CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma.

BACKGROUND: One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment. RESEARCH QUESTION: What are the most relevant changes in CT scan parameters over time for assessing response to treatment? STUDY DESIGN AND METHODS: In this ancillary study of a randomized clinical trial (NEBULAMB), patients with asthma with available CT scan and without exacerbation during a 4-month allergic bronchopulmonary aspergillosis exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT scan parameters were assessed by systematic analyses of CT scan findings at initiation and end of treatment. CT scans were assessed by two radiologists blinded to the clinical data. Radiologic parameters were determined by selecting those showing significant changes over time. Improvement of at least one, without worsening of the others, defined the radiologic response. Agreement between radiologic changes and clinical and immunologic responses was likewise investigated. RESULTS: Among the 139 originally randomized patients, 132 were included. We identified five CT scan parameters showing significant changes at end of treatment: mucoid impaction extent, mucoid impaction density, centrilobular micronodules, consolidation/ground-glass opacities, and bronchial wall thickening (P < .05). These changes were only weakly associated with one another, except for mucoid impaction extent and density. No agreement was observed between clinical, immunologic, and radiologic responses, assessed as an overall response, or considering each of the parameters (Cohen κ, -0.01 to 0.24). INTERPRETATION: Changes in extent and density of mucoid impaction, centrilobular micronodules, consolidation/ground-glass opacities, and thickening of the bronchial walls were found to be the most relevant CT scan parameters to assess radiologic response to treatment. A clinical, immunologic, and radiologic multidimensional approach should be adopted to assess outcomes, probably with a composite definition of response to treatment. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02273661; URL: www. CLINICALTRIALS: gov).

QRS-T angle: is it a specific parameter associated with sudden cardiac death in type 2 diabetes? Results from the SURDIAGENE and the Mini-Finland prospective cohorts.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with a high risk of sudden cardiac death (SCD), but the risk of dying from another cause (non-SCD) is proportionally even higher. The aim of the study was to identify easily available ECG-derived features associated with SCD, while considering the competing risk of dying from non-SCD causes. METHODS: In the SURDIAGENE (Survie, Diabete de type 2 et Genetique) French prospective cohort of individuals with type 2 diabetes, 15 baseline ECG parameters were interpreted among 1362 participants (mean age 65 years; HbA1c 62±17 mmol/mol [7.8±1.5%]; 58% male). Competing risk models assessed the prognostic value of clinical and ECG parameters for SCD after adjusting for age, sex, history of myocardial infarction, N-terminal pro b-type natriuretic peptide (NT-proBNP), HbA1c and eGFR. The prospective Mini-Finland cohort study was used to externally validate our findings. RESULTS: During median follow-up of 7.4 years, 494 deaths occurred including 94 SCDs. After adjustment, frontal QRS-T angle ≥90° (sub-distribution HR [sHR] 1.68 [95% CI 1.04, 2.69], p=0.032) and NT-proBNP level (sHR 1.26 [95% CI 1.06, 1.50] per 1 log, p=0.009) were significantly associated with a higher risk of SCD. Nevertheless, frontal QRS-T angle was the only marker not to be associated with causes of death other than SCD (sHR 1.08 [95% CI 0.84, 1.39], p=0.553 ). These findings were replicated in the Mini-Finland study subset of participants with diabetes (sHR 2.22 [95% CI 1.05, 4.71], p=0.04 for SCD and no association for other causes of death). CONCLUSIONS/INTERPRETATION: QRS-T angle was specifically associated with SCD risk and not with other causes of death, opening an avenue for refining SCD risk stratification in individuals with type 2 diabetes.

Bisphenol A and chlorinated derivatives of bisphenol A assessment in end stage renal disease patients: Impact of dialysis therapy.

