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Relacorilant + Nab-Paclitaxel in Patients With Recurrent, Platinum-Resistant Ovarian Cancer: A Three-Arm, Randomized, Controlled, Open-Label Phase II Study

J Clin Oncol. 2023 Jun 26:JCO2202624. doi: 10.1200/JCO.22.02624. Online ahead of print.

ABSTRACT

PURPOSE: Despite therapeutic advances, outcomes for patients with platinum-resistant/refractory ovarian cancer remain poor. Selective glucocorticoid receptor modulation with relacorilant may restore chemosensitivity and enhance chemotherapy efficacy.

METHODS: This three-arm, randomized, controlled, open-label phase II study (ClinicalTrials.gov identifier: NCT03776812) enrolled women with recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer, or ovarian carcinosarcoma treated with ≤4 prior chemotherapeutic regimens. Patients were randomly assigned 1:1:1 to (1) nab-paclitaxel (80 mg/m2) + intermittent relacorilant (150 mg the day before, of, and after nab-paclitaxel); (2) nab-paclitaxel (80 mg/m2) + continuous relacorilant (100 mg once daily); or (3) nab-paclitaxel monotherapy (100 mg/m2). Nab-paclitaxel was administered on days 1, 8, and 15 of each 28-day cycle. The primary end point was progression-free survival (PFS) by investigator assessment; objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety were secondary end points.

RESULTS: A total of 178 women were randomly assigned. Intermittent relacorilant + nab-paclitaxel improved PFS (hazard ratio [HR], 0.66; log-rank test P = .038; median follow-up, 11.1 months) and DOR (HR, 0.36; P = .006) versus nab-paclitaxel monotherapy, while ORR was similar across arms. At the preplanned OS analysis (median follow-up, 22.5 months), the OS HR was 0.67 (P = .066) for the intermittent arm versus nab-paclitaxel monotherapy. Continuous relacorilant + nab-paclitaxel showed numerically improved median PFS but did not result in significant improvement over nab-paclitaxel monotherapy. Adverse events were comparable across study arms, with neutropenia, anemia, peripheral neuropathy, and fatigue/asthenia being the most common grade ≥3 adverse events.

CONCLUSION: Intermittent relacorilant + nab-paclitaxel improved PFS, DOR, and OS compared with nab-paclitaxel monotherapy. On the basis of protocol-prespecified Hochberg step-up multiplicity adjustment, the primary end point did not reach statistical significance (P < .025). A phase III evaluation of this regimen is underway (ClinicalTrials.gov identifier: NCT05257408).

PMID:37364223 | DOI:10.1200/JCO.22.02624

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Effect of toothpaste tablets on gloss and surface roughness of resin-based composite materials

Am J Dent. 2023 Jun;36(3):156-1160.

ABSTRACT

PURPOSE: To evaluate the effects of toothpaste tablets on the gloss and surface roughness of resin-based composite materials and determine the relationship between gloss and roughness.

METHODS: Rectangular jigs were designed and printed. Wells (2 mm deep x 7 mm diameter) were filled with Filtek Supreme Ultra A2B, light-cured and polished. A small-area glossmeter was used for gloss (GU) measurements and a profilometer for roughness measurements (Ra) at baseline and after challenge with each toothpaste. An automated tooth-brushing machine was set at 120 strokes/minute for a total of 10,000 strokes to evaluate four test groups with 16 specimens in each group. NC: Brushing with distilled water; TABS: Colgate Anywhere Travel Tooth Tabs; CP: Colgate Cavity Protection Toothpaste and AW: Colgate Whitening Advanced Toothpaste. Kruskal-Wallis test was used to test the difference in gloss and surface roughness among the groups and Pearson correlation was used to compare the relationship between gloss and roughness.

RESULTS: There was no statistically significant difference in gloss and roughness among the four groups at baseline. At post-brushing, there was a statistically significant difference among the groups (P< 0.001) with increased roughness and decreased gloss for CP and AW when compared to TABS. There was a statistically significant correlation between post-brushing roughness and post-brushing gloss (P< 0.001, rho: -0.815). Thus, the higher the surface roughness the lower the gloss.

CLINICAL SIGNIFICANCE: Toothpaste tablets retain better gloss and roughness of resin-based composite materials when compared to conventional toothpastes.

PMID:37364194

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Tooth color change and tolerability evaluation of a hydrogen peroxide whitening strip compared to a strip, paste, and rinse regimen containing plant-based oils and Dead Sea salt

Am J Dent. 2023 Jun;36(3):151-155.

ABSTRACT

PURPOSE: To assess tooth color changes and tolerability with use of a hydrogen peroxide whitening strip compared to a regimen of a strip, rinse and paste for tooth whitening.

