The development of non-infectious subunit vaccines greatly increases the safety of prophylactic immunization, but also reinforces the need for a new generation of immunostimulatory adjuvants. Because ...adverse effects are a paramount concern in prophylactic immunization, few new adjuvants have received approval for use anywhere in the developed world. The vaccine adjuvant monophosphoryl lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like receptor agonists likely to be used as vaccine adjuvants on a mass scale in human populations. Much remains to be learned about this compound's mechanism of action, but recent developments have made clear that it is unlikely to be simply a weak version of lipopolysaccharide. Instead, monophosphoryl lipid A's structure seems to have fortuitously retained several functions needed for stimulation of adaptive immune responses, while shedding those associated with pro-inflammatory side effects.
Background
A single flexible sigmoidoscopy at around the age of 60 years has been proposed as an effective strategy for colorectal cancer (CRC) screening.
Methods
We conducted a randomized controlled ...trial to evaluate the effect of flexible sigmoidoscopy screening on CRC incidence and mortality. A questionnaire to assess the eligibility and interest in screening was mailed to 236 568 men and women, aged 55-64 years, who were randomly selected from six trial centers in Italy. Of the 56 532 respondents, interested and eligible subjects were randomly assigned to the intervention group (invitation for flexible sigmoidoscopy; n = 17 148) or the control group (no further contact; n = 17 144), between June 14, 1995, and May 10, 1999. Flexible sigmoidoscopy was performed on 9911 subjects. Intention-to-treat and per-protocol analyses were performed to compare the CRC incidence and mortality rates in the intervention and control groups. Per-protocol analysis was adjusted for noncompliance.
Results
A total of 34 272 subjects (17 136 in each group) were included in the follow-up analysis. The median follow-up period was 10.5 years for incidence and 11.4 years for mortality; 251 subjects were diagnosed with CRC in the intervention group and 306 in the control group. Overall incidence rates in the intervention and control groups were 144.11 and 176.43, respectively, per 100 000 person-years. CRC-related death was noted in 65 subjects in the intervention group and 83 subjects in the control group. Mortality rates in the intervention and control groups were 34.66 and 44.45, respectively, per 100 000 person-years. In the intention-to-treat analysis, the rate of CRC incidence was statistically significantly reduced in the intervention group by 18% (rate ratio RR = 0.82, 95% confidence interval CI = 0.69 to 0.96), and the mortality rate was non-statistically significantly reduced by 22% (RR = 0.78; 95% CI = 0.56 to 1.08) compared with the control group. In the per-protocol analysis, both CRC incidence and mortality rates were statistically significantly reduced among the screened subjects; CRC incidence was reduced by 31% (RR = 0.69; 95% CI = 0.56 to 0.86) and mortality was reduced by 38% (RR = 0.62; 95% CI = 0.40 to 0.96) compared with the control group.
Conclusion
A single flexible sigmoidoscopy screening between ages 55 and 64 years was associated with a substantial reduction of CRC incidence and mortality.
The axial arrangement of long scintillation crystals is a promising concept in PET instrumentation to address the need for optimized resolution and sensitivity. Individual crystal readout and arrays ...of wavelength shifter strips placed orthogonally to the crystals lead to a 3D-detection of the annihilations photons. A fully operational demonstrator scanner, developed by the AX-PET collaboration, proved the potential of this concept in terms of energy and spatial resolution as well as sensitivity. This paper describes a feasibility study, performed on axial prototype detector modules with 100mm long LYSO crystals, read out by the novel digital Silicon Photomultipliers (dSiPM) from Philips. With their highly integrated readout electronics and excellent intrinsic time resolution, dSiPMs allow for compact, axial detector modules which may extend the potential of the axial PET concept by time of flight capabilities (TOF-PET). A coincidence time resolution of 211ps (FWHM) was achieved in the coincidence of two axial modules read out by dSiPMs, fully maintaining the demonstrated performance of the AX-PET detector.
Background: This study estimates prevalence, management, and relief of pain during the last 3 months of life of a representative sample of dying cancer patients in Italy. Patients and methods: This ...is a mortality followback survey (the Italian Survey of the Dying of Cancer). Caregivers were interviewed, after the patient's death, about pain experienced by the patients in all settings of care. Results: According to caregivers' reports, 82.3% 95% confidence interval (CI) 79.9% to 84.4% patients experienced pain, and 61.0% (95% CI 57.9% to 64.0%) very distressing pain. The younger population experienced a higher prevalence of pain in respect to older patients (P < 0.01). Patients with tumors of the central nervous system experienced the lowest prevalence (51.9%). According to caregivers' reports, only 59.5% (95% CI 3.7% to 65.0%) received analgesic treatment with opioids for moderate to severe pain. Not surprisingly, pain was ‘only partially relieved’ or ‘not relieved at all’ in 54% of the patients with very distressing pain. Conclusions: Although potentially slightly biased, the results from this survey regarding undermedication and poor treatment results for cancer related pain are unequivocal. The research agenda should focus on testing the effectiveness of interventions to improve the quality of pain assessment and management.
