Abstract Background Although patients with idiopathic VTE are at higher than normal risk of asymptomatic atherosclerosis and of cardiovascular events, the impact of cardiovascular risk factors on VTE ...is poorly understood. Objective To assess the prevalence of the metabolic syndrome and of its components in patients with early-onset idiopathic VTE. Methods As many as 323 patients referred to our Thrombosis Ward for a recent (< 6-months) early-onset idiopathic venous thromboembolism (VTE), were compared with 868 gender- and age-matched subjects, in whom a history of venous thrombosis had been excluded, referred during the same period time to our Ward. All had undergone a clinical assessment for smoking habits and for the presence of the components of the metabolic syndrome. Results The metabolic syndrome was detected in 76/323 cases (23.5%) and in 81/868 controls (9.3%) (p < 0.001; OR:2.990; 95%C.I.:2.119-4.217). Smoking was more common in patients with idiopathic VTE than in controls. In addition to the metabolic syndrome as a whole, its major individual determinants (arterial hypertension, impaired fasting glucose plasma levels, abdominal obesity, hypertriglyceridemia, low HDL-cholesterol) significantly correlated with idiopathic VTE (p always < 0.05). The prevalence of thrombotic events was lower in females than in males (p = 0.000; OR:2.217), the latter being most often hypertensives, smokers, hypertriglyceridemics, carriers of a metabolic syndrome and of impaired fasting glucose than females. In a multivariate analysis, arterial hypertension, impaired fasting glucose, abdominal obesity, and hypercholesterolemia independently predicted idiopathic venous events. Conclusions Both metabolic syndrome as a whole and its major components individually considered, independently predict early-onset idiopathic VTE.
Premenopausal women undergoing chemotherapy are at high risk for premature ovarian failure and its long-term consequences. Data on potential markers to evaluate ovarian reserve pre- and posttreatment ...are limited. Anti-Müllerian hormone (AMH) known for ovarian reserve in reproductive medicine could be a surrogate marker and was assessed in premenopausal breast cancer patients of the SUCCESS A study (EUDRA-CT no. 2005-000490-21).
We identified 170 premenopausal patients, age ≤ 40 years at trial entry, who received FEC-Doc as taxane-anthracylince based chemotherapy. Blood samples were taken at three time points: Before, four weeks after and two years after adjuvant chemotherapy. Serum AMH-levels were evaluated in a central laboratory by a quantitative immunoassay AMH Gen II ELISA (Beckman Coulter, Brea, USA).
Median age was 36 years (21–40 years). Median serum AMH-level before chemotherapy was 1.37 ng/ml (range < 0.1–11.3 ng/ml). Four weeks after chemotherapy AMH-levels dropped in 98.6% of the patients to <0.1 ng/ml (range < 0.1–0.21 ng/ml).
After two years, 73.3% (n = 101) showed no evidence of ovarian function recovery (AMH <0.1 ng/ml, range < 0.1–3.9 ng/ml). Permanent chemotherapy induced amenorrhea occurred only in 50.6% of the patients.
In this analysis, premenopausal patients showed a high rate of ovarian impairment reflected by low AMH-levels after chemotherapy.
•Data on markers to evaluate ovarian reserve in the context of chemotherapy are limited.•We examined AMH-levels in 170 patients ≤40 years who received FEC-Doc chemotherapy.•Low AMH-levels two years after chemotherapy were observed in 73.3% of the patients.•Age was the most important factor on gonadal function after cytotoxic treatment.
Objective. The aim of the study was to evaluate the pattern of the lymphoid organization in the synovial tissue of patients affected with juvenile idiopathic arthritis (JIA).
Methods. A total of 40 ...JIA patients who underwent synoviectomy or synovial biopsies were enrolled. The mean age at surgery was 15.1 yrs (range 6-30 yrs) and the mean disease duration was 6.7 yrs (range 3 months to 22.2 yrs). Tissue specimens were grouped according to the following criteria: (i) diffuse perivascular infiltrate without lymphoid organization, (ii) T cell-B cell aggregates with or without germinal centre reaction.
