Brain functional connectivity alterations associated with neuropsychological performance 6-9 months following SARS-CoV-2 infection.

Neuropsychological deficits and brain damage following SARS-CoV-2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6-9 months following SARS-CoV-2 infection. SARS-CoV-2 infection causes long-term memory and executive dysfunctions, related to large-scale functional brain connectivity alterations.

Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study.

BACKGROUND: Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients. METHODS: We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions. RESULTS: Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3-21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1-11) after LST limitations. CONCLUSIONS: In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.

Sex-related differences in adult patients with status epilepticus: a seven-year two-center observation.

BACKGROUND: Conflicting findings exist regarding the influence of sex on the development, treatment, course, and outcome of status epilepticus (SE). Our study aimed to investigate sex-related disparities in adult SE patients, focusing on treatment, disease course, and outcome at two Swiss academic medical centers. METHODS: In this retrospective study, patients treated for SE at two Swiss academic care centers from Basel and Geneva from 2015 to 2021 were included. Primary outcomes were return to premorbid neurologic function, death during hospital stay and at 30 days. Secondary outcomes included characteristics of treatment and disease course. Associations with primary and secondary outcomes were assessed using multivariable logistic regression. Analysis using propensity score matching was performed to account for the imbalances regarding age between men and women. RESULTS: Among 762 SE patients, 45.9% were women. No sex-related differences were found between men and women, except for older age and lower frequency of intracranial hemorrhages in women. Compared to men, women had a higher median age (70 vs. 66, p = 0.003), had focal nonconvulsive SE without coma more (34.9% vs. 25.5%; p = 0.005) and SE with motor symptoms less often (52.3% vs. 63.6%, p = 0.002). With longer SE duration (1 day vs. 0.5 days, p = 0.011) and a similar proportion of refractory SE compared to men (36.9% vs. 36.4%, p = 0.898), women were anesthetized and mechanically ventilated less often (30.6% vs. 42%, p = 0.001). Age was associated with all primary outcomes in the unmatched multivariable analyses, but not female sex. In contrast, propensity score-matched multivariable analyses revealed decreased odds for return to premorbid neurologic function for women independent of potential confounders. At hospital discharge, women were sent home less (29.7% vs. 43.7%, p < 0.001) and to nursing homes more often (17.1% vs. 10.0%, p = 0.004). CONCLUSIONS: This study identified sex-related disparities in the clinical features, treatment modalities, and outcome of adult patients with SE with women being at a disadvantage, implying that sex-based factors must be considered when formulating strategies for managing SE and forecasting outcomes.

Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease.

INTRODUCTION: CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown. METHODS: We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction. We analyzed a cohort of patients who benefitted from renal catheterization and a retrospective cohort of patients hospitalized in the intensive care unit. RESULTS: Renal biopsies of CKD and kidney allograft patients revealed a stage-dependent decrease in the renal gluconeogenic pathway. Two animal models of CKD and one model of kidney fibrosis confirm gluconeogenic downregulation in injured proximal tubule cells. This shift resulted in an alteration of renal glucose production and lactate clearance during an exogenous lactate load. The isolated perfused kidney technique in animal models and renal venous catheterization in CKD patients confirmed decreased renal glucose production and lactate clearance. In CKD patients hospitalized in the intensive care unit, systemic alterations of glucose and lactate levels were more prevalent and associated with increased mortality and a worse renal prognosis at follow-up. Decreased expression of the gluconeogenesis pathway and its regulators predicted faster histologic progression of kidney disease in kidney allograft biopsies. CONCLUSION: Renal gluconeogenic function is impaired in CKD. Altered renal gluconeogenesis leads to systemic metabolic changes with a decrease in glucose and increase in lactate level, and is associated with a worse renal prognosis.

Performance of the Cepheid Methicillin-Resistant Staphylococcus aureus/S. aureus Skin and Soft Tissue Infection PCR Assay on Respiratory Samples from Mechanically Ventilated Patients for S. aureus Screening during the Phase 2 Double-Blind SAATELLITE Study.

