Cancer incidence in immunocompromised patients: a single-center cohort study.

BACKGROUND: Diminished immune defense plays an important role in cancer development. Cancer risk in immunocompromised patients may differ. Identifying individuals with elevated cancer risk can inform strategies for routine cancer screening. This study aimed to understand and compare cancer incidence and risk in three patient groups: recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT); diagnosis of primary or secondary immunodeficiency disorder (PID/SID); and recipients of tumor necrosis factor inhibitor (TNF-i) therapy. METHODS: This retrospective cohort study used the University of Utah Health System database and Huntsman Cancer Institute tumor registry. Patients aged ≥18 years with SOT/HSCT, PID/SID or ≥ 3 months of TNF-i therapy were included. The date of transplant, diagnosis of PID/SID, or 1st TNF-i medication order date was defined as the index date. We calculated cumulative cancer incidence by Kaplan-Meier method. A Cox-proportional hazard regression model with a stepwise variable selection process was used to identify independent risk factors associated with the time to onset of a new primary cancer. RESULTS: In total, 13,887 patients were included which comprised of 2982 (21%) SOT/HSCT, 7542 (54%) PID/SID and 3363 (24%) patients receiving TNF-i. The mean (SD) age ranged from 46.8 (15) years - 50.4 (18.2) years. The proportion of white patients ranged from 72.3-84.8%. The estimated cumulative cancer incidence was 11.5% in the SOT/HSCT cohort, 14.3% in the PID/SID cohort, and 8.8% in the TNF-i cohort. The multivariable model adjusted for age, benign in-situ disease, Charlson Comorbidity Index, hypertension/cardiovascular disease/end stage renal disease, gender, race/ethnicity, and renal cyst as significant risk factors. The adjusted hazard ratios for cancer development in SOT/HSCT and PID/SID cohorts compared to the TNF-i cohort over the full follow-up period were 1.57 (95% CI: 1.16-2.13) and 2.14 (95% CI: 1.65-2.77), respectively. CONCLUSION: A significantly increased risk of cancer was observed in PID/SID patients and SOT/HSCT patients compared to TNF-i patients. Age ≥ 50 years, male gender, and clinical comorbidities were additional factors impacting cancer risk. PID/SID and SOT/HSCT patients may benefit from more intensive cancer screening.

Polymorphism in the serotonin transporter gene polymorphisms ( 5-HTTLPR) modifies the association between significant life events and depression in people with multiple sclerosis.

BACKGROUND: In the general population, variation in the serotonin-transporter-linked polymorphic region ( 5-HTTLPR) has been shown to modify the association between stressful events and depression/anxiety. This has not been examined in people with multiple sclerosis (MS). OBJECTIVE: We examined the interaction between significant life events (SLE), 5-HTTLPR and depression/anxiety. METHODS: A population-based longitudinal cohort of 198 people with MS was followed biannually for 2.5 years. Depression and anxiety symptoms were measured at each review using the Hospital Anxiety and Depression Scale (HADS). SLEs were assessed using a questionnaire based on the Social Readjustment Rating Scale. RESULTS: We found an interaction between SLE load in the previous 12 months and functional variation in the 5-HTTLPR allele type in predicting depression, with the association between SLE load and depression being stronger for those with S/S allele type (ß = 0.21 (95% confidence interval (CI): 0.09-0.33) per 10-unit increase) and S/L (ß = 0.14 (95% CI: 0.05-0.24)) compared to L/L allele type (ß = 0.04 (95% CI: -0.05 to 0.24); pinteraction < 0.001). No convincing evidence of an interaction was found with anxiety. CONCLUSION: We found that the association between SLE load and MS depression severity was stronger among those with one or two copies of the short allele of the 5-HTTLPR. The identification of a gene-environment interaction between SLEs and depression in a population where depression is partly disease-driven is novel.

Effects of nitrogen fertilization on soil nutrient concentration and phosphatase activity and forage nutrient uptake from a grazed pasture system.

Over a 3-year period, the effect of differing N-application regimes on soil extractable-P concentration, soil phosphatase activity, and forage P uptake in a P-enriched grazed-pasture system was investigated. In the fall of each year, six 0.28-ha plots were overseeded with triticale ( × Triticosecale rimpaui Wittm.) and crimson clover (Trifolium incarnatum) into a tall fescue (Lolium arundinacea)/bermudagrass (Cynodon dactylon) sod and assigned to 1 of 3 N-fertilizer treatments (n = 2): 100% of N recommendation in a split application (100N), 50% in a single application (50N), and 0% of N recommendation (0N) for triticale. Cattle commenced grazing the following spring and grazed until May. In the summer, plots were overseeded with cowpea (Vigna unguiculata), fertilized at the same rates by reference to N recommendations for bermudagrass, and grazed by cattle until September. There were no effects of N fertilization on soil phosphatase activity, electrical conductivity, or concentrations of water-soluble P. Concentrations of extractable P decreased in plots receiving 50N, but increasing N fertilization to 100N resulted in no further reduction in extractable P. Forage biomass, foliar P concentrations, and forage P mass were not affected by N fertilization rates at the plant-community level, but responses were observed within individual forage species. Results are interpreted to mean that N fertilization at 50% of the agronomic recommendation for the grass component can increase forage P mass of specific forages and decrease soil extractable P, thus providing opportunity for decreasing P losses from grazed pasture.

