Belgian patients of the European Registry for Hidradenitis Suppurativa (ERHS-Be): data, scores and phenotypes since 2015.

Introduction Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease, characterized by painful and recurrent lesions in apocrine gland-bearing skin areas. It is a heterogeneous disease, which makes assessment and data collection difficult. Questionnaires with detailed items, such as the Belgian European Registry for Hidradenitis Suppurativa (ERHS-Be), are useful to study HS and its associated comorbidities. The aim of this registry is to uncover new factors associated with HS, understand HS patients' clinical profiles and efficacy of treatments. Material and methods The ERHS-Be registry is based on questionnaires, with sections for socio-demographic data, medical and HS history, clinical examination and treatment plan. It allows identification of different clinical phenotypes and automatic calculation of severity scores. Results At present, 606 patients are included in the ERHS-Be (67% women, 33% men). Mean age at first visit is 38.5 years. Tobacco use is present in 72.6% of patients. A family history of HS is noted in 42% of patients. Comorbidities are documented in this cohort: depression is present in 43.8% of patients, arthritis in 27.8%, obesity in 31.5%, hypertension in 10.6%, diabetes mellitus in 6.4% and dyslipidemia in 12.4%. Moreover, 7.7% of patients suffer from IBD and 27.4% have a pilonidal sinus. History of severe acne is found in 32.1% of patients and psoriasis in 9.3%. Thirteen percent of women in our cohort suffer from polycystic ovarian syndrome. Severity of disease is quantified in 533 patients: for instance, Hurley I, II and III scores proportions are respectively 32.3%, 52.7% and 15%, while the mean IHS4 score is 5.2. This registry also enables determination of relative phenotype proportions in our cohort, according to different classifications. Conclusion The ERHS-Be questionnaires allow systematic and larger data collection, including detailed comorbidities, phenotypes and severity of disease. Analysis of this large database will contribute to a better understanding and management of HS, at a time where new therapeutic options are becoming available.

A regular screening for hepatitis delta virus among chronic hepatitis B carriers improves the diagnostic of this infection and of subsequent cirrhosis development.

BACKGROUND AND OBJECTIVE: The prevalence of Hepatitis Delta Virus (HDV) is underestimated and the assessment of fibrosis is recommended for this infection. We tested the diagnostic impact of an annual screening for HDV serology in Hepatitis B Surface Antigen (HBs Ag) chronic carriers and followed the progression of fibrosis in these patients. METHODS: Between January 2014 and October 2021, we annually tested all chronic HBs Ag-positive patients for HDV antibody (HDV Ab). Each HDV Ab positive patient underwent annually repeated elastometry. Patients with detectable HDV RNA levels (group 1) were compared to those with undetectable HDV RNA (group 2). RESULTS: We identified 610 chronic HBs Ag-positive patients, and repeated screening for HDV Ab was performed in 534 patients. Sixty (11%) patients were HDV Ab positive at baseline and were considered as "coinfected". Seven cases of HDV superinfection were diagnosed through repeated screening. In co-infected patients, cirrhosis was initially diagnosed in 12/60 patients and developed in six patients during follow-up. HDV RNA PCR was performed in 57/67 patients and 27 had detectable levels (group 1). Cumulative incidence of cirrhosis at 7 years was 13.8% (95% CI 0-30) in group 1 and 0 (95% CI 0-0) in group 2 (p = 0.026). CONCLUSION: A systematic screening for HDV in chronic HB Ag carriers revealed a high prevalence of HDV Ab. Repeated serological screening enables the diagnosis of superinfections in asymptomatic patients. Regular assessment of fibrosis using elastometry leads to the identification of incidental cirrhosis in patients with detectable HDV RNA.

Intravenous Hemin, a potential heme oxygenase-1 activator, does not protect from post-ERCP acute pancreatitis in humans: Results of a randomized multicentric multinational placebo-controlled trial.