Patients with end stage kidney disease treated by dialysis (ESKDD) process dialysis sessions to remove molecules usually excreted by kidneys. However, dialysis therapy could also contribute to endocrine disruptors (ED) burden. Indeed, materials like dialyzer filters, ultrapure dialysate and replacement fluid could exposed ESKDD patients to Bisphenol A (BPA) and chlorinated derivatives of BPA (ClxBPAs). Thus, our aim was to compare BPA and ClxBPAs exposure between ESKDD patients, patients with stage 5 chronic kidney disease (CKD5) not dialyzed and healthy volunteers. Then we describe the impact of a single dialysis session, according to dialysis modalities (hemodialysis therapy (HD) versus online hemodiafiltration therapy (HDF)) and materials used with pre-post BPA and ClxBPAs concentrations. The plasma levels of BPA and four ClxBPAs, were assessed for 64 ESKDD patients in pre and post dialysis samples (32 treated by HD and 32 treated by HDF) in 36 CKD5 patients and in 24 healthy volunteers. BPA plasma concentrations were 22.5 times higher for ESKDD patients in pre-dialysis samples versus healthy volunteers (2.208 ± 5.525 ng/mL versus 0.098 ± 0.169 ng/mL) (p < 0.001). BPA plasma concentrations were 16 times higher for CKD5 patients versus healthy volunteers, but it was not significant (1.606 ± 3.230 ng/mL versus 0.098 ± 0.169 ng/mL) (p > 0.05). BPA plasma concentrations for ESKDD patients in pre-dialysis samples were 1.4 times higher versus CKD5 patients (2.208 ± 5.525 ng/mL versus 1.606 ± 3.230 ng/mL) (p < 0.001). For healthy volunteers, ClxBPAs were never detected, or quantified while for CKD5 and ESKDD patients one ClxBPAs at least has been detected or quantified in 14 patients (38.8%) and 24 patients (37.5%), respectively. Dialysis therapy was inefficient to remove BPA either for HD (1.983 ± 6.042 ng/mL in pre-dialysis versus 3.675 ± 8.445 ng/mL in post-dialysis) or HDF (2.434 ± 5.042 ng/mL in pre-dialysis versus 7.462 ± 15.960 ng/mL in post dialysis) regarding pre-post BPA concentrations (p > 0.05). The same result was observed regarding ClxBPA analysis. Presence of polysulfone in dialyzer fibers overexposed ESKDD patients to BPA in pre-dialysis samples with 3.054 ± 6.770 for ESKDD patients treated with a polysulfone dialyzer versus 0.708 ± 0.638 (p = 0.040) for ESKDD patients treated without a polysulfone dialyzer and to BPA in post-dialysis samples with 6.629 ± 13.932 for ESKDD patients treated with a polysulfone dialyzer versus 3.982 ± 11.004 (p = 0.018) for ESKDD patients treated without a polysulfone dialyzer. This work is to our knowledge the first to investigate, the impact of a dialysis session and materials used on BPA and ClxBPAs plasma concentrations and to compare these concentrations to those found in CKD5 patients and in healthy volunteers.

Sex difference in the risk of extubation failure in ICUs.

BACKGROUND: Little attention has been paid to potential differences in prognosis between mechanically ventilated males and females in intensive care units (ICUs). We hypothesized that a sex gap in the risk of extubation failure in ICUs may exist. METHODS: Post hoc analysis of a large-scale clinical trial including patients at high risk of extubation failure in ICUs, with the aim of assessing the risk of extubation failure according to sex. The primary outcome was reintubation within the 7 days following extubation. RESULTS: Out of 641 patients, 425 (66%) were males and 216 (34%) were females. Males were more likely to be admitted for cardiac arrest and to have underlying ischemic heart disease whereas females were more likely to be admitted for coma and to have obesity. Whereas the rate of reintubation at 48 h was significantly higher in males than in females (11.0% vs. 6.0%; difference, + 5.0 [95% CI, 0.2 to 9.2]; P = 0.038), the rate of reintubation at day 7 did not significantly differ between males and females (16.7% vs. 11.1%; difference, + 5.6% [95%CI, - 0.3 to 10.8], P = 0.059). Using multivariable logistic regression analysis, male sex was independently associated with reintubation within the 7 days following extubation (adjusted OR 1.70 [95% CI, 1.01 to 2.89]; P = 0.048), even after adjustment on reason for admission, body-mass index, severity score, respiratory rate before extubation, and noninvasive ventilation after extubation. CONCLUSION: In this post hoc analysis of a clinical trial including a homogeneous subset of patients at high risk of extubation failure, sex was independently associated with reintubation. The role of sex on outcomes should be systematically examined in future studies of critically ill patients.

