Paraneoplastic syndromes include, by definition, any symptomatic and non-metastatic condition ass... more Paraneoplastic syndromes include, by definition, any symptomatic and non-metastatic condition associated with a neoplasm. Paraneoplastic movement disorders are a heterogeneous group of syndromes encompassing both hyperkinetic and hypokinetic conditions, characterized by acute/sub-acute onset, rapidly progressive evolution, and multifocal localizations with several overlapping features. These movement disorders are immune-mediated, as shown by the rapid onset and by the presence of antineuronal antibodies in biological samples of patients, fundamental for the diagnosis. Antineuronal antibodies could be targeted against intracellular or neuronal surface antigens. Paraneoplastic movement disorders associated with anti-neuronal surface antigens antibodies respond more frequently to immunotherapy. The underlying tumors may be different, according to the clinical presentation, age, and gender of patients. Our search considered articles involving human subjects indexed in PubMed. Abstracts were independently reviewed for eligibility criteria by one author and validated by at least one additional author. In this review, we sought to critically reappraise the clinical features and the pathophysiological mechanisms of paraneoplastic movement disorders, focusing on diagnostic and therapeutic strategies. Our main aim is to make clinicians aware of paraneoplastic movement disorders, and to provide assistance in the early diagnosis and management of these rare but life-threatening conditions.
853 (HR: 0.938; 95% CI: 0.898-0.980). Nevertheless, there was no significant correlation between ... more 853 (HR: 0.938; 95% CI: 0.898-0.980). Nevertheless, there was no significant correlation between severity and prognosis according to our definition. EP severity varies greatly among patients [1, 5]. Former studies have generally evaluated the condition of patients using the Psoriasis Area and Severity Index (PASI), however, this failed to reflect general condition and systemic involvement in patients. To assess the severity of EP, we therefore proposed that the following should be considered: hyperthermia, swelling and exudation of skin lesions, oedema of the lower limbs, and superficial lymphadenopathy. These characteristics were chosen because they are common manifestations in EP patients and indicate systemic inflammatory reaction as well as skin barrier destruction. We believe that this practical method improved our ability to identify and manage moderate-to-severe EP patients, who would expect longer hospital stays and have a higher chance of developing comorbidities such as an...
Programmed death receptor-1 (PD-1) and its ligand (PD-L1) interaction negatively regulates T cell... more Programmed death receptor-1 (PD-1) and its ligand (PD-L1) interaction negatively regulates T cell function in head and neck squamous cell carcinoma (HNSCC). Overexpression of PD-1 reduces intracellular Ca2+ fluxes, and thereby T cell effector functions. In HNSCC patients, PD-1 blockade increases KCa3.1 and Kv1.3 activity along with Ca2+ signaling and mobility in CD8+ peripheral blood T cells (PBTs). The mechanism by which PD-L1/PD-1 interaction regulates ion channel function is not known. We investigated the effects of blocking PD-1 and PD-L1 on ion channel functions and intracellular Ca2+ signaling in CD8+ PBTs of HNSCC patients and healthy donors (HDs) using single-cell electrophysiology and live microscopy. Anti-PD-1 and anti-PD-L1 antibodies increase KCa3.1 and Kv1.3 function in CD8+ PBTs of HNSCC patients. Anti-PD-1 treatment increases Ca2+ fluxes in a subset of HSNCC patients. In CD8+ PBTs of HDs, exposure to PD-L1 reduces KCa3.1 activity and Ca2+ signaling, which were restore...
Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay ... more Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay remains unclear. We systematically reviewed studies (PubMed 1967–2019) reporting gene variants associated with both parkinsonism and cancer. Somatic variants were examined in cancer samples, whereas germline variants were examined in cancer patients with both symptomatic and asymptomatic (carriers) genetic parkinsonisms. Pooled proportions were calculated with random-effects meta-analyses. Out of 9,967 eligible articles, 60 were included. Of the 28 genetic variants associated with parkinsonism, six were also associated with cancer. In cancer samples, SNCA was predominantly associated with gastrointestinal cancers, UCHL1 with breast cancer, and PRKN with head-and-neck cancers. In asymptomatic carriers, LRRK2 was predominantly associated with gastrointestinal and prostate cancers, PRKN with prostate and genitourinary tract cancers, GBA with sarcoma, and 22q11.2 deletion with leukemia. In s...
e18551 Background: Treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) i... more e18551 Background: Treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) involves a combination of surgery, chemotherapy, and radiotherapy (RT). RT for HNSCC is a known risk factor for the development of hypothyroidism. Recently, anti-PD1 therapies have been approved for recurrent and metastatic HNSCC and are moving to the forefront of HNSCC care. Similarly, thyroid dysfunction is a common immune-related adverse event following anti-PD1 therapy. Whether the addition of anti-PD1 to RT increases the likelihood of developing hypothyroidism remains unknown. Methods: The rate of hypothyroidism in HNSCC patients receiving RT (+/- chemotherapy and surgery) was compared to HNSCC patients receiving RT + anti-PD1 therapy either concurrently or after RT. Exclusion criteria were preexisting thyroid dysfunction, RT dose < 45 Gy and patients with incomplete treatment records. We defined clinical hypothyroidism as an elevation of TSH with low T3, T4 or elevation of TSH wi...
Hypothyroidism is a relatively common complication of head and neck squamous cell carcinoma (HNSC... more Hypothyroidism is a relatively common complication of head and neck squamous cell carcinoma (HNSCC) treatment. The objective of this study was to determine whether the addition of programmed death ligand‐1 (PD‐1) or programmed death ligand‐1 (PD‐L1) inhibition (anti‐PD‐1/PD‐L1 therapy) to standard treatment increases the risk of hypothyroidism in HNSCC.