OBJECTIVE: Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk. METHODS: In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay. RESULTS: A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups. CONCLUSION: We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01855841).

Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm: A Meta-Analysis.

Importance: International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable. Objective: To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm. Data Sources: Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis. Study Selection: The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score. Data Extraction and Synthesis: Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation. Main Outcomes and Measures: The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5. Results: A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups. Conclusions and Relevance: In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.

The effect of increased positive end expiratory pressure on brain tissue oxygenation and intracranial pressure in acute brain injury patients.

Cerebral hypoxia is an important cause of secondary brain injury. Improving systemic oxygenation may increase brain tissue oxygenation (PbtO2). The effects of increased positive end-expiratory pressure (PEEP) on PbtO2 and intracranial pressure (ICP) needs to be further elucidated. This is a single center retrospective cohort study (2016-2021) conducted in a 34-bed Department of Intensive Care unit. All patients with acute brain injury under mechanical ventilation who were monitored with intracranial pressure and brain tissue oxygenation (PbtO2) catheters and underwent at least one PEEP increment were included in the study. Primary outcome was the rate of PbtO2 responders (increase in PbtO2 > 20% of baseline) after PEEP increase. ΔPEEP was defined as the difference between PEEP at 1 h and PEEP at baseline; similarly ΔPbtO2 was defined as the difference between PbtO2 at 1 h after PEEP incrementation and PbtO2 at baseline. We included 112 patients who underwent 295 episodes of PEEP increase. Overall, the median PEEP increased form 6 (IQR 5-8) to 10 (IQR 8-12) cmH2O (p = 0.001), the median PbtO2 increased from 21 (IQR 16-29) mmHg to 23 (IQR 18-30) mmHg (p = 0.001), while ICP remained unchanged [from 12 (7-18) mmHg to 12 (7-17) mmHg; p = 0.42]. Of 163 episode of PEEP increments with concomitant PbtO2 monitoring, 34 (21%) were PbtO2 responders. A lower baseline PbtO2 (OR 0.83 [0.73-0.96)]) was associated with the probability of being responder. ICP increased in 142/295 episodes of PEEP increments (58%); no baseline variable was able to identify this response. In PbtO2 responders there was a moderate positive correlation between ΔPbtO2 and ΔPEEP (r = 0.459 [95% CI 0.133-0.696]. The response in PbtO2 and ICP to PEEP elevations in brain injury patients is highly variable. Lower PbtO2 values at baseline could predict a significant increase in brain oxygenation after PEEP increase.

A machine learning-based classification of adult-onset diabetes identifies patients at risk of liver-related complications.

Background & aims: Diabetes mellitus is a major risk factor for fatty liver disease development and progression. A novel machine learning method identified five clusters of patients with diabetes, with different characteristics and risk of diabetic complications using six clinical and biological variables. We evaluated whether this new classification could identify individuals with an increased risk of liver-related complications. Methods: We used a prospective cohort of patients with a diagnosis of type 1 or type 2 diabetes without evidence of advanced fibrosis at baseline recruited between 2000 and 2020. We assessed the risk of each diabetic cluster of developing liver-related complications (i.e. ascites, encephalopathy, variceal haemorrhage, hepatocellular carcinoma), using competing risk analyses. Results: We included 1,068 patients, of whom 162 (15.2%) were determined to be in the severe autoimmune diabetes subgroup, 266 (24.9%) had severe insulin-deficient diabetes, 95 (8.9%) had severe insulin-resistant diabetes (SIRD), 359 (33.6%) had mild obesity-related diabetes, and 186 (17.4%) were in the mild age-related diabetes subgroup. In multivariable analysis, patients in the SIRD cluster and those with excessive alcohol consumption at baseline had the highest risk for liver-related events. The SIRD cluster, excessive alcohol consumption, and hypertension were independently associated with clinically significant fibrosis, evaluated by liver biopsy or transient elastography. Using a simplified classification, patients assigned to the severe and mild insulin-resistant groups had a three- and twofold greater risk, respectively, of developing significant fibrosis compared with those in the insulin-deficient group. Conclusions: A novel clustering classification adequately stratifies the risk of liver-related events in a population with diabetes. Our results also underline the impact of the severity of insulin resistance and alcohol consumption as key prognostic risk factors for liver-related complications. Impact and implications: Diabetes represents a major risk factor for NAFLD development and progression. This study examined the ability of a novel machine-learning approach to identify at-risk diabetes subtypes for liver-related complications. Our results suggest that patients that had severe insulin resistance had the highest risk of liver-related outcomes and fibrosis progression. Moreover, excessive alcohol consumption at the diagnosis of diabetes was the strongest risk factor for developing liver-related events.