Results. Synovial tissues from 12 JIA patients did not show any sign of lymphoid organization, whereas 28 patients displayed a variable number of T-B cell aggregates. Typical features consistent with a germinal centre reaction were present in two JIA patients only. Lymphoid organization in JIA patients did not correlate with the duration and severity of the disease or with the degree of synovial inflammation, but did positively correlate with the presence of anti-nuclear antibodies. Moreover, a diffuse lymphocyte infiltration was significantly related to the presence of an acute phase of inflammation and the presence of lymphoid aggregates correlated with the degree of plasma cells infiltration.
Conclusions. Lymphoid neogenesis in JIA represents a phase in the immunopathological process that characterize the development of inflammatory synovitis. It is not related to disease activity or severity, but appears to be more frequent in patients with circulating anti-nuclear antibodies.
Estimates of the burden of severe acute respiratory syndrome coronavirus 2 reinfections are limited by the scarcity of population-level studies incorporating genomic support. We conducted a ...systematic study of reinfections in Madrid, Spain, supported by genomic viral analysis and host genetic analysis, to cleanse laboratory errors and to discriminate between reinfections and recurrences involving the same strain. Among the 41,195 cases diagnosed (March 2020-March 2021), 93 (0.23%) had 2 positive reverse transcription PCR tests (55-346 days apart). After eliminating cases with specimens not stored, of suboptimal sequence quality, or belonging to different persons, we obtained valid data from 22 cases. Of those, 4 (0.01%) cases were recurrences involving the same strain; case-patients were 39-93 years of age, and 3 were immunosuppressed. Eighteen (0.04%) cases were reinfections; patients were 19-84 years of age, and most had no relevant clinical history. The second episode was more severe in 8 cases.
Partial breast irradiation for the treatment of early-stage breast cancer patients can be performed by means of Intra Operative electron Radiation Therapy (IOeRT). One of the main limitations of this ...technique is the absence of a treatment planning system (TPS) that could greatly help in ensuring a proper coverage of the target volume during irradiation. An IOeRT TPS has been developed using a fast Monte Carlo (MC) and an ultrasound imaging system to provide the best irradiation strategy (electron beam energy, applicator position and bevel angle) and to facilitate the optimisation of dose prescription and delivery to the target volume while maximising the organs at risk sparing. The study has been performed in silico, exploiting MC simulations of a breast cancer treatment. Ultrasound-based input has been used to compute the absorbed dose maps in different irradiation strategies and a quantitative comparison between the different options was carried out using Dose Volume Histograms.
The system was capable of exploring different beam energies and applicator positions in few minutes, identifying the best strategy with an overall computation time that was found to be completely compatible with clinical implementation. The systematic uncertainty related to tissue deformation during treatment delivery with respect to imaging acquisition was taken into account.
The potential and feasibility of a GPU based full MC TPS implementation of IOeRT breast cancer treatments has been demonstrated in-silico. This long awaited tool will greatly improve the treatment safety and efficacy, overcoming the limits identified within the clinical trials carried out so far.
•A fast GPU based MC has been developed for IOeRT breast treatment planning.•The input is an ultrasound image with defined PTV and OARs.•Different applicator positions, dimensions and angles and beam energies are tested.•Plan is optimised using absorbed dose maps and related DVHs.•Results in the context of conventional and FLASH irradiations are discussed.
Empirical L 2 -distance test statistics for ergodic diffusions De Gregorio, A; Iacus, S M
Statistical inference for stochastic processes : an international journal devoted to time series analysis and the statistics of continuous time processes and dynamic systems,
07/2019, Volume:
22, Issue:
2
Journal Article
Open access
The aim of this paper is to introduce a new type of test statistic for simple null hypothesis on one-dimensional ergodic diffusion processes sampled at discrete times. We deal with a quasi-likelihood ...approach for stochastic differential equations (i.e. local gaussian approximation of the transition functions) and define a test statistic by means of the empirical L2-distance between quasi-likelihoods. We prove that the introduced test statistic is asymptotically distribution free; namely it weakly converges to a χ2 random variable. Furthermore, we study the power under local alternatives of the parametric test. We show by the Monte Carlo analysis that, in the small sample case, the introduced test seems to perform better than other tests proposed in literature.
