ICU admission for solid cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized the management of cancer. They can induce immune-related adverse events (irAE) leading to intensive care unit (ICU) admission. We aimed to describe irAEs for ICU admissions in solid cancer patients treated with ICIs. METHODS: This prospective multicenter study was conducted in France and Belgium. Adult patients with solid tumor and treated with systemic ICIs within the last 6 months, requiring non-programmed ICU admission were included. Patients admitted for microbiologically documented sepsis were excluded. Imputability of irAEs in ICU admissions was described according to the WHO-UMC classification system at ICU admission and at ICU discharge. The use of immunosuppressant treatment was reported. RESULTS: 115 patients were eligible. Solid tumor was mainly lung cancer (n = 76, 66%) and melanoma (n = 18, 16%). They were mainly treated with an anti-PD-(L)1 alone (n = 110, 96%). Main ICU admission reasons were acute respiratory failure (n = 66, 57%), colitis (n = 14, 13%), and cardiovascular disease (n = 13, 11%). ICU admission was considered "likely" associated with irAE for 48% (n = 55) of patients. Factors independently associated with irAE were a good ECOG performance status (PS) (ECOG-PS of 0 or 1 vs. ECOG-PS of 2-3, odds ratio [OR] = 6.34, 95% confidence interval [95% CI] 2.13-18.90, and OR = 3.66, 95% CI 1.33-10.03, respectively), and a history of irAE (OR = 3.28, 95% CI 1.19-9.01). Steroids were prescribed for 41/55 (75%) patients with ICU admission "likely" related to irAE. Three patients were subsequently treated with immunosuppressants. CONCLUSION: IrAEs accounted for half of ICU admissions in cancer patients receiving ICIs. They could be treated with steroids. Identifying the imputability of irAEs in ICU admissions remains a challenge.

Post-cardiac surgery fungal mediastinitis: clinical features, pathogens and outcome.

OBJECTIVES: The occurrence of mediastinitis after cardiac surgery remains a rare and severe complication associated with poor outcomes. Whereas bacterial mediastinitis have been largely described, little is known about their fungal etiologies. We report incidence, characteristics and outcome of post-cardiac surgery fungal mediastinitis. METHODS: Multicenter retrospective study among 10 intensive care units (ICU) in France and Belgium of proven cases of fungal mediastinitis after cardiac surgery (2009-2019). RESULTS: Among 73,688 cardiac surgery procedures, 40 patients developed fungal mediastinitis. Five were supported with left ventricular assist device and five with veno-arterial extracorporeal membrane oxygenation before initial surgery. Twelve patients received prior heart transplantation. Interval between initial surgery and mediastinitis was 38 [17-61] days. Only half of the patients showed local signs of infection. Septic shock was uncommon at diagnosis (12.5%). Forty-three fungal strains were identified: Candida spp. (34 patients), Trichosporon spp. (5 patients) and Aspergillus spp. (4 patients). Hospital mortality was 58%. Survivors were younger (59 [43-65] vs. 65 [61-73] yo; p = 0.013), had lower body mass index (24 [20-26] vs. 30 [24-32] kg/m2; p = 0.028) and lower Simplified Acute Physiology Score II score at ICU admission (37 [28-40] vs. 54 [34-61]; p = 0.012). CONCLUSION: Fungal mediastinitis is a very rare complication after cardiac surgery, associated with a high mortality rate. This entity should be suspected in patients with a smoldering infectious postoperative course, especially those supported with short- or long-term invasive cardiac support devices, or following heart transplantation.

Distinct Expression Patterns of Interleukin-22 Receptor 1 on Blood Hematopoietic Cells in SARS-CoV-2 Infection.