High-flow nasal cannula oxygen versus conventional oxygen therapy for acute respiratory failure due to COVID-19: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of high-flow nasal cannula oxygen therapy (HFNC) in patients with acute respiratory failure due to COVID-19 remains uncertain. We aimed at assessing whether HFNC is associated with reduced risk of intubation or mortality in patients with acute respiratory failure due to COVID-19 compared with conventional oxygen therapy (COT). METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, and CENTRAL databases for randomized controlled trials (RCTs) and observational studies comparing HFNC vs. COT in patients with acute respiratory failure due to COVID-19, published in English from inception to December 2022. Pediatric studies, studies that compared HFNC with a noninvasive respiratory support other than COT and those in which intubation or mortality were not reported were excluded. Two authors independently screened and selected articles for inclusion, extracted data, and assessed the risk of bias. Fixed-effects or random-effects meta-analysis were performed according to statistical heterogeneity. Primary outcomes were risk of intubation and mortality across RCTs. Effect estimates were calculated as risk ratios and 95% confidence interval (RR; 95% CI). Observational studies were used for sensitivity analyses. RESULTS: Twenty studies were analyzed, accounting for 8383 patients, including 6 RCTs (2509 patients) and 14 observational studies (5874 patients). By pooling the 6 RCTs, HFNC compared with COT significantly reduced the risk of intubation (RR 0.89, 95% CI 0.80 to 0.98; p = 0.02) and reduced length of stay in hospital. HFNC did not significantly reduce the risk of mortality (RR 0.93, 95% CI 0.77 to 1.11; p = 0.40). CONCLUSIONS: In patients with acute respiratory failure due to COVID-19, HFNC reduced the need for intubation and shortened length of stay in hospital without significant decreased risk of mortality. Trial registration The study was registered on the International prospective register of systematic reviews (PROSPERO) at https://www.crd.york.ac.uk/prospero/ with the trial registration number CRD42022340035 (06/20/2022).

Paving the Way for Personalized Medicine in First Kidney Transplantation: Interest of a Creatininemia Latent Class Analysis in Early Post-transplantation.

Plasma creatinine is a marker of interest in renal transplantation but data on its kinetics in the first days following transplantation are scarce. The aim of this study was to identify clinically relevant subgroups of creatinine trajectories following renal transplantation and to test their association with graft outcome. Among 496 patients with a first kidney transplant included in the French ASTRE cohort at the Poitiers University hospital, 435 patients from donation after brain death were considered in a latent class modeling. Four distinct classes of creatinine trajectories were identified: "poor recovery" (6% of patients), "intermediate recovery" (47%), "good recovery" (10%) and "optimal recovery" (37%). Cold ischemia time was significantly lower in the "optimal recovery" class. Delayed graft function was more frequent and the number of hemodialysis sessions was higher in the "poor recovery" class. Incidence of graft loss was significantly lower in "optimal recovery" patients with an adjusted risk of graft loss 2.42 and 4.06 times higher in "intermediate recovery" and "poor recovery" patients, respectively. Our study highlights substantial heterogeneity in creatinine trajectories following renal transplantation that may help to identify patients who are more likely to experience a graft loss.

A real-time automated sleep scoring algorithm to detect refreshing sleep in conscious ventilated critically ill patients.

OBJECTIVES: Due to the noisy environment, a very large number of patients admitted to intensive care units (ICUs) suffer from sleep severe disruption. These sleep alterations have been associated with a prolonged need for assisted ventilation or even with death. Sleep scoring in the critically ill is very challenging and requires sleep experts, limiting relevant studies to a few experienced teams. In this context, an automated scoring system would be of interest for researchers. In addition, real-time scoring could be used by nurses to protect patients' sleep. We devised a sleep scoring algorithm working in real time and compared this automated scoring against visual scoring. METHODS: We analyzed retrospectively 45 polysomnographies previously recorded in non-sedated and conscious ICU patients during their weaning phase. For each patient, one EEG channel was processed, providing automated sleep scoring. We compared total sleep time obtained with visual scoring versus automated scoring. The proportion of sleep episodes correctly identified was calculated. RESULTS: Automated total sleep time and visual sleep time were correlated; the automatic system overestimated total sleep time. The median [25th-75th] percentage of sleep episodes lasting more than 10 min detected by algorithm was 100% [73.2 - 100.0]. Median sensitivity was 97.9% [92.5 - 99.9]. CONCLUSION: An automated sleep scoring system can identify nearly all long sleep episodes. Since these episodes are restorative, this real-time automated system opens the way for EEG-guided sleep protection strategies. Nurses could cluster their non-urgent care procedures, and reduce ambient noise so as to minimize patients' sleep disruptions.

