Purpose To critically assess the evidence base regarding outcomes following cataract surgery in uveitic cases. Design Systematic evidence-based review and meta-analysis. Methods A comprehensive search query was performed on MEDLINE, EMBASE, CINHAL, and CENTRAL databases. Relevant publications were identified by reviewing query results and reference list searches. Results A total of 89 articles met eligibility criteria. Among uveitic eyes with quiet or mostly quiet uveitis before cataract surgery, 20/40 visual acuity or better (≥20/40) was achieved in 68% following phacoemulsification, 72% following extracapsular cataract extraction, and 40% following pars plana lensectomy. More eyes undergoing cataract surgery with intraocular lens (IOL) implantation than eyes left aphakic achieved ≥20/40 postoperatively (71% vs 52%). Eyes receiving acrylic IOLs or heparin-surface-modified (HSM) polymethylmethacrylate had better visual outcomes than those receiving non-HSM polymethylmethacrylate or silicone IOLs. Active uveitis at the time of cataract surgery was associated with worse visual outcomes. Compared with other uveitis cases, the proportion achieving 20/40 or better post cataract surgery was better for Fuchs heterochromic cyclitis cases and worse for uveitis related to Behçet disease, Vogt-Koyanagi-Harada disease, or sympathetic ophthalmia, and also posterior uveitis in general. Conclusion Cataract surgery in eyes with uveitis resulted in normal range levels of visual acuity in most cases. The review suggests that preoperative control of uveitis, use of an acrylic or HSM IOL, and a diagnosis of Fuchs heterochromic cyclitis were associated with better outcomes. Posterior-involving uveitides tended to do worse, likely because of vision-limiting complications of uveitis. Average results may not be applicable to specific clinical scenarios.
This White Paper provides a summary of presentations and discussions at a Cardiovascular Safety Outcome Trials Think Tank cosponsored by the Cardiac Safety Research Consortium, the US Food and Drug Administration, and the American College of Cardiology, held at American College of Cardiology's Heart House, Washington, DC, on February 19, 2014. Studies to assess cardiovascular (CV) risk of a new drug are sometimes requested by regulators to resolve ambiguous safety signals seen during its development or among other members of its class. Think Tank participants thought that important considerations in undertaking such studies were as follows: (1) plausibility —how likely it is that a possible signal indicating risk is real, based on strength of evidence, and/or whether a plausible mechanism of action for potential CV harm has been identified; (2) relevance —what relative and absolute CV risk would need to be excluded to determine that the drug had an acceptable benefit-to-risk balance for its use in the intended patient population; and (3) how plausibility and relevance influence the timing and approach to further safety assessment.
CD4 T cells deficient in signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) exhibit a selective impairment in adhesion to antigen-presenting B cells but not dendritic cells (DCs), resulting in defective germinal center formation. However, the nature of this selective adhesion defect remained unclear. We found that whereas T cell:DC interactions were primarily integrin dependent, T cell:B cell interactions had both an early integrin-dependent phase and a sustained phase that also required SAP. We further found that the SLAM family member CD84 was required for prolonged T cell:B cell contact, optimal T follicular helper function, and germinal center formation in vivo. Moreover, both CD84 and another SLAM member, Ly108, mediated T cell adhesion and participated in stable T cell:B cell interactions in vitro. Our results reveal insight into the dynamic regulation of T cell:B cell interactions and identify SLAM family members as critical components of sustained T cell:B cell adhesion required for productive humoral immunity. ► Sustained T cell:B cell adhesion requires both integrin- and SAP-dependent pathways ► SAP-associated receptors CD84 and Ly108 are expressed on follicular T helper cells ► CD84 is required for optimal germinal center formation and T cell:B cell adhesion ► Multiple SAP-associated SLAM receptors help mediate T cell:B cell interactions in vitro
This article reviews current knowledge of the effects of maternal anemia and iron deficiency on pregnancy outcome. A considerable amount of information remains to be learned about the benefits of maternal iron supplementation on the health and iron status of the mother and her child during pregnancy and postpartum. Current knowledge indicates that iron deficiency anemia in pregnancy is a risk factor for preterm delivery and subsequent low birth weight, and possibly for inferior neonatal health. Data are inadequate to determine the extent to which maternal anemia might contribute to maternal mortality. Even for women who enter pregnancy with reasonable iron stores, iron supplements improve iron status during pregnancy and for a considerable length of time postpartum, thus providing some protection against iron deficiency in the subsequent pregnancy. Mounting evidence indicates that maternal iron deficiency in pregnancy reduces fetal iron stores, perhaps well into the first year of life. This deserves further exploration because of the tendency of infants to develop iron deficiency anemia and because of the documented adverse consequences of this condition on infant development. The weight of evidence supports the advisability of routine iron supplementation during pregnancy.