The new pandemic virus SARS-CoV-2 is characterized by uncontrolled hyper-inflammation in severe cases. As the IL-22/IL-22R1 axis was reported to be involved in inflammation during viral infections, we characterized the expression of IL-22 receptor1, IL-22 and IL-22 binding protein in COVID-19 patients. Blood samples were collected from 19 non-severe and 14 severe patients on the day they presented (D0), at D14, and six months later, and from 6 non-infected controls. The IL-22R1 expression was characterized by flow cytometry. Results were related to HLA-DR expression of myeloid cells, to plasma concentrations of different cytokines and chemokines and NK cells and T lymphocytes functions characterized by their IFN-γ, IL-22, IL-17A, granzyme B and perforin content. The numbers of IL-22R1+ classical, intermediate, and non-classical monocytes and the proportions of IL-22R1+ plasmacytoid DC (pDC), myeloid DC1 and DC2 (mDC1, mDC2) were higher in patients than controls at D0. The proportions of IL-22R1+ classical and intermediate monocytes, and pDC and mDC2 remained high for six months. High proportions of IL-22R1+ non-classical monocytes and mDC2 displayed HLA-DRhigh expression and were thus activated. Multivariate analysis for all IL-22R1+ myeloid cells discriminated the severity of the disease (AUC=0.9023). However, correlation analysis between IL-22R1+ cell subsets and plasma chemokine concentrations suggested pro-inflammatory effects of some subsets and protective effects of others. The numbers of IL-22R1+ classical monocytes and pDC were positively correlated with pro-inflammatory chemokines MCP-1 and IP-10 in severe infections, whereas IL-22R1+ intermediate monocytes were negatively correlated with IL-6, IFN-α and CRP in non-severe infections. Moreover, in the absence of in vitro stimulation, NK and CD4+ T cells produced IFN-γ and IL-22, and CD4+ and CD8+ T cells produced IL-17A. CD4+ T lymphocytes also expressed IL-22R1, the density of its expression defining two different functional subsets. In conclusion, we provide the first evidence that SARS-CoV-2 infection is characterized by an abnormal expression of IL22R1 on blood myeloid cells and CD4+ T lymphocytes. Our results suggest that the involvement of the IL-22R1/IL-22 axis could be protective at the beginning of SARS-CoV-2 infection but could shift to a detrimental response over time.

Static compliance of the respiratory system in COVID-19 related ARDS: an international multicenter study.

BACKGROUND: Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14. METHODS: In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation. RESULTS: The mean Crs in 372 patients was 37.6 ± 13 mL/cmH2O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO2/FiO2 ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98-1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13-3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88-0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH2O vs 37.8 ± 11.4 mL/cmH2O, p < 0.001). The decrease in Crs was not associated with day-28 outcome. CONCLUSION: In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH2O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.

Frequency, risk factors, and outcomes of non-occlusive mesenteric ischaemia after cardiac arrest.

PURPOSE: Mesenteric ischaemia after successfully resuscitated cardiac arrest (CA) has been insufficiently studied. We aimed to assess the frequency, risk factors, and outcomes of non-occlusive mesenteric ischaemia (NOMI) after CA. METHODS: We retrospectively included patients admitted to a CA centre with sustained return of spontaneous circulation between 2007 and 2017. NOMI was suspected based on clinical symptoms and classified as possible if no tests were feasible or the only test was a negative abdominal computed tomography (CT) scan and as confirmed if diagnosed by endoscopy, CT, or surgery. RESULTS: Of 1343 patients, 82 (6%) had suspected NOMI, including 33 (2.5%) with confirmed NOMI. Investigations for suspected NOMI were done in 47/82 (57%) patients (CT, n = 30; lower digestive endoscopy, n = 14; and upper digestive endoscopy, n = 12); 11 patients underwent surgery. By multivariate analysis, factors associated with suspected NOMI were female sex (OR, 1.8; 95%CI, 1.1-2.9, p = 0.02), cardiovascular comorbidities (OR, 1.6; 95%CI, 1.0-2.7; p = 0.047), admission lactate >5 mmol/L (OR, 2.0; 95%CI, 1.2-3.4; p = 0.01), low flow >17 min (OR, 2.2; 95%CI, 1.3-3.8; p = 0.003), and inotropic score >7 µg/kg/min (OR, 1.8; 95%CI, 1.1-3.2; p = 0.03). ICU mortality was 96% (79/82), with 61% of patients dying from multi-organ failure (MOF) and 35% from post-anoxic brain injury. Of the eight patients who regained consciousness, 5 finally died from MOF, leaving 3 patients discharged alive from the ICU with a good neurologic outcome. CONCLUSIONS: NOMI may affect 2.5-6% of patients after CA. Mortality was extremely high in patients, and very few survived with a good neurological outcome.