Treatment of Acne with Isotretinoin Should Be Avoided in Patients with Hidradenitis Suppurativa "Conglobata Phenotype".

BACKGROUND: Acne conglobata (AC) and nodulocystic acne have long been confused clinically, despite the presentation and the response to treatment being different. AC and hidradenitis suppurativa (HS) resemble each other; a subtype of HS called "conglobata phenotype" has recently been reported in a large Dutch cohort. Acne vulgaris and HS are often associated. Isotretinoin is typically ineffective in treating HS and may even aggravate it, but it is often indispensable in treating acne vulgaris. OBJECTIVE: The aim of the study was to assess whether isotretinoin may be used safely in adults with both HS and acne vulgaris and when it might be contraindicated. MATERIALS AND METHODS: Belgian HS patients from the European Registry for Hidradenitis Suppurativa Registry (ERHS) reporting a history of severe acne of the face and/or the back, and who have ever used isotretinoin for their acne, were all selected. Patients whose acne worsened on isotretinoin were compared to patients whose acne did not worsen (improvement or no change). RESULTS: Among the 82 selected patients, 10 (12.2%) report that their acne was aggravated while taking isotretinoin, while 72 (87.8%) report that their acne was not aggravated on isotretinoin. Of the 10 HS patients whose acne worsened with isotretinoin, 9 (90%) were men (p = 0.04) and 8 (80%) were HS "conglobata phenotype" (p < 0.001). In contrast, 47 (65.3%) of the 72 patients whose acne did not worsen on isotretinoin belonged to the HS "regular phenotype" (p = 0.01). On multivariate analysis, the item most strongly associated with poor response to isotretinoin was the HS "conglobata phenotype," followed by body mass index (BMI) (worse response to isotretinoin if BMI >25 kg/m2). Additionally, of 26 patients who received isotretinoin while their HS had already started, only 6 (23.1%) reported isotretinoin effectiveness on their HS. CONCLUSION: Subject to confirmation by larger studies, our study suggests that isotretinoin should be avoided in the treatment of acne in HS patients with the HS "conglobata phenotype," as it may worsen the acne, likewise being male or having a BMI above 25 seems to increase this risk of a bad therapeutic outcome. Patients with an HS "regular phenotype" appear to be at a reduced risk of isotretinoin treatment worsening their acne.

Overview and comparison of the clinical scores in hidradenitis suppurativa: A real-life clinical data.

