Seasonal Variation in Vitamin D3 Levels Is Paralleled by Changes in the Peripheral Blood Human T Cell Compartment

It is well-recognized that vitamin D3 has immune-modulatory properties and that the variation in ultraviolet (UV) exposure affects vitamin D3 status. Here, we investigated if and to what extent seasonality of vitamin D3 levels are associated with changes in T cell numbers and phenotypes. Every three months during the course of the entire year, human PBMC and whole blood from 15 healthy subjects were sampled and analyzed using flow cytometry. We observed that elevated serum 25(OH)D3 and 1,25(OH)2D3 levels in summer were associated with a higher number of peripheral CD4+ and CD8+ T cells. In addition, an increase in naïve CD4+CD45RA+ T cells with a reciprocal drop in memory CD4+CD45RO+ T cells was observed. The increase in CD4+CD45RA+ T cell count was a result of heightened proliferative capacity rather than recent thymic emigration of T cells. The percentage of Treg dropped in summer, but not the absolute Treg numbers. Notably, in the Treg population, the levels of forkhead box protein 3 (Foxp3) expression were increased in summer. Skin, gut and lymphoid tissue homing potential was increased during summer as well, exemplified by increased CCR4, CCR6, CLA, CCR9 and CCR7 levels. Also, in summer, CD4+ and CD8+ T cells revealed a reduced capacity to produce pro-inflammatory cytokines. In conclusion, seasonal variation in vitamin D3 status in vivo throughout the year is associated with changes in the human peripheral T cell compartment and may as such explain some of the seasonal variation in immune status which has been observed previously. Given that the current observations are limited to healthy adult males, larger population-based studies would be useful to validate these findings

A propensity score-matched comparison of biodegradable polymer vs second-generation durable polymer drug-eluting stents in a real-world population

10.1111/1755-5922.12319CARDIOVASCULAR THERAPEUTICS36

Long-term antipsychotic treatment in schizophrenia: systematic review and network meta-analysis of randomised controlled trials

Background: For treatment of patients diagnosed with schizophrenia, comparative long-term effectiveness of antipsychotic drugs to reduce relapses when minimising adverse effects is of clinical interest, hence prompting this review. Aims To evaluate the comparative long-term effectiveness of antipsychotic drugs. Method We systematically searched electronic databases for reports of randomised controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing relapse risks in schizophrenia. We conducted network meta-analysis of 18 antipsychotics and placebo. Results: Studies of 10 177 patients in 56 reports were included; treatment duration averaged 48 weeks (range 4–156). Olanzapine was significantly more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI 0.14–0.88) or haloperidol (OR=0.50, 95% CI 0.30–0.82); and fluphenazine decanoate was more effective than chlorpromazine (OR=0.31, 95% CI 0.11–0.88) in relapse reduction. Fluphenazine decanoate, haloperidol, haloperidol decanoate and trifluoperazine produced more extrapyramidal adverse effects than olanzapine or quetiapine; and olanzapine was associated with more weight gain than other agents. Conclusions: Except for apparent superiority of olanzapine and fluphenazine decanoate over chlorpromazine, most agents showed intermediate efficacy for relapse prevention and differences among them were minor. Typical antipsychotics yielded adverse neurological effects, and olanzapine was associated with weight gain. The findings may contribute to evidence-based treatment selection for patients with chronic psychotic disorders. Declaration of interest R.J.B. received grants from the Bruce J. Anderson Foundation and the McLean Private Donors Psychopharmacology Research Fund. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence

Cost-Effectiveness of Serum Galactomannan Surveillance during Mould-Active Antifungal Prophylaxis

Serial galactomannan (GM) monitoring can aid the diagnosis of invasive aspergillosis (IA) and optimise treatment decisions. However, widespread adoption of mould-active prophylaxis has reduced the incidence of IA and challenged its use. We evaluated the cost-effectiveness of prophylaxis-biomarker strategies. A Markov model simulating high-risk patients undergoing routine GM surveillance with mould-active versus non-mould-active prophylaxis was constructed. The incremental cost for each additional quality-adjusted life-year (QALY) gained over a lifetime horizon was calculated. In 40- and 60-year-old patients receiving mould-active prophylaxis coupled with routine GM surveillance, the total cost accrued was the lowest at SGD 11,227 (USD 8255) and SGD 9234 (USD 6790), respectively, along with higher QALYs gained (5.3272 and 1.1693). This strategy, being less costly and more effective, dominated mould-active prophylaxis with no GM monitoring or GM surveillance during non-mould-active prophylaxis. The prescription of empiric antifungal treatment was influential in the cost-effectiveness. When the GM test sensitivity was reduced from 80% to 30%, as might be anticipated with the use of mould-active prophylactic agents, the conclusion remained unchanged. The likelihood of GM surveillance with concurrent mould-active prophylaxis being cost-effective was 77%. Routine GM surveillance remained cost-effective during mould-active prophylaxis despite lower IA breakthroughs. Cost-saving from reduced empirical antifungal treatment was an important contributing factor

When to Test for Anti-Interferon-gamma Autoantibody?

10.1093/cid/ciaa129CLINICAL INFECTIOUS DISEASES717E199-E19

Peripheral T cell (subset) numbers throughout the four seasons.

<p>A) Percentage (of live gate) and absolute numbers of CD4⁺ T cells. B) Percentage (of live gate) and absolute numbers of CD8⁺ T cells, over time. C) Percentage (within CD4⁺ T cells) and absolute counts, of CD4⁺CD45RA⁺ T cells. D) Percentage (within CD4⁺ T cells) and absolute counts, of CD4⁺CD45RO⁺ T cells. E) Percentage and absolute counts of Ki-67-expressing CD4⁺CD45RA⁺ T cells. Whole blood samples obtained from 15 healthy volunteers during each season were analyzed for the respective markers using flow cytometry. Ki-67 analysis was performed on PBMC. Data show results of viable cells from 15 healthy donors. * p<0.05 as compared to winter.</p

Skin, lymphoid tissue and gut homing receptor expression on CD4⁺CD25^hiCD127⁻ regulatory T cells.

<p>Percentage of Treg (within CD4⁺ T cells) and their level of expression (MFI) of A) CCR4, B) CCR6, C) CLA, D) CCR7 and E) CCR9 during the four seasons of the year. Whole blood from 15 healthy volunteers during each season was analyzed for the respective markers using flow cytometry. Data show results from 15 healthy donors. * p<0.05 as compared to winter.</p

Skin, lymphoid tissue and gut homing receptor expression on CD4⁺ T cells.

<p>Percentage and level of expression (MFI) of A) CCR4, B) CCR6, C) CLA, D) CCR7 and E) CCR9 by CD4⁺ T cells during the different seasons of the year. Whole blood from 15 healthy volunteers during each season was analyzed for the respective markers using flow cytometry. Data show results from 15 healthy donors. * p<0.05 as compared to winter.</p