Predictors in the treatment of malignant central airway obstruction with silicone stents.

PURPOSE: To examine the role of the silicone stent in palliation of malignant central airway obstruction and identify potential preprocedural predictors for postprocedural outcome. METHODS: Patients treated with endoscopic insertion of tracheobronchial silicone stents for malignant central airway obstruction at Aarhus University Hospital from 2012 to 2022 were identified from electronic medical records. Statistical analyses were carried out to identify factors affecting Days Alive and Out of Hospital, complications and overall survival. RESULTS: 81 patients underwent a total of 90 tracheobronchial stent insertions. Days Alive and Out of Hospital (DAOH) for the first 30 days were affected negatively by urgent intervention, p < 0.001, preprocedural non-invasive respiratory support, p < 0.001, and preprocedural intubation, p = 0.02. Post-procedural oncological treatment was associated with a significant improved DAOH, p = 0.04. Symptomatology and lesion characteristics were not significantly associated with any impact on DAOH. Overall survival was poor (mean survival was 158 days), and only significantly affected by severe degree of dyspnea, p = 0.02, and postprocedural oncological treatment, p < 0.001. Complication where registered in 25.6% of cases within the first 30 days was observed. Procedure-related mortality was 3.7%. Based on chart annotations by an ENT-surgeon, 95% of the patients experienced relief of symptoms following stent insertion. CONCLUSIONS: Palliative tracheobronchial airway stenting with silicone stents is found to have a beneficial impact, more research is required for identification of predictors for postprocedural outcome based on preprocedural classifications.

Incidence and malignant transformation of glottic precursor lesions in Denmark.

Objectives: Glottic precursor lesion (GPL) is a well-known premalignant condition, but the existing knowledge of incidence and malignant potential is based on subpopulation studies. In this first, nationwide study we report data from all verified cases of GPL in Denmark during a 10-year period with focus on incidence and malignant transformation of GPL.Methods: Patients were identified by a search for GPL in the time period from 01.01.2000 to 31.12.2009 using the Danish Pathology Data Base, Patobank, which is a nationwide source of all cyto- and histopathological data obtained in Denmark. Data were validated and supplemented by medical chart review.Results: A 10-year national cohort of 965 patients (median age 60 years, male-female ratio 2:1) with histologically verified GPL was analyzed. The overall malignant transformation rate was 18.3% (mild dysplasia 7.7%, moderate dysplasia 19.8%, severe dysplasia 28.5%, and carcinoma in situ 40.3%) with a median progression time of 29 months. Eighty-eight percent of patients were active or former smokers. A significantly larger proportion of male patients (24.1%) experienced malignant transformation compared to females (6.6%) (p < .001).Conclusion: This nationwide population-based study of GPL patients confirmed a stable incidence of GPL in Denmark from January 2000 to December 2009 and a considerable malignant potential, correlated to the grading of GPL according to the World Health Organization classification of laryngeal precursor lesions from 2005, WHOC2005. The recent update, WHOC2017, of low-grade versus high-grade lesions may thus contain less nuanced prognostic information than WHOC2005.Level of evidence: 2b retrospective cohort study.

Interrater variation of vascular classifications used in enhanced laryngeal contact endoscopy.

PURPOSE: Combined use of contact endoscopy (CE) and Narrow Band Imaging (NBI, Olympus®) is suggested for the visualization of specific vascular changes indicative of glottic neoplasia. We investigated the interrater reliability and agreement in 3 recognized classification systems of vascular changes applied to images from CE + NBI in patients suspected for glottic neoplasia. METHODS: Six experienced head and neck surgeons familiar with NBI rated 120 images obtained by CE + NBI by 3 classification systems of vascular changes as suggested by Ni et al. (N-C), Puxeddu et al. (P-C), and the European Laryngological Society (ELS-C). Three raters were experienced in CE, and three raters had only limited experience with CE. Crude agreement and Fleiss' kappa with 95% confidence interval were estimated for all 6 raters, and for the 2 levels of expertise for each original classification system and for dichotomized versions of the N-C and the P-C based on suggested neoplastic potential. RESULTS: The interrater crude agreement and the corresponding kappa values for the ELS-C were good and significantly higher than those for the N-C and P-C for all raters, irrespective of the level of experience with CE (p < 0.0001). There were no significant differences between the N-C and the P-C (p = 0.16). Kappa was considerably improved for both the N-C and the P-C to a level not different from the ELS-C (p = 0.21-0.71) when their 5 original categories were pooled into dichotomized classifications. CONCLUSION: Difficulties in reliably classifying vascular changes in CE + NBI are evident. Two-tier classification systems are the most reliable.

