Albumin reprograms the B cell transcriptional landscape and improves neutrophil antimicrobial function in patients with decompensated cirrhosis.

Background & Aims: Patients with acutely decompensated (AD) cirrhosis are immunocompromised and particularly susceptible to infections. This study investigated the immunomodulatory actions of albumin by which this protein may lower the incidence of infections. Methods: Blood immunophenotyping was performed in 11 patients with AD cirrhosis and 10 healthy volunteers (HV). Bulk and single-cell RNA sequencing (scRNA-seq) and flow cytometry were performed in peripheral blood mononuclear cells (PBMCs) from 20 patients with AD cirrhosis and 34 HV exposed to albumin. Albumin's effects on degranulation, phagocytosis, chemotaxis, and swarming of neutrophils from six patients with AD cirrhosis and nine HV were assessed by measuring myeloperoxidase enzymatic activity, the engulfment of fluorescent-labeled Escherichia coli and zymosan, and interactions of neutrophils with Candida albicans at single-cell resolution in microfluidic chambers, respectively. Whole blood RNA sequencing (RNA-seq) analyses were performed in 49 patients admitted for severe AD cirrhosis, of whom 30 received albumin during hospitalization. Results: Compared with HV, patients with AD cirrhosis showed severe lymphopenia and defective neutrophil antimicrobial function. Bulk and scRNA-seq analyses revealed significantly (false discovery rate [FDR] <0.05) increased signatures related to B cells, myeloid cells, and CD4+ T cells in PBMCs incubated with albumin. Changes in the B cell population were confirmed by flow cytometry. Neutrophils exposed to albumin also exhibited augmented chemotactic and degranulation responses, enhanced phagocytosis, and increased pathogen-restrictive swarming. RNA-seq data analysis in patients who had received albumin revealed specific upregulation of signatures related to B cells and neutrophils together with transcriptional changes in CD4+ T cells (FDR <0.05). Conclusions: The finding that albumin promotes the transcriptional reprogramming and expansion of the B cell compartment and improves neutrophil antimicrobial functions indicates mechanisms that may lower the incidence of infections in patients with severe AD cirrhosis receiving albumin therapy. Impact and implications: Patients with acutely decompensated cirrhosis receiving albumin as treatment have a lower incidence of infections. The reason for this protection is currently unknown, but the present study provides data that support the ability of albumin to boost the antimicrobial functions of immune cells in these patients. Moreover, these findings encourage the design of controlled clinical studies specifically aimed at investigating the effects of albumin administration on the immune system.

Antibiotic prophylaxis in digestive endoscopy: Guidelines from the French Society of Digestive Endoscopy.

Digestive endoscopy is a highly dynamic medical discipline, with the recent adoption of new endoscopic procedures. However, comprehensive guidelines on the role of antibiotic prophylaxis in these new procedures have been lacking for many years. The Guidelines Commission of the French Society of Digestive Endoscopy (SFED) convened in 2023 to establish guidelines on antibiotic prophylaxis in digestive endoscopy for all digestive endoscopic procedures, based on literature data up to September 1, 2023. This article summarizes these new guidelines and describes the literature review that fed into them.

Hepatic compartment syndrome, a rare complication after any liver insult or liver transplantation: Three case reports and literature review.

Hepatic compartment syndrome (HCS) is a rare but life-threatening entity that consists of a decreased portal flow due to intraparenchymal hypertension secondary to subcapsular liver hematoma. Lethal liver failure can be observed. We report three cases, and review the literature. A 54-year-old male was admitted for extensive hepatic subcapsular hematoma after blunt abdominal trauma. Initially, he underwent embolization of the hepatic artery's right branch, after which he presented clinical deterioration, major cytolysis (310 times the upper limit of normal [ULN]), and liver failure with a prothrombin time (PT) at 31.0%. A 56-year-old male underwent liver transplantation for acute alcoholic hepatitis. On postoperative day 2, he presented a hemorrhagic shock associated with deterioration of liver function (cytolysis 21 ULN, PT 39.0%) due to extensive hepatic subcapsular hematoma. A 59-year-old male presented a hepatic subcapsular hematoma five days after a cholecystectomy, revealed by abdominal pain with liver dysfunction (cytolysis 10 ULN, PT 63.0%). All patients ultimately underwent urgent surgery for liver capsule excision, hematoma evacuation, and liver packing, if needed. The international literature was screened for this entity. These three patients' outcomes were favorable, and all were alive at postoperative day 90. The literature review found 15 reported cases. HCS can occur after any direct or indirect liver trauma. Surgical decompression is the main treatment, and there is probably no place for arterial embolization, which may increase the risk of liver necrosis. A 13.3% mortality rate is reported. HCS is a rare complication of subcapsular liver hematoma that compresses the liver parenchyma, and leads to liver failure. Urgent surgical decompression is needed.