Renal function decline and heart failure hospitalisation in patients with type 2 diabetes: Dynamic predictions from the prospective SURDIAGENE cohort.

AIMS: For type 2 diabetes persons, we assessed the association between renal function decline and heart failure hospitalisation (HFH) and validated dynamic HFH predictions (DynHFH) based on repeated estimated Glomerular Filtration Rate (eGFR) values. METHODS: We studied 1413 patients from the SURDIAGENE cohort. From a joint model for longitudinal CKD-EPI measures and HFH risk, we calculated the probability of being HFH-free in the next five years. RESULTS: The mean eGFR decline was estimated at 1.48 ml/min/1.73 m2 per year (95 % CI from 1.23 to 1.74). We observed that eGFR decline was significantly associated with the HFH risk (adjHR = 1.15 for an increase in yearly decline of 1 ml/min/1.73 m2, 95 % CI from 1.03 to 1.26) independently of 7 baseline variables (from clinical, biological and ECG domains). Discrimination was good along the prediction times: AUC at 0.87 (95 %CI from 0.84 to 0.91) at patient inclusion and 0.77 (95 %CI from 0.67 to 0.87) at seven years' follow-up. CONCLUSIONS: Renal function decline was significantly associated with the HFH risk. In the era of computer-assisted medical decisions, the DynHFH, a tool that dynamically predicts HFH in type 2 diabetes persons (https://shiny.idbc.fr/DynHFH), might be helpful for precision medicine and the implementation of stratified medical decision-making.

Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece.

BACKGROUND: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown. METHODS: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation. RESULTS: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group). CONCLUSIONS: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.).

Impact of the Kidney Transplantation Moratorium in France Because of the COVID-19 Pandemic: A Cohort-based Study.

BACKGROUND: The COVID-19 pandemic has resulted in worldwide kidney transplantation (KT) moratoriums. The impacts of these moratoriums on the life expectancy of KT candidates remain unclear. METHODS: We simulated the evolution of several French candidate populations for KT using a multistate semi-Markovian approach and according to moratorium durations ranging from 0 to 24 mo. The transition rates were modeled from the 63 927 French patients who began dialysis or were registered on the waiting list for KT between 2011 and 2019. RESULTS: Among the 8350 patients active on the waiting list at the time of the French KT moratorium decided on March 16, 2020, for 2.5 mo, we predicted 4.0 additional months (confidence interval [CI], 2.8-5.0) on the waiting list and 42 additional deaths (CI, -70 to 150) up to March 16, 2030, compared with the scenario without moratorium. In this population, we reported a significant impact for a 9-mo moratorium duration: 135 attributable deaths (CI, 31-257) up to March 16, 2030. Patients who became active on the list after March 2020 were less impacted; there was a significant impact for an 18-mo moratorium (175 additional deaths [CI, 21-359]) in the 10 862 prevalent end-stage renal disease patients on March 16, 2020 and for a 24-mo moratorium (189 additional deaths [CI, 10-367]) in the 16 355 incident end-stage renal disease patients after this date. CONCLUSION: The temporary moratorium of KT during a COVID-19 peak represents a sustainable decision to free up hospitals' resources if the moratorium does not exceed a prolonged period.

Effect of High-Flow Nasal Cannula Oxygen vs Standard Oxygen Therapy on Mortality in Patients With Respiratory Failure Due to COVID-19: The SOHO-COVID Randomized Clinical Trial.

Importance: The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial. Objective: To determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs). Design, Setting, and Participants: The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022. Interventions: Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354). Main Outcomes and Measures: The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events. Results: Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean [SD] age, 61 [12] years; 214 women [30%]). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, -1.2% [95% CI, -5.8% to 3.4%]; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% [160/357] vs 53% [186/354]; absolute difference, -7.7% [95% CI, -14.9% to -0.4%]; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 [IQR, 11-28] vs 23 [IQR, 10-28] days; absolute difference, 0.5 days [95% CI, -7.7 to 9.1]; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group. Conclusions and Relevance: Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT04468126.

How Women Perceive Severity of Complications after Pelvic Floor Repair?

