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IMPORTANCE: The PCSK9 inhibitor evolocumab reduced major vascular events in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, yet the types and sizes of myocardial outcomes in FOURIER have not been previously explored. OBJECTIVE: To assess the types and sizes of myocardial infarction (MI) and the effect of evolocumab on MI by subtype. DESIGN, SETTING, AND PARTICIPANTS: A prespecified analysis of a multicenter double-blind randomized clinical trial. Patients were randomized to evolocumab or placebo and followed up for a median of 2.2 years. The study included 27 564 patients with stable atherosclerotic disease receiving statin therapy. Clinical end points were evaluated by the Thrombolysis in Myocardial Infarction clinical events committee. Rates presented are 3-year Kaplan-Meier estimates. Data were collected from 2013 to 2016 and analyzed from June 2017 to December 2019. MAIN OUTCOMES AND MEASURES: Myocardial infarction was defined based on the third universal MI definition, and further classified according to MI type (universal MI subclass, ST-segment elevation myocardial infarction [STEMI] vs non–STEMI) and by MI size (determined by peak troponin level). RESULTS: A total of 27 564 patients were randomized, with a mean (SD) age of 62.5 (9.0) years, and 20 795 (75%) were male. Of these, 1107 patients experienced a total of 1288 MIs. Most MIs (68%) were atherothrombotic (type 1), with 15% from myocardial oxygen supply-demand mismatch (type 2) and 15% percutaneous coronary intervention–related (type 4). Sudden death (type 3) and coronary artery bypass grafting–related (type 5) accounted for a total of 21 MIs (

Many new photovoltaic (PV) applications, such as the concentrating PV (CPV) systems, are appearing on the market. The main characteristic of CPV systems is to concentrate sunlight on a receiver by means of optical devices and to decrease the solar cells area required. A low CPV (LCPV) system allows optimizing the PV effect with high increase of generated electric power as well as decrease of active surface area. In this paper, an economic analysis and a life cycle assessment (LCA) study of a particular LCPV scheme is presented and its environmental impacts are compared with those of a PV traditional system. The LCA study was performed with the software tool SimaPro 8.0.2, using the Econinvent 3.1 database. A functional unit of 1 kWh of electricity produced was chosen. Carbon Footprint, Ecological Footprint and ReCiPe 2008 were the methods used to assess the environmental impacts of the LCPV plant compared with a corresponding traditional system. All the methods demonstrated the environmental convenience of the LCPV system. The innovative system allowed saving 16.9% of CO2 equivalent in comparison with the traditional PV plant. The environmental impacts saving was 17% in terms of Ecological Footprint, and, finally, 15.8% with the ReCiPe method.

Objective: The aim of this study is to report on the role of neuroendoscopy during the management of hydrocephalus that led to the diagnosis of intracranial tumoral dissemination and the subsequent finding of a spinal cord glioma. Methods and Results: We present two children each with an intramedullary astrocytoma that presented initially with hydrocephalus without spinal cord symptoms. In both cases leptomeningeal gliomatous dissemination was asserted during routine endoscopy for the management of hydrocephalus. The diagnosis of a cervical and a lower thoracic intramedullary tumor was made soon after on magnetic resonance imaging. Conclusions: Spinal cord MRI with contrast should be considered initially in selected cases of hydrocephalus without evident diagnosis. The intraoperative diagnosis of gliomatous dissemination and secondary hydrocephalus due to unrecognized spinal cord gliomas was possible, in our experience, with the routine use of the neuroendoscope.

This review outlines the present state of applications of seismic isolation to civil buildings in Europe (with particular reference to Italy), including the countries formerly belonging to the USSR. Some information is also given on the use of other passive innovative antiseismic devices, like energy dissipators and shock transmitters, as well as on applications to bridges, viaducts and industrial plants. The adopted innovative antiseismic systems are described. Research projects, mainly in the framework of Programmes funded by the European Commission, which have been completed recently or are in progress, are briefly outlined. The available or proposed design rules and guidelines and statistics of applications (based on the outcome of recent international seminars) are included. Some examples of applications are briefly illustrated. Finally, the perspectives for future applications are discussed, highlighting the issues which have so far restrained a wider use of innovative antiseismic techniques in Europe.

