Influence of artificial intelligence on the diagnostic performance of endoscopists in the assessment of Barrett's esophagus: a tandem randomized and video trial.

BACKGROUND: This study evaluated the effect of an artificial intelligence (AI)-based clinical decision support system on the performance and diagnostic confidence of endoscopists in their assessment of Barrett's esophagus (BE). METHODS: 96 standardized endoscopy videos were assessed by 22 endoscopists with varying degrees of BE experience from 12 centers. Assessment was randomized into two video sets: group A (review first without AI and second with AI) and group B (review first with AI and second without AI). Endoscopists were required to evaluate each video for the presence of Barrett's esophagus-related neoplasia (BERN) and then decide on a spot for a targeted biopsy. After the second assessment, they were allowed to change their clinical decision and confidence level. RESULTS: AI had a stand-alone sensitivity, specificity, and accuracy of 92.2%, 68.9%, and 81.3%, respectively. Without AI, BE experts had an overall sensitivity, specificity, and accuracy of 83.3%, 58.1%, and 71.5%, respectively. With AI, BE nonexperts showed a significant improvement in sensitivity and specificity when videos were assessed a second time with AI (sensitivity 69.8% [95%CI 65.2%-74.2%] to 78.0% [95%CI 74.0%-82.0%]; specificity 67.3% [95%CI 62.5%-72.2%] to 72.7% [95%CI 68.2%-77.3%]). In addition, the diagnostic confidence of BE nonexperts improved significantly with AI. CONCLUSION: BE nonexperts benefitted significantly from additional AI. BE experts and nonexperts remained significantly below the stand-alone performance of AI, suggesting that there may be other factors influencing endoscopists' decisions to follow or discard AI advice.

Risk factors for total laryngectomy associated proximal esophageal stricture formation in head and neck cancer patients.

BACKGROUND: Development of esophageal strictures is common after the total laryngectomy of head and neck cancer patients. While endoscopic techniques like dilatation by balloon or Salvary bougies are well established, risk factors and pathophysiology for development of refractory strictures are less well understood. OBJECTIVE: To evaluate risk factors associated with occurrence and recurrence of total-laryngectomy-associated esophageal strictures in head and neck cancer patients. METHODS: We analyzed retrospectively a cohort of 170 head and neck squamous cell carcinoma patients, who underwent total laryngectomy between 2007 and 2017. The outcome measure was laryngectomy-associated proximal esophageal stricture needing an endoscopic dilatation by using a balloon or Savary dilators. RESULTS: Of the 170 patients in the cohort, 32 (18.8%) developed strictures. Mean time between surgery and first endoscopic intervention was 24.4 months. Significant predictive factors were age ≥ 65 (p=0.017), nodal status N> 1 (p=0.003), continued alcohol abuse after surgery (p=0.005) and diabetes mellitus (p=0.005). In a subgroup, 17 of 32 patients developed refractory strictures and needed more than three dilatations to relieve dysphagia. Postoperative mean (p=0.016) and maximum (p=0.015) C-reactive protein (CRP) were predictive for refractory strictures. CONCLUSION: Symptomatic strictures occurred in 18.8% of the cases. Age, nodal status N>1, continued alcohol abuse and diabetes mellitus were predictive factors. For refractory stenosis (>3 dilatations needed) mean and maximum postoperative CRP were predictive. This may indicate that systemic inflammatory response post-surgery is involved in the stricture formation process.

A deep learning model enables accurate prediction and quantification of pulmonary edema from chest X-rays.