Comparison of mannitol and hypertonic saline solution for the treatment of suspected brain herniation during prehospital management of traumatic brain injury patients.

BACKGROUND AND IMPORTANCE: Occurrence of mydriasis during the prehospital management of traumatic brain injury (TBI) may suggest severe intracranial hypertension (ICH) subsequent to brain herniation. The initiation of hyperosmolar therapy to reduce ICH and brain herniation is recommended. Whether mannitol or hypertonic saline solution (HSS) should be preferred is unknown. OBJECTIVES: The objective of this study is to assess whether HSS, compared with mannitol, is associated with improved survival in adult trauma patients with TBI and mydriasis. DESIGN/SETTING AND PARTICIPANTS: A retrospective observational cohort study using the French Traumabase national registry to compare the ICU mortality of patients receiving either HSS or mannitol. Patients aged 16 years or older with moderate to severe TBI who presented with mydriasis during prehospital management were included. OUTCOME MEASURES AND ANALYSIS: We performed propensity score matching on a priori selected variables [i.e. age, sex and initial Coma Glasgow Scale (GCS)] with a ratio of 1 : 3 to ensure comparability between the two groups. The primary outcome was ICU mortality. The secondary outcomes were regression of pupillary abnormality during prehospital management, pulsatility index and diastolic velocity on transcranial Doppler within 24 h after TBI, early ICU mortality (within 48 h), ICU and hospital length of stay. RESULTS: Of 31 579 patients recorded in the registry between 2011 and 2021, 1417 presented with prehospital mydriasis and were included: 1172 (82.7%) received mannitol and 245 (17.3%) received HSS. After propensity score matching, 720 in the mannitol group matched 240 patients in the HSS group. Median age was 41 years [interquartile ranges (IQR) 26-60], 1058 were men (73%) and median GCS was 4 (IQR 3-6). No significant difference was observed in terms of characteristics and prehospital management between the two groups. ICU mortality was lower in the HSS group (45%) than in the mannitol group (54%) after matching [odds ratio (OR) 0.68 (0.5-0.9), P  = 0.014]. No differences were identified between the groups in terms of secondary outcomes. CONCLUSION: In this propensity-matched observational study, the prehospital osmotherapy with HSS in TBI patients with prehospital mydriasis was associated with a lower ICU mortality compared to osmotherapy with mannitol.

Predictive role of hepatic venous pressure gradient in bleeding events among patients with cirrhosis undergoing orthotopic liver transplantation.

Background & Aims: Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes. The proportion of this risk related to portal hypertension is unclear. Hepatic venous pressure gradient (HVPG) is the gold standard for estimating portal hypertension. The aim of this study was to analyze the ability of HVPG to predict intraoperative major bleeding events during OLT in patients with cirrhosis. Methods: We retrospectively analyzed a prospective database including all patients with cirrhosis who underwent OLT between 2010 and 2020 and had liver and right heart catheterizations as part of their pre-transplant assessment. The primary endpoint was the occurrence of an intraoperative major bleeding event. Results: The 468 included patients had a median HVPG of 17 mmHg [interquartile range, 13-22] and a median MELD on the day of OLT of 16 [11-24]. Intraoperative red blood cell transfusion was required in 72% of the patients (median 2 units transfused), with a median blood loss of 1,000 ml [575-1,500]. Major intraoperative bleeding occurred in 156 patients (33%) and was associated with HVPG, preoperative hemoglobin level, severity of cirrhosis at the time of OLT (MELD score, ascites, encephalopathy), hemostasis impairment (thrombocytopenia, lower fibrinogen levels), and complications of cirrhosis (sepsis, acute-on-chronic liver failure). By multivariable regression analysis with backward elimination, HVPG, preoperative hemoglobin level, MELD score, and tranexamic acid infusion were associated with the primary endpoint. Three categories of patients were identified according to HVPG: low-risk (HVPG <16 mmHg), high-risk (HVGP ≥16 mmHg), and very high-risk (HVPG ≥20 mmHg). Conclusions: HVPG predicted major bleeding events in patients with cirrhosis undergoing OLT. Including HVPG as part of pre-transplant assessment might enable better anticipation of the intraoperative course. Impact and implications: Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes but the proportion of this risk related to portal hypertension is unclear. Our work shows that hepatic venous pressure gradient (HVPG), the gold standard for estimating portal hypertension, is a strong predictor of major bleeding events and blood loss volume in patients with cirrhosis undergoing OLT. Three groups of patients can be identified according to their risk of major bleeding events: low-risk patients with HVPG <16 mmHg, high-risk patients with HVPG ≥16 mmHg, and very high-risk patients with HVPG ≥20 mmHg. HVPG could be systematically included in the pre-transplant assessment to anticipate intraoperative course and tailor patient management.

