No abstract

IMPORTANCE Anakinra, an interleukin 1β recombinant receptor antagonist, may have potential to treat colchicine-resistant and corticosteroid-dependent recurrent pericarditis. OBJECTIVE To determine the efficacy of anakinra for colchicine-resistant and corticosteroid-dependent recurrent pericarditis. DESIGN, SETTING, AND PARTICIPANTS The Anakinra-Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP) double-blind, placebo-controlled, randomized withdrawal trial (open label with anakinra followed by a double-blind withdrawal step with anakinra or placebo until recurrent pericarditis occurred) conducted among 21 consecutive patients enrolled at 3 Italian referral centers between June and November 2014 (end of follow-up, October 2015). Included patients had recurrent pericarditis (with Ն3 previous recurrences), elevation of C-reactive protein, colchicine resistance, and corticosteroid dependence. INTERVENTIONS Anakinra was administered at 2 mg/kg per day, up to 100 mg, for 2 months, then patients who responded with resolution of pericarditis were randomized to continue anakinra (n = 11) or switch to placebo (n = 10) for 6 months or until a pericarditis recurrence. MAIN OUTCOMES AND MEASURES The primary outcomes were recurrent pericarditis and time to recurrence after randomization. RESULTS Eleven patients (7 female) randomized to anakinra had a mean age of 46.5 (SD, 16.3) years; 10 patients (7 female) randomized to placebo had a mean age of 44 (SD, 12.5) years. All patients were followed up for 12 months. Median follow-up was 14 (range, 12-17) months. Recurrent pericarditis occurred in 9 of 10 patients (90%; incidence rate, 2.06% of patients per year) assigned to placebo and 2 of 11 patients (18.2%; incidence rate, 0.11% of patients per year) assigned to anakinra, for an incidence rate difference of −1.95% (95% CI, −3.3% to −0.6%). Median flare-free survival (time to flare) was 72 (interquartile range, 64-150) days after randomization in the placebo group and was not reached in the anakinra group (P <.001). During anakinra treatment, 20 of 21 patients (95.2%) experienced transient local skin reactions: 1 (4.8%) herpes zoster, 3 (14.3%) transaminase elevation, and 1 (4.8%) ischemic optic neuropathy. No patient permanently discontinued the active drug. No adverse events occurred during placebo treatment. CONCLUSION AND RELEVANCE In this preliminary study of patients with recurrent pericarditis with colchicine resistance and corticosteroid dependence, the use of anakinra compared with placebo reduced the risk of recurrence over a median of 14 months. Larger studies are needed to replicate these findings as well as to assess safety and longer-term efficacy.

MD; for the COPPS-2 Investigators IMPORTANCE Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postop-erative effusions may be responsible for increased morbidity and health care costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial. OBJECTIVE To determine the efficacy and safety of perioperative use of oral colchicine in reducing postpericardiotomy syndrome, postoperative AF, and postoperative pericardial or pleural effusions. DESIGN, SETTING, AND PARTICIPANTS Investigator-initiated, double-blind, placebo-controlled, randomized clinical trial among 360 consecutive candidates for cardiac surgery enrolled in 11 Italian centers between March 2012 and March 2014. At enrollment, mean age of the trial participants was 67.5 years (SD, 10.6 years), 69% were men, and 36% had planned valvular surgery. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to colchicine. INTERVENTIONS Patients were randomized to receive placebo (n=180) or colchicine (0.5 mg twice daily in patients 70 kg or 0.5 mg once daily in patients <70 kg; n=180) starting between 48 and 72 hours before surgery and continued for 1 month after surgery. MAIN OUTCOMES AND MEASURES Occurrence of postpericardiotomy syndrome within 3 months; main secondary study end points were postoperative AF and pericardial or pleural effusion. RESULTS The primary end point of postpericardiotomy syndrome occurred in 35 patients (19.4%) assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference, 10.0%; 95% CI, 1.1%-18.7%; number needed to treat = 10). There were no significant differences between the colchicine and placebo groups for the secondary end points of postoperative AF (colchicine, 61 patients [33.9%]; placebo, 75 patients [41.7%]; absolute difference, 7.8%; 95% CI, −2.2% to 17.6%) or postoperative pericardial/pleural effusion (colchicine, 103 patients [57.2%]; placebo, 106 patients [58.9%]; absolute difference, 1.7%; 95% CI, −8.5% to 11.7%), although there was a reduction in postoperative AF in the prespecified on-treatment analysis (placebo, 61/148 patients [41.2%]; colchicine, 38/141 patients [27.0%]; absolute difference, 14.2%; 95% CI, 3.3%-24.7%). Adverse events occurred in 21 patients (11.7%) in the placebo group vs 36 (20.0%) in the colchicine group (absolute difference, 8.3%; 95% CI; 0.76%-15.9%; number needed to harm = 12), but discontinuation rates were similar. No serious adverse events were observed. CONCLUSIONS AND RELEVANCE Among patients undergoing cardiac surgery, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastro-intestinal adverse effects reduced the potential benefits of colchicine in this setting.

No single parameter, including nodule size, satisfactorily identifies a subset of patients to be electively investigated by FNAC, although several may be useful in this regard.

Objective: To evaluate if a nodule with shape taller than wide (anteroposterior/transverse diameter ratio, A/TR1) is a good predictor of malignancy independent of the size. Methods: We retrospectively examined the cytological and histological results of 7455 nodules (5198 patients) referred for ultrasound-guided-fine needle aspiration cytology (US-FNAC) in our hospital from January 1991 to September 2004. Results: A suitable FNAC was obtained from 6135 nodules (4495 patients); 34.6% were less than 1 cm in diameter (small nodules, SN). A diagnosis of carcinoma was histologically confirmed in 284/349 suspicious lesions after FNAC. The size of carcinoma nodules was not significantly associated with the occurrence of extracapsular growth (large nodules (LN): 10.5%, SN: 4.9%, NS) and lymph node metastasis (LN: 23.6%, SN: 25.0%, NS). Malignant lesions showed microcalcifications more frequently than benign nodules (72.2 vs 28.7%; P!0.001; (odds ratio, OR(confidence intervals, CI)Z9.9(7.2-13.4)). Similarly, A/TR1 (76 vs 40%; P!0.001; OR(CI)Z8.6(5.5-13.1)), blurred margins (52.8 vs 18.8%; P!0.001; OR(CI)Z7.7(5.6-10.2)), solid hypo-echoic appearance (80.6 vs 52.4%; P!0.001; OR(CI)Z 3.2(2.2-4.3)) and intranodular vascular pattern (type 2) (61.6 vs 49.7%; P!0.001; OR(CI)Z 1.7(1.3-2.3)) were significantly more frequent in malignant than in benign nodules. Conclusions: Our data show that no single parameter, including nodule size, satisfactorily identifies a subset of patients to be electively investigated by FNAC. We concluded that A/TR1 with at least two of US features (microcalcification, blurred margins, hypo-echoic pattern) is today the best compromise between missing cancers and cost-benefit.