Introduction International guidelines regarding the management of immune effector cell-associated neurotoxicity syndrome (ICANS) recommend several paraclinical assessments, including MRI, lumbar ...puncture (LP) and EEG based on ICANS grade. However, the impact of these paraclinical investigations has not yet been evaluated. Methods Here, we aimed to analyze the role of MRI, LP and EEG in the management of ICANS in a cohort of real-life patients treated with CAR T-cells at the University Hospital of Rennes, France. The primary endpoint was to assess the therapeutic modifications induced by each paraclinical investigation. The secondary endpoints were to assess the specific abnormalities and differential diagnoses founded on MRI, LP and EEG. We also performed subgroup analysis for each ICANS grade. Results Between August 2018 and January 2023, 190 consecutive patients were treated with CAR T-cells. A total of 91 (48%) patients developed an ICANS including 25 grade 1 (13%), 32 grade 2 (17%), 21 grade 3 (11%) and 12 grade 4 (6%). MRI was performed in 71 (78%) patients with ICANS. The most common result was a normal MRI, corresponding to 80 % of MRI. One of the most frequent abnormal result was aspecific hypersignal, which occurred in 4 (6%) patients with ICANS. Notably, there was no oedema depicted on MRI, even in the most severe ICANS grade 4. Overall, 3 MRI (4% of all MRI) generated therapeutic modification (Figure 1). Two MRI which described strokes in patients with ICANS grade 3 led to initiation or increase of APT therapy. One patient with ICANS grade 1 received APT as MRI described a stroke event but reclassified as normal a posteriori. Lumbar puncture was performed in 43 (47%) patients. A high rate of LP was abnormal in our cohort (86%). There were 3 preemptive therapeutic modifications for unconfirmed infection (7%) (Figure 1). Two LP led to probabilistic antivirals introduction (aciclovir) in patient with ICANS grade 1 and 2 because of lymphocytic meningitis. One LP led to probabilistic antifungals introduction (voriconazole) in patient with ICANS grade 3 for a suspected Aspergillus spp. meningitis, which was not confirmed after infectious disease physician's expertise. Systematic EEG performed in 51 (56%) patients requested without clinical signs of epilepsy were analyzed. Only 18% of EEG were normal (Table 1). The most common finding was encephalopathy in 45% of patients. Notably, 6 EEG (12%) reported seizure or status epilepticus in patients with no abnormal movements. Finally, 8 EEG (16%) led to therapeutic modification in the entire cohort (Figure 1). All EEG which found seizure or status epilepticus led to an increase in AE prophylaxis by levetiracetam or introduction of a new AE (mainly phenytoin). Discussion The therapeutic impact varied between paraclinical investigations. On one hand, systematic EEG based on ICANS grade only was often followed by therapeutic modification (16% of cases). On the other hand, systematic LP was never associated with relevant therapeutic modification, even in case of severe ICANS, and this broad LP policy resulted in initiation of antimicrobial agents for unconfirmed infections in three patients (7%). Moreover, the need for systematic MRI assessment is also questionable, as only 4% of MRI led to a therapeutic modification and no MRI found oedema, which is one of the main concerns of treating physicians managing severe ICANS. Our study shows that EEG is the paraclinical assessment with the greatest therapeutic impact while MRI and LP appear to have a limited therapeutic impact. Our results emphasize the role of EEG in the current guidelines, but questions the need for systematic MRI and LP, which might be left to the discretion of the treating physician.
This study aimed to compare ventilatory parameters recorded in the first days of acute respiratory distress syndrome (ARDS) and mortality at day 60 between coronavirus disease 2019 (COVID-19) and ...influenza ARDS patients with arterial oxygen tension (
)/inspiratory oxygen fraction (
) ≤150 mmHg.
We compared 244 COVID-19 ARDS patients with 106 influenza ARDS patients. Driving pressure, respiratory system compliance (
), ventilator ratio, corrected minute ventilation (
'
) and surrogate of mechanical power (index=(4×driving pressure)+respiratory rate) were calculated from day 1 to day 5 of ARDS. A propensity score analysis and a principal component analysis (PCA) were performed.
