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Association of Intraoperative Frozen Section Controls With Improved Margin Assessment During Transoral Robotic Surgery for Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

JAMA Otolaryngol Head Neck Surg. 2022 Sep 22. doi: 10.1001/jamaoto.2022.2840. Online ahead of print.

ABSTRACT

IMPORTANCE: Intraoperative margin assessment is an important technique for ensuring complete tumor resection in malignant cancers. However, in patients undergoing transoral robotic surgery (TORS) for oropharyngeal carcinomas, tissue artifact may provide pathologic uncertainty.

OBJECTIVE: To assess the benefit of providing frozen section control samples (“positive tumor biopsies”) for use during intraoperative margin assessment for patients undergoing TORS for human papillomavirus (HPV)-16-positive oropharyngeal squamous cell carcinoma (OPSCC).

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, patients receiving curative-intent TORS for biopsy-proven HPV-16-positive OPSCC performed by a single attending surgeon (A.H.M.) at Ronald Reagan UCLA Medical Center from 2017 to 2021 were included in a retrospective data analysis. Exclusion criteria included HPV-negative status, participation in clinical trials, and tumors of unknown primary origin.

MAIN OUTCOMES AND MEASURES: Survival outcomes investigated included overall and disease-free survival. Adverse pathologic outcomes measured included occurrence of nondiagnostic margins and margin reversal from frozen to fixed pathology.

RESULTS: Of the 170 patients included (mean [SD] age, 61.8 [9.9] years; 140 [82%] male), 50% of patients (n = 85) received a frozen section control. Use of a frozen section control was associated with statistically significantly improved sensitivity of intraoperative margin assessment, from 82.8% to 88.9% (difference, 6.1%; 95% CI, 3.9%-8.3%). Eleven percent (n = 18) of all tumors evaluated exhibited at least 1 nondiagnostic intraoperative margin, and 11% (n = 18) experienced margin reversal from frozen to fixed pathology. In patients with nondiagnostic margins, use of frozen section controls was associated with statistically significantly reduced time spent in the operating room (Cohen d, 1.14; 95% CI, 0.12-2.14).

CONCLUSIONS AND RELEVANCE: In this cohort study, frozen intraoperative margins assessed during TORS resections of HPV-16-positive OPSCC were diagnostically challenging. Adverse pathologic outcomes, such as margin status reversal from positive on frozen pathology to negative on formal analysis, were common. Providing intraoperative frozen section control biopsies may offer clarity in cases with nondiagnostic margins, reducing the need for additional sampling and time spent in the operating room.

PMID:36136328 | DOI:10.1001/jamaoto.2022.2840

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Visual Outcomes and Optical Quality of Accommodative, Multifocal, Extended Depth-of-Focus, and Monofocal Intraocular Lenses in Presbyopia-Correcting Cataract Surgery: A Systematic Review and Bayesian Network Meta-analysis

JAMA Ophthalmol. 2022 Sep 22. doi: 10.1001/jamaophthalmol.2022.3667. Online ahead of print.

ABSTRACT

IMPORTANCE: A bayesian network meta-analysis (NMA) can help compare the various types of multifocal and monofocal intraocular lenses (IOLs) used in clinical practice.

OBJECTIVE: To compare outcomes of presbyopia-correcting IOLs frequently recommended in clinical practice through a bayesian NMA based on a systematic review.

DATA SOURCES: Medline (PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched on May 15, 2021, from inception.

STUDY SELECTION: Based on the research question, randomized clinical trials assessing multifocal IOLs in patients who underwent bilateral cataract extraction were searched. Nonrandomized studies, studies in patients with unilateral or contralateral cataract extractions, duplicated studies, conference abstracts, and nonpeer-reviewed articles were excluded.

DATA EXTRACTION AND SYNTHESIS: Descriptive statistics and outcomes were extracted. The NMA was conducted to compare different types of IOLs. The mean differences for continuous variables, odds ratios for binary variables, 95% credible intervals (CrIs), and ranks of interventions were estimated.

MAIN OUTCOMES AND MEASURES: The outcomes examined included binocular visual acuities by distance and optical quality, including glare, halos, and spectacle independence.

