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This retrospective monocentric cohort study analyzed patients with head and neck cancer according their nutritional status and association of percutaneous endoscopic gastrostomy (PEG) from admission to six months after treatment at a tertiary hospital in Germany from 2017 to 2019. A total of 289 patients (76.5% men; median age 62 years; 63.3% stage IV) were included. Univariate analyses and ANOVAs with repeated measures were performed to analyze differences over time. The percentage of patients requiring PEG was 14.9% (43 of 289 patients) before start of treatment (Z0), 14% (40 of 286 patients alive) after one week (Z1), 22.7% (58 of 255 patients) after six weeks (Z2) and 23% (53 of 230 patients) after six months (Z3) from the end of treatment. PEG placement was associated with alcohol or nicotine consumption, in oropharyngeal and hypopharyngeal carcinoma, squamous cell carcinoma, cancer stage III/IV, chemotherapy and impairment of food intake (all p < 0.05). Weight loss between Z1 and Z3 with PEG did not differ from patients without PEG at Z0 ( p = 0.074), although patients with PEG at Z0 had a lower mean weight at the beginning. PEG was important for a quarter of the patients alive at Z3 and helped to prevent weight loss.

Objective: The prevalence of long-/post-COVID-associated chemosensory symptoms is reported in the literature to be significantly higher than clinical reality reflects., Methods: 1. N= 4062 adults acutely infected with SARS-CoV-2 and their symptoms transmitted by the Jena health office to the Robert Koch Institute between March 2020 and September 2021 were evaluated. 2. Part of the same cohort (N = 909 of 4062) answered an extensive questionnaire at least 3 months after the start of the infection, including existing chemosensory post-COVID-associated complaints. 3. Fourteen post-COVID Jena patients with chemosensory symptoms who had become acutely infected during the same period were diagnosed, treated and advised in our ENT specialist outpatient clinic., Results: The prevalence of chemosensory symptoms at the onset of infection was 19% (600/3187). About every second written respondent of the formerly acutely infected (441/890) remembered chemosensory symptoms during their COVID-19 infection. Of these, around 38% (167/441) complained of persistent chemosensory post-COVID symptoms after an average of 14.5 months. Only 2.3% (14/600) of the previously acutely infected patients with chemosensory symptoms sought medical help in a special consultation. Quantitative chemosensory damage could only be objectified in half, i.e. 1.2% (7/600) of the total cohort., Conclusions: Despite a high prevalence of subjective chemosensory symptoms in acutely and formerly SARS-CoV-2 infected people, there is only a low need for specialized treatment, so that, unlike other post-COVID-associated complaints, the healthcare system as a whole appears to be less significantly burdened., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The use of polyetheretherketone (PEEK) for cementless femoral total knee arthroplasty (TKA) components is of interest due to several potential advantages, e.g. the use in patients with metal hypersensitivity. Additionally, the stiffness of PEEK closer resembles the stiffness of bone, and therefore, peri-prosthetic stress-shielding may be avoided. When introducing a new implant material for cementless TKA designs, it is important to study its effect on the primary fixation, which is required for the long-term fixation. Finite element (FE) studies can be used to study the effect of PEEK as implant material on the primary fixation, which may be dependent on patient factors such as age, gender and body weight index (BMI). Therefore, the research objectives of this study were to investigate the effect of PEEK vs cobalt-chrome (CoCr) and patient characteristics on the primary fixation of a cementless femoral component. 280 FE models of 70 femora were created with varying implant material and gait and squat activity. Overall, the PEEK models generated larger peak micromotions than the CoCr models. Distinct differences were seen in the micromotion distributions between the PEEK and CoCr models for both the gait and squat models. The micromotions of all femoral models significantly increased with BMI. Neither gender nor age of the patients had a significant effect on the micromotions. This population study gives insights into the primary fixation of a cementless femoral component in a cohort of FE models with varying implant material and patient characteristics., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.B. is a paid employee of Invibio Ltd. and had a role in the study design and review of the manuscript. N.V. is a paid consultant for Invibio Ltd. D.J. is a paid consultant for Invibio Ltd and receives research support as a principal investigator from Invibio Ltd. The other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Prognostic factors for overall survival (OS), percutaneous endoscopic gastrostomy (PEG) dependency, and long-term speech rehabilitation via voice prosthesis (VP) after laryngectomy for laryngeal or hypopharyngeal cancer were investigated in a retrospective population-based study in Thuringia, Germany. A total of 617 patients (68.7% larynx; hypopharynx; 31.3%; 93.7% men; median age 62 years; 66.0% stage IV) from 2001 to 2020 were included. Kaplan-Meier and Cox multivariable regression analyses were performed. 23.7% of patients received a PEG. 74.7% received a VP. Median OS was 131 months. Independent factors for lower OS were stage IV (compared to stage II; hazard ratio [HR] = 3.455; confidence interval [CI] 1.395-8.556) and laryngectomy for a recurrent disease (HR = 1.550; CI 1.078-2.228). Median time to PEG removal was 7 months. Prior partial surgery before laryngectomy showed a tendency for independent association for later PEG removal (HR = 1.959; CI 0.921-4.167). Postoperative aspiration needing treatment was an independent risk factor (HR = 2.679; CI 1.001-7.167) for later definitive VP removal. Laryngectomy continuously plays an important role in a curative daily routine treatment setting of advanced laryngeal or hypopharyngeal cancer in Germany. Long-term dependency on nutrition via PEG is an important issue, whereas use of VP is a stable long-term measure for voice rehabilitation., (© 2024. The Author(s).)

