Summary Pulmonary hypertension is associated with sudden death and is a risk factor for mortality in adult patients with sickle cell disease. The high mortality despite only mild‐to‐moderate increases in pulmonary vascular resistance remains an unresolved paradox. Accordingly, little is known about the cardiovascular effects of stressors, such as vaso‐occlusive pain crisis (VOC) and exercise, which may acutely increase pulmonary pressures and impair right heart function. We therefore evaluated pulmonary artery pressures by echocardiogram in 25 patients with sickle cell disease in steady‐state and during VOC, and by right heart catheterisation with exercise in a second cohort of 21 patients to determine whether pulmonary hypertension worsens during acute cardiopulmonary stress. TRV increased during VOC (P < 0·001), and the increased pulmonary pressures during VOC were associated with decreases in haemoglobin levels (P < 0·001), and increases in lactate dehydrogenase (P < 0·001) and plasma haemoglobin levels (P = 0·03). During exercise stress performed during cardiac catheterisation, mean pulmonary artery pressures (P < 0·001) and pulmonary vascular resistance increased (P < 0·001) in all subjects. These data suggest that acute elevations in pulmonary pressures during VOC or exercise may contribute to morbidity and mortality in patients with sickle cell disease.

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Very few multidimensional tools are available for measurement of pain in children and adolescents. We critically reviewed the scientific literature to examine the psychometrics and utility of the Adolescent Pediatric Pain Tool (APPT), a multidimensional self-report tool that evaluates the intensity, location, and quality (including affective, evaluative, sensory, and temporal) dimensions of pain. The APPT is available in English and Spanish for children and adolescents, and was modeled after the McGill Pain Questionnaire in adults. We found good evidence for construct validity, reliability, and sensitivity of the APPT for the measurement of pediatric pain. The APPT was used to measure pain in children with different conditions, such as cancer, sickle cell disease, orthopedic, traumatic injuries, and allergy testing. Although the APPT was designed to assess the multiple dimensions of pain, the majority of the reports included results only for the intensity ratings. Unlike the numerical and pediatric faces rating scales, which are widely used in clinical practice and research, the APPT is not limited to the single dimension of pain intensity. It measures multiple dimensions, and may be able to discriminate between nociceptive and neuropathic pain. The APPT is one of a few multidimensional pain measures that can help to advance the science of pediatric pain and its management. When the APPT is used in practice or research, the multiple dimensions of pain may be characterized and compared in different painful conditions. It may guide the use of multimodal interventions in children and adolescents with a variety of pain conditions.

Background/Objectives: The high incidence of

Despite extended RBC typing, alloimmunization may still occur due to RBC variants that are not detected on routine screening and transfusions at institutions where extended RBC typing is not done. Extended RBC typing should be the standard of care for patients with SCD. Prospective genotyping may reduce allosensitization to rare variants not detected on routine screening.

Summary Background Dietary emulsifiers are the latest food additives to be associated with intestinal, cardiovascular and metabolic health. Most recently, there are postulations around certain emulsifiers playing a role in the development of Crohn's disease. Aim To review the use of food‐based emulsifiers, their content in the food supply and mechanisms by which they might exert potentially detrimental biological effects. Methods Information on emulsifiers and thickeners relevant to human health was critically examined. Results The term, “emulsifier,” has been used loosely and has included thickeners as well as agents that truly promote emulsions. These comprise proteins, phospholipids and carbohydrates, alone or in combination, and play roles in optimising food appearance, texture and mouthfeel, delivering or disguising flavours and achieving palatable low‐fat foods. Their presence in the food supply is common, but not “ubiquitous” as frequently stated. Strict regulations limit the amount added to foods, but the lack of established methodologies to measure the actual food content of these diverse compounds limits our knowledge of consumption. Emulsifiers and thickeners have effects on the gut microbiota, mucosal barrier and inflammatory pathways, and can induce disease in experimental models. However, differentiating pharmacological from physiological effects and translating findings in experimental animals to humans raise uncertainties about the relevance of such effects. Conclusions There is limited evidence to directly link emulsifiers and thickeners to human disease, but multiple potential pathogenic mechanisms. Knowledge of actual dietary intake and high‐quality interventional studies is needed to enable the risks associated with their intake to be understood.

SummaryIn addition to vaso-occlusion by sickled erythrocytes, the pathophysiology of sickle cell disease (SCD) is compounded by the diminished bioavailability of nitric oxide (NO), associated with vasoconstriction, endothelial activation and cell adhesion. We tested the ability of sodium nitrite, which can be converted to NO by deoxyhaemoglobin at acid pH and low oxygen tension, to improve blood flow in patients with SCD. In a phase I/II clinical trial, sodium nitroprusside, NG-monomethyl-L-arginine, and sodium nitrite were infused sequentially into the brachial artery in 14 patients at steady state. In a dose-dependent manner, sodium nitrite infusion rates of 0AE4, 4 and 40 lmol/ min into the brachial artery augmented mean venous plasma nitrite concentrations (P < 0AE0001) and stimulated forearm blood flow up to 77 ± 11% above baseline (P < 0AE0001), measured by venous occlusion strain gauge plethysmography. This nitrite response was blunted significantly compared to controls without SCD, as previously seen with other NO donors. Sodium nitrite infusions were well tolerated without hypotension, clinically significant methaemoglobinaemia or other untoward events. The unique pharmacological properties of nitrite as a hypoxia-potentiated vasodilator and cytoprotective agent in the setting of ischaemia-reperfusion injury make this anion a plausible NO donor for future clinical trials in SCD.