RESULTS: This NMA included 27 studies comprising 2605 patients. For uncorrected near visual acuity, trifocal IOLs (mean difference, -0.32 [95% CrI, -0.46 to -0.19]) and old bifocal diffractive IOLs (mean difference, -0.33 [95% CrI, -0.50 to -0.14]) afforded better visual acuity than monofocal IOLs. Regarding uncorrected intermediate visual acuity, extended depth-of-focus IOLs provided better visual acuity than monofocal IOLs. However, there were no differences between extended depth-of-focus and trifocal diffractive IOLs in pairwise comparisons. For uncorrected distant visual acuity, all multifocal IOLs were comparable with monofocal IOLs. There were no statistical differences between multifocal and monofocal IOLs regarding contrast sensitivity, glare, or halos.

CONCLUSIONS AND RELEVANCE: For patients considering a multifocal IOL due to presbyopia, bilateral implantation of a trifocal IOL might be an optimal option for patients without compromising distant visual acuity.

PMID:36136323 | DOI:10.1001/jamaophthalmol.2022.3667

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Differences in Cancer Phenotypes Among Frequent CHEK2 Variants and Implications for Clinical Care-Checking CHEK2

JAMA Oncol. 2022 Sep 22. doi: 10.1001/jamaoncol.2022.4071. Online ahead of print.

ABSTRACT

IMPORTANCE: Germline CHEK2 pathogenic variants (PVs) are frequently detected by multigene cancer panel testing (MGPT), but our understanding of PVs beyond c.1100del has been limited.

OBJECTIVE: To compare cancer phenotypes of frequent CHEK2 PVs individually and collectively by variant type.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was carried out in a single diagnostic testing laboratory from 2012 to 2019. Overall, 3783 participants with CHEK2 PVs identified via MGPT were included. Medical histories of cancer in participants with frequent PVs, negative MGPT (wild type), loss-of-function (LOF), and missense were compared.

MAIN OUTCOMES AND MEASURES: Participants were stratified by CHEK2 PV type. Descriptive statistics were summarized including median (IQR) for continuous variables and proportions for categorical characteristics. Differences in age and proportions were assessed with Wilcoxon rank sum and Fisher exact tests, respectively. Frequencies, odds ratios (ORs), 95% confidence intervals were calculated, and P values were corrected for multiple comparisons where appropriate.

RESULTS: Of the 3783 participants with CHEK2 PVs, 3473 (92%) were female and most reported White race. Breast cancer was less frequent in participants with p.I157T (OR, 0.66; 95% CI, 0.56-0.78; P<.001), p.S428F (OR, 0.59; 95% CI. 0.46-0.76; P<.001), and p.T476M (OR, 0.74; 95% CI, 0.56-0.98; P = .04) PVs compared with other PVs and an association with nonbreast cancers was not found. Following the exclusion of p.I157T, p.S428F, and p.T476M, participants with monoallelic CHEK2 PV had a younger age at first cancer diagnosis (P < .001) and were more likely to have breast (OR, 1.83; 95% CI, 1.66-2.02; P < .001), thyroid (OR, 1.63; 95% CI, 1.26-2.08; P < .001), and kidney cancer (OR, 2.57; 95% CI, 1.75-3.68; P < .001) than the wild-type cohort. Participants with a CHEK2 PV were less likely to have a diagnosis of colorectal cancer (OR, 0.62; 95% CI, 0.51-0.76; P < .001) compared with those in the wild-type cohort. There were no significant differences between frequent CHEK2 PVs and c.1100del and no differences between CHEK2 missense and LOF PVs.

CONCLUSIONS AND RELEVANCE: CHEK2 PVs, with few exceptions (p.I157T, p.S428F, and p.T476M), were associated with similar cancer phenotypes irrespective of variant type. CHEK2 PVs were not associated with colorectal cancer, but were associated with breast, kidney, and thyroid cancers. Compared with other CHEK2 PVs, the frequent p.I157T, p.S428F, and p.T476M alleles have an attenuated association with breast cancer and were not associated with nonbreast cancers. These data may inform the genetic counseling and care of individuals with CHEK2 PVs.

