Intensive care medicine (ICM) has the particularity of being a multidisciplinary specialty and its literature reflects this multidisciplinarity. However, the proportion of each field in this ...literature and its trend dynamics are not known. The objective of this study was to analyze the ICM literature, extract latent topics and search for the presence of research trends.
Abstracts of original articles from the top ICM journals, from their inception until December 31st, 2019, were included. This corpus was fed into a structural topic modeling algorithm to extract latent semantic topics. The temporal distribution was then analyzed and the presence of trends was searched by Mann-Kendall trends tests.
Finally, 49,276 articles from 10 journals were included. After topic modeling analysis and experts' feedback, 124 research topics were selected and labeled. Topics were categorized into 19 categories, the most represented being respiratory, fundamental and neurological research. Increasing trends were observed for research on mechanical ventilation and decreasing trends for cardiopulmonary resuscitation.
This study reviewed all articles from major ICM journals in a comprehensive way. It provides a better understanding of ICM research landscape by analyzing the temporal evolution of latent research topics in the ICM literature.
•Research in intensive care is multidisciplinary and covers a wide range of topics.•Topic modeling, a machine learning algorithm, allows the extraction of latent research topics from published articles.•Respiratory topics represent an important part of intensive care research and has an increasing trend.•Resuscitation research has a declining publication trend.
Secondary hemolytic uremic syndrome (HUS) is a heterogeneous group of thrombotic microangiopathies associated with various underlying conditions. Whether it belongs to the spectrum of ...complement-mediated HUS remains controversial. We analysed the presentation, outcome, and frequency of complement gene rare variants in a cohort of 110 patients with secondary HUS attributed to drugs (29%), autoimmune diseases (24%), infections (17%), malignancies (10%), glomerulopathies (9%), extra-renal organ transplantation (8%), and pancreatitis (3%). The frequency of complement gene rare variants was similar in patients with secondary HUS (5%) and in healthy individuals (6% and 8% in French and European controls, respectively). At diagnosis, 40% of patients required dialysis and 18% had neurological manifestations. Fifty percent of patients received plasmatherapy and 35% were treated with eculizumab. Haematological and complete renal remission was achieved in 80% and 24% of patients, respectively. Thirty-nine percent of patients progressed to chronic kidney disease (stages 3-4) and an additional 37% reached end-stage renal disease. Eleven percent of patients died, most often from complications of the underlying cause of HUS. Only one patient experienced an HUS relapse. Patients treated with eculizumab presented with more severe HUS and were more likely to require dialysis at the time of diagnosis as compared to patients not treated with eculizumab. Rates of hematological remission, chronic kidney disease (stages 3-4), and end-stage renal disease were similar in the two groups. Secondary HUS is an acute nonrelapsing form of HUS, not related to complement dysregulation. The efficacy of eculizumab in this setting is not yet established.
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Increasing numbers of studies in chronic diseases have been published showing the relationship between body composition (BC) parameters (i.e. skeletal muscle mass (SMM) and adipose tissue (AT)) and ...outcomes. For patients admitted to intensive care unit (ICU), BC parameters have rarely been described as a prognostic marker of outcome. The primary objective was to evaluate the relationship between body composition at ICU admission and major clinical outcomes. Secondary objectives were to assess the relationship between BC parameters and other parameters (systemic inflammatory markers, Sequential Organ Failure Assessment (SOFA) score, albumin level) at ICU admission, and between BC alterations during ICU stay and outcomes.
This retrospective study enrolled 25 adult patients who had two abdominal CT scans for clinical indication: first, within 48 hours of ICU admission (initial assessment), and second, 7 to 14 days later (late assessment). Skeletal Muscle radiodensity (SMD), cross-sectional area of SMM, Visceral Adipose Tissue (VAT) and Subcutaneous Adipose Tissue (SAT) were measured at the third lumbar vertebra. Cox regression analysis was used to determine the association between these parameters and mortality.
Patients' mean age was 64.6 years. Their mean BMI was 27.7 kg/m2 (SD = 6.0). ICU mortality was 36%. There was no correlation between BC parameters at initial assessment and ICU outcomes. We observed a negative correlation between SMM index and SOFA score at initial assessment (r = -0.458, p = 0.037). There was a significant loss of VAT between two CT assessments which was associated with mortality (-22.34cm2 / m2 in non-survivors versus -6.22 cm2 / m2 in survivors, p = 0.039). Loss of SMD was greater with the occurrence of an infection than without (Delta SMD = -5.642 vs +1.957, p = 0.04).