Introduction: Partly due to its clinical heterogeneity, hidradenitis suppurativa (HS) is difficult to score accurately; illustrated by the large number of disease scores. In 2016, a systematic review by Ingram et al. reported the use of about thirty scores, and since then, this number has increased further. Our aim is twofold: to provide a succinct but detailed narrative review of the scores used to date, and to compare these scores with each other for individual patients. Materials and methods: The review of the literature was done among articles in English and French, on Google, Google scholar, Pubmed, ScienceDirect and Cochrane. To illustrate the differences between scores, data from some Belgian patients included in the European Registry for HS were selected. A first series of patients compares the severity of the following scores: Hurley, Hurley Staging refined, three versions of Sartorius score (2003, 2007, 2009), Hidradenitis Suppurativa Physician Global Assessment (HS-PGA), International Hidradenitis Suppurativa Severity Scoring System (IHS4), Severity Assessment of Hidradenitis Suppurativa (SAHS), Hidradenitis Suppurativa Severity Index (HSSI), Acne Inversa Severity Index (AISI), the Static Metascore, and one score that is not specific to HS: Dermatology Life Quality Index (DLQI). A second set of patients illustrates how some scores change over time and with treatment: Hurley, Hurley Staging refined, Sartorius 2003, Sartorius 2007, HS-PGA, IHS4, SAHS, AISI, Hidradenitis Suppurativa Clinical Response (HiSCR), the very new iHS4-55, the Dynamic Metascore, and DLQI. Results: Nineteen scores are detailed in this overview. We illustrate that for some patients, the scores do not predictably and consistently correlate with each other, either in an evaluation of the severity at a time-point t, or in the evaluation of the response to a treatment. Some patients in this cohort may be considered responders according to some scores, but non-responders according to others. The clinical heterogeneity of the disease, represented by its many phenotypes, seems partly to explain this difference. Conclusion: These examples illustrate how the choice of a score can lead to different interpretations of the response to a treatment, or even potentially change the results of a randomized clinical trial.

Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest.

INTRODUCTION: Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA. METHODS: After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C. RESULTS: Thirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls. CONCLUSIONS: In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury.

C-Reactive protein kinetics after cardiac surgery: A retrospective multicenter study.

Background: Recognition of postoperative infection after cardiac surgery is challenging. Biomarkers may be very useful to recognize infection at early stage, but the literature is controversial. Methods: We conducted a retrospective study at two large University Hospitals, including adult patients undergoing cardiac surgery (excluding those with preoperative infections, cirrhotic or immunocompromised). We evaluated the kinetics of C-Reactive Protein (CRP) and White Cell Count (WCC) during the first postoperative week. Primary outcomes were CRP and WCC changes according to the development of postoperative infection. In order to evaluate the influence of cardiopulmonary bypass on biomarker kinetics, we also studied CRP and WCC changes in patients without postoperative infection and undergoing on- vs off-pump coronary-artery bypass grafting. Results: Among 429 included, 45 patients (10.5%) had evidence of postoperative infection. Patients with postoperative infection had higher CRP and WCC values than those without infection, with between-groups difference becoming significant from postoperative day 2 for CRP (120.6 ± 3.6 vs. 134.6 ± 7.9, P < 0.01), and from postoperative day 3 for WCC (10.5 ± 0.5 vs. 9.9 ± 0.2, P = 0.02). Over the postoperative period, CRP and WCC showed significant within-group changes regardless of development of postoperative infection (P < 0.001 for both). We found no differences in CRP and WCC kinetics between patients undergoing on- vs off-pump procedure. Conclusions: During the first week after cardiac surgery, CRP increases one day earlier than WCC in patients developing postoperative infections, with such difference becoming significant on the second postoperative day. In not infected patients, use of cardiopulmonary bypass does not influence CRP and WCC kinetics.

Effects of rapid fluid infusion on hemoglobin concentration: a systematic review and meta-analysis.