The reliability of computational models in orthopedic biomechanics depends often on the accuracy of the bone material properties. It is widely recognized that the mechanical response of trabecular bone is time-dependent, yet it is often ignored for the sake of simplicity. Previous investigations into the viscoelastic properties of trabecular bone have not explored the relationship between nonlinear stress relaxation and bone mineral density. The inclusion of this behavior could enhance the accuracy of simulations of orthopedic interventions, such as of primary fixation of implants. Although methods to quantify the viscoelastic behavior are known, the time period during which the viscoelastic properties should be investigated to obtain reliable predictions is currently unclear. Therefore, this study aimed to: 1) Investigate the duration of stress relaxation in bovine trabecular bone; 2) construct a material model that describes the nonlinear viscoelastic behavior of uniaxial stress relaxation experiments on trabecular bone; and 3) implement bone density into this model. Uniaxial compressive stress relaxation experiments were performed with cylindrical bovine femoral trabecular bone samples (n = 16) with constant strain held for 24 h. Additionally, multiple stress relaxation experiments with four ascending strain levels with a holding time of 30 min, based on the results of the 24-h experiment, were executed on 18 bovine bone cores. The bone specimens used in this study had a mean diameter of 12.80 mm and a mean height of 28.70 mm. A Schapery and a Superposition model were used to capture the nonlinear stress relaxation behavior in terms of applied strain level and bone mineral density. While most stress relaxation happened in the first 10 min (up to 53 %) after initial compression, the stress relaxation continued even after 24 h. Up to 69 % of stress relaxation was observed at 24 h. Extrapolating the results of 30 min of experimental data to 24 h provided a good fit for accuracy with much improved experimental efficiency. The Schapery and Superposition model were both capable of fitting the repeated stress relaxation in a sample-by-sample approach. However, since bone mineral density did not influence the time-dependent behavior, only the Superposition model could be used for a group-based model fit. Although the sample-by-sample approach was more accurate for an individual specimen, the group based approach is considered a useful model for general application., Competing Interests: Declaration of competing interest Two authors are employees of Depuy Synthes, however due to the fundamental nature of this study, there are no competing financial interests or personal relationships that could have appeared to influence the work in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Sleep-disordered breathing is highly prevalent in patients with heart failure and is related to increased mortality and morbidity. The gold standard for sleep diagnostic is polysomnography in a sleep laboratory. Measurement of peripheral arterial tone with a wrist-worn diagnostic device is a promising method to detect sleep-disordered breathing without major technical effort., Methods: We prospectively enrolled patients with heart failure with reduced ejection fraction for measurement of the peripheral arterial tone and polysomnography simultaneously during one night in the sleep laboratory. Raw data of polysomnography was analyzed blindly by sleep core lab personnel and compared with automatic algorithm-based sleep results of measurement of the peripheral arterial tone., Results: A total of 25 patients provided comparable sleep results. All patients had sleep-disordered breathing and were identified by measurement of the peripheral arterial tone. The comparison of apnea-hypopnea index between peripheral arterial tone 38.8 ± 17.4/h and polysomnography 44.5 ± 17.9/h revealed a bias of - 5.7 ± 9.8/h with limits of agreement of ± 19.2/h in Bland-Altman analysis but showed high and significant Pearson correlation (r = 0.848, p < 0.001)., Conclusion: The findings suggest that measurement of the peripheral arterial tone may be useful to identify sleep-disordered breathing in patients with heart failure with reduced ejection fraction., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The diagnostic of peripheral pulmonary nodules (PPN) is a particular challenge in interventional bronchology, which is why navigation systems such as electromagnetic navigation (ENB) are increasingly being used. The 4D-ENB represents the most current development of the ENB. It utilizes inspiratory and expiratory CT scans for mapping and thus helps compensate for respiratory movements-induced CT-to-body divergence. The aim of this work was to present the first clinical data and experiences using the 4D-ENB method for diagnosis of PPNs., Methods: We retrospectively describe the results of the first nine consecutive patient cases diagnosed at Klinikum Braunschweig using 4D-ENB in a unimodal diagnostic procedure., Results: Of the first 9 PPNs examined by 4D-ENB, navigation and puncture of the lesion was successful in 8 patients (89%). Diagnostic biopsy was could be carried out in six out of nine patients (67%). There were no significant procedure-related complications., Conclusion: Our preliminary data suggest that 4D-ENB is a promising new alternative for the diagnosis of PPNs. To further improve diagnostic yield, 4D-END, which lacks real-time visualization, should be embedded in a multimodal diagnostic procedure with rEBUS and/or fluoroscopy., Competing Interests: Thomas Bitter erhält Vortragshonorare und Reisekostenunterstützung von Olympus Europe. Die anderen Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Polyetheretherketone (PEEK) is of interest as implant material for cementless tibial total knee arthroplasty (TKA) components due to its potential advantages. One main advantage is that the stiffness of PEEK closely resembles the stiffness of bone, potentially avoiding peri-prosthetic stress-shielding. When introducing a new implant material for cementless TKA designs, it is essential to study its effect on the primary fixation. The primary fixation may be influenced by patient factors such as age, gender, and body mass index (BMI). Therefore, the research objectives of this finite element (FE) study were to investigate the effect of material (PEEK vs. titanium) and patient characteristics on the primary fixation (i.e., micromotions) of a cementless tibial tray component. A total of 296 FE models of 74 tibiae were created with either PEEK or titanium material properties, under gait and squat loading conditions. Overall, the PEEK models generated larger peak micromotions than the titanium models. Differences were seen in the micromotion distributions between the PEEK and titanium models for both the gait and squat models. The micromotions of all tibial models significantly increased with BMI, while gender and age did not influence micromotions.

The effect of long-term periprosthetic bone loss on the process of aseptic loosening of tibial total knee arthroplasty (TKA) is subject to debate. Contradicting studies can be found in literature, reporting either bone resorption or bone formation before failure of the tibial tray. The aim of the current study was to investigate the effects of bone resorption on failure of tibial TKA, by simulating clinical postoperative bone density changes in finite element analysis (FEA) models and FEA models were created of two tibiae representing cases with good and poor initial bone quality which were subjected to a walking configuration and subsequently to a traumatic stumbling load. Bone failure was simulated using a crushable foam model incorporating progressive yielding. Repetitive loading under a level walking load did not result in failure of the periprosthetic bone in neither the good nor poor bone quality tibia at the baseline bone densities. When applying a stumble load, a collapse of the tibial reconstruction was noticed in the poor bone quality model. Incorporating postoperative bone loss led to a significant increase of the failure risk, particularly for the poor bone quality model in which subsidence of the tibial component was substantial. Our results suggest bone loss can lead to an increased risk of a collapse of the tibial component, particularly in case of poor bone quality at the time of surgery. The study also examined the probability of medial or lateral subsidence of the implant and aimed to improve clinical implications. The FEA model simulated plastic deformation of the bone and implant subsidence, with further validation required via mechanical experiments., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Introduction: Olfactory disorders are among the four most common post-COVID-19 complaints. The aim of our prospective study from a university ENT post-COVID consultation (PCS) was to substantiate the symptoms with psychophysical test results., Methods: After an ENT examination, 60 post-COVID-19 patients (41 women) were asked in writing about their medical history. Their ability to smell was tested using the extended Sniffin' Sticks test battery and their ability to taste was determined using the 3-drop test. From these data, three quantitative olfactory (RD) and gustatory (SD) diagnoses could be defined from normal value tables. Every second patient took part in a control examination., Results: Up to the first examination, 60 patients reported smell and 51 taste disorders; their average duration was 11 months in both cases. Objectified pathologic RD and SD had 87% and 42% of the total cohort, respectively. Every third patient suffered from an objectified combination of olfactory and gustatory damage. About every second patient complained of parosmia. Parosmic patients with two visits came earlier for a check-up. Six months after the initial examination, the detection thresholds, the TDI and the RD had improved in these patients. The self-assessment of olfactory ability had not changed., Conclusions: Objectified pathologic RD persisted in our PCS for a mean of 1.5 years from the onset of infection. Parosmics had a better prognosis. For the healthcare system and especially for the patients affected, they continue to be a burden even after the pandemic., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Polyetheretherketone (PEEK) has been proposed as alternative material for total knee arthroplasty implants due to its low stiffness, which may reduce stress-shielding. In cementless fixation, a proper primary fixation is required for long-term fixation. Previous research showed that the lower stiffness of a cementless PEEK femoral component results in larger micromotions at the implant-bone interface compared to a cobalt-chrome femoral component. A titanium inlay on the PEEK implant surface may improve the primary fixation while maintaining the favourable stiffness properties. Therefore, the effect of thickness and stiffness of a titanium inlay on the primary fixation and stress-shielding was investigated. A finite element model of the femur and femoral component was created with five titanium inlay variants. The micromotions and strain energy density (SED) were quantified as outcome measures. The distal thin - proximal thick variant showed the largest resulting micromotions (51.2 µm). Relative to the all-PEEK femoral component, the addition of a titanium inlay reduced the micromotions with 30 % to 40 % without considerably affecting the stress-shielding capacity (strain energy difference of 6 % to 10 %). Differences in micromotions (43.0-51.2 µm) and SED between the variants were relatively small. In conclusion, the addition of a titanium inlay could lead to a reduction of the micromotions without substantially affecting the SED distribution., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/ personal relationships which may be considered as potential competing interests: A.B. is a paid employee of Invibio Ltd. and had a role in the study design and review of the manuscript. N.V. is a paid consultant for Invibio Ltd. D.J. is a paid consultant for Invibio Ltd. and receives research support as a principal investigator from Invibio Ltd. The other authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