Our results show alterations in body composition during ICU stay with a loss of muscle quality (decreased SMD) and adipose tissue. These findings require confirmation in future studies but already show that BC assessments at ICU admission and BC alterations during ICU stay are important factors for outcome in critically ill patients.
Thrombotic microangiopathy is a well-described complication of cancer treatment. Its incidence has increased these last decades, as a result of a better awareness of this complication in cancer ...patients in one hand, but also of a larger array of therapeutic compounds including anti-vascular endothelium growth factor (VEGF) drugs. It is therefore mandatory to recognize these conditions since they have a significant impact in thrombotic microangiopathies management and prognosis. Practitioners should be aware of the more classical antineoplastic agents associated with thrombotic microangiopathies, the mechanisms by which they induce them, and the resulting management and prognosis. Since malignancy itself can induce thrombotic microangiopathies, it is also mandatory to know how to distinguish rapidly those caused by antineoplastic agents from those associated with cancer, for an adapted management. Thrombotic microangiopathies associated with chemotherapy remain of dismal prognosis. A better understanding of pathophysiology in these forms of thrombotic microangiopathies, in association with a more empirical approach through the use of new therapeutic agents that can also help in the understanding on new mechanisms a posteriori, should improve their prognosis. The preliminary encouraging results reported with complement blockers in this field could represent a convincing example.
The patient's brother had died at the same age, from pulmonary veno-occlusive disease associated with hypertrophic cardiomyopathy. 1 year previously he had been diagnosed with end-stage kidney ...disease of unknown origin; he had had no history of cognitive impairment. The most frequent and severe presentation occurs in neonates.1,2 Pulmonary artery hypertension (PAH) and renal TMA have been described in early-onset cblC deficiency, whereas isolated neuropsychiatric symptoms prevail in adult-onset forms.1,2 A case of adult-onset renal TMA had similar renal outcomes to our patient.3 The family history and coexistence of a specific glomerulopathy in our patient suggest that PAH, renal TMA, and the glomerular lesions are consequences of the variants in MMACHC.
We describe what we believe to be the first two cases of patients who received an allograft in intensive care unit (ICU) despite severe septic shock with multi-organ failure (MOF).
One patient had ...aggressive large B-cell lymphoma. After allograft, the patient initially improved after withdrawing norepinephrine and renal replacement therapy but he subsequently died thirty-two days later because of a new relapse of the disease. The second patient had acute myeloid leukemia type 1 with a need for an allograft after a first complete remission. She was discharged from ICU at D23 after allograft and still alive 7 months later with complete remission. For the two patients, allograft conditioning was performed before admission to our ICU. These two cases highlight one major problem in such situations which is to find the best time to perform the allograft, particularly in ventilated patients with septic shock and MOF. We performed the allograft when we thought that the risk-benefit ratio was in favor of restoring immunity.
Allograft should be considered as a rescue therapy in ICU for patients with aplasia, during septic shock with multi-organ failure, however close multidisciplinary discussion is required between intensivists and onco-hematologists.
Thrombocytopenia is a common, multifactorial, finding in ICU. Hemophagocytosis is one of the main explanatory mechanisms, possibly integrated into hemophagocytic lymphohistiocytosis syndrome, of ...infectious origin in the majority of cases in ICU. The hemophagocytic lymphohistiocytosis is probably underdiagnosed in the ICU, although it is associated with dramatic outcomes. The main objectives of this work were to identify the frequency of secondary hemophagocytic lymphohistiocytosis, and the main prognostic factors for mortality.
We conducted a retrospective observational study in all adult patients admitted with suspected or diagnosed hemophagocytic lymphohistiocytosis, between January 1, 2000, and August 22, 2012.
A total of 106 patients (42%) had significant hemophagocytosis on bone marrow examination, performed for exploration of thrombocytopenia, bicytopenia, or pancytopenia.
The median age was 56 (45-68) and the median Simplified Acute Physiology Score 2 was 55 (38-68). The main reason for ICU admission was hemodynamic instability (58%), predominantly related to sepsis (45% cases). The main precipitating factor found was a bacterial infection in 81 of 106 patients (76%), including 32 (30%) with Escherichia coli infection. Forty six of 106 patients (43%) died in the ICU. They were significantly older, had higher Simplified Acute Physiology Score 2, plasma lactate deshydrogenase bilirubin, and serum ferritin. The fibrinogen and the percentage of megakaryocytes were significantly lower in nonsurvivors when compared with survivors. In multivariate analysis, only serum ferritin significantly predicted death related to hemophagocytosis. A serum ferritin greater than 2,000 μg/L predicted death with a sensitivity of 71% and a specificity of 76%. A decreased percentage of megakaryocytes also predicted patient death in the ICU.