BACKGROUND: A quantitative assessment of pulmonary edema is important because the clinical severity can range from mild impairment to life threatening. A quantitative surrogate measure, although invasive, for pulmonary edema is the extravascular lung water index (EVLWI) extracted from the transpulmonary thermodilution (TPTD). Severity of edema from chest X-rays, to date is based on the subjective classification of radiologists. In this work, we use machine learning to quantitatively predict the severity of pulmonary edema from chest radiography. METHODS: We retrospectively included 471 X-rays from 431 patients who underwent chest radiography and TPTD measurement within 24 h at our intensive care unit. The EVLWI extracted from the TPTD was used as a quantitative measure for pulmonary edema. We used a deep learning approach and binned the data into two, three, four and five classes increasing the resolution of the EVLWI prediction from the X-rays. RESULTS: The accuracy, area under the receiver operating characteristic curve (AUROC) and Mathews correlation coefficient (MCC) in the binary classification models (EVLWI < 15, ≥ 15) were 0.93 (accuracy), 0.98 (AUROC) and 0.86(MCC). In the three multiclass models, the accuracy ranged between 0.90 and 0.95, the AUROC between 0.97 and 0.99 and the MCC between 0.86 and 0.92. CONCLUSION: Deep learning can quantify pulmonary edema as measured by EVLWI with high accuracy.

Accurate prediction of histological grading of intraductal papillary mucinous neoplasia using deep learning.

BACKGROUND: Risk stratification and recommendation for surgery for intraductal papillary mucinous neoplasm (IPMN) are currently based on consensus guidelines. Risk stratification from presurgery histology is only potentially decisive owing to the low sensitivity of fine-needle aspiration. In this study, we developed and validated a deep learning-based method to distinguish between IPMN with low grade dysplasia and IPMN with high grade dysplasia/invasive carcinoma using endoscopic ultrasound (EUS) images. METHODS: For model training, we acquired a total of 3355 EUS images from 43 patients who underwent pancreatectomy from March 2015 to August 2021. All patients had histologically proven IPMN. We used transfer learning to fine-tune a convolutional neural network and to classify "low grade IPMN" from "high grade IPMN/invasive carcinoma." Our test set consisted of 1823 images from 27 patients, recruiting 11 patients retrospectively, 7 patients prospectively, and 9 patients externally. We compared our results with the prediction based on international consensus guidelines. RESULTS: Our approach could classify low grade from high grade/invasive carcinoma in the test set with an accuracy of 99.6 % (95 %CI 99.5 %-99.9 %). Our deep learning model achieved superior accuracy in prediction of the histological outcome compared with any individual guideline, which have accuracies between 51.8 % (95 %CI 31.9 %-71.3 %) and 70.4 % (95 %CI 49.8-86.2). CONCLUSION: This pilot study demonstrated that deep learning in IPMN-EUS images can predict the histological outcome with high accuracy.

Spatio-temporal superconducting dynamics driven by THz fields from topological spintronic terahertz emitters.

Metastructures of spintronic THz emitters can be engineered to have a well-defined topology characterized by a topological charge. The emitted THz radiation possesses a phase-locked transversal and longitudinal components with the ratio of which being tunable by the topological charge of the underlying metastructure. The THz fields so produced are employed to drive and spatio-temporally modulate the superconducting order parameter in a type II superconductor. Using a time-dependent Landau-Ginzburg approach, it is demonstrated how the topology of the THz fields is reflected in a texturing of the superconducting phase and density. Full numerical simulations illustrate the emergence and the nanoscale steering of Abrikosov vortices as well as the local modification of the superconducting density and transport properties of nanoscale samples with different geometries. The study highlights the potential of metamaterials based on spintronic THz emitters as a coherent source for spatially and vectorially modulated THz radiation.

Thickness-dependent slow light gap solitons in three-dimensional coupled photonic crystal waveguides.

The thickness-dependent multimodal nature of three-dimensional (3D) coupled photonic crystal waveguides is investigated with the aim of realizing a medium for controlled optical gap soliton formation in the slow light regime. In the linear case, spectral properties of the modes (dispersion diagrams), location of the gap regions versus the thickness of the 3D photonic crystal, and the near-field distributions at frequencies in the slow light region are analyzed using a full-wave electromagnetic solver. In the nonlinear regime (Kerr-type nonlinearity), we infer an existence of crystal-thickness-dependent temporal solitons with stable pulse envelope and use the solitonic pulses for driving quantum transitions in localized quantum systems within the photonic crystal waveguide. The results may be useful for applications in optical communications, multiplexing systems, nonlinear physics, and ultrafast spectroscopy.