Paraneoplastic syndromes include, by definition, any symptomatic and non-metastatic condition ass... more Paraneoplastic syndromes include, by definition, any symptomatic and non-metastatic condition associated with a neoplasm. Paraneoplastic movement disorders are a heterogeneous group of syndromes encompassing both hyperkinetic and hypokinetic conditions, characterized by acute/sub-acute onset, rapidly progressive evolution, and multifocal localizations with several overlapping features. These movement disorders are immune-mediated, as shown by the rapid onset and by the presence of antineuronal antibodies in biological samples of patients, fundamental for the diagnosis. Antineuronal antibodies could be targeted against intracellular or neuronal surface antigens. Paraneoplastic movement disorders associated with anti-neuronal surface antigens antibodies respond more frequently to immunotherapy. The underlying tumors may be different, according to the clinical presentation, age, and gender of patients. Our search considered articles involving human subjects indexed in PubMed. Abstracts were independently reviewed for eligibility criteria by one author and validated by at least one additional author. In this review, we sought to critically reappraise the clinical features and the pathophysiological mechanisms of paraneoplastic movement disorders, focusing on diagnostic and therapeutic strategies. Our main aim is to make clinicians aware of paraneoplastic movement disorders, and to provide assistance in the early diagnosis and management of these rare but life-threatening conditions.
853 (HR: 0.938; 95% CI: 0.898-0.980). Nevertheless, there was no significant correlation between ... more 853 (HR: 0.938; 95% CI: 0.898-0.980). Nevertheless, there was no significant correlation between severity and prognosis according to our definition. EP severity varies greatly among patients [1, 5]. Former studies have generally evaluated the condition of patients using the Psoriasis Area and Severity Index (PASI), however, this failed to reflect general condition and systemic involvement in patients. To assess the severity of EP, we therefore proposed that the following should be considered: hyperthermia, swelling and exudation of skin lesions, oedema of the lower limbs, and superficial lymphadenopathy. These characteristics were chosen because they are common manifestations in EP patients and indicate systemic inflammatory reaction as well as skin barrier destruction. We believe that this practical method improved our ability to identify and manage moderate-to-severe EP patients, who would expect longer hospital stays and have a higher chance of developing comorbidities such as an...
Programmed death receptor-1 (PD-1) and its ligand (PD-L1) interaction negatively regulates T cell... more Programmed death receptor-1 (PD-1) and its ligand (PD-L1) interaction negatively regulates T cell function in head and neck squamous cell carcinoma (HNSCC). Overexpression of PD-1 reduces intracellular Ca2+ fluxes, and thereby T cell effector functions. In HNSCC patients, PD-1 blockade increases KCa3.1 and Kv1.3 activity along with Ca2+ signaling and mobility in CD8+ peripheral blood T cells (PBTs). The mechanism by which PD-L1/PD-1 interaction regulates ion channel function is not known. We investigated the effects of blocking PD-1 and PD-L1 on ion channel functions and intracellular Ca2+ signaling in CD8+ PBTs of HNSCC patients and healthy donors (HDs) using single-cell electrophysiology and live microscopy. Anti-PD-1 and anti-PD-L1 antibodies increase KCa3.1 and Kv1.3 function in CD8+ PBTs of HNSCC patients. Anti-PD-1 treatment increases Ca2+ fluxes in a subset of HSNCC patients. In CD8+ PBTs of HDs, exposure to PD-L1 reduces KCa3.1 activity and Ca2+ signaling, which were restore...
Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay ... more Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay remains unclear. We systematically reviewed studies (PubMed 1967–2019) reporting gene variants associated with both parkinsonism and cancer. Somatic variants were examined in cancer samples, whereas germline variants were examined in cancer patients with both symptomatic and asymptomatic (carriers) genetic parkinsonisms. Pooled proportions were calculated with random-effects meta-analyses. Out of 9,967 eligible articles, 60 were included. Of the 28 genetic variants associated with parkinsonism, six were also associated with cancer. In cancer samples, SNCA was predominantly associated with gastrointestinal cancers, UCHL1 with breast cancer, and PRKN with head-and-neck cancers. In asymptomatic carriers, LRRK2 was predominantly associated with gastrointestinal and prostate cancers, PRKN with prostate and genitourinary tract cancers, GBA with sarcoma, and 22q11.2 deletion with leukemia. In s...
e18551 Background: Treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) i... more e18551 Background: Treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) involves a combination of surgery, chemotherapy, and radiotherapy (RT). RT for HNSCC is a known risk factor for the development of hypothyroidism. Recently, anti-PD1 therapies have been approved for recurrent and metastatic HNSCC and are moving to the forefront of HNSCC care. Similarly, thyroid dysfunction is a common immune-related adverse event following anti-PD1 therapy. Whether the addition of anti-PD1 to RT increases the likelihood of developing hypothyroidism remains unknown. Methods: The rate of hypothyroidism in HNSCC patients receiving RT (+/- chemotherapy and surgery) was compared to HNSCC patients receiving RT + anti-PD1 therapy either concurrently or after RT. Exclusion criteria were preexisting thyroid dysfunction, RT dose < 45 Gy and patients with incomplete treatment records. We defined clinical hypothyroidism as an elevation of TSH with low T3, T4 or elevation of TSH wi...
Hypothyroidism is a relatively common complication of head and neck squamous cell carcinoma (HNSC... more Hypothyroidism is a relatively common complication of head and neck squamous cell carcinoma (HNSCC) treatment. The objective of this study was to determine whether the addition of programmed death ligand‐1 (PD‐1) or programmed death ligand‐1 (PD‐L1) inhibition (anti‐PD‐1/PD‐L1 therapy) to standard treatment increases the risk of hypothyroidism in HNSCC.
Uploads
Papers by Martina Chirra