METHODS: This was a single-center, parallel-group, double-blind, randomized controlled clinical trial. Qualified generally healthy adult participants were assigned to one of two treatment groups. The test group included peroxide-free strips, a fluoride-free whitening toothpaste, and a whitening mouthwash (all Lumineux Oral Essentials); all test products contain plant-based oils (coconut, sage, and lemon peel) and Dead Sea salt. The control group included hydrogen peroxide whitening strips (Crest 3DWhitestrips Classic White) and a sodium fluoride non-whitening toothpaste (Crest). Both groups used a soft manual toothbrush (Oral-B). Strips (for both groups) and rinse (for test group) were used once daily. Changes in tooth color were assessed objectively and quantitatively by digital image analysis after 7, 10 and 14 treatments.

RESULTS: 50 participants were enrolled and randomized to treatment and 48 completed the trial. Participants had an average age of 40.8 years (range 18 to 62 years) and 64% were female. At the end of treatment, the test group did not provide statistically significant changes in yellowness (b*) or lightness (L*) from baseline (P≥ 0.411), whereas the control group demonstrated a statistically significant mean yellowness reduction (SD) of 1.55 (0.703) and a mean lightness improvement (SD) of 1.57 (1.141) compared to baseline (P< 0.001 for both). The control group also provided statistically significantly greater mean yellowness reductions and mean lightness improvements compared to the test group at all time points (P< 0.002). Products in both groups were well tolerated, with minor oral irritation and tooth sensitivity representing the most common findings during treatment.

CLINICAL SIGNIFICANCE: The Crest Whitestrips control whitening strip provided significant tooth whitening efficacy, whereas the Lumineux Oral Essentials test regimen containing plant-based oils and Dead Sea salt did not. This evidence is important for dental professionals to consider when making recommendations for patients seeking at-home whitening treatments.

PMID:37364193

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Effects of prophylaxis polishing pastes on the surface properties of enamel and dental restorations

Am J Dent. 2023 Jun;36(3):123-129.

ABSTRACT

PURPOSE: To determine the effects of rubber-cup polishing with different prophylaxis polishing pastes (PPP) on the color stability and surface properties of enamel and dental restorations.

METHODS: Direct (DC) and indirect composite (IC) samples were produced in disc-shaped plexiglass molds (10 x 2 mm). Computer-aided design and computer-aided manufacturing (CAD-CAM) composite blocks (CC) were sliced at a 2 mm thickness and the vestibular enamel surfaces (ES) of human incisors were included. A total of 96 samples were prepared and randomly divided into three subgroups (n= 8). The color, surface gloss and roughness measurements were performed before and after rubber-cup polishing at 2000 rpm for 12 seconds. Analysis of variance was used for statistical evaluation.

RESULTS: No significant difference was observed between the surface roughness change values after polishing with all three PPPs in DC, IC, and ES. However, in the CC group, Cleanic paste caused the highest roughness values and gloss reduction. The highest color change has occurred in the ES, and the least was observed in IC and CC groups. The type of PPP has a significant effect on the color stability and surface properties of enamel and dental restorations as well as the restorative material type.

CLINICAL SIGNIFICANCE: Prophylaxis polishing pastes may have detrimental effects on the surface properties of restorative materials in relation to the type of abrasive they contained and the roughness value.

PMID:37364189

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Effect of different adhesive application approaches on bond strength in over-etched dentin

Am J Dent. 2023 Jun;36(3):118-122.

ABSTRACT

PURPOSE: To investigate the effect of over-etching and subsequent use of different adhesive application approaches including active, double, preheated, and ultrasonic application on dentin bond strength.

METHODS: Dentin specimens from sound human third molars were prepared and allocated into six groups (n= 10 per group). In Group 1 (negative control), the dentin specimens were over-etched with phosphoric acid for 30 seconds, and a two-step etch-and-rinse adhesive (Prime & Bond XP; Dentsply Sirona) was applied for 20 seconds according to the manufacturer’s instructions. In test Groups 2-5, the application of the adhesive varied: In Group 2, the adhesive was actively rubbed into the dentin surface, whereas in Group 3, a second adhesive layer was applied after light-curing of the first one. In Group 4, the adhesive was heated to 68°C prior to application, and in Group 5, the adhesive was ultrasonically activated. Acid-etching for 15 seconds and adhesive application for 20 seconds was performed in the positive control group (Group 6) according to the manufacturer’s instructions. After light-curing and composite build-up [Ceram.x Spectra ST (HV); Dentsply Sirona], microtensile bond strength and fracture types were determined. Data were statistically analyzed by Kruskal-Wallis rank test, followed by post-hoc pairwise comparisons using Conover tests and P-value adjustment according to Holm (α= 0.05).