BACKGROUND: Rapid fluid administration may decrease hemoglobin concentration (Hb) by a diluting effect, which could limit the increase in oxygen delivery (DO2) expected with a positive response to fluid challenge in critically ill patients. Our aim was to quantify the decrease in Hb after rapid fluid administration. METHODS: Our protocol was registered in PROSPERO (CRD42020165146). We searched PubMed, the Cochrane Database, and Embase from inception until February 15, 2022. We selected studies that reported Hb before and after rapid fluid administration (bolus fluid given over less than 120 min) with crystalloids and/or colloids in adults. Exclusion criteria were studies that included bleeding patients, or used transfusions or extracorporeal circulation procedures. Studies were divided according to whether they involved non-acutely ill or acutely ill (surgical/trauma, sepsis, circulatory shock or severe hypovolemia, and mixed conditions) subjects. The mean Hb difference and, where reported, the DO2 difference before and after fluid administration were extracted. Meta-analyses were conducted to assess differences in Hb before and after rapid fluid administration in all subjects and across subgroups. Random-effect models, meta-regressions and subgroup analyses were performed for meta-analyses. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. RESULTS: Sixty-five studies met our inclusion criteria (40 in non-acutely ill and 25 in acutely ill subjects), with a total of 2794 participants. Risk of bias was assessed as "low" for randomized controlled trials (RCTs) and 'low to moderate' for non-RCTs. Across 63 studies suitable for meta-analysis, the Hb decreased significantly by a mean of 1.33 g/dL [95% CI - 1.45 to - 1.12; p < 0.001; I2 = 96.88] after fluid administration: in non-acutely ill subjects, the mean decrease was 1.56 g/dL [95% CI - 1.69 to - 1.42; p < 0.001; I2 = 96.71] and in acutely ill patients 0.84 g/dL [95% CI - 1.03 to - 0.64; p = 0.033; I2 = 92.91]. The decrease in Hb was less marked in patients with sepsis than in other acutely ill patients. The DO2 decreased significantly in fluid non-responders with a significant decrease in Hb. CONCLUSIONS: Hb decreased consistently after rapid fluid administration with moderate certainty of evidence. This effect may limit the positive effects of fluid challenges on DO2 and thus on tissue oxygenation.

Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock.

BACKGROUND: Angiotensin II is one of the vasopressors available for use in septic shock. However, its effects on the septic myocardium remain unclear. The aim of the study was to compare the effects of angiotensin II and norepinephrine on cardiac function and myocardial oxygen consumption, inflammation and injury in experimental septic shock. METHODS: This randomized, open-label, controlled study was performed in 20 anesthetized and mechanically ventilated pigs. Septic shock was induced by fecal peritonitis in 16 animals, and four pigs served as shams. Resuscitation with fluids, antimicrobial therapy and abdominal drainage was initiated one hour after the onset of septic shock. Septic pigs were randomly allocated to receive one of the two drugs to maintain mean arterial pressure between 65 and 75 mmHg for 8 h. RESULTS: There were no differences in MAP, cardiac output, heart rate, fluid balance or tissue perfusion indices in the two treatment groups but myocardial oxygen consumption was greater in the norepinephrine-treated animals. Myocardial mRNA expression of interleukin-6, interleukin-6 receptor, interleukin-1 alpha, and interleukin-1 beta was higher in the norepinephrine than in the angiotensin II group. CONCLUSIONS: In septic shock, angiotensin II administration is associated with a similar level of cardiovascular resuscitation and less myocardial oxygen consumption, and inflammation compared to norepinephrine.

Factors Associated With Brain Tissue Oxygenation Changes After RBC Transfusion in Acute Brain Injury Patients.

OBJECTIVES: Anemia is common after acute brain injury and can be associated with brain tissue hypoxia. RBC transfusion (RBCT) can improve brain oxygenation; however, predictors of such improvement remain unknown. We aimed to identify the factors associated with PbtO2 increase (greater than 20% from baseline value) after RBCT, using a generalized mixed model. DESIGN: This is a multicentric retrospective cohort study (2012-2020). SETTING: This study was conducted in three European ICUs of University Hospitals located in Belgium, Switzerland, and Austria. PATIENTS: All patients with acute brain injury who were monitored with brain tissue oxygenation (PbtO2) catheters and received at least one RBCT. INTERVENTION: Patients received at least one RBCT. PbtO2 was recorded before, 1 hour, and 2 hours after RBCT. MEASUREMENTS AND MAIN RESULTS: We included 69 patients receiving a total of 109 RBCTs after a median of 9 days (5-13 d) after injury. Baseline hemoglobin (Hb) and PbtO2 were 7.9 g/dL [7.3-8.7 g/dL] and 21 mm Hg (16-26 mm Hg), respectively; 2 hours after RBCT, the median absolute Hb and PbtO2 increases from baseline were 1.2 g/dL [0.8-1.8 g/dL] (p = 0.001) and 3 mm Hg (0-6 mm Hg) (p = 0.001). A 20% increase in PbtO2 after RBCT was observed in 45 transfusions (41%). High heart rate (HR) and low PbtO2 at baseline were independently associated with a 20% increase in PbtO2 after RBCT. Baseline PbtO2 had an area under receiver operator characteristic of 0.73 (95% CI, 0.64-0.83) to predict PbtO2 increase; a PbtO2 of 20 mm Hg had a sensitivity of 58% and a specificity of 73% to predict PbtO2 increase after RBCT. CONCLUSIONS: Lower PbtO2 values and high HR at baseline could predict a significant increase in brain oxygenation after RBCT.