We investigated the performance of the Xpert methicillin-resistant Staphylococcus aureus (MRSA)/S. aureus skin and soft tissue (SSTI) quantitative PCR (qPCR) assay in SAATELLITE, a multicenter, double-blind, phase 2 study of suvratoxumab, a monoclonal antibody (MAb) targeting S. aureus alpha-toxin, for reducing the incidence of S. aureus pneumonia. The assay was used to detect methicillin-susceptible S. aureus (MSSA) and MRSA in lower respiratory tract (LRT) samples from mechanically ventilated patients. LRT culture results were compared with S. aureus protein A (spa) gene cycle threshold (CT) values. Receiver operating characteristic (ROC) and Youden index were used to determine the CT cutoff for best separation of culture-S. aureus-negative and S. aureus-positive patients. Of 720 screened subjects, 299 (41.5%) were S. aureus positive by qPCR, of whom 209 had culture data: 162 (77.5%) were S. aureus positive and 47 (22.5%) were S. aureus negative. Culture results were negatively affected by antibiotic use and cross-laboratory variability. An inverse linear correlation was observed between CT values and quantitative S. aureus culture results. A spa CT value of 29 (≈2 × 103 CFU/mL) served as the best cutoff for separation between culture-negative and culture-positive samples. The associated area under the ROC curve was 83.8% (95% confidence interval [CI], 78 to 90%). Suvratoxumab provided greater reduction in S. aureus pneumonia or death than placebo in subjects with low S. aureus load (CT ≥ 29; relative risk reduction [RRR], 50.0%; 90% CI, 2.7 to 74.4%) versus the total study population (RRR, 25.2%; 90% CI, -4.3 to 46.4%). The qPCR assay was easy to perform, sensitive, and standardized and provided better sensitivity than conventional culture for S. aureus detection. Quantitative PCR CT output correlated with suvratoxumab efficacy in reducing S. aureus pneumonia incidence or death in S. aureus-colonized, mechanically ventilated patients.

An interventional quasi-experimental study to evaluate the impact of a rapid screening strategy in improving control of nosocomial extended-spectrum beta-lactamase-producing Enterobacterales and carbapenemase-producing organisms in critically ill patients.

INTRODUCTION: Rapid molecular tests could accelerate the control of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenemase-producing organisms (CPO) in intensive care units (ICUs). OBJECTIVE AND METHODS: This interventional 12-month cohort study compared a loop-mediated isothermal amplification (LAMP) assay performed directly on rectal swabs with culturing methods (control period, 6 months), during routine ICU screening. Contact precautions (CP) were implemented for CPO or non-E. coli ESBL-producing Enterobacterales (nEcESBL-PE) carriers. Using survival analysis, we compared the time intervals from admission to discontinuation of unnecessary preemptive CP among patients at-risk and the time intervals from screening to implementation of CP among newly identified carriers. We also compared diagnostic performances, and nEcESBL-PE/CPO acquisition rates. This study is registered, ISRCTN 23588440. RESULTS: We included 1043 patients. During the intervention and control phases, 92/147 (62.6%) and 47/86 (54.7%) of patients at-risk screened at admission were candidates for early discontinuation of preemptive CP. The LAMP assay had a positive predictive value (PPV) of 44.0% and a negative predictive value (NPV) of 99.9% for CPO, and 55.6% PPV and 98.2% NPV for nEcESBL-PE. Due to result notification and interpretation challenges, the median time from admission to discontinuation of preemptive CP increased during the interventional period from 80.5 (95% CI 71.5-132.1) to 88.3 (95% CI 57.7-103.7) hours (p = 0.47). Due to the poor PPV, we had to stop using the LAMP assay to implement CP. No difference was observed regarding the incidence of nEcESBL-PE and CPO acquisition. CONCLUSION: A rapid screening strategy with LAMP assays performed directly on rectal swabs had no benefit for infection control in a low-endemicity setting.

Early prone positioning in acute respiratory distress syndrome related to COVID-19: a propensity score analysis from the multicentric cohort COVID-ICU network-the ProneCOVID study.

