【In Press】Clinical outcomes of patterned laser trabeculoplasty as adjuvant therapy in open-angle glaucoma and ocular hypertension

AIM: To assess the efficacy and safety of patterned laser trabeculoplasty (PLT) as an adjunctive treatment in open-angle glaucoma (OAG) or ocular hypertension (OHT) patients who were under antiglaucoma medical treatment. METHODS: This study was a retrospective review of primary or secondary OAG patients and OHT patients with medically uncontrolled (≥18 mm Hg) intraocular pressure (IOP) who underwent 360º PLT from June 2016 to August 2016. Follow-up visits at week 1, and 1, 3 and 6mo were performed. IOP, best corrected visual acuity (BCVA), complications and eye drop glaucoma medication were recorded at each follow-up visit. Success was defined as IOP reduction ≥20% from baseline. RESULTS: Forty one eyes of 25 patients were included in this study. Pre-treatment mean IOP was 20.2±1.6 mm Hg. After PLT, IOP was 19.3±5.2, 16.1±2.7, 17.1±3.7 and 16.3±3.5 mm Hg, at 1wk, 1, 3 and 6mo, respectively. IOP reduction from baseline was statistically significant from the first month, remaining stable at 6mo (P<0.001). PLT success at 6mo of follow-up was 48.7%. The number of glaucoma medication per eye (P=0.10) and the mean BCVA both remained constant (P=0.37). Complications included transient IOP spikes in 4 eyes (9.7%) and peripheral anterior synechiae in 7 eyes (17.1%). CONCLUSION: PLT is an effective and safe method for the management of patients with OHT or OAG as an adjunctive therapy. Additional larger studies should be designed to verify the long-term stability of IOP reduction with this laser technology.     

Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study

New treatments, particularly second‐line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody–drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single‐arm, open‐label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non‐Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1–2 prior lines of therapy. In part 1, no dose‐limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment‐emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non‐Japanese patients.     

Effectiveness of fetal fibronectin testing compared with digital cervical assessment of women with preterm contractions

The purpose of this study is to determine the effectiveness of fetal fibronectin (FFN) compared to assessment of cervical dilation (CD) in clinical management of women with symptomatic preterm labor (PTL). Pregnant women presenting to Thomas Jefferson University Hospital between May 1, 2001 and November 30, 2002 with symptomatic PTL underwent FFN sampling and had a complete clinical evaluation including a pelvic bimanual examination. Inclusion criteria were singleton pregnancy, gestational age (GA) between 24 (0) and 33 (6) weeks, CD < 3 cm, and intact amniotic membranes. FFN samples were sent out and results were available within 4-12 hours. Clinical management including tocolysis, antenatal steroids, and hospitalization was determined based on digital CD assessment and FFN status. A dilated cervix was defined as CD > 1 cm. Ninety-three patients were included. Spontaneous preterm delivery (SPTD) at < 37 weeks occurred in 20 of 93 (21.5%) patients. Medical therapy use was significantly higher in patients with dilated cervix than in those with a closed cervix (all P values < 0.05). Tocolysis and steroid use in FFN-negative patients and FFN-positive patients were not significantly different. Furthermore, tocolytic use was higher in FFN-negative patients than in women with positive FFN (50% versus 42.1%; P = 0.53). Use of antenatal steroids was similar in patients with CD >/= 1 cm and a positive FFN (54.5% versus 47.4%; P = 0.92). Compared with FFN-negative patients, women with closed cervix were less likely to undergo interventions. In symptomatic PTL patients, CD determined clinical management more than FFN status. Overall, the use of FFN was not effective in decreasing "unnecessary" clinical interventions.     

Agar Biopolymer Films for Biodegradable Packaging: A Reference Dataset for Exploring the Limits of Mechanical Performance

This article focuses on agar biopolymer films that offer promise for developing biodegradable packaging, an important solution for reducing plastics pollution. At present there is a lack of data on the mechanical performance of agar biopolymer films using a simple plasticizer. This study takes a Design of Experiments approach to analyze how agar-glycerin biopolymer films perform across a range of ingredients concentrations in terms of their strength, elasticity, and ductility. Our results demonstrate that by systematically varying the quantity of agar and glycerin, tensile properties can be achieved that are comparable to agar-based materials with more complex formulations. Not only does our study significantly broaden the amount of data available on the range of mechanical performance that can be achieved with simple agar biopolymer films, but the data can also be used to guide further optimization efforts that start with a basic formulation that performs well on certain property dimensions. We also find that select formulations have similar tensile properties to thermoplastic starch (TPS), acrylonitrile butadiene styrene (ABS), and polypropylene (PP), indicating potential suitability for select packaging applications. We use our experimental dataset to train a neural network regression model that predicts the Young’s modulus, ultimate tensile strength, and elongation at break of agar biopolymer films given their composition. Our findings support the development of further data-driven design and fabrication workflows.     