Value of pre- and intraoperative diagnostic methods in suspected glottic neoplasia.

PURPOSE: To evaluate the individual and combined ability of videostroboscopy (VS), high-speed digital imaging (HSDI), enhanced endoscopy (EE) and saline infusion (SI) to predict neoplasia, defined as glottic precursor lesion (GPL) or T1a glottic cancer, in patients suspected for glottic neoplasia. METHODS: A nationwide prospective cohort study of patients treated by cordectomy for suspected GPL or T1a glottic cancer from August 1st 2016 to October 31st 2018 was conducted in the five Danish University Departments of Head and Neck surgery. Sensitivity, specificity, negative and positive predictive values, and area under Receiver Operating Curves (AUC-ROC) were calculated with 95% confidence intervals with respect to the histological diagnosis. Logistic regression with an imputation model for missing data was applied. RESULTS: 261 patients aged 34-91 years participated; 79 (30.3%) with non-neoplasia (i.e., inflammation, papilloma, hyperkeratosis) and 182 (69.7%) neoplasia, hereof 95 (36.4%) with GPL and 87 (33.3%) with T1a glottic cancer. Data from 188 VS, 60 HSDI, 100 preoperative EE, 209 intraoperative EE, and 234 SI were analyzed. In the complete case analysis the AUC-ROC of each diagnostic test was low, but increased when the tests were combined and especially if the combination included EE. However, multinomial logistic regression with imputation showed significant association (p < 0.05) only between age, male gender, and perpendicular vasculature in intraoperative EE, and the endpoint neoplasia. CONCLUSIONS: Intraoperative EE was the most accurate diagnostic method in detecting neoplasia. The prediction ability of methods applied preoperatively was more limited, but improved when test modalities were combined.

The GPU-enabled divide-expand-consolidate RI-MP2 method (DEC-RI-MP2).

We report porting of the Divide-Expand-Consolidate Resolution of the Identity second-order Møller-Plesset perturbation (DEC-RI-MP2) method to the graphic processing units (GPUs) using OpenACC compiler directives. It is shown that the OpenACC compiler directives implementation efficiently accelerates the rate-determining step of the DEC-RI-MP2 method with minor implementation effort. Moreover, the GPU acceleration results in a better load balance and thus in an overall scaling improvement of the DEC algorithm. The resulting cross-platform hybrid MPI/OpenMP/OpenACC implementation has scalable and portable performance on heterogeneous HPC architectures. The GPU-enabled code was benchmarked using a reduced version of the S12L test set of Stefan Grimme (Grimme, Chem. Eur. J. 2012, 18, 9955) consisting of supramolecular complexes up to 158 atoms and 4292 contracted basis functions (cc-pVTZ). The test set results demonstrate the general applicability of the DEC-RI-MP2 method showing results consistent with the DEC-RI-MP2 introductory paper (Baudin et al., J. Chem. Phys. 2016, 144, 054102) on molecules of complicated electronic structures. © 2016 Wiley Periodicals, Inc.

The Laplace transformed divide-expand-consolidate resolution of the identity second-order Møller-Plesset perturbation (DEC-LT-RIMP2) theory method.

The divide-expand-consolidate resolution of the identity second-order Møller-Plesset perturbation (DEC-RI-MP2) theory method introduced in Baudin et al. [J. Chem. Phys. 144, 054102 (2016)] is significantly improved by introducing the Laplace transform of the orbital energy denominator in order to construct the double amplitudes directly in the local basis. Furthermore, this paper introduces the auxiliary reduction procedure, which reduces the set of the auxiliary functions employed in the individual fragments. The resulting Laplace transformed divide-expand-consolidate resolution of the identity second-order Møller-Plesset perturbation method is applied to the insulin molecule where we obtain a factor 9.5 speedup compared to the DEC-RI-MP2 method.