For biomechanical simulations of orthopaedic interventions, it is imperative to implement a material model that can realistically reproduce the nonlinear behavior of the bone structure. However, a proper material model that adequately combines the trabecular and cortical bone response is not yet widely identified. The current paper aims to investigate the possibility of using an isotropic crushable foam (ICF) model dependent on local bone mineral density (BMD) for simulating the femoral fracture risk. The elastoplastic properties of fifty-nine human femoral trabecular cadaveric bone samples were determined and combined with existing cortical bone properties to characterize two forms of the ICF model, a continuous and discontinuous model. Subsequently, the appropriateness of this combined material model was evaluated by simulating femoral fracture experiments, and a comparison with earlier published results of a softening Von-Mises (sVM) material model was made. The obtained mechanical properties of the trabecular bone specimens were comparable to previous findings. Furthermore, the ultimate failure load predicted by the simulations of femoral fractures was on average 79% and 90% for the continuous and discontinuous forms of the ICF model and 82% of the experimental value for the sVM material model. Also, the fracture locations predicted by ICF models were comparable to the experiments. In conclusion, a nonlinear material model dependent on BMD was characterized for human femoral bone. Our findings indicate that the ICF model could predict the femoral bone strength and reproduce the variable fracture locations in the experiments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Soltanihafshejani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The aim of this study was to develop and validate a clinical prediction model to predict overall survival in patients with nonmetastatic, resected gallbladder cancer (GBC)., Background: Although several tools are available, no optimal method has been identified to assess survival in patients with resected GBC., Methods: Data from a Dutch, nation-wide cohort of patients with resected GBC was used to develop a prediction model for overall survival. The model was internally validated and a cohort of Australian GBC patients who underwent resection was used for external validation. The performance of the American Joint Committee on Cancer (AJCC) staging system and the present model were compared., Results: In total, 446 patients were included; 380 patients in the development cohort and 66 patients in the validation cohort. In the development cohort median survival was 22 months (median follow-up 75 months). Age, T/N classification, resection margin, differentiation grade, and vascular invasion were independent predictors of survival. The externally validated C-index was 0.75 (95%CI: 0.69-0.80), implying good discriminatory capacity. The discriminative ability of the present model after internal validation was superior to the ability of the AJCC staging system (Harrell C-index 0.71, [95%CI: 0.69-0.72) vs. 0.59 (95% CI: 0.57-0.60)]., Conclusion: The proposed model for the prediction of overall survival in patients with resected GBC demonstrates good discriminatory capacity, reasonable calibration and outperforms the authoritative AJCC staging system. This model can be a useful tool for physicians and patients to obtain information about survival after resection and is available from https:// gallbladderresearch.shinyapps.io/Predict&#95;GBC&#95;survival/., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Disorders of the sense of smell and taste are often complained as a long-COVID symptom. In a special long-COVID consultation (ENT-LCS), we wanted to figure out how large the proportion of pathological olfactory or gustatory diagnoses actually is in this cohort., Methods: 48 adult patients who visited the ENT-LCS because of their own suffering were asked about their history, rated their ability to smell (SER) and taste (SES) with school grades and completed the extended Sniffin' Sticks test and the 3-drop test as a taste test. Diagnoses were made from the SDI smell score and the total taste score using normative values. Correlations were calculated between the measured scores and the self-assessment and between SER and SES., Results: Pathological chemosensory diagnoses were present in 90%. Pathological olfactory diagnoses were twice as common as gustatory ones. No pathological diagnosis could be verified in 10% of the cohort. Anosmia-ageusia syndrome was diagnosed in six patients. SER correlated strongly with SDI. SES correlated moderately with SScore-total. SER correlated strongly with SES., Conclusions: There is a risk of smell-taste confusion when interpreting reported chemosensory symptoms. This is another reason why reference is made to the importance of quantifying the chemical senses with validated tests., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Cardiac decompensation is associated with worse prognosis in patients with heart failure. Reliable methods to predict cardiac decompensation events are not yet available. Sleep-disordered breathing (SDB) is a frequent comorbidity in heart failure, and it has been shown to correlate with heart failure severity. This prospective observational trial investigated SDB characteristics in patients with heart failure with the aim to identify patterns that may predict early cardiac decompensation. Patients with heart failure with diagnosed SDB and hospitalised for cardiac decompensation were prospectively enrolled and treated with adaptive servo-ventilation (ASV). SDB characteristics, daily body weight and clinical cardiac decompensation events were collected over a 1-year follow-up. Clinical events were categorised by an independent clinical event committee. A total of 43 patients were enrolled (81% male, mean [SD] age 71 [11] years, body mass index 30 kg/m 2 , 95% New York Heart Association function class III or IV, mean [SD] left ventricular ejection fraction 37% [11%], median apnea-hypopnoea index [AHI] of 37 events/h). A total of 48 cardiac decompensation events were recorded during the 1-year study period. Respiratory rate was found to be significantly lower in patients with cardiac decompensation. The AHI and applied inspiratory pressure ASV-device support were significantly increased 10 days before a clinical cardiac decompensation event. Device usage was also found to be significantly decreased 2 nights before cardiac decompensation. Device-derived respiratory data in ASV therapy devices for SDB may therefore serve as a monitoring tool to predict early clinical cardiac decompensation events. Prediction and avoidance of cardiac decompensation, in turn, may attenuate serious health consequences in patients with heart failure., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Patients with femoral metastases are at risk of fracturing bones. It is important to prevent fractures in order to maintain mobility and quality of life. The BOne Strength (BOS) score is based on a computed tomography (CT)-based patient-specific finite element (FE) computer model that objectively calculates bone strength. In this pilot study, the added clinical value of the BOS score towards treatment-related decision making was assessed. In December 2019, the BOS score was implemented in four radiotherapy centers. The BOS scores and fracture risks of individual patients were calculated and returned to the physician to assist in treatment decisions. The physicians filled out a questionnaire, which was qualitatively analyzed. A follow-up to identify fractures and/or death was performed after six months. Until June 2021, 42 BOS scores were delivered (20 high, 9 moderate, and 13 low fracture risk). In 48%, the BOS score led to an adaptation of treatment plans. Physicians indicated that the BOS score provided objective insight into fracture risk, was reassuring for physicians and patients, and improved multidisciplinary discussions and shared decision making. In conclusion, the BOS score is an objective tool to assess fracture risk in femoral bone metastases and aids physicians and patients in making a more informed decision regarding the most appropriate treatment.

Introduction: Hemodynamic assessment is crucial after heart transplantation (HTX) or left ventricular assist device (LVAD) implantation. Gold-standard is invasive assessment via thermodilution (TD). Noninvasive pulse contour analysis (NPCA) is a new technology that is supposed to determine hemodynamics completely noninvasive. We aimed to validate this technology in HTX and LVAD patients and conducted a prospective single-center cohort study., Methods: Patients after HTX or LVAD implantation underwent right heart catheterization including TD. NPCA using the CNAP Monitor (V.5.2.14; CNSystems Medizintechnik AG, Graz, Austria) was performed simultaneously. Three TD measurements were compared with simultaneous NPCA measurements for hemodynamic assessment. To describe the agreement between TD and NPCA, Bland-Altman analysis was done., Results: In total, 28 patients were prospectively enrolled (HTX: n = 10, LVAD: n = 18). Bland-Altman analysis revealed a mean bias of +1.05 l/min (limits of agreement ± 4.09 l/min, percentage error 62.1%) for cardiac output (CO). In LVAD patients, no adequate NPCA signal could be obtained. In 5 patients (27.8%), any NPCA signal could be detected, but was considered as low signal quality., Conclusion: In conclusion, according to our limited data in a small cohort of HTX and LVAD patients, NPCA using the CNAP Monitor seems not to be suitable for noninvasive evaluation of the hemodynamic status., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Cardiac olfactory stimulus reactions could expand the range of objectifying test methods for testing olfactory function. In a pilot study, it was investigated whether and how pleasant and unpleasant odors change the heart rate (HR) and its variability., Methodology: 32 healthy people with normal smell function inhaled nasally for seven minutes the smell of four Sniffin' Sticks (banana, fish, garlic and rose) alternating with blanks. At the same time, the ECG was recorded and offline the NN intervals (distance of the R-waves) and six parameters of the heart rate variability were determined and compared with the values of a blank irritation using generalized estimation equations (GEE). In addition, the values of the subjective assessment of intensity and hedonic valence of the four odors were correlated with the heart rate., Results: The unpleasant odor fish smell increased the heart rate slightly but significantly in the first stimulus minute. The fish smell increased a single heart rate variability parameter (LF/HF) during the continuous stimulation, too, and showed a significant moderate correlation between HR and the scaling of intensity and hedonics in the first stimulus minute. The pleasant and the garlic odors did not affect the analyzed cardiac parameters., Conclusions: Olfactory evoked changes in HR should be further investigated as an indicator of the integrity of olfactory function. The most promising and time- and cost-effective is probably an 1-minute irritation with the unpleasant fishy smell from the identification set of the Sniffin' Sticks during the ECG recording., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) ( n  = 57) or standard of care (control) ( n  = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P  = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P  = 0.50; maximal inspiratory pressure increased by 16.6 cm H 2 O and 4.8 cm H 2 O, respectively (difference [95% CI], 11.8 [5 to 19]), P  = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P  = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

