Natural History and Predictors of Progression to Sjögren's Syndrome Among Participants of the Sjögren's International Collaborative Clinical Alliance Registry

Objective

To explore changes in the phenotypic features of Sjögren's syndrome (SS), and in SS status among participants in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry over a 2–3‐year interval.

Methods

All participants in the SICCA registry who were found to have any objective measures of salivary hypofunction, dry eye, focal lymphocytic sialadenitis in minor salivary gland biopsy, or anti‐SSA/SSB antibodies were recalled over a window of 2 to 3 years after their baseline examinations to repeat all clinical examinations and specimen collections to determine whether there was any change in phenotypic features and in SS status.

Results

As of September 15, 2013, a total of 3,514 participants had enrolled in SICCA, and among 3,310 eligible, 771 presented for a followup visit. Among participants found to have SS using the 2012 American College of Rheumatology (ACR) classification criteria, 93% again met the criteria after 2 to 3 years, and this proportion was 89% when using the 2016 ACR/European League Against Rheumatism (EULAR) criteria. Among those who did not meet ACR or ACR/EULAR criteria at baseline, 9% and 8%, respectively, had progressed and met them at followup. Those with hypergammaglobulinemia and hypocomplementemia at study entry were, respectively, 4 and 6 times more likely to progress to SS by ACR criteria than those without these characteristics (95% confidence interval 1.5–10.1 and 1.8–20.4, respectively).

Conclusion

While there was stability over a 2–3‐year period of both individual phenotypic features of SS and of SS status, hypergammaglobulinemia and hypocomplementemia at study entry were predictive of progression to SS.

     

R219K polymorphism of the ABCA1 gene and its modulation of the variations in serum high-density lipoprotein cholesterol and triglycerides related to age and adiposity in white versus black young adults. The Bogalusa heart study

Mutations in adenosine triphosphate (ATP)-binding cassette transporter 1 (ABCA1) gene have been established as the molecular defect in Tangier disease and familial hypoalphalipoproteinemia, uncommon genetic disorders characterized by deficient or depressed high-density lipoprotein (HDL) cholesterol and increased triglycerides. However, information regarding the frequency of common variants, including Arg219Lys (R219K) within the coding region of the ABCA1 gene and their effect on these phenotypes in the general population is limited. This study examined the frequency and phenotypic effect of R219K variant in a community-based sample of 887 white and 390 black young adults aged 20 to 38 years. The frequency of the variant allele (K219) was higher in blacks than in whites (0.595 v 0.262, P<.001), with carriers (KK+RK) representing 83.8% of blacks versus 44.2% of whites. After adjusting for age, body mass index (BMI), and sex, the genotype effect on HDL cholesterol and natural logarithm of triglycerides was not apparent in whites or blacks. However, significant interaction effects of genotype and age on HDL cholesterol (P<.001) and genotype and BMI on triglycerides (P=.029) were found in whites. Carriers (KK+RK), unlike noncarriers (RR) showed a positive relationship between age and HDL cholesterol (regression coefficient beta=0.28, P=.029 for carriers v beta=-0.18, P=.112 for noncarriers). In addition, the variant allele attenuated the adverse positive relationship between BMI and triglycerides (beta=0.032, P<.001 for carriers v beta=0.046, P<.001 for noncarriers). These results indicate that the K219 allele frequency differs markedly between blacks and whites, and that the variant-allele modulates the association between age and HDL cholesterol, as well as body fatness and triglycerides in a beneficial manner only in whites.     

Post-natal thyroid function in low birth weight infants; a longitudinal assessment of free thyroxine and thyroid hormone binding globulin

Because the concentrations of serum free thyroxine (FT4) and thyroid hormone binding globulin (TBG) have not been fully evaluated in preterm infants at the immediate post-natal period, we studied the longitudinal changes of serum FT4 and TBG, along with thyroxine (T4) and thyroid stimulating hormone (TSH), at birth (cord blood), 2 days, 1 week and 2 weeks of age in 7 infants with birth body weight less than or equal to 1000 g, 7 infants with body weight 1001 to 1350 g, 11 infants with body weight 1351 to 2499 g, and 11 full-term infants. Free T4 concentrations were measured by Corning Medical radioimmunoassay (RIA) kit. The infants with extremely low birth weight (ELBW) (body weight less than or equal to 1000 g) showed precipitous declines of total T4 and, to a lesser extent, of FT4 concentrations at 1 and 2 weeks of age. These post-natal T4 and FT4 decreases in ELBW neonates have not previously been reported. The clinical significance of this finding remains, speculative, but it may be due to metabolic or nutritional problems related to extreme prematurity itself. This study suggests that measurement of FT4 is a useful adjunct to the assessment of ELBW infants with very low T4 values, if done between 1 to 2 weeks of age, and could be used as a primary hypothyroid screening tool instead of T4 measurements, provided that an FT4 assay is developed that uses the elute of blood spotted on filter paper.     