Hemophagocytosis is common in thrombocytopenic patients with sepsis, frequently included in a postinfectious hemophagocytic lymphohistiocytosis setting. Our study reveals that ferritin could be a reliable prognostic marker in these patients, and hold particular interest in discussing a specific treatment for hemophagocytic lymphohistiocytosis.
Carfilzomib, a new proteasome inhibitor indicated for patients with relapsed/refractory myeloma, has been associated with cases of thrombotic microangiopathy (CFZ-TMA). The role of variants in the ...complement alternative pathway and therapeutic potential of complement blockade with eculizumab remain to be determined.
We report 37 cases of CFZ-TMA recorded in the French reference center for TMA with their clinical characteristics, genetic analysis and outcome according to treatments.
A trigger was identified in more than half of cases, including 8 influenza and 5 SARS-CoV-2 cases. All patients presented with acute kidney injury (AKI) (KDIGO stage 3 in 31 (84%) patients) while neurological (n=13, 36%) and cardiac damage (n=7, 19%) were less frequent. ADAMTS13 and complement activity were normal (n= 28 and 18 patients tested) and no pathogenic variant in the alternative complement pathway was found in 7 patients tested.TMA resolved in most (n=34, 94%) patients but 12 (44%) still displayed stage 3 AKI at discharge. Nineteen (51%) patients were treated with therapeutic plasma exchange, 14 (38%) patients received corticosteroids and 18 (50%) were treated with eculizumab. However none of these treatments demonstrated a significant impact on outcomes.
This study is the largest case series of CFZ-TMA since its approval in 2012. Patients present with severe AKI and experience frequent sequelae. Complement variants and blockade therapy do not seem to play a role in the pathophysiology and prognosis of the disease.
Cancer-related thrombotic microangiopathy (CR-TMA) is a rare entity associated with a dismal prognosis. Usually, CR-TMA is associated with mucin-producing carcinomas among which stomach, breast, ...prostate, lung and pancreas tumours are the most frequent.
We describe for the first time three cases of CR-TMA due to adrenocortical carcinoma (ACC). All of them had mechanical hemolytic anemia and thrombocytopenia without any other identifiable cause. Bicytopenia was diagnosed either simultaneously with ACC or at the time of metastatic evolution. Two patients had acute kidney injury (AKI) with severe pathological findings on kidney biopsy. Despite total adrenalectomy, chemotherapy, and specific treatment of TMA with plasma-exchanges, renal failure and hemolytic anemia remained. The only manifestation of CR-TMA in the third patient was hemolytic anemia, which resolved after surgical removal of ACC. The evolutions in these patients suggests ACC-related TMA may be related to a circulating factor.
CR-TMAs are rare. Here we describe the first case series of ACC-related TMA, among which two had renal involvement. This entity is associated with dismal renal prognosis despite specific treatment of TMA. According to patients' evolution, the persistence of TMA may reflect an uncontrolled malignancy.
Hospital death rates following ICU admission of cirrhotic patients remain high. Identifying patients at high risk of mortality after few days of aggressive management is imperative for providing ...adequate interventions. Herein, we aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) combined with usual organ failure scores in the outcome prediction of cirrhotic patients hospitalized more than 3 days in ICU.
We conducted a retrospective bicentric study in two cohorts of cirrhotic patients hospitalized more than 3 days in French university hospital ICUs. At admission and day 3, we calculated several clinico-biological scores grading liver disease and organ failure severity and calculated the NLR. The primary outcome was 28-day mortality.
The test cohort included 116 patients. At day 28, 43 (37.1%) patients had died. Variations of MELD score (ΔMELD), SOFA score (ΔSOFA), CLIF-SOFA score (ΔCLIF-SOFA) and NLR (ΔNRL) between admission and day 3 were significantly associated with 28-day mortality in univariate analysis. When included in bivariate analysis ΔNLR remained a significant predictor of 28-day mortality independently of these severity scores. Kaplan-Meier curves and statistics using reclassification methods showed a better 28-day mortality risk prediction using ΔNRL in association with ΔSOFA in comparison to ΔSOFA alone. These results were confirmed in an external validation cohort, including 101 critically ill cirrhotic patients.
ΔNLR is an independent predictor of mortality in the critically ill cirrhotic patients' population who requires intensive care supportive treatment and should be used in association with ΔSOFA as a prognostic biomarker.
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