Peripheral nervous system adverse events associated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) represent an effective cancer immunotherapy yet are associated with immune-related adverse events (irAEs). The aim of this study was to characterize irAEs involving the peripheral nervous system (PNS-irAEs) in a real-world cohort of ICI-treated patients. METHODS: Cancer patients treated with ICIs between January 2014 and March 2022 were included. Patients with PNS-irAEs were identified and divided into two groups: (1) cranial/peripheral neuropathies and (2) myasthenia gravis (MG) and/or myositis. Clinical characteristics and outcomes, measured with the modified Rankin Scale (mRS), were compared among the two groups. RESULTS: Among 920 ICI-treated patients, 20 patients (2.17%) developed a PNS-irAEs. The median latency from ICI exposure was 8.8 weeks and the median time from onset to clinical nadir was 3.5 weeks. Eleven patients developed a neuropathy: polyneuropathy (n = 4), cranial neuropathy (n = 3), small-fiber neuropathy (n = 3), brachial plexopathy (n = 1). Nine patients presented MG and/or myositis: concomitant MG and myositis (n = 6), isolated myositis (n = 2), exacerbation of MG (n = 1). Immunosuppressive treatment and/or ICI withdrawal determined a significant clinical improvement, expressed by a mRS reduction, in the neuropathy group (p = 0.004), but not in the MG/myositis group (p = 0.11). Overall, death due to irAEs occurred in four patients (20%), all with MG/myositis. Compared to patients with neuropathies, those with MG/myositis had a shorter latency onset (p = 0.036), developed more frequently concomitant non-neurologic irAEs (p = 0.028) and showed a higher mortality rate (p = 0.026). CONCLUSIONS: In our large cohort of ICI-treated patients, 2.17% developed PNS-irAEs. Compared to ir-neuropathies, ir-MG/myositis tend to occur earlier from ICI exposure and present a worse response to treatment and a higher mortality.

Excess mortality in people with mental illness: findings from a Northern Italy psychiatric case register.

PURPOSE: People with mental disorders show mortality rates up to 22.2 times higher than that of the general population. In spite of progressive increase in life expectancy observed in the general population, the mortality gap of people suffering from mental health problems has gradually widened. The aim of this paper was to study mortality rates in people suffering from mental illness in a cohort of people (16,981 subjects) in the local mental health register of the province of Modena during the decade 2006-2015. METHODS: Standardized Mortality Ratios (SMRs) were calculated to compare the mortality of people with mental disorders to the mortality of people living in the province of Modena and the excess of mortality was studied in relation to the following variables: gender, age group, diagnosis and causes of death. In addition, Poisson regression analysis was performed to study the association between patient characteristics and mortality. RESULTS: An overall excess mortality of 80% was found in subjects under the care of mental health services as compared to the reference population (SMR = 1.8, 95% CI 1.7-1.9). Subjects in the 15-44 year group presented the highest SMR (9.2, 95% CI 6.9-11.4). The most prevalent cause of death was cancer (28.1% of deaths). At the Poisson regression, the diagnosis "Substance abuse and dependence" showed the highest relative risk (RR) (4.00). Moreover, being male, single, unemployed and with a lower qualification was associated with higher RRs. CONCLUSIONS: Our study confirms that subjects with mental illness have higher SMR. Noteworthy, the overall higher risk of mortality was observed in the younger age group.