Systemic thrombolysis for acute pulmonary embolism (PE) carries up to a 20% risk of major bleeding, including a 2% to 5% risk of hemorrhagic stroke. We evaluated the safety and effectiveness of ...catheter-directed therapy (CDT) as an alternative treatment of acute PE.
One hundred one consecutive patients receiving CDT for acute PE were prospectively enrolled in a multicenter registry. Massive PE (n = 28) and submassive PE (n = 73) were treated with immediate catheter-directed mechanical or pharmacomechanical thrombectomy and/or catheter-directed thrombolysis through low-dose hourly drug infusion with tissue plasminogen activator (tPA) or urokinase. Clinical success was defined as meeting all the following criteria: stabilization of hemodynamics; improvement in pulmonary hypertension, right-sided heart strain, or both; and survival to hospital discharge. Primary safety outcomes were major procedure-related complications and major bleeding events.
Fifty-three men and 48 women (average age, 60 years range, 22-86 years; mean BMI, 31.03 ± 7.20 kg/m2) were included in the study. The average thrombolytic doses were 28.0 ± 11 mg tPA (n = 76) and 2,697,101 ± 936,287 International Units for urokinase (n = 23). Clinical success was achieved in 24 of 28 patients with massive PE (85.7%; 95% CI, 67.3%-96.0%) and 71 of 73 patients with submassive PE (97.3%; 95% CI, 90.5%-99.7%). The mean pulmonary artery pressure improved from 51.17 ± 14.06 to 37.23 ± 15.81 mm Hg (n = 92) (P < .0001). Among patients monitored with follow-up echocardiography, 57 of 64 (89.1%; 95% CI, 78.8%-95.5%; P < .0001) showed improvement in right-sided heart strain. There were no major procedure-related complications, major hemorrhages, or hemorrhagic strokes.
CDT improves clinical outcomes in patients with acute PE while minimizing the risk of major bleeding. At experienced centers, CDT is a safe and effective treatment of both acute massive and submassive PE.
ClinicalTrials.gov; No.: NCT01097928; URL: www.clinicaltrials.gov.
We consider parametric hypotheses testing for multidimensional ergodic diffusion processes observed at discrete time. We propose a family of test statistics related to the so called ϕ-divergence ...measures. It is proved that the test statistics in this family are all asymptotically distribution free and converge to the chi squared distribution. In the case of contiguous alternatives, it is also possible to study in detail the power function of the tests.
Although all the tests in this family are asymptotically equivalent, the second order expansion of the test statistics suggest a different behavior for the power function of the test in finite samples. We show by the Monte Carlo analysis that, in the small sample case, the performance of the test depends on the choice of the function ϕ and on the statistical model. The simulations show further that there is no uniformly most powerful test in this class.
In order to translate the FLASH effect in clinical use and to treat deep tumors, Very High Electron Energy irradiations could represent a valid technique. Here, we address the main issues in the ...design of a VHEE FLASH machine. We present preliminary results for a compact C-band system aiming to reach a high accelerating gradient and high current necessary to deliver a Ultra High Dose Rate with a beam pulse duration of 3μs.
The proposed system is composed by low energy high current injector linac followed by a high acceleration gradient structure able to reach 60–160 MeV energy range. To obtain the maximum energy, an energy pulse compressor options is considered. CST code was used to define the specifications RF parameters of the linac. To optimize the accelerated current and therefore the delivered dose, beam dynamics simulations was performed using TSTEP and ASTRA codes.
The VHEE parameters Linac suitable to satisfy FLASH criteria were simulated. Preliminary results allow to obtain a maximum energy of 160 MeV, with a peak current of 200 mA, which corresponds to a charge of 600 nC.
A promising preliminary design of VHEE linac for FLASH RT has been performed. Supplementary studies are on going to complete the characterization of the machine and to manufacture and test the RF prototypes.
•Novel modality for radiotherapy reduces healthy tissue toxicities; the FLASH effect.•FLASH irradiation is obtained with ultra-high dose-rate short bursts.•Linear accelerator-based machine is designed for FLASH experiments.•Small footprint laboratory for very-high energy electron for pre-clinical studies.
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