RESULTS: Active, double, preheated, or ultrasonic adhesive application showed no significant effect on dentin bond strength when compared to the control groups. Predominantly adhesive failures were observed in all groups.

CLINICAL SIGNIFICANCE: A modification of adhesive application by using active, double, preheated, or ultrasonic application does not improve bonding to accidentally over-etched dentin.

PMID:37364188

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A Habitat Model for Disease Vector Aedes aegypti in the Tampa Bay Area, FloridA

J Am Mosq Control Assoc. 2023 Jun 1;39(2):96-107. doi: 10.2987/22-7109.

ABSTRACT

Within the contiguous USA, Florida is unique in having tropical and subtropical climates, a great abundance and diversity of mosquito vectors, and high rates of human travel. These factors contribute to the state being the national ground zero for exotic mosquito-borne diseases, as evidenced by local transmission of viruses spread by Aedes aegypti, including outbreaks of dengue in 2022 and Zika in 2016. Because of limited treatment options, integrated vector management is a key part of mitigating these arboviruses. Practical knowledge of when and where mosquito populations of interest exist is critical for surveillance and control efforts, and habitat predictions at various geographic scales typically rely on ecological niche modeling. However, most of these models, usually created in partnership with academic institutions, demand resources that otherwise may be too time-demanding or difficult for mosquito control programs to replicate and use effectively. Such resources may include intensive computational requirements, high spatiotemporal resolutions of data not regularly available, and/or expert knowledge of statistical analysis. Therefore, our study aims to partner with mosquito control agencies in generating operationally useful mosquito abundance models. Given the increasing threat of mosquito-borne disease transmission in Florida, our analytic approach targets recent Ae. aegypti abundance in the Tampa Bay area. We investigate explanatory variables that: 1) are publicly available, 2) require little to no preprocessing for use, and 3) are known factors associated with Ae. aegypti ecology. Out of our 4 final models, none required more than 5 out of the 36 predictors assessed (13.9%). Similar to previous literature, the strongest predictors were consistently 3- and 4-wk temperature and precipitation lags, followed closely by 1 of 2 environmental predictors: land use/land cover or normalized difference vegetation index. Surprisingly, 3 of our 4 final models included one or more socioeconomic or demographic predictors. In general, larger sample sizes of trap collections and/or citizen science observations should result in greater confidence in model predictions and validation. However, given disparities in trap collections across jurisdictions, individual county models rather than a multicounty conglomerate model would likely yield stronger model fits. Ultimately, we hope that the results of our assessment will enable more accurate and precise mosquito surveillance and control of Ae. aegypti in Florida and beyond.

PMID:37364184 | DOI:10.2987/22-7109

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A Comparison of Oak Leaf and Fescue Hay Infusion-Baited Gravid Trap Collections-An Analysis Steeped in the Context of La Crosse Virus Vector Surveillance Effectiveness

J Am Mosq Control Assoc. 2023 Jun 1;39(2):138-141. doi: 10.2987/23-2116.

ABSTRACT

Neuroinvasive La Crosse virus disease remains the primary cause of pediatric arboviral encephalitis in the USA. In spite of the persistent public health burden, there are limited entomologic surveillance options that target both native and invasive La Crosse virus (LACV) vectors. In this study we used Reiter/Cummings tacklebox gravid traps to compare white oak (Quercus alba) and hay (predominately Festuca arundinacea) infusions within a LACV-endemic area of western North Carolina. Paired gravid traps (approximately 1,728 total trap-hours for each infusion) yielded 485 mosquitoes, with 3 species (Aedes japonicus [n = 265], Ae. triseriatus [n = 156], and Culex restuans [n = 45]) accounting for 96.1% of the total collection. The hay-infusion traps collected 2.5 times more Ae. triseriatus and 1.3 times more Ae. japonicus than the oak-infusion traps. The sum differences in overall collections for these 2 species by infusion type were statistically significant (χ2 = 9.61, df = 1, P = 0.0019). Poisson ratio tests to compare capture rates suggest that hay infusions were more effective for capturing Ae. triseriatus, but that hay and white oak leaf infusions had equivocal capture rates for Ae. japonicus (an invasive LACV accessory vector) and Cx. restuans (an enzootic West Nile virus vector). These results are discussed in the context of operational considerations for LACV vector surveillance.

PMID:37364182 | DOI:10.2987/23-2116

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Accurate age-grading of field-aged mosquitoes reared under ambient conditions using surface-enhanced Raman spectroscopy and artificial neural networks

J Med Entomol. 2023 Jun 26:tjad067. doi: 10.1093/jme/tjad067. Online ahead of print.