BACKGROUND: Delaying time to prone positioning (PP) may be associated with higher mortality in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). We evaluated the use and the impact of early PP on clinical outcomes in intubated patients hospitalized in intensive care units (ICUs) for COVID-19. METHODS: All intubated patients with ARDS due to COVID-19 were involved in a secondary analysis from a prospective multicenter cohort study of COVID-ICU network including 149 ICUs across France, Belgium and Switzerland. Patients were followed-up until Day-90. The primary outcome was survival at Day-60. Analysis used a Cox proportional hazard model including a propensity score. RESULTS: Among 2137 intubated patients, 1504 (70.4%) were placed in PP during their ICU stay and 491 (23%) during the first 24 h following ICU admission. One hundred and eighty-one patients (36.9%) of the early PP group had a PaO2/FiO2 ratio > 150 mmHg when prone positioning was initiated. Among non-early PP group patients, 1013 (47.4%) patients had finally been placed in PP within a median delay of 3 days after ICU admission. Day-60 mortality in non-early PP group was 34.2% versus 39.3% in the early PP group (p = 0.038). Day-28 and Day-90 mortality as well as the need for adjunctive therapies was more important in patients with early PP. After propensity score adjustment, no significant difference in survival at Day-60 was found between the two study groups (HR 1.34 [0.96-1.68], p = 0.09 and HR 1.19 [0.998-1.412], p = 0.053 in complete case analysis or in multiple imputation analysis, respectively). CONCLUSIONS: In a large multicentric international cohort of intubated ICU patients with ARDS due to COVID-19, PP has been used frequently as a main treatment. In this study, our data failed to show a survival benefit associated with early PP started within 24 h after ICU admission compared to PP after day-1 for all COVID-19 patients requiring invasive mechanical ventilation regardless of their severity.

Nebulized antibiotics for ventilator-associated pneumonia: methodological framework for future multicenter randomized controlled trials.

PURPOSE OF REVIEW: Although experimental evidence supports the use of nebulized antibiotics in ventilator-associated pneumonia (VAP), two recent multicenter randomized controlled trials (RCTs) have failed to demonstrate any benefit in VAP caused by Gram-negative bacteria (GNB). This review examines the methodological requirements concerning future RCTs. RECENT FINDINGS: High doses of nebulized antibiotics are required to reach the infected lung parenchyma. Breath-synchronized nebulizers do not allow delivery of high doses. Mesh nebulizers perform better than jet nebulizers. Epithelial lining fluid concentrations do not reflect interstitial lung concentrations in patients receiving nebulized antibiotics. Specific ventilator settings for optimizing lung deposition require sedation to avoid patient's asynchrony with the ventilator. SUMMARY: Future RCTs should compare a 3-5 day nebulization of amikacin or colistimethate sodium (CMS) to a 7-day intravenous administration of a new cephalosporine/ß-lactamase inhibitor. Inclusion criteria should be a VAP or ventilator-associated tracheobronchitis caused by documented extensive-drug or pandrug resistant GNB. If the GNB remains susceptible to aminoglycosides, nebulized amikacin should be administered at a dose of 40 mg/kg/day. If resistant to aminoglycosides, nebulized CMS should be administered at a dose of 15 millions international units (IU)/day. In VAP caused by pandrug-resistant GNB, 15 millions IU/day nebulized CMS (substitution therapy) should be compared with a 9 millions IU/day intravenous CMS.

Thiamine, Ascorbic Acid, and Hydrocortisone As a Metabolic Resuscitation Cocktail in Sepsis: A Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis.

OBJECTIVES: Sepsis is a common condition in the ICU. Despite much research, its prognosis remains poor. In 2017, a retrospective before/after study reported promising results using a combination of thiamine, ascorbic acid, and hydrocortisone called "metabolic resuscitation cocktail" and several randomized controlled trials assessing its effectiveness were performed. DESIGN: We conducted a systematic review and meta-analysis of randomized controlled trials in septic ICU patients to assess the effects of this combination therapy. SETTING: PubMed, Embase, and the Cochrane library databases were searched from inception to March of 2021. Data were extracted independently by two authors. The main outcome was the change in Sequential Organ Failure Assessment score within 72 hours. Secondary outcomes included renal composite endpoints (acute kidney injury) Kidney Disease - Improving Global Outcome organization stage 3 or need for renal replacement therapy, vasopressor duration, and 28-day mortality. SUBJECTS: We included randomized controlled trials with patients admitted to the ICU with sepsis or septic shock. INTERVENTION: The trials compared a combination of thiamine, ascorbic acid, and hydrocortisone to standard care or placebo in patients admitted to ICU with sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS: We included eight randomized controlled trials (n = 1,335 patients). Within 72 hours, the median of mean improvement was -1.8 and -3.2 in the control and intervention groups, respectively (eight randomized controlled trials, n = 1,253 patients); weighted mean difference -0.82 (95% CI, -1.15 to -0.48). Data were homogeneous and the funnel plot did not suggest any publication bias. Duration of vasopressor requirement was significantly reduced in the intervention group (six randomized controlled trials). There was no evidence of a difference regarding the ICU mortality and the renal composite outcome (acute kidney injury KDIGO 3 or need for renal replacement therapy, seven randomized controlled trials). CONCLUSIONS: Metabolic resuscitation cocktail administrated in ICU septic patients improves change in Sequential Organ Failure Assessment score within 72 hours. However, this improvement is modest and its clinical relevance is questionable. The impact on renal failure and mortality remains unclear.