Efficacy of tranexamic acid as compared to aprotinin in open heart surgery in children

Background:

Coagulopathy is a major issue in children undergoing high-risk pediatric cardiac surgery. Use of anti-fibrinolytics is well documented in adults, but recently there are questions raised about safety and effectiveness of their use on routine use. Tranexamic acid is a potent anti-fibrinolytic, but its role is not fully understood in children. This study aims to study the benefits tranexamic acid in controlling postoperative bleeding in pediatric cardiac surgical patients.

Methods and Results:

Fifty consecutive children who underwent cardiac surgery were randomized prospectively to receive either aprotinin (Group A; n = 24) or tranexamic acid (Group B; n = 26) from September 2009 to February 2010 were studied. Primary end points were early mortality, postoperative drainage, reoperation for bleeding and complications. Mean age and body weight was smaller in Group A (Age: 48.55 vs. 64.73 months; weight 10.75 vs. 14.80 kg) respectively. Group A had more cyanotic heart disease than Group B (87.5% vs. 76.92%). Mean cardiopulmonary bypass time (144.33 vs. 84.34 min) and aortic cross-clamp time (78.5 vs. 41.46 min) were significantly higher in group A. While the blood and products usage was significantly higher in Group A, there was no difference in indexed postoperative drainage in first 4, 8 and 12 h and postoperative coagulation parameters. Mean C-reactive protein was less in Group A than B and renal dysfunction was seen more in Group A (25% vs. 7.6%). Mortality in Group A was 16.66% and 7.6% in Group B.

Conclusion:

Anti-fibrinolytics have a definitive role in high-risk children who undergo open-heart surgery. Tranexamic acid is as equally effective as aprotinin with no additional increase in morbidity or mortality.

Ultramini Abstract:

Coagulopathy has been a major issue in pediatric cardiac surgery, and anti-fibrinolytics have been used fairly regularly in various settings. This study aims to evaluate the efficacy of tranexamic acid as compared against that of aprotinin in a randomized model. Tranexamic acid proves to be equally effective with less toxicity with no added mortality.     

Siglec-7 expression is reduced on a natural killer (NK) cell subset of obese humans

Obesity leads to an altered adipocytokine production negatively effecting the function of natural killer cells (NK cells), which are important effector cells of the innate immune system. NK cells provide a defence against tumour cells or virus infected cells and have different activating and inhibitory surface receptors to distinguish between normal and transformed cells. One group of the inhibitory receptors are the sialic acid-binding immunoglobulin-like lectins (Siglecs). The aim of this study was to compare the expression of Siglecs-7, -9 and -10 on NK cells from normal weight and obese subjects. Therefore peripheral blood mononuclear cells (PBMC) were isolated from 10 normal weight (BMI < 25 kg/m²) and 11 obese (BMI > 30 kg/m²) blood donors and analysed by flow cytometry. Moreover, the amount of sialic acid on NK cell was determined using a fluorescent labelled lectin that binds terminal sialic acids. Percentages of immune cells were not altered between normal weight and obese individuals. CD56^bright NK cells from obese subjects had a reduced expression of Siglec-7 while the expression of Siglec-9 was not altered. The reduction of Siglec-7 expression on CD56^bright NK cells might be a marker for their dysfunction. Moreover, Siglecs-7, -9 and -10 are not expressed on the NK cell lines NK-92 and NKL. When comparing the two NK cell subpopulations CD56^bright and CD56^dim, CD56^bright NK cells had a higher amount of sialic acids on their surface compared to CD56^dim NK cells regardless of body weight.     

A novel MIS technique for posterior cruciate ligament avulsion fractures

Objective

Open surgical approaches to treat tibial avulsion fractures of the posterior cruciate ligament (PCL) often use large incisions involving extensive muscle dissection and retraction. The objective of this study was to describe a new mini-invasive approach targeting the fractured zone, to minimize surgical dissection and improve recovery and rehabilitation.