Search

Bronchiolitis obliterans syndrome (BOS), the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group), and 26 samples at or after BOS diagnosis (diagnosis group). An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group). We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A), and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy occurring mostly in older immunocompromized Caucasian males. A growing incidence of MCC has been reported in epidemiological studies. Treatment of MCC usually consists of surgical excision, pathological lymph node evaluation, and adjuvant radiotherapy. This paper reports the experience of a single tertiary center institution with 17 head and neck Merkel cell carcinoma patients. Median followup for the cohort was 37.5 months. After five years, recurrence-free survival, disease specific survival, and overall survival were 85%, 90%, and 83%, respectively. Our limited data support the use of adjuvant radiotherapy. We also report two cases of MCC located at the vestibule of the nose and two cases of spontaneous regression after diagnostic biopsy. About 40% of our patients were referred to our center for surgical revision and pathological lymph node evaluation. Increased awareness of MCC and an interdisciplinary approach are essential in the management of MCC.

Collective scattering of spatially coherent radiation by separated point emitters induces inter-particle forces. For particles close to nano-photonic structures as, for example, nano-fibers, hollow core fibers or photonic waveguides, this pair-interaction induced by monochromatic light is periodic and virtually of infinite range. Here we show that the shape and range of the optical interaction potential can be precisely controlled by spectral design of the incoming illumination. If each particle is only weakly coupled to the confined guided modes the forces acting within a particle ensemble can be decomposed to pairwise interactions. These forces can be tailored to almost arbitrary spatial dependence as they are related to Fourier transforms with coefficients controlled by the intensities and frequencies of the illuminating lasers. We demonstrate the versatility of the scheme by highlighting some examples of unconventional pair potentials. Implementing these interactions in a chain of trapped quantum particles could be the basis of a versatile quantum simulator with almost arbitrary all-to-all interaction control.

Collective coherent light scattering by polarizable particles creates surprisingly strong, long range inter-particle forces originating from interference of the light scattered by different particles. While for monochromatic laser beams this interaction decays with the inverse distance, we show here that in general the effective interaction range and geometry can be controlled by the illumination bandwidth and geometry. As generic example we study the modifications inter-particle forces within a 1D chain of atoms trapped in the field of a confined optical nanofiber mode. For two particles we find short range attraction as well as optical binding at multiple distances. The range of stable distances shrinks with increasing light bandwidth and for a very large bandwidth field as e.g. blackbody radiation. We find a strongly attractive potential up to a critical distance beyond which the force gets repulsive. Including multiple scattering can even lead to the appearance of a stable configuration at a large distance. Such broadband scattering forces should be observable contributions in ultra-cold atom interferometers or atomic clocks setups. They could be studied in detail in 1D geometries with ultra-cold atoms trapped along or within an optical nanofiber. Broadband radiation force interactions might also contribute in astrophysical scenarios as illuminated cold dust clouds.

Even though endoscopic removal of inverted papillomas has gained popularity, many studies advocate supplementary external approaches. The impact of including the current surgical staging system into the pre-operative clinical and radiological assessment has not been systematically evaluated. We present our experience with total endoscopic management of inverted papillomas and compare the accuracy of the pre-operative predicted extent of surgery, with the actually performed surgery.From 1997 to 2005 data from 51 patients with inverted papillomas were prospectively collected and subsequently reviewed. All have been operated on endoscopically without an external approach.The overall recurrence rate was 3.9 per cent. Pre-operative prediction of extent of surgery was accurate in 26 of 51 (51 per cent). The main reasons for the inaccurate pre-operative prediction were the variable sizes and locations of the inverted papilloma bases, particularly in the maxillary sinus and the frontal recess. Our results encourage us to recommend endoscopic management as the standard treatment of benign inverted papillomas. [ABSTRACT FROM AUTHOR]

