Effects of anticoagulation therapy with vitamin K antagonists on hospitalizations and emergency room accesses in Grosseto (Italy).

INTRODUCTION: A lot of drug groups are associated with preventable drug-related admissions. Coumarin derivatives, prescribed for the treatment and prevention of deep vein thrombosis or pulmonary embolism or prevention of systemic embolism or stroke in patients with prosthetic heart valves or atrial fibrillation, are often associated with bleeding. The aim of our study was to analyze how the anticoagulant therapy with VKAs could affects the hospitalizations and the visits to emergency room in the elderly population (> 65 years old). METHODS: In 2013 we conducted a cross sectional study analyzing the database of all pharmaceutical prescriptions, selecting patients living in Grosseto (Italy), which received at least two prescriptions of coumarin derivatives in 2012. We analyzed the admissions to hospital and the accesses to the emergency rooms (ERs) made by each patient, focusing especially on those related to bleeding. For each access to ER we recorded the date, time of stay, diagnosis and outcome. For each hospitalization the information we recorded were the date of admission and discharge diagnosis. RESULTS: 3684 patients were included in our study. 261 (7.1%) patients visited the emergency room for bleeding; 37 (1%) for intracranial bleeding. The accesses made by men were higher than those made by women. The average time of stay in ER was 349 minutes. The admissions to hospital were 96 (2.6%); 42 (1.1%) were admitted to hospital with a diagnosis of major vascular event. 53 patients (20.3%), accessed to the ER more than one time. The 11.5% was admitted to the hospital more than one time. CONCLUSIONS: Our study showed that VKAs are responsible of an increase of the accesses to ER and of the admissions to hospital. However, it would be interesting to enlarge the sample size including patients living in other provinces or in other regions, with a lower age and treated also with TSOACs, in order to evaluate the real cost-effectiveness of anticoagulant therapy.

Lung metastasis from TTF-1 positive sigmoid adenocarcinoma. pitfalls and management.

The lung is a frequent site of metastatic involvement, and in many cases the differential diagnosis between a metastasis and a primary carcinoma is a substantial question. TTF-1 is considered as a reliable marker for differential diagnosis in distinguishing primary lung carcinoma and metastasis, especially when dealing with an adenocarcinoma or a large-cell carcinoma. It was generally thought that adenocarcinomas arising in the gastrointestinal tract do not express TTF-1. Recently, it has been reported that a small percentage (1.8%-5.8%) of intestinal adenocarcinoma TTF-1 positive show differences in sensitivity/specificity depending on the antibody clones. We report a case of lung localization of a TTF-1 positive adenocarcinoma in a patient with a history of colon adenocarcinoma. Based on the current results and previous reports, we propose the following criteria for diagnosing lung metastasis from TTF-1 positive intestinal adenocarcinoma. 1) Clinical features and anamnestic history are diagnostic milestones, and provide very important information as a prognostic parameter of primary carcinoma and the time interval between the two localizations (primary and metastasis). 2) The histologic features are compatible with an enteric differentiation. 3) TTF-1 must be tested in the primary carcinoma. 4) In lung lesions, in association with TTF-1, it could be useful to test other immunohistochemical markers such as CDX-2 and NapsinA. 5) Testing other immunohistochemical or molecular markers in either lesion is not very useful. Heterogeneity between primary and metastatic lesions has been reported in the literature. Application of the above-mentioned criteria would simplify diagnosis of lung metastases from TTF-1 positive intestinal adenocarcinoma.

Zoledronic acid enhances Vδ2 T-lymphocyte antitumor response to human glioma cell lines.

Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain tumor in humans, responds modestly to treatment: most patients survive less than one year after diagnosis, despite both classical and innovative treatment approaches. A recent paper focused on γδ T-cell response in GBM patients, suggesting the application of an immunomodulating strategy based on γδ T-cells which is already in clinical trials for other tumors. Human Vγ2 T-cells recognize changes in the mevalonate metabolic pathway of transformed cells by activating cytotoxic response, and by cytokine and chemokine release. Interestingly, this activation may also be induced in vivo by drugs, such as zoledronic acid, that induce the accumulation of Vγ2 T-cell ligand Isopentenyl-pyrophosphate by blocking the farnesyl pyrophosphate synthase enzyme. The aim of our work is to confirm whether bisphosphonate treatment would make glioma cell lines more susceptible to lysis by in vitro expanded γδ T-cells, improving their antitumor activity. We expanded in vitro human Vγ2 T-cells by phosphoantigen stimulation and tested their activity against glioma cell lines. Co-culture with glioma cells induced Vγ2 T-cell differentiation in effector/memory cells, killing glioma cells by the release of perforin. Interestingly, glioma cells were directly affected by zoledronic acid; moreover, treatment increased their activating ability on Vγ2 T-cells, inducing an effective antitumor cytotoxic response. Taken together, our results show that aminobisphosphonate drugs may play a dual role against GBM, by directly affecting tumor cells, and by enhancing the antitumor response of Vγ2 T-cells. Our results confirm the practicability of this approach as a new immunotherapeutic strategy for GBM treatment.

Notes on the history of the radiological study of Egyptian mummies: from X-rays to new imaging techniques.

A few centuries after the practice of mummification was finally abolished in the seventh century A.D., mummies began to capture the collective imagination, exerting a mysterious fascination that continues to this day. From the beginning, the radiological study of Egyptian mummies permitted the collection not only of medical data but also of anthropological and archaeological evidence. The first radiological study of an Egyptian mummy was performed by Flinders Petrie shortly after the discovery of X-rays in 1895, and since then, radiology has never stopped investigating these special patients. By the end of the 1970s, computed tomography (CT) scanning permitted more in-depth studies to be carried out without requiring the mummies to be removed from their cartonnage. CT images can be used to obtain a three-dimensional reconstruction of the mummy that provides important new information, in part thanks to the virtual endoscopy technique known as "fly through". Moreover, starting from CT data and using sophisticated graphics software, one can reconstruct an image of the face of the mummified individual at the time of his or her death. The history of imaging, from its origins until now, from the simplest to the most sophisticated technique, allows us to appreciate why these studies have been, and still are, fundamental in the study of Egyptian mummies.

[Bioavailability of a delayed-action aminophylline preparation]. / Biodisponibilità di un preparato ritardo di aminofillina.

Absorption of theophylline from one commercial product labelled as aminophylline sustained release was compared to the absorption from an oral solution of aminophylline in a single-dose bioavailability study. Aminomal-R tablets had bioavailability (101.2 +/- 19) statistically indistinguishable from that of the standard but showed significantly slower absorption (peak times of 3.6 +/- 1.1 h vs 1.3 +/- 0.8 h) and lower peak plasma concentrations (16.8 +/- 4.7 mg/l/1 g aminoph. dose vs 21.1 +/- 4.2 mg/l/1 g aminoph. dose). Projections of plasma concentrations upon multiple dosing were made from single dose data: the dosage interval (every 12 h) concentration ratio which reflects both the frequency of dosing and the entry of the drug into and removal from the body was of 1.8 vs 3.1.