Mechanical ventilation with high tidal volumes (VT) has been common practice in operating theatres because this strategy recruits collapsed lung tissue and improves ventilation-perfusion mismatch, thus decreasing the need for high inspired oxygen concentrations. Positive end-expiratory pressure (PEEP) was not used routinely because it was thought to impair cardiovascular function. Over the past two decades there have been advances in our understanding of the causes and importance of ventilation-induced lung injury based on studies in animals with healthy lungs, and trials in critically ill patients with and without acute respiratory distress syndrome. Recent data from randomised controlled trials in patients receiving ventilation during general anaesthesia for surgery have demonstrated that lung-protective strategies (use of low VT, use of PEEP if indicated, and avoidance of excessive oxygen concentrations) are also of importance during intraoperative ventilation.
Biotechnological advances now enable the design of fully human antibodies to target specific antigens in a growing number of diseases. Monoclonal antibodies (mAbs) differ from traditional small chemical molecules in several ways: (1) biological production ‒ they are grown in and extracted from cell cultures; (2) specificity ‒ they demonstrate high target specificity, with a low risk of drug-drug interactions; (3) administration ‒ they are delivered parenterally (intravenously or subcutaneously); (4) dosage interval ‒ their extended half-lives generally allow for spaced dosing (from weekly to monthly). In cardiology, fully human mAbs directed against proprotein convertase subtilisin / kexin type 9 (PCSK9) have shown to be effective in reducing low-density lipoprotein cholesterol (LDL-C) in phase II clinical trials among patients with familial hypercholesterolaemia (FH). PCSK9 inhibitors have just received approval for the treatment of FH and clinical atherosclerotic disease, and patients not at target under maximally tolerated statin therapy or intolerant to statins. Large-scale phase III trials are currently assessing the role of PCSK9 inhibitors in the secondary prevention setting for patients with acute coronary syndromes (ACS) and poorly controlled LDL-C under evidence-based therapies. Another area currently under investigation for fully human mAbs in secondary prevention is their potential ability to inhibit inflammatory pathways. In this context, canakinumab, a specific mAb inhibiting interleukin-1β (IL-1β), has already received approval for the treatment of systemic juvenile idiopathic arthritis. The canakinumab anti-inflammatory thrombosis outcomes trial (CANTOS) is an ongoing trial assessing whether inhibition of IL-1β could reduce the occurrence of cardiovascular adverse events in 17,200 patients with ACS and with defined persisting inflammation.
Exosomes are nanovesicles, generally 50 to 90 nm in diameter, that correspond to the intraluminal vesicles of the endosomal multivesicular bodies and are secreted upon fusion of multivesicular bodies with the plasma membrane. Their molecular content is highly selected and includes not only specific proteins and lipids, but also RNA species, such as messenger RNAs (mRNAs) and microRNAs (miRNAs), which are delivered and active in target cells. As they are released in body fluids, exosomes can shuttle molecules for long distances. In the CNS they have been shown to regulate neuronal development and regeneration, and to modulate synaptic functions. In neurodegenerative diseases, they have an important role in propagating neurotoxic misfolded protein from one cell to another and, as recent data show, possibly other molecules contributing to neurotoxicity. Some exosomal lipids such as gangliosides GM1 and GM3 enhance the aggregation of alpha-synuclein, and RNA exosomal cargo is also altered during pathologies such as Alzheimer’s disease, prion diseases and amyotrophic lateral sclerosis.
The aim of this review is to focus on the regulation of CNS exosomal function and highlight pathways that might have a role in the neurodegenerative process. The identification of the novel exosomal molecules involved in neurodegenerative diseases could provide important insights into the pathogenesis and contribute to the finding of novel diagnostic biomarkers and therapeutic approaches.
The epidemics of classical bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) related to BSE-infected food are coming to an end. The decline in concern about these diseases may invite complacency and questions whether surveillance for human prion diseases is still necessary. This article reviews the main points of surveillance and why it is still needed: animal sources for human prion infection other than BSE cannot be excluded; the potentially increasing circulation of prions between humans by blood, blood products and medical procedures; the prevalence of vCJD prion carriers in the UK; and the scientific study of prion diseases as paradigm for other neurodegenerative diseases with “prion-like” spread of pathological proteins. We conclude that continuation of detailed surveillance of human prion disorders would be prudent in view of all these points that deserve clarification.
Arthritis encompasses a heterogeneous group of diseases characterised by inflammation that leads not only to joint damage, bone erosion, severe pain and disability, but also affects other organs of the body, resulting in increased morbidity and mortality. Although the mechanisms underlying the pathogenesis of joint diseases are for the most part unknown, a number of nutrient and non-nutrient components of food have been shown to affect the inflammatory process and, in particular, to influence clinical disease progression.