On day 1 of ARDS, COVID-19 patients had significantly higher
/
(median (interquartile range) 97 (79-129.2)
83 (62.2-114) mmHg; p=0.001), and lower driving pressure (13.0 (11.0-16.0)
14.0 (12.0-16.7) cmH
O; p=0.01), ventilatory ratio (2.08 (1.73-2.49
2.52 (1.97-3.03); p<0.001),
'
(12.7 (10.2-14.9)
14.9 (11.6-18.6) L·min
; p<0.001) and index (80 (70-89)
84 (75-94); p=0.004). PCA demonstrated an important overlap of ventilatory parameters recorded on day 1 between the two groups. From day 1 to day 5, repeated values of
/
, arterial carbon dioxide tension, ventilatory ratio and
'
differed significantly between influenza and COVID-19 patients in the unmatched and matched populations. Mortality at day 60 did not differ significantly after matching (29%
21.7%; p=0.43).
Ventilation was more impaired in influenza than in COVID-19 ARDS patients on the first day of ARDS with an important overlap of values. However, mortality at day 60 did not differ significantly in the matched population.
To determine whether immersive virtual patient simulation (IVPS) on the MedicActiv platform is influential in improving student academic performance in module validation tests.
In this prospective ...randomized controlled study a comparison was made between IVPS training combined with regular faculty courses versus courses alone. The primary endpoint was module validation grades. Secondary endpoints were satisfaction scores (overall interest, ergonomics, realism, immersion, and training efficiency).
Angers School of Medicine, France.
2018 to 2019 class of fourth-year students, included on a voluntary basis. In the first semester 51 students were included, of whom 13 were excluded for lack of compliance (6 and 7 from the IVPS and control groups, respectively). In the second semester we included 57 students, of whom 10 were excluded for lack of compliance (2 and 8 from the IVPS and control groups, respectively).
Mean age was 21 years (±0.8). There were 85 female and 23 male students. In the first semester mean grades were 13.4 ± 1.6 versus 11/.9 ± 2.4 in the IVPS and control groups, respectively (p = 0.038). In the second semester mean grades were 15.3 ± 2.5 versus 11.9 ± 3.6 in the IVPS and control groups, respectively p < 0.001. The entire study population was pooled (n = 85): mean grades were 14.5 ± 2.4 versus 11.9 ± 3 in the IVPS group and the control group, respectively, p < 0.001. The satisfaction questionnaire response rate was 54% (46/85). Score percentages ≥4 regarding overall interest, ergonomics, realism, immersion and training efficiency were 89%, 85%, 100%, 93%, and 93% respectively.
Complementing conventional university education with simulation of virtual consultation cases on the MedicActiv platform improved student academic performance as compared with students studying regular courses. Students reported high levels of satisfaction with overall interest, ergonomics, realism, immersion and training efficiency on the MedicActiv platform.
•Data from a large cohort of CAR T-cell–treated patients question guidelines regarding diagnostic investigations in ICANS management.•Our results emphazise for the first time the role of EEG in the ...current guidelines but questions the need for systematic MRI and LP.
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International guidelines regarding the management of immune effector cell–associated neurotoxicity syndrome (ICANS) recommend several diagnostic investigations, including magnetic resonance imaging (MRI), lumbar puncture (LP), and electroencephalogram (EEG) based on ICANS grade. However, the impact of these investigations has not yet been evaluated. Here, we aimed to describe the role of MRI, LP, and EEG in the management of ICANS in a cohort of real-life patients treated with chimeric antigen receptor (CAR) T cells at the University Hospital of Rennes, France. Between August 2018 and January 2023, a total of 190 consecutive patients were treated with CAR T cells. Among those, 91 (48%) developed ICANS. MRI was performed in 71 patients (78%) with ICANS, with a therapeutic impact in 4% of patients, despite frequent abnormal findings. LP was performed in 43 patients (47%), which led to preemptive antimicrobial agents in 7% of patients, although no infection was eventually detected. Systematic EEG was performed in 51 patients (56%), which led to therapeutic modifications in 16% of patients. Our study shows that EEG is the diagnostic investigation with the greatest therapeutic impact, whereas MRI and LP appear to have a limited therapeutic impact. Our results emphasize the role of EEG in the current guidelines but question the need for systematic MRI and LP, which might be left to the discretion of the treating physician.
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