Factors Associated With Pulmonary Embolism Among Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: A Multicenter Study Among 375 Patients.

Risk factors associated with pulmonary embolism in coronavirus disease 2019 acute respiratory distress syndrome patients deserve to be better known. We therefore performed a post hoc analysis from the COronaVirus-Associated DIsease Study (COVADIS) project, a multicenter observational study gathering 21 ICUs from France (n = 12) and Belgium (n = 9). Three-hundred seventy-five consecutive patients with moderate-to-severe acute respiratory distress syndrome and positive coronavirus disease 2019 were included in the study. At day 28, 15% were diagnosed with pulmonary embolism. Known risk factors for pulmonary embolism including cancer, obesity, diabetes, hypertension, and coronary artery disease were not associated with pulmonary embolism. In the multivariate analysis, younger age (< 65 yr) (odds ratio, 2.14; 1.17-4.03), time between onset of symptoms and antiviral administration greater than or equal to 7 days (odds ratio, 2.39; 1.27-4.73), and use of neuromuscular blockers greater than or equal to 7 days (odds ratio, 1.89; 1.05-3.43) were independently associated with pulmonary embolism. These new findings reinforce the need for prospective studies that will determine the predictors of pulmonary embolism among patients with severe coronavirus disease 2019.

Meningococcaemia causing necrotizing cellulitis associated with acquired complement deficiency after gastric bypass surgery: a case report.

BACKGROUND: Neisseria meningitidis has rarely been described as an agent of necrotic soft tissue infection. CASE PRESENTATION: We report a case of a septic shock with necrotizing cellulitis due to Neisseria meningitidis serogroup W, treated by urgent extensive surgical debridement followed by skin grafts. The invasive meningococcal disease occurred together with a complement deficiency, possibly acquired after bypass surgery that took place 1 year before. CONCLUSIONS: Necrotic tissue infections should be considered part of the invasive meningococcal diseases spectrum and should prompt clinicians to look for complement deficiencies. Gastric bypass surgery associated malnutrition may be implicated but further verification is needed.

Non-occlusive Mesenteric Ischemia as a Fatal Complication in Acute Pancreatitis: A Case Series.

BACKGROUND: Vascular complications of severe acute pancreatitis are well known and largely described unlike non-occlusive mesenteric ischemia, which is a rare and potentially fatal complication. Non-occlusive mesenteric ischemia is an acute mesenteric ischemia without thrombotic occlusion of blood vessels, poorly described as a complication of acute pancreatitis. METHODS: We retrospectively reviewed a prospectively maintained registry of all pancreatic diseases referred to our center from 2013 to 2018, in order to determine the causes of early death. We identified three patients who died within 48 h after hospital admission from severe acute pancreatitis complicated by irreversible non-occlusive mesenteric ischemia. Their clinical presentation, management, and outcomes were herein reported. RESULTS: Three consecutive patients with severe acute pancreatitis developed non-occlusive mesenteric ischemia within the first 5 days after onset of symptoms and died 48 h after non-occlusive mesenteric ischemia diagnosis despite optimal intensive care management and surgery, giving a prevalence of 3/609 (0.5%). Symptoms were unspecific with consequently potential delayed diagnosis and management. High doses of norepinephrine required for hemodynamic support (n = 3) potentially leading to splanchnic vessels vasoconstriction, transient hypotension (n = 3), and previous severe ischemic cardiomyopathy (n = 1) could be involved as precipitating factors of non-occlusive mesenteric ischemia. CONCLUSION: Non-occlusive mesenteric ischemia can be a fatal complication of acute pancreatitis but is also challenging to diagnose. Priority is to reestablish a splanchno-mesenteric perfusion flow. Surgery should be offered in case of treatment failure or deterioration but is still under debate in early stage, to interrupt the vicious circle of intestinal hypoperfusion and ischemia.

Individualized antibiotic therapy in the treatment of severe infections.

