CAR t-cell therapy in BOlogNa-NEUrotoxicity TReatment and Assessment in Lymphoma (CARBON-NEUTRAL): proposed protocol and results from an Italian study.

OBJECTIVE: To investigate neurotoxicity clinical and instrumental features, incidence, risk factors, and early and long-term prognosis in lymphoma patients who received CAR T-cell therapy. METHODS: In this prospective study, consecutive refractory B-cell non-Hodgkin lymphoma patients who received CAR T-cell therapy were included. Patients were comprehensively evaluated (neurological examination, EEG, brain MRI, and neuropsychological test) before and after (two and twelve months) CAR T-cells. From the day of CAR T-cells infusion, patients underwent daily neurological examinations to monitor the development of neurotoxicity. RESULTS: Forty-six patients were included in the study. The median age was 56.5 years, and 13 (28%) were females. Seventeen patients (37%) developed neurotoxicity, characterized by encephalopathy frequently associated with language disturbances (65%) and frontal lobe dysfunction (65%). EEG and brain FDG-PET findings also supported a predominant frontal lobe involvement. The median time at onset and duration were five and eight days, respectively. Baseline EEG abnormalities predicted ICANS development in the multivariable analysis (OR 4.771; CI 1.081-21.048; p = 0.039). Notably, CRS was invariably present before or concomitant with neurotoxicity, and all patients who exhibited severe CRS (grade ≥ 3) developed neurotoxicity. Serum inflammatory markers were significantly higher in patients who developed neurotoxicity. A complete neurological resolution following corticosteroids and anti-cytokines monoclonal antibodies was reached in all patients treated, except for one patient developing a fatal fulminant cerebral edema. All surviving patients completed the 1-year follow-up, and no long-term neurotoxicity was observed. CONCLUSIONS: In the first prospective Italian real-life study, we presented novel clinical and investigative insights into ICANS diagnosis, predictive factors, and prognosis.

Cognitive functions: evaluation and changes after transcatheter aortic valve implantation in elderly patients.

AIM: To assess the prevalence and postprocedural evolution of cognitive impairment (CI) in patients undergoing transcatheter aortic valve implantation. METHODS: 62 patients were enrolled. Mini Mental state examination (MMSE), verbal memory test (VMT), visual search test (VST) and phonemic verbal fluency (PVF) were used to evaluate the cognitive status. CI was considered when a pathological result of MMSE was confirmed by VMT, VST and PVF. RESULTS: A total of 26.2% patients had CI at baseline. MMSE, VMT, VST and PVF were pathologic in 39, 16.1, 8.1 and 22.6% of the patients, respectively. Overall, no significant differences in cognitive function in any dimension were observed from baseline up to 1-year follow-up. CONCLUSION: CI is frequent in patients undergoing transcatheter aortic valve implantation, though the procedure does not forge cognitive status.

[Cognitive and quality of life trajectory after either surgical or transcatheter aortic valve replacement in high-risk patients]. / Evoluzione dello stato cognitivo e della qualità di vita in pazienti con stenosi aortica ad alto rischio clinico sottoposti a sostituzione valvolare chirurgica o per via transcatetere.

RATIONALE: The impact of transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (AVR) on cognitive status and quality of life in high-risk patients has been incompletely investigated. METHODS: We conducted a prospective, multicenter study including all patients treated with TAVI and high-risk patients undergoing AVR (age ≥80 years or logistic EuroSCORE ≥15%) at participating centers. Multidimensional geriatric evaluation including Mini Mental State Examination (MMSE), EuroQol 5D (EQ5D) and Minnesota Living With Heart Failure Questionnaire (MLHFQ) were performed at baseline and at 3- and 12-month follow-up. RESULTS: A total of 518 patients (151 AVR and 367 TAVI) were enrolled in 10 Italian institutions. Patients receiving AVR were older (82.7 ± 2.4 years), with a lower logistic EuroSCORE (12.5 ± 7.1%) as compared with TAVI patients (81.5 ± 6.2 years and 19.6 ± 14.0%, respectively, p=0.001 and p<0.001). Overall, 35.5% of patients showed some degree of cognitive impairment at baseline, with no differences between groups. No significant changes in the cognitive status were observed between baseline and follow-up and between groups at any time point. TAVI patients had a lower quality of life at baseline as compared with AVR patients. Generic and heart failure-related quality of life improved significantly after either procedure. CONCLUSIONS: In high-risk patients, both TAVI and AVR are associated with a significant improvement of quality of life up to 1 year without a detrimental effect on cognitive function.

[Quality of life after transcatheter aortic valve implantation: a Comprehensive literature review and critical appraisal]. / La qualità di vita dopo impianto transcatetere di valvola aortica: revisione e valutazione critica della letteratura.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a very effective treatment option for patients with severe aortic stenosis who are either not suitable candidates or at high risk for surgical aortic valve replacement (AVR). Patients undergoing TAVI are often very elderly and their clinical status is burdened with multiple comorbidities, therefore evaluation of quality of life (QoL) might be challenging. We sought to provide an overview of available data on QoL changes after TAVI and critical insights on the instruments used to detect these changes. METHODS: This analysis focuses on studies that evaluated QoL after TAVI with standardized questionnaires. Out of 706 items identified through literature search, 23 studies were included in the final review: 2 randomized controlled trials (one comparing QoL pre- vs post-TAVI, one TAVI vs AVR vs medical therapy) and 21 observational studies (19 studies comparing QoL pre- and post-TAVI and 2 studies TAVI vs AVR). The instruments used in all studies were not specific for TAVI patients. RESULTS: Most studies reported a significant improvement in QoL after TAVI, greater for physical aspects compared with psychological components, which persisted at mid and long-term follow-up. A short-term benefit was found for transfemoral TAVI patients as compared with transapical TAVI and AVR; however, these differences tended to disappear over time. CONCLUSIONS: The study highlights an improvement in QoL after TAVI that persists over time. As different instruments resulted to be more sensitive to detect different aspects, multidimensional assessments - capable of combining disease-specific and disease-non-specific measures - should foster clinical research in order to have a more complete picture of QoL of TAVI patients.