BACKGROUND: The Clavien-Dindo classification, used to describe postoperative complications, does not take into account patient perception of severity. Our main objective was to assess women's perception of postoperative pelvic floor repair complications and compare it to the classification of Clavien-Dindo. METHODS: Women and surgeons participating in the VIGI-MESH registry concerning pelvic floor repair surgery were invited to quote their perception of complication severity through a survey based on 30 clinical vignettes. For each vignette, four grades of severity were proposed: "not serious", "a little serious", "serious", "very serious". RESULTS: Among the 1146 registered women, we received 529 responses (46.2%) and 70 of the 141 surgeons (49.6%) returned a completed questionnaire. A total of 25 of the 30 vignettes were considered classifiable according to the Clavien-Dindo classification. The women's classification was concordant with Clavien-Dindo for 52.0% (13/25) of the classifiable vignettes. The women's and surgeons' responses were discordant for 20 of the 30 clinical vignettes (66.7%). Loss of autonomy (self-catheterization, long-term medication use) or occurrence of sequelae (organ damage or severe persistent pain) were perceived by women as more serious than Clavien-Dindo classification or than surgeons' perceptions. CONCLUSIONS: Women's perception of pelvic floor repair surgery seems different from the Clavien-Dindo classification. Lack of repair and long-term disability seem to be two major factors in favor of perception of the surgical complication as serious.

Nutritional biomarkers and heart failure requiring hospitalization in patients with type 2 diabetes: the SURDIAGENE cohort.

BACKGROUND: Heart failure (HF) is a growing complication and one of the leading causes of mortality in people living with type 2 diabetes (T2D). Among the possible causes, the excess of red meat and the insufficiency of vegetables consumption are suspected. Such an alimentation is associated with nutritional biomarkers, including trimethylamine N-oxide (TMAO) and its precursors. Here, we aimed to study these biomarkers as potential prognostic factors for HF in patients with T2D. METHODS: We used the SURDIAGENE (SURvival DIAbetes and GENEtics) study, a large, prospective, monocentric cohort study including 1468 patients with T2D between 2001 and 2012. TMAO and its precursors (trimethylamine [TMA], betaine, choline, and carnitine) as well as thio-amino-acids (cysteine, homocysteine and methionine) were measured by liquid chromatography-tandem mass spectrometry. The main outcome was HF requiring Hospitalization (HFrH) defined as the first occurrence of acute HF leading to hospitalization and/or death, established by an adjudication committee, based on hospital records until 31st December 2015. The secondary outcomes were the composite event HFrH and/or cardiovascular death and all-cause death. The association between the biomarkers and the outcomes was studied using cause-specific hazard-models, adjusted for age, sex, history of coronary artery disease, NT-proBNP, CKD-EPI-derived eGFR and the urine albumin/creatinine ratio. Hazard-ratios (HR) are expressed for one standard deviation. RESULTS: The data of interest were available for 1349/1468 of SURDIAGENE participants (91.9%), including 569 (42.2%) women, with a mean age of 64.3 ± 10.7 years and a median follow-up of 7.3 years [25th-75th percentile, 4.7-10.8]. HFrH was reported in 209 patients (15.5%), HFrH and/or cardiovascular death in 341 (25.3%) and all-cause death in 447 (33.1%). In unadjusted hazard-models, carnitine (HR = 1.20, 95% CI [1.05; 1.37]), betaine (HR = 1.34, [1.20; 1.50]), choline (HR = 1.35, [1.20; 1.52]), TMAO (HR = 1.32, [1.16; 1.50]), cysteine (HR = 1.38, [1.21; 1.58]) and homocysteine (HR = 1.28, [1.17; 1.39]) were associated with HFrH, but not TMA and methionine. In the fully adjusted models, none of these associations was significant, neither for HFrH nor for HFrH and/or CV death, when homocysteine only was positively associated with all-cause death (HR = 1.16, [1.06; 1.27]). CONCLUSIONS: TMAO and its precursors do not appear to be substantial prognosis factors for HFrH, beyond usual cardiac- and kidney-related risk factors, whereas homocysteine is an independent risk factor for all-cause death in patients with T2D.

Predictors of Risk Stratification and Value of Point-of-Care of High-Sensitivity Cardiac Troponin-I in EMS Management of Non-ST-Segment Elevation Myocardial Infarction: A Retrospective Study.

