The epigenetic factor PCAF regulates vascular inflammation and is essential for intimal hyperplasia development.

Objective: Genetic P300/CBP-associated factor (PCAF) variation affects restenosis-risk in patients. PCAF has lysine acetyltransferase activity and promotes nuclear factor kappa-beta (NFκB)-mediated inflammation, which drives post-interventional intimal hyperplasia development. We studied the contributing role of PCAF in post-interventional intimal hyperplasia.

TLR accessory molecule RP105 (CD180) is involved in post-interventional vascular remodeling and soluble RP105 modulates neointima formation.

Background: RP105 (CD180) is TLR4 homologue lacking the intracellular TLR4 signaling domain and acts a TLR accessory molecule and physiological inhibitor of TLR4-signaling. The role of RP105 in vascular remodeling, in particular post-interventional remodeling is unknown.

Methods And Results: TLR4 and RP105 are expressed on vascular smooth muscle cells (VSMC) as well as in the media of murine femoral artery segments as detected by qPCR and immunohistochemistry.

Lysine acetyltransferase PCAF is a key regulator of arteriogenesis.

Objective: Therapeutic arteriogenesis, that is, expansive remodeling of preexisting collaterals, using single-action factor therapies has not been as successful as anticipated. Modulation of factors that act as a master switch for relevant gene programs may prove more effective. Transcriptional coactivator p300-CBP-associated factor (PCAF) has histone acetylating activity and promotes transcription of multiple inflammatory genes.

Blocking toll-like receptors 7 and 9 reduces postinterventional remodeling via reduced macrophage activation, foam cell formation, and migration.

Objective: The role of toll-like receptors (TLRs) in vascular remodeling is well established. However, the involvement of the endosomal TLRs is unknown. Here, we study the effect of combined blocking of TLR7 and TLR9 on postinterventional remodeling and accelerated atherosclerosis.

Future potential biomarkers for postinterventional restenosis and accelerated atherosclerosis.

New circulating and local arterial biomarkers may help the clinician with risk stratification or diagnostic assessment of patients and selecting the proper therapy for a patient. In addition, they may be used for follow-up and testing efficacy of therapy, which is not possible with current biomarkers. Processes leading to postinterventional restenosis and accelerated atherosclerosis are complex due to the many biological variables mediating the specific inflammatory and immunogenic responses involved.

Genetic variation in PCAF, a key mediator in epigenetics, is associated with reduced vascular morbidity and mortality: evidence for a new concept from three independent prospective studies.

Aims: This study was designed to investigate the counterbalancing influence of genetic variation in the promoter of the gene encoding P300/CBP associated factor (PCAF), a lysine acetyltransferase (KAT), on coronary heart disease (CHD) and mortality.

Methods And Results: The association of genetic variation in the PCAF-gene with CHD, restenosis and mortality was investigated in three large cohorts. The results were combined to examine overall effects on CHD mortality and on restenosis risk.

Annexin A5 therapy attenuates vascular inflammation and remodeling and improves endothelial function in mice.

Objective: Annexin A5 (AnxA5) has antithrombotic, antiapoptotic, and antiinflammatory properties; we investigated its effectiveness against vascular inflammation, remodeling, and dysfunction in accelerated atherosclerosis.

Methods And Results: AnxA5 (1 mg/kg per day or vehicle) was investigated in vascular injury models in hypercholesterolemic apolipoprotein E (ApoE)3*Leiden mice. AnxA5 treatment reduced adhesion and infiltration of leukocytes by 71% to 69% (P=0.

Bond failure in clinical practice.

Background: It has been suggested that the small bonding pads and prominent profiles of self-ligating brackets may lead to high failure rates when compared with conventional edgewise brackets.

Aims: To compare the bond failure rates of a self-ligating bracket (Speed, Strite Industries, Cambridge, Canada) and a twin edgewise bracket (Mini-Diamond, Ormco, Orange, CA, U.S.

Permanent diversion rates after neoadjuvant therapy and coloanal anastomosis for rectal cancer.

Background: The aim of this study was to assess the rate of permanent diversion in patients undergoing coloanal anastomosis after neoadjuvant therapy for rectal cancer.

Methods: We performed a retrospective review of patients with rectal cancer who underwent a total mesorectal excision of a tumor within 9 cm of the anal verge.

Results: There were 201 patients who underwent resection with coloanal anastomosis, with a mean follow-up period of 51 months.

Risk of late bleeding following hemorrhoidal banding in patients on antithrombotic prophylaxis.

Background: The risk of bleeding following rubber band ligation of internal hemorrhoids is 1%-2%. This risk may be increased in patients taking antithrombotic therapy. The goal of the current study was to find a safer approach to banding without increasing the risk of bleeding.

Clinical outcomes of complicated diverticulitis managed nonoperatively.

Background: Surgical resection is typically recommended for patients with computed tomography (CT)-confirmed complicated diverticulitis. This study was designed to assess outcomes of patients with complicated diverticulitis managed nonoperatively.

Methods: A retrospective study covering 14 years evaluated patients with complicated diverticulitis diagnosed by CT scan.

The utility of intraluminal impedance in patients with gastroesophageal reflux disease-like symptoms but normal endoscopy and 24-hour pH testing.

Background & Aims: Fifty percent of patients with gastroesophageal reflux disease-like symptoms and negative endoscopy have negative 24-hour pH testing, suggesting that symptoms are not caused by abnormal esophageal acid exposure. Multichannel intraluminal impedance (MII)-24-hour pH allows the recognition of major acid, minor acid, nonacid, and gas reflux. Recorded symptoms can be correlated with all reflux events (eg, acid, minor acid, nonacid, and gas) and a symptom score can be generated.