Reexamination of a Meta-Analysis of the Effect of Antioxidant Supplementation on Mortality and Health in Randomized Trials

A recent meta-analysis of selected randomized clinical trials (RCTs), in which population groups of differing ages and health status were supplemented with various doses of β-carotene, vitamin A, and/or vitamin E, found that these interventions increased all-cause mortality. However, this meta-analysis did not consider the rationale of the constituent RCTs for antioxidant supplementation, none of which included mortality as a primary outcome. As the rationale for these trials was to test the hypothesis of a potential benefit of antioxidant supplementation, an alternative approach to a systematic evaluation of these RCTs would be to evaluate this outcome relative to the putative risk of greater total mortality. Thus, we examined these data based on the primary outcome of the 66 RCTs included in the meta-analysis via a decision analysis to identify whether the results provided a positive (i.e., benefit), null or negative (i.e., harm) outcome. Our evaluation indicated that of these RCTs, 24 had a positive outcome, 39 had a null outcome, and 3 had a negative outcome. We further categorized these interventions as primary (risk reduction in healthy populations) or secondary (slowing pathogenesis or preventing recurrent events and/or cause-specific mortality) prevention or therapeutic (treatment to improve quality of life, limit complications, and/or provide rehabilitation) studies, and determined positive outcomes in 8 of 20 primary prevention studies, 10 of 34 secondary prevention studies, and 6 out of 16 therapeutic studies. Seven of the eight RCTs with a positive outcome in primary prevention included participants in a population where malnutrition is frequently described. These results suggest that analyses of potential risks from antioxidant supplementation should be placed in the context of a benefit/risk ratio

The immune system and the impact of zinc during aging

The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence

Nutritional therapy and infectious diseases: a two-edged sword

The benefits and risks of nutritional therapies in the prevention and management of infectious diseases in the developed world are reviewed. There is strong evidence that early enteral feeding of patients prevents infections in a variety of traumatic and surgical illnesses. There is, however, little support for similar early feeding in medical illnesses. Parenteral nutrition increases the risk of infection when compared to enteral feeding or delayed nutrition. The use of gastric feedings appears to be as safe and effective as small bowel feedings. Dietary supplementation with glutamine appears to lower the risk of post-surgical infections and the ingestion of cranberry products has value in preventing urinary tract infections in women

Trace elements in hemodialysis patients: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Hemodialysis patients are at risk for deficiency of essential trace elements and excess of toxic trace elements, both of which can affect health. We conducted a systematic review to summarize existing literature on trace element status in hemodialysis patients.</p> <p>Methods</p> <p>All studies which reported relevant data for chronic hemodialysis patients and a healthy control population were eligible, regardless of language or publication status. We included studies which measured at least one of the following elements in whole blood, serum, or plasma: antimony, arsenic, boron, cadmium, chromium, cobalt, copper, fluorine, iodine, lead, manganese, mercury, molybdenum, nickel, selenium, tellurium, thallium, vanadium, and zinc. We calculated differences between hemodialysis patients and controls using the differences in mean trace element level, divided by the pooled standard deviation.</p> <p>Results</p> <p>We identified 128 eligible studies. Available data suggested that levels of cadmium, chromium, copper, lead, and vanadium were higher and that levels of selenium, zinc and manganese were lower in hemodialysis patients, compared with controls. Pooled standard mean differences exceeded 0.8 standard deviation units (a large difference) higher than controls for cadmium, chromium, vanadium, and lower than controls for selenium, zinc, and manganese. No studies reported data on antimony, iodine, tellurium, and thallium concentrations.</p> <p>Conclusion</p> <p>Average blood levels of biologically important trace elements were substantially different in hemodialysis patients, compared with healthy controls. Since both deficiency and excess of trace elements are potentially harmful yet amenable to therapy, the hypothesis that trace element status influences the risk of adverse clinical outcomes is worthy of investigation.</p

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

It is often challenging for the clinician interested in cystic fibrosis (CF) to interpret molecular genetic results, and to integrate them in the diagnostic process. The limitations of genotyping technology, the choice of mutations to be tested, and the clinical context in which the test is administered can all influence how genetic information is interpreted. This paper describes the conclusions of a consensus conference to address the use and interpretation of CF mutation analysis in clinical settings

