Information on the species causing Candida peritonitis, their in vitro susceptibility, antifungal strategies in this setting and patient outcome is still scarce. AmarCand was a prospective, ...non-interventional study in 271 adult intensive-care unit (ICU) patients with proven invasive Candida infection who received systemic antifungal therapy (France, 2005–2006). Of these ICU patients, 93 (median age 65 years, simplified acute physiology score II 52) had Candida peritonitis, including 73 nosocomial peritonitis, 53 concomitant bacterial peritoneal infections and 26 candidaemias. Candida species were C. albicans (n = 63/108 isolates, 58%), C. glabrata (n = 22, 20%), C. krusei (n = 9), C. kefyr (n = 5), C. parapsilosis (n = 3), C. tropicalis (n = 3), C. ciferii (n = 2) and C. lusitaniae (n = 1). Of tested isolates, 28% were fluconazole-resistant or susceptible dose-dependent (C. albicans 3/32, C. glabrata 9/14, C. krusei 4/4). Empiric antifungal treatment was started 1 day (median) after peritonitis diagnosis, with fluconazole (n = 72 patients), caspofungin (n = 12), voriconazole (n = 3), amphotericin B (n = 2), or a combination (n = 4). Following susceptibility testing, empiric antifungal treatment was judged inadequate in 9/45 (20%) patients and modified in 30 patients (fluconazole was replaced by caspofungin (n = 14) or voriconazole (n = 4)). Mortality in ICU was 38% (35/93) and was not influenced by type of Candida species, fluconazole susceptibility, time to treatment, candidaemia, nosocomial acquisition, or concomitant bacterial infection. No specific factors for death were identified. In summary, a high proportion of fluconazole-resistant or susceptible dose-dependent strains was cultured. These results confirm the high mortality rates of Candida peritonitis and plead for additional investigation in this population. Antifungal treatment for severe cases of Candida peritonitis in ICU patients remains the standard care.
A multicenter, randomized, controlled trial compared early with delayed strategies of renal-replacement therapy in patients with early-stage septic shock who had severe acute kidney injury. There was ...no significant between-group difference in overall mortality at 90 days.
Abstract
Aims
Out-of-hospital cardiac arrest (OHCA) without return of spontaneous circulation (ROSC) despite conventional resuscitation is common and has poor outcomes. Adding extracorporeal membrane ...oxygenation (ECMO) to cardiopulmonary resuscitation (extracorporeal-CPR) is increasingly used in an attempt to improve outcomes.
Methods and results
We analysed a prospective registry of 13 191 OHCAs in the Paris region from May 2011 to January 2018. We compared survival at hospital discharge with and without extracorporeal-CPR and identified factors associated with survival in patients given extracorporeal-CPR. Survival was 8% in 525 patients given extracorporeal-CPR and 9% in 12 666 patients given conventional-CPR (P = 0.91). By adjusted multivariate analysis, extracorporeal-CPR was not associated with hospital survival odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.8–2.1; P = 0.24. By conditional logistic regression with matching on a propensity score (including age, sex, occurrence at home, bystander CPR, initial rhythm, collapse-to-CPR time, duration of resuscitation, and ROSC), similar results were found (OR, 0.8; 95% CI, 0.5–1.3; P = 0.41). In the extracorporeal-CPR group, factors associated with hospital survival were initial shockable rhythm (OR, 3.9; 95% CI, 1.5–10.3; P = 0.005), transient ROSC before ECMO (OR, 2.3; 95% CI, 1.1–4.7; P = 0.03), and prehospital ECMO implantation (OR, 2.9; 95% CI, 1.5–5.9; P = 0.002).
Conclusions
In a population-based registry, 4% of OHCAs were treated with extracorporeal-CPR, which was not associated with increased hospital survival. Early ECMO implantation may improve outcomes. The initial rhythm and ROSC may help select patients for extracorporeal-CPR.
