Lacosamide in monotherapy in BTRE (brain tumor-related epilepsy): results from an Italian multicenter retrospective study.

PURPOSE: Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. METHODS: We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). RESULTS: Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1-2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. CONCLUSIONS: This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

EAN consensus statement for management of patients with neurological diseases during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19. METHODS: A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co-chairs rated importance on a five-point Likert scale. Results were graded by importance and reported as consensus statements. RESULTS: In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty-nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co-chairs of 29 SPs. Whilst general recommendations related to prevention of COVID-19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. CONCLUSION: This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID-19 pandemic that provides immediate guidance for neurologists. In this fast-evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.

The international European Academy of Neurology survey on neurological symptoms in patients with COVID-19 infection.

BACKGROUND AND PURPOSE: Although the main clinical features of COVID-19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. The incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID-19 Task Force initiated a survey on neurological symptoms observed in patients with COVID-19 infection. METHODS: A 17-question online survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on 9 April 2020. RESULTS: By 27 April 2020, proper data were collected from 2343 responders (out of 4199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID-19 mainly in emergency rooms and in COVID-19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID-19 (neuro COVID-19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%) and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID-19; they were most commonly recognized in patients with multiple general symptoms and occurred at any time during infection. CONCLUSION: Neurologists are currently and actively involved in the management of neurological issues related to the COVID-19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID-19, neurological disease characteristics and the contribution of neurological manifestations to outcome.

Cigarette smoking and histologic type of lung cancer in men.

STUDY OBJECTIVES: To determine whether intensity, duration, age at initiation, and cessation of cigarette smoking act differently in the development of various histologic types of lung cancer. DESIGN: A case-control study among deceased men who underwent autopsy, a procedure that involves approximately 73% of all local deaths. SETTING: The Province of Trieste in northeastern Italy PARTICIPANTS: Seven hundred fifty-five patients with lung cancer, including 267 with squamous cell carcinoma, 218 with small cell carcinoma, 90 with large cell carcinoma, 158 with adenocarcinoma, and 22 with other histologic types, and 755 control subjects who had died of causes other than chronic lung diseases and certain tumors. Information on smoking habits, residential history, and occupational exposure was obtained from each subject's next of kin. RESULTS: Compared with nonsmokers, the odds ratio (OR) for current smokers was 13.4 for all types combined, 18.8 for squamous cell carcinoma, 14.3 for small cell carcinoma, 34.3 for large cell carcinoma, and 7.9 for adenocarcinoma. Intensity of smoking, duration, age at starting, and dose were all directly associated with all histologic types of lung cancer, although the OR was lower for adenocarcinoma than for other cell types. When results were restricted to ever smokers, exposure-response curves were similar across histologic types. The risk of lung cancer attributable to smoking was 88% for all types combined, 91% for squamous cell carcinoma, 89% for small cell carcinoma, 95% for large cell carcinoma, and 82% for adenocarcinoma. CONCLUSIONS: This study confirms that cigarette smoking causes all types of lung cancer, but the proportion of cases attributable to smoking is lower for adenocarcinoma than for other types, due to a higher proportion of nonsmokers.

Cancer of the oldest old. What we have learned from autopsy studies.