The use of a more compliant material, such as polyetheretherketone (PEEK), for a cementless femoral component is a potential solution to prevent aseptic loosening caused by peri-prosthetic stress-shielding. Long-term fixation of a cementless femoral component is achieved by a proper primary fixation of the bone-implant interface, which is influenced by the interference fit and frictional properties of the implant surface. This computational study investigates the sensitivity of micromotions and interface gaps of a cementless PEEK femoral component to the interference fit and coefficient of friction. 24 finite element models of the femur and femoral component were created with variations in implant material, interference fit and coefficient of friction. Peak loads of a jogging activity were applied on the models. Micromotions and interface gaps were both sensitive to the interference fit, coefficient of friction and implant material. Besides the implant material, the micromotions and interface gaps of the implant were most sensitive to the interference fit. Compared to the cobalt-chrome (CoCr) femoral component, the PEEK femoral component generated higher micromotions and interface gaps when equal interference fit and friction values were applied. However, increasing the interference fit and friction of the PEEK component resulted in micromotion values comparable with the CoCr component. This result leads to possibilities using cementless PEEK femoral components., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The prevalence of long-term olfactory and gustatory dysfunction in participants suffering from sudden chemosensory loss due to coronavirus disease 2019 (COVID-19) is unknown. Furthermore, evaluations of the reliability of participants' self-reporting of olfactory function (SOF) and gustatory function (SGF) using extended objective psychophysical testing are missing., Methods: In this population-based cohort study in a PCR-tested community in Thuringia, Germany, olfactory function was extensively examined 4 months after a COVID-19 outbreak using the "Sniffin Sticks" test battery to determine the TDI a score, i.e., the sum of results obtained for threshold, discrimination, and identification scores averaged for both nasal sides. Gustatory function was assessed using the three-drop test resulting in the gustatory composite score (CS g ). The data were compared with SOF and SGF., Results: Of 43 adult convalescents (median age: 68 years; 58% female) after SARS-CoV‑2 infection, 18 participants (42%) had olfactory complaints due to SOF, one participant (2%) complained of taste disturbance due to SGF. The TDI a was 22.0 ± 5.9. Normosmia, hyposmia, and anosmia were seen in 17, 18, and eight participants, respectively. TDI a correlated with SOF (r s  = -0.434, p = 0.004); CS g was 23.5 ± 2.7. Normogeusia and hypogeusia were objectified in 39 and four participants, respectively. The prevalence of long-term olfactory dysfunction and gustatory dysfunction in the study group was 60.5 and 9.3%, respectively., Conclusion: The SOF was reliable, especially for participants who felt a sudden chemosensory dysfunction during the outbreak. At 4 months after SARS-CoV‑2 infection, a high proportion of participants were dysosmic, whereas nearly all of them had normal taste function., (© 2021. The Author(s).)

Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes. Polymethylmethacrylate (PMMA) cement is the most commonly used bone substitute in clinical orthopedics in view of its reliability. However, the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone tumors. Here, we introduce porosity into PMMA cement by adding carboxymethylcellulose (CMC) to facilitate such local delivery of chemotherapeutic drugs, while retaining sufficient mechanical properties for bone reconstruction in load-bearing sites. Our results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC content. Upon incorporation of ≥3% CMC, the PMMA-based cements released up to 18% of the loaded cisplatin, in contrast to cements containing lower amounts of CMC which only released less than 2% of the cisplatin over 28 days. This release of cisplatin efficiently killed osteosarcoma cells in vitro and the fraction of dead cells increased to 91.3% at day 7, which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based cements. Additionally, tibias filled with PMMA-based cements containing up to 3% of CMC exhibit comparable compressive strengths as compared to intact tibias. In conclusion, we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical levels. As such, these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites., (© 2022 The Authors.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Finite element (FE) simulations can be used to evaluate the mechanical behavior of human bone and allow for quantitative prediction of press-fit implant fixation. An adequate material model that captures post-yield behavior is essential for a realistic simulation. The crushable foam (CF) model is a constitutive model that has recently been proposed in this regard. Compression tests under uniaxial and confined loading conditions were performed on 59 human trabecular bone specimens. Three essential material parameters were obtained as a function of bone mineral density (BMD) to develop the isotropic CF model. The related constitutive rule was implemented in FE models and the results were compared to the experimental data. The CF model provided an accurate simulation of uniaxial compression tests and the post-yield behavior of the stress-strain was well-matched with the experimental results. The model was able to reproduce the confined response of the bone up to 15% of strain. This model allows for simulation of the mechanical behavior of the cellular structure of human bone and adequately predicts the post-yield response of trabecular bone, particularly under uniaxial loading conditions. The model can be further improved to simulate bone collapse due to local overload around orthopaedic implants., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Breathing changes induced by repeated short olfactory stimuli are used as an objective indicator of the integrity of the olfactory system. Until now, it has not been investigated whether chemosensorically induced changes in inspiratory and expiratory time parameters can be suppressed intentionally. The same applies to breathing changes due to weak CO 2 stimuli., Methodology: 34 healthy adult normosmics were stimulated during relaxed regular nasal breathing using a flow olfactometer with nine differently concentrated H 2 S and three weak CO 2 stimulation pulses. They were instructed to intentionally maintain regular nasal breathing during the stimulation. A significant breathing change was present if the duration of the inspiration (DIN) or the expiration (DEX) of the first stimulatory breath was outside the double standard deviation of the mean of five prestimulatory regular breaths. These could be shortened or extended the DIN or DEX., Results: Despite high motivation, the chemosensorically induced breathing changes could not be suppressed intentionally. Rest breathing reacted to both stimulants by changes in both the inspiratory and the expiratory time parameters. However, it outweighed the expiratory reactions. CO 2 evoked more breathing changes than H 2 S. The frequency of reaction rate of H 2 S stimuli was not concentration-dependent. Strong H 2 S stimuli induced more frequent shortening than prolongation of DEX., Conclusions: Chemosensorically triggered breathing changes cannot be suppressed intentionally. They therefore provide an additional objective tool to check the functionality of nasal chemosensory afferents., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Moderate-to-severe obstructive sleep apnea (OSA) is highly prevalent in heart failure patients with reduced left ventricular ejection fraction (HFrEF), and is associated with worsening cardiac function and increased mortality., Objectives: The automatic positive airway pressure (APAP) trial tested the impact of APAP treatment on changes for the pre-specified endpoints: changes in peak oxygen uptake (peak VO 2 ), percent-predicted peak VO 2 and oxygen uptake at anaerobic threshold (VO 2 -AT)., Methods: This randomized, controlled pilot study included patients with chronic, stable HFrEF who had moderate-to-severe OSA. Patients were randomized 1:1 to either APAP (AutoSet™, ResMed) or nasal strips (control) for 6 months., Results: 76 patients have been randomized and 58 had complete data for final analysis. There was a statistically significant change in the APAP intervention arm for the primary endpoint percent-predicted peak VO 2 in comparison to control (67 ± 17 to 73 ± 19%; p = 0.01). Additional primary endpoints peak VO 2 and VO 2 -AT showed a trend in increase in the APAP group. Moreover, there were significant improvements within the APAP group for hypoxemia, left ventricular function and quality of life from baseline to 6 months, but not within the control group (p = 0.001 and p = 0.037, respectively)., Conclusion: APAP intervention was shown to significantly improve outcome compared to control group, represented in percent-predicted peak VO 2 , an established surrogate marker for cardiovascular prognosis in HFrEF. APAP has additional beneficial effects on hypoxemia, cardiac function and quality of life.