PMID:36136322 | DOI:10.1001/jamaoncol.2022.4071

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Comparison of High-Sensitivity C-Reactive Protein vs C-reactive Protein for Cardiovascular Risk Prediction in Chronic Cardiac Disease

J Appl Lab Med. 2022 Sep 22:jfac069. doi: 10.1093/jalm/jfac069. Online ahead of print.

ABSTRACT

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is a biomarker used for risk prediction for cardiovascular disease by assessing low concentration of inflammation. Measurements of regular CRP have become very sensitive with a lower detection limit of 0.3 mg/L. This study aimed to compare and explore the association between CRP and hs-CRP.

METHODS: Data from 607 consecutive patients referred for cardiovascular risk assessment with hs-CRP were reviewed retrospectively. In total, 570 patients were included in the analysis and classified into 3 (low-, medium-, and high-risk) groups (hs-CRP cutoff: <1, 1-3, >3 mg/L). Correlation between hs-CRP and CRP was assessed with the kappa statistic and visualized with a Bland-Altman plot. The association between hs-CRP and occurrence of the composite outcome (acute myocardial infarction, stroke, coronary intervention [percutaneous coronary intervention or bypass surgery], or death) was determined with Cox regression analysis and visualized with Kaplan-Meier curves.

RESULTS: A total number reclassification occurred in 8.6% of the cases for CRP risk groups, which demonstrates an agreement of 91.4% (kappa 0.87; P < 0.001). The correlation between CRP and hs-CRP was significant (P < 0.001), Spearman regression R2 = 0.98. A Bland-Altman plot displayed an average difference of 0.19 mg/L (95%CI, 0.17 to 0.23) between the CRP and hs-CRP. Cardiovascular events were more likely to occur in patients who were older, with hs-CRP or CRP >3 mg/L and a history of coronary artery disease.

CONCLUSIONS: The usual laboratory tests for CRP values in the lower range highly correlate with the hs-CRP tests and can therefore replace the costlier hs-CRP measurements.

PMID:36136302 | DOI:10.1093/jalm/jfac069

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Impact of COVID-19 infection on the dialysis population prospective, observational, nationwide study

Int Urol Nephrol. 2022 Sep 22. doi: 10.1007/s11255-022-03368-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Hemodialysis (HD) patients are at increased risk of severe COVID-19 infection but infection rates vary. Our objectives are to describe COVID-19 positive HD patients’ characteristics, infection rates, and factors associated with mortality in HD COVID-19 cases in Kuwait.

METHODS: Data on demographics, comorbidities, and treatments received, as well as mortality for HD patients admitted to hospitals for COVID-19, from 1/March to 31/July 2020, prospectively collected and analyzed.

RESULTS: A total of 141 infected HD patients were admitted (Mean age 58 ± 16.1; Males 56%), representing 7% of the total HD population and 0.2% of all COVID-19 cases during the study period. Of those 141 infected HD patients, 27 (19%) died, and this represents 6% of total COVID-19-related mortality and 27% of the total HD mortality. In contrast, total covid-19-related mortality of all positive cases was only 0.7%, and total HD mortality during the study period was only 5%. COVID-19-positive HD patients who died were older and 59% were males. However, the differences were not statistically significant. Of the 61 infected HD patients who needed to be switched to continuous kidney replacement therapy (CKRT), 34% died, and of the 29 infected HD patients who needed admission to intensive care, 65% died.

CONCLUSION: HD population represents a small fraction of the total population; however, positive HD COVID-19 cases represent a sizable proportion of COVID-19 cases and a significant percentage of total COVID-19-related mortality, and total HD mortality.

PMID:36136260 | DOI:10.1007/s11255-022-03368-1

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Fish oil administration combined with resistance exercise training improves strength, resting metabolic rate, and inflammation in older adults

Aging Clin Exp Res. 2022 Sep 22. doi: 10.1007/s40520-022-02250-5. Online ahead of print.

ABSTRACT

BACKGROUND: While fish oil (FO) has attracted great attention due to their health-enhancing properties, its potential to enhance benefits from resistance exercise training (RET) has not been fully elucidated yet.