The meaning of ataxia is failure of coordination. Ataxic patients are not able to define the width, velocity, and rhythms of muscle contractions and cannot coordinate more muscle groups which are synchronously activated. The ataxia can be determined by (1) injury of the proprioceptive afferences, (2) labyrinthic injury, and (3) injury of cerebellum or its connections which are reciprocally connected to the cerebral cortex (neocerebellum), the spinal cord (paleocerebellum), and the vestibular system (archeocerebellum).

The high prevalence of bone metastases in breast cancer and the risk that spinal and femoral osteoporosis may add further morbidity provide a rationale for bisphosphonate therapy in patients with skeletal metastases from mammary carcinoma. We investigated the effects of oral clodronate given during 9 months, with a 24-month follow-up, on bone mineral density (BMD), on biochemical markers of bone remodeling, and on osseous complications in 67 women with documented relapsing breast cancer, aged 58.7 +/- 1.5 years (x +/- SEM). Patients with active cancer disease were randomly allocated to two groups, with or without clodronate treatment (1600 mg/day, orally). Twenty-six women considered in complete remission (52.4 +/- 2.4 years) were also studied. Expressed in deviation from gender- and age-matched normals (z score), base-line BMD at the levels of lumbar spine (LS), femoral neck (FN), and midfemoral shaft (FS) was +0.10 +/- 0.22 vs. -0.12 +/- 0.25, +0.03 +/- 0.19 vs. -0.54 +/- 0.24, and +0.08 +/- 0.14 vs. -0.02 +/- 0.22, in patients with active breast cancer and in subjects in remission, respectively. After 9 months of treatment, fasting urinary calcium to creatinine ratio was lower (0.26 +/- 0.04 vs. 0.40 +/- 0.04 mmol/mmol creatinine, p < 0.02) and serum osteocalcin was stabilized (-2.1 +/- 1.1 vs. +7.0 +/- 3.3 micrograms/L, as compared with pretreatment values, p < 0.02), in the clodronate-treated group. The rate of osseous complications (pathological fracture, hypercalcemic episode, scintigraphic or radiological evidence of metastasis development, chemo- or radiotherapy for bone disease progression) was 28.8 events per 100 patient-year in the clodronate-treated group vs. 39.0 in controls, and 31.5 vs. 40.5, after 9 and 15 months of follow-up, respectively. In 15 women without evident LS bone metastasis (7 clodronate-treated and 8 controls), LS BMD increased in the clodronate-treated group by +5.2 +/- 2.5% vs. -0.3 +/- 1.4%, and +8.1 +/- 4.7 vs. -0.9 +/- 1.7, after 10.3 +/- 0.4 and 17.3 +/- 1.2 months, respectively (p < 0.01), as compared with pretreatment values. These results indicate that clodronate treatment decreased bone turnover and attenuated cancer-related bone morbidity. In addition, clodronate increased LS BMD in apparently unaffected bone of women with relapsing breast cancer.

Cavernous angiomas are common lesions of the CNS characterized by abnormally dilated blood vessels lined by a thin endothelium, closely clustered together and not separated by normal neural tissue. They are more frequently found intracranially. In the spine, a common location is the vertebral bodies. Intradural extramedullary and intramedullary cavernous angiomas are less frequent lesions, while purely epidural locations are uncommon. Spinal dumbbell-shaped epidural cavernous angiomas are exceedingly rare, and only six cases have been reported in the literature. We describe one additional case whose MRI appearance was indistinguishable from that of a neurinoma, which is a much more common lesion. Surgical treatment is advised and complete radiological evaluation is necessary to rule out concomitant localizations in other organs.

20 consecutive patients with nausea and vomiting secondary to cisplatin chemotherapy uncontrolled by serotonin-antagonist and corticosteroid prophylaxis during their first cycle received adjuvant prop

Using data from the Geneva Cancer Registry, we found that in 2002–2004, breast cancer incidence in women aged 25–39 years increased by 46.7% per year (95% CI: 7.1–74.0, P=0.015), which surveillance or detection bias may not fully explain.