Treatment of COVID-19-associated ARDS with umbilical cord-derived mesenchymal stromal cells in the STROMA-CoV-2 multicenter randomized double-blind trial: long-term safety, respiratory function, and quality of life.

BACKGROUND: The STROMA-CoV-2 study was a French phase 2b, multicenter, double-blind, randomized, placebo-controlled clinical trial that did not identify a significant efficacy of umbilical cord-derived mesenchymal stromal cells in patients with SARS-CoV-2-induced acute respiratory distress syndrome. Safety on day 28 was found to be good. The aim of our extended study was to assess the 6- and 12-month safety of UC-MSCs administration in the STROMA-CoV-2 cohort. METHODS: A detailed multi-domain assessment was conducted at 6 and 12 months following hospital discharge focusing on adverse events, lung computed tomography-scan, pulmonary and muscular functional status, and quality of life in the STROMA-CoV-2 cohort including SARS-CoV-2-related early (< 96 h) mild-to-severe acute respiratory distress syndrome. RESULTS: Between April 2020 and October 2020, 47 patients were enrolled, of whom 19 completed a 1-year follow-up. There were no significant differences in any endpoints or adverse effects between the UC-MSCs and placebo groups at the 6- and 12-month assessments. Ground-glass opacities persisted at 1 year in 5 patients (26.3%). Furthermore, diffusing capacity for carbon monoxide remained altered over 1 year, although no patient required oxygen or non-invasive ventilatory support. Quality of life revealed declines in mental, emotional and physical health throughout the follow-up period, and the six-minute walking distance remained slightly impaired at the 1-year patient assessment. CONCLUSIONS: This study suggests a favorable safety profile for the use of intravenous UC-MSCs in the context of the first French wave of SARS-CoV-2-related moderate-to-severe acute respiratory distress syndrome, with no adverse effects observed at 1 year.

Association of severe postpartum hemorrhage and development of psychological disorders: Results from the prospective and multicentre HELP MOM study.

OBJECTIVE: Post-partum hemorrhage (PPH) is the leading preventable cause of worldwide maternal morbidity and mortality. Risk factors for psychological disorders following PPH are currently unknown. HELP-MOM study aimed to determine the incidence and identify risk factors for psychological disorders following PPH. METHODS: HELP-MOM study was a prospective, observational, national, and multicentre study including patients who experienced severe PPH requiring sulprostone. The primary endpoint was the occurrence of psychological disorders (anxiety and/or post-traumatic disorder and/or depression) following PPH, assessed at 1, 3, and 6 months after delivery using HADS, IES-R, and EPDS scales. RESULTS: Between November 2014 and November 2016, 332 patients experienced a severe PPH and 236 (72%) answered self-questionnaires at 1, 3, and 6 months. A total of 161 (68%) patients declared a psychological disorder following severe PPH (146 (90.1%) were screened positive for anxiety, 96 (58.9%) were screened positive for post-traumatic stress disorder, and 94 (57.7%) were screened positive for post-partum depression). In multivariable analysis, the use of intra-uterine tamponnement balloon was associated with a lower risk to be screened positive for psychological disorder after severe PPH (OR = 0.33 [IC95% 0.15-0.69], p = 0.004, and after propensity score matching (OR=0.34 [IC95% 0.12-0.94], p = 0.04)). Low hemoglobin values during severe PPH management were associated with a higher risk of being screened positive for psychological disorders. Finally, we did not find differences in desire or pregnancy between patients without or with psychological disorders occurring in the year after severe PPH. DISCUSSION: Severe PPH was associated with significant psychosocial morbidity including anxiety, post-traumatic disorder, and depression. This should engage a psychological follow-up. Large cohorts are urgently needed to confirm our results. REGISTRATION: ClinicalTrials.gov under number NCT02118038.