Introduction: Sepsis is a frequent and life-threatening clinical entity and antibiotic treatment is one of the most important interventions, together with source control and hemodynamic resuscitation. Guidelines have highlighted the importance of an early (i.e. within 1-3 h from recognition) and appropriate (i.e. the pathogen is sensitive in vitro to the administered drug) antimicrobial therapy in this setting.Areas covered: Antibiotic therapy should be individualized according to several issues, including early pathogen identification, optimal drug regimens based on pharmacokinetic/pharmacodynamics (PK/PD) and adequate duration using both clinical and biological biomarkers. This narrative review has considered the most relevant studies evaluating these issues.Expert opinion: Rapid identification pathogen resistance profile (i.e. the minimal inhibitory concentration for the available antimicrobials), real-time measurement of drug concentrations with regimen adjustment on MIC and daily measurement of procalcitonin to guide duration of therapy are the main issues to individualize the antibiotic management in critically ill patients.

False-positive galactomannan assay in broncho-alveolar lavage after enteral nutrition solution inhalation: a case report.

Introduction. Diagnosis of invasive aspergillosis is challenging and the gold standard for definite diagnosis remains histopathological tissue examination. However, invasive procedures such as lung biopsy are often not feasible in critically ill patients. The detection of fungal cell wall components like Aspergillus galactomannan in broncho-alveolar lavage remains a key component of the diagnostic procedure. False-positive of the Aspergillus galactomannan assay is not frequent. Case presentation. We report a case of positive galactomannan in broncho-alveolar lavage fluid after enteral nutrition aspiration without signs of invasive aspergillosis. Galactomannan was positive in the enteral nutrition solution. Conclusion. Physicians should be aware of this previously unrecognized cause of false-positive galactomannan in broncho-alveolar fluid which can result in unnecessary treatments.

Pheochromocytoma Crisis in the ICU: A French Multicenter Cohort Study With Emphasis on Rescue Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe the characteristics, management, and outcome of patients admitted to ICUs for pheochromocytoma crisis. DESIGN: A 16-year multicenter retrospective study. SETTING: Fifteen university and nonuniversity ICUs in France. PATIENTS: Patients admitted in ICU for pheochromocytoma crisis. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 34 patients with a median age of 46 years (40-54 yr); 65% were males. At admission, the median Sequential Organ Failure Assessment score was 8 (4-12) and median Simplified Acute Physiology Score II 49.5 (27-70). The left ventricular ejection fraction was consistently decreased with a median value of 30% (15-40%). Mechanical ventilation was required in 23 patients, mainly because of congestive heart failure. Vasoactive drugs were used in 23 patients (68%) and renal replacement therapy in eight patients (24%). Extracorporeal membrane oxygenation was used as a rescue therapy in 14 patients (41%). Pheochromocytoma was diagnosed by CT in 33 of 34 patients. When assayed, urinary metanephrine and catecholamine levels were consistently elevated. Five patients underwent urgent surgery, including two during extracorporeal membrane oxygenation. Overall ICU mortality was 24% (8/34), and overall 90-day mortality was 27% (9/34). Crude 90-day mortality was not significantly different between patients managed with versus without extracorporeal membrane oxygenation (22% vs 30%) (p = 0.7) despite higher severity scores at admission in the extracorporeal membrane oxygenation group. CONCLUSIONS: Mortality is high in pheochromocytoma crisis. Routinely considering this diagnosis and performing abdominal CT in patients with unexplained cardiogenic shock may allow an earlier diagnosis. Extracorporeal membrane oxygenation and adrenalectomy should be considered as a therapeutic in most severe cases.

Targeted temperature management after intraoperative cardiac arrest: a multicenter retrospective study.

PURPOSE: Few outcome data are available about temperature management after intraoperative cardiac arrest (IOCA). We describe targeted temperature management (TTM) (32-34 °C) modalities, adverse events, and association with 1-year functional outcome in patients with IOCA. METHODS: Patients admitted to 11 ICUs after IOCA in 2008-2013 were studied retrospectively. The main outcome measure was 1-year functional outcome. RESULTS: Of the 101 patients [35 women and 66 men; median age, 62 years (interquartile range, 42-72)], 68 (67.3%) were ASA PS I to III and 57 (56.4%) had emergent surgery. First recorded rhythms were asystole in 44 (43.6%) patients, pulseless electrical activity in 36 (35.6%), and ventricular fibrillation/tachycardia in 20 (19.8%). Median times from collapse to cardiopulmonary resuscitation and return of spontaneous circulation (ROSC) were 0 min (0-0) and 10 min (4-20), respectively. The 30 (29.7%) patients who received TTM had an increased risk of infection (P = 0.005) but not of arrhythmia, bleeding, or metabolic/electrolyte disorders. By multivariate analysis, one or more defibrillation before ROSC was positively associated with a favorable functional outcome at 1-year (OR 3.06, 95% CI 1.05-8.95, P = 0.04) and emergency surgery was negatively associated with 1-year favorable functional outcome (OR 0.36; 95% CI 0.14-0.95, P = 0.038). TTM use was not independently associated with 1-year favorable outcome (OR 0.82; 95% CI 0.27-2.46, P = 0.72). CONCLUSIONS: TTM was used in less than one-third of patients after IOCA. TTM was associated with infection but not with bleeding or coronary events in this setting. TTM did not independently predict 1-year favorable functional outcome after IOCA in this study.

