MICRA: Microstructural image compilation with repeated acquisitions.

We provide a rich multi-contrast microstructural MRI dataset acquired on an ultra-strong gradient 3T Connectom MRI scanner comprising 5 repeated sets of MRI microstructural contrasts in 6 healthy human participants. The availability of data sets that support comprehensive simultaneous assessment of test-retest reliability of multiple microstructural contrasts (i.e., those derived from advanced diffusion, multi-component relaxometry and quantitative magnetisation transfer MRI) in the same population is extremely limited. This unique dataset is offered to the imaging community as a test-bed resource for conducting specialised analyses that may assist and inform their current and future research. The Microstructural Image Compilation with Repeated Acquisitions (MICRA) dataset includes raw data and computed microstructure maps derived from multi-shell and multi-direction encoded diffusion, multi-component relaxometry and quantitative magnetisation transfer acquisition protocols. Our data demonstrate high reproducibility of several microstructural MRI measures across scan sessions as shown by intra-class correlation coefficients and coefficients of variation. To illustrate a potential use of the MICRA dataset, we computed sample sizes required to provide sufficient statistical power a priori across different white matter pathways and microstructure measures for different statistical comparisons. We also demonstrate whole brain white matter voxel-wise repeatability in several microstructural maps. The MICRA dataset will be of benefit to researchers wishing to conduct similar reliability tests, power estimations or to evaluate the robustness of their own analysis pipelines.

Cross-scanner and cross-protocol multi-shell diffusion MRI data harmonization: Algorithms and results.

Cross-scanner and cross-protocol variability of diffusion magnetic resonance imaging (dMRI) data are known to be major obstacles in multi-site clinical studies since they limit the ability to aggregate dMRI data and derived measures. Computational algorithms that harmonize the data and minimize such variability are critical to reliably combine datasets acquired from different scanners and/or protocols, thus improving the statistical power and sensitivity of multi-site studies. Different computational approaches have been proposed to harmonize diffusion MRI data or remove scanner-specific differences. To date, these methods have mostly been developed for or evaluated on single b-value diffusion MRI data. In this work, we present the evaluation results of 19 algorithms that are developed to harmonize the cross-scanner and cross-protocol variability of multi-shell diffusion MRI using a benchmark database. The proposed algorithms rely on various signal representation approaches and computational tools, such as rotational invariant spherical harmonics, deep neural networks and hybrid biophysical and statistical approaches. The benchmark database consists of data acquired from the same subjects on two scanners with different maximum gradient strength (80 and 300 â€‹mT/m) and with two protocols. We evaluated the performance of these algorithms for mapping multi-shell diffusion MRI data across scanners and across protocols using several state-of-the-art imaging measures. The results show that data harmonization algorithms can reduce the cross-scanner and cross-protocol variabilities to a similar level as scan-rescan variability using the same scanner and protocol. In particular, the LinearRISH algorithm based on adaptive linear mapping of rotational invariant spherical harmonics features yields the lowest variability for our data in predicting the fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK) and the rotationally invariant spherical harmonic (RISH) features. But other algorithms, such as DIAMOND, SHResNet, DIQT, CMResNet show further improvement in harmonizing the return-to-origin probability (RTOP). The performance of different approaches provides useful guidelines on data harmonization in future multi-site studies.

Right ventricular failure in septic shock: characterization, incidence and impact on fluid responsiveness.

OBJECTIVE: Incidence of right ventricular (RV) failure in septic shock patients is not well known, and tricuspid annular plane systolic excursion (TAPSE) could be of limited value. We report the incidence of RV failure in patients with septic shock, its potential impact on the response to fluids, as well as TAPSE values. DESIGN: Ancillary study of the HEMOPRED prospective multicenter study includes patients under mechanical ventilation with circulatory failure. SETTING: This is a multicenter intensive care unit study PATIENTS: Two hundred and eighty-two patients with septic shock were analyzed. Patients were classified in three groups based on central venous pressure (CVP) and RV size (RV/LV end-diastolic area, EDA). In group 1, patients had no RV dilatation (RV/LVEDA < 0.6). In group 2, patients had RV dilatation (RV/LVEDA ≥ 0.6) with a CVP < 8 mmHg (no venous congestion). RV failure was defined in group 3 by RV dilatation and a CVP ≥ 8 mmHg. Pulse pressure variation (PPV) was systematically recorded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 41% of patients were in group 1, 17% in group 2 and 42% in group 3. A correlation between RV size and CVP was only observed in group 3. Higher RV size was associated with a lower response to passive leg raising for a given PPV. A large overlap of TAPSE values was observed between the 3 groups. 63.5% of patients with RV failure had a normal TAPSE. CONCLUSIONS: RV failure, defined by critical care echocardiography (RV dilatation) and a surrogate of venous congestion (CVP ≥ 8 mmHg), was frequently observed in septic shock patients and negatively associated with response to a fluid challenge despite significant PPV. TAPSE was unable to discriminate patients with or without RV failure.