Evaluation of iron metabolism in hospitalized COVID-19 patients.

BACKGROUND: Iron metabolism dysregulation may play a role in organ failure observed in Coronavirus disease 2019 (COVID-19). This study aimed to explore the whole iron metabolism in hospitalized COVID-19 patients and evaluate the impact of tocilizumab. METHODS: We performed an observational multicentric cohort study, including patients with PCR-provenCOVID-19 from the intensive care unit (ICU) (n = 66) and medical ward (n = 38). We measured serum interleukin-6 (IL-6), ferritin, glycosylated ferritin (GF), transferrin, iron, and hepcidin. The primary outcome was death. RESULTS: Among the 104 patients, we observed decreased median GF percentage (35 %; IQ 23-51.5), low iron concentration (7.5 µmol/L; IQ 4-14), normal but low transferrin saturation (TSAT; 21%; IQ 11-33) and increased median hepcidin concentration (58.7 ng/mL; IQ 20.1-92.1). IL-6, ferritin, and GF were independently and significantly associated with death (p = 0.026, p = 0.023, and p = 0.009, respectively). Surprisingly, we observed a decorrelation between hepcidin and IL-6 concentrations in some patients. These findings were amplified in tocilizumab-treated patients. CONCLUSION: Iron metabolism is profoundly modified in COVID-19. The pattern we observed presents differences with a typical inflammation profile. We observed uncoupled IL-6/hepcidin levels in some patients. The benefit of additive iron chelation therapy should be questionable in this setting.

Refining Auxiliary Orthotopic Liver Transplantation (AOLT) Improves Outcomes in Adult Patients With Acute Liver Failure.

OBJECTIVE: To investigate whether and how experience accumulation and technical refinements simultaneously implemented in auxiliary orthotopic liver transplantation (AOLT) may impact on outcomes. BACKGROUND: AOLT for acute liver failure (ALF) provides the unique chance of complete immunosuppression withdrawal after adequate native liver remnant regeneration but is a technically demanding procedure. Our department is a reference center for ALF and an early adopter of AOLT. METHODS: This is a single-center retrospective before/after study of a prospectively maintained cohort of 48 patients with ALF who underwent AOLT between 1993 and 2019. In 2012, technical refinements were implemented to improve outcomes: (i) favoring the volume of the graft rather than that of the native liver, (ii) direct anastomosis of graft hepatic artery with recipient right hepatic artery instead of the use of large size vessels, (iii) end-to-side hepaticocholedocostomy instead of bilioenteric anastomosis. Early experience (1993-2011) group (n=26) and recent experience (2012-2019) group (n=22) were compared. Primary endpoint was 90-day severe morbidity rate (Clavien-Dindo≥IIIa) and secondary endpoints were overall patient survival and complete immunosuppression withdrawal rates. RESULTS: Compared with the earlier experience group, the recent experience group was associated with a lower severe complication rate (27% vs 65%, P <0.001), as well as less biliary (18% vs 54%, P =0.017) and arterial (0% vs 15%, P =0.115) complications. The 1-, 3-, and 5-year patient survival was significantly improved (91%, 91%, 91% vs 76%, 61%, 60%, P =0.045). The rate of complete immunosuppression withdrawal increased to 94% vs 70%, ( P =0.091) with no need of long-term graft explant. CONCLUSION: These technical refinements favoring the liver graft and reducing morbidity may promote AOLT implementation among LT centers.

Improving clinical suspicion of acute mesenteric ischemia among patients with acute abdomen: a cross-sectional study from an intestinal stroke center.