Purpose
Radiofrequency (RF) treatment has played an increasing role in the management of benign thyroid nodules in recent years. The aim of this retrospective study was to evaluate the efficacy of RF ...treatment on volume reduction in functioning and non-functioning thyroid nodules.
Patients and methods
We reviewed the medical records of patients who had thyroid nodule RF ablation at our department between August 2017 and May 2018. Patients underwent a periodical follow-up with ultrasound examinations and thyroid function tests at 1, 3, 6 and 12 months from RF. Complications were assessed using the reporting standards of Interventional societies.
Results
43 patients were submitted to thyroid nodule RF ablation treatment. Patients were subdivided into two groups, those with functioning (17 patients) or non-functioning nodules. At baseline (i.e. pre-RF treatment), the two groups of patients were superimposable for gender, age, BMI, nodule volume and maximum nodule diameter. The volume reduction of all 43 nodules was 69.1 ± 17.3% (range 26.0–94.5%) with no difference between functioning and non-functioning lesions (72.9 ± 18.1% vs 66.7 ± 16.7%,
p
= 0.254). A total energy delivered per nodule was 16.5 ± 6.8 kJ, with no difference between functioning and non-functioning lesions (14.5 ± 7.2 kJ vs. 18.2 ± 6.3 kJ,
p
= 0.083, respectively). No major complications were observed.
Conclusions
Radiofrequency ablation is a clinically effective and safe outpatient treatment in patients with benign nodules. In particular, we showed that a single treatment is effective in restoring euthyroidism in patients with autonomously functioning thyroid nodules.
Purpose: In juvenile onset systemic lupus erythematosus (JoSLE), evidence for the association between vitamin D status, lupus activity, and bone health is very limited and not conclusive. The aim of ...this study was, therefore, to assess in JoSLE patients the possible relevance of vitamin D deficiency in disease and bone parameters. Methods: Fifty-seven JoSLE patients were initially compared to 37 age, race and body mass index (BMI) -matched healthy controls. The serum concentration of 25 hydroxyvitamin D (25OHD) was determined by radioimmunoassay. Patients with 25OHD deficiency (≤20 ng/mL) were compared to those with levels >20 ng/mL. Disease activity was evaluated by SLE Disease Activity Index (SLEDAI). Bone mineral density (BMD) and body composition (BC) were measured using dual-energy X-ray absorptiometry (DXA). Results: 25OHD levels were similar in patients and controls (21.44 ± 7.91 vs 22.54 ± 8.25 ng/mL, p = 0.519), regardless of supplementation (65% of patients and none in controls). Thirty-one patients with 25OHD deficiency (≤20 ng/mL) were further compared to the 26 JoSLE patients with levels >20 ng/mL. These two groups were well-balanced regarding vitamin D confounding variables: age (p = 0.100), ethnicity (p = 1.000), BMI (p = 0.911), season (p = 0.502), frequency of vitamin D supplementation (p = 0.587), creatinine (p = 0.751), renal involvement (p = 0.597), fat mass (p = 0.764), lean mass (p = 0.549), previous/current use of glucocorticoids(GC) (p = 1.0), immunosuppressors (p = 0.765), and mean current daily dose of GC (p = 0.345). Patients with vitamin D deficiency had higher SLEDAI (3.35 ± 4.35 vs 1.00 ± 2.48, p = 0.018), lower C4 levels (12.79 ± 6.78 vs 18.38 ± 12.24 mg/dL, p = 0.038), lower spine BMD (0.798 ± 0.148 vs 0.880 ± 0.127 g/cm2, p = 0.037) and whole body BMD (0.962 ± 0.109 vs 1.027 ± 0.098 g/cm2, p = 0.024). Conclusion: JoSLE vitamin D deficiency, in spite of conventional vitamin D supplementation, affects bone and disease activity status independent of therapy and fat mass reinforcing the recommendation to achieve adequate levels.
Purpose
Endocrine therapy (ET) is the mainstream adjuvant treatment for ER-positive breast cancer (BC). We analysed 9293 ER-positive BC patients diagnosed in nine European countries in 2009–2013 to ...investigate how comorbidities at diagnosis, age, stage and subtype affected ET use over time, and relapse.
