Using HIV Surveillance and Clinic Data to Optimize Data to Care Efforts in Community Health Centers in Massachusetts: The Massachusetts Partnerships for Care Project.

BACKGROUND: We describe Data to Care processes of the Massachusetts Partnerships for Care (MA P4C) project and identify factors associated with engagement, retention, and viral suppression outcomes. METHODS: The Massachusetts Department of Public Health and participating community health centers generated lists of patients not in care based on a temporal gap in laboratory results, missed clinic visits, and provider concern regarding engagement. The Massachusetts Department of Public Health and community health centers reviewed the lists monthly and identified out-of-care patients in need of linkage or re-engagement. RESULTS: Between October 2015 and June 2017, of 1418 patients potentially out of care, 83 (5.9%) were confirmed to be out of care. Forty-four of those out of care (53%) received services or were re-engaged in care within 90 days, 45 (54%) were retained in care, and 40 (48%) were virally suppressed. The odds of being re-engaged or retained were lower for patients who were 6 months out-of-care (vs. those newly diagnosed). Patients with an AIDS-defining condition had increased odds of retention and viral suppression. The odds of viral suppression were reduced for patients who reported exposure categories other than men who have sex with men and were younger (30-49 years vs. ≥50 years). CONCLUSIONS: Although rates of re-engagement, retention, and viral suppression were low, the MA P4C Data to Care procedures provided a means for accurate ascertainment of out-of-care status. Future Data to Care programs should investigate the factors that contribute to disengagement from care.

Randomised, double-blind, placebo-controlled trial of IL1-trap, rilonacept, in systemic sclerosis. A phase I/II biomarker trial.

OBJECTIVES: This clinical trial was designed to study the safety and efficacy of blocking IL-1 in skin fibrosis of patients with diffuse cutaneous systemic sclerosis (dcSSc), and to test the hypothesis that inhibition of IL-1 by rilonacept will downregulate expression of the 2G SSc gene biomarker as a surrogate for the modified Rodnan skin score (MRSS). METHODS: 19 dcSSc patients were randomised 2:1 active treatment:placebo in this double blinded trial. Study patients received weekly treatments with either subcutaneous rilanocept 320 mg loading dose at day 0 and then 160 mg for each of the 5 subsequent weekly doses, or placebo. Skin biopsies were taken to test 2G SSc biomarker gene expression at day 0 before treatment and one week after the final study drug dose, comparing gene expression changes between rilonacept- and placebo-treated patients, as well as the change in gene expression at week 6 compared to baseline in rilonacept-treated patients. Safety assessments extended to 6 weeks after the final dose of study drug or placebo. Other secondary outcome measures included global and IL-1-regulated gene expression, serum biomarkers and the MRSS. RESULTS: Rilonacept compared to placebo-treated patients did not show any treatment-related effect on the 2G SSc biomarker. Rilonacept treatment also failed to alter IL-6 expression in skin, serum IL-6, C-reactive protein, or CCL18, a marker of IL-6 activity in SSc. CONCLUSIONS: In this small trial we did not observe any effect of blocking IL-1 on clinical skin disease or biomarkers of IL-1 activity.

Inhibition of ß-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82.

Several studies have suggested that Wnts might contribute to skin fibrosis in systemic sclerosis (SSc) by affecting the differentiation of pluripotent dermal cells. We tested C-82, a therapeutic that inhibits canonical Wnt signaling by blocking the interaction of the protein CBP with ß-Catenin and inhibiting Wnt-activated genes. We used a trial design formulating C-82 for topical application and conducting a placebo-controlled, double-blinded clinical trial in which patients with diffuse cutaneous SSc were treated with C-82 or placebo on opposite forearms. C-82- compared with placebo-treated forearms did not show any clinical effect. Skin biopsies performed before and after treatment showed a very weak trend toward improvement in the C-82-treated skin of biomarkers of local skin disease, THBS1 and COMP. However, on microarray analysis C-82 treatment strongly up-regulated two clusters of genes that correlate negatively with the severity of SSc skin disease. These clusters are highly associated with metabolism and one gene, PLIN2, expressed only by sebocytes and subcutaneous fat cells. These changes in gene expression strongly support a role for Wnts in differentiation of pluripotent cells into profibrotic fibroblasts and the potential for C-82 with longer treatment to promote fat regeneration in SSc skin.

Taurolidine antiadhesive properties on interaction with E. coli; its transformation in biological environment and interaction with bacteria cell wall.

The taurine amino-acid derivative, taurolidine, bis-(1,1-dioxoperhydro-1,2,4-thiabiazinyl-4)methane, shows broad antibacterial action against gram-positive and gram-negative bacteria, mycobacteria and some clinically relevant fungi. It inhibits, in vitro, the adherence of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. Taurolidine is unstable in aqueous solution and breaks down into derivatives which are thought to be responsible for the biological activity. To understand the taurolidine antibacterial mechanism of action, we provide the experimental single crystal X-ray diffraction results together with theoretical methods to characterize the hydrolysis/decomposition reactions of taurolidine. The crystal structure features two independent molecules linked through intermolecular H-bonds with one of them somewhat positively charged. Taurolidine in a biological environment exists in equilibrium with taurultam derivatives and this is described theoretically as a 2-step process without an energy barrier: formation of cationic taurolidine followed by a nucleophilic attack of O(hydroxyl) on the exocyclic C(methylene). A concerted mechanism describes the further hydrolysis of the taurolidine derivative methylol-taurultam. The interaction of methylol-taurultam with the diaminopimelic NH(2) group in the E. coli bacteria cell wall (peptidoglycan) has a negative DeltaG value (-38.2 kcal/mol) but a high energy barrier (45.8 kcal/mol) suggesting no reactivity. On the contrary, taurolidine docking into E. coli fimbriae protein, responsible for bacteria adhesion to the bladder epithelium, shows it has higher affinity than mannose (the natural substrate), whereas methylol-taurultam and taurultam are less tightly bound. Since taurolidine is readily available because it is administered in high doses after peritonitis surgery, it may successfully compete with mannose explaining its effectiveness against bacterial infections at laparoscopic lesions.