COVID-19 encephalopathy: Clinical and neurobiological features.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has been associated with neurological complications, including acute encephalopathy. To better understand the neuropathogenesis of this acute encephalopathy, we describe a series of patients with coronavirus disease 2019 (COVID-19) encephalopathy, highlighting its phenomenology and its neurobiological features. On May 10, 2020, 707 patients infected by SARS-CoV-2 were hospitalized at the Geneva University Hospitals; 31 (4.4%) consecutive patients with an acute encephalopathy (64.6 ± 12.1 years; 6.5% female) were included in this series, after exclusion of comorbid neurological conditions, such as stroke or meningitis. The severity of the COVID-19 encephalopathy was divided into severe and mild based on the Richmond Agitation Sedation Scale (RASS): severe cases (n = 14, 45.2%) were defined on a RASS < -3 at worst presentation. The severe form of this so-called COVID-19 encephalopathy presented more often a headache. The severity of the pneumonia was not associated with the severity of the COVID-19 encephalopathy: 28 of 31 (90%) patients did develop an acute respiratory distress syndrome, without any difference between groups (p = .665). Magnetic resonance imaging abnormalities were found in 92.0% (23 of 25 patients) with an intracranial vessel gadolinium enhancement in 85.0% (17 of 20 patients), while an increased cerebrospinal fluid/serum quotient of albumin suggestive of blood-brain barrier disruption was reported in 85.7% (6 of 7 patients). Reverse transcription-polymerase chain reaction for SARS-CoV-2 was negative for all patients in the cerebrospinal fluid. Although different pathophysiological mechanisms may contribute to this acute encephalopathy, our findings suggest the hypothesis of disturbed brain homeostasis and vascular dysfunction consistent with a SARS-CoV-2-induced endotheliitis.

SARS-CoV-2 infection as a trigger of humoral response against apolipoprotein A-1.

BACKGROUND: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights into the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We aimed at determining (a) the association between anti-SARS-CoV-2 and anti-apoA-1 humoral response and (b) the degree of linear homology between SARS-CoV-2, apoA-1 and Toll-like receptor 2 (TLR2) epitopes. DESIGN: Bioinformatics modelling coupled with mimic peptides engineering and competition experiments were used to assess epitopes sequence homologies. Anti-SARS-CoV-2 and anti-apoA-1 IgG as well as cytokines were assessed by immunoassays on a case-control (n = 101), an intensive care unit (ICU; n = 126) and a general population cohort (n = 663) with available samples in the pre and post-pandemic period. RESULTS: Using bioinformatics modelling, linear sequence homologies between apoA-1, TLR2 and Spike epitopes were identified but without experimental evidence of cross-reactivity. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (P < .0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-day kinetics, reaching 82% for anti-apoA-1 seropositivity. In the general population, SARS-CoV-2-exposed individuals displayed higher anti-apoA-1 IgG seropositivity rates than nonexposed ones (34% vs 16.8%; P = .004). CONCLUSION: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.

Serial measurement of pancreatic stone protein for the early detection of sepsis in intensive care unit patients: a prospective multicentric study.