AIMS: The aim of this study was to investigate effects of FO administration during 12 weeks of programmed RET on muscular strength, resting metabolic rate (RMR), and systemic inflammation in healthy older adults.

METHODS: Twenty-eight healthy older adults were randomly assigned to three experimental groups: sedentary control (CON), resistance exercise training (RET), or RET combined with FO (RET-FO). A one-repetition (1RM) of maximum muscle strength, RMR, substrate oxidation, and blood inflammatory biomarkers were assessed before and after the intervention. Statistical significance was set at p ≤ 0.05.

RESULTS: 1RM muscle strength was significantly increased in RET and RET-FO while substantially decreased in CON. RMR greatly increased in RET and RET-FO with no change in CON. RET-FO exhibited significantly increased fatty acid oxidation, but no change was found in CON and RET. Systemic interleukin 6 (IL-6) and C-reactive protein (CRP) were significantly decreased from baseline in RET-FO while no change was observed in CON and RET.

CONCLUSION: Our data indicate chronic RET reversed aging-induced loss of muscle strength and improved RMR, while FO administration combined with RET appears to enhance fat metabolism and mildly reduce some indicators of systemic inflammation.

PMID:36136236 | DOI:10.1007/s40520-022-02250-5

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Comprehensive evaluation of end-point free energy techniques in carboxylated-pillar[6]arene host-guest binding: I. Standard procedure

J Comput Aided Mol Des. 2022 Sep 22. doi: 10.1007/s10822-022-00475-0. Online ahead of print.

ABSTRACT

Despite the massive application of end-point free energy methods in protein-ligand and protein-protein interactions, computational understandings about their performance in relatively simple and prototypical host-guest systems are limited. In this work, we present a comprehensive benchmark calculation with standard end-point free energy techniques in a recent host-guest dataset containing 13 host-guest pairs involving the carboxylated-pillar[6]arene host. We first assess the charge schemes for solutes by comparing the charge-produced electrostatics with many ab initio references, in order to obtain a preliminary albeit detailed view of the charge quality. Then, we focus on four modelling details of end-point free energy calculations, including the docking procedure for the generation of initial condition, the charge scheme for host and guest molecules, the water model used in explicit-solvent sampling, and the end-point methods for free energy estimation. The binding thermodynamics obtained with different modelling schemes are compared with experimental references, and some practical guidelines on maximizing the performance of end-point methods in practical host-guest systems are summarized. Further, we compare our simulation outcome with predictions in the grand challenge and discuss further developments to improve the prediction quality of end-point free energy methods. Overall, unlike the widely acknowledged applicability in protein-ligand binding, the standard end-point calculations cannot produce useful outcomes in host-guest binding and thus are not recommended unless alterations are performed.

PMID:36136209 | DOI:10.1007/s10822-022-00475-0

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Mercury(II) and lead(II) ions removal using a novel thiol-rich hydrogel adsorbent; PHPAm/Fe3O4@SiO2-SH polymer nanocomposite

Environ Sci Pollut Res Int. 2022 Sep 22. doi: 10.1007/s11356-022-23055-z. Online ahead of print.