Optical fibres confine and guide light almost unattenuated and thus convey light forces to polarizable nano-particles over very long distances. Radiation pressure forces arise from scattering of guided photons into free space while gradient forces are based on coherent scattering between different fibre modes or propagation directions. Interestingly, even scattering between co-propagating modes induces longitudinal forces as the transverse confinement of the light modes creates mode dependent longitudinal wave-vectors and photon momenta. We generalize a proven scattering matrix based approach to calculate single as well as inter-particle forces to include several forward and backward propagating modes. We show that an injection of the higher order mode only in a two mode fibre will induce a stationary tractor force against the injection direction, when the mode coupling to the lower order mode dominates against backscattering and free space losses. Generically this arises for non-absorbing particles at the centre of a waveguide. The model also gives improved predictions for inter-particle forces in evanescent nanofibre fields as experimentally observed recently. Surprisingly strong tractor forces can also act on whole optically bound arrays. [ABSTRACT FROM AUTHOR]

Aims: Low-grade non-intestinal-type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal- and salivary-type neoplasms. Therefore, further characterisation is needed for clearer biological understanding and classification., Methods and Results: Clinical, histological and molecular characterisation of four cases of biphasic, low-grade adenocarcinomas of the sinonasal tract was performed. All patients were male, aged between 48 and 78 years, who presented with polypoid masses in the nasal cavity. Microscopically, virtually all tumours were dominated by tubulo-glandular biphasic patterns, microcystic, focal (micro)papillary, oncocytic or basaloid features. Immunohistochemical staining confirmed biphasic differentiation with an outer layer of myoepithelial cells. Molecular profiling revealed HRAS (p.G13R, p.Q61R) mutations, and concomitant AKT1 (p.E17K, p.Q79R) mutations in two cases. Two cases showed potential in-situ/precursor lesions adjacent to the tumour. Follow-up periods ranged from 1 to 30 months, with one case relapsing locally after 12 and > 20 years., Conclusion: This study further corroborates a distinct biphasic low-grade neoplasm of the sinonasal tract with seromucinous differentiation. Although morphological and molecular features overlap with salivary gland epithelial-myoepithelial carcinoma, several arguments favour categorising these tumours within the spectrum of LGSNAC., (© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.)

Adenoid cystic carcinoma (AdCC) is a salivary gland neoplasm that infrequently appears in the sinonasal region. The aim of this study was to evaluate the outcome and clinicopathological parameters of sinonasal AdCC. A retrospective analysis was conducted on all cases of AdCC affecting the nasal cavity or paranasal sinuses between 2000 and 2018 at the University Hospital Zurich. Tumor material was examined for morphological features and analyzed for molecular alterations. A total of 14 patients were included. Mean age at presentation was 57.7 years. Sequencing revealed MYB::NFIB gene fusion in 11/12 analyzable cases. Poor prognostic factors were solid variant (p < 0.001), histopathological high-grade transformation (p < 0.001), and tumor involvement of the sphenoid sinus (p = 0.02). The median recurrence-free survival (RFS) and OS were 5.2 years and 11.3 years. The RFS rates at 1-, 5-, and 10-year were 100%, 53.8%, and 23.1%. The OS rates at 1-, 5-, and 10- years were 100%, 91.7%, and 62.9%, respectively. In Conclusion, the solid variant (solid portion > 30%), high-grade transformation, and sphenoid sinus involvement are negative prognostic factors for sinonasal AdCC. A high prevalence of MYB::NFIB gene fusion may help to correctly classify diagnostically challenging (e.g. metatypical) cases., (© 2024. The Author(s).)

Our goal with this survey is to provide an overview of the state of the art deep learning methods for face generation and editing using StyleGAN. The survey covers the evolution of StyleGAN, from PGGAN to StyleGAN3, and explores relevant topics such as suitable metrics for training, different latent representations, GAN inversion to latent spaces of StyleGAN, face image editing, cross-domain face stylization, face restoration, and even Deepfake applications. We aim to provide an entry point into the field for readers that have basic knowledge about the field of deep learning and are looking for an accessible introduction and overview.

