No abstract

BackgroundIdentification of serum proteins that track with disease course in sarcoidosis may have clinical and pathologic importance. We previously identified up-regulated transcripts for interferon-inducible chemokines CXCL9, and CXCL10, in blood of sarcoidosis patients compared to controls. The objective of this study was to determine whether proteins encoded by these transcripts were elevated in serum and identified patients with remitting vs. chronic progressive sarcoidosis longitudinally.MethodsSerum levels of CXCL9, CXCL10, and proteins associated with inflammation and/or disease activity (sIL2R, ACE, ESR and CRP) were measured in a prospective cohort of sarcoidosis subjects and controls. Comparisons were made between groups and clinical course using pulmonary function measures and a severity score developed by Wasfi et al.ResultsIn a cross-sectional analysis of 36 non-immunosuppressed sarcoidosis subjects, serum CXCL9, CXCL10, and sIL2R were significantly elevated compared to 46 controls (p < 0.0001). CXCL9 and CXCL10 were strongly inter-correlated (p = 0.0009). CXCL10 and CXCL9 were inversely correlated with FVC% predicted and DLCO% predicted, respectively. CXCL10 and CXCL9 significantly correlated with sarcoidosis severity score. sIL2R, ESR, CRP, and ACE serum levels did not correlate with pulmonary function measures or severity score. In the longitudinal analysis of 26 subjects, changes in serum CXCL10 level over time corresponded with progression versus remission of disease.ConclusionsInterferon-γ–inducible chemokines, CXCL9 and CXCL10, are elevated in sarcoidosis and inter-correlated with each other. Chemokine levels correlated with measures of disease severity. Serial measurements of CXCL10 corresponded to clinical course.

The STOP-D is a self-administered, self-report measure using two independent items that provide severity scores for depression and anxiety. The tool performs very well compared with other previously validated measures. Requiring no additional scoring and being free, STOP-D offers a simple and valid method for identifying hospitalized cardiac patients who are experiencing psychological distress. This crucial first step triggers initiation of appropriate monitoring and intervention, thus reducing the likelihood of the adverse cardiac outcomes associated with psychological distress.

We performed a literature review of composite metrics for describing the quality of glycemic control, as measured by continuous glucose monitors (CGMs). Nine composite metrics that describe CGM data were identified. They are described in detail along with their advantages and disadvantages. The primary benefit to using composite metrics in clinical practice is to be able to quickly evaluate a patient's glycemic control in the form of a single number that accounts for multiple dimensions of glycemic control. Very little data exist about (1) how to select the optimal components of composite metrics for CGM; (2) how to best score individual components of composite metrics; and (3) how to correlate composite metric scores with empiric outcomes. Nevertheless, composite metrics are an attractive type of scoring system to present clinicians with a single number that accounts for many dimensions of their patients' glycemia. If a busy health care professional is looking for a single-number summary statistic to describe glucose levels monitored by a CGM, then a composite metric has many attractive features.

We found few and variable operational definitions of PHD, despite American College of Cardiology/American Heart Association recommendations to report specific intervals. Worryingly, definitions of symptom onset, the most elusive component of PHD to establish, are uncommon. We recommend that researchers (a) report two PHD delay intervals (onset to decision to seek care, and decision to seek care to hospital arrival), and (b) develop, validate and use a definition of symptom onset. This will increase clarity and confidence in the conclusions from, and comparisons within and between studies.

Little is known about how the health status of incoming refugees to the United States compares to that of the general population. We used logistic regression to assess whether country of origin is associated with prevalence of hypertension, obesity, type-II diabetes, and tobacco-use among Iranian, Ukrainian and Vietnamese refugees arriving in California from 2002 to 2011 (N = 21,968). We then compared the prevalence among refugees to that of the Californian general population (CGP). Ukrainian origin was positively associated with obesity and negatively with smoking, while the opposite was true for Vietnamese (p < 0.001). Iranian origin was positively associated with type-II diabetes and smoking (p < 0.001). After accounting for age and gender differences, refugees had lower prevalence of obesity and higher prevalence of smoking than CGP. Individually, all refugee groups had lower type-II diabetes prevalence than CGP. Grouping all refugees together can hide distinct health needs associated with country of origin.

Summary Invariant natural killer T (iNKT) cells are integral components of immune responses during many chronic diseases, yet their surface phenotypes, subset distribution, and polyfunctional capacity in this environment are largely unknown. Therefore, using flow cytometry, we determined iNKT phenotypic and functional characteristics in subjects with the chronic inflammatory disease sarcoidosis and matched controls. We found that sarcoidosis subjects displayed lower iNKT frequencies, which correlated with lung fibrosis, C-reactive protein levels, and other measures of clinical disease. The CD4− CD8− (DN) iNKT cell population was selectively lower in diseased individuals and the remaining DN iNKT cells exhibited higher frequencies of the activation markers CD69 and CD56. Functionally, both total IFN-gamma+ and the dual-functional IFN-gamma+ TNF-alpha+ iNKT cells were decreased in sarcoidosis subjects and these functional defects correlated with total iNKT circulating frequencies. As the loss of polyfunctionality can reflect functional exhaustion, we measured the surface antigens PD-1 and CD57 and found that levels inversely correlated with dual-functional iNKT cell percentages. These findings reveal that, similar to traditional T cells, iNKT cells may also undergo functional exhaustion, and that circulating iNKT frequencies reflect these defects. PD-1 antagonists may therefore be attractive therapeutic candidates for sarcoidosis and other iNKT-mediated chronic diseases.

Background Well-differentiated thyroid carcinoma has a favorable prognosis, but patients with multiple recurrences have drastically lower survival. Filipinos in the US are known to have high thyroid cancer incidence and recurrence rates. It is unknown whether Filipinos also have higher thyroid cancer mortality rates. Methods We studied thyroid cancer mortality in Filipino, non-Filipino Asian (NFA), and non-Hispanic White (NHW) adults using US death records (2003–2012) and US Census data. Age-adjusted mortality rates (AMRs) and proportional mortality ratios (PMRs) were calculated. Gender, nativity status, age at death, and educational attainment were also examined. Results We examined 19,940,952 deaths. AMR due to thyroid cancer was highest in Filipinos (1.72 deaths per 100,000, 95% CI 1.51–1.95) compared to NFAs (1.03 per 100,000, 95% CI 0.95–1.12) and NHWs (1.17 per 100,000, 95% CI 1.16–1.18). Compared to NHWs, higher proportionate mortality was observed in Filipino women (3–5 times higher) across all age groups, and Filipino men had 2–3 times higher PMR in the subgroup over the age of 55. Filipinos that completed higher education had notably higher PMR (5.0) than their counterparts who had not (3.5). Conclusions Negative prognostic factors for thyroid cancer traditionally include “age greater than 45 years” and “male gender.” We demonstrate that Filipinos die of thyroid cancer at higher rates than NFAs and NHWs of similar ages. Highly-educated Filipinos and Filipino women may be especially at risk for poor thyroid cancer outcomes. Filipino ethnicity should be factored into clinical decision-making in the management of thyroid cancer.