Nevin Manimala

J Clin Oncol. 2022 Oct 26:JCO2102371. doi: 10.1200/JCO.21.02371. Online ahead of print.

ABSTRACT

PURPOSE: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas.

PATIENTS AND METHODS: Eligible patients whose tumors screened positively for NF2 mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy.

RESULTS: Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events.

CONCLUSION: GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.

PMID:36288512 | DOI:10.1200/JCO.21.02371

Environ Sci Technol. 2022 Oct 26. doi: 10.1021/acs.est.2c04150. Online ahead of print.

ABSTRACT

As the largest emission source in the Pan-Third Pole region, residential solid fuel combustion gains increasing public concern regarding air pollution-associated health impacts. This study firstly developed emission inventories by combining energy statistics, fuel-mix survey, and detailed emission factors considering different fuel types, stove types, and altitudes, and we achieved full regional coverage and increased spatial resolution from 9 × 9 km to 1 km × 1 km. Total CO₂, CO, PM_2.5, SO₂, and NO_x emissions (coefficient of variation) were estimated to be 823 Mt (24%), 53 Mt (28%), 4525 kt (48%), 1388 kt (55%), and 1275 kt (46%) in 2020. India, Pakistan, and Bangladesh combined contributed 73, 57, 65, 67, and 69% of total CO₂, CO, PM_2.5, SO₂, and NO_x emissions, respectively, due to the large population. The Qinghai-Tibet Plateau had the second-highest emission intensity, mainly due to the high fuel consumption per capita. Unlike the emissions of the Pan-Third Pole in existing Asian inventories, dung cake combustion dominated total PM_2.5, SO₂, and NO_x emissions rather than firewood combustion with proportions of 54, 70, and 67%, respectively. The effect of altitude on combustion efficiencies increased PM_2.5 emissions by about 21% from the region. The method and results can provide technical guidance for emission inventory refinement in the Pan-Third Pole and other regions.

PMID:36288504 | DOI:10.1021/acs.est.2c04150

Int J Prosthodont. 2022 Oct 21. doi: 10.11607/ijp.7984. Online ahead of print.

ABSTRACT

PURPOSE: To compare the accuracy of milled vs printed complete denture bases and teeth and to assess the position of the teeth on the corresponding denture bases.

MATERIALS AND METHODS: Two different manufacturing techniques were used in this study. In group A, 10 complete dentures were digitally designed and fabricated by milling prepolymerized blocks of polymethyl methacrylate. In group B, 10 complete dentures were digitally designed and fabricated using the 3D printing technique. The accuracy of the maxillary and mandibular denture bases and teeth and the position of the teeth on the corresponding denture bases were evaluated using Geomagic Control X software. Data were presented as mean and SD values. Statistical analysis of the resultant data was performed using Student t test. The significance level was set at P ≤ .05.

RESULTS: The results revealed lower surface deviations of the maxillary and mandibular milled denture bases (group A) with values of 0.158 ± 0.024 and 0.117 ± 0.022, respectively. Lower surface deviations of the printed teeth (group B) were found with values of 0.18 ± 0.016 for the maxillary teeth and 0.153 ± 0.02 for the mandibular teeth, and for position of teeth on the corresponding denture bases, the values were 0.4 ± 0.08 for the maxillary teeth and 1.003 ± 0.027 for the position of the mandibular teeth.

CONCLUSION: The milling technique yields complete denture bases with superior accuracy, while printing technology provides denture teeth with better accuracy and positioning on the corresponding denture bases.

PMID:36288493 | DOI:10.11607/ijp.7984

Int J Prosthodont. 2022 Oct 21. doi: 10.11607/ijp.7332. Online ahead of print.

ABSTRACT

PURPOSE: To determine the effects of scanning protocol, number of implants, and implant splinting on the accuracy of digital scanning in the edentulous arch.

