Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality.
With the Cochrane Collaboration methodology, ...we reviewed all randomised trials comparing antioxidant supplements with placebo for prevention of gastrointestinal cancers. We searched electronic databases and reference lists (February, 2003). Outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were analysed with fixed-effect and random-effects model meta-analyses and were reported as relative risk with 95% CIs.
We identified 14 randomised trials (n=170 525). Trial quality was generally high. Heterogeneity of results was low to moderate. Neither the fixed-effect (relative risk 0·96, 95% CI 0·88–1·04) nor random-effects meta-analyses (0·90, 0·77–1·05) showed significant effects of supplementation with β-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer incidences. In seven high-quality trials (n=131 727), the fixed-effect model showed that antioxidant significantly increased mortality (1·06, 1·02–1·10), unlike the random-effects meta-analysis (1·06, 0·98–1·15). Low-quality trials showed no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high-quality and low-quality trials was significant (Z=2·10, p=0·04 by test of interaction). β-carotene and vitamin A (1·29, 1·14–1·45) and β-carotene and vitamin E (1·10, 1·01–1·20) significantly increased mortality, whereas β-carotene alone only tended to increase mortality (1·05, 0·99–1·11). In four trials (three with unclear or inadequate methodology), selenium showed significant beneficial effect on the incidence of gastrointestinal cancer.
We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers on the contrary, they seem to increase overall mortality. The potential preventive effect of selenium should be studied in adequate randomised trials.
Aim
To systematically review the clinical features and outcomes of paediatric patients developing neurological complications associated with a rotavirus infection.
Methods
A systematic literature ...review and meta‐analysis was performed, including articles published from 1984 to 2020. Neurological complications were classified into four groups: encephalitis, cerebellitis, encephalo‐cerebellitis and benign convulsions with mild gastroenteritis (CwG).
Results
Out of 68 reports that fulfilled the research criteria, 99 cases of CwG, 39 cases of encephalitis, 18 cases of encephalo‐cerebellitis and five cases of cerebellitis were collected. Ninety‐five patients were from Asia. Median age was 22 (IQR 14–29) months, and the children who developed CwG were significantly younger (19, IQR 12–24 months, p < 0.0001) than the others. Status epilepticus was observed in 23% and 5% of the encephalitis and CwG groups respectively. The most frequently described neuroimaging finding were lesions of the splenium of corpus callosum. Four deaths were reported in the encephalitis group, whereas no fatal events were described in the other groups. Among the surviving children, the encephalo‐cerebellitis group showed the most severe long‐term outcome. All cases of CwG recovered completely.
Conclusion
Older age at diagnosis and the development of encephalo‐cerebellitis are associated with a higher risk of long‐term complications.
Summary
Recent advances suggest that organic substances of different origins might have different aggregate stability dynamics. We investigated the extent to which contrasting soil types affect the ...dynamics of aggregation after the addition of crop residues (R) and of biochar at two doses (BC20, 20 Mg ha−1; BC40, 40 Mg ha−1) in a 2‐year experiment. To evaluate disaggregation, we measured a set of physical–chemical and structure‐related properties of clay and sandy loam aggregates sieved to 1–2 mm, including wet aggregate stability after different pretreatments combined with laser diffraction analysis. The electrochemical properties of the colloidal suspension were also analysed to identify changes in soil chemistry affected by organic inputs. Different amounts of added biochar and soil types produced contrasting effects on wet aggregate stability. In sandy loam, the increased soil surface area from added biochar (at either dose) offset the initial small soil organic carbon (SOC) content and subsequently promoted SOC‐controlled aggregation. Conversely in clay soil, the larger biochar dose (BC40) strengthened the repulsive forces between particles with the same charge and monovalent cations, which led to chemical perturbation and some aggregate breakdown not found with BC20. Pore structure also changed in clay aggregates. A shift towards more micropores (30–5 μm, + 29% more than in the control) and ultramicropores (5–0.1 μm, + 22% more than in the control), which contributed to aggregate stabilization, resulted when biochar was added, but not for residue. Our results suggest that biochar promotes aggregate stability, which, in turn, improves the physical fertility of soil, especially if it has a coarse texture and small organic carbon content. Further study is needed of the physical–chemical interactions between added biochar and surface‐charged clay‐rich soils.
Highlights
Aggregate dynamics are poorly understood because of complex interactions between organic inputs and soil type.
A multidisciplinary approach was used to study aggregation dynamics.
Large biochar input changed soil chemical properties that weakened stability in clay aggregates.
Aggregate stability depended on biochar dose and soil type.
Dissection of the carotid artery (CaAD) may result in aneurysm formation. The present study was undertaken to evaluate the time of onset of post-dissection extracranial carotid artery aneurysms ...(ECAA) following CaAD, and to analyse independent risk factors for the development of these aneurysms.
From four European stroke centres, 360 patients with extracranial CaAD were included. The time between the estimated dissection onset and aneurysm formation was analysed, and the clinical risk factors increasing the probability of aneurysm were assessed.
The median duration of follow up was 5.2 months (range 0 – 24 months). A total of 75 post-dissection ECAAs were identified in 70 patients (19.4%, 95% confidence interval CI 15.7 – 23.8). In 52 of 70 (74%) patients, the ECAA was diagnosed at the initial clinical work up of CaAD diagnosis, with the median estimated time of dissection onset to ECAA diagnosis being six days (interquartile range IQR 0 – 25). In the remaining 18 (26%) patients who had normal carotid arteries at the initial imaging, the aneurysm diagnosis was made a median of 6.2 months (189 days) from the original imaging (IQR 128 – 198). A Cox proportional hazards model showed that both multiple artery dissections (hazard ratio HR 2.58, 95% CI 1.54 – 4.33) and arterial tortuosity (HR 1.79, 95% CI 1.08 – 2.95) were associated with presence of ipsilateral ECAA.