Cancer in the oldest old is a novel problem, due to the recent burgeoning of the population aged 85 and older. This article addresses three critical questions related to cancer in the oldest old: Does the incidence of cancer increase after age 95? Is cancer a common cause of death for the oldest old? Is cancer accurately diagnosed in the oldest old? The authors analyzed a group of 507 autopsies of elderly, divided in three age groups, 75 90 years, 95 99, and over 99 (centenarians). The prevalence of cancer was 35% among the younger persons and 20% and 16% respectively for those aged 95 99 and for the centenarians. A fourth of the patients in the younger group died from cancer but only 9.5% of the people between 95 and 98 years and 7.1% of the centenarians died from cancer. The cancer was the direct cause of death for 67% of the younger persons and 41% of patients belonging to the two oldest groups. The prevalence of metastases was 63% for tumors occurring in persons aged 75 90, 32% in persons aged 95 98, and 29% in the centenarians. Cancer had been accurately diagnosed prior to death in 67.4% of persons aged 75 90, in 38.5% of those aged 95 99, and 29.4% of the centenarian. Cancer as cause of death had been underestimated in 16% of the cases in the younger persons and in almost 50% of cases of the oldest old. This study suggests that the incidence of cancer and the importance of cancer as a cause of death may decline after age 95 and that the clinical diagnoses underestimate significantly both the incidence of cancer and the prevalence of cancer deaths in the oldest old.

[Comparison of epidemiologic methods in a case-control study of lung cancer and air pollution in Trieste, Italy]. / Confronto di metodi di epidemiologia analitica in uno studio caso-controllo su inquinamento atmosferico e tumore polmonare a Trieste.

To investigate the relationship between air pollution and histologic type of lung cancer we conducted a case-control study among deceased men in Trieste, Italy. 755 cases of lung cancer and 755 controls were identified through the local autopsy registry. Information on smoking habits, occupation and place of residence was obtained from the subject's next-of-kin. Air pollution at the residence of each subject was estimated from the average value of total particulate at the nearest monitoring station. Spatial models and logistic regression were used to evaluate the effect of residence and air pollution on LC after adjustment for age, smoking habits, likelihood of exposure to occupational carcinogens and social group. The risk of lung cancer increased with increasing level of air pollution for all types of lung cancer combined (P = 0.022), for small cell carcinoma (P = 0.016) and for large cell carcinoma (P = 0.049). Compared with inhabitants of the residential area, residents of the rural area had a relative risk (RR) of 0.6 (95% confidence interval (CI): 0.4-1.0). The RR was 1.5 (1.0-2.2) for residents of the center of the city and 1.4 (1.0-2.1) for residents of the industrial area. In the center of the city the excess risk was almost completely restricted to small cell carcinoma (RR = 2.0) and to large cell carcinoma (RR = 2.6). In the industrial area the risk was increased especially for adenocarcinoma (RR = 2.1). These results provide evidence that air pollution is a moderate risk factor for certain histologic types of lung cancer.

[Methodological issues and first results of a record linkage between AIDS and Cancer Registries in Italy]. / Incrocio tra i Registri Tumori italiani e il Registro nazionale AIDS: aspetti metodologici e primi risultati.Cancer and AIDS Registry Linkage Study.

We report herein, the first results of a record linkage between the Italian AIDS Registry and 13 population-based Cancer Registries (about 8-million population in 1991). An anonymous linkage process was carried out on about 339,000 cancer notifications and 6,067 AIDS ones reported between 1982 and 1994. Out of 243 Kaposi's sarcomas (KS) below age 50 years recorded at either type of registry, 90 (37%) were reported as such by both. Sixty-eight percent of individuals with KS at Cancer Registries could be identified at the AIDS Registry. Sixty-two percent of individuals with KS and 65% of individuals reported as having non-Hodgkin's lymphoma (NHL) at RAIDS could be also found at Cancer Registries. Among 6,067 persons with AIDS 15-69 years old, observed and expected numbers of cancer and age-standardised incidence ratios (SIR) on a total of 25,759 person-years were computed. Significantly increased SIR was found for Hodgkin's disease (8.9; 95% CI: 4.4-16.0), invasive carcinoma of the cervix uteri (15.5; 95% CI: 4.0-40.1), and non-melanomatous skin cancer (3.0, 95%, CI: 1.3-5.9). As in previous studies, KS and NHL were greatly increased (SIR = 1,300 and 59, respectively). The risk for all cancer types, after exclusion of KS and NHL, was approximately twice the risk of the general population. An increased SIR of Hodgkin's disease in persons with AIDS is thus confirmed, though many-fold smaller than for NHL. An association with invasive carcinoma of the cervix is also shown at a population level. These data indicate the potential of AIDS and Cancer Registries for improving cancer assessment in individuals with HIV/AIDS and elucidating the role of immune system on cancer onset.