Septic shock with no diagnosis at 24 hours: a pragmatic multicenter prospective cohort study.

BACKGROUND: The lack of a patent source of infection after 24 hours of management of shock considered septic is a common and disturbing scenario. We aimed to determine the prevalence and the causes of shock with no diagnosis 24 hours after its onset, and to compare the outcomes of patients with early-confirmed septic shock to those of others. METHODS: We conducted a pragmatic, prospective, multicenter observational cohort study in ten intensive care units (ICU) in France. We included all consecutive patients admitted to the ICU with suspected septic shock defined by clinical suspicion of infection leading to antibiotic prescription plus acute circulatory failure requiring vasopressor support. RESULTS: A total of 508 patients were admitted with suspected septic shock. Among them, 374 (74 %) had early-confirmed septic shock, while the 134 others (26 %) had no source of infection identified nor microbiological documentation retrieved 24 hours after shock onset. Among these, 37/134 (28 %) had late-confirmed septic shock diagnosed after 24 hours, 59/134 (44 %) had a condition mimicking septic (septic shock mimicker, mainly related to adverse drug reactions, acute mesenteric ischemia and malignancies) and 38/134 (28 %) had shock of unknown origin by the end of the ICU stay. There were no differences between patients with early-confirmed septic shock and the remainder in ICU mortality and the median duration of ICU stay, of tracheal intubation and of vasopressor support. The multivariable Cox model showed that the risk of day-60 mortality did not differ between patients with or without early-confirmed septic shock. A sensitivity analysis was performed in the subgroup (n = 369/508) of patients meeting the Sepsis-3 definition criteria and displayed consistent results. CONCLUSIONS: One quarter of the patients admitted in the ICU with suspected septic shock had no infection identified 24 hours after its onset and almost half of them were eventually diagnosed with a septic shock mimicker. Outcome did not differ between patients with early-confirmed septic shock and other patients.

Putting scales into evolutionary time: the divergence of major scale insect lineages (Hemiptera) predates the radiation of modern angiosperm hosts.

The radiation of flowering plants in the mid-Cretaceous transformed landscapes and is widely believed to have fuelled the radiations of major groups of phytophagous insects. An excellent group to test this assertion is the scale insects (Coccomorpha: Hemiptera), with some 8,000 described Recent species and probably the most diverse fossil record of any phytophagous insect group preserved in amber. We used here a total-evidence approach (by tip-dating) employing 174 morphological characters of 73 Recent and 43 fossil taxa (48 families) and DNA sequences of three gene regions, to obtain divergence time estimates and compare the chronology of the most diverse lineage of scale insects, the neococcoid families, with the timing of the main angiosperm radiation. An estimated origin of the Coccomorpha occurred at the beginning of the Triassic, about 245 Ma [228-273], and of the neococcoids 60 million years later [210-165 Ma]. A total-evidence approach allows the integration of extinct scale insects into a phylogenetic framework, resulting in slightly younger median estimates than analyses using Recent taxa, calibrated with fossil ages only. From these estimates, we hypothesise that most major lineages of coccoids shifted from gymnosperms onto angiosperms when the latter became diverse and abundant in the mid- to Late Cretaceous.

Adaptive Radiation in Socially Advanced Stem-Group Ants from the Cretaceous.