A Sustainable Cold-Recycled Solution for the Surface Finishing of Unpaved Rural Roads

This paper presents the results of an experimental investigation which was carried out with the purpose of assessing the performance-related properties of an emulsion-based cold-recycled mixture to be employed as a sustainable solution for the surface finishing of unpaved rural roads. This mixture contained significant quantities of recycled components (reclaimed asphalt and mineral sludge), and its composition was fine-tuned by following an innovative mix design procedure. Properties of these mixtures were studied by means of laboratory tests which considered key parameters, such as flowability, indirect tensile stiffness modulus, indirect tensile strength, moisture susceptibility and resistance to permanent deformation. It was found that, by means of the proposed mix design procedure, optimal dosages of the recycled components can be identified, thereby ensuring the achievement of the desired properties in terms of high workability and adequate stiffness and strength.     

Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: Lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues

Purpose

To compare the performance of PET/MRI imaging using MR attenuation correction (MRAC) (DIXON-based 4-segment -map) in breast cancer patients with that of PET/CT using CT-based attenuation correction and to compare the quantification accuracy in lesions and in normal organ tissues.

Methods

A total of 36 patients underwent a whole-body PET/CT scan 1 h after injection and an average of 62 min later a second scan using a hybrid PET/MRI system. PET/MRI and PET/CT were compared visually by rating anatomic allocation and image contrast. Regional tracer uptake in lesions was quantified using volumes of interest, and maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) were calculated. Metabolic tumor volume (MTV) of each lesion was computed on PET/MRI and PET/CT. Tracer uptake in normal organ tissue was assessed as SUVmax and SUVmean in liver, spleen, left ventricular myocardium, lung, and muscle.

Results

Overall 74 FDG positive lesions were visualized by both PET/CT and PET/MRI. No significant differences in anatomic allocation scores were found between PET/CT and PERT/MRI, while contrast score of lesions on PET/MRI was significantly higher. Both SUVmax and SUVmean of lesions were significantly higher on PET/MRI than on PET/CT, with strong correlations between PET/MRI and PET/CT data (ρ = 0.71–0.88). MTVs of all lesions were 4% lower on PET/MRI than on PET/CT, but no statistically significant difference was observed, and an excellent correlation between measurements of MTV with PET/MRI and PET/CT was found (ρ = 0.95–0.97; p < 0.0001). Both SUVmax and SUVmean were significantly lower by PET/MRI than by PET/CT for lung, liver and muscle, no significant difference was observed for spleen, while either SUVmax and SUVmean of myocardium were significantly higher by PET/MRI. High correlations were found between PET/MRI and PET/CT for both SUVmax and SUVmean of the left ventricular myocardium (ρ = 0.91; p < 0.0001), while moderate correlations were found for the other normal organ tissues (ρ = 0.36–0.61; p < 0.05).

Conclusions

PET/MRI showed equivalent performance in terms of qualitative lesion detection to PET/CT. Despite significant differences in tracer uptake quantification, due to either methodological and biological factors, PET/MRI and PET/CT measurements in lesions and normal organ tissues correlated well. This study demonstrates that integrated whole-body PET/MRI is feasible in a clinical setting with high quality and in a short examination time.     