Summary Mucositis is still a leading side effect of high dose chemotherapy and irradiation delivered in autologous and allogeneic bone marrow transplantation. In this double blind randomised study, we tested the efficacy of sucralfate for the prevention of mucositis induced by such conditioning treatments. Treatment was started one day before conditioning regimen and patients were prospectively evaluated. The main endpoint was severe mucositis that was more frequent in the placebo group than in the sucralfate group (47% vs. 29%, P = 0.07). This trend was confirmed after adjustment on total body irradiation (TBI) (P = 0.06), the sole stratification parameter. Interestingly, patients receiving sucralfate showed a significant reduction of diarrhoea (25% vs. 53%, P = 0.005). Overall, the preventive administration of sucralfate appears to be an effective procedure to diminish the occurrence of severe oral and intestinal mucositis in patients treated by high dose chemotherapy alone or combined with TBI before bone marrow transplantation.

Background: In vitro data demonstrated a dose-response relationship for doxorubicin in ovarian cancer (OC) cell lines. However, this dose-response question for doxorubicin was never carefully addressed in OC patients. These data and the more favorable toxicity profile of the anthracycline analogue epirubicin prompted us to study high-dose epirubicin (HDE) in relapsed OC patients. Patients and Methods: This phase I study included 19 OC patients with measurable or evaluable disease and no more than one prior (cisplatin-containing) chemotherapy regimen. Dose escalation was not allowed in individual patients. Epirubicin was administered by rapid intravenous infusion (2 (at least 3 patients per dose level). None of the patients received hematopoietic growth factors. We defined the maximum tolerated dose (MTD) as the dose at which we observed WHO grade 4 hematologic toxicity in ≥50% and/or WHO grade 3 nonhematologic toxicity in ≥30% of the patients. Results: The MTD was 200 mg/m2, with DLT being both hematologic (leukopenia and/or thrombocytopenia) and nonhematologic (mucositis). Objective responses were observed in 6 patients (response rate 32%), 3 of them occurring in 10 patients with primary platinum resistance. Conclusions: HDE is tolerable and has activity in second-line after cisplatin-based chemotherapy in OC patients. The recommended dose for phase II trials in such patients is 150 mg/m2, with escalation to 180 mg/m2 if toxicity permits.

Summary Background The primary aim was to induce a high number of pCR in early (FIGO IC, IIB + C) – and advanced (FIGO ffl – IV) – stage ovarian cancer with a surgery plus 4 cycles of cisplatin and meiphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. Patients and methods 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm iv. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accele rator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinical CR or pathological PR with microscopical residual disease. Results 146/218 patients (67%, 95% CI: 61%–73%) responded to PAMIP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c = clinical, p = pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TIF) and survival. Only 5 1/118 (43%) patients in remission received WAR Early-stage patients < = 55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p = 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p = 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (33%) or incompleteness (33%) of irradiation in the majority of patients. Conclusions PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are needed.

Nausea and vomiting remain one of the most distressing and unpleasant side-effects of cancer chemotherapy [1, 2]. These symptoms cause significant delayed psychological morbidity such as anticipatory nausea/vomiting or depression [3] and are the most frequently cited reasons patients give for not wanting to continue chemotherapy or even start treatment. Recently, selective serotonin antagonists (5HT3-antagonists) have shown considerable antiemetic potency during highly emetogenic therapies with fewer side-effects [4, 5]. Despite these improvements, 20–30 % of patients undergoing Cisplatin chemotherapy still remain unresponsive to the most efficient antiemetic regimens available i.e. 5HT3-antagonists plus Dexamethasone [6].

Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.