Characteristics and Outcomes of Patients in the ICU With Respiratory Syncytial Virus Compared With Those With Influenza Infection: A Multicenter Matched Cohort Study.

BACKGROUND: The characteristics and outcomes of adult patients with respiratory syncytial virus (RSV) infection who require ICU admission are poorly defined. Although several studies in adults with RSV infection have been published in recent years, they did not focus specifically on patients with critical illness. RESEARCH QUESTION: What are the characteristics and outcomes of adult patients in the ICU with RSV infection and how do they compare with those of patients in the ICU with influenza infection? STUDY DESIGN AND METHODS: This retrospective, multicenter study in France and Belgium (17 sites) compared the characteristics and outcomes of adult patients in the ICU with RSV infection vs those with influenza infection between November 2011 and April 2018. Each patient with RSV infection was matched by institution and date of diagnosis with a patient with influenza infection. In-hospital mortality was compared between the two groups, with adjustment for prognostic factors in a multivariate model (sex, age, main underlying conditions, and concurrent bloodstream infection). RESULTS: Data from 618 patients (309 with RSV infection and 309 with influenza infection) were analyzed. Patients with RSV infection were significantly more likely to have an underlying chronic respiratory condition (60.2% vs 40.1%; P < .001) and to be immunocompromised (35% vs 26.2%; P = .02) than patients with influenza infection. Several differences in clinical signs and biological data at diagnosis were found between the groups. In-hospital mortality was not significantly different between the two groups (23.9% in the RSV group vs 25.6% in the influenza group; P = .63), even after adjustment for prognostic factors in a multivariate model. INTERPRETATION: Adult patients in the ICU with RSV infection differ from adult patients in the ICU with influenza in terms of comorbidities and characteristics at diagnosis. RSV infection was associated with high in-hospital mortality, approaching 25%. In multivariate analysis, RSV infection was associated with a similar odds of in-hospital death compared with influenza infection.

Early Pupillometry Assessment in Traumatic Brain Injury Patients: A Retrospective Study.

BACKGROUND: The aim of this study was to evaluate whether the early assessment of neurological pupil index (NPi) values derived from automated pupillometry could predict neurological outcome after traumatic brain injury (TBI). METHODS: Retrospective observational study including adult (>18 years) TBI patients admitted from January 2018 to December 2020, with available NPi on admission. Abnormal NPi was considered if <3. Unfavorable neurological outcome (UO) at hospital discharge was considered for a Glasgow Outcome Scale of 1-3. RESULTS: 100 patients were included over the study period (median age 48 (34-69) years and median GCS on admission 11 (6-15)); 49 (49%) patients had UO. On admission, 20 (20%) patients had an abnormal NPi (NPi < 3); median worst (i.e., from both eyes) NPi was 4.2 (3.2-4.5). Median worst and mean NPi on admission were significantly lower in the UO group than others (3.9 (1.7-4.4) vs. 4.4 (3.7-4.6); p = 0.005-4.0 (2.6-4.5) vs. 4.5 (3.9-4.7); p = 0.002, respectively). The ROC curve for the worst and mean NPi showed a moderate accuracy to predict UO (AUC 0.66 (0.56-0.77); p = 0.005 and 0.68 (0.57-0.78); p = 0.002). However, in a generalized linear model, the prognostic role of NPi on admission was limited. CONCLUSIONS: Low NPi on admission has limited prognostic value in TBI.