INTRODUCTION: The European Society of Cardiology (ESC) 2020 guidelines propose an algorithm for in-hospital management of non-ST-elevation myocardial infarction (NSTEMI) based on risk stratification according to clinical, electrocardiographic, and biological data. However, out-of-hospital management is not codified. STUDY OBJECTIVE: The objective of the present study was to evaluate the role of high-sensitivity cardiac troponin-I in out-of-hospital management of NSTEMI by Emergency Medical Services (EMS). METHODS: This monocentric, retrospective, observational study analyzed the files of all patients having received a troponin assay in the EMS of Beaujon University Hospital, AP-HP (Paris region, France) from January 1, 2020 through December 31, 2020. Patients were classified as low risk, high risk, or very high risk according to the ESC 2020 algorithm at the time of their hospital treatment. The relationship between troponin in point-of-care and risk level according to time to onset of pain was analyzed using logistic regression. A search for predictors of risk level was performed using multivariate analysis. A P value <.05 was considered significant. RESULTS: Out of 309 patients in the file, 233 were included. Men were 61% and the median age was 63 years. A positive troponin assay was associated with high-risk or very high-risk stratification regardless of the time to onset of pain (P <.0001). Predictive factors for being classified as high or very high risk in hospital were: a history of atrial fibrillation (P = .03), electrocardiogram (ECG) modifications such as negative T wave or ST-segment depression (P <.0001), and positive troponin (P <.0001). CONCLUSION: The use of point-of-care troponin in EMS, combined with clinical and electrical criteria, allows risk stratification of NSTEMI patients from the prehospital management stage and optimization of referral to an appropriate care pathway. Patients classified as low risk should be referred to the emergency department (ED) and patients classified as high risk or very high risk to the cardiac intensive care unit or percutaneous coronary intervention (PCI) center.

High-flow nasal oxygen alone or alternating with non-invasive ventilation in critically ill immunocompromised patients with acute respiratory failure: a randomised controlled trial.

BACKGROUND: Although non-invasive ventilation (NIV) is recommended for immunocompromised patients with acute respiratory failure in the intensive care unit (ICU), it might have deleterious effects in the most severe patients. High-flow nasal oxygen (HFNO) alone might be an alternative method to reduce mortality. We aimed to determine whether HFNO alone could reduce the rate of mortality at day 28 compared with HFNO alternated with NIV. METHODS: FLORALI-IM is a multicentre, open-label, randomised clinical trial conducted in 29 ICUs (28 in France and one in Italy). Adult immunocompromised patients with acute respiratory failure, defined as respiratory rate of 25 breaths per min or more and a partial pressure of arterial oxygen to inspired fraction of oxygen ratio of 300 mm Hg or lower, were randomly assigned (1:1) to HFNO alone (HFNO alone group) or NIV alternating with HFNO (NIV group). Key exclusion criteria were severe hypercapnia above 50 mm Hg, patients who could strongly benefit from NIV (ie, those with underlying chronic lung disease, with cardiogenic pulmonary oedema, or who were postoperative), severe shock, impaired consciousness defined as Glasgow coma score ≤12, urgent need for intubation, do not intubate order, and contraindication to NIV. Patients were assigned using computer-generated permuted blocks and were stratified according to centre and to the type of immunosuppression using a centralised web-based management system. In the HFNO alone group, patients were continuously treated by HFNO with a gas flow rate of 60 L/min or the highest tolerated. In the NIV group, patients were treated with NIV with a first session of at least 4 h, and then by sessions for a minimal duration of 12 h a day, with a dedicated ventilator, targeting a tidal volume below 8 mL/kg of predicted bodyweight, and with a positive end-expiratory level of at least 8 cm H2O. NIV sessions were interspaced with HFNO delivered as in the HFNO alone group. The primary outcome was mortality at day 28 and was assessed in the intention-to-treat population. Secondary outcomes were mortality in the ICU, in hospital, at day 90 and at day 180, intubation at day 28, length of stay in the ICU and in hospital, number of ventilator-free days at day 28, number of oxygenation technique-free days at day 28, and efficacy and tolerance of oxygenation techniques. The trial is registered with ClinicalTrials.gov, NCT02978300, and is complete. FINDINGS: Between Jan 21, 2017 to March 4, 2019, of 497 eligible patients, 300 were randomly assigned but one patient withdrew consent, leaving 299 patients included in the intention-to-treat analysis (154 assigned to the HFNO alone group and 145 assigned to NIV group). Mortality rate at day 28 was 36% (95% CI 29·2 to 44·2; 56 of 154 patients) in the HFNO alone group and 35% (27·9 to 43·2; 51 of 145 patients) in the NIV group (absolute difference 1·2% [95% CI -9·6 to 11·9]; p=0·83). None of the other prespecified secondary outcomes were different between groups except for greater decreased discomfort after initiation of HFNO than with NIV (-4 mm on visual analogic scale [IQR -18 to 4] vs 0 mm [-16 to 17]; p=0·040). INTERPRETATION: In critically ill immunocompromised patients with acute respiratory failure, the mortality rate did not differ between HFNO alone and NIV alternating with HFNO. However, study power was limited, so results should be interpreted with caution. FUNDING: French Ministry of Health.

