensitivity reaction to cladribine, and her dyspnea was related to cardiogenic pulmonary edema and, possibly, cladribine hypersensitivity. The case of this patient illustrates the diagnostic challenges raised by ICU patients with hematological malignancies. Possible diagnoses in our patient were selective immune deficiency related to hairy cell leukemia, cladribine toxicity, heart failure with pulmonary edema, acute lung injury during neutropenia recovery, and infection. She improved within a few days with diuretic therapy and cladribine discontinuation.

A Rapidly Reversible Cause of Pulmonary Embolism

Lymphoma cell proliferation in the blood vessels of parenchymal organs may result in vessel obstruction and ischaemia. We report the case of a patient who had intravascular lymphoma with predominant pulmonary involvement. A 38-year-old man was referred to the intensive care unit for acute respiratory failure and prolonged fever. Appropriate investigations failed to demonstrate any bacterial, viral, parasitic, or mycobacterial infection. Chest computed tomography ruled out proximal or sub-segmental pulmonary embolism, but the ventilation/perfusion lung scan indicated a high probability of pulmonary embolism. Examination of a skin biopsy established the diagnosis of intravascular lymphoma. Intravascular lymphoma is a rare disease characterised by exclusive or predominant growth of neoplastic cells within the lumina of small blood vessels. Lung involvement is common but rarely at the forefront of the clinical picture. In the case described here, immediate chemotherapy combined with adequate supportive care ensured a full recovery.

ARDS During Neutropenia Recovery

Acute respiratory failure is a major cause of morbidity in cancer patients and the most common organ failure leading to ICU admission in neutropenic patients. In these patients, acute respiratory failure often stems from a combination of factors that may be closely intertwined, such as infection and cardiogenic edema or alveolar hemorrhage. Several lines of evidence point to an association between neutropenia recovery and declining oxygenation with exacerbation of pre-existing pulmonary disease. Overall, the prevalence of acute respiratory failure during neutropenia recovery may be as high as 50% in patients with risk factors. These factors include the occurrence of pneumonia during neutropenia, delayed or prolonged neutropenia, a fast rate of neutrophil recovery, and invasive pulmonary aspergillosis. In addition, several clinical and laboratory findings suggest that granulocyte colony-stimulating factor may exacerbate the clinical manifestations of neutropenia recovery. Here, we review the evidence suggesting that neutropenia recovery may be associated with exacerbation of acute respiratory failure, and we discuss the factors suspected to be associated with respiratory failure during neutropenia recovery.

Managing Critically Ill Cancer Patients: Another Medical Success Story

A few decades have passed since intensive care unit (ICU) beds have been available for critically ill patients with cancer. Although the initial reports showed dismal prognosis, recent data suggest that an increased number of cancer patients benefit from ICU support, with decreased mortality rates. Advances in the management of the underlying malignancies and support of organ dysfunctions have led to survival gains in patients with life-threatening complications from the malignancy itself, as well as infectious and toxic adverse effects related to the oncological treatments. In this review, we will appraise the prognostic factors and discuss the overall perspective related to the management of critically ill patients with cancer. The prognostic significance of certain factors has changed over time. For example, neutropenia or autologous bone marrow transplantation carries less adverse prognostic implication than 2 decades ago. Similarly, because hematologists and oncologists select patients for ICU admission based on the characteristics of the malignancy, the underlying malignancy rarely influences short-term survival after ICU admission. Since the recent data do not clearly support the benefit of ICU support to unselected critically ill allogeneic BMT recipients, more outcome research is needed in this subgroup. Because of the overall increased survival that has been reported in critically ill cancer patients, we outline easy-to-use and evidence-based ICU admission triage criteria that may help avoid depriving life support to cancer patients who can benefit. Lastly, we propose a research agenda to address unanswered questions.