Prediction of Insufficient Beta-Lactam Concentrations in Extracorporeal Membranous Oxygenation Patients.

BACKGROUND: The aim of this study was to identify predictors of insufficient beta-lactam concentrations in patients undergoing extracorporeal membrane oxygenation (ECMO). METHODS: Retrospective analysis of all patients receiving ECMO support and treated with ceftazidime or cefepime (CEF), piperacillin/tazobactam (TZP), or meropenem (MEM). Trough drug concentrations (Cmin) were measured before the subsequent dose, according to the decision of the attending physician. Insufficient drug concentrations were identified if Cmin was below the clinical breakpoint of Pseudomonas aeruginosa. RESULTS: A total of 222 Cmin (CEF, n = 41; TZP, n = 85; MEM, n = 96) from 110 patients were included; insufficient concentrations were observed in 26 (12%) antibiotic assessments; 21 (81%) of those occurred during MEM therapy. Insufficient Cmin were associated with a shorter time from initiation of antibiotics to measurement, a lower single dose of antibiotic, a higher creatinine clearance (CrCL), lower sequential organ failure assessment (SOFA) scores, and less use of continuous renal replacement therapy (CRRT) when compared to others. CONCLUSIONS: Insufficient broad-spectrum beta-lactam concentrations were observed in 12% of drug measurement during ECMO therapy. Higher than recommended drug regimens could be considered in the very early phase of therapy and in those patients with augmented renal clearance and with less severe organ dysfunction.

Optimal Cerebral Perfusion Pressure Guided by Brain Oxygen Pressure Measurement.

Background: Although increasing cerebral perfusion pressure (CPP) is commonly accepted to improve brain tissue oxygen pressure (PbtO2), it remains unclear whether recommended CPP targets (i. e., >60 mmHg) would result in adequate brain oxygenation in brain injured patients. The aim of this study was to identify the target of CPP associated with normal brain oxygenation. Methods: Prospectively collected data including patients suffering from acute brain injury and monitored with PbtO2, in whom daily CPP challenge using vasopressors was performed. Initial CPP target was >60 mmHg; norepinephrine infusion was modified to have an increase in CPP of at least 10 mmHg at two different steps above the baseline values. Whenever possible, the same CPP challenge was performed for the following days, for a maximum of 5 days. CPP "responders" were patients with a relative increase in PbtO2 from baseline values > 20%. Results: A total of 53 patients were included. On the first day of assessment, CPP was progressively increased from 73 (70-76) to 83 (80-86), and 92 (90-96) mmHg, which resulted into a significant PbtO2 increase [from 20 (17-23) mmHg to 22 (20-24) mmHg and 24 (22-26) mmHg, respectively; p < 0.001]. Median CPP value corresponding to PbtO2 values > 20 mmHg was 79 (74-87) mmHg, with 2 (4%) patients who never achieved such target. Similar results of CPP targets were observed the following days. A total of 25 (47%) were PbtO2 responders during the CPP challenge on day 1, in particular if low PbtO2 was observed at baseline. Conclusions: PbtO2 monitoring can be an effective way to individualize CPP values to avoid tissue hypoxia. Low PbtO2 values at baseline can identify the responders to the CPP challenge.

Cerebral autoregulation in anoxic brain injury patients treated with targeted temperature management.

