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The aim was to develop an RT-qPCR targeting Aspergillus fumigatus and compare its performance to that of Aspergillus fumigatus qPCR for the diagnosis of invasive aspergillosis (IA). Samples from patients of the Lyon University hospitals for whom a suspicion of IA led to the realization of an Aspergillus fumigatus qPCR molecular diagnostic test over a 2-year period were included. The patients were classified according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC-MSGERC) criteria for suspected IA; RT-qPCR and qPCR assays were performed on all included samples. The sensitivities and specificities of RT-qPCR and qPCR were calculated and compared using the results of the EORTC-MSGERC classification as reference. The cycle threshold (Ct) results were compared according to IA classification and sample type. Among the 193 samples analyzed, 91 were classified as IA excluded, 46 as possible IA, 53 as probable IA, and 3 as proven IA. For all sample types, RT-qPCR was significantly more sensitive than qPCR for all IA classifications with an additional 17/102 samples detected ( P -value < 0.01). For plasma samples, sensitivity was significantly higher and specificity significantly lower using RT-qPCR for all IA classifications ( P -value < 0.001). The mean Ct obtained with RT-qPCR were significantly lower than those obtained with qPCR for all IA classifications and all sample types ( P -value < 0.001 and P -value < 0.0001, respectively). RT-qPCR presents a higher sensitivity than qPCR for the diagnosis of IA due to Aspergillus fumigatus , particularly in samples with an intrinsically low fungal load.IMPORTANCE Aspergillus fumigatus belongs to the critical priority group of the World Health Organization fungal priority pathogens list. Invasive aspergillosis (IA) is a life-threatening infection with poor prognosis and challenging diagnosis. PCR has been integrated into the 2020 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions for IA diagnosis. However, due to frequent low fungal burdens, its sensitivity needs to be improved. This work presents an innovative method for detecting total nucleic acids, corresponding to both ribosomal RNA and DNA, that enables IA diagnosis with greater sensitivity than conventional techniques, especially in non-invasive samples such as blood, enhancing the monitoring of this infection in high-risk patients.

Purpose: Approximately 30% of people infected with COVID-19 require hospitalization, and 20% of them are admitted to an intensive care unit (ICU). Most of these patients experience symptoms of fatigue weeks post-ICU, so understanding the factors associated with fatigue in this population is crucial., Methods: Fifty-nine patients (38-78 yr) hospitalized in ICU for COVID-19 infection for 32 (6-80) d, including 23 (3-57) d of mechanical ventilation, visited the laboratory on two separate occasions. The first visit occurred 52 ± 15 d after discharge and was dedicated to questionnaires, blood sampling, and cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function and performance fatigability were performed in the second visit 7 ± 2 d later., Results: Using the FACIT-F questionnaire, 56% of patients were classified as fatigued. Fatigued patients had worse lung function score than non-fatigued (i.e., 2.9 ± 0.8 L vs 3.6 ± 0.8 L; 2.4 ± 0.7 L vs 3.0 ± 0.7 L for forced vital capacity and forced expiratory volume in 1 s, respectively), and forced vital capacity was identified as a predictor of being fatigued. Maximal voluntary activation was lower in fatigued patients than non-fatigued patients (82% ± 14% vs 91% ± 3%) and was the only neuromuscular variable that discriminated between fatigued and non-fatigued patients. Patient-reported outcomes also showed differences between fatigued and non-fatigued patients for sleep, physical activity, depression, and quality of life ( P < 0.05)., Conclusions: COVID-19 survivors showed altered respiratory function 4 to 8 wk after discharge, which was further deteriorated in fatigued patients. Fatigue was also associated with lower voluntary activation and patient-reported impairments (i.e., sleep satisfaction, quality of life, or depressive state). The present study reinforces the importance of exercise intervention and rehabilitation to counteract cardiorespiratory and neuromuscular impairments of COVID-19 patients admitted in ICU, especially individuals experiencing fatigue., (Copyright © 2024 by the American College of Sports Medicine.)

