Infants with Down syndrome and congenital heart disease have altered peri-operative immune responses.

BACKGROUND: Infants with Down syndrome (DS) have an altered immune response. We aimed to characterise the inflammatory response in infants with DS and congenital heart disease (CHD) peri-operatively in comparison to infants with CHD and a normal chromosomal complement, and to healthy infants pre-operatively. METHODS: Infants with DS/CHD, infants without DS but with CHD (CHD only) and healthy infants were prospectively recruited and serial serum cytokines evaluated peri-operatively using multiplex ELISA: tumour necrosis factor (TNF)-α and TNF-ß; interferon (IFN)-γ, interleukin (IL)-1α, IL-2, IL-6, IL-8, IL-18, IL-1ß, IL-10, and IL-1ra; vascular endothelial growth factor (VEGF); granulocyte macrophage colony-stimulating factor (GM-CSF); and erythropoietin (EPO). RESULTS: Ninety-four infants were recruited including age-matched controls (n = 10), DS/CHD (n = 55), and CHD only (n = 29). Children with DS/CHD had significantly lower concentrations of several cytokines (IL-10, IL-6, IL-8, IL-1ß, VEGF) in the pre- and post-operatively vs CHD only and controls. EPO and GM-CSF were significantly higher in DS/CHD (p value <0.05). CONCLUSIONS: Children with DS/CHD had significantly lower concentrations of several cytokines compared to controls or children with CHD only. EPO and GM-CSF were significantly higher in children with DS/CHD. The assessment of the immune response may be suitable for the predictable clinical outcomes in these children. IMPACT: This study demonstrated that children with Down syndrome (DS) and congenital heart disease (CHD) have significant alterations in pro-inflammatory and anti-inflammatory immune responses peri-operatively. These changes may contribute to adverse clinical outcomes, including sepsis, chylothorax, and autoimmunity. They may impact the pathogenesis and outcome post-operatively and long term in this population. Children with DS and CHD have significantly lower cytokine concentrations, increased EPO and GM-CSF, and decreased VEGF pre- and post-operatively. Assessing their inflammatory state peri-operatively may facilitate the development of a predictive model that can inform tailored management of these infants using novel therapies including immunomodulation.

The patient-centered medical home: a case study in transforming the military health system.

This case study describes the Military Health System's (MHS) patient-centered medical home (PCMH) initiative and how it is being delivered across the MHS by the Army, Navy, and Air Force. The MHS, an integrated delivery model that includes both military treatment facilities and civilian providers and health care institutions, is transforming its primary care platforms from the traditional acute, episodic system to the PCMH model of care to maximize patient experience, satisfaction, health care quality, and readiness and to control cost growth. Preliminary performance measures are analyzed to assess the impact of PCMH implementation on the core primary care processes of the MHS. This study also discusses lessons learned and recommendations for improving health care performance through the PCMH care model.

Patient-centered medical home: an emerging primary care model and the military health system.

The patient-centered medical home (PCMH) is a primary care model that aims to provide quality care that is coordinated, comprehensive, and cost-effective. PCMH is hinged upon building a strong patient-provider relationship and using a team-based approach to care to increase continuity and access. It is anticipated that PCMH can curb the growth of health care costs through better preventative medicine and lower utilization of services. The Navy, Air Force, and Army are implementing versions of PCMH, which includes the use of technologies for improved documentation, better disease management, improved communication between the care teams and patients, and increased access to care. This article examines PCMH in the Military Health System by providing examples of the transition from each of the branches. The authors argue that the military must overcome unique challenges to implement and sustain PCMH that civilian providers may not face because of the deployment of patients and staff, the military's mission of readiness, and the use of both on-base and off-base care by beneficiaries. Our objective is to lay out these considerations and to provide ways that they have been or can be addressed within the transition from traditional primary care to PCMH.

Differences in expression of junctional adhesion molecule-A and beta-catenin in multiple sclerosis brain tissue: increasing evidence for the role of tight junction pathology.

Previously we have employed antibodies to the tight junction (TJ)-associated proteins ZO-1 and occludin to describe endothelial tight junction abnormalities, in lesional and normal appearing white matter, in primary and secondary progressive multiple sclerosis (MS). This work is extended here by use of antibodies to the independent TJ-specific proteins and junctional adhesion molecule A & B (JAM-A, JAM-B). We have also assessed the expression in MS of beta-catenin, a protein specific to the TJ-associated adherens junction. Immunocytochemistry and semiquantitative confocal microscopy for JAM-A and beta-catenin was performed on snap-frozen sections from MS cases (n=11) and controls (n=6). Data on 1,443 blood vessels was acquired from active lesions (n=13), inactive lesions (n=13), NAWM (n=20) and control white matter (n=13). In MS abnormal JAM-A expression was found in active (46%) and inactive lesions (21%), comparable to previous data using ZO-1. However, a lower level of TJ abnormality was found in MS NAWM using JAM-A (3%) compared to ZO-1 (13%). JAM-B was strongly expressed on a small number of large blood vessels in control and MS tissues but at too low a level for quantitative analysis. By comparison with the high levels of abnormality observed with the TJ proteins, the adherens junction protein beta-catenin was normally expressed in all MS and control tissue categories. These results confirm, by use of the independent marker JAM-A, that TJ abnormalities are most frequent in active white matter lesions. Altered expression of JAM-A, in addition to affecting junctional tightness may also both reflect and affect leukocyte trafficking, with implications for immune status within the diseased CNS. Conversely, the adherens junction component of the TJ, as indicated by beta-catenin expression is normally expressed in all MS and control tissue categories.

Improvements in glycemic control in type 2 diabetes patients switched from sulfonylurea coadministered with metformin to glyburide-metformin tablets.

OBJECTIVE: To evaluate the change in hemoglobin A1C (A1C) in patients with type 2 diabetes switched from coadministration of a sulfonylurea (SU), glyburide or glipizide, and metformin (SU+Met) to a single glyburide-metformin tablet. METHODS: A retrospective cohort study design of patients with type 2 diabetes treated at 3 Veterans Affairs Medical Centers and 1 Department of Defense Medical Center was utilized. One hundred percent of patients receiving glyburide-metformin tablets were screened for inclusion. Patients with at least 6 months of prior SU+Met combination therapy and a baseline A1C measured within 35 days prior to or 3 days after switch to glyburide-metformin tablets were included. At least one documented follow-up A1C at >or=90 days after the switch to glyburide-metformin was required for inclusion. Glycemic control, complications, lipid parameters, concomitant medications, and weight were analyzed prior to and following the switch to glyburide-metformin. RESULTS: Seventy-two patient records were included after the disqualification criteria excluded 488 prospective patients. The mean age of the 72 patients was 62 years; average body mass index was 32.9 kg/m2, average baseline A1C was 8.3%, and the average time since diagnosis was 7.6 years. The mean reduction in A1C was 0.6% (P=0.002) at a mean follow-up of 196 days after the switch to glyburide-metformin tablets. Improvement in glycemic control was predominantly seen in patients with a baseline A1C >or=8% in whom a 1.3% mean reduction in A1C (P=0.0002) was achieved despite a lower mean final dose of glyburide. CONCLUSION: The results of this study suggest that in type 2 diabetic patients with an A1C >or=8%, switching from coadministration of a sulfonylurea plus metformin to combination glyburide-metformin tablets may provide an improvement in glycemic control in the range of a 1.2 to 1.4 absolute percentage point decrease in A1C. A randomized, prospective trial comparing these 2 methods of treatment is needed, however, to determine the precise effect provided by the unique formulation of glyburide in the glyburide-metformin tablet.