Background: Respiratory dyssynchrony (RD) is a phenomenon that may be reflected by reduced breathing efficiency (CO 2 output relative to minute ventilation, V̇E/V̇CO 2 slope) or by Exercise oscillatory ventilation (EOV). Low breathing efficiency and EOV indicate a worse prognosis in chronic heart failure patients with reduced ejection fraction (HFrEF). However, only little is known about their role in other forms of structural myocardial diseases. In this study, we assessed the prognostic impact of RD in hypertrophic non-obstructive cardiomyopathy (HNCM) as a subgroup of patients with heart failure and preserved ejection fraction (HFpEF)., Methods and Results: We selected n = 132 HNCM patients (pts) who underwent cardiopulmonary exercise testing (CPET) during baseline assessment. The average follow-up was 4.3 ± 3.6 years. The primary endpoint was a composite of death, heart transplantation (HTX), and implantation of a ventricular assist device (VAD). Respiratory dyssynchrony, as measured by EOV, was recorded in 18 pts. (14%), and as measured by a V̇E/V̇CO 2 relationship of higher than 34 in 34 pts. (26%). In total, 22 (16.7%) pts. met the endpoint. Multivariate COX regression Analysis were made for EOV, V̇E/V̇CO 2 and the combination of EOV andV̇E/V̇CO 2 . All parameters correlated significantly with the endpoint: EOV (hazard ratio [HR]: 3.7; p = 0.006), V̇E/V̇CO 2 > 34 (HR: 5.6; p = 0.001) and EOV andV̇E/V̇CO 2 : (HR: 6.1; p ≤ 0.001)., Conclusion: This is the first study to demonstrate the prognostic impact of RD on pts. with HNCM, and to investigate EOV as a novel factor to aid risk stratification in HNCM., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: This cross-sectional, multi-centric study aimed to investigate the differences in quality of life among patients with olfactory dysfunction (OD) of different origin, and to identify factors associated with olfactory-related quality of life (QOL)., Methods: Seven hundred sixty-three adults were recruited from 8 Smell & Taste clinics in Germany, Switzerland, and Austria. Olfactory-related QOL was assessed by the Questionnaire of Olfactory Disorders (QOD). Olfactory function was assessed with the "Sniffin' Sticks" test; self-assessment was performed with visual analog scales., Results: Patients with post-infectious and post-traumatic OD showed poorer olfactory-related QOL than patients with sinonasal and idiopathic OD. The olfactory-related QOL was positively associated with the "Sniffin' Sticks" test score, self-assessed olfactory function, disease duration, and age, with younger olfactory dysfunction patients showing lower QOL. Female patients presented with poorer olfactory-related QOL. In addition, the results showed that self-assessment of olfactory function explained more of the variance in olfactory-related QOL than olfactory function evaluated by the Sniffin’ Sticks test., Conclusions: In addition to the psychophysical testing results, several factors such as disease cause, disease duration, sex, or self- assessed olfactory dysfunction should be taken into account when assessing the individual severity of the smell loss.

Purpose: During cochlear implant (CI) surgery, visual detection of the stapedius reflex as movements of the stapes tendon, electrically elicited via the CI, is a standard measure to confirm the system's functionality. Direction visualization of the stapedius muscle (SM) movements might be more reliable, but a safe access to the small SM is not defined. A new surgical planning tool for pre-operative evaluation of the accessibility to the stapedius muscle (SM) during a cochlear implantation (CI) via a retrofacial approach was now evaluated., Methods: A surgical planning tool was developed in MATLAB using an image processing algorithm to evaluate drilling feasibility. A flat-panel computed tomography (CT) combining a rotational angiographic C-arm units with flat-panel detectors (Dyna-CT) was used. In total, 30 3D Dyna-CT-based temporal bone reconstructions were evaluated by automatized algorithms, generating a series of trajectories and comparing their feasibility and safety to reach the SM via a retrofacial approach. The predictability of the surgical planning tool results was tested in 5 patients., Results: The surgical planning tool showed that a retrofacial access to the SM would be feasible in 25/30 cases. Moreover, the evaluation of the predictability of the results obtained with the surgical planning tool conducted during 5 CI surgeries confirmed the results. Both the surgical planning tool and the results on SM accessibility via retrofacial approach during CI showed that this is safe and feasible only when the SM-exposed area was > 25% of its total, the distance between the SM and the facial nerve was > 0.8 mm, and the surgical corridor diameter was > 3 mm., Conclusion: The surgical planning tool seems to be useful for the pre-operative evaluation of the accessibility to the SM during a CI surgery via a retrofacial approach. Further prospective studies are needed to validate the results in larger cohorts.