Influence of extracorporeal cytokine adsorption on hemodynamics in severe acute pancreatitis: Results of the matched cohort pancreatitis cytosorbents inflammatory cytokine removal (PACIFIC) study.

BACKGROUND: Outcome of severe acute pancreatitis (SAP) highly depends on the degree of systemic inflammation and organ failure. Although treatment approaches targeting the inflammatory cascade have failed in pancreatitis, recent studies suggest that extracorporeal cytokine adsorption effectively reduces concentrations of pro-inflammatory cytokines and potentially improves the outcome of sepsis. METHODS: Sixteen patients with SAP, presenting within 7 days upon onset of pain, an APACHE-II score of ≥10 and ≥1 marker of poor prognosis, received 2 consecutive 24-h treatments with CytoSorb® extracorporeal cytokine adsorption (intervention group). Hemodynamics, organ failure, and mortality were compared with an APACHE-II score-matched retrospective control group of 32 patients. RESULTS: The primary objective (20% decrease in the vasopressor dependency index or 20% increase in the cardiac index) was reached in 68.8% of the intervention and 28.1% of the control patients (p = 0.007), respectively. The cytokine adsorption significantly reduced IL-6 (-1998 pg/ml, p = 0.005) serum levels and resulted in stable CRP (p = 0.101) and decreased PCT (p = 0.003) levels in contrast to increased CRP (p = 0.014) and stable PCT levels (p = 0.695) in the control group. While mortality and improvement of respiratory failure were similar in both groups, renal failure significantly improved (change of KDIGO classification 72 h postcytokine adsorption [-1 vs. 0, p = 0.005]) and the SOFA score significantly decreased (day 5: -1.8 ± 2.0 vs. 1 ± 3.8, p = 0.013) in the intervention group. CONCLUSION: Cytokine adsorption might be an effective treatment option to stabilize hemodynamics in SAP. It decreases levels of the pro-inflammatory marker IL-6 and stabilizes organ function according to serial SOFA score assessments.

MEK1/2 regulates APOBEC3B and polymerase iota-induced mutagenesis in head and neck cancer cells.

Resistance to chemotherapy provides a major challenge in treatment of metastatic cancer. Prolonged exposure to almost any drug regimen leads to the formation of resistant subclones in almost all advanced solid tumors. Tumor heterogeneity because of intrinsic genetic instability is seen as one of the major contributing factors. In this work, we present evidence that genetic instability measured by mutation frequency is induced by treatment with the EGFR inhibitor afatinib or cisplatin in head and neck squamous cancer cells. We find that APOBEC3B and polymerase iota are upregulated, and inhibition of MEK1/2 by U0126 leads to downregulation on the protein level. Costimulation of afatnib and cisplatin with U0126 leads to a significantly lower mutation frequency. These findings may represent a molecular mechanism for dynamically controlling genetic instability during chemotherapy in head and neck squamous cell carcinoma (HNSCC) cancer cells.

Extracorporeal carbon dioxide removal with the Advanced Organ Support system in critically ill COVID-19 patients.

Disturbed oxygenation is foremost the leading clinical presentation in COVID-19 patients. However, a small proportion also develop carbon dioxide removal problems. The Advanced Organ Support (ADVOS) therapy (ADVITOS GmbH, Munich, Germany) uses a less invasive approach by combining extracorporeal CO2 -removal and multiple organ support for the liver and the kidneys in a single hemodialysis device. The aim of our study is to evaluate the ADVOS system as treatment option in-COVID-19 patients with multi-organ failure and carbon dioxide removal problems. COVID-19 patients suffering from severe respiratory insufficiency, receiving at least two treatments with the ADVOS multi system (ADVITOS GmbH, Munich, Germany), were eligible for study inclusion. Briefly, these included patients with acute kidney injury (AKI) according to KDIGO guidelines, and moderate or severe ARDS according to the Berlin definition, who were on invasive mechanical ventilation for more than 72 hours. In total, nine COVID-19 patients (137 ADVOS treatment sessions with a median of 10 treatments per patient) with moderate to severe ARDS and carbon dioxide removal problems were analyzed. During the ADVOS treatments, a rapid correction of acid-base balance and a continuous CO2 removal could be observed. We observed a median continuous CO2 removal of 49.2 mL/min (IQR: 26.9-72.3 mL/min) with some treatments achieving up to 160 mL/min. The CO2 removal significantly correlated with blood flow (Pearson 0.421; P < .001), PaCO2 (0.341, P < .001) and HCO 3 - levels (0.568, P < .001) at the start of the treatment. The continuous treatment led to a significant reduction in PaCO2 from baseline to the last ADVOS treatment. In conclusion, it was feasible to remove CO2 using the ADVOS system in our cohort of COVID-19 patients with acute respiratory distress syndrome and multiorgan failure. This efficient removal of CO2 was achieved at blood flows up to 300 mL/min using a conventional hemodialysis catheter and without a membrane lung or a gas phase.