The Mediterranean diet model has already been linked to a number of beneficial health effects: both fat and non-fat components of the Mediterranean dietary pattern have been shown to exert important anti-inflammatory activities by affecting the arachidonic acid cascade, the expression of some proinflammatory genes, and the activity of immune cells. N-3 polyunsaturated fatty acids, in particular, have been shown to affect lymphocyte and monocyte functions, crucially involved in adaptive and innate immunity.
Although some aspects concerning the mechanisms of action through which the Mediterranean diet pattern exerts its beneficial effects remain to be elucidated, arthritis patients may potentially benefit from it in view of their increased cardiovascular risk and the treatment they require which may have side effects.
As a result of a huge effort of the international community, the burden of malaria dropped impressively during the last decade. One of the reasons is probably the availability of effective and safe treatments such as artemisinin derivatives. However, along with the greater use of intravenous artesunate recently in severe malaria, as recommended by the World Health Organization, a new adverse event has been described: post-artesunate delayed haemolysis (PADH). It appears after the end of the treatment in a phase of clinical improvement. Even though several causes may act as co-factors, the mechanism of pitting of the infected erythrocytes is most probably the main explanation. After the description of four PADH cases, we hereby present a short review of the current knowledge on this problem.
OBJECTIVE: The aim of this study was to develop a generic instrument for the use of patients, named the Knee Osteoarthrtis Patient Education Questionnaire (KOPEQ), to assess the validity of a preoperative educational intervention and to make a preliminary test of its psychometric properties.
METHODS: A patient-reported outcome instrument was designed, using the conceptual framework of Wilson and Cleary as a methodological guide. Likert items with a five-point scale were chosen for the scoring option. The feasibility and interpretability of administering the KOPEQ was tested through conducting interviews with targeted patients. Items of the KOPEQ were linked to the International Classification of Functioning, Disability and Health (ICF). Psychometric testing contained internal consistency for reliability, and factor analysis for validity properties.
RESULTS: A final list of 16 items was derived and linked to the ICF. Targeted patients confirmed in interviews, that all 16 questions were highly understandable and that the length of the questionnaire was feasible and acceptable. There was a good internal consistency for the 16-item KOPEQ with a Cronbach’s alpha of 0.83 (95% confidence interval 0.71–0.94). Sixty-one percent of the variance was explained by a four-factor model and the factors were named “didactics”, “addressability”, “empowerment” and “theory”. Results of a factor analysis provided a loading of the separate items between 0.469 and 0.958.
CONCLUSIONS: The KOPEQ can help to provide health professionals with reliable feedback on how patients assessed the applied patient education intervention. Interviews with patients and a factor analysis revealed new and important insight.
Key words: patient edication; questionnaire; knee; osteoarthritis
QUESTIONS UNDER STUDY: Optimal oxygen saturation (SpO2) targets for extremely low gestational age neonates (ELGANs, gestational age [GA] <28 weeks) are unknown. Conflicting results from five recently published multicentre trials, which randomised ELGANs to high (91 to 95%) or low (85 to 89%) SpO2 targets from birth up to a corrected GA of 36 weeks, prompted us to examine our experience with two different SpO2policies.
METHODS: We retrospectively compared outcomes of two cohorts of ELGANs which were exposed to two different SpO2 target policies adapted to the infants’ corrected GA. Between 1 January 2000 and 30 June 2007, SpO2 targets were 85 to 95% at <30 weeks and 88 to 97% at ≥30 weeks (high SpO2 target cohort, n = 157). Between 1 July 2007 and 31 December 2011, SpO2 targets were lowered to 80 to 90% at <30 weeks, 85 to 95% between 30 and 34 weeks and finally 88 to 97% at ≥34 weeks (low SpO2 target cohort, n = 84).
RESULTS: There were no statistically significant differences between the high and low SpO2 target cohorts in mortality rates (15.9 vs 17.9%, risk ratio [RR] 0.89; 95% confidence interval [CI] 0.50–1.60), incidences of severe retinopathy of prematurity (2.3 vs 0%, RR 3.68; 95% CI 0.19–70.3), or moderate/severe bronchopulmonary dysplasia (14.4 vs 21.1%, RR 0.68; 95% CI 0.37–1.26).
CONCLUSIONS:Adapting SpO2 targets to the advancing corrected GA seems safe and is associated with low incidences of short-term complications. Mortality rates did not vary with the two different SpO2 target policies utilised and were comparable to those reported from recently published randomised controlled SpO2 target trials.