BACKGROUND: The early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU). METHODS: This was a multicentric international prospective observational clinical study conducted in 14 ICUs in France, Switzerland, Italy, and the United Kingdom. Adult ICU patients at risk of nosocomial sepsis were included. A biomarker-blinded adjudication committee identified sepsis events and the days on which they began. The association of clinical sepsis diagnoses with the trajectories of PSP, CRP, and PCT in the 3 days preceding these diagnoses of sepsis were tested for markers of early sepsis detection. The performance of the biomarkers in sepsis diagnosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Of the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3-8 days). Clinical sepsis diagnosis was associated with an increase in biomarkers value over the 3 days preceding this diagnosis [PSP (p = 0.003), PCT (p = 0.025) and CRP (p = 0.009)]. PSP started to increase 5 days before the clinical diagnosis of sepsis, PCT 3 and CRP 2 days, respectively. The area under the ROC curve at the time of clinical sepsis was similar for all markers (PSP, 0.75; CRP, 0.77; PCT, 0.75). CONCLUSIONS: While the diagnostic accuracy of PSP, CRP and PCT for sepsis were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary to clinical diagnose sepsis. This observation justifies further evaluation of the potential clinical benefit of serial PSP measurement in the management of critically ill patients developing nosocomial sepsis. Trial registration The study has been registered at ClinicalTrials.gov (no. NCT03474809), on March 16, 2018. https://www.clinicaltrials.gov/ct2/show/NCT03474809?term=NCT03474809&draw=2&rank=1 .

Measured and Estimated Glomerular Filtration Rate in the ICU: A Prospective Study.

OBJECTIVES: To compare estimated glomerular filtration rate using classical static and kinetic equations with measured glomerular filtration rate assessed by plasma iohexol clearance in a mixed population of critical care patients. PATIENTS: Unselected patients older than 18 and admitted to a general ICU. DESIGN: Interventional prospective single center study. INTERVENTION: Measurement of glomerular filtration rate by the plasma clearance of an IV single dose of iohexol and estimation of glomerular filtration rate with creatinine or cystatin C-based standard and kinetic equations as well as urinary creatinine clearance. MEASUREMENTS AND MAIN RESULTS: Sixty-three patients were included with a median age of 66 years old. The median measured glomerular filtration rate was 51 mL/min/1.73 m (interquartile range, 19-85 mL/min/1.73 m). All used equations displayed significant biases, high errors, and poor accuracy when compared with measured glomerular filtration rate, overestimating renal function. The highest accuracy and lowest error were observed with cystatin C-based chronic kidney disease epidemiology collaboration equations. Both modification of diet in renal disease and Cockcroft-Gault equations displayed the lowest performance. Kinetic models did not improve performances, except in patients with unstable creatinine levels. Creatinine- but not cystatin C-based estimations largely derived over ICU stay, which appeared more related to sarcopenia than fluid balance. Finally, estimated glomerular filtration rate misclassified patients according to classical glomerular filtration rate categories in approximately half of the studied cases. CONCLUSIONS: All known estimated glomerular filtration rate equations displayed high biases and unacceptable errors when compared with measured glomerular filtration rate in a mixed ICU population, with the lowest performance related to creatinine-based equations compared with cystatin C. In the ICU, we advocate for caution when using creatinine based estimated glomerular filtration rate equations. Drifting of serum creatinine levels over time should also be taken into consideration when assessing renal function in the ICU.

Influenza-associated aspergillosis in critically-ill patients-a retrospective bicentric cohort study.

Influenza was recently reported as a risk factor for invasive aspergillosis (IA). We aimed to describe prognostic factors for influenza-associated IA (IAA) and poor outcome and mortality in critically ill patients in Switzerland. All adults with confirmed influenza admitted to the ICU at two Swiss tertiary care centres during the 2017/2018 influenza season were retrospectively evaluated. IAA was defined by clinical, mycological and radiological criteria: a positive galactomannan in bronchoalveolar lavage or histopathological or cultural evidence in respiratory specimens of Aspergillus spp., any radiological infiltrate and a compatible clinical presentation. Poor outcome was defined as a composite of in-hospital mortality, ICU length of stay (LOS), invasive ventilation for > 7 days or extracorporeal membrane oxygenation. Of 81 patients with influenza in the ICU, 9 (11%) were diagnosed with IAA. All patients with IAA had poor outcome compared to 26 (36%) patients without IAA (p < 0.001). Median ICU-LOS and mortality were 17 vs. 3 days (p < 0.01) and 3/9 (33%) vs. 13/72 (18%; p = 0.37) in patients with vs. without IAA, respectively. Patients with IAA had significantly longer durations of antibiotic therapy, vasoactive support and mechanical ventilation. Aspergillus was the most common respiratory co-pathogen (9/40, 22%) followed by classical bacterial co-pathogens. IAA was not associated with classical risk factors. Aspergillus is a common superinfection in critically ill influenza patients associated with poor outcome and longer duration of organ supportive therapies. Given the absence of classical risk factors for aspergillosis, greater awareness is necessary, particularly in those requiring organ supportive therapies.