ABSTRACT

The abundant release of toxic heavy metals into wastewater has been a serious threat to human health, aquatic environments, plants, and animals; thus, it is critical to purify wastewater of these pollutants through a proper treatment process. A novel hydrogel compound was synthesized using partially hydrolyzed polyacrylamide (PHPAm) and functionalized Fe3O4-coated magnetic nanoparticles (PHPAm/Fe3O4@SiO2-SH) that is efficient in removal of mercury and lead from wastewater. This new magnetic nanoadsorbent is characterized using scanning electron microscope, Fourier-transform infrared, thermogravimetric analysis, vibrating sample magnetometer, and energy-dispersive X-ray analysis. The central composite design under response surface methodology (CCD-RSM) was applied in designing the experiments to optimize the main parameters affecting the adsorption capacity: initial concentration (77.50 mg L-1), pH (6.11 and 6.48), adsorbent dosage (25 mg), and contact time (115 and 106 min) for both Hg2+ and Pb2+ adsorption, respectively. Quadratic models were used for variable predictions and analysis of variance was applied to evaluate the statistical parameters and investigate the interactions of the variables. The high determination coefficient (R2 0.99) for both metals indicates a good correlation between actual and predicted response values. Additionally, thermodynamic modeling showed an endothermic and exothermic for Hg2+ and Pb2+, respectively, and also the spontaneous nature of both metals’ adsorption process within the temperature range of 288-318 K. Mercury and lead kinetic studies were in agreement with pseudo-second-order modeling, and the equilibrium results revealed that the Langmuir isotherm best fit the experimental data with maximum adsorption capacities of 256.41 and 227.27 (mg g-1) for Hg2+ and Pb2+, respectively. Overall, PHPAm/Fe3O4@SiO2-SH is thought to have highly promising potential for investigating heavy metals in wastewater treatment, and will make important contributions to similar studies that may be conducted in the future.

PMID:36136188 | DOI:10.1007/s11356-022-23055-z

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Source identification and health risks of nitrate contamination in shallow groundwater: a case study in Subei Lake basin

Environ Sci Pollut Res Int. 2022 Sep 22. doi: 10.1007/s11356-022-23129-y. Online ahead of print.

ABSTRACT

Nitrate pollution of groundwater has become a global concern as it can affect drinking water quality and human health. In this paper, an extensive hydrochemical investigation was performed to assess the spatial distribution, source identification, and health risk of groundwater nitrate pollution in the Subei Lake basin. The prevalent pollutant, nitrate (NO3), was identified based on descriptive statistical method and box plots, and most of the other parameters of groundwater samples met water standards and can be used for drinking purpose. The results showed that nearly 23.53% of groundwater samples displays the NO3 concentrations higher than the limit of 50 mg/L recommended by the World Health Organization, and the highest nitrate content (199 mg/L) is mainly distributed around the Mukai Lake. Piper triangle diagram demonstrated that the dominated anions of hydrochemical types exhibit a gradual evolving trend from HCO3 to SO42- and Cl with increasing nitrate concentration. The correspondence analysis suggested that agricultural activities are identified as the most possible source of nitrate contamination, while the higher content of other parameters in individual groundwater samples may be controlled by natural factors. The impacts of pollutant NO3 on human health were quantified using human health risk assessment method, and results showed that the order of non-carcinogenic health risk values through drinking water intake is Infants>Children>Adult males>Adult females, and 65%, 53%, 41%, and 35% of samples exceed the acceptable risk level (hazard quotient=1), respectively. The main findings obtained from this study can provide valuable insight on drinking water safety and groundwater pollution prevention.

PMID:36136183 | DOI:10.1007/s11356-022-23129-y

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Computer-guided buccal cortical plate separation for removal of calcified benign odontogenic tumors affecting the mandibular angle region

Maxillofac Plast Reconstr Surg. 2022 Sep 22;44(1):30. doi: 10.1186/s40902-022-00354-6.

ABSTRACT

PURPOSE: Surgical removal of intra-bony calcific benign lesions is technically challenging regarding its accessibility, proximity to vital structures, and deteriorating effect on the remaining bony structures.

METHODS: Computer-guided buccal cortical plate separation was performed for ten patients using patient-specific osteotomy locating guides and pre-bent plates. The guide was designed to outline the osteotomy, the buccal cortical plate was separated, the lesion was removed, and finally, the pre-bent plates were used to fix the separated cortex.

RESULTS: Surgical procedures were uneventful for all patients, operation time was 39.5 ± 13.01 min, postoperative pain decreased within the follow-up time intervals, and there was a statistical significant difference between the time intervals (P value < 0.001). Edema and trismus were acceptable. One case showed nerve affection which resolved after 4 weeks.

CONCLUSION: Computer-guided buccal cortical plate separation for removal of intra-bony calcified benign lesions provides a promising approach, especially for inexperienced surgeons.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05329974 . Registered on 6 April 2022-retrospectively registered.

PMID:36136180 | DOI:10.1186/s40902-022-00354-6