MATERIALS AND METHODS: A resin-based model of an edentulous mandible with six implants was scanned with a coordinate measurement machine as a reference and then with two intraoral scanner (IOS) systems (TRIOS 3 and Primescan). Ten scans were taken per IOS in three experiments, and each scan was compared to the reference to evaluate trueness and precision. Analysis involved using engineering software (GOM Inspect) to measure linear and angular discrepancies. In experiment 1, three scanning protocols were compared (linear, zigzag, and half-arch). In experiment 2, three clinical situations were simulated. In experiment 3, the effect of implant splinting with a suture thread was measured. Normal distribution of data was examined with Shapiro-Wilk test. Levene test was used for equality of variance (αα = .05). Statistical differences in distance and angular deviations were analyzed by Student t test or ANOVA with post hoc Tukey test (α = .05).

RESULTS: The best results in terms of trueness and precision were obtained with a linear scanning protocol and six implants: TRIOS 3 = trueness 52 µm/0.42 degrees, precision 40 µm/0.26 degrees; and Primescan = trueness 24 µm/0.28 degrees, precision 18 μm/0.27 degrees. The scanning protocol did not significantly affect distance or angular deviation accuracy. Trueness and precision significantly decreased with four implants using both Primescan and TRIOS 3. Splinting implants negatively affected accuracy with both scanners.

CONCLUSION: Both IOS systems achieved clinically satisfying accuracy in distance (< 100 μm) and angular (< 0.5 degrees) deviation with six implants and a linear scanning protocol. With four implants, angular deviations sometimes differed between implants within the same digital scan depending on the IOS and the clinical situation.

PMID:36288490 | DOI:10.11607/ijp.7332

Int J Prosthodont. 2022 Oct 21. doi: 10.11607/ijp.7821. Online ahead of print.

ABSTRACT

PURPOSE: To examine the effects of anodization and different surface modifications of titanium on bond strength to 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) resin cement.

MATERIALS AND METHODS: Grade 5 titanium alloy disks (n = 160) were assigned to one of five prebonding surface treatment study groups (polished; polished and anodized; polished, etched, and anodized; sandblasted; sandblasted and anodized). Disks were adhesively bonded with 10-MDP cement (Panavia 21; bonding area: 3.3 mm in diameter) to resin cylinders. In each study group, tensile bond strength tests were conducted after 24 ± 1 hours and after 6 months (180 ± 2 days) of water storage (n = 16 specimens per water storage subgroup). Debonded specimens were stereomicroscopically analyzed to determine their fracture mode. Statistics included one-way and multifactorial analysis of variance and Tukey post hoc tests (α = .05).

RESULTS: Anodization and water storage did not significantly (P ≥ .389) affect tensile bond strength. Although subgroups of polished samples had significantly (P ≤ .031) lower bond strengths (subgroup mean values: 20 to 26 MPa) than etched or sandblasted samples (subgroup mean values: 29 to 33 MPa), they nonetheless exceeded the empirical threshold of 10 MPa used as a criterion for clinical recommendation. The fracture mode of all test specimens was predominantly cohesive.

CONCLUSION: Anodization of titanium surfaces can be performed without weakening the adhesion of 10-MDP-based resin cement to titanium.

PMID:36288488 | DOI:10.11607/ijp.7821

Int J Prosthodont. 2022 Oct 21. doi: 10.11607/ijp.7824. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the trueness of five intraoral scanners for a fully edentulous model with seven implants.

MATERIALS AND METHODS: The study model was created from gypsum with seven implant analogs that were placed with 2-mm gingival height and 0-degree angle at tooth sites 47, 45, 43, 31, 33, 35, and 37. The study model was scanned 10 times (n = 10) with five intraoral scanners (CS3600, Emerald S, Primescan, TRIOS 3, TRIOS 4). The study model was digitized with a high-resolution industrial desktop scanner, and the data were imported into a software (Geomagic Studio 2012) as the reference model. The trueness assessment was made digitally with superimposition using the software. Linear measurements were calculated by the differences between the centers of the scan bodies on the study vs the reference model. Volumetric deviations were calculated with root mean square values. Data obtained in the study were analyzed statistically. One-way analysis of variance and Tukey tests were used to evaluate significant interactions. A value of P < .05 was accepted as statistically significant.

RESULTS: In linear measurements, TRIOS 4 showed the best trueness results, followed by TRIOS 3, Emerald S, Primescan, and CS3600. TRIOS 4 showed statistically truer results than CS3600 (P = .029). However, no statistically significant difference was found between groups in volumetric measurements (P < .05).