Cross-scanner and cross-protocol diffusion MRI data harmonisation: A benchmark database and evaluation of algorithms.

Diffusion MRI is being used increasingly in studies of the brain and other parts of the body for its ability to provide quantitative measures that are sensitive to changes in tissue microstructure. However, inter-scanner and inter-protocol differences are known to induce significant measurement variability, which in turn jeopardises the ability to obtain 'truly quantitative measures' and challenges the reliable combination of different datasets. Combining datasets from different scanners and/or acquired at different time points could dramatically increase the statistical power of clinical studies, and facilitate multi-centre research. Even though careful harmonisation of acquisition parameters can reduce variability, inter-protocol differences become almost inevitable with improvements in hardware and sequence design over time, even within a site. In this work, we present a benchmark diffusion MRI database of the same subjects acquired on three distinct scanners with different maximum gradient strength (40, 80, and 300 mT/m), and with 'standard' and 'state-of-the-art' protocols, where the latter have higher spatial and angular resolution. The dataset serves as a useful testbed for method development in cross-scanner/cross-protocol diffusion MRI harmonisation and quality enhancement. Using the database, we compare the performance of five different methods for estimating mappings between the scanners and protocols. The results show that cross-scanner harmonisation of single-shell diffusion data sets can reduce the variability between scanners, and highlight the promises and shortcomings of today's data harmonisation techniques.

Dynamics of White Matter Plasticity Underlying Working Memory Training: Multimodal Evidence from Diffusion MRI and Relaxometry.

Adaptive working memory (WM) training may lead to cognitive benefits that are associated with white matter plasticity in parietofrontal networks, but the underlying mechanisms remain poorly understood. We investigated white matter microstructural changes after adaptive WM training relative to a nonadaptive comparison group. Microstructural changes were studied in the superior longitudinal fasciculus, the main parietofrontal connection, and the cingulum bundle as a comparison pathway. MRI-based metrics were the myelin water fraction and longitudinal relaxation rate R1 from multicomponent relaxometry (captured with the mcDESPOT approach) as proxy metrics of myelin, the restricted volume fraction from the composite hindered and restricted model of diffusion as an estimate of axon morphology, and fractional anisotropy and radial diffusivity from diffusion tensor imaging. PCA was used for dimensionality reduction. Adaptive training was associated with benefits in a "WM capacity" component and increases in a microstructural component (increases in R1, restricted volume fraction, fractional anisotropy, and reduced radial diffusivity) that predominantly loaded on changes in the right dorsolateral superior longitudinal fasciculus and the left parahippocampal cingulum. In contrast, nonadaptive comparison activities were associated with the opposite pattern of reductions in WM capacity and microstructure. No group differences were observed for the myelin water fraction metric suggesting that R1 was a more sensitive "myelin" index. These results demonstrate task complexity and location-specific white matter microstructural changes that are consistent with tissue alterations underlying myelination in response to training.

Assessment of the effects of inspiratory load on right ventricular function.