Increased serum S100A12 levels are associated with higher risk of acute heart failure in patients with type 2 diabetes.

AIMS: The hyperglycaemic stress induces the release of inflammatory proteins such as S100A12, one of the endogenous ligands of the receptors for advanced glycation end products (RAGE). Chronic activation of RAGE has multiple deleterious effects in target tissues such as the heart and the vessels by promoting oxidative stress, inflammation by the release of cytokines, macrophages infiltration, and vascular cell migration and proliferation, causing ultimately endothelial cell and cardiomyocyte dysfunction. The aim of our study was to investigate the prognostic value of circulating S100A12 beyond established cardiovascular risk factors (CVRF) for heart failure (HF) and major adverse cardiovascular events (MACE) in a cohort of patients with type 2 diabetes. METHODS AND RESULTS: Serum S100A12 concentrations were measured at baseline in 1345 type 2 diabetes patients (58% men, 64 ± 11 years) recruited in the SURDIAGENE prospective cohort. Endpoints were the occurrence of acute HF requiring hospitalization (HHF) and MACE. We used a proportional hazard model adjusted for established CVRF (age, sex, duration of diabetes, estimated glomerular filtration rate, albumin/creatinine ratio, history of coronary artery disease) and serum S100A12. During the median follow-up of 84 months, 210 (16%) and 505 (38%) patients developed HHF and MACE, respectively. Baseline serum S100A12 concentrations were associated with an increased risk of HHF [hazard ratio (HR) (95% confidence interval) 1.28 (1.01-1.62)], but not MACE [1.04 (0.90-1.20)]. After adjustment for CVRF, S100A12 concentrations remained significantly associated with an increased risk of HHF [1.29 (1.01-1.65)]. In a sub-analysis, patients with high probability of pre-existing HF [N terminal pro brain natriuretic peptide (NT-proBNP) >1000 pg/mL, n = 87] were excluded. In the remaining 1258 patients, the association of serum S100A12 with the risk of HHF tended to be more pronounced [1.39 (1.06-1.83)]. When including the gold standard HF marker NT-proBNP in the model, the prognostic value of S100A12 for HHF did not reach significance. Youden method performed at 7 years for HHF prediction yielded an optimal cut-off for S100A12 concentration of 49 ng/mL (sensitivity 53.3, specificity 52.2). Compared with those with S100A12 ≤ 49 ng/mL, patients with S100A12 > 49 ng/mL had a significantly increased risk of HHF in the univariate model [HR = 1.58 (1.19-2.09), P = 0.0015] but also in the multivariate model [HR = 1.63 (1.23-2.16), P = 0.0008]. After addition of NT-proBNP to the multivariate model, S100A12 > 49 ng/mL remained associated with an increased risk of HHF [HR = 1.42 (1.07-1.90), P = 0.0160]. However, the addition of S100A12 categories on top of multivariate model enriched by NT-pro BNP did not improve the ability of the model to predict HHF (relative integrated discrimination improvement = 1.9%, P = 0.1500). CONCLUSIONS: In patients with type 2 diabetes, increased serum S100A12 concentration is independently associated with risk of HHF, but not with risk of MACE. Compared with NT-proBNP, the potential clinical interest of S100A12 for the prediction of HF events remains limited. However, S100A12 could be a candidate for a multimarker approach for HF risk assessment in diabetic patients.

Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

BACKGROUND: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. METHODS: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. RESULTS: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. CONCLUSIONS: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.