BACKGROUND: Early diagnosis of acute mesenteric ischemia (AMI) is essential for a favorable outcome. Selection of patients requiring a dedicated multiphasic computed tomography (CT) scan remains a clinical challenge. METHODS: In this cross-sectional diagnostic study conducted from 2016 to 2018, we compared the presentation of AMI patients admitted to an intestinal stroke center to patients with acute abdominal pain of another origin admitted to the emergency room (controls). RESULTS: We included 137 patients-52 with AMI and 85 controls. Patients with AMI [median age: 65 years (interquartile range 55-74)] had arterial and venous AMI in 65% and 35% of cases, respectively. Relative to controls, AMI patients were significantly older, more likely to have risk factors or a history of cardiovascular disease, and more likely to present with sudden-onset and morphine-requiring abdominal pain, hematochezia, guarding, organ dysfunction, higher white blood cell and neutrophil counts, and higher plasma C-reactive protein (CRP) and procalcitonin concentrations. On multivariate analysis, two independent factors were associated with the diagnosis of AMI: the sudden-onset (OR = 20, 95%CI 7-60, p < 0.001) and the morphine-requiring nature of the acute abdominal pain (OR = 6, 95%CI 2-16, p = 0.002). Sudden-onset and/or morphine-requiring abdominal pain was present in 88% of AMI patients versus 28% in controls (p < 0.001). The area under the receiver operating characteristic curve for the diagnosis of AMI was 0.84 (95%CI 0.77-0.91), depending on the number of factors. CONCLUSIONS: Sudden onset and the need for morphine are suggestive of AMI in patients with acute abdominal pain and should prompt multiphasic CT scan including arterial and venous phase images for confirmation.

Guidelines on perioperative optimization protocol for the adult patient 2023.

OBJECTIVE: The French Society of Anesthesiology and Intensive Care Medicine [Société Française d'Anesthésie et de Réanimation (SFAR)] aimed at providing guidelines for the implementation of perioperative optimization programs. DESIGN: A consensus committee of 29 experts from the SFAR was convened. A formal conflict-of-interest policy was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. METHODS: Four fields were defined: 1) Generalities on perioperative optimization programs; 2) Preoperative measures; 3) Intraoperative measures and; 4) Postoperative measures. For each field, the objective of the recommendations was to answer a number of questions formulated according to the PICO model (population, intervention, comparison, and outcomes). Based on these questions, an extensive bibliographic search was carried out using predefined keywords according to PRISMA guidelines and analyzed using the GRADE® methodology. The recommendations were formulated according to the GRADE® methodology and then voted on by all the experts according to the GRADE grid method. As the GRADE® methodology could have been fully applied for the vast majority of questions, the recommendations were formulated using a "formalized expert recommendations" format. RESULTS: The experts' work on synthesis and application of the GRADE® method resulted in 30 recommendations. Among the formalized recommendations, 19 were found to have a high level of evidence (GRADE 1±) and ten a low level of evidence (GRADE 2±). For one recommendation, the GRADE methodology could not be fully applied, resulting in an expert opinion. Two questions did not find any response in the literature. After two rounds of rating and several amendments, strong agreement was reached for all the recommendations. CONCLUSIONS: Strong agreement among the experts was obtained to provide 30 recommendations for the elaboration and/or implementation of perioperative optimization programs in the highest number of surgical fields.

MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming.

Recent data have shown that liver fibrosis can regress even at later stages of cirrhosis and shifting the immune response from pro-inflammatory towards a resolutive profile is considered as a promising option. The immune regulatory networks that govern the shift of the inflammatory phenotype and thus potential reversal of liver fibrosis are lesser known. Here we show that in precision-cut human liver slices obtained from patients with end-stage fibrosis and in mouse models, inhibiting Mucosal-Associated Invariant T (MAIT) cells using pharmacological or antibody-driven approaches, limits fibrosis progression and even regresses fibrosis, following chronic toxic- or non-alcoholic steatohepatitis (NASH)-induced liver injury. Mechanistic studies, combining RNA sequencing, in vivo functional studies (performed in male mice) and co-culture experiments indicate that disruption of the MAIT cell-monocyte/macrophage interaction results in resolution of fibrosis both by increasing the frequency of restorative Ly6Clo at the expenses of pro-fibrogenic Ly6Chi monocyte-derived macrophages and promoting an autophagic phenotype in both subsets. Thus, our data show that MAIT cell activation and the consequential phenotype shift of liver macrophages are important pathogenic features of liver fibrosis and could be targeted by anti-fibrogenic therapy.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia.

PURPOSE: Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. METHODS: The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. RESULTS: Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. CONCLUSIONS: In these international guidelines, ERS, ESICM, ESCMID, and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment, and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

Team-family conflicts over end-of-life decisions in ICU: A survey of French physicians' beliefs.

