Uveitis, a rare but important complication of adjuvant zoledronic acid for early-stage breast cancer.

Bisphosphonates such as zoledronic acid are an important part of adjuvant therapy to reduce the risk of recurrence in early-stage breast cancer. Uveitis remains one of the lesser-known side effects of zoledronic acid; prompt recognition is essential to ensure patients receive appropriate and timely care to help prevent permanent vision loss. We report a case of anterior uveitis in a postmenopausal woman who presented with visual symptoms after receiving the first dose of zoledronic acid. This case report serves to educate and increase awareness of the risk of uveitis in patients who are given zoledronic acid. This is the first and only reported case of zoledronic acid when used in the adjuvant setting for the treatment of breast cancer.

Class I Histone Deacetylase Inhibition for the Treatment of Sustained Atrial Fibrillation.

Current therapies are less effective for treating sustained/permanent versus paroxysmal atrial fibrillation (AF). We and others have previously shown that histone deacetylase (HDAC) inhibition reverses structural and electrical atrial remodeling in mice with inducible, paroxysmal-like AF. Here, we hypothesize an important, specific role for class I HDACs in determining structural atrial alterations during sustained AF. The class I HDAC inhibitor N-acetyldinaline [4-(acetylamino)-N-(2-amino-phenyl) benzamide] (CI-994) was administered for 2 weeks (1 mg/kg/day) to Hopx transgenic mice with atrial remodeling and inducible AF and to dogs with atrial tachypacing-induced sustained AF. Class I HDAC inhibition prevented atrial fibrosis and arrhythmia inducibility in mice. Dogs were divided into three groups: 1) sinus rhythm, 2) sustained AF plus vehicle, and 3) sustained AF plus CI-994. In group 3, the time in AF over 2 weeks was reduced by 30% compared with group 2, along with attenuated atrial fibrosis and intra-atrial adipocyte infiltration. Moreover, group 2 dogs had higher atrial and serum inflammatory cytokines, adipokines, and atrial immune cells and adipocytes compared with groups 1 and 3. On the other hand, groups 2 and 3 displayed similar left atrial size, ventricular function, and mitral regurgitation. Importantly, the same histologic alterations found in dogs with sustained AF and reversed by CI-994 were also present in atrial tissue from transplanted patients with chronic AF. This is the first evidence that, in sustained AF, class I HDAC inhibition can reduce the total time of fibrillation, atrial fibrosis, intra-atrial adipocytes, and immune cell infiltration without significant effects on cardiac function.