Across terrestrial ecosystems, modern ants are ubiquitous. As many as 94 out of every 100 individual arthropods in rainforests are ants, and they constitute up to 15% of animal biomass in the Amazon. Moreover, ants are pervasive agents of natural selection as over 10,000 arthropod species are specialized inquilines or myrmecomorphs living among ants or defending themselves through mimicry. Such impact is traditionally explained by sociality: ants are the first major group of ground-dwelling predatory insects to become eusocial, increasing efficiency of tasks and establishing competitive superiority over solitary species. A wealth of specimens from rich deposits of 99 million-year-old Burmese amber resolves ambiguity regarding sociality and diversity in the earliest ants. The stem-group genus Gerontoformica maintained distinct reproductive castes including morphotypes unknown in solitary aculeate (stinging) wasps, providing insight into early behavior. We present rare aggregations of workers, indicating group recruitment as well as an instance of interspecific combat; such aggression is a social feature of modern ants. Two species and an unusual new genus are described, further expanding the remarkable diversity of early ants. Stem-group ants are recovered as a paraphyletic assemblage at the base of modern lineages varying greatly in size, form, and mouthpart structure, interpreted here as an adaptive radiation. Though Cretaceous stem-group ants were eusocial and adaptively diverse, we hypothesize that their extinction resulted from the rise of competitively superior crown-group taxa that today form massive colonies, consistent with Wilson and Hölldobler's concept of "dynastic succession."

Timing and causes of death in septic shock.

BACKGROUND: Most studies about septic shock report a crude mortality rate that neither distinguishes between early and late deaths nor addresses the direct causes of death. We herein aimed to determine the modalities of death in septic shock. METHODS: This was a 6-year (2008-2013) monocenter retrospective study. All consecutive patients diagnosed for septic shock within the first 48 h of intensive care unit (ICU) admission were included. Early and late deaths were defined as occurring within or after 3 days following ICU admission, respectively. The main cause of death in the ICU was determined from medical files. A multinomial logistic regression analysis using the status alive as the reference category was performed to identify the prognostic factors associated with early and late deaths. RESULTS: Five hundred forty-three patients were included, with a mean age of 66 ± 15 years and a high proportion (67 %) of comorbidities. The in-ICU and in-hospital mortality rates were 37.2 and 45 %, respectively. Deaths occurred early for 78 (32 %) and later on for 166 (68 %) patients in the ICU (n = 124) or in the hospital (n = 42). Early deaths were mainly attributable to intractable multiple organ failure related to the primary infection (82 %) and to mesenteric ischemia (6.4 %). In-ICU late deaths were directly related to end-of-life decisions in 29 % of patients and otherwise mostly related to ICU-acquired complications, including nosocomial infections (20.4 %) and mesenteric ischemia (16.6 %). Independent determinants of early death were age, malignancy, diabetes mellitus, no pathogen identification, and initial severity. Among 3-day survivors, independent risk factors for late death were age, cirrhosis, no pathogen identification, and previous corticosteroid treatment. CONCLUSIONS: Our study provides a comprehensive assessment of septic shock-related deaths. Identification of risk factors of early and late deaths may determine differential prognostic patterns.

Predictors of functional outcome after intraoperative cardiac arrest.

BACKGROUND: Few outcome data are available about intraoperative cardiac arrest (IOCA). The authors studied 90-day functional outcomes and their determinants in patients admitted to the intensive care unit after IOCA. METHODS: Patients admitted to 11 intensive care units in a period of 2000-2013 were studied retrospectively. The main outcome measure was a day-90 Cerebral Performance Category score of 1 or 2. RESULTS: Of the 140 patients (61 women and 79 men; median age, 60 yr [interquartile range, 46 to 70]), 131 patients (93.6%) had general anesthesia, 80 patients (57.1%) had emergent surgery, and 73 patients (52.1%) had IOCA during surgery. First recorded rhythms were asystole in 73 patients (52.1%), pulseless electrical activity in 44 patients (31.4%), and ventricular fibrillation/ventricular tachycardia in 23 patients (16.4%). Median times from collapse to cardiopulmonary resuscitation and return of spontaneous circulation were 0 min (0 to 0) and 10 min (5 to 20), respectively. Postcardiac arrest shock was identified in 114 patients (81.4%). Main causes of IOCA were preoperative complications (n = 46, 32.9%), complications of anesthesia (n = 39, 27.9%), and complications of surgical procedures (n = 36, 25.7%). On day 90, 63 patients (45.3%) were alive with Cerebral Performance Category score 1/2. Independent predictors of day-90 Cerebral Performance Category score 1/2 were day-1 Logistic Organ Dysfunction score (odds ratio, 0.78 per point; 95% CI, 0.71 to 0.87; P = 0.0001), ventricular fibrillation/tachycardia as first recorded rhythm (odds ratio, 4.78; 95% CI, 1.38 to 16.53; P = 0.013), and no epinephrine therapy during postcardiac arrest syndrome (odds ratio, 3.14; 95% CI, 1.29 to 7.65; P = 0.012). CONCLUSIONS: By day 90, 45% of IOCA survivors had good functional outcomes. The main outcome predictors were directly related to IOCA occurrence and postcardiac arrest syndrome; they suggest that the intensive care unit management of postcardiac arrest syndrome may be amenable to improvement.

