Latest evidence of microwave ablation for papillary thyroid microcarcinoma compared with surgery: A systematic review and meta-analysis.

Background: The most typical thyroid gland malignant lesion is papillary thyroid cancer (PTC). In many nations, the prevalence of thyroid cancer (TC) is rising, particularly papillary thyroid microcarcinoma (PTMC). Microwave ablation (MWA) has been gradually carried out in some patients with benign thyroid nodules, some low-risk PTMC, and metastatic lymph nodes in the neck. The role and safety of MWA remain controversial topics. So we conducted this study to provide the latest evidence of MWA for PTMC compared with surgery. Methods: Patients' postoperative outcomes (duration of hospital stay and hospitalization expenditures), intraoperative outcomes (surgery time, blood loss, and incision size), and follow-up outcomes were all examined (complication rate, recurrence rate, and lymph node metastasis). The effectiveness and safety of MWA versus surgery for PTMC patients were compared using the weighted mean difference (WMD) and odds ratio (OR). Results: In total, we included 7 articles (7 trial comparisons) which contained 1, 567 PTMC patients. The results showed that MWA had significant advantages in operative time (WMD = -53.47, 95% CI: -67.62 to -39.32), postoperative hospital stay (WMD =-4.59, 95% CI: -6.40 to -2.77), hospitalization costs (WMD= -70.06, 95% CI: -90.93 to -49.19), blood loss (WMD =-28.07, 95% CI: -33.77 to -22.38), incisions size (WMD =-59.69, 95% CI: -67.79 to -51.59), and complication rates (OR = 0.28; 95% CI: 0.18 to 0.42) compared with surgery. It also showed that recurrence rates and risk of lymph node metastasis are similar to surgery. Conclusions: For PTMC patients, MWA could be an efficient, safe, and affordable therapy.

A phase 1 evaluation of the pharmacokinetic/pharmacodynamic interaction of the anti-malarial agents KAF156 and piperaquine.

BACKGROUND: KAF156 is a novel imidazolopiperazine anti-malarial with activity against pre-erythrocytic liver stages, asexual and sexual blood stages. Based on in vitro data, a two-way pharmacokinetic interaction was hypothesized for KAF156 use in combination with piperaquine (PPQ) as both drugs are CYP3A4 substrates and inhibitors. Potential combination effects on the QT interval were also assessed. METHODS: This was an open-label, parallel-group, single-dose study in healthy volunteers randomized to three parallel arms (1:1:1) of 800 mg KAF156 + 1280 mg PPQ, 800 mg KAF156 alone and 1280 mg PPQ alone. Triplicate ECGs were done up to 48 h post-dose. Routine safety and pharmacokinetic assessments were carried out up to 61 days. RESULTS: Of the 72 healthy male subjects recruited, 68 completed the study. Co-administration of PPQ and KAF156 had no overall effect on AUC of either compound, but the Cmax values of both KAF156 (~ 23%) and piperaquine (~ 70%) increased. Both drugs given alone or in combination were well tolerated with no deaths or serious adverse events (SAEs). AEs were observed at the frequency of 87.5, 79.2 and 58.3% respectively for KAF156 + PPQ, PPQ and KAF156 arms. The most common AEs were nausea and headache. There were no Grade 3 or 4 events. There were no ECG related AEs, no QTcF interval > 480 ms and no QTcF interval increase from baseline > 60 ms. There was a positive ∆QTcF trend in the KAF156 + PPQ arm when either KAF156 or piperaquine concentration increases, but there was no significant difference between the combination arm and other arms in maximum ∆QTcF. CONCLUSIONS: No safety/cardiac risk or drug interaction was identified which would preclude use of a KAF156 and PPQ combination in future studies.

Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria.

BACKGROUND: KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. METHODS: We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). RESULTS: Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. CONCLUSIONS: KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01753323 .).