Increased inflammatory low-density neutrophils in severe obesity and effect of bariatric surgery: Results from case-control and prospective cohort studies.

BACKGROUND: Low-density neutrophils (LDN) are increased in several inflammatory diseases and may also play a role in the low-grade chronic inflammation associated with obesity. Here we explored their role in obesity, determined their gene signatures, and assessed the effect of bariatric surgery. METHODS: We compared the number, function, and gene expression profiles of circulating LDN in morbidly obese patients (MOP, n=27; body mass index (BMI) > 40 Kg/m2) and normal-weight controls (NWC, n=20; BMI < 25 Kg/m2) in a case-control study. Additionally, in a prospective longitudinal study, we measured changes in the frequency of LDN after bariatric surgery (n=36) and tested for associations with metabolic and inflammatory parameters. FINDINGS: LDN and inflammatory markers were significantly increased in MOP compared to NWC. Transcriptome analysis showed increased neutrophil-related gene expression signatures associated with inflammation, neutrophil activation, and immunosuppressive function. However, LDN did not suppress T cells proliferation and produced low levels of reactive oxygen species (ROS). Circulating LDN in MOP significantly decreased after bariatric surgery in parallel with BMI, metabolic syndrome, and inflammatory markers. INTERPRETATION: Obesity increases LDN displaying an inflammatory gene signature. Our results suggest that LDN may represent a neutrophil subset associated with chronic inflammation, a feature of obesity that has been previously associated with the appearance and progression of co-morbidities. Furthermore, bariatric surgery, as an efficient therapy for severe obesity, reduces LDN in circulation and improves several components of the metabolic syndrome supporting its recognized anti-inflammatory and beneficial metabolic effects. FUNDING: This work was supported in part by grants from the National Institutes of Health (NIH; 5P30GM114732-02, P20CA233374 - A. Ochoa and L. Miele), Pennington Biomedical NORC (P30DK072476 - E. Ravussin & LSU-NO Stanley S. Scott Cancer Center and Louisiana Clinical and Translational Science Center (LACaTS; U54-GM104940 - J. Kirwan).

Two Cases of Armour Thyroid Interference in Thyroglobulin Monitoring for Thyroid Cancer.

Thyroglobulin (Tg) monitoring is the biochemical standard for surveillance of recurrent differentiated thyroid cancer (DTC). Several assays are available to quantify Tg levels: immunometric assay (IMA), radioimmunoassay (RIA), and the newer liquid chromatography tandem mass spectrometry (LC-MS). It is well known that a number of entities can interfere with the accuracy of testing, and at this point in time, no one assay perfectly balances high sensitivity with low risk of interference. In this case study, we present two cases in which treatment with desiccated thyroid extract (Armour thyroid) led to a sudden elevation in Tg, which resolved when Armour thyroid was discontinued. This elevation occurred when Tg was measured with both IMA and LC-MS, which suggests direct interference from porcine Tg rather than heterophilic or thyroglobulin antibody (TgAb) interference. We suggest that patients with a history of DTC not be treated with desiccated thyroid extracts consistent with guidelines. Furthermore, more advances need to be made in the area of Tg testing to improve specificity and avoid detection of nonhuman Tg and other similar proteins.

Phoma Infections: Classification, Potential Food Sources, and Its Clinical Impact.

Phoma species are phytopathogens that are widely distributed in the environment, most commonly found in aquatic systems and soil. Phoma spp. have the potential to be pathogenic in plants, animals and humans; the latter is a rare occurrence. However, as our immunocompromised population increases, so do the reports of these infections. Medical advances have allowed for the increase in solid organ transplantation; chemotherapies to treat malignancies; and the use of other immunosuppressive agents, which have resulted in a greater population at risk when exposed to diverse fungi including Phoma spp. These fungi have been isolated from water sources, food, and crops; thus acting as opportunistic pathogens when the right host is exposed. Phoma spp. contaminates common food sources such as potatoes and maize, a common species isolated being Phoma sorghina. Though there is potential for causing infection via consumption of contaminated foods, there is insufficient data detailing what levels of organism can lead to an infection, and a regulated process for detecting the organism. The spectrum of disease is wide, depending on the host, ranging from cutaneous infections to invasive diseases. Mortality, however, remains low.