PURPOSE OF REVIEW: The right ventricle (RV) plays a pivotal role during respiratory failure because of its high sensitivity to small loading changes during inspiration. Both RVs, preload and afterload, are altered during inspiration, either in spontaneous breathing or during mechanical ventilation. Some clinical situations especially affect RV load during inspiration, for example acute asthma and acute respiratory distress syndrome. The aim of this review is to explain and to summarize the different mechanisms leading to RV failure in these situations. RECENT FINDINGS: Research has recently reemphasized the importance to well known physiology of the venous return which is a contributor of RV preload. Authors recently focused on the mean systemic filling pressure which is one of the determinants of venous return. Venous return may change in opposite direction according to the type of ventilation (spontaneous or assisted). Recent works have also demonstrated the crucial impact of lung inflation and driving pressure on RV afterload, and have confirmed the deleterious effect of severe RV failure, described as acute cor pulmonale. In most situations of RV overload induced by inspiration, significant pulse pressure variations are observed, either called 'pulsus paradoxus' in spontaneously breathing patients or 'reverse pulsus paradoxus' in mechanically ventilated patients. SUMMARY: RV is very sensitive to abnormal inspiration, which is always responsible for an increase in its afterload. Pulse pressure variations, central venous pressure and especially echocardiography may monitor RV function in abnormal clinical situations. The pulmonary artery catheter was also proposed although now less used.

Acute respiratory distress syndrome: the heart side of the moon.

PURPOSE OF REVIEW: Circulatory failure is a frequent complication during acute respiratory distress syndrome (ARDS) and is associated with a poor outcome. This review aims at clarifying the mechanisms of circulatory failure during ARDS. RECENT FINDINGS: For the past decades, the right ventricle (RV) has gained a crucial interest since many authors confirmed the high incidence of acute cor pulmonale during ARDS and showed a potential role of the acute cor pulmonale in the poor outcome of ARDS patients. The most important recent progress demonstrated in ARDS ventilatory strategy is represented by the prone position, which has a huge beneficial effect on RV afterload. This review will focus on the mechanisms responsible for the RV dysfunction/failure during ARDS and on the strategy, which allows improving the right ventricular function. SUMMARY: The RV has a pivotal role in the circulatory failure of ARDS patients. The ventilatory strategy during ARDS has to pay a peculiar attention to the RV to rigorously control its afterload.

Value and determinants of the mean systemic filling pressure in critically ill patients.

Mean systemic filling pressure (Pmsf) is a major determinant of venous return. Its value is unknown in critically ill patients (ICU). Our objectives were to report Pmsf in critically ill patients and to look for its clinical determinants, if any. We performed a prospective study in 202 patients who died in the ICU with a central venous and/or arterial catheter. One minute after the heart stopped beating, intravascular pressures were recorded in the supine position after ventilator disconnection. Parameters at admission, during the ICU stay, and at the time of death were prospectively collected. One-minute Pmsf was 12.8 ± 5.6 mmHg. It did not differ according to gender, severity score, diagnosis at admission, fluid balance, need for and duration of mechanical ventilation, or length of stay. Nor was there any difference according to suspected cause of death, classified as shock (cardiogenic, septic, and hemorrhagic) and nonshock, although a large variability of values was observed. The presence of norepinephrine at the time of death (102 patients) was associated with a higher 1-min Pmsf (14 ± 6 vs. 11.4 ± 4.5 mmHg), whereas the decision to forgo life-sustaining therapy (34 patients) was associated with a lower 1-min Pmsf (10.9 ± 3.8 vs. 13.1 ± 5.3 mmHg). In a multiple-regression analysis, norepinephrine (ß = 2.67, P = 0.0004) and age (ß = -0.061, P = 0.022) were associated with 1-min Pmsf. One-minute Pmsf appeared highly variable without any difference according to the kind of shock and fluid balance, but was higher with norepinephrine.