BACKGROUND: Little is known about the prevalence of altered CAR in anoxic brain injury and the association with patients' outcome. We aimed at investigating CAR in cardiac arrest survivors treated by targeted temperature management and its association to outcome. METHODS: Retrospective analysis of prospectively collected data. INCLUSION CRITERIA: adult cardiac arrest survivors treated by targeted temperature management (TTM). EXCLUSION CRITERIA: trauma; sepsis, intoxication; acute intra-cranial disease; history of supra-aortic vascular disease; severe hemodynamic instability; cardiac output mechanical support; arterial carbon dioxide partial pressure (PaCO2) > 60 mmHg; arrhythmias; lack of acoustic window. Middle cerebral artery flow velocitiy (FV) was assessed by transcranial Doppler (TCD) once during hypothermia (HT) and once during normothermia (NT). FV and blood pressure (BP) were recorded simultaneously and Mxa calculated (MATLAB). Mxa is the Pearson correlation coefficient between FV and BP. Mxa > 0.3 defined altered CAR. Survival was assessed at hospital discharge. Cerebral Performance Category (CPC) 3-5 assessed 3 months after CA defined unfavorable neurological outcome (UO). RESULTS: We included 50 patients (Jan 2015-Dec 2018). All patients had out-of-hospital cardiac arrest, 24 (48%) had initial shockable rhythm. Time to return of spontaneous circulation was 20 [10-35] min. HT (core body temperature 33.7 [33.2-34] °C) lasted for 24 [23-28] h, followed by rewarming and NT (core body temperature: 36.9 [36.6-37.4] °C). Thirty-one (62%) patients did not survive at hospital discharge and 36 (72%) had UO. Mxa was lower during HT than during NT (0.33 [0.11-0.58] vs. 0.58 [0.30-0.83]; p = 0.03). During HT, Mxa did not differ between outcome groups. During NT, Mxa was higher in patients with UO than others (0.63 [0.43-0.83] vs. 0.31 [- 0.01-0.67]; p = 0.03). Mxa differed among CPC values at NT (p = 0.03). Specifically, CPC 2 group had lower Mxa than CPC 3 and 5 groups. At multivariate analysis, initial non-shockable rhythm, high Mxa during NT and highly malignant electroencephalography pattern (HMp) were associated with in-hospital mortality; high Mxa during NT and HMp were associated with UO. CONCLUSIONS: CAR is frequently altered in cardiac arrest survivors treated by TTM. Altered CAR during normothermia was independently associated with poor outcome.

The burden of implementation: A mixed methods study on barriers to an ICU follow-up program.

PURPOSE: It has been suggested that ICU follow-up clinics can offer support for ICU survivors and their relatives. However, implementation of such clinics can be challenging. We explored the barriers to implementation of an ICU follow-up program from the healthcare providers' perspective. METHODS: This was a mixed methods study with a triangulation design conducted over the 7-month pilot period of an ICU follow-up program. RESULTS: The quantitative analysis showed that two main tasks within the program took the most time to be completed: training and tracking. Training new healthcare professionals to acquire the necessary competences for the follow-up clinic was the most time-consuming task [30 min (IQR 13-56)]. Tracking patients, which consists of keeping records of a patient during the hospital stay and when discharged, was the second most time-consuming task [15 min (IQR 10-20)]. We recorded 291 items of qualitative data from the 12 team members who participated. The qualitative analysis identified three domains that were crucial barriers for program implementation: Luhr et al. (2019) [1] organization (37.1%), Máca et al. (2017) [2] engagement (38.5%), and (Gayat et al., 2018 [3]) resources (24%). In agreement with the quantitative data, training and tracking were perceived by participants as laborious tasks and key barriers to implementation of the ICU follow-up program. Despite the expectation that resources would be the most important barrier, they were not considered as such by our participants being only mentioned in 13.4% of our qualitative reports; when mentioned, this barrier was related mostly to insufficient numbers of staff members. CONCLUSIONS: Awareness of those barriers can help healthcare providers and ICU managers in developing strategies adapted to overcome constraints, thus facilitating the implementation process.