Extremely high-dose insulin requirement in a diabetic patient with COVID-19: a case report.

BACKGROUND: Detailed description of hyperglycemia management in diabetic patients infected with SARS-CoV-2 remain limited, although patients with diabetes show higher complication and mortality rate than patients without diabetes. Transient non-severe increased insulin requirement in patients hospitalized for medical conditions such as sepsis or myocardial infarction is a well-known phenomenon. However, extremely high-dose insulin requirement remains a very rarely reported entity. Here, we report the case of an extreme and transitory insulin requirement episode in a type 2 diabetic patient presenting an acute respiratory distress syndrome caused by SARS-CoV-2. CASE PRESENTATION: A 57-year-old man resident in Geneva, Switzerland, previously known for type 2 diabetes for 3 years was admitted for an aggravation of his dyspnea. His type 2 diabetes was treated only with metformin and his latest Hb1Ac was 6.1%. Chest CT SCAN showed a bilateral multilobar ground-glass opacification. Twenty-four hours after his admission he presented a worsening of dyspnea and severe hypoxemia requiring a transfer to the intensive care unit rapidly followed by oro-tracheal intubation for mechanical ventilation support. A bronchoalveolar lavage was performed and test of SARS-CoV-2 by RT-qPCR assay was positive. At day 3, he presented a rapidly progressive insulin requirement at a rate of up to 50 units/hour intravenous insulin aspart. Despite the high insulin doses, he maintained an elevated plasma glucose level at 270 mg/dL on average. His extremely high-dose insulin requirement "resolved" at day 9, and the insulin infusion rate was rapidly reduced. CONCLUSIONS: This case may reflect a specific and profound impact of SARS-CoV-2 on metabolic homeostasis, in particular in diabetic patients that appear more prone to complications of COVID-19 infection. Yet, the mechanisms behind this remain to be elucidated. The optimal management of hyperglycemia of diabetic patients infected with SARS-CoV-2 has yet not be defined, however insulin remain the mainstay of treatment approach. Report of extreme dysregulation of chronic conditions such as diabetes in patients with COVID-19 may help clinicians to better take care of patients during the pandemic of SARS-CoV-2. To the best of our knowledge this is the first description of extremely high-dose insulin requirement in patient with COVID-19.

[Palliative and intensive care collaborative approach in the management of therapeutic withdrawals: lessons learned from the COVID-19 experience]. / Approche collaborative des soins palliatifs et des soins intensifs dans la gestion des retraits thérapeutiques - Ce qu'il faut retenir de l'expérience du COVID-19.

During the COVID-19 pandemic, many of the usual aspects of therapeutic withdrawals had to be adapted. Preparing and supporting patients, next of kin and staff to death was particularly challenging. Palliative care was integrated into the process of therapeutic withdrawals in intensive care units during this crisis. Continuing education related to end-of-life issues and defining collaboration with palliative care is essential for intensive care teams.

Durant la pandémie Coronavirus Disease 19, certains aspects habituels des retraits thérapeutiques ont dû être adaptés. L'accompagnement des patients et de leurs proches au décès ainsi que le soutien aux équipes de soins ont amené à résoudre de nouveaux défis. L'intégration des soins palliatifs dans les processus de retraits thérapeutiques aux soins intensifs a pu être mise en œuvre durant cette crise sanitaire. La formation continue aux questions en lien avec la fin de vie et l'établissement de plans de collaboration avec les soins palliatifs est essentielle aux soins intensifs.

[Why a post-intensive care consultation ?] / Pourquoi une consultation post-soins intensifs ?

The progress of intensive care medicine allows the survival of patients with severe critical illness. However, the quality of life of patients with a prolonged stay in intensive care unit (ICU) can be poor. The physical and psychological consequences are due more to the intensive care than the primary diagnoses. Moreover, a stay of a beloved in an ICU impacts heavily on the relatives. The service of Geneva ICU developed a specific model of care for patients with a prolonged stay and seeks to establish a follow-up consultation for these patients. The aim would be to fill the memory gaps, explain the events during their stay, and detect potential complications. This project fits in the follow-up of complex situations in tight collaboration with the family doctors of such patients.