Background: The detection rate of olfactory chemosensory event-related EEG Potentials (oCSERP) and trigeminal chemosensory event-related EEG Potentials (tCSERP) is also dependent on the stimulants and the evaluator of the averaged EEG curves., Methods: In 45 subjects with age-appropriate normal olfactory capacity (NP) and 20 anosmics (AN), oCSERP (stimulation by hydrogen sulphide, H 2 S 6 ppm and phenylethyl alcohol, PEA 30 % v/v,) and tCSERP (irritation with CO 2 20-60 % v/v, intensity standardized) were derived by default. Two investigators categorized the averaged EEG curves in: CSERP recognizable, no CSERP recognizable and artefact. Investigator 1 knew whether the subject was a NP or an AN, and which stimulants was used, whereas investigator 2 lacked this information., Results: AN needed higher trigeminal stimulus concentrations but showed same intensity ratings compared to NP. The attention (tracking game) did not deteriorate in the course of test. The detection rate of H 2 S-CSERP was higher than that of PEA-CSERP. The match of H 2 S-CSERP detection rates between the two investigators was higher than that of PEA-CSERP and CO 2 -CSERP., Conclusion: For the standard derivation of oCSERP, stimulation with H 2 S is usually sufficient. Stimulation with PEA and CO 2 as well as a blinded investigator is not necessary., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Background: In the attentive waking state, pleasant odours often prolong inhalation while unpleasant odours often shorten the exhalation. It should be checked whether this induced breathing pattern is maintained even during sleep., Methodology: 23 healthy normosmic adults were examined by polysomnography for one night and randomized pulsed either with H 2 S, phenylethyl alcohol (PEA) or CO 2 via a flow olfactometer. The determination of the sleep stages was based on the standard polysomnography curves. From the breathing curves (respiratory nasal pressure breathing, thoracic or abdominal belt breathing) a low-artefact curve was selected and seven breaths were measured from their breathing signal around the trigger impulse. The duration of inspiration (DIN) and the duration of the expiration (DEX) were determined from the six prestimulatory breaths and from breath with the stimulus onset and thus defined a reaction index (RI) indicating whether there is a significant change in shortening or prolonging DIN and/or DEX. These different RI were corrected by the spontaneous baseline RI and analysed according to the type of stimulus and the sleep stages., Results: Reaction indices with reductions of DEX were larger than spontaneous RI and RI for PEA and H 2 S stimulation. In the case of CO 2 irritation, RI with reductions of DIN and DEX were larger than with olfactory stimulation. All RI were equal in their amount between sleep stages. In REM, the difference between olfactory RI with shortened DEX between H 2 S and PEA stimulation was greatest., Conclusion: When stimulated with an unpleasant smell in sleep, the respiratory reaction pattern from the awake state is preserved. RI with shortened DEX can be considered as an imperfect arousal., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The active butanol detection thresholds (B-DT), determined using the sniffin' sticks, show a high intra- and inter-individual test-retest reliability, although the internal stimulus concentration may vary considerably depending on the dilution of the external stimulus concentration with odorless ambient air during active sniffing. There are various hypotheses for this surprising result. In this study, it should be tested whether a larger respiratory effort (vigor) under physical stress changes the active B-DT., Methods: In 28 young, healthy, normosmic adults, sitting on a stationary bicycle ergometer at rest phase, during aerobic exercise and in the recovery phase, the monorhinal B-DT using Sniffin' Sticks were determined. Various vital parameters such as blood pressure, heart frequency, body temperature, respiratory frequency and blood lactate characterized the three test phases. The individual stress perception was estimated according to the Borg scale., Results: The B-DT did not change in the three test phases. All examined vital parameters were significantly larger in the loading phase than in the resting phase. In the case of a moderate to severe stress sensation (Borg-scale: 13-15), an aerobic physical stress could be confirmed on the basis of the vital parameters., Conclusions: The investigations support the hypothesis that vigor is not the decisive factor for a constant olfactory perception of external equal stimulus concentrations. The integration of internal stimulus concentration and nasal flow velocity and the empirical evaluation of the current odor concentration probably play a greater role., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Gallbladder cancer (GBC) is rare in Western populations and data about treatment and outcomes are scarce. This study aims to analyze survival and identify opportunities for improvement using population-based data from a low-incidence country. GBC patients diagnosed between 2005 and 2016 with GBC were identified from the Netherlands Cancer Registry. Patients were grouped according to time period (2005-2009/2010-2016) and disease stage. Trends in treatment and overall survival (OS) were analyzed. In total 1834 patients were included: 661 (36%) patients with resected, 278 (15%) with non-resected non-metastatic, and 895 (49%) with metastatic GBC. Use of radical versus simple cholecystectomy (12% vs. 26%, p < 0.001) in early (pT1b/T2) GBC increased. More patients with metastatic GBC received chemotherapy (11% vs. 29%, p < 0.001). OS improved from 4.8 months (2005-2009) to 6.1 months (2010-2016) ( p = 0.012). Median OS increased over time (2005-2009 vs. 2010-2016) in resected (19.4 to 26.8 months, p = 0.038) and metastatic (2.3 vs. 3.4 months, p = 0.001) GBC but not in unresected, non-metastatic GBC. In early GBC, patients with radical cholecystectomy had a median OS of 76.7 compared to 18.4 months for simple cholecystectomy ( p < 0.001). Palliative chemotherapy showed superior ( p < 0.001) survival in metastatic (7.3 versus 2.1 months) and non-resected non-metastatic (7.7 versus 3.5 months) GBC. In conclusion, survival of GBC remains poor. Radical surgery and palliative chemotherapy appear to improve prognosis but remain under-utilized.

Introduction: Tumor-targeted imaging is a promising technique for the detection of lymph node metastases (LNM) and primary tumors. It remains unclear which biomarker is the most suitable target to distinguish malignant from healthy tissue in esophageal adenocarcinoma (EAC)., Objective: We performed an immunohistochemistry study to identify viable tumor markers for tumor-targeted imaging of EAC., Methods: We used samples from 72 patients with EAC to determine the immunohistochemical expression of ten potential tumor biomarkers for EAC (carbonic anhydrase IX [CA-IX], carcinoembryonic antigen [CEA], hepatic growth factor receptor, epidermal growth factor receptor, epithelial membrane antigen [EMA], epithelial cell adhesion molecule [EpCAM], human epidermal growth factor receptor 2 [HER-2], urokinase plasminogen activator receptor, vascular endothelial growth factor-A [VEGF-A], and VEGF receptor 2). Immunohistochemistry was performed on tissue microarrays of LNM (n = 48), primary EACs (n = 62), fibrotic tissues (n = 11), nonmalignant lymph nodes (n = 24), and normal esophageal and gastric tissues (n = 40). Tumor marker staining was scored on intensity and percentage of positive cells., Results: EMA and EpCAM showed strong expression in LNM (> 95%) and primary EACs (> 95%). Significant expression was also observed for LNM and EAC using VEGF-A (85 and 92%), CEA (68 and 54%), and CA-IX (4 and 34%). The other tumor biomarkers showed expression of 0-15% for LNM and primary EAC. Except for VEGF-A, nonmalignant lymph node staining was scored as slight or absent., Conclusions: High expression rates and correlation between LNM in EAC combined with low expression rates in healthy lymph nodes and esophagus tissues were observed for EpCAM and CEA, meaning these are promising targets for tumor-targeted imaging approaches for lymph nodes in patients with EAC.

Purpose: Evaluation of 3D Dyna-CTs to improve cochlear implantation (CI) planning and intraoperative electrically elicited stapedius reflex threshold (ESRT) measurements., Methods: A prospective observational cohort study was performed. Anonymized data collection of Dyna-CTs and CI surgeries in which a retrofacial approach was implemented to access the stapedius muscle. 3D Dyna-CTs of 30 patients and the intraoperative confirmation of the predication in 5/30 patients during CI surgery were evaluated. Inter-rater reliability was also analyzed along with the predictive value of this evaluation., Results: 36 representative structures of the middle and inner ear and 3D renderings of the Dyna-CTs were evaluated by four otoneurological surgeons. Fleiss' kappa values for the evaluation of the visibility were high (> 0.7) for most of the anatomical structures. The stapedius muscle was visible in 90% of the cases. Using the 3D data, the retrofacial access to the stapedius muscles was estimated as feasible in 86.7%. Fleiss' kappa value of the evaluation of the accessibility was 0.942. The intraoperative exploration of the stapedius muscle confirmed the preoperative prediction in all five selected patients (four patients with predicted accessibility and one patient with predicted inaccessibility)., Conclusions: The use of Dyna-CT and 3D rendering is a helpful tool for preoperative planning of cochlear implantations and ESRT measurements from the stapedius muscle via the retrofacial approach.

Purpose: In heart failure with reduced ejection fraction (HFrEF), the effects of automatic positive airway pressure therapy (APAP) for obstructive sleep apnea (OSA) on sleep quality and sympatho-vagal balance (SVB) are unknown., Methods: In this randomized controlled trial (6 months of APAP vs. nasal strips as control), sleep quality and SVB in patients with HFrEF and OSA were monitored. The distinction was made between different breathing conditions (5-min segments of OSA or normal breathing [NB] during stable N2 sleep) at baseline (T0), APAP initiation (T1), and 6 months of successful APAP treatment (T2)., Results: Of 75 patients enrolled, 61 were men with average age of 65 ± 12 years and LVEF of 31 ± 9%; 37 patients were randomized into the APAP and 38 into the control (nasal strips only) group. At T0, OSA was associated with a 17% increase in the low-frequency/high-frequency component ratio of heart rate variability (LF/HF) versus baseline, suggesting an increase in sympathetic drive (SVB) with OSA compared with normal breathing. Respiratory indices and oxygen saturation all significantly improved at both T1 and T2, but at 6 months, APAP had no clinically relevant effect on objective sleep quality versus control. In fact, in patients with HFrEF (n = 23 with data suitable for HRV analysis), there was even a trend (p = 0.097) towards an additional 17% increase in LF/HF at T2 in the therapy group, suggesting (undesired) increased SVB in the APAP group., Conclusion: Treatment of OSA in patients with systolic HF improves respiratory indices but does not have a favorable effect on sleep quality. While OSA per se was associated with an increase in sympathetic drive, APAP treatment was not associated with a reduction in sympathetic drive. After 6 months of treatment, there was even a trend towards additional increases in sympathetic drive in the APAP group.