Thyrotoxic hypokalemic periodic paralysis (TPP) is characterized by acute attacks of weakness, hypokalemia, and thyrotoxicosis of various etiologies. These transient attacks resemble those of patients with familial hypokalemic periodic paralysis (hypoKPP) and resolve with treatment of the underlying hyperthyroidism. Because of the phenotypic similarity of these conditions, we hypothesized that TPP might also be a channelopathy. While sequencing candidate genes, we identified a previously unreported gene (not present in human sequence databases) that encodes an inwardly rectifying potassium (Kir) channel, Kir2.6. This channel, nearly identical to Kir2.2, is expressed in skeletal muscle and is transcriptionally regulated by thyroid hormone. Expression of Kir2.6 in mammalian cells revealed normal Kir currents in whole-cell and single-channel recordings. Kir2.6 mutations were present in up to 33% of the unrelated TPP patients in our collection. Some of these mutations clearly alter a variety of Kir2.6 properties, all altering muscle membrane excitability leading to paralysis. ► mutations are associated with thyrotoxic hypokalemic periodic paralysis, TPP ► encodes an inward rectifying potassium channel, Kir 2.6 ► Thyroid hormones regulate KCNJ18 both transcriptionally and posttranscriptionally
In the United States, intake of n-3 fatty acids is approximate to 1.6 g/d (approximate to 0.7% of energy), of which 1.4 g is alpha-linolenic acid (ALA; 18:3) and 0.1-0-.2 g is eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6). The primary sources of ALA are vegetable oils, principally soybean and canola. The predominant sources of EPA and DHA are fish and fish oils. Intake data indicate that the ratio of n-6 to n-3 fatty acids is approximate to 9.8:1. Food disappearance data between 1985 and 1994 indicate that the ratio of n-6 to n-3 fatty acids has decreased from 12.4:1 to 10.6.1. This reflects a change in the profile of vegetable oils consumed and, in particular, an approximate 5.5-fold increase in canola oil use. The ratio of n-6 to n-3 fatty acids is still much higher than that recommended (ie, 2.3:1). Lower ratios increase endogenous conversion of ALA to EPA and DHA. Attaining the proposed recommended combined EPA and DHA intake of 0.65 g/d will require an approximately 4-fold increase in fish consumption in the United States. Alternative strategies, such as food enrichment and the use of biotechnology to manipulate the EPA and DHA as well as ALA contents of the food supply, will become increasingly important in increasing n-3 fatty acid intake in the US population.
Recent research suggests that several of the major diseases of later life, including coronary heart disease, hypertension, and type 2 diabetes, originate in impaired intrauterine growth and development. These diseases may be consequences of "programming," whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology, and metabolism. Evidence that coronary heart disease, hypertension, and diabetes are programmed came from longitudinal studies of 25 000 UK men and women in which size at birth was related to the occurrence of the disease in middle age. People who were small or disproportionate (thin or short) at birth had high rates of coronary heart disease, high blood pressure, high cholesterol concentrations, and abnormal glucose-insulin metabolism. These relations were independent of the length of gestation, suggesting that cardiovascular disease is linked to fetal growth restriction rather than to premature birth. Replication of the UK findings has led to wide acceptance that low rates of fetal growth are associated with cardiovascular disease in later life. Impaired growth and development in utero seem to be widespread in the population, affecting many babies whose birth weights are within the normal range. Although the influences that impair fetal development and program adult cardiovascular disease remain to be defined, there are strong pointers to the importance of the fetal adaptations invoked when the maternoplacental nutrient supply fails to match the fetal nutrient demand.