Background: Invasive candidiasis is still recognized as a major cause of morbidity and mortality. To support clinicians in the optimal use of antifungals for the treatment of invasive candidiasis, a computerized decision support system (CDSS) was developed based on institutional guidelines., Objectives: To evaluate the correlation of this newly developed CDSS with clinical practices, we set-up a retrospective multicentre cohort study with the aim of providing the concordance rate between the CDSS recommendation and the medical prescription (NCT05656157)., Patients and Methods: Adult patients who received caspofungin or fluconazole for the treatment of an invasive candidiasis were included. The analysis of factors associated with concordance was performed using mixed logistic regression models with department as a random effect., Results: From March to November 2022, 190 patients were included from three centres and eight departments: 70 patients from centre A, 84 from centre B and 36 from centre C. Overall, 100 patients received caspofungin and 90 received fluconazole, mostly (59%; 112/190) for empirical/pre-emptive treatment. The overall percentage of concordance between the CDSS and medical prescriptions was 91% (173/190) (confidence interval 95%: 82%-96%). No significant difference in concordance was observed considering the centres (P > 0.99), the department of inclusion (P = 0.968), the antifungal treatment (P = 0.656) or the indication of treatment (P = 0.997). In most cases of discordance (n = 13/17, 76%), the CDSS recommended fluconazole whereas caspofungin was prescribed. The clinical usability evaluated by five clinicians was satisfactory., Conclusions: Our results demonstrated the high correlation between current antifungal clinical practice and this user-friendly and institutional guidelines-based CDSS., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The clinical features and short-term prognosis of patients admitted to the intensive care unit for herpes hepatitis are lacking. Of 33 patients admitted between 2006 and 2022, 22 were immunocompromised, 4 were pregnant women, and 23 died. Sixteen patients developed a hemophagocytic syndrome. Acyclovir was initiated a median (interquartile range) of 1 (0-3) day after admission., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Bacterial infections are the most frequent precipitating event in patients with acute decompensation of cirrhosis (AD) and are associated with high mortality. Early diagnosis is challenging due to cirrhosis-related systemic inflammation. Here we investigated the potential of circulating microRNAs to diagnose bacterial infections and predict survival in cirrhotic patients with AD. High throughput profiling of circulating microRNAs was performed using the Nanostring technology in 57 AD patients and 24 patients with compensated cirrhosis (CC). Circulating miRs profiling showed that: (a) miRs differentially detected in AD vs. CC were mostly down-regulated; (b) a composite score including absolute neutrophil count, C reactive protein and miR-362-3p could diagnose bacterial infection with an excellent performance (AUC of 0.825 [95% CI = 0.671-0.980; p < 0.001]); (c) a composite score including miR-382-5p, miR-592 and MELD-Na improved 6-month survival prediction. Circulating miRs are strongly dysregulated in patients with AD and may help to improve bacterial infection diagnosis and survival prediction., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Intra-Abdominal Candidiasis (IAC) is frequent and associated with high mortality in intensive care unit (ICU) patients. Antifungal treatments may be overused due to a lack of diagnostic tools to rule out IAC. Serum 1,3-Beta-D-Glucan (BDG) concentrations are used to diagnose Candida infections, its concentration in peritoneal fluid (PF) may help to confirm or invalidate the diagnosis of IAC. We performed a non-interventional, prospective, multicenter study, at the Hospices Civils de Lyon, France, in seven ICU located in three different hospitals from December 2017 to June 2018. IAC was defined as the isolation of Candida in a sample collected from the intra-abdominal cavity under sterile conditions in patients displaying clinical evidence of intra-abdominal infection. Among the 113 included patients, 135 PF samples corresponding to 135 intra-abdominal infection episodes were collected and BDG concentrations were assessed. IAC accounted for 28 (20.7%) of the intra-abdominal infections. Antifungals were administered empirically to 70 (61.9%) patients; among