Background: Adaptive servoventilation (ASV) effectively treats nocturnal respiratory events in patients with heart failure and reduced ejection fraction (HFrEF) and central sleep apnoea (CSA), but increased mortality has been reported. This study investigated changes in sleep architecture during ASV treatment in HFrEF patients., Methods: A retrospective analysis of polysomnographic datasets for 30 ASV-treated patients with stable HFrEF and moderate-to-severe CSA was performed, including blinded analyses of total sleep time (TST), and percentage of REM and non-REM sleep (stages N1-N3)., Results: Follow-up was 109 ± 32 days; mean device usage was 6.0 ± 1.1 h/day. During ASV there was reduction of N1 (34 ± 20%/TST to 13 ± 5%/TST, p < 0.001) and N3 sleep (4 ± 6%/TST to 1 ± 4%/TST, p = 0.020), and increase of N2 (44 ± 14%/TST to 62 ± 7%/TST, p < 0.001) and REM-sleep (18 ± 8%/TST to 24 ± 6%/TST, p = 0.002)., Conclusions: Disturbances of sympatho-vagal balance during ASV might help explain increased mortality during ASV. Since sympathetic tone is highest in REM-sleep and vagal predominance occurs during N3 sleep, these findings generate new hypotheses for the increased mortality seen in SERVE-HF., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The existence of functionally relevant accessory olfactory organs in humans is still a matter of controversy. A vomeronasal organ (VNO) with sensory and non-sensory epithelia exists only in macrosmatic mammals. A similar structure is regularly observed in humans during fetal development. The postnatal persistence of a VNO like epithelial duct has been described in about 10 %. Here we studied tissue samples of nasal mucosa from adults. In all individuals we found epithelial cells in the lower part of the nasal septum which exhibited morphological features of sensory neurons and which showed immunostaining for olfactory marker protein OMP. These cells were interposed by ciliated cells, goblet cells and small intraepithelial capillaries. Only occasionally we found such cells within a morphologically defined epithelial duct. A clear separation of sensory and non-sensory epithelia could not be observed. In most cases we found OMP positive groups of cells either in epithelial cavities or just embedded in respiratory epithelium. With RT-PCR we could confirm the presence of OMP encoding mRNA thus supporting the idea of intrinsic expression of this protein in the nasal mucosa. We conclude that accessory chemosensory structures are regularly conserved in adult humans in the approximate anatomical location of the VNO of microsmatic animals. Their functional importance is yet to be determined., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Fretting and corrosion at the taper-head interface in total hip arthroplasty has been reported as a potential cause of early failure of the implant system. The finite element (FE) method can be used to study the mechanics at the taper junction that are difficult to assess experimentally. Taper mismatch is one of the factors that can influence the performance of the taper junction. In this study we have assessed the effect of taper mismatch, in combination with assembly force on the volumetric wear. The study showed that higher assembly forces and smaller mismatches result in the least volumetric wear.

Objectives: Pulmonary hypertension (PH) is extremely common in acute decompensated heart failure (ADHF) patients and predicts increased mortality. Obstructive sleep apnea (OSA), highly prevalent in congestive heart failure patients, may contribute to further elevated pulmonary pressures. This study evaluates the impact of positive airway pressure (PAP) therapy on PH in patients admitted for ADHF with OSA., Methods: A two-center randomized control trial comparing standard of care (SOC) therapy for ADHF versus addition of PAP therapy in patients with concomitant OSA., Results: Twenty-one consecutive patients were enrolled with 1:1 randomization to SOC versus SOC plus 48-hour PAP therapy protocol. In the intervention arm, the mean pulmonary artery systolic pressure (PASP) difference before therapy and after 48 hours of PAP therapy was -15.8 ± 3.2 (58.6 ± 2.5 mm Hg to 42.8 ± 2.7) versus the SOC arm where the mean PASP difference was -5.2 ± 2.6 (62.7 ± 3.3 mm Hg reduced to 57.5 ± 3.9) (p = 0.025). In addition, ejection fraction in the intervention arm improved (3.4 ± 1.5% versus -0.5 ± 0.5 %) (p = 0.01). Significant improvement was also noted in tricuspid annular plane systolic excursion (TAPSE) and right ventricular systolic area in the intervention arm but not in NT-pro-BNP or 6-minute walk distance., Conclusions: In patients with ADHF and OSA, addition of 48 hours of PAP therapy to SOC treatment significantly reduced PH. In addition, PAP therapy was able to improve right and left ventricular function. ClinicalTrials.gov identifier: NCT02963597., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.

Functional endoscopic sinus surgery (FESS) is the minimal-invasive standard procedure for surgical treatment of patients with chronic rhinosinusitis. FESS follows the principle to remove all pathologies within the paranasal sinuses while sparing normal mucosa and all functionally relevant anatomical structures. To understand the functional integrity and the principles of FESS, it is important to have fundamental knowledge of the anatomy of the paranasal sinuses, especially of the orifices to the different sinuses. Normally based on a computed tomography of the paranasal sinuses in two section planes, the FESS surgeon has to reproduce the individual anatomy and to plan the individual extent of the FESS. The severity of the disease and the extent of surgery can be classified. In this review the knowledge to be known by an otorhinolaryngologist is reflected and the main steps of FESS are explained. The equipment will be described. Typical complications of FESS and complication management will be elucidated., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Clear cell renal cell carcinoma (ccRCC) comprises more than 80% of all renal cancers and when metastasized leads to a 5-year survival rate of only 10%. The high rate of therapy failure and resistance development calls for reliable methods that provide information on the actionable biological pathways and predict optimal treatment protocols for individual patients. We here applied targeted RNA sequencing (t/RNA-NGS) using single molecule Molecular Inversion Probes on tumor nephrectomy samples of five ccRCC patients, comparing tumor with healthy kidney tissues. Transcriptome profiling focused on expression of genes with involvement in ccRCC biology that can be targeted with clinically available drugs. Results confirm high expression of vascular endothelial growth factor-A (VEGF-A) in tumor tissue relative to healthy-appearing kidney, in line with the angiogenic nature of ccRCC. PDGFRα and KIT, targets of the multi-kinase inhibitor sunitinib which is one of the current choices of first-line drug in metastasized ccRCC patients, were expressed at relatively low levels in tumor tissues, whereas significantly increased in normal kidney. Of all measured druggable tyrosine kinases, MET, AXL, or EGFR were expressed at higher levels in tumors than in normal kidney tissues, although intertumor differences were observed. Using cancer cell lines we show that t/RNA-NGS gene expression profiles can be used to predict in vitro sensitivity to targeted drugs. In conclusion, t/RNA-NGS analysis may provide insights into the (druggable) molecular make-up of individual renal cancers, and may guide personalized therapy of renal cell cancers.