Antiplatelet antibodies detected by the MAIPA assay in newly diagnosed immune thrombocytopenia are associated with chronic outcome and higher risk of bleeding.

Immune thrombocytopenia (ITP) results in part from the presence of platelet antibodies, which can be demonstrated by the Monoclonal Antibody-Specific Immobilization of Platelet Antigens (MAIPA) assay. The aim of our study was to correlate the presence of antiplatelet autoantibodies and the natural history of ITP. We performed a retrospective, single-center study of 108 adults with newly diagnosed ITP who had indirect MAIPA assay performed at disease onset. Chronic ITP was defined by the presence of thrombocytopenia after 1 year. Bleeding diathesis was evaluated with a bleeding score. At baseline, patients with a positive indirect MAIPA have a greater bleeding score than patients with negative MAIPA assay [median (interquartile) = 8 (6-12) vs 2 (0-6), p = 0.002]. Patients with a positive indirect MAIPA also had a higher rate of chronic ITP (92.9 vs 68.7 %, p = 0.06). In multivariate analysis, a positive indirect MAIPA result and a platelet count at onset ≥10 × 10(9)/L remained independently associated with chronic ITP [adjusted OR (aOR) = 8.01; 95 % confidence interval (CI), 0.98-66.6; p = 0.05 and aOR = 3.09; 95 % CI, 1.18-8.10; p = 0.02, respectively]. Furthermore, when we analyzed together the results of direct (n = 41) and indirect MAIPA, the same results were observed. Thus, indirect MAIPA positivity at disease onset is associated with more severe hemorrhage and predicts a chronic course in adult ITP patients. MAIPA assay could be useful in the management of ITP patients when it is performed at diagnosis.

Toll-like receptor 2 deficiency increases resistance to Pseudomonas aeruginosa pneumonia in the setting of sepsis-induced immune dysfunction.

BACKGROUND: Sepsis is characterized by a dysregulated inflammatory response followed by immunosuppression that favors the development of secondary infections. Toll-like receptors (TLRs) are major regulators of the host's response to infections. How variability in TLR signaling may impact the development of sepsis-induced immune dysfunction has not been established. We sought to establish the role of TLR2, TLR4, and TLR5 in postseptic mice with Pseudomonas aeruginosa pneumonia. METHODS: We used an experimental model of sublethal polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wild-type, tlr2(-/-), tlr4(-/-), tlr5(-/-), tlr2 4(-/-) mice that underwent CLP were secondarily subjected to P. aeruginosa pulmonary infection. RESULTS: Postseptic wild-type and tlr4(-/-) and tlr5(-/-) mice displayed high susceptibility to P. aeruginosa pneumonia. In contrast, TLR2-deficient mice, either tlr2(-/-)or tlr2 4(-/-), that underwent CLP were resistant to the secondary pulmonary infection. As compared to wild-type mice, tlr2(-/-) mice displayed improvement in bacterial clearance, decreased bacteremic dissemination, and attenuated lung damage. Furthermore, tlr2(-/-) mice exhibited a pulmonary proinflammatory cytokine balance, with increased production of tumor necrosis factor α and decreased release of interleukin 10. CONCLUSIONS: In a model of secondary P. aeruginosa pneumonia in postseptic mice, TLR2 deficiency improves survival by promoting efficient bacterial clearance and restoring a proinflammatory cytokine balance in the lung.