The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours

Aberrant activation of intracellular signalling pathways confers malignant properties on cancer cells. Targeting intracellular signalling pathways has been a productive strategy for drug development, with several drugs acting on signalling pathways already in use and more continually being developed. The JAK/STAT signalling pathway provides an example of this paradigm in haematological malignancies, with the identification of JAK2 mutations in myeloproliferative neoplasms leading to the development of specific clinically effective JAK2 inhibitors, such as ruxolitinib. It is now clear that many solid tumours also show activation of JAK/STAT signalling. In this review, we focus on the role of JAK/STAT signalling in solid tumours, examining the molecular mechanisms that cause inappropriate pathway activation and their cellular consequences. We also discuss the degree to which activated JAK/STAT signalling contributes to oncogenesis. Studies showing the effect of activation of JAK/STAT signalling upon prognosis in several tumour types are summarised. Finally, we discuss the prospects for treating solid tumours using strategies targeting JAK/STAT signalling, including what can be learned from haematological malignancies and the extent to which results in solid tumours might be expected to differ

Syndrome de la fissure orbitaire supérieure post-traumatique : mise au point

International audienceThe traumatic superior orbital fissure syndrome is an uncommon complication of craniomaxillofacial trauma. The diagnosis is clinical and associates ophtalmoplegia (constantly at initial clinical examination), ptosis and anaesthesia of the forehead. Young men victim of road traffic accidents are most often affected. CT-scan usually shows facial and/or craniofacial fractures more or less spreading towards the superior orbital fissure. The absence of fracture seen at the X-rays does not eliminate the diagnosis. Initial management should be multidisciplinary (maxillofacial surgeons, ophthalmologists and neurosurgeons) and conducted early if possible. It combines high-dose corticosteroids and decompression surgery if necessary. Abstention may be indicated in cases of delayed diagnosis with spontaneous improvement. Symptoms improve early but follow-up should be extended over several months given the recovery time.Le syndrome de la fissure orbitaire supérieure post-traumatique est une complication rare des traumatismes craniomaxillo-faciaux. Le diagnostic est clinique et associe une ophtalmoplégie (constante lors de l’examen initial), un ptosis et une anesthésie frontale. Les hommes jeunes victimes d’un accident de la voie publique sont les plus souvent atteints. Le scanner montre le plus souvent des fractures faciales et/ou cranio-faciales irradiant plus ou moins au niveau du toit de l’orbite en direction de la fissure orbitaire supérieure mais l’absence radiologique de fracture n’élimine pas le diagnostic. La prise en charge initiale doit être pluridisciplinaire (chirurgiens maxillo-faciaux, ophtalmologistes et neurochirurgiens) et si possible précoce. Elle associe une corticothérapie à fortes doses et une chirurgie de décompression si besoin. L’abstention peut être indiquée en cas de retard diagnostique avec amélioration spontanée. La régression des symptômes est précoce mais le suivi doit être prolongé sur plusieurs mois compte tenu du délai de récupération

Reconstruction faciale complexe sur mesure : un cas de remplacement total de l’articulation temporo-mandibulaire, de l’arcade zygomatique et du zygoma

International audienceIntroductionTotal prosthetic replacement of the temporo-mandibular joint (TMJ) has become a common procedure, but it is usually limited to the TMJ itself. We report about one case of complex prosthetic joint reconstruction extending to the neighbouring bony structures.CaseA 57-year-old patient, operated several times for a cranio-facial fibrous dysplasia, presented with a recurring TMJ ankylosis and a complexe latero-facial bone loss on the right side. We performed a reconstruction procedure including the TMJ, the zygomatic arch and the malar bone by mean of custom made composite prosthesis (chrome–cobalt–molybdenum-titanium and polyethylene). Five years postoperatively, mouth opening, nutrition, pain and oral hygiene were significantly improved.DiscussionNowadays technical possibilities allow for complex facial alloplastic reconstructions with good medium term results.IntroductionLe remplacement total prothétique de l’articulation temporo-mandibulaire (ATM) est devenu une intervention courante, mais ce remplacement prothétique se cantonne habituellement à l’ATM. Nous présentons le cas d’une reconstruction prothétique complexe sur mesure étendue l’articulation et les structures osseuses voisines.ObservationUn patient de 57 ans, multi-opéré pour une dysplasie fibreuse crânio-faciale droite, présentait une récidive d’ankylose de l’ATM droite et une perte de substance osseuse latéro-faciale droite complexe. Nous sommes intervenus pour procéder à une reconstruction incluant l’ATM, l’arcade zygomatique et le zygoma à l’aide d’une prothèse sur mesure composite (chrome–cobalt–molybdène-titane et polyéthylène). À 5 ans postopératoires, l’ouverture buccale, l’alimentation, la douleur et l’hygiène buccodentaire étaient significativement améliorées.DiscussionGrâce aux possibilités techniques actuelles, des reconstructions alloplastiques faciales complexes peuvent être envisagées avec de bons résultats à moyen terme