Abstract Aims Gut dysfunction is suspected to play a major role in the pathophysiology of post-resuscitation disease through an increase in intestinal permeability and endotoxin release. However this ...dysfunction often remains occult and is poorly investigated. The aim of this pilot study was to explore intestinal failure biomarkers in post-cardiac arrest patients and to correlate them with endotoxemia. Methods Following resuscitation after cardiac arrest, 21 patients were prospectively studied. Urinary intestinal fatty acid-binding protein (IFABP), which marks intestinal permeability, plasma citrulline, which reflects the functional enterocyte mass, and whole blood endotoxin were measured at admission, days 1–3 and 6. We explored the kinetics of release and the relationship between IFABP, citrulline and endotoxin values. Results IFABP was extremely high at admission and normalized at D3 (6668 pg/mL vs 39 pg/mL, p = 0.01). Lowest median of citrulline ( N = 20–40 μmol/L) was attained at D2 (11 μmol/L at D2 vs 24 μmol/L at admission, p = 0.01) and tended to normalize at D6 (21 μmol/L). During ICU stay, 86% of patients presented a detectable endotoxemia. Highest endotoxin level was positively correlated with highest IFABP level ( R2 = 0.31, p = 0.01) and was inversely correlated with lowest plasma citrulline levels ( R2 = 0.55, p < 0.001). Endotoxin levels increased between admission and D2 in patients with post-resuscitation shock, whereas it decreases in patients with no shock (median +0.33 EU vs −0.19 EU, p = 0.03). Highest endotoxin level was positively correlated with D3 SOFA score ( R2 = 0.45, p = 0.004). Conclusion Biomarkers of intestinal injury are altered after cardiac arrest and are associated with endotoxemia. This could worsen post-resuscitation shock and organ failure.
Summary
In order to assess the prognostic value of inhibitory anti‐ADAMTS13 antibodies in thrombotic thrombocytopenic purpura (TTP), we performed a multicentre prospective study of 33 adult patients ...with idiopathic acquired TTP. Patients were treated with high‐dose plasma infusion and therapeutic plasma exchange. Patients without (group 1, n = 12) and with (group 2, n = 21) detectable inhibitory anti‐ADAMTS13 antibodies were compared for clinical presentation, treatment and outcome. Both groups were comparable for clinical presentation. All patients in group 1 achieved a sustained complete remission within a median of 7 d 95% confidence interval (CI), 4–18, which required a median plasma volume of 235 ml/kg (range, 131–1251). In group 2, 17 patients achieved a durable complete remission within a median of 23 d (95% CI, 11–32) (P = 0·001). Median plasma volume was 718 ml/kg (range, 219–3107) (P = 0·02). In group 2, there was a trend for more episodes of flare‐up than in group 1 (13 vs. 3, respectively, P = 0·07). Four patients, all from group 2, died (P = not significant). The relapse rate was comparable between both groups. We suggest that TTP with detectable inhibitory anti‐ADAMTS13 antibodies displays a worse prognosis, relative to a delayed platelet count recovery, a higher plasma volume requirement to achieve complete remission, and a trend for more frequent episodes of flare‐up.
Summary
Background
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.
Objectives
To assess the predictive value of cTnI in patients with TTP for death or refractoriness.
Patients/Methods
The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS‐13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission.
Results
Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty‐two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 μg L−1) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 μg L−1 was the only independent factor in predicting death (odds ratio OR 2.87; 95% confidence interval CI 1.13–7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27–7.3; P = 0.01).
Conclusions
A CTnI level of > 0.25 μg L−1 at presentation in patients with TTP appears to be an independent factor associated with a three‐fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP.