CC2 oscillator strengths within the local framework for calculating excitation energies (LoFEx).

In a recent work [P. Baudin and K. Kristensen, J. Chem. Phys. 144, 224106 (2016)], we introduced a local framework for calculating excitation energies (LoFEx), based on second-order approximated coupled cluster (CC2) linear-response theory. LoFEx is a black-box method in which a reduced excitation orbital space (XOS) is optimized to provide coupled cluster (CC) excitation energies at a reduced computational cost. In this article, we present an extension of the LoFEx algorithm to the calculation of CC2 oscillator strengths. Two different strategies are suggested, in which the size of the XOS is determined based on the excitation energy or the oscillator strength of the targeted transitions. The two strategies are applied to a set of medium-sized organic molecules in order to assess both the accuracy and the computational cost of the methods. The results show that CC2 excitation energies and oscillator strengths can be calculated at a reduced computational cost, provided that the targeted transitions are local compared to the size of the molecule. To illustrate the potential of LoFEx for large molecules, both strategies have been successfully applied to the lowest transition of the bivalirudin molecule (4255 basis functions) and compared with time-dependent density functional theory.

The molecular gradient using the divide-expand-consolidate resolution of the identity second-order Møller-Plesset perturbation theory: The DEC-RI-MP2 gradient.

We report an implementation of the molecular gradient using the divide-expand-consolidate resolution of the identity second-order Møller-Plesset perturbation theory (DEC-RI-MP2). The new DEC-RI-MP2 gradient method combines the precision control as well as the linear-scaling and massively parallel features of the DEC scheme with efficient evaluations of the gradient contributions using the RI approximation. We further demonstrate that the DEC-RI-MP2 gradient method is capable of calculating molecular gradients for very large molecular systems. A test set of supramolecular complexes containing up to 158 atoms and 1960 contracted basis functions has been employed to demonstrate the general applicability of the DEC-RI-MP2 method and to analyze the errors of the DEC approximation. Moreover, the test set contains molecules of complicated electronic structures and is thus deliberately chosen to stress test the DEC-RI-MP2 gradient implementation. Additionally, as a showcase example the full molecular gradient for insulin (787 atoms and 7604 contracted basis functions) has been evaluated.

Nuclei-selected atomic-orbital response-theory formulation for the calculation of NMR shielding tensors using density-fitting.

An atomic orbital density matrix based response formulation of the nuclei-selected approach of Beer, Kussmann, and Ochsenfeld [J. Chem. Phys. 134, 074102 (2011)] to calculate nuclear magnetic resonance (NMR) shielding tensors has been developed and implemented into LSDalton allowing for a simultaneous solution of the response equations, which significantly improves the performance. The response formulation to calculate nuclei-selected NMR shielding tensors can be used together with the density-fitting approximation that allows efficient calculation of Coulomb integrals. It is shown that using density-fitting does not lead to a significant loss in accuracy for both the nuclei-selected and the conventional ways to calculate NMR shielding constants and should thus be used for applications with LSDalton.

Efficient linear-scaling second-order Møller-Plesset perturbation theory: The divide-expand-consolidate RI-MP2 model.

The Resolution of the Identity second-order Møller-Plesset perturbation theory (RI-MP2) method is implemented within the linear-scaling Divide-Expand-Consolidate (DEC) framework. In a DEC calculation, the full molecular correlated calculation is replaced by a set of independent fragment calculations each using a subset of the total orbital space. The number of independent fragment calculations scales linearly with the system size, rendering the method linear-scaling and massively parallel. The DEC-RI-MP2 method can be viewed as an approximation to the DEC-MP2 method where the RI approximation is utilized in each fragment calculation. The individual fragment calculations scale with the fifth power of the fragment size for both methods. However, the DEC-RI-MP2 method has a reduced prefactor compared to DEC-MP2 and is well-suited for implementation on massively parallel supercomputers, as demonstrated by test calculations on a set of medium-sized molecules. The DEC error control ensures that the standard RI-MP2 energy can be obtained to the predefined precision. The errors associated with the RI and DEC approximations are compared, and it is shown that the DEC-RI-MP2 method can be applied to systems far beyond the ones that can be treated with a conventional RI-MP2 implementation.