them, 23 (32.9%) had an IAC. The median [IQR] BDG value was significantly higher in IAC (8100 [3000;15000] pg/mL) than in non-IAC samples (1961 [332;10650] pg/mL). BDG concentrations were higher in PF with Fecaloid aspect and in case of positive bacterial culture. For a BDG threshold of 125 pg/mL, the negative predictive value to assess IAC was 100%. In conclusion, low BDG PF concentrations could be used to rule out IAC. https://clinicaltrials.gov/ct2/show/NCT03469401., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: In the context of COVID-19 pandemic, antifungal overuse may have occurred in our hospitals as it has been previously reported for antibacterials., Methods: To investigate the impact of COVID-19 on antifungal consumption, a multicenter retrospective study including four medical sites and 14 intensive care units (ICU) was performed. Antifungal consumption and incidences of invasive fungal diseases before and during COVID-19 pandemic, for non-COVID-19 patients and COVID-19 patients, were described., Results: An increase in voriconazole consumption was observed in 2020 compared with 2019 for both the whole hospital and the ICU (+ 40.3% and + 63.7%, respectively), whereas the incidence of invasive aspergillosis significantly increased in slightly lower proportions in the ICU (+ 46%). Caspofungin consumption also increased in 2020 compared to 2019 for both the whole hospital and the ICU (+ 34.9% and + 17.0%, respectively) with an increased incidence of invasive candidiasis in the whole hospital and the ICU but in lower proportions (+ 20.0% and + 10.9%, respectively)., Conclusions: We observed an increased consumption of antifungals including voriconazole and caspofungin in our hospital during the COVID-19 pandemic and explained in part by an increased incidence of invasive fungal diseases in COVID-19 patients. These results are of utmost importance as it raises concern about the urgent need for appropriate antifungal stewardship activities to control antifungal consumption., (© 2022. The Author(s).)

Objectives: The aim of the current study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration., Design: Prospective nonrandomized study., Setting: Patients hospitalized in ICU for COVID-19 infection., Patients: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU., Interventions: None., Measurements and Main Results: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status., Conclusions: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration., Competing Interests: Dr. Millet’s institution received funding from Idex Lyon Fellowship and Idex Lyon COVID. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

There is growing evidence that liver transplantation (LT) is the most effective treatment for acute-on-chronic liver failure grade-3 (ACLF-3). This study examines whether and how this evidence translates into practice by analyzing the variability in intensive care unit (ICU) admissions, listing strategies, and LT activity for patients with ACLF-3 across transplantation centers in Europe. Consecutive patients who were admitted to the ICU with ACLF-3, whether or not they were listed and/or transplanted with ACLF-3, between 2018 and 2019 were included across 20 transplantation centers. A total of 351 patients with ACLF-3 were included: 33 had been listed prior to developing ACLF-3 and 318 had not been listed at the time of admission to the ICU. There was no correlation between the number of unlisted patients with ACLF-3 admitted to the ICU and the number listed or transplanted while in ACLF-3 across centers. By contrast, there was a correlation between the number of patients listed and the number transplanted while in ACLF-3. About 21% of patients who were listed while in ACLF-3 died on the waiting list or were delisted. The percentage of LT for patients with ACLF-3 varied from 0% to 29% for those transplanted with decompensated cirrhosis across centers (average = 8%), with an I 2 index of 68% (95% confidence interval, 49%-80%), showing substantial heterogeneity among centers. The 1-year survival for all patients with ACLF-3 was significantly higher in centers that listed and transplanted more patients with ACLF-3 (>10 patients) than in centers that listed and transplanted fewer: 36% versus 20%, respectively (p = 0.012). Patients with ACLF-3 face inequity of access to LT across Europe. Waitlisting strategies for patients with ACLF-3 influence their access to LT and, ultimately, their survival., (© 2022 American Association for the Study of Liver Diseases.)