Methods
Adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs) of receiving ET were estimated according to Charlson comorbidity, age, stage and subtype using logistic regression. The 2-year cumulative incidence and adjusted sub-hazard ratios (SHRs) of relapse were estimated using competing risk analysis, with all-cause death as the competing event. The z-test was used to assess differences in the proportion of patients receiving ET in 1996–1998 and 2009–2013.
Results
Ninety percent of the patients started adjuvant ET, range 96% (Belgium, Estonia, Slovenia, Spain)—75% (Switzerland). ORs of starting ET were lower for women aged > 75 years, with severe comorbidities, or luminal B HER2-positive cancer. The factors independently increasing the risk of relapse were: not receiving ET (SHR 2.26, 95%CI 1.02–5.03); severe comorbidity (SHR 1.94, 95%CI 1.06–3.55); luminal B, either HER2 negative (SHR 3.06, 95%CI 1.61–5.79) or positive (SHR 3.10, 95%CI 1.36–7.07); stage II (SHR 3.20, 95%CI 1.56–6.57) or stage III (SHR 7.41, 95%CI 3.48–15.73). ET use increased significantly but differently across countries from 51–85% in 1996–1998 to 86–96% in 2009–2013.
Conclusions
ER-positive BC patients in Europe are increasingly prescribed ET but between-country disparities persist. Older women and women with severe comorbidity less frequently receive ET. ET omission and severe comorbidity independently predict early disease relapse.
The AX-PET demonstrator—Design, construction and characterization Beltrame, P.; Bolle, E.; Braem, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2011, Letnik:
654, Številka:
1
Journal Article
Recenzirano
Axial PET is a novel geometrical concept for Positron Emission Tomography (PET), based on layers of long scintillating crystals axially aligned with the bore axis. The axial coordinate is obtained ...from arrays of wavelength shifting (WLS) plastic strips placed orthogonally to the crystals. This article describes the design, construction and performance evaluation of a demonstrator set-up which consists of two identical detector modules, used in coincidence. Each module comprises 48 LYSO crystals of 100
mm length and 156 WLS strips. Crystals and strips are readout by Geiger-mode Avalanche Photo Diodes (G-APDs). The signals from the two modules are processed by fully analog front-end electronics and recorded in coincidence by a VME-based data acquisition system. Measurements with point-like
22Na sources, with the modules used both individually and in coincidence mode, allowed for a complete performance evaluation up to the focal plane reconstruction of point sources. The results obtained are in good agreement with expectations and proved the set-up to be ready for the next evaluation phase with PET phantoms filled with radiotracers.
Summary
Predictors of bone mineral density (BMD) loss are additional tools in the management of osteoporosis in premenopausal women with systemic lupus erythematosus (SLE). This study provides ...original evidence that N-terminal propeptide of type 1 collagen (P1NP), the most specific bone formation marker, is a predictor of BMD loss in this group of women.
Introduction
SLE is associated with a high risk of low bone mass/fractures but this risk is still controversial in premenopausal women. Our aim was to determine the 1 year incidence of BMD loss in premenopausal SLE women and the value of bone turnover markers as predictors of this complication.
Methods
This study enrolled a convenience sample of 63 premenopausal SLE patients. BMD was evaluated by dual X-ray absorptiometry at lumbar spine and hip at baseline and after 12 months. BMD changes above the least significant change were considered significant. Serum levels of P1NP and CTX (electrochemiluminescence), OPG, and RANKL (ELISA) were determined at baseline.
Results
Mean age was 31.1 ± 6.8 years, and disease duration was 5.25 ± 3.8 years. 36.5 % of patients presented BMD loss and 17.5 % BMD gain at lumbar spine and/or hip. Patients were divided in three groups: BMD loss (BL), no BMD change (NC), and BMD gain (BG). Patients with BL and NC received similar cumulative/mean/maximum glucocorticoid doses during the study, but patients with BG received lower doses (
p
< 0.05). Baseline P1NP levels were different in the groups (BL: 36.95 ± 23.37 vs. NC: 54.63 ± 30.82 vs. BG: 84.09 ± 43.85 ng/mL;
p
= 0.031 BL vs. NC,
p
< 0.001 BL vs. BG, and
p
= 0.039 NC vs. BG). There was no difference in CTX, OPG, or RANKL levels. After multivariate analysis, P1NP remained as an independent risk factor for BMD loss (
p
< 0.03).
Conclusions
This study provides original evidence that lower levels of P1NP, the most specific bone formation marker, are predictive of BMD loss over 12 months in premenopausal SLE patients.
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