This post hoc cohort analysis showed substantially delayed development of ipsilateral ECAA in patients with CaAD, months after baseline. Multiple dissections and arterial tortuosity are associated with the presence of ECAA and can be used in future prediction models of ECAA development in patients with CaAD.
The E3 ubiquitin ligase (E3) WWP1 is an oncogenic factor implicated in the maintenance of different types of epithelial cancers. The role of WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) ...in haematological neoplasms remains unknown. Acute myeloid leukaemia (AML) is characterized by the expansion of malignant myeloid cells blocked at different stages of differentiation. Here we report that the expression of WWP1 is significantly augmented in a large cohort of primary AML patients and in AML cell lines, compared with haematopoietic cells from healthy donors. We show that WWP1 inactivation severely impairs the growth of primary AML blasts and cell lines in vitro. In vivo, we observed a reduced leukaemogenic potential of WWP1-depleted AML cells upon transplantation into immunocompromised mice. Mechanistically, WWP1 inactivation induces the accumulation of its protein substrate p27
, which ultimately contributes to G
/G
cell cycle arrest of AML blasts. In addition, WWP1 depletion triggers the autophagy signalling and reduces survival of leukaemic cells. Collectively, our findings provide molecular insights into the anti-cancer potential of WWP1 inhibition, suggesting that this E3 is a promising biomarker and druggable target in AML.
Background
Percutaneous vertebroplasty is currently an alternative for treating vertebral fractures of the thoracic and lumbar spine, providing both pain control and vertebral stabilization. In the ...cervical spine, however, percutaneous vertebroplasty is technically challenging because of the complex anatomy of this region.
Questions/purposes
We evaluated the technical feasibility, complication rate, and ability of percutaneous vertebroplasty to provide pain relief in patients with painful metastatic cervical fractures.
Methods
We retrospectively reviewed 62 patients (24 men) who, between May 2005 and May 2009, underwent vertebroplasty to treat painful metastatic cervical fractures. Each patient was evaluated by a visual analog scale for pain, number of pain analgesics, and CT and MRI before, the day after, and at 3 months after the procedure.
Results
Two of the 62 patients had asymptomatic cement leakage in the soft tissues. We observed no delayed complications. Mean pretreatment and 24-hour posttreatment visual analog scale pain scores were 7.9 ± 1.7 and 1.5 ± 2, respectively. Immediately after surgery, the pain completely disappeared in 25 (40%) patients. Administration of analgesics was suspended in 34 (55%) patients whereas in 27 (39%) patients the median analgesics use decreased from two pills per day (range, 0–3) to 0 (range, 0–3). In two (3%) patients, analgesics administration was continued due to the persistence of pain. At 3 months, the patients reported a mean visual analog scale pain score of 1.7 ± 2.
Conclusions
Our data suggest, in selected patients, percutaneous vertebroplasty may be performed with a high technical success rate combined with a low complication rate, providing immediate pain relief lasting at least 3 months and a reduction in the use of analgesic drugs.
Level of Evidence
Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
CONTEXT: Antioxidant supplements are used for prevention of several diseases. OBJECTIVE: To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention ...trials. DATA SOURCES AND TRIAL SELECTION: We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials. DATA EXTRACTION: We included 68 randomized trials with 232 606 participants (385 publications). DATA SYNTHESIS: When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality. CONCLUSIONS: Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.
Abstract The new Regulation (EU) No. 536/2014 for clinical trials of medicinal products for human is part of a European regulatory framework in which the European Commission has wished to give a ...strong impetus to scientific research and industrial progress. It is a new regulation that fills a series of regulatory gaps in the Clinical Trials through the creation of a uniform framework for the authorization of clinical trials by all interested Member States with a single assessment of the results. The Regulation thus facilitates cross-border cooperation to make the clinical tests wider and encourage the development of special treatments, for example for rare diseases, but above all streamlines the rules on clinical trials across European Union (EU), introducing simplified rules for experimentation so-called 'low level of intervention', on which much has been discussed and still arouses concern, providing for authorized medicines or used off-label in the presence of scientific evidence published on efficacy and safety and to benefit from they will be mainly the pediatric and oncological therapeutic areas. The applications and any communication will be submitted paperlessly via a new electronic EU portal. The complex processing procedures and shorter time limits are to be stressed in comparison to the previously valid regulations. This is a major challenge for all stakeholders, but on the other hand it should contribute to the future role of the EU in the development of innovative medicines.
Aim
To compare infrared tympanic and infrared contact forehead thermometer measurements with traditional rectal digital thermometers.
Methods
A total of 254 children (137 girls) aged one to 24 months ...(median 7 months) consulting a private paediatric practice because of fever were prospectively recruited. Body temperature was measured using the three different devices.
Results
The median and interquartile range for rectal, tympanic and forehead thermometers were 37.6 (37.1–38.4)°C, 37.5 (37.0–38.1)°C and 37.5 (37.1–37.9)°C, respectively (p < 0.01). The limits of agreement in the Bland‐Altman plots were −0.73 to +1.04°C for the tympanic thermometer and −1.18 to +1.64°C for the forehead thermometer. The specificity of both the tympanic and forehead thermometers for detecting fever above 38°C was good, but sensitivity was low. Forehead measurements were susceptible to the use of a radiant warmer.
Conclusion
Both the tympanic and forehead devices recorded lower temperatures than the rectal thermometers. The limits of agreement were particularly wide for the forehead thermometer and considerable for the tympanic thermometer. In the absence of valid alternatives, because of the ease to use and little degree of discomfort, tympanic thermometers can still be used with some reservations. Forehead thermometers should not be used in paediatric practice.
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