CONCLUSION: All of the intraoral scanners used in the study showed favorable deviation values in an edentulous model with seven implants. TRIOS 4 showed the best trueness values. The latest generation of intraoral scanners can be used in full-arch implant impressions.

PMID:36288487 | DOI:10.11607/ijp.7824

J Pediatr Endocrinol Metab. 2022 Oct 26. doi: 10.1515/jpem-2022-0305. Online ahead of print.

ABSTRACT

OBJECTIVES: Use of complementary and alternative medicine (CAM) is widespread. This study aimed to investigate the use of CAM in children with central precocious puberty (PP) who used gonadotropin-releasing hormone analog (GnRHa) treatment.

METHODS: Parents of 108 patients who were diagnosed as having PP were involved in the study. A questionnaire was administered to the parents during follow-ups. The patients were divided into two groups according to the use of CAM.

RESULTS: Forty (37%) patients had used CAM. Parents who graduated from primary school tended not to use CAM (χ ² =10.463; p=0.015). There was no other statistically significant difference between the sociodemographic features (p>0.05). The most common information source was physicians (40%). Seventy-five percentage of CAM users and 44.1% of non-CAM users knew/heard about herbal medicine (χ ² =8.517; p=0.004) and herbal medicine was the most common type of CAM used. 80% of parents in the CAM group and 54.4% of parents in the non-CAM group knew at least one biologically based therapy that had estrogenic activity (χ ² =6.082; p=0.014). Seventy-one percentage of parents in the CAM group and 29% of parents in the non-CAM group stated that they would consider using CAM in the future (χ ²=16.979; p<0.001).

CONCLUSIONS: The use of CAM among patients with PP is high. Although most CAM therapies are harmless, there may be adverse effects or drug interactions with current conventional treatment in children. Health professionals should be aware and inquire about the use and type of CAM, considering the medical history at every patient encounter.

PMID:36288430 | DOI:10.1515/jpem-2022-0305

Vestn Oftalmol. 2022;138(5):39-46. doi: 10.17116/oftalma202213805139.

ABSTRACT

Intrastromal keratoplasty has recently been widely used in the surgical treatment of keratoconus (KC). In 2013, a new type of interlamellar keratoplasty operation was developed – bandage therapeutic-optical keratoplasty (BTOK).

PURPOSE: Evaluation of the long-term outcomes of surgical treatment of stages II and III progressive KC with BTOK technique.

MATERIAL AND METHODS: The study included 107 patients (126 eyes): group 1 with stage II KC – 78 eyes, 100% of these patients were observed for 1 year, 52 eyes (66%) for 3 years, and 18 eyes (23%) for 5 years; group 2 – 48 eyes with stage III KC, with 100% of them observed for 1 year, 39 eyes (81%) for 3 years, and 12 eyes (25%) – 5 years. All patients received a customized allograft in the form of an intrastromal corneal ring segment (ICRS).

RESULTS: During the first year after BTOK surgery, the uncorrected and corrected visual acuity (UCVA and CVA) in the first group increased by 0.5±0.04 (p<0.05) and 0.2±0.02 (p<0.05), respectively, in the second group – by 0.46±0.05 (p<0.05) and 0.47±0.05 (p<0.05) due to a decrease in refractive indices in the central 3.0 mm zone. In the first group, mean refraction in the central 3.0 mm zone (K_m) was within 45±3.75 (p<0.05), in the second – 48.63±.2 diopters (p<0.05), while maximum refraction in the central 3.0 mm zone (K_max) decreased from 50.02±2.20 (p<0.05) to 44.61±1.03 diopters (p<0.05) in the first group, from 58.21±3.43 (p<0.05) to 50.45±3.46 diopters (p<0.05) in the second group. The values of UCVA, CVA and refractive indices of the central corneal zone in the first and second groups did not change statistically significantly after three and five years. Minimum corneal thickness in the first group increased from 476.23±13.35 to 485.08±15.80 µm (p<0.05), in the second – from 412.73±38.63 to 422.00±42.25 µm (p<0.05).

CONCLUSION: BTOK surgery can be used in patients with stages II and III KC to improve the visual functions, strengthen the ectatic cornea and stop the progression of the disease.