This meta-analysis aims to investigate the outcome of sinonasal adenoid cystic carcinoma (snAdCC). We followed PRISMA guidelines and included studies reporting 5-year overall survival (OS) rates for snAdCC. Eligible studies were identified through a literature search and assessed using JBI critical appraisal checklist. A total of 17 studies were included comprising 2259 patients (mean age: 58.1 years, 52.7% female, 47.3% male). The meta-analysis demonstrated that the 5-year OS, 10-year OS, and 5-year disease-free survival (DFS) were 68%, 40%, and 47.2%, respectively. Descriptive statistics on study level showed high rates of locally advanced tumor stages at diagnosis: 23% cT3, 53% cT4, 3.4% N+, and 4.2% M+. 29.7% of the tumors were in the nasal cavity, 67.6% in the paranasal sinuses. The maxillary, ethmoid, sphenoid, and frontal sinus were affected in 50.9%, 7.2%, 4%, and 0.5%, of cases. A combination of surgery and radiotherapy was used in 45.4% of the patients and 19.3% of patients received surgery only. In conclusion, these findings emphasize the significance of thorough surveillance for individuals with snAdCC to identify any potential recurrence or progression of the disease.

Drug-resistant Pseudomonas aeruginosa (PA) poses an emerging threat to human health with urgent need for alternative therapeutic approaches. Here, we deciphered the B cell and antibody response to the virulence-associated type III secretion system (T3SS) in a cohort of patients chronically infected with PA. Single-cell analytics revealed a diverse B cell receptor repertoire directed against the T3SS needle-tip protein PcrV, enabling the production of monoclonal antibodies (mAbs) abrogating T3SS-mediated cytotoxicity. Mechanistic studies involving cryoelectron microscopy identified a surface-exposed C-terminal PcrV epitope as the target of highly neutralizing mAbs with broad activity against drug-resistant PA isolates. These anti-PcrV mAbs were as effective as treatment with conventional antibiotics in vivo. Our study reveals that chronically infected patients represent a source of neutralizing antibodies, which can be exploited as therapeutics against PA., Competing Interests: Declaration of interests A patent application encompassing aspects of this work has been filed by the University of Cologne, listing A.S., C.K., F.K., and J.R. as inventors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The purpose of this retrospective study was to investigate response of sinonasal mucosal melanoma (SMM) patients to treatment with immune checkpoint inhibitors (ICI), using hybrid PET imaging. Fifteen SMM patients underwent hybrid PET imaging before and three months after initiation of ICI. The disease-specific survival (DSS) was calculated. Quantitative PET parameters of the primary tumor and their association with DSS and therapy response were investigated. Nine of the fifteen (60%) patients responded to ICI therapy. Patients with therapy response depicted on hybrid PET imaging had better DSS than those without (p = 0.0058). Quantitative PET parameters of the initial PET harbored no association with DSS or therapy response. However, these findings lack of sufficient statistical power and must be interpreted with caution. The first restaging PET-imaging after ICI initiation can help stratify patients with regard to DSS., (© 2023. The Author(s).)

Purpose: We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery., Methods: Retrospective study on a consecutive cohort of treatment-naïve patients undergoing ETT pituitary gland surgery. Additionally, a systematic review and meta-analysis with focus on the rhinologic outcome, including postoperative smell function was performed., Results: The institutional series incorporated 168 patients. A concomitant endoscopic septoplasty was performed in 29/168 patients (17.3%). A nasoseptal flap was used for reconstruction of large skull-base defects or high-flow CSF leaks in 4/168 (2.4%) patients. Early postoperative rhinologic complications (< 4 weeks) included epistaxis (3%), acute rhinosinusitis (1.2%) and late postoperative complications (≥ 8 weeks) comprised prolonged crusting (15.6%), symptomatic synechiae (11.9%) and septal perforation (0.6%). Postoperative smell function was not impaired (Fisher's exact test, p = 1.0). The systematic review included 19 studies on 1533 patients with a median postoperative epistaxis rate of 1.4% (IQR 1.0-2.2), a postoperative acute rhinosinusitis rate of 2.3% (IQR 2.1-3.0), a postoperative synechiae rate of 7.5% (IQR 1.8-19.1) and a postoperative septal perforation rate of 2.2% (IQR 0.5-5.4). Seven studies including a total of 206 patients reported adequate outcome measures for smell function before and after ETT surgery. Only 2/7 studies reported an impairment of smell function postoperatively, especially in patients with nasoseptal flap harvesting., Conclusion: Early and late postoperative rhinologic complication rates after ETT surgery for pituitary lesions seem to be low. A thorough evaluation of smell function, in particular in patients at risk for nasoseptal flap harvesting, may be an important factor in optimal postoperative care., (© 2023. The Author(s).)