Longitudinal Nutritional Intakes in Italian Pregnant Women in Comparison with National Nutritional Guidelines

Background: Nutritional quality during pregnancy is crucial for mother and child health and their short/long-term outcomes. The aim of this study is to evaluate the adherence to nutritional recommendations in Italy during the three pregnancy trimesters in Normal Weight (NW) and Over Weight (OW) women. Methods: Data from a multicenter randomized controlled trial included 176 women (NW = 133; OW = 43) with healthy singleton pregnancies enrolled within 13 + 6 weeks of gestation. Dietary intake was assessed every trimester by a Food Frequency Questionnaire. Results: OW and NW had similar gestational weight gain. However, as Institute of Medicine (IOM) recommend lower gestational weight gain (GWG) for OW, they exceeded the suggested range. In both groups, caloric intake during the three trimesters never met recommendations. Protein intake in first and second trimester was higher than recommendations, as was sugars percentage. Dietary fiber intake was lower in OW. Polyunsaturated fatty acids, calcium, iron and folic acid requirements were never satisfied, while sodium intake exceeded recommendations. Conclusions: NW and OW women in Italy do not adhere to nutritional recommendations during pregnancy, with lower caloric intake, protein and sugars excess and inadequacies in micronutrients intake. Pregnant women in Italy should be provided with an adequate counseling and educational intervention as well as supplementation when indicated.     

Acute Effects of Caffeine on Overall Performance in Basketball Players—A Systematic Review

Caffeine supplementation has become increasingly popular among athletes. The benefits of caffeine include delaying the negative effects of fatigue, maintaining a high level of physical and mental performance, and improving certain abilities necessary for sport success. Given the complex nature of basketball, caffeine could be a legal, ergogenic stimulant substance, which will positively affect overall basketball performance. The purpose of this systematic review was to summarize evidence for the effect of acute caffeine ingestion on variables related to the basketball performance. Web of Science, PubMed, Scopus and ProQuest, MEDLINE, and ERIC databases were searched up to February 2021. Studies that measured the acute effect of caffeine on basketball performance were included and analyzed. Eight studies published between 2000 and 2021 were included in the analysis. Pre-exercise caffeine intake increased vertical jump height, running time at 10 and 20 m without the ball, overall basketball performance (number of body impacts, number of free throws, rebounds, and assists) during simulated games, and reduced the time required to perform a basketball-specific agility test. Equivocal results between caffeine and placebo groups were found for aerobic capacity, free throw and three-point accuracy, and dribbling speed. Pre-exercise caffeine ingestion did not affect RPE, but insomnia and urinary excretion were increased. The pre-exercise ingestion of 3 and 6 mg/kg caffeine was found to be effective in increasing several physical performance variables in basketball players during sport-specific testing and simulated matches. However, considering the intermittent nature and complexity of basketball, and individual differences between players, future studies are needed.     

On the Utility of ToxCast-Based Predictive Models to Evaluate Potential Metabolic Disruption by Environmental Chemicals

Background: Research suggests environmental contaminants can impact metabolic health; however, high costs prohibit in vivo screening of putative metabolic disruptors. High-throughput screening programs, such as ToxCast, hold promise to reduce testing gaps and prioritize higher-order (in vivo) testing.Objectives: We sought to a) examine the concordance of in vitro testing in 3T3-L1 cells to a targeted literature review for 38 semivolatile environmental chemicals, and b) assess the predictive utility of various expert models using ToxCast data against the set of 38 reference chemicals.Methods: Using a set of 38 chemicals with previously published results in 3T3-L1 cells, we performed a metabolism-targeted literature review to determine consensus activity determinations. To assess ToxCast predictive utility, we used two published ToxPi models: a) the 8-Slice model published by Janesick et al. (2016) and b) the 5-Slice model published by Auerbach et al. (2016). We examined the performance of the two models against the Janesick in vitro results and our own 38-chemical reference set. We further evaluated the predictive performance of various modifications to these models using cytotoxicity filtering approaches and validated our best-performing model with new chemical testing in 3T3-L1 cells.Results: The literature review revealed relevant publications for 30 out of the 38 chemicals (the remaining 8 chemicals were only examined in our previous 3T3-L1 testing). We observed a balanced accuracy (average of sensitivity and specificity) of 0.86 comparing our previous in vitro results to the literature-derived calls. ToxPi models provided balanced accuracies ranging from 0.55 to 0.88, depending on the model specifications and reference set. Validation chemical testing correctly predicted 29 of 30 chemicals as per 3T3-L1 testing, suggesting good adipogenic prediction performance for our best adapted model.Discussion: Using the most recent ToxCast data and an updated ToxPi model, we found ToxCast performed similarly to that of our own 3T3-L1 testing in predicting consensus calls. Furthermore, we provide the full ranked list of largely untested chemicals with ToxPi scores that predict adipogenic activity and that require further investigation. https://doi.org/10.1289/EHP6779