Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment.

Our objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy. We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucleo(t)side analogue-treated patients who achieved HBsAg loss with peg-interferon-α(peg-IFN-α) add-on or switch treatment in a randomised clinical trial. Cytokines/chemokines from plasma were compared between those with/without HBsAg loss, at baseline, before and after HBsAg loss. Peg-IFN-α treatment resulted in higher levels of IL-27, IL-12p70, IL-18, IL-13, IL-4, IL-22 and GM-CSF prior to HBsAg loss. Probabilistic network analysis of cytokines, chemokines and soluble factors suggested a dynamic dendritic cell driven NK and T cell immune response associated with HBsAg loss. Bayesian network analysis showed a dominant myeloid-driven type 1 inflammatory response with a MIG and I-TAC central module contributing to HBsAg loss in the add-on arm. In the switch arm, HBsAg loss was associated with a T cell activation module exemplified by high levels of CD40L suggesting T cell activation. Our findings show that more than one immune pathway to HBsAg loss was found with peg-IFN-α therapy; by myeloid-driven Type 1 response in one instance, and T cell activation in the other.

Met-Flow, a strategy for single-cell metabolic analysis highlights dynamic changes in immune subpopulations.

A complex interaction of anabolic and catabolic metabolism underpins the ability of leukocytes to mount an immune response. Their capacity to respond to changing environments by metabolic reprogramming is crucial to effector function. However, current methods lack the ability to interrogate this network of metabolic pathways at single-cell level within a heterogeneous population. We present Met-Flow, a flow cytometry-based method capturing the metabolic state of immune cells by targeting key proteins and rate-limiting enzymes across multiple pathways. We demonstrate the ability to simultaneously measure divergent metabolic profiles and dynamic remodeling in human peripheral blood mononuclear cells. Using Met-Flow, we discovered that glucose restriction and metabolic remodeling drive the expansion of an inflammatory central memory T cell subset. This method captures the complex metabolic state of any cell as it relates to phenotype and function, leading to a greater understanding of the role of metabolic heterogeneity in immune responses.

Causes of delay in door-to-balloon time in south-east Asian patients undergoing primary percutaneous coronary intervention.

OBJECTIVE: To evaluate causes and impact of delay in the door-to-balloon (D2B) time for patients undergoing primary percutaneous coronary intervention (PPCI). SUBJECTS AND METHODS: From January 2009 to December 2012, 1268 patients (86% male, mean age of 58 ± 12 years) presented to our hospital for ST-elevation myocardial infarction (STEMI) and underwent PPCI. They were divided into two groups: Non-delay defined as D2B time ≤ 90 mins and delay group defined as D2B time > 90 mins. Data were collected retrospectively on baseline clinical characteristics, mode of presentation, angiographic findings, therapeutic modality and inhospital outcome. RESULTS: 202 patients had delay in D2B time. There were more female patients in the delay group. They were older and tend to self-present to hospital. They were less likely to be smokers and have a higher prevalence of prior MI. The incidence of posterior MI was higher in the delay group. They also had a higher incidence of triple vessel disease. The 3 most common reasons for D2B delay was delay in the emergency department (39%), atypical clinical presentation (37.6%) and unstable medical condition requiring stabilisation/computed tomographic imaging (26.7%). The inhospital mortality was numerically higher in the delay group (7.4% versus 4.8%, p = 0.12). CONCLUSIONS: Delay in D2B occurred in 16% of our patients undergoing PPCI. Several key factors for delay were identified and warrant further intervention.

Clinical outcomes of elderly South-East Asian patients in primary percutaneous coronary intervention for ST-elevation myocardial infarction.

OBJECTIVE: To evaluate the clinical characteristics and in-hospital outcomes of elderly South-East Asian patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: From January 2009 to December 2012, 1268 patients (86.4% male, mean age of 58.4 ± 12.2 years) presented to our hospital for ST-elevation myocardial infarction (STEMI) and underwent PPCI. They were divided into two groups: elderly group defined as age ≥ 70 years and non-elderly group defined as age < 70 years. Data were collected retrospectively on baseline clinical characteristics, door-to-balloon (D2B) time, angiographic findings, therapeutic modality and hospital course. RESULTS: The elderly group constituted 19% of the study population with mean age 76.6 ± 5.0 years. There was a higher proportion of female gender and ethnic Chinese patients in the elderly group when compared with the non-elderly group. The former was less likely to be smokers and have a significantly higher prevalence of hypertension. The mean D2B time was significantly longer in the elderly group. They also had a significantly higher incidence of triple vessel disease and obstructive left main disease. The use of radial artery access, glycoprotein 2b/3a inhibitors and drug-eluting stents during PPCI were also significantly lower. In-hospital mortality was significantly higher in the elderly group. The rate of cardiogenic shock and inhospital complications were also significantly higher. CONCLUSIONS: Our registry showed that in-hospital mortality rate in elderly South-East Asian patients undergoing PPCI for STEMI was high. Further studies into the optimal STEMI management strategy for these elderly patients are warranted.