Purpose: Immunotherapy using immune checkpoint inhibitors (ICI) has revolutionized cancer treatment in recent years, particularly in melanoma. While response to immunotherapy is associated with high tumor mutational burden (TMB), PD-L1 expression, and microsatellite instability in several cancers, tumors lacking these biomarkers can still respond to this treatment. Especially, mucosal melanoma, commonly exhibiting low TMB compared to cutaneous melanoma, may respond to immunotherapy with immune checkpoint inhibitors. Therefore, the aim of our study was to investigate novel biomarkers in mucosal melanoma that predict response to combined ipilimumab and nivolumab., Methods: We investigated 10 tumor samples from 10 patients (three responders, seven non-responders) before treatment and six tumor samples from five patients after progression using a targeted Next Generation Sequencing (NGS) gene expression panel. The findings were corroborated with an independent method (i.e., immunohistochemical staining) on the same 10 tumor samples before treatment and, to increase the cohort, in addition on three tumor samples before treatment of more recent patients (one responder, two non-responders)., Results: With the targeted gene expression panel, we found the three tumor testis antigens CTAG1B (NY-ESO-1), MAGE-A3, and MAGE-A4 to be predominantly expressed in responding tumors. This marker panel was either not or not completely expressed in non-responders (p < 0.01). Using immunohistochemistry for all three markers, we could confirm the elevated expression in tumors responding to the ipilimumab/nivolumab combination therapy., Conclusion: In conclusion, these three biomarkers await validation in a larger patient cohort and could be easily used in future routine diagnostics to predict the outcome of ipilimumab/nivolumab combination therapy in mucosal melanoma patients., (© 2022. The Author(s).)

Background: Despite improvements in closure techniques by using a vital nasoseptal flap, the use of sealing materials, and improved neurosurgical techniques, cerebrospinal fluid (CSF) leak after transsphenoidal surgery still is a clinically relevant problem. Liqoseal® (Polyganics bv, Groningen, The Netherlands) is a CE-approved bioresorbable sealant patch for use as an adjunct to standard methods of cranial dural closure to prevent CSF leakage. This study aims to evaluate the application of Liqoseal in transsphenoidal surgery ex vivo and in vivo., Methods: 1. We created an ex vivo setup simulating the sphenoidal anatomy, using a fluid pump and porcine dura positioned on a conus with the anatomical dimensions of the sella to evaluate whether the burst pressure of Liqoseal applied to a bulging surface was above physiological intracranial pressure. Burst pressure was measured with a probe connected to dedicated computer software. Because of the challenging transsphenoidal environment, we tested in 4 groups with varying compression weight and time for the application of Liqoseal. 2. We subsequently describe the application of Liqoseal® in 3 patients during transsphenoidal procedures with intraoperative CSF leakage to prevent postoperative CSF leakage., Results: 1. Ex vivo: The overall mean burst pressure in the transsphenoidal setup was 231 (± 103) mmHg. There was no significant difference in mean burst pressure between groups based on application weight and time (p = 0.227). 2. In Vivo: None of the patients had a postoperative CSF leak. No nose passage problems were observed. One patient had a postoperative meningitis and ventriculitis, most likely related to preoperative extensive CSF leakage. Postoperative imaging did not show any local infection, swelling, or other device-related adverse effects., Conclusions: We assess the use of Liqoseal® to seal a dural defect during an endoscopic transsphenoidal procedure as to be likely safe and potentially effective., (© 2023. The Author(s).)