The sensitivity and specificity of single photon emission tomography with 57Co-labelled bleomycin (57Co-BLM) for the detection of cancer was determined from a prospective study involving a large group of patients selected to investigate roentgenographic abnormalities. Eighty-four of the 104 patients studied had malignant disease, of whom 76 had a positive scintigram. Eighteen of the 20 patients with benign disorders had a negative scintigram. The sensitivity and specificity was therefore 90.5 and 90% respectively. For the subset of patients who underwent investigation below the diaphragm, the sensitivity was 85.7%, while for investigation above the diaphragm, it reached 95.2% (this excluded reconstructions on the bladder level, because it produced large artifacts). This study leads to the conclusion that SPECT can be used specifically to investigate unidentified X-ray abnormality and diagnose malignancy using 57Co-BLM. In addition, we propose further investigation to evaluate the usefulness of this method in staging cancer.

Research on tumour localization of radiolabelled antibodies was initiated almost 30 years ago by Pressman [1] and Bale [2], who showed that labelled antibodies against Wagner osteosarcoma or Walker carcinoma cells were concentrated in vivo by these tumours.

Plasma levels of CA 125 were determined in 113 patients with ovarian cancer of epithelial origin. Of these, 69 patients had CA 125 measured before the first laparotomy and 84.6% of them had a CA 125 level greater than 35 U/ml. In 87 of the 113 patients whose tumour was producing CA 125, a good correlation was observed between the CA 125 levels and the clinical follow-up: 95.7% of the patients in remission had levels less than 35 U/ml, whereas all the patients with no change or with a progressive disease had levels greater than 35 U/ml. Furthermore in recurrent disease the levels of CA 125 were also increased (greater than 35 U/ml) in 92.3% of the patients. Thus, CA 125 measurements at regular intervals are of great clinical value in following the evolution of a tumour or the success of a therapy, but unfortunately do not allow detection of an ovarian tumour at an early stage.

Procalcitonin (PCT), recognised as a marker of sepsis, was investigated in a porcine model of endotoxic shock. The results showed that continuous IV infusion (1–4 h) of LPS (40 μg/kg) in pigs was able to induce a generalised increase of PCT expression in lung, heart, kidney and liver. The increase in PCT was significant only in kidney and was accompanied by an increase in IL-6 gene expression. In vitro results demonstrated that peripheral blood mononuclear cells (PBMCs), as well as endothelial cells, were potentially capable of contributing to in vivo extrathyroidal PCT production. These findings support previous data from pigs concerning the occurrence of widespread activation of PCT extrathyroidal gene expression during endotoxic shock in pigs. Nevertheless, the levels of PCT detected were very low, suggesting the need for additional studies to validate the pig as a reliable animal model for investigating the role of PCT in sepsis.

Objective Most strategies against intimal hyperplasia developed in several preclinical models failed in terms of clinical application, often due to a discrepancy between animal and human disease. The aim of this study was to setup for the first time a porcine vascular injury model with mild hypercholesterolemia able to significantly increase the degree of stenosis resembling human settings and investigate the pathogenetic role of hypercholesterolemia on protective genes and inflammatory response affecting matrix deposition and cell proliferation. Methods Pigs were fed with standard (SD, n = 7) or high-cholesterol diet (HCD, n = 7) for 120 days. A balloon angioplasty injury was induced in carotid arteries. Results Hypercholesterolemia induced a mild significant increase of total and LDL cholesterolemia. HCD significantly increased the degree of stenosis (48 ± 3% vs. 13 ± 4%, p = 0.001), with induction of cell proliferation, matrix deposition, TGF-β1/TGFβRII and MMP2 expression and reduction of collagen. The reduced expression of the protective gene heme oxygenase-1 and inducible-nitric oxide synthase in HCD was associated to a systemic inflammation with a significant increase in circulating leukocytes, serum IFN-γ and TNF-α and a local inflammatory response with an increase of CD3-positive cell infiltrates. There was a significant correlation between CD3 infiltrates and the degree of stenosis. Conclusion We developed for the first time a porcine vascular injury model with mild hypercholesterolemia able to significantly increase the degree of stenosis and showed the pathogenetic role of hypercholesterolemia on intimal hyperplasia. New therapeutical strategies to prevent restenosis can be tested in this preclinical hypercholesterolemic model resembling human disease.