Objective: To compare old patients hospitalized in ICU for respiratory distress due to COVID-19 with old patients hospitalized in ICU for a non-COVID-19-related reason in terms of autonomy and quality of life., Design: Comparison of two prospective multi-centric studies., Setting: This study was based on two prospective multi-centric studies, the Senior-COVID-Rea cohort (COVID-19-diagnosed ICU-admitted patients aged over 60) and the FRAGIREA cohort (ICU-admitted patients aged over 70)., Patients: We included herein the patients from both cohorts who had been evaluated at day 180 after admission (ADL score and quality of life)., Interventions: None., Measurements and Main Results: A total of 93 COVID-19 patients and 185 control-ICU patients were included. Both groups were not balanced on age, body mass index, mechanical ventilation, length of ICU stay, and ADL and SAPS II scores. We modeled with ordered logistic regression the influence of COVID-19 on the quality of life and the ADL score. After adjustment on these factors, we observed COVID-19 patients were less likely to have a loss of usual activities (aOR [95% CI] 0.47 [0.23; 0.94]), a loss of mobility (aOR [95% CI] 0.30 [0.14; 0.63]), and a loss of ADL score (aOR [95% CI] 0.30 [0.14; 0.63]). On day 180, 52 (56%) COVID-19 patients presented signs of dyspnea, 37 (40%) still used analgesics, 17 (18%) used anxiolytics, and 14 (13%) used antidepressant., Conclusions: COVID-19-related ICU stay was not associated with a lower quality of life or lower autonomy compared to non-COVID-19-related ICU stay., (© 2022. The Author(s).)

The SARS-COV2 pandemic induces tensions on health systems and ethical dilemmas. Practitioners need help tools to define patients not candidate for ICU admission. A multicentre observational study was performed to evaluate the impact of age and geriatric parameters on 30-day mortality in patients aged ≥60 years of age. Patients or next of kin were asked to answer a phone questionnaire assessing geriatric covariates 1 month before ICU admission. Among 290 screened patients, 231 were included between March 7 and May 7, 2020. In univariate, factors associated with lower 30-day survival were: age (per 10 years increase; OR 3.43, [95%CI: 2.13-5.53]), ≥3 CIRS-G grade ≥2 comorbidities (OR 2.49 [95%CI: 1.36-4.56]), impaired ADL, (OR 4.86 [95%CI: 2.44-9.72]), impaired IADL8 (OR 6.33 [95%CI: 3.31-12.10], p<0.001), frailty according to the Fried score (OR 4.33 [95%CI: 2.03-9.24]) or the CFS ≥5 (OR 3.79 [95%CI: 1.76-8.15]), 6-month fall history (OR 3.46 [95%CI: 1.58-7.63]). The final multivariate model included age (per 10 years increase; 2.94 [95%CI:1.78-5.04], p<0.001) and impaired IADL8 (OR 5.69 [95%CI: 2.90-11.47], p<0.001)). Considered as continuous variables, the model led to an AUC of 0.78 [95% CI: 0.72, 0.85]. Age and IADL8 provide independent prognostic factors for 30-day mortality in the considered population. Considering a risk of death exceeding 80% (82.6% [95%CI: 61.2% - 95.0%]), patients aged over 80 years with at least 1 IADL impairment appear as poor candidates for ICU admission., Competing Interests: Conflict of interest statement All the authors declare grants from Hospices Civils de Lyon, during the conduct of the study, no other competing interests with the considered topic. CF reports outside of the present work consulting/advisory roles for GSK, Leo Pharma, Pfizer, MSD Oncology, Teva, AstraZeneca, Baxter, Eisai, Janssen, and Novartis; research funding from Chugai Pharma, Pfizer, Pierre Fabre, and Astellas Pharma; and travel/accommodation/expenses from Janssen Oncology, Pierre Fabre, and Leo Pharma. The Hospices Civils de Lyon gave funding for Clinical Research Assistants, statistical analysis and manuscript editing. The funder of the study had no role in study design, data collection, data analysis, data interpretation. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The corresponding author drafted the manuscript. All authors critically reviewed the manuscript and approved the final version for submission., (Copyright: © 2022 Falandry et al.)