Right ventricular injury in patients with COVID-19-related ARDS eligible for ECMO support: a multicenter retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membrane oxygenation (ECMO) has been proposed in this setting, but optimal criteria to select target patients remain unknown. Our hypothesis is that evaluation of right ventricular (RV) function could be helpful. The aims of our study were to report the incidence and outcomes of patients eligible for ECMO according to EOLIA criteria, and to identify a subgroup of patients with RV injury, which could be a target for ECMO. METHODS: Retrospective observational study involving 3 French intensive care units (ICUs) of teaching hospitals. Patients with confirmed SARS-CoV-2 infection between March 2020 and March 2021, presenting ARDS and with available echocardiography, were included. Patients were classified in three groups according to whether or not they met the EOLIA criteria and the presence of RV injury (RVI) ("EOLIA -", "EOLIA + RVI -" and "EOLIA + RVI + "). RVI was defined by the association of RV to left ventricular end-diastolic area ratio > 0.8 and paradoxical septal motion. Kaplan-Meier survival curves were used to analyze outcome as well as a Cox model for 90 day mortality. RESULTS: 915 patients were hospitalized for COVID-19, 418 of them with ARDS. A total of 283 patients with available echocardiography were included. Eighteen (6.3%) patients received ECMO. After exclusion of these patients, 107 (40.5%) were classified as EOLIA -, 126 (47.5%) as EOLIA + RVI -, and 32 (12%) as EOLIA + RVI + . Ninety-day mortality was 21% in the EOLIA-group, 44% in the EOLIA + RVI-group, and 66% in the EOLIA + RVI + group (p < 0.001). After adjustment, RVI was statistically associated with 90-day mortality (HR = 1.92 [1.10-3.37]). CONCLUSIONS: Among COVID-19-associated ARDS patients who met the EOLIA criteria, those with significant RV pressure overload had a particularly poor outcome. This subgroup may be a more specific target for ECMO. This represented 12% of our cohort compared to 60% of patients who met the EOLIA criteria only. How the identification of this high-risk subset of patients translates into patient-centered outcomes remains to be evaluated.

Evaluation of left ventricular systolic function revisited in septic shock.

The meta-analysis of Huang and coworkers failed to find any evidence for a protective effect of a decreased left ventricular (LV) ejection fraction (EF). These results have to be interpreted with caution since in most studies included in the meta-analysis patients with LV systolic dysfunction received inotropic drugs. We have some arguments suggesting that such a treatment may improve macrocirculation and microcirculation and finally prognosis. This paper allows us to clarify the meaning of LV function in septic shock patients. In all experimental models of septic shock using the load-independent parameter of LV systolic function, LV contractility impairment, called septic cardiomyopathy, has been reported to be constant. However, LVEF reflects the coupling between LV contractility and LV afterload. A normal LVEF may be observed when the arterial tone is severely depressed, as in septic shock, despite seriously impaired intrinsic LV contractility. LV systolic function, evaluated using an echocardiograph or another device, is then more a reflection of arterial tone (and its correction) than of intrinsic LV contractility. As a consequence, the incidence of LV systolic dysfunction greatly depends on the time of the evaluation, reflecting the fact that, during resuscitation and treatment, vasoplegia and then LV afterload are corrected, thus unmasking septic cardiomyopathy. With these points in mind, we can revisit the results of Margaret Parker's original study: it is not that the patients with a low EF survived better, but rather that the other patients had an increased mortality due to persistent profound vasoplegia.

[A nursing team's approach]. / Approche d'une équipe soignante.

The proportion of elderly people admitted to intensive care has increased over recent years. Apart from the questions relating to the medical treatment, admission criteria and level of care, it is sometimes difficult to identify the consequences for the non-medical staff of an intensive care department of two units (12 intensive care beds and 8 continuing care beds).

[The importance of geriatrics-intensive care collaboration]. / L'importance de i'association gériatres-réanimateurs.

As is the case with all medical and surgical departments, the proportion of elderly patients in intensive care departments is gradually increasing.At Ambroise Pare hospital, in Boulogne-Billancourt, a natural collaboration has been set up between intensive care staff and geriatricians to adapt the care provided and to limit situations of unreasonable therapeutic obstinacy, notably thanks to a standardised gathering of information.

Echocardiography phenotypes of right ventricular involvement in COVID-19 ARDS patients and ICU mortality: post-hoc (exploratory) analysis of repeated data from the ECHO-COVID study.