PMID:36288416 | DOI:10.17116/oftalma202213805139

Vestn Oftalmol. 2022;138(5):30-38. doi: 10.17116/oftalma202213805130.

ABSTRACT

In recent years, a new class of extended depth of focus (EDOF) intraocular lenses (IOLs) has become available on the market. There is only a limited number of scientific papers comparing trifocal and EDOF IOL data, and the results are often contradictory.

PURPOSE: Comparative analysis of the results of trifocal and EDOF IOL implantation in patients with presbyopia and/or cataract.

MATERIAL AND METHODS: This prospective study included 72 patients (144 eyes) after bilateral implantation of either Tecnis Symfony EDOF IOL (18 patients, 36 eyes; group I) or AcrySof PanOptix trifocal IOL (54 patients, 108 eyes; group II). In 18 patients out of 72 (25%) the implantation involved mini-monovision, i.e. the calculation of the IOL power on the nondominant eye was performed at -0.5 D. The average follow-up period for the patients was 7.1±1.2 months.

RESULTS: There was a significant (p<0.05) increase in uncorrected near visual acuity (UCNVA), uncorrected intermediate visual acuity (UCIVA) and uncorrected distance visual acuity (UCDVA) at the maximum follow-up time compared to the preoperative indices in all groups. Group II was characterized by slightly better UCNVA dynamics (0.85±0.13 versus 0.2±0.04 before surgery, as comparted to 0.78±0.11 versus 0.19±0.06 before surgery in group I), but differences were not statistically significant (p>0.05). Statistically significant differences (p=0.046) were observed when comparing best corrected near vision acuity (BCNVA) in groups I and II (0.79±0.05 and 0.98±0.08, respectively) at 6 months compared to the preoperative period (0.62±0.09 and 0.6±0.11, respectively).

CONCLUSION: Trifocal IOL implantation was associated with acceptable near and far vision correction and a higher frequency of adverse optical phenomena, while implantation of the EDOF IOL was associated with slightly better correction of intermediate vision and a significantly lower incidence of halo and glare. Patients were satisfied with the outcomes of surgery in all cases.

PMID:36288415 | DOI:10.17116/oftalma202213805130

Vestn Oftalmol. 2022;138(5):22-28. doi: 10.17116/oftalma202213805122.

ABSTRACT

PURPOSE: To study features of anatomical and morphometric parameters of the structures of anterior eye segment in young patients with moderate and high hyperopia in order to identify the signs of an increased risk of developing primary angle-closure glaucoma (PACG) and its acute attack.

MATERIAL AND METHODS: The study included 160 eyes (80 patients) with axial length (AL) of less than 23 mm. Patients with moderate or high hyperopia were divided into two groups according to their age ranges (the 1^st – 27 patients (54 eyes) under 40 years old; the 2^nd – 27 patients (54 eyes) of 41-50 years old, the comparison group – 26 patients (52 eyes) of 42-50 years old with the initial stage of PACG. AL of the eyes, anterior chamber (AC) depth in the central zone, lens thickness (LT) in the optical zone were measured using IOL Master 700 («Carl Zeiss Meditec AG», Germany). AC volume and peripheral AC depth were measured using rotating Scheimpflug camera Pentacam («Oculus», Germany).

RESULTS: While the average values of AL in patients of the 1^st and 2^nd groups were comparable, a statistically significant decrease in AC depth and a significant increase in LT were revealed in the 2^nd group. There was a statistically significant increase in LT, a decrease in peripheral AC depth and AC volume in the comparison group relative to the 2^nd group. In the 1^st group: in 2 eyes of one 38-year-old patient the maximum proximity of all 3 indices to the median values of the group of patients with PACG was found; in 4 eyes of two other patients (35 and 38 years old), a combination of small AC volume with increased LT or small AC volume with small AC on the periphery was noted.

CONCLUSION: Significant differences in terms of LT, peripheral AC depth and AC volume were found between age-comparable (41-50 years old) healthy individuals with short eyes and patients with initial PACG. In 11% of the eyes of healthy patients with hyperopia aged 21 to 40 years, there was a combination of two or three of the studied morphometric signs, which may indicate the risk of developing PACG.

PMID:36288414 | DOI:10.17116/oftalma202213805122