Orbital spaces in the divide-expand-consolidate coupled cluster method.

The theoretical foundation for solving coupled cluster singles and doubles (CCSD) amplitude equations to a desired precision in terms of independent fragment calculations using restricted local orbital spaces is reinvestigated with focus on the individual error sources. Four different error sources are identified theoretically and numerically and it is demonstrated that, for practical purposes, local orbital spaces for CCSD calculations can be identified from calculations at the MP2 level. The development establishes a solid theoretical foundation for local CCSD calculations for the independent fragments, and thus for divide-expand-consolidate coupled cluster calculations for large molecular systems with rigorous error control. Based on this theoretical foundation, we have developed an algorithm for determining the orbital spaces needed for obtaining the single fragment energies to a requested precision and numerically demonstrated the robustness and precision of this algorithm.

The explicitly correlated same number of optimized parameters (SNOOP-F12) scheme for calculating intermolecular interaction energies.

We augment the recently introduced same number of optimized parameters (SNOOP) scheme [K. Kristensen et al., J. Chem. Phys. 142, 114116 (2015)] for calculating interaction energies of molecular dimers with an F12 correction and generalize the method to enable the determination of interaction energies of general molecular clusters. The SNOOP, uncorrected (UC), and counterpoise (CP) schemes with/without an F12 correction are compared for the S22 test set of Jurecka et al. [Phys. Chem. Chem. Phys. 8, 1985 (2006)]-which consists of 22 molecular dimers of biological importance-and for water and methane molecular clusters. The calculations have been performed using the Resolution of the Identity second-order Møller-Plesset perturbation theory method. We conclude from the results that the SNOOP scheme generally yields interaction energies closer to the complete basis set limit value than the UC and CP approaches, regardless of whether the F12 correction is applied or not. Specifically, using the SNOOP scheme with an F12 correction yields the computationally most efficient way of achieving accurate results at low basis set levels. These conclusions hold both for molecular dimers and more general molecular clusters.

Explicitly correlated second-order Møller-Plesset perturbation theory in a Divide-Expand-Consolidate (DEC) context.

We present the DEC-RIMP2-F12 method where we have augmented the Divide Expand-Consolidate resolution-of-the-identity second-order Møller-Plesset perturbation theory method (DEC-RIMP2) [P. Baudin et al., J. Chem. Phys. 144, 054102 (2016)] with an explicitly correlated (F12) correction. The new method is linear-scaling, massively parallel, and it corrects for the basis set incompleteness error in an efficient manner. In addition, we observe that the F12 contribution decreases the domain error of the DEC-RIMP2 correlation energy by roughly an order of magnitude. An important feature of the DEC scheme is the inherent error control defined by a single parameter, and this feature is also retained for the DEC-RIMP2-F12 method. In this paper we present the working equations for the DEC-RIMP2-F12 method and proof of concept numerical results for a set of test molecules.

A Lagrangian framework for deriving triples and quadruples corrections to the CCSD energy.

Using the coupled cluster Lagrangian technique, we have determined perturbative corrections to the coupled cluster singles and doubles (CCSD) energy that converge towards the coupled cluster singles, doubles, and triples (CCSDT) and coupled cluster singles, doubles, triples, and quadruples (CCSDTQ) energies, considering the CCSD state as the unperturbed reference state and the fluctuation potential as the perturbation. Since the Lagrangian technique is utilized, the energy corrections satisfy Wigner's 2n + 1 rule for the cluster amplitudes and the 2n + 2 rule for the Lagrange multipliers. The energy corrections define the CCSD perturbation series, CCSD(T-n) and CCSD(TQ-n), which are term-wise size extensive to any order in the perturbation. A detailed comparison of the CCSD(TQ-n) series and the CC(2)PT(n) series of Hirata et al. [J. Chem. Phys. 114, 3919 (2001)] has been performed, revealing some deficiencies of the latter related to the target energy of the series and its lack of size extensivity.

Charge-constrained auxiliary-density-matrix methods for the Hartree-Fock exchange contribution.

Three new variants of the auxiliary-density-matrix method (ADMM) of Guidon, Hutter, and VandeVondele [J. Chem. Theory Comput. 6, 2348 (2010)] are presented with the common feature that they have a simplified constraint compared with the full orthonormality requirement of the earlier ADMM1 method. All ADMM variants are tested for accuracy and performance in all-electron B3LYP calculations with several commonly used basis sets. The effect of the choice of the exchange functional for the ADMM exchange-correction term is also investigated.