Background: Lymph node metastases (LNM) are an ominous prognostic factor in gallbladder cancer (GBC) and, when present, should preclude surgery. However, uncertainty remains regarding the optimal imaging modality for pre-operative detection of LNM and international guidelines vary in their recommendations. The purpose of this study was to systematically review the diagnostic accuracy of computed tomography (CT) versus magnetic resonance imaging (MRI) in the detection of LNM of GBC., Methods: A literature search of studies published until November 2017 concerning the diagnostic accuracy of CT or MRI regarding the detection of LNM in GBC was performed. Data extraction and risk of bias assessment was performed independently by two reviewers. The sensitivity of CT and MRI in the detection of LNM was reviewed. Additionally, estimated summary sensitivity, specificity and diagnostic accuracy of MRI were calculated in a patient based meta-analysis., Results: Nine studies including 292 patients were included for narrative synthesis and 5 studies including 158 patients were selected for meta-analysis. Sensitivity of CT ranged from 0.25 to 0.93. Estimated summary diagnostic accuracy parameters of MRI were as follows: sensitivity 0.75 (95% CI 0.6 - 0.85), specificity 0.83 (95% CI 0.74 - 0.90), LR + 4.52 (95% CI 2.55-6.48) and LR- 0.3 (95% CI 0.15 - 0.45). Small (<10 mm) LNM were most frequently undetected on pre-operative imaging. Due to a lack of data, no subgroup analysis comparing the diagnostic accuracy of CT versus MRI could be performed., Conclusion: The value of current imaging strategies for the pre-operative assessment of nodal status in GBC remains unclear, especially regarding the detection of small LNM. Additional research is warranted in order to establish uniformity in international guidelines, improve pre-operative nodal staging and to prevent futile surgery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Diffuse gliomas often carry point mutations in isocitrate dehydrogenase ( IDH1 mut ), resulting in metabolic stress. Although IDH mut gliomas are difficult to culture in vitro, they thrive in the brain via diffuse infiltration, suggesting brain-specific tumor-stroma interactions that can compensate for IDH-1 deficits. To elucidate the metabolic adjustments in clinical IDH mut gliomas that contribute to their malignancy, we applied a recently developed method of targeted quantitative RNA next-generation sequencing to 66 clinical gliomas and relevant orthotopic glioma xenografts, with and without the endogenous IDH-1 R132H mutation. Datasets were analyzed in R using Manhattan plots to calculate distance between expression profiles, Ward's method to perform unsupervised agglomerative clustering, and the Mann Whitney U test and Fisher's exact tests for supervised group analyses. The significance of transcriptome data was investigated by protein analysis, in situ enzymatic activity mapping, and in vivo magnetic resonance spectroscopy of orthotopic IDH1 mut - and IDH wt -glioma xenografts. Gene set enrichment analyses of clinical IDH1 mut gliomas strongly suggest a role for catabolism of lactate and the neurotransmitter glutamate, whereas, in IDH wt gliomas, processing of glucose and glutamine are the predominant metabolic pathways. Further evidence of the differential metabolic activity in these cancers comes from in situ enzymatic mapping studies and preclinical in vivo magnetic resonance spectroscopy imaging. Our data support an evolutionary model in which IDH mut glioma cells exist in symbiosis with supportive neuronal cells and astrocytes as suppliers of glutamate and lactate, possibly explaining the diffuse nature of these cancers. The dependency on glutamate and lactate opens the way for novel approaches in the treatment of IDH mut gliomas.-Lenting, K., Khurshed, M., Peeters, T. H., van den Heuvel, C. N. A. M., van Lith, S. A. M., de Bitter, T., Hendriks, W., Span, P. N., Molenaar, R. J., Botman, D., Verrijp, K., Heerschap, A., ter Laan, M., Kusters, B., van Ewijk, A., Huynen, M. A., van Noorden, C. J. F., Leenders, W. P. J. Isocitrate dehydrogenase 1-mutated human gliomas depend on lactate and glutamate to alleviate metabolic stress.

Background: In a previous study, the detection threshold for H2S during aerobic exercise worsened with forced nasal breathing. The cause remained unclear. It is to be examined how the detection threshold changes with exclusive mouth breathing., Material and Methods: During a resting phase, an aerobic physical load and subsequent recovery phase, different H2S concentrations were applied inspiratory-synchronously intranasal using a flow-olfactometer in a staircase procedure. The missing nasal breathing was objectified online and offline. The reaction times were determined. In parallel, various vital parameters have been measured., Results: The passive detection thresholds for H2S between the load and recovery phases did not differ. In the resting phase, the threshold was highest. The reaction times were not different in the three experimental phases., Conclusion: An increased sympathetic tone, resulting from an approximately half-hour aerobic exercise, did not change the passive olfactory threshold for H2S during oral respiration compared to the subsequent recovery period. The high olfactory threshold in the resting phase might be explained by initial adaptation difficulties to the experimental conditions., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: To clarify whether unmasking of central sleep apnea during continuous positive airway pressure (CPAP) initiation can be identified from initial diagnostic polysomnography (PSG) in patients with heart failure with reduced ejection fraction (HFREF) and obstructive sleep apnea (OSA) MATERIALS AND METHODS: Forty-three consecutive patients with obstructive sleep apnea and central sleep apnea (OSA/CSA) in HFREF were matched with 43 HFREF patients with OSA and successful CPAP initiation. Obstructive apneas during diagnostic PSG were then analyzed for cycle length (CL), ventilation length (VL), apnea length (AL), time to peak ventilation (TTPV), and circulatory delay (CD). We calculated duty ratio (DR) as the ratio of VL/CL and mathematic loop gain (LG)., Results: While AL was similar, CL, VL, TTPV, CD, and DR was significantly longer in patients with OSA/CSA compared to those with OSA, and LG was significantly higher. Receiver operator curves identified optimal cutoff values of 50.2 s for CL (area under the curve (AUC) 0.85, 29.2 s for VL (AUC 0.92), 11.5 s for TTPV (AUC 0.82), 26.4 s for CD (AUC 0.79), and 3.96 (AUC 0.78)) respectively for LG to identify OSA/CSA., Conclusion: OSA/CSA in HFREF can be identified by longer CL, VL, TTPV, and CD from obstructive events in initial diagnostic PSG. The underlying mechanisms seem to be the presence of an increased LG.

Current finite element (FE) models predicting failure behavior comprise single vertebrae, thereby neglecting the role of the posterior elements and intervertebral discs. Therefore, this study aimed to develop a more clinically relevant, case-specific non-linear FE model of two functional spinal units able to predict failure behavior in terms of (i) the vertebra predicted to fail; (ii) deformation of the specimens; (iii) stiffness; and (iv) load to failure. For this purpose, we also studied the effect of different bone density-mechanical properties relationships (material models) on the prediction of failure behavior. Twelve two functional spinal units (T6-T8, T9-T11, T12-L2, and L3-L5) with and without artificial metastases were destructively tested in axial compression. These experiments were simulated using CT-based case-specific non-linear FE models. Bone mechanical properties were assigned using four commonly used material models. In 10 of the 11 specimens our FE model was able to correctly indicate which vertebrae failed during the experiments. However, predictions of the three-dimensional deformations of the specimens were less promising. Whereas stiffness of the whole construct could be strongly predicted (R 2  = 0.637-0.688, p < 0.01), we obtained weak correlations between FE predicted and experimentally determined load to failure, as defined by the total reaction force exhibiting a drop in force (R 2  = 0.219-0.247, p > 0.05). Additionally, we found that the correlation between predicted and experimental fracture loads did not strongly depend on the material model implemented, but the stiffness predictions did. In conclusion, this work showed that, in its current state, our FE models may be used to identify the weakest vertebra, but that substantial improvements are required in order to quantify in vivo failure loads. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodical, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:3208-3218, 2018., (© 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodical, Inc. on behalf of Orthopaedic Research Society.)