Since sinonasal intestinal-type adenocarcinomas (ITAC) show resemblance to colorectal adenocarcinomas, we aimed to investigate novel prognostic factors of outcome, with particular focus on the role of tumor budding (TB). Retrospective clinico-pathological single-institution study on consecutive ITAC patients between 1996 and 2020. Histopathological parameters including conventional subtypes and TB features (low, intermediate, high) were evaluated with the aid of pancytokeratin (AE1/AE3) immunohistochemical staining. Parameters were correlated to clinical data and outcome. A total of 31 ITAC patients were included. Overall, 19/31 patients (61.3%) presented with stage III/IV disease. Presence of lymph node or distant metastases was rare (1/31 patient, 3.2%). Treatment protocols consisted of tumor resection in 30/31 patients (96.8%) and primary radiochemotherapy in 1/31 patient (3.2%). Adjuvant radiation therapy was conducted in 20/30 surgically treated patients (66.7%). The 3- and 5-year overall survival (OS) was 83.9% and 78.3% and the 3- and 5-years disease-specific survival (DSS) 83.7% % and 78.5%, respectively. The presence of intermediate/high TB (defined as ≥ 5 buds) was associated with both, worse DSS (log rank p = 0.03) and OS (log rank p = 0.006). No patient with low TB revealed progressive disease or died of the disease. No association between TB and tumor stage or conventional tumor subtype was found. Tumor budding seems to be an independent prognostic factor of worse outcome in ITAC., (© 2022. The Author(s).)

The xanthophyll zeaxanthin (Zx) serves important photoprotective functions in chloroplasts and is particularly involved in the dissipation of excess light energy as heat in the antenna of photosystem II (PSII). Zx accumulates under high-light (HL) conditions in thylakoid membranes and is reconverted to violaxanthin by Zx epoxidase (ZEP) in low light or darkness. ZEP activity is completely inhibited under long-lasting HL stress, and the ZEP protein becomes degraded along with the PSII subunit D1 during photoinhibition of PSII. This ZEP inactivation ensures that high levels of Zx are maintained under harsh HL stress. The mechanism of ZEP inactivation is unknown. Here, we investigated ZEP inactivation by reactive oxygen species (ROS) under in vitro conditions. Our results show that ZEP activity is completely inhibited by hydrogen peroxide (H2O2), whereas inhibition by singlet oxygen or superoxide seems rather unlikely. Due to the limited information about the amount of singlet oxygen and superoxide accumulating under the applied experimental conditions, however, a possible inhibition of ZEP activity by these two ROS cannot be generally excluded. Despite this limitation, our data support the hypothesis that the accumulation of ROS, in particular H2O2, might be responsible for HL-induced inactivation of ZEP under in vivo conditions., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The question how to treat the clinically negative neck in sinonasal malignancies is controversial., Objectives: To investigate patterns of treatment failure and to assess outcome measures in patients with primary sinonasal malignancies., Methods: Retrospective cohort study of patients treated for primary malignant sinonasal malignancies., Results: Lymph node (LN) metastases at initial presentation were present in 8 of 152 patients (5.3%). Ipsi- and contralateral LN levels 1 and 2 were identified as nodal basins at risk. We found a 5-year overall survival (OS) of 75.2% and disease free survival of 61.1%. Among patients with cN0 neck, nodal recurrence free survival was not different between patients with and without elective neck treatment ( P   =  .23). On logistic regression analysis, we found initial T classification as an independent factor for achievement of complete remission (CR) and OS., Conclusions: LN metastases at initial presentation are rare and initial T classification was identified as the most important prognostic factor for OS and CR, emphasizing the need for a thorough initial staging of the primary tumor.

Background: Whole-body hybrid positron emission tomography (PET) imaging is increasingly used for sinonasal tumors. However, only empirical data exist on the additional, clinically relevant information derived from these techniques., Methods: This study included 96 regionalized magnetic resonance imaging (MRI) of the sinonasal tract/neck and separate hybrid FDG-PET/CT or FDG-PET/MRI in 74 patients. Additional radiological information (ARI) obtained from each hybrid examination was analyzed and its clinically relevance was determined. Clinically relevant information (CRI) was categorized with regard to primary tumor site, regional lymph node metastases, distant metastases, second primary tumors, and non-neoplastic findings., Results: A total of 45/96 (46.9%) hybrid PET examinations revealed ARI. CRI was found in 32/96 (33.3%) examinations and concerned the primary tumor site (6.1%), regional lymph node metastases (4.1%), distant metastases (14.3%), second primary tumors (7.3%), and non-neoplastic findings (5.1%)., Conclusions: Hybrid PET imaging yields additional radiological information translating into clinically relevant information in a substantial proportion of patients with sinonasal tumors., (© 2021 The Authors. Head & Neck published by Wiley Periodicals LLC.)