A decrease in adult hippocampal neurogenesis has been linked to age-related cognitive impairment. However, the mechanisms involved in this age-related reduction remain elusive. Glucocorticoid ...hormones (GC) are important regulators of neural stem/precursor cells (NSPC) proliferation. GC are released from the adrenal glands in ultradian secretory pulses that generate characteristic circadian oscillations. Here, we investigated the hypothesis that GC oscillations prevent NSPC activation and preserve a quiescent NSPC pool in the aging hippocampus. We found that hippocampal NSPC populations lacking expression of the glucocorticoid receptor (GR) decayed exponentially with age, while GR-positive populations decayed linearly and predominated in the hippocampus from middle age onwards. Importantly, GC oscillations controlled NSPC activation and GR knockdown reactivated NSPC proliferation in aged mice. When modeled in primary hippocampal NSPC cultures, GC oscillations control cell cycle progression and induce specific genome-wide DNA methylation profiles. GC oscillations induced lasting changes in the methylation state of a group of gene promoters associated with cell cycle regulation and the canonical Wnt signaling pathway. Finally, in a mouse model of accelerated aging, we show that disruption of GC oscillations induces lasting changes in dendritic complexity, spine numbers and morphology of newborn granule neurons. Together, these results indicate that GC oscillations preserve a population of GR-expressing NSPC during aging, preventing their activation possibly by epigenetic programming through methylation of specific gene promoters. Our observations suggest a novel mechanism mediated by GC that controls NSPC proliferation and preserves a dormant NSPC pool, possibly contributing to a neuroplasticity reserve in the aging brain.
Purpose
Whether epinephrine or norepinephrine is preferable as the continuous intravenous vasopressor used to treat post-resuscitation shock is unclear. We assessed outcomes of patients with ...post-resuscitation shock after out-of-hospital cardiac arrest according to whether the continuous intravenous vasopressor used was epinephrine or norepinephrine.
Methods
We conducted an observational multicenter study of consecutive patients managed in 2011–2018 for post-resuscitation shock. The primary outcome was all-cause hospital mortality, and secondary outcomes were cardiovascular hospital mortality and unfavorable neurological outcome (Cerebral Performance Category 3–5). A multivariate regression analysis and a propensity score analysis were performed, as well as several sensitivity analyses.
Results
Of the 766 patients included in five hospitals, 285 (37%) received epinephrine and 481 (63%) norepinephrine. All-cause hospital mortality was significantly higher in the epinephrine group (OR 2.6; 95%CI 1.4–4.7;
P
= 0.002). Cardiovascular hospital mortality was also higher with epinephrine (aOR 5.5; 95%CI 3.0–10.3;
P
< 0.001), as was the proportion of patients with CPC of 3–5 at hospital discharge. Sensitivity analyses produced consistent results. The analysis involving adjustment on a propensity score to control for confounders showed similar findings (aOR 2.1; 95%CI 1.1–4.0;
P
= 0.02).
Conclusion
Among patients with post-resuscitation shock after out-of-hospital cardiac arrest, use of epinephrine was associated with higher all-cause and cardiovascular-specific mortality, compared with norepinephrine infusion. Until additional data become available, intensivists may want to choose norepinephrine rather than epinephrine for the treatment of post-resuscitation shock after OHCA.
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II. We hypothesized that losartan ...compared to usual care decreases mortality and is safe in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of losartan versus usual care on 28-day mortality in patients hospitalized for acute COVID-19. Methods Eligibility criteria included adults admitted for acute COVID-19. Exclusion criteria were hypotension, hyperkalemia, acute kidney injury, and use of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors within 7 days. Participants were randomized to losartan 25–100 mg/day orally for the hospital duration or 3 months or the control arm (usual care) in 29 hospitals in Canada and France. The primary outcome was 28-day mortality. Secondary outcomes were hospital mortality, organ support, and serious adverse events (SAEs). Results The trial was stopped early because of a serious safety concern with losartan. In 341 patients, any SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P = .01; hypotension: 30.4% vs 15.3%, respectively, P < .001) in both ward and intensive care patients. The 28-day mortality did not differ between losartan (6.5%) versus usual care (5.9%) (odds ratio, 1.11 95% confidence interval, .47–2.64; P = .81), nor did organ dysfunction or secondary outcomes. Conclusions Caution is needed in deciding which patients to start or continue using ARBs in patients hospitalized with pneumonia to mitigate risk of hypotension, acute kidney injury, and other side effects. ARBs should not be added to care of patients hospitalized for acute COVID-19. Clinical Trials Registration NCT04606563.
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