ABSTRACT

Age-grading mosquitoes are significant because only older mosquitoes are competent to transmit pathogens to humans. However, we lack effective tools to do so, especially at the critical point where mosquitoes become a risk to humans. In this study, we demonstrated the capability of using surface-enhanced Raman spectroscopy and artificial neural networks to accurately age-grade field-aged low-generation (F2) female Aedes aegypti mosquitoes held under ambient conditions (error was 1.9 chronological days, in the range 0-22 days). When degree days were used for model calibration, the accuracy was further improved to 20.8 degree days (approximately equal to 1.4 chronological days), which indicates the impact of temperature fluctuation on prediction accuracy. This performance is a significant advancement over binary classification. The great accuracy of this method outperforms traditional age-grading methods and will facilitate effective epidemiological studies, risk assessment, vector intervention monitoring, and evaluation.

PMID:37364175 | DOI:10.1093/jme/tjad067

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A National Survey of the Training and Practice Patterns of Practicing Pediatric Advanced Endoscopists in the United States

J Pediatr Gastroenterol Nutr. 2023 Jun 27. doi: 10.1097/MPG.0000000000003864. Online ahead of print.

ABSTRACT

BACKGROUND AIMS: Pediatric advanced endoscopy consists primarily of Endoscopic Retrograde Cholangiopancreatography (ERCP) and Endoscopic Ultrasound (EUS) and is becoming more common in pediatrics. This study aims to characterize the current landscape of pediatric advanced endoscopy training and practice by directly surveying independently practicing pediatric advanced endoscopists (PAEs). We also aim to ascertain expert opinion on competency in pediatric ERCP and EUS.

METHODS: A 66-question REDCap survey and a 73-question Qualtrics survey were distributed to members of the ERCP Special Interest Group of North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Respondents currently performing ERCP or EUS independently in children were included. Statistical analysis was performed using Mann-Whitney U test.

RESULTS: Of 41 PAEs surveyed, 38 (92.7%) responded and 27 independent practitioners were included. 13 respondents performed EUS. PAEs who completed an advanced endoscopy fellowship (AEF) were more comfortable performing ASGE grade 3/4 ERCPs (p<0.0008) and felt more prepared to practice EUS independently than other trainees. Expert opinion of PAEs felt a threshold of 200 procedures was needed to attain competency in either ERCP or EUS. Pediatric duodenoscope exposure improved comfort in performing ERCP in children <10kg (p=0.009).

CONCLUSIONS: Training of pediatric gastroenterologists in ERCP and EUS are highly variable, though the skills attained are similar. AEF-trained specialists reported greater training volumes and felt more prepared to practice independently than those who did not. Competency thresholds determined by expert PAEs for ERCP and EUS agree with American Society for Gastrointestinal Endoscopy guidelines for adult advanced endoscopy trainees.

PMID:37364161 | DOI:10.1097/MPG.0000000000003864

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Endoscopic endonasal approach for acromegaly: surgical outcomes using 2018 consensus criteria for remission

Arch Endocrinol Metab. 2023 Jun 19;67(6):e000650. doi: 10.20945/2359-3997000000650.

ABSTRACT

OBJECTIVE: The primary aim is to analyze the endoscopic endonasal surgical results in short-term and two-year follow-ups according to the 11th Acromegaly Consensus statement (2018). Indeed, prognostic factors and complications were analyzed.

SUBJECTS AND METHODS: 40 patients who underwent endoscopic endonasal surgery by acromegaly between 2013 to 2020 was analyzed. Patients were considered in remission if an upper limit of normal (ULN) IGF-1 was less than 1.0 at the six-month and two-year follow-ups. Moreover, we assessed the Knosp grade, tumor volumetry, ULN, T2 signal in MRI, reoperation, and complications.

RESULTS: The mean age of admission was 46.7 years. Thirty-two patients were in remission after six months of surgery (80%), decreasing to 76.32% at the two-year follow-up. All microadenomas presented remission (n = 6). Regarding the complications, three patients had permanent panhypopituitarism (7.5%); postoperative cerebrospinal fluid (CSF) leaks did not occur in this series. The hyperintense signal on the T2 MRI and a higher tumor volumetry were the single predictor’s factors of non-emission in a multivariate regression logistic analysis (p < 0.05). Preoperative hormone levels (GH and IGF-1) were not a prognostic factor for remission. The re-operated patients who presented hypersignal already had a high predictor of clinical-operative failure.

CONCLUSION: The endoscopic endonasal surgery promotes high short-term and two-year remission rates in acromegaly; the tumor’s volumetry and the T2 hypersignal were statistically significant prognostic factors in non-remission – the complications presented at similar rates in comparison to the literature. In invasive GH-secreting tumors, we should offer these patients a multi-disciplinary approach to improve acromegalic patients’ remission rates.

PMID:37364152 | DOI:10.20945/2359-3997000000650