Le progrès de la médecine intensive permet la survie de patients gravement atteints dans leur santé. Toutefois, les conditions de survie de ces patients, surtout après un séjour prolongé aux soins intensifs (SI), sont parfois difficiles. Les atteintes physiques et psychiques à moyen et long termes sont propres aux événements vécus aux SI, plus que les conséquences des diagnostics d'admission aux SI. De plus, ce séjour impacte lourdement sur les proches de ces patients. Les SI de Genève ont mis en place une structure de suivi durant le séjour prolongé de patients et souhaite aujourd'hui leur offrir un suivi après les SI. Le but est de combler les lacunes de mémoire de leur séjour, expliquer les événements incompris et détecter d'éventuelles complications. Ce projet s'insère dans le suivi complexe de ces patients avec les médecins traitants.

Can calculation of energy expenditure based on CO2 measurements replace indirect calorimetry?

BACKGROUND: Methods to calculate energy expenditure (EE) based on CO2 measurements (EEVCO2) have been proposed as a surrogate to indirect calorimetry. This study aimed at evaluating whether EEVCO2 could be considered as an alternative to EE measured by indirect calorimetry. METHODS: Indirect calorimetry measurements conducted for clinical purposes on 278 mechanically ventilated ICU patients were retrospectively analyzed. EEVCO2 was calculated by a converted Weir's equation using CO2 consumption (VCO2) measured by indirect calorimetry and assumed respiratory quotients (RQ): 0.85 (EEVCO2_0.85) and food quotient (FQ; EEVCO2_FQ). Mean calculated EEVCO2 and measured EE were compared by paired t test. Accuracy of EEVCO2 was evaluated according to the clinically relevant standard of 5% accuracy rate to the measured EE, and the more general standard of 10% accuracy rate. The effects of the timing of measurement (before or after the 7th ICU day) and energy provision rates (<90 or ≥90% of EE) on 5% accuracy rates were also analyzed (chi-square tests). RESULTS: Mean biases for EEVCO2_0.85 and EEVCO2_FQ were -21 and -48 kcal/d (p = 0.04 and 0.00, respectively), and 10% accuracy rates were 77.7 and 77.3%, respectively. However, 5% accuracy rates were 46.0 and 46.4%, respectively. Accuracy rates were not affected by the timing of the measurement, or the energy provision rates at the time of measurements. CONCLUSIONS: Calculated EE based on CO2 measurement was not sufficiently accurate to consider the results as an alternative to measured EE by indirect calorimetry. Therefore, EE measured by indirect calorimetry remains as the gold standard to guide nutrition therapy.

[Sepsis : particularities in the elderly patients]. / Sepsis chez le sujet âgé : quelles spécificités ?

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection. The clinical presentation of sepsis in the elderly is very variable and sepsis is therefore challenging to diagnose in this population. The new sepsis definitions published in 2016, which are based on objective clinical and biological scores, should lead to earlier recognition and diagnosis. Treatment should start as soon as possible because the specific pathophysiological changes of aging increase the risk of a sudden deterioration to septic shock. Physicians should treat elderly patients with sepsis according to internationally recommended guidelines but should take into account specific aspects related to the elderly. These aspects include the presence of specific comorbidities and the need to clarify the overall objectives of care when deciding to admit a patient to the intensive care unit.

Le sepsis est une pathologie fréquente, caractérisée par une réponse inflammatoire systémique inappropriée, consécutive à une infection, à l'origine de dysfonctions d'organes mettant en jeu le pronostic vital. Chez le sujet âgé, le sepsis est souvent de diagnostic difficile. De nouvelles définitions, aidées par des scores clinico-biologiques, permettent une reconnaissance plus précoce des états septiques à risque de mauvaise évolution. La précocité de la prise en charge, chez des sujets âgés aux défenses immunitaires et réserves physiologiques diminuées, est un élément essentiel du pronostic. Les principes de prise en charge du sepsis chez le sujet âgé diffèrent peu du sujet plus jeune avec néanmoins la problématique de l'admission ou non en milieu de soins intensifs en fonction du niveau de soins préalablement défini, des comorbidités du patient et des objectifs de soins.