Comparison of Transoral and Transcervical Ultrasonography with MRI for the Diagnostic Work-Up of Oropharynx Tumors: A Protocol for a Multicenter Clinical Trial (SPOTUS).

This study protocol for a prospective, multicenter, diagnostic, clinical trial describes the integration of transoral and transcervical ultrasonography (US) in the initial clinical work-up of patients referred to tertiary head and neck cancer centers with suspected oropharyngeal cancer. The study evaluates the blinded detection rate of oropharyngeal tumors and their US-estimated size and T-stage before histopathology and cross-sectional imaging are available. Magnetic resonance imaging (MRI) scans will be prospectively rated while blinded to T-site histopathology and US. The primary outcome measures of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values, and overall accuracy, will be reported for both US and MRI. A sub-analysis of prospectively rated 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) scans in patients with clinically suspected unknown primary tumors will also be compared to US and MRI. Secondary outcome measures, including a comparison of tumor size estimation between US, MRI, and CT, will also be reported. This prospective multicenter study will provide clinically impactful information regarding the use of transoral and transcervical US for the diagnostic work-up of oropharyngeal cancer.

Insights into the dynamics of evaporation and proton migration in protonated water clusters from large-scale Born-Oppenheimer direct dynamics.

Large-scale on-the-fly Born-Oppenheimer molecular dynamics simulations using recent advances in linear scaling electronic structure theory and trajectory integration techniques have been performed for protonated water clusters around the magic number (H(2)O)(n)H(+) , for n = 20 and 21. Besides demonstrating the feasibility and efficiency of the computational approach, the calculations reveal interesting dynamical details. Elimination of water molecules is found to be fast for both cluster sizes but rather insensitive to the initial geometry. The water molecules released acquire velocities compatible with thermal energies. The proton solvation shell changes between the well-known Eigen and Zundel motifs and is characterized by specific low-frequency vibrational modes, which have been quantified. The proton transfer mechanism largely resembles that of bulk water but one interesting variation was observed.

Attractive electron-electron interactions within robust local fitting approximations.

An analysis of Dunlap's robust fitting approach reveals that the resulting two-electron integral matrix is not manifestly positive semidefinite when local fitting domains or non-Coulomb fitting metrics are used. We present a highly local approximate method for evaluating four-center two-electron integrals based on the resolution-of-the-identity (RI) approximation and apply it to the construction of the Coulomb and exchange contributions to the Fock matrix. In this pair-atomic resolution-of-the-identity (PARI) approach, atomic-orbital (AO) products are expanded in auxiliary functions centered on the two atoms associated with each product. Numerical tests indicate that in 1% or less of all Hartree-Fock and Kohn-Sham calculations, the indefinite integral matrix causes nonconvergence in the self-consistent-field iterations. In these cases, the two-electron contribution to the total energy becomes negative, meaning that the electronic interaction is effectively attractive, and the total energy is dramatically lower than that obtained with exact integrals. In the vast majority of our test cases, however, the indefiniteness does not interfere with convergence. The total energy accuracy is comparable to that of the standard Coulomb-metric RI method. The speed-up compared with conventional algorithms is similar to the RI method for Coulomb contributions; exchange contributions are accelerated by a factor of up to eight with a triple-zeta quality basis set. A positive semidefinite integral matrix is recovered within PARI by introducing local auxiliary basis functions spanning the full AO product space, as may be achieved by using Cholesky-decomposition techniques. Local completion, however, slows down the algorithm to a level comparable with or below conventional calculations.

Workup and treatment of voice problems.

Voice problems, also called hoarseness or dysphonia, can cause significant morbidity with communication difficulties and social isolation. This review summarises the causes and treatment of voice problems. Common causes of voice problems are related to inflammation, non-physiological usage of the voice, benign lesions of the vocal cords and damage to the nerves innervating the larynx. Nonetheless, it is important to keep malignancy in mind as a differential diagnosis. Referral to an otorhinolaryngologist is recommended for voice problems in adults with a duration of more than two weeks.