Background: The difference between arterial and central venous carbon dioxide partial pressure (PCO 2 gap), a marker of oxygen delivery (DO 2 ) and oxygen consumption (VO 2 ) adequacy, has been evaluated as a promising prognostic tool in intensive care unit (ICU) patients. We therefore sought to study the association between intraoperative PCO 2 gap and postoperative complications (POC) in the perioperative setting of elective major abdominal surgery., Methods: We conducted a single-centre prospective observational study. All adult patients who underwent major planned abdominal surgery were eligible. PCO 2 gap was measured every 2 h during surgery, at ICU admission and repeated 12 h and 24 h later. Severe POC within 28 days after surgery were defined as complications graded 3 or more according to Clavien-Dindo classification. Following a univariate analysis, a multivariable analysis using a logistic regression model was performed., Results: Ninety patients were included and divided into two groups according to the occurrence of POC. No significant difference was found between groups regarding baseline characteristics at inclusion. Thirty-nine (43%) patients developed postoperative complications. The median [IQR] intraoperative PCO 2 gap was significantly higher in patients who had complications (6.5 [5.5-7.3] mmHg) compared to those who did not (5.0 [3.9-5.8] mmHg; p < 0.001). The area under the receiver operating characteristic curve for occurrence of POC was 0.78 for the PCO 2 gap. After multivariable analysis, PCO 2 gap was found independently associated with POC (OR: 14.9, 95% CI [4.68-60.1], p < 0.001) with a threshold value of 6.2 mmHg. The duration of surgery (OR: 1.01, 95% CI [1.00; 1.01], p = 0.04) and the need for vasoactive support during surgery (OR: 5.76, 95% CI [1.72; 24.1], p = 0.006) were also independently associated with POC., Conclusion: Intraoperative PCO 2 gap is a relevant predictive factor of severe postoperative complications in high-risk elective surgery patients., Trial Registration: ClinicalTrials.gov, NCT03914976., (Copyright © 2022 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD)., Methods: We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity <50% associated with bilirubin ≥250 μmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the dialysis flow rate was equal to 1,000 mL/h., Results: Twenty crossovers have been performed. Baseline biochemical characteristics (bilirubin, ammonia, bile acids, creatinine, and urea) were not statistically different between MARS and SPAD. Both ECAD have led to a significant reduction in total bilirubin (-83 ± 67 μmol/L after MARS; -122 ± 118 μmol/L after SPAD session), conjugated bilirubin (-82 ± 61 μmol/L after MARS; -105 ± 96 μmol/L after SPAD session), and bile acid levels (-64 ± 75 μmol/L after MARS; -56 ± 56 μmol/L after SPAD session), all nondifferent comparing MARS to SPAD., Conclusion: A simple-to-perform SPAD therapy with equal to MARS dialysate flow parameters provides the same efficacy in bilirubin and bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program., (© 2021 S. Karger AG, Basel.)

