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Sorafenib has recently been recognized as an important standard option for the management of patients with differentiated thyroid cancer. Although data concerning cardiac safety are available in pan-tumor studies, no data are available on its use in everyday clinical practice in patients with thyroid cancer. In the off-label program of our institution, we enrolled 14 patients with different histological types of thyroid cancer suitable for treatment with sorafenib. Our aims were to evaluate cardiac safety factors—LVEF (left ventricular ejection fraction), heart rate and blood pressure—the cardiac markers NT-proBNP and troponin I, radiological response evaluated by CT and 18FDG-PET (according to RECIST 1.1 criteria) and biomarker reduction (Eastern Cooperative Oncology Group Performance Status: ECOG PS) 0–2. Patients with ECOG PS 2 accounted for 36 %. After starting sorafenib, many patients displayed reduced or stabilized metabolic activity in target lesions (clinical benefit = 44 %), radiologic reduction or stabilization (74 %) and decreased cancer markers (90 %). Lung metastases displayed the largest reductions in size. Median overall survival (OS) was 7 months and median progression-free survival (PFS) was 3 months. No sign of cardiotoxicity was observed in almost all patients. LVEF was altered in two patients and proved symptomatic in one. Sorafenib seems to be effective in reducing disease progression in the early stages of treatment (3–6 months). Responses varied considerably according to the criteria investigated. Cardiac toxicities did not raise concerns and were in line with data reported in other malignancies. However, cardiac monitoring is recommended.

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral–pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case–control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16–4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27–0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05–0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02–6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02–1.61), bladder cancer (OR = 1.38, 95% CI = 1.06–1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.

We did a retrospective study of 1920 episodes of community-acquired pneumonia (CAP) in 27 community hospitals and analysed inter-hospital variability in length of hospital stay (LOS), mortality and readmission rates. The overall adjusted LOS (mean±S.D.) was 10·0±9·8 days. LOS increased according to the Pneumonia Severity Index (PSI) risk class: 7·3 days for class I to 11·3 days for class V (P<0·001). In a multiple regression model, LOS increased (P<0·001) according to the hospital (inter-hospital variability), PSI risk class, complications during hospitalization, admission to ICU, need of oxygen and transfer to a nursing home. Hospitals with shorter LOS did not show an increased readmission rate (adjusted OR 1·02, 95% CI 0·51–2·03, P=0·97) and post-discharge mortality (adjusted OR 1·20, 95% CI 0·70–2·05, P=0·51). There are significant inter-hospital variations in LOS in patients with CAP which are related to differences in clinical management. The reduction of these differences will further improve efficiency and quality of care.