INTRODUCTION: Conflicts between relatives and physicians may arise when decisions are being made about limiting life-sustaining therapies (LST). The aim of this study was to describe the motives for, and management of team-family conflicts surrounding LST limitation decisions in French adult ICUs. METHODS: Between June and October 2021, French ICU physicians were invited to answer a questionnaire. The development of the questionnaire followed a validated methodology with the collaboration of consultants in clinical ethics, a sociologist, a statistician and ICU clinicians. RESULTS: Among 186 physicians contacted, 160 (86%) answered all the questions. Conflicts over LST limitation decisions were mainly related to requests by relatives to continue treatments considered to be unreasonably obstinate by ICU physicians. The absence of advance directives, a lack of communication, a multitude of relatives, and religious or cultural issues were frequently mentioned as factors contributing to conflicts. Iterative interviews with relatives and proposal of psychological support were the most widely used tools in attempting to resolve conflict, while the intervention of a palliative care team, a local ethics resource or the hospital mediator were rarely solicited. In most cases, the decision was suspended at least temporarily. Possible consequences include stress and psychological exhaustion among caregivers. Improving communication and anticipation by knowing the patient's wishes would help avoid these conflicts. CONCLUSION: Team-family conflicts during LST limitation decisions are mainly related to requests from relatives to continue treatments deemed unreasonable by physicians. Reflection on the role of relatives in the decision-making process seems essential for the future.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia.

BACKGROUND: Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and while European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. MATERIALS AND METHODOLOGY: The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. RESULTS: Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. CONCLUSIONS: In these international guidelines, ERS, ESICM, ESCMID and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

Risk factors of second ventilator-associated pneumonia in trauma patients: a retrospective cohort study.

BACKGROUND: Ventilator acquired pneumonia (VAP) is a frequent and serious complication in ICU. Second episodes of VAP are common in trauma patients and may be related to severity of underlying conditions, treatment or bacterial factors of the first VAP. The aim of this study was to identify risk factors of second VAP episodes in trauma injured patients (defined as the development of a new pulmonary infection during or remotely following the first episode). DESIGN: This is a single-center, retrospective cohort study of trauma injured patients who underwent a first episode of VAP between January 1, 2013 and December 31, 2020 at Beaujon Hospital. RESULTS: A total of 533 patients with a first episode of VAP were analyzed, mostly with head and/or thoracic traumatic injury. A second episode of VAP occurred in one hundred sixty-seven patients (31.3%). The main risk factors found was the degree of hypoxemia at the time of the first episode [PaO2/FiO2 ratio 100-200, OR 3.12 (1.77-5.69); < 100, OR 5.80 (2.70-12.8)] and severe traumatic brain injury characterized by an initial GCS ≤ 8 [OR 1.65 (1.01-2.74)]. CONCLUSION: Depth of hypoxemia during the first VAP episode and severity of the initial brain injury are the main risk factors for VAP second episode in trauma injured patients.

Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial.

PURPOSE: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients. METHODS: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomly assigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferon gamma-1b (100 µg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome was a composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 with interim safety analyses after enrolling 50 and 100 patients. RESULTS: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b, and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41-66) years; 37 (33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55 participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquired pneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94-3.29; P = 0.08). Serious adverse events were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in the placebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroup of patients with decreased CCL17 response to interferon-gamma treatment. CONCLUSIONS: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment.

Evaluation of transcranial Doppler use in patients with acute liver failure listed for emergency liver transplantation.

PURPOSE: Acute liver failure (ALF) is characterized by hepatic encephalopathy (HE) often due to intracranial hypertension (ICH). The risk/benefit-balance of intraparenchymal pressure catheter monitoring is controversial during ALF. AIMS: Perform an evaluation of transcranial Doppler (TCD) use in patients with ALF listed for emergency liver transplantation. MATERIAL AND METHODS: Single center retrospective cohort study including all patients registered on high emergency LT list between 2012 and 2018. All TCD measurements performed during ICU stay after listing and after LT (when performed) were recorded. TCD was considered abnormal when pulsatility index (PI) was >1.2. RESULTS: Among 106 patients with ALF, forty-seven (44%) had a TCD while on list. They had more severe liver and extrahepatic organ failure. When performed, TCD was abnormal in 51% of patients. These patients more frequently developed ICH events (45% vs. 13%, p = .02) and more frequently required increase in sedative drugs and vasopressors. While 22% of patients with normal TCD spontaneously survived, all of those with abnormal TCD died or were transplanted (p = .02). All transplanted patients who had abnormal exams normalized their TCD within 2 (1-2) days after LT. CONCLUSION: TCD may be a useful non-invasive tool for ICH detection and management, then guide sedation withdrawal.