PURPOSE: Exploratory study to evaluate the association of different phenotypes of right ventricular (RV) involvement and mortality in the intensive care unit (ICU) in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). METHODS: Post-hoc analysis of longitudinal data from the multicenter ECHO-COVID observational study in ICU patients who underwent at least two echocardiography examinations. Echocardiography phenotypes were acute cor pulmonale (ACP, RV cavity dilatation with paradoxical septal motion), RV failure (RVF, RV cavity dilatation and systemic venous congestion), and RV dysfunction (tricuspid annular plane systolic excursion ≤ 16 mm). Accelerated failure time model and multistate model were used for analysis. RESULTS: Of 281 patients who underwent 948 echocardiography studies during ICU stay, 189 (67%) were found to have at least 1 type of RV involvements during one or several examinations: ACP (105/281, 37.4%), RVF (140/256, 54.7%) and/or RV dysfunction (74/255, 29%). Patients with all examinations displaying ACP had survival time shortened by 0.479 [0.284-0.803] times when compared to patients with all examinations depicting no ACP (P = 0.005). RVF showed a trend towards shortened survival time by a factor of 0.642 [0.405-1.018] (P = 0.059), whereas the impact of RV dysfunction on survival time was inconclusive (P = 0.451). Multistate analysis showed that patients might transit in and out of RV involvement, and those who exhibited ACP in their last critical care echocardiography (CCE) examination had the highest risk of mortality (hazard ratio (HR) 3.25 [2.38-4.45], P < 0.001). CONCLUSION: RV involvement is prevalent in patients ventilated for COVID-19 ARDS. Different phenotypes of RV involvement might lead to different ICU mortality, with ACP having the worst outcome.

Initial resuscitation guided by the Surviving Sepsis Campaign recommendations and early echocardiographic assessment of hemodynamics in intensive care unit septic patients: a pilot study.

OBJECTIVE: To compare therapeutic interventions during initial resuscitation derived from echocardiographic assessment of hemodynamics and from the Surviving Sepsis Campaign guidelines in intensive care unit septic patients. DESIGN AND SETTING: Prospective, descriptive study in two intensive care units of teaching hospitals. METHODS: The number of ventilated patients with septic shock who were studied was 46. Transesophageal echocardiography was first performed (T1<3 hrs after intensive care unit admission) to adapt therapy according to the following predefined hemodynamic profiles: fluid loading (index of collapsibility of the superior vena cava≥36%), inotropic support (left ventricular fractional area change<45% without relevant index of collapsibility of the superior vena cava), or increased vasopressor support (right ventricular systolic dysfunction, unremarkable transesophageal echocardiography study consistent with sustained vasoplegia). Agreement for treatment decision between transesophageal echocardiography and Surviving Sepsis Campaign guidelines was evaluated. A second transesophageal echocardiography assessment (T2) was performed to validate therapeutic interventions. RESULTS: Although transesophageal echocardiography and Surviving Sepsis Campaign approaches were concordant to manage fluid loading in 32 of 46 patients (70%), echocardiography led to the absence of blood volume expansion in the remaining 14 patients who all had a central venous pressure<12 mm Hg. Accordingly, the agreement was weak between transesophageal echocardiography and Surviving Sepsis Campaign for the decision of fluid loading (κ: 0.37 [0.16;0.59]). With a cut-off value<8 mm Hg for central venous pressure, κ was 0.33 [-0.03;0.69]. Inotropes were prescribed based on transesophageal echocardiography assessment in 14 patients but would have been decided in only four patients according to Surviving Sepsis Campaign guidelines. As a result, the agreement between the two approaches for the decision of inotropic support was weak (κ: 0.23 [-0.04;0.50]). No right ventricular dysfunction was observed. No patient had anemia and only three patients with transesophageal echocardiography documented left ventricular systolic dysfunction had a central venous oxygen saturation<70%. CONCLUSIONS: A weak agreement was found in the prescription of fluid loading and inotropic support derived from early transesophageal echocardiography assessment of hemodynamics and Surviving Sepsis Campaign guidelines in patients presenting with septic shock.

ICU strain and outcome in COVID-19 patients-A multicenter retrospective observational study.