Spin-Resolved Quantum Scars in Confined Spin-Coupled Two-Dimensional Electron Gas.

Quantum scars refer to an enhanced localization of the probability density of states in the spectral region with a high energy level density. Scars are discussed for a number of confined pure and impurity-doped electronic systems. Here, we studied the role of spin on quantum scarring for a generic system, namely a semiconductor-heterostructure-based two-dimensional electron gas subjected to a confining potential, an external magnetic field, and a Rashba-type spin-orbit coupling. Calculating the high energy spectrum for each spin channel and corresponding states, as well as employing statistical methods known for the spinless case, we showed that spin-dependent scarring occurs in a spin-coupled electronic system. Scars can be spin mixed or spin polarized and may be detected via transport measurements or spin-polarized scanning tunneling spectroscopy.

Increased extravascular lung water index (EVLWI) reflects rapid non-cardiogenic oedema and mortality in COVID-19 associated ARDS.

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = - 0.60; p = 0.001) and within-subjects correlation (r = - 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.

Extracorporeal multiorgan support including CO2-removal with the ADVanced Organ Support (ADVOS) system for COVID-19: A case report.

A substantial part of COVID-19-patients suffers from multi-organ failure (MOF). We report on an 80-year old patient with pulmonary, renal, circulatory, and hepatic failure. We decided against the use of extracorporeal membrane oxygenation (ECMO) due to old age and a SOFA-score of 13. However, the patient was continuously treated with the extracorporeal multi-organ- "ADVanced Organ Support" (ADVOS) device (ADVITOS GmbH, Munich, Germany). During eight 24h-treatment-sessions blood flow (100-300 mL/min), dialysate flow (160-320 mL/min) and dialysate pH (7.6-9.0) were adapted to optimize arterial PaCO2 and pH. Effective CO2 removal and correction of acidosis could be demonstrated by mean arterial- versus post-dialyzer values of pCO2 (68.7 ± 13.8 vs. 26.9 ± 11.6 mmHg; p < 0.001). The CO2-elimination rate was 48 ± 23mL/min. The initial vasopressor requirement could be reduced in parallel to pH-normalization. Interruptions of ADVOS-treatment repeatedly resulted in reversible deteriorations of paCO2 and pH. After 95 h of continuous extracorporeal decarboxylating therapy the patient had markedly improved circulatory parameters compared to baseline. In the context of secondary pulmonary infection and progressive liver failure, the patient had a sudden cardiac arrest. In accordance with the presumed patient will, we decided against mechanical resuscitation. Irrespective of the outcome we conclude that extracorporeal CO2 removal and multiorgan-support were feasible in this COVID-19-patient. Combined and less invasive approaches such as ADVOS might be considered in old-age-COVID-19 patients with MOF.

Imprinting photon orbital angular momentum during laser-assisted photoemission from quantum wells.

We study theoretically the transfer of the light field orbital angular momentum (OAM) to propagating electrons upon photoemission from quantum well states. Irradiation with a Laguerre-Gaussian mode laser pulse elevates the quantum well state into a laser-dressed Volkov state that can be detected in an angular and energy-resolved manner while varying the characteristics of the driving fields. We derive the photoemission cross section for this process using the S-matrix theory and illustrate how the OAM is embodied in the photoelectron angular pattern with the aid of numerical calculations. The results point to a new type of time-resolved spectroscopy, in which the electronic orbital motion is addressed exclusively, with the potential for a new insight in spin-orbitally or orbitally coupled systems.