[Lung cancer in the province of Trieste]. / Cancro polmonare nella Provincia di Trieste.

In our study we analyzed a file of 756 males with lung cancer and an equal number of controls matched by sex, age and year of death. All the subjects were resident in the Trieste area, died between 1979-81 and 1985-86 and underwent autopsy at the Istitute of Pathological Anatomy of the University of Trieste. The aim of the research was to analyze and quantify the risk to develop lung cancer in those exposed to asbestos, and well-recognized carcinogens (list A of I.A.R.C.) or suspected (list B). We have also analyzed the relative risk (R.R.) for lung cancer among those subjects with environmental exposure to air pollution in industrial and urban areas. The study was set up in the Trieste province, a geographic area which is particularly suitable for epidemiological studies. We have demonstrated on excess of risk for males exposed to asbestos (R.R. = 1.99) and to other well known carcinogens (R.R. = 2.28). The capability in differentiating the relative risk of smoking and professional exposure to oncogenetic substances allowed us to detect an excess of risk for people living in industrial and urban areas, when compared to those living in rural and peripheral areas.

Malignant tumors at very old ages.

Unselected autopsy findings of nonagerians reviewed by the authors in the last 20 years, confirm a decline in malignant tumors at very old ages. Two main factors are thought to be responsible for this evidence: a less aggressive biological behavior of cancer in the oldest old; the crucial role played by comorbidity as the cause of death.

[Occupation and lung cancer risk in the province of Trieste: a case-control study]. / Occupazione e rischio di tumore polmonare nella provincia di Trieste: uno studio caso-controllo.

To investigate the relationship between occupation and lung cancer, a case-control study was performed in the province of Trieste, Italy, where metallurgical and mechanical industries, dock activities and shipbuilding and ship repairing are predominant. Through the local Cancer Registry, pathology records of 938 men who died of primary lung cancer (ICD 162) in a five-year period were examined. Residential, smoking and occupational histories were obtained from interviews of next of kin of 756 cases and 756 age-matched male controls (+/- 2 years). Occupational exposures to lung carcinogens were assessed according to a job-title based approach, identifying industries/occupations with well-recognized lung carcinogen exposures (list A) and industries/occupations with suspected lung carcinogen exposures (list B). Exposure to asbestos was classified as absent, possible or definite. After adjustment for cigarette smoking (four levels) and residence (three levels), a significant association was found between lung cancer and occupations in list A (RR = 2.28, 95% CI = 1.70-3.07) and in list B (RR = 1.33, 95% CI = 1.04-1.71). A significant excess risk was found for workers with definite exposure to asbestos when compared to those with no exposure to lung carcinogens (RR = 1.99, 95% CI = 1.43-2.76). A very high relative risk was observed among heavy smokers with definite exposure to asbestos (RR = 42.8). A stratified analysis showed that the combined effect of asbestos and smoking was compatible with that expected under a multiplicative model. The overall attributable risk in the population (ARp) for cigarette smoking was found to be 87.6%. The ARp fraction for occupations with well-established exposures to lung carcinogens (list A) was 16.2%. The ARp fraction increased to 25.5% (85% CI = 1.4-34.6) when occupations with suspected exposure to lung carcinogens (list B) were included. The ARp fraction for possible or definite exposure to asbestos was 20.1% (95% CI = 11.6-28.6).

Air pollution and lung cancer in Trieste, Italy.

