Reintroduction of immune-checkpoint inhibitors after immune-related meningitis: a case series of melanoma patients

Immune-checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated antigen-4 and programmed cell death ligand-1) are associated with several immune-related neurological disorders. Cases of meningitis related to ICIs are poorly described in literature and probably underestimated. Several guidelines are available for the acute management of these adverse events, but the safety of resuming ICIs in these patients remains unclear. We conducted a retrospective case series of immune-related meningitis associated with ICIs that occurred between October 1 2015 and October 31 2019 in two centers: Saint-Louis and Cochin hospitals, Paris, France. Diagnosis was defined by a (1) high count of lymphocytes (>8 cells/mm3) and/or high level of proteins (>0.45 g/L) without bacteria/virus or tumor cells detection, in cerebrospinal fluid and (2) normal brain and spine imaging. Patients were followed-up for at least 6 months from the meningitis onset. Seven cases of immune-related meningitis are here reported. Median delay of meningitis occurrence after ICIs onset was 9 days. Steroid treatment was introduced in four patients at a dose of 1 mg/kg (prednisone), allowing a complete recovery within 2 weeks. The other three patients spontaneously improved within 3 weeks. Given the favorable outcome, ICIs were reintroduced in all patients. The rechallenge was well tolerated and no patients experienced meningitis recurrence. In conclusion, in our series, the clinical course was favorable and steroids were not always required. Resuming ICIs in these patients appeared safe and can thus be considered in case of isolated meningitis. However, a careful analysis of the risk/benefit ratio should be done on a case-by-case basis

Risk assessment in miscellaneous food processing industries including producers of vegetables and spices

Risk Assessment of Microbial Problems and Preventive Actions in Food Industry - 2nd Open Seminar Arranged by SAFOODNET - Food Safety and Hygiene Networking Within New Member States and Associated Candidate Countries; Istanbul; Turkey; 22 October 2007 through 23 October 2007Testing foods for pathogenic and spoilage bacteria is the cornerstone to ensuring a safe and wholesome food supply. The methods for monitoring of microbial contamination are based on the following principles: → Cultivation of microbes in the presence of different energy sources, → Analysis of their macromolecular composition and their metabolic byproducts, → Use of specific immunological reagents for bacterial classification and identification

Immunotherapy with CpG-ODN in neoplastic meningitis: A phase I trial

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Descriptive and retrospective analysis of diffuse glioma patients with symptomatic SARS-CoV2 infection during the first wave of the pandemic

International audienceBackgroundLittle is known about diffuse glioma patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2).MethodsWe performed a descriptive and retrospective analysis of 41 diffuse glioma patients with symptomatic SARS-CoV2 infection during the first wave of the COVID-19 pandemic.ResultsConfusion with or without fever was the most common neurological symptom (32%) supporting SARS-CoV2 testing in glioma patients with acute and unexplained confusion. Sixteen patients (39%) died after a median delay of 13 days. While multiple clinical, biological, and pathological features, COVID-19- or diffuse glioma-related, at hospital admission appeared to have a pejorative prognostic impact, none was significantly associated with death. Oncological treatments were interrupted at COVID-19 diagnosis and re-initiated with a median delay of 30 days after the end of COVID-19 symptoms.ConclusionsInterestingly, our retrospective study describes for the first time the characteristics of a cohort of diffuse glioma patients with symptomatic COVID-19. Diffuse glioma patients with poorly symptomatic COVID-19 did not come to the attention of physicians and were not enrolled in the study skewing the denominator for prognostic analysis. Further studies are warranted to specify prognosis of overall population of diffuse glioma patients with COVID-19, including asymptomatic patients, and interactions of prognostic factors of both COVID-19 and diffuse gliomas

Description of neurotoxicity in a series of patients treated with CAR T-cell therapy

International audienceAbstract Chimeric antigen receptor-modified T (CAR T) cell therapy is a highly promising treatment for haematological malignancies but is frequently associated with cytokine release syndrome and neurotoxicity. Between July 2018 and July 2019, all patients treated with CD19-targeted CAR T-cell therapy for relapsing lymphoma were followed-up longitudinally to describe neurological symptoms and their evolution over time. Four different French centres participated and 84 patients (median age 59 years, 31% females) were included. Neurotoxicity, defined as the presence of at least one neurological symptom appearing after treatment infusion, was reported in 43% of the patients. The median time to onset was 7 days after infusion with a median duration of 6 days. More than half of the patients (64%) had grade 1–2 severity and 34% had grade 3–4. CRS was observed in 80% of all patients. The most frequent neurological symptoms were cognitive signs, being severe in 36%, and were equally distributed between language disorders and cognitive disorders without language impairment. Non-pyramidal motor disorders, severe in 11%, were reported in 42% of the patients. Elevation of C-reactive protein (CRP) within 4 days after treatment was significantly correlated with the occurrence of grade 3–4 neurotoxicity. Although sometimes severe, neurotoxicity was almost always reversible. The efficacy of steroids and antiepileptic drugs remains unproven in the management of neurotoxicity. Neurotoxicity associated with CAR T-cell therapies occurs in more than 40% of patients. The clinical pattern is heterogeneous but cognitive disorders (not limited to language disorders) and, to a minor degree, non-pyramidal motor disorders, appeared as a signature of severe neurotoxicity