Introduction: With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission., Methods and Analysis: This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients' outcomes., Ethics and Dissemination: The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals., Trial Registration Number: NCT04422340., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Liver transplantation (LT) during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging given the urgent need to reallocate resources to other areas of patient care. Available guidelines recommend reorganizing transplant care, but data on clinical experience in the context of SARS-CoV-2 pandemic are scarce. Thus, we report strategies and preliminary results in LT during the peak of the SARS-CoV-2 pandemic from a single center in France. Our strategy to reorganize the transplant program included 4 main steps: optimization of available resources, especially intensive care unit capacity; multidisciplinary risk stratification of LT candidates on the waiting list; implementation of a systematic SARS-CoV-2 screening strategy prior to transplantation; and definition of optimal recipient-donor matching. After implementation of these 4 steps, we performed 10 successful LTs during the peak of the pandemic with a short median intensive care unit stay (2.5 days), benchmark posttransplant morbidity, and no occurrence of SARS-CoV-2 infection during follow-up. From this preliminary experience we conclude that efforts in resource planning, optimal recipient selection, and organ allocation strategy are key to maintain a safe LT activity. Transplant centers should be ready to readapt their practices as the pandemic evolves., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Candidemia is a major cause of mortality in the intensive care unit (ICU). According to the Infectious Diseases Society of America (IDSA), an echinocandin is recommended as initial therapy and fluconazole as an alternative. In a context of echinocandin resistance development, the question arising is whether azoles are a suitable alternative to echinocandins for the treatment of candidemia in critically ill patients., Methods: A 3-year (2015-2017) retrospective multicentric cohort study was conducted. Adult patients with a diagnosis of candidemia during the ICU stay and treated with echinocandins or azoles were included. Demographic, clinical data, mycological data, and antifungal treatments were collected. Kaplan-Meier survival analysis, univariate analysis, and a multivariate logistic regression analysis using a propensity score with the inverse probability of treatment weighting method were performed., Findings: Seventy-nine patients (n = 79) were analyzed. Treatment success, as well as survival on day 90 (Kaplan-Meier survival analysis, log rank test, p = 0.542), were comparable between patients who received echinocandins (caspofungin (n = 47)) or azoles (fluconazole (n = 29) or voriconazole (n = 3)). A multivariable analysis demonstrated that higher SOFA score on the day of candidemia diagnosis and absence of adequate Candida source control were independently associated with a greater risk of 90-day mortality, whereas azoles treatment was not associated with an excess 90-day mortality., Interpretation: This study confirms that the use of azoles recommended for candidemia, mostly fluconazole, as a first-line therapy is a reasonable alternative to caspofungin for ICU patients in our institution. This needs to be included in local guidelines through antifungal stewardship programs., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Hospital-acquired infections (HAIs) in intensive care units (ICUs) are associated with increased length of stay (LOS). The objective of this study was to graphically describe by heat mapping LOS of patients hospitalized in ICUs related to the occurrence of HAI and severity at admission measured by the Simplified Acute Physiological Score II (SAPSII)., Methods: Adult patients hospitalized in ICUs of Lyon University Hospitals (France) were included in an active standardized surveillance study of HAI from January 1, 1995-December 31, 2012. Surveillance included adult patients aged ≥18 years hospitalized ≥2 days. Patient follow-up ended at ICU discharge or death. LOS was calculated in days from differences between dates of entry and discharge from ICUs. HAIs recorded were pneumonia, bacteremia, and urinary tract infection. The heat map was designed with a spreadsheet software., Results: A total of 34,694 patients were analyzed. Among infected patients, 72.3% had 1 infected site (IS), 23% had 2 ISs, and 4.7% had 3 ISs. Median LOS was 24 days in infected patients (20.4 days among patients with 1 IS, 34.2 days among patients with 2 ISs, and 45.3 days among patients with 3 ISs) and 5 days in noninfected patients (P < .001). Two groups of multi-infected patients with long LOSs were identified with the heat map., Conclusions: The heat map facilitated easy-to-implement semi-quantitative visualization of increasing LOS through the SAPSIIs and number of ISs., (Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this article is to provide a systematic review of the evidence supporting the use of milrinone for the management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH)., Design: Primary outcomes were functional neurological status and the incidence of cerebral infarction. Search strategies adapted to the different databases were developed by a professional librarian. Medline, EMBASE, the Cochrane Library database, Web of Science, SCOPUS, BIOSIS, Global Health, Health Star, Open SIGLE, Google Scholar and the New York Academy of Medicine Gray Literature were searched as well as clinical trials databases and the proceedings of several scientific meetings. Quality of the evidence for these outcomes across studies was adjudicated using the GRADE Working Group criteria., Results: The search resulted in 284 citations after elimination of duplicates. Of those 9 conference proceedings and 15 studies met inclusion criteria and consisted of case reports, case series and two comparative studies: one non-randomized study with physiological outcomes only and a case series with historical controls. There was considerable variation in dosing and in co-interventions and no case control or randomized controlled studies were found., Conclusion: There is currently only very low quality evidence to support the use of milrinone to improve important outcomes in patients with delayed cerebral ischemia secondary to subarachnoid hemorrhage. Further research is needed to clarify the value and risks of this medication in patients with SAH.