To investigate the relation between air pollution and histologic type of lung cancer, the authors conducted a case-control study among men who had died in Trieste, Italy, from 1979 to 1981 and from 1985 to 1986. Through the local autopsy registry, 755 cases of lung cancer and 755 controls were identified. Information on smoking habits, occupation, and place of residence was obtained from each subject's next of kin. Air pollution at the residence of each subject was estimated from the average value of total particulate at the nearest monitoring station. Logistic regression was used to evaluate the effect of residence and air pollution on lung cancer after adjustment for age, smoking habits, likelihood of exposure to occupational carcinogens, and social group. The risk of lung cancer increased with increasing level of air pollution for all types of lung cancer combined (p = 0.022), for small cell carcinoma (p = 0.016), and for large cell carcinoma (p = 0.049). Compared with inhabitants of the residential area, residents of the rural area had a relative risk (RR) of 0.6 (95% confidence interval (CI) 0.4-1.0). The RR was 1.5 (95% CI 1.0-2.2) for residents of the center of the city and 1.4 (95% CI 1.0-2.1) for residents of the industrial area. In the center of the city, the excess risk was almost completely restricted to small cell carcinoma (RR = 2.0) and to large cell carcinoma (RR = 2.6). In the industrial area, the risk was increased especially for adenocarcinoma (RR = 2.1). These results provide evidence that air pollution is a moderate risk factor for certain histologic types of lung cancer.

Cancer risk in first-degree relatives of children with malignant tumours (Province of Trieste, Italy).

We conducted a population-based cohort study in the province of Trieste, Italy, to assess whether the first-degree relatives of children with malignancies had an increased risk of cancer compared with the general population. We examined cancers occurring in all first-degree relatives of children who experienced malignancies under the age of 15 years between 1971 and 1993 (probands). A cohort of the 394 relatives of the 125 probands contributed 7,939 person-years of observation. Among the relatives as a whole, we found a statistically significant increased risk of developing all malignancies except non-melanoma skin carcinoma (21 observed relatives with cancer and 12.46 expected, for a standardized incidence ratio [SIR] of 1.69), of developing breast cancer (SIR = 3.09) and of developing haemolymphatic system neoplasms (SIR = 4.03). This was mainly due to the excess cancer risk in the relatives of probands with intracranial tumours, who showed a significant 3.1-fold risk for developing all cancers but non-melanoma skin tumours. Our findings and the previously reported steep rise in the incidence of childhood brain tumours in our area may imply that not only genetic factors but also shared environmental agents might be involved in the observed aggregation of cancer in the families of probands with intracranial tumours.

Occupational exposure and lung cancer risk in a coastal area of northeastern Italy.

A case-control study of lung cancer and occupational exposure was conducted in a coastal area of Northeastern Italy where metallurgical and mechanical industries, docks and shipyards are located. Cases comprised 756 men who died of primary lung cancer in a 5-year period. Controls comprised 756 male subjects dying from other causes during the same period. Occupational exposures to lung carcinogens were assessed according to a job title-based approach, using two separate lists of industries/occupations recognized as being causally associated (list A) or suspected of being causally associated (list B) with lung cancer in humans. Exposure to asbestos was classified as absent, possible, or definite. After adjustment for cigarette smoking and place of residence, a significant association was found between lung cancer and occupations in both list A [relative risk (RR) = 2.25, 95% confidence interval (CI) = 1.68-3.03] and list B (RR = 1.33, 95% CI = 1.03-1.71). A significant excess risk was found for workers with definite exposure to asbestos as compared to those with no exposure to lung carcinogens (RR = 1.98, 95% CI = 1.42-2.75). Among occupations with recognized exposure to lung carcinogens other than asbestos, a significant excess risk for lung cancer was observed in iron and metalware workers. In occupational groups with definite exposure to asbestos, elevated risk estimates were found for shipyard workers, dockworkers, carpenters, and electricians. The combined effect of smoking and asbestos was found to be compatible with that expected under a multiplicative model. The overall population-attributable risk (ARp) for cigarette smoking was found to be 87.5%.(ABSTRACT TRUNCATED AT 250 WORDS)