Performance of the CellaVision(®) DM96 system for detecting red blood cell morphologic abnormalities.

BACKGROUND: Red blood cell (RBC) analysis is a key feature in the evaluation of hematological disorders. The gold standard light microscopy technique has high sensitivity, but is a relativity time-consuming and labor intensive procedure. This study tested the sensitivity and specificity of gold standard light microscopy manual differential to the CellaVision(®) DM96 (CCS; CellaVision, Lund, Sweden) automated image analysis system, which takes digital images of samples at high magnification and compares these images with an artificial neural network based on a database of cells and preclassified according to RBC morphology. METHODS: In this study, 212 abnormal peripheral blood smears within the Calgary Laboratory Services network of hospital laboratories were selected and assessed for 15 different RBC morphologic abnormalities by manual microscopy. The same samples were reassessed as a manual addition from the instrument screen using the CellaVision(®) DM96 system with 8 microscope high power fields (×100 objective and a 22 mm ocular). The results of the investigation were then used to calculate the sensitivity and specificity of the CellaVision(®) DM96 system in reference to light microscopy. RESULTS: The sensitivity ranged from a low of 33% (RBC agglutination) to a high of 100% (sickle cells, stomatocytes). The remainder of the RBC abnormalities tested somewhere between these two extremes. The specificity ranged from 84% (schistocytes) to 99.5% (sickle cells, stomatocytes). CONCLUSIONS: Our results showed generally high specificities but variable sensitivities for RBC morphologic abnormalities.

Performance of CellaVision DM96 in leukocyte classification.

BACKGROUND: Leukocyte differentials are an important component of clinical care. Morphologic assessment of peripheral blood smears (PBS) may be required to accurately classify leukocytes. However, manual microscopy is labor intensive. The CellaVision DM96 is an automated system that acquires digital images of leukocytes on PBS, pre-classifies the cell type, and displays them on screen for a Technologist or Pathologist to approve or reclassify. Our study compares the results of the DM96 with manual microscopy. METHODS: Three hundred and fifty-nine PBS were selected and assessed by manual microscopy with a 200 leukocyte cell count. They were then reassessed using the CellaVision DM96 with a 115 leukocyte cell count including reclassification when necessary. Correlation between the manual microscopy results and the CellaVision DM96 results was calculated for each cell type. RESULTS: The correlation coefficients (r (2)) range from a high of 0.99 for blasts to a low of 0.72 for metamyelocytes. CONCLUSIONS: The correlation between the CellaVision DM96 and manual microscopy was as good or better than the previously published data. The accuracy of leukocyte classification depended on the cell type, and in general, there was lower correlation for rare cell types. However, the correlation is similar to previous studies on the correlation of manual microscopy with an established reference result. Therefore, the CellaVision DM96 is appropriate for clinical implementation.

Platelet count estimation using the CellaVision DM96 system.

INTRODUCTION: Rapid and accurate determination of platelet count is an important factor in diagnostic medicine. Traditional microscopic methods are labor intensive with variable results and are highly dependent on the individual training. Recent developments in automated peripheral blood differentials using a computerized system have shown many advantages as a viable alternative. The purpose of this paper was to determine the reliability and accuracy of the CellaVision DM 96 system with regards to platelet counts. MATERIALS AND METHODS: One hundred twenty seven peripheral blood smears were analyzed for platelet count by manual microscopy, an automated hematology analyzer (Beckman Counter LH 780 or Unicel DXH 800 analyzers) and with the CellaVision DM96 system. Results were compared using the correlations and Bland-Altman plots. RESULTS: Platelet counts from the DM96 system showed an R(2) of 0.94 when compared to manual platelet estimates and an R(2) of 0.92 when compared to the automated hematology analyzer results. Bland-Altman plots did not show any systematic bias.

Ammonia emissions from field-simulated cattle defecation and urination.

Atmospheric ammonia (NH(3)) is a concern because of its environmental impact. The greatest contribution to atmospheric NH(3) comes from agricultural sources. This study quantified NH(3) volatilization from cattle defecation and urination on pasture under field conditions in Auburn, Alabama. Treatments consisted of beef feces, dairy feces, dairy urine, and a control. The experiment was conducted during four seasons from June 2003 to April 2004. Fresh feces or urine was applied onto grass swards, and NH(3) volatilization was measured up to 14 d after application using an inverted chamber method. Dairy urine was the only significant source of NH(3). Ammonia nitrogen (N) loss differed among seasons, ranging from 1.8% in winter to 20.9% during the warmer summer months. Cumulative volatilization was best described in this experiment by the equation % NH(3)-N loss = N(max) (1 - e(-ct))(i). The highest rate of NH(3) volatilization generally occurred within 24 h. This study suggests that NH(3) volatilization from cattle urine on pasture is significant and varies with season, whereas NH(3) volatilization from cattle feces is negligible.