Cardiac surgery triggers an inflammatory stress response, leading to protein catabolism, a process that even high-dose insulin therapy alone cannot reverse. To determine whether hyperinsulinemic-normoglycemic clamp and perioperative amino acid (AA) supplementation improves whole body protein balance, 20 patients scheduled for elective coronary artery bypass grafting surgery were randomly assigned to have intra- and postoperative hyperinsulinemic-normoglycemic clamp, with or without intravenous AA supplementation. Primed continuous infusions of [6,6- 2 H 2 ]glucose and l-[1- 13 C]leucine were used to quantify whole body protein and glucose metabolism before and after surgery. Adipose tissue and serum cytokines were also analyzed to measure their responsiveness to the anabolic effect of AA administration. During hyperinsulinemic-normoglycemic clamp, AA supplementation successfully stimulated whole body protein synthesis, resulting in a positive whole body protein balance after surgery (insulin: -13.6 ± 4.5 vs. insulin + AA: 2.1 ± 5.4 μmol·kg -1 ·h -1 , P < 0.001). Endogenous glucose production was equally suppressed in both groups (insulin: 0.0 ± 3.8 vs. insulin + AA 1.6 ± 1.6 μmol·kg -1 ·min -1 , P = 0.230). AA supplementation led to significant changes in serum and tissue IL-6 (insulin: 246.6 ± 111.2 vs. insulin + AA: 124.5 ± 79.3 pg/ml, P = 0.011). In conclusion, hyperinsulinemic-normoglycemic clamp technique, together with AA supplementation, can induce an anabolic state after open-heart surgery, as quantified by a positive whole body protein balance., (Copyright © 2016 the American Physiological Society.)

Background: Prolonged controlled mechanical ventilation (CMV) in humans and experimental animals results in diaphragm fibre atrophy and injury. In animals, prolonged CMV also triggers significant declines in diaphragm myofibril contractility. In humans, the impact of prolonged CMV on myofibril contractility remains unknown. The objective of this study was to evaluate the effects of prolonged CMV on active and passive human diaphragm myofibrillar force generation and myofilament protein levels., Methods and Results: Diaphragm biopsies were obtained from 13 subjects undergoing cardiac surgery (control group) and 12 brain-dead organ donors (CMV group). Subjects in each group had been mechanically ventilated for 2-4 and 12-74 h, respectively. Specific force generation of diaphragm myofibrils was measured with atomic force cantilevers. Rates of force development (Kact), force redevelopment after a shortening protocol (Ktr) and relaxation (Krel) in fully activated myofibrils (pCa(2+)=4.5) were calculated to assess myosin cross-bridge kinetics. Myofilament protein levels were measured with immunoblotting and specific antibodies. Prolonged CMV significantly decreased active and passive diaphragm myofibrillar force generation, Kact, Ktr and Krel. Myosin heavy chain (slow), troponin-C, troponin-I, troponin-T, tropomyosin and titin protein levels significantly decreased in response to prolonged CMV, but no effects on α-actin, α-actinin or nebulin levels were observed., Conclusions: Prolonged CMV in humans triggers significant decreases in active and passive diaphragm myofibrillar force generation. This response is mediated, in part, by impaired myosin cross-bridge kinetics and decreased myofibrillar protein levels., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Barriers to the implementation of the Centers for Disease Control and Prevention (CDC) guidelines for surgical site infection (SSI) surveillance have been described in resource-limited settings. This study aimed to estimate the SSI incidence rate in a Cambodian hospital and to compare different modalities of SSI surveillance. We performed an active prospective study with post-discharge surveillance. During the hospital stay, trained surveyors collected the CDC criteria to identify SSI by direct examination of the surgical site. After discharge, a card was given to each included patient