Radioiodine Remnant Ablation for Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

Importance: Postoperative radioactive iodine (RAI) remnant ablation for differentiated thyroid cancer (DTC) facilitates the early detection of recurrence and represents an adjuvant therapy that targets persistent microscopic disease. The optimal activity of RAI in low- and intermediate-risk DTC remains controversial. Objective: To evaluate the long-term cure rate of different RAI activities in low- and intermediate-risk DTC. Secondary outcomes included successful remnant ablation, adverse effects, and hospital length of stay. Data Source: A systematic search of the databases PubMed, Cochrane Collaboration, Embase, Scopus, and Web of Science was performed to identify randomized clinical trials (RCTs) and observational studies that compared long-term outcomes (>12 months) for American Thyroid Association-classified low- and intermediate-risk DTC based on receipt of either low-activity or high-activity RAI postoperatively. Study Selection: All RCTs or observational studies evaluating patients with low- and intermediate-risk DTC who were treated initially with total/near-total thyroidectomy, followed by remnant RAI ablation with either low or high activities. Eligible studies had to present odds ratio, relative risk (RR), or hazard ratio estimates (with 95% CIs), standard errors, or the number of events necessary to calculate these for the outcome of interest rate. Data Extraction: Two investigators reviewed the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Dichotomous variables were pooled as risk ratios and continuous data as weighted-mean differences. Quality assessment of the included studies was performed using the Newcastle-Ottawa and Jadad scales. Main Outcomes and Measures: Disease recurrence was the primary outcome. Secondary outcomes included successful ablation, adverse effects, and length of stay. Results: Ten studies that included 3821 patients met inclusion criteria, including 6 RCTs and 4 observational studies. There was no difference in long-term cure recurrence rates (RR, 0.88; 95% CI, 0.62-1.27, P = .50) or successful remnant ablation (RR, 0.95; 95% CI, 0.87-1.03; P = .20) between low-activity and high-activity RAI. Conclusions and Relevance: In this systematic review and meta-analysis, low-activity RAI was comparable with high-activity RAI regarding successful ablation and recurrence rates. This suggests that low-activity RAI is preferable to high-activity in low- and intermediate-risk DTC because of its similar efficacy but reduced morbidity. Trial Registration: PROSPERO Identifier: CRD42020166780.

Response surface methodology and artificial neural network approach for the optimization of ultrasound-assisted extraction of polyphenols from garlic.

This paper aimed to establish the optimal conditions for ultrasound-assisted extraction of polyphenols from domestic garlic (Allium sativum L.) using response surface methodology (RSM) and artificial neural network (ANN) approach. A 4-factor-3-level central composite design was used to optimize ultrasound-assisted extraction (UAE) to obtain a maximum yield of target responses. Maximum values of the two output parameters: 19.498 mg GAE/g fresh weight of sample total phenolic content and 1.422 mg RUT/g fresh weight of sample total flavonoid content were obtained under optimum extraction conditions: 13.50 min X1, 59.00 °C X2, 71.00% X3 and 20.00 mL/g X4. Root mean square error for training, validation, and testing were 0.0209, 3.6819 and 1.8341, respectively. The correlation coefficient between experimentally obtained total phenolic content and total flavonoid content and values predicted by ANN were 0.9998 for training, 0.9733 for validation, and 0.9821 for testing, indicating the good predictive ability of the model. The ANN model had a higher prediction efficiency than the RSM model. Hence, RSM can demonstrate the interaction effects of basic inherent UAE parameters on target responses, whereas ANN can reliably model the UAE process with better predictive and estimation capabilities.

Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial.

BACKGROUND: Primary open angle glaucoma and ocular hypertension are habitually treated with eye drops that lower intraocular pressure. Selective laser trabeculoplasty is a safe alternative but is rarely used as first-line treatment. We compared the two. METHODS: In this observer-masked, randomised controlled trial treatment-naive patients with open angle glaucoma or ocular hypertension and no ocular comorbidities were recruited between 2012 and 2014 at six UK hospitals. They were randomly allocated (web-based randomisation) to initial selective laser trabeculoplasty or to eye drops. An objective target intraocular pressure was set according to glaucoma severity. The primary outcome was health-related quality of life (HRQoL) at 3 years (assessed by EQ-5D). Secondary outcomes were cost and cost-effectiveness, disease-specific HRQoL, clinical effectiveness, and safety. Analysis was by intention to treat. This study is registered at controlled-trials.com (ISRCTN32038223). FINDINGS: Of 718 patients enrolled, 356 were randomised to the selective laser trabeculoplasty and 362 to the eye drops group. 652 (91%) returned the primary outcome questionnaire at 36 months. Average EQ-5D score was 0·89 (SD 0·18) in the selective laser trabeculoplasty group versus 0·90 (SD 0·16) in the eye drops group, with no significant difference (difference 0·01, 95% CI -0·01 to 0·03; p=0·23). At 36 months, 74·2% (95% CI 69·3-78·6) of patients in the selective laser trabeculoplasty group required no drops to maintain intraocular pressure at target. Eyes of patients in the selective laser trabeculoplasty group were within target intracoluar pressure at more visits (93·0%) than in the eye drops group (91·3%), with glaucoma surgery to lower intraocular pressure required in none versus 11 patients. Over 36 months, from an ophthalmology cost perspective, there was a 97% probability of selective laser trabeculoplasty as first treatment being more cost-effective than eye drops first at a willingness to pay of £20 000 per quality-adjusted life-year gained. INTERPRETATION: Selective laser trabeculoplasty should be offered as a first-line treatment for open angle glaucoma and ocular hypertension, supporting a change in clinical practice. FUNDING: National Institute for Health Research, Health and Technology Assessment Programme.

Design and testing for a nontagged F1-V fusion protein as vaccine antigen against bubonic and pneumonic plague.

A two-component recombinant fusion protein antigen was re-engineered and tested as a medical counter measure against the possible biological threat of aerosolized Yersinia pestis. The active component of the proposed subunit vaccine combines the F1 capsular protein and V virulence antigen of Y. pestis and improves upon the design of an earlier histidine-tagged fusion protein. In the current study, different production strains were screened for suitable expression and a purification process was optimized to isolate an F1-V fusion protein absent extraneous coding sequences. Soluble F1-V protein was isolated to 99% purity by sequential liquid chromatography including capture and refolding of urea-denatured protein via anion exchange, followed by hydrophobic interaction, concentration, and then transfer into buffered saline for direct use after frozen storage. Protein identity and primary structure were verified by mass spectrometry and Edman sequencing, confirming a purified product of 477 amino acids and removal of the N-terminal methionine. Purity, quality, and higher-order structure were compared between lots using RP-HPLC, intrinsic fluorescence, CD spectroscopy, and multi-angle light scattering spectroscopy, all of which indicated a consistent and properly folded product. As formulated with aluminum hydroxide adjuvant and administered in a single subcutaneous dose, this new F1-V protein also protected mice from wild-type and non-encapsulated Y. pestis challenge strains, modeling prophylaxis against pneumonic and bubonic plague. These findings confirm that the fusion protein architecture provides superior protection over the former licensed product, establish a foundation from which to create a robust production process, and set forth assays for the development of F1-V as the active pharmaceutical ingredient of the next plague vaccine.