PURPOSE: To compare the characteristics, management, and prognosis of patients admitted to intensive care units (ICU) for coronavirus disease (COVID)-19 during the first two waves of the outbreak and to evaluate the relationship between ICU strain (ICU demand due to COVID-19 admissions) and mortality. METHODS: In a multicentre retrospective study, 1166 COVID-19 patients admitted to five ICUs in France between 20 February and 31 December 2020 were included. Data were collected at each ICU from medical records. A Cox proportional-hazards model identified factors associated with 28-day mortality. RESULTS: 640 patients (55%) were admitted during the first wave (February to June 2020) and 526 (45%) during the second wave (July to December 2020). ICU strain was lower during the second wave (-0.81 [-1.04 --0.31] vs. 1.18 [-0.34-1.29] SD when compared to mean COVID-19 admission in each center during study period, P<0.001). Patients admitted during the second wave were older, had more profound hypoxemia and lower SOFA. High flow nasal cannula was more frequently used during the second wave (68% vs. 39%, P<0.001) and intubation was less frequent (46% vs. 69%, P<0.001). Neither 28-day mortality (30% vs. 26%, P = 0.12) nor hospital mortality (37% vs. 31%, P = 0.27) differed between first and second wave. Overweight and obesity were associated with lower 28-day mortality while older age, underlying chronic kidney disease, severity at ICU admission as assessed by SOFA score and ICU strain were associated with higher 28-day mortality. ICU strain was not associated with hospital mortality. CONCLUSION: The characteristics and the management of patients varied between the first and the second wave of the pandemic. Rather than the wave, ICU strain was independently associated with 28-day mortality, but not with hospital mortality.

Early echocardiography by treating physicians and outcome in the critically ill: An ancillary study from the prospective multicenter trial FROG-ICU.

PURPOSE: This study aimed to investigate the association between the use of early echocardiography performed by the treating physician certified in critical care ultrasound and mortality in ICU patients. MATERIALS AND METHODS: FROG-ICU was a multi-center cohort designed to investigate the outcome of critically ill patients. Of the 1359 patients admitted to centers where echocardiography was available, 372 patients underwent echocardiography during the initial 3 days. RESULTS: Of the ICU patients admitted for cardiac disease, 47.4% underwent echocardiography, and those patients had the lowest left ventricular ejection fraction 40 [31-58] % and the lowest cardiac output 4.2 [3.2-5.7] L/min compared to patients admitted for other causes (p < 0.001 for both). One-year mortality was 36.8% and 39.9% in patients with and without echocardiography, respectively [HR 0.92 (95% CI 0.75-1.11)]. This result was confirmed after multivariable Cox regression analysis [HR 0.88 (95% CI 0.71-1.08)]. Subgroup analyses suggest that among patients admitted to ICU for cardiac disease, those managed with echocardiography had a lower risk of one-year mortality [HR 0.65 (95% CI 0.43-0.98)]. CONCLUSIONS: Early echocardiography by treating physicians was not associated with short- or long-term survival in ICU patients. In subgroups, early echocardiography improved survival in ICU patients admitted for cardiac disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01367093.

Echocardiography findings in COVID-19 patients admitted to intensive care units: a multi-national observational study (the ECHO-COVID study).

PURPOSE: Severely ill patients affected by coronavirus disease 2019 (COVID-19) develop circulatory failure. We aimed to report patterns of left and right ventricular dysfunction in the first echocardiography following admission to intensive care unit (ICU). METHODS: Retrospective, descriptive study that collected echocardiographic and clinical information from severely ill COVID-19 patients admitted to 14 ICUs in 8 countries. Patients admitted to ICU who received at least one echocardiography between 1st February 2020 and 30th June 2021 were included. Clinical and echocardiographic data were uploaded using a secured web-based electronic database (REDCap). RESULTS: Six hundred and seventy-seven patients were included and the first echo was performed 2 [1, 4] days after ICU admission. The median age was 65 [56, 73] years, and 71% were male. Left ventricle (LV) and/or right ventricle (RV) systolic dysfunction were found in 234 (34.5%) patients. 149 (22%) patients had LV systolic dysfunction (with or without RV dysfunction) without LV dilatation and no elevation in filling pressure. 152 (22.5%) had RV systolic dysfunction. In 517 patients with information on both paradoxical septal motion and quantitative RV size, 90 (17.4%) had acute cor pulmonale (ACP). ACP was associated with mechanical ventilation (OR > 4), pulmonary embolism (OR > 5) and increased PaCO2. Exploratory analyses showed that patients with ACP and older age were more likely to die in hospital (including ICU). CONCLUSION: Almost one-third of this cohort of critically ill COVID-19 patients exhibited abnormal LV and/or RV systolic function in their first echocardiography assessment. While LV systolic dysfunction appears similar to septic cardiomyopathy, RV systolic dysfunction was related to pressure overload due to positive pressure ventilation, hypercapnia and pulmonary embolism. ACP and age seemed to be associated with mortality in this cohort.

Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life-experience of the French Network.

We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.