to be presented to all practitioners examining the surgical site. Among 167 patients, direct examination of the surgical site identified a cumulative incidence rate of 14 infections per 100 patients. An independent review of medical charts presented a sensitivity of 16%. The sensitivity of the purulent drainage criterion to detect SSIs was 83%. After hospital discharge, 87% of the patients provided follow-up data, and nine purulent drainages were reported by a practitioner (cumulative incidence rate: 20%). Overall, the incidence rate was dependent on the surveillance modalities. The review of medical charts to identify SSIs during hospitalization was not effective; the use of a follow-up card with phone calls for post-discharge surveillance was effective., (Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

Introduction: Ventilator-associated respiratory infection (VARI) is an important cause of morbidity in critically-ill patients. Clinical trials performed in heterogeneous populations have suggested there are limited benefits from invasive diagnostic testing to identify patients at risk or to target antimicrobial therapy. However, multiple patient subgroups (for example, immunocompromised, antibiotic-treated) have traditionally been excluded from randomization. We hypothesized that a prospective surveillance study would better identify patients with suspected VARI (sVARI) at high risk for adverse clinical outcomes, and who might be specifically targeted in future trials., Methods: We performed a prospective observational study in all patients ventilated for greater than 48 hours. sVARI was identified by surveillance for changes in white blood cell count, temperature, sputum, and/or new chest X-ray infiltrates. Indices of disease co-morbidity, as well as mortality, duration of mechanical ventilation, and length of hospital or ICU stay were correlated with sVARI., Results: Of 1806 patients admitted to the ICU over 14 months, 267 were ventilated for greater than 48 hours, and 77 developed sVARI. Incidence of sVARI was associated with iatrogenic immunosuppression or admission for respiratory illness. Any sVARI, whether suspected ventilator-associated pneumonia (sVAP) or ventilator-associated tracheobronchitis (sVAT), was associated with increased length of stay and duration of mechanical ventilation., Conclusions: Clinical surveillance for sVARI identifies patients at risk for increased morbidity. Iatrogenically immunosuppressed patients, a subgroup previously excluded from randomized clinical trials, represent a growing proportion of the critically-ill at risk for sVARI who might be targeted for future investigations on diagnostic or therapeutic modalities.

According to UN, Cambodia is one of the poorest countries in the World. Respiratory diseases are current public health priorities. In this context, a new bronchoscopy unit (BSU) was created in the respiratory medicine department of Preah Kossamak hospital (PKH) thanks to a tight cooperation between a French and a Cambodian team. Aim of this study was to describe conditions of introduction of this equipment. Two guidelines for practice are available. They are respectively edited by the French and British societies of pulmonology. These guidelines were reviewed and compared to the conditions in which BS was introduced in PKH. Each item from guidelines was combined to a categorical value: "applied", "adapted" or "not applied". In 2009, 54 bronchoscopies were performed in PKH, mainly for suspicion of infectious or tumour disease. In total, 52% and 46% of the French and British guideline items respectively were followed in this Cambodian unit. Patient safety items are those highly followed. By contrast "staff safety" items were those weakly applied. Implementation of EBS in developing countries seems feasible in good conditions of quality and safety for patients. However, some recommendations cannot be applied due to local conditions., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)