Improved overall survival in head and neck cancer patients after specific therapy of distant metastases.

PURPOSE: While metastases directed therapy for oligometastatic disease is recommended in different cancer entities, the treatment of solitary metastases in head and neck squamous cell carcinoma (HNSCC) patients is not clearly defined. METHODS: A retrospective analysis was performed on data from 143 HNSCC patients treated between 2001 and 2016 in a tertiary university hospital. Clinical factors and outcome were measured using the median survival of patients receiving metastases specific therapy in comparison with matched control patients. RESULTS: In 37 patients, distant metastases were treated specifically with either surgery and/or stereotactic ablative radiotherapy and had with 23.97 months a more than three times higher median survival than 10 untreated matched controls with potentially treatable distant metastases (7.07 months). CONCLUSIONS: Our retrospective analysis demonstrates a significant survival benefit for HNSCC patients who received a specific therapy regarding distant metastasis irrespective of localization as compared to a matched control cohort.

HNSCC cells resistant to EGFR pathway inhibitors are hypermutated and sensitive to DNA damaging substances.

Despite remarkable successes with targeted therapies in the treatment of cancer, resistance can occur which limits the clinical outcome. In this study, we generated and characterized resistant cell clones derived from two different head and neck squamous cell carcinoma (HNSCC) cell lines (Cal27, UD-SCC-5) by long-term exposure to five targeted- and chemotherapeutics (afatinib, MK2206, BEZ235, olaparib and cisplatin). The resistant tumor cell clones showed an increased ERK1/2 expression and an altered expression of the stem-cell markers CD44, ALDH1, Oct4, Sox2, Nanog and Bmi1. None of the single markers alone was predictive for resistance to all five targeted- and chemotherapeutics. Furthermore, long-term exposure of tumor cells to these five drugs resulted in an eightfold increase in the mutational rate compared to untreated cells. Interestingly, targeted- and chemotherapy resistant cell clones remained sensitive to irradiation. Lastly, clones that were resistant to afatinib, MK2206 or BEZ235 showed cross-resistance to further treatment with therapeutics that affect the same signaling pathway, but remained sensitive to those affecting different pathways such as cisplatin and olaparib. In contrast, cell clones which were once resistant to cisplatin or olaparib were found to be multidrug-resistant. These data might indicate that patients with HNSCC benefit more by a first line targeted therapy followed by cisplatin as a second line therapy.

Semiautomatic algorithm for lymph node analysis corrected for partial volume effects in combined positron emission tomography-computed tomography.

Positron emission tomography-computed tomography (PET-CT) is superior compared to stand-alone PET in evaluation of malignancies. Few studies have employed high-resolution structural information to correct PET. We designed a semiautomatic algorithm using CT and PET to obtain a partial volume corrected (PVC) standardized uptake value (SUV) and a combined morphologic and functional parameter (multimodal SUV) for lymph node assessment. Lesions were segmented by a semiautomatic algorithm in CT images. Lesion volume was used for PVC and for calculating the multimodal SUV. The method was applied to 47 lymph nodes (30 patients) characterized as suspicious in 18F-fluorodeoxyglucose-PET-CT. In phantoms, PVC improved significantly the measured uptake of the lesion. In patients, 36 lymph nodes could be segmented without problems; in 11 lesions, a manual interaction was necessary. SUVs before PVC (mean 1.29) increased significantly (p < .0005) after PVC (mean 2.8). If SUV 2.5 was used as a threshold value to distinguish between benign and malignant lesions, 11 of the 47 lesions changed from benign to malignant after the PVC. The mean multimodal SUV was 0.39 mL for the benign lesions and 4.47 mL for the malignant lesions. In this work we presented a method for quantitative analysis of lymph nodes in PET-CT. PVC leads to significant differences in SUV.