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Objectives: To investigate characteristics and outcomes of critically ill cancer patients with marked hyperferritinemia. Methods: A single‐center retrospective analysis comprising cancer patients with a ferritin level >10.000 μg/L treated in the intensive care unit (ICU) between 2012 and 2022 was conducted. Results: A total of 117 patients were included in the analysis. The median age was 59 years (range: 15–86 years). Females accounted for 48% of cases. 90% of patients had a hematologic malignancy. The median maximum ferritin level was 27.349 μg/L (range: 10.300–426.073 μg/L). The diagnostic criteria of septic shock were fulfilled in 51% of cases; 31% of patients had hemophagocytic lymphohistiocytosis (HLH) according to the HLH‐2004 criteria. Mechanical ventilation, renal replacement therapy and the use of vasopressors were necessary in 59%, 35% and 70% of cases, respectively. The ICU, hospital, 90‐day and 1‐year survival rates were 33.3%, 23.1%, 23.7% and 11.7%. Patients with septic shock had a worse survival than those without septic shock (p =.001); the survival of patients who fulfilled the HLH‐2004 criteria did not differ from those who did not (p =.88). Conclusion: Critically ill cancer patients with marked hyperferritinemia have poor outcomes. The present data may help to make informed decisions for this patient group. [ABSTRACT FROM AUTHOR]

Although several promising approaches for the treatment of relapsed/refractory diffuse large B‐cell lymphoma (rrDLBCL) have been approved recently, it remains unclear which patients will ultimately achieve long‐term responses. Circulating tumor (ct)DNA sequencing has emerged as a valuable tool to assess minimal residual disease (MRD). Correlations between MRD and outcomes have been shown in previously untreated DLBCL, but data on the repeated assessment of MRD in the dynamic course of rrDLBCL is limited. Here, we present an approach leveraging cost‐ and time‐sensitivity of digital droplet (dd)PCR to repeatedly assess MRD in rrDLBCL and present proof‐of‐principle for its ability to predict outcomes. [ABSTRACT FROM AUTHOR]

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare disorder typically characterized by the clinical triad including a sudden onset of fever, painful skin lesions, and neutrophilia. The histopathological findings are a dense neutrophilic infiltrate and oedema of the dermis and epidermis without evidence of a vasculitis. Besides treatment of the underlying cause, sweet syndrome is typically treated with high‐dose corticosteroids leading to a relapse‐free response in 70% of patients. However, if left unrecognized or untreated, the condition may lead to serious complications. Here, we report on the case of a 38‐year‐old patient in whom, under the assumption of the presence of necrotizing fasciitis, exarticulation of the right arm was performed. In the absence of pathogen detection and insufficient response to anti‐infective therapies, the diagnosis of a sweet syndrome was assumed and, later, confirmed by an excellent response to high‐dose administration of systematic glucocorticoids. The case emphasizes the need to be aware of this rare syndrome, which can be easily misdiagnosed due to its close resemblance to infection and stresses the need of further research to define distinct diagnostic tools. [ABSTRACT FROM AUTHOR]

Background: Burkitt lymphoma (BL) and diffuse large B‐cell lymphoma (DLBCL) are aggressive B‐cell non‐Hodgkin lymphomas (B‐NHL) with a generally favorable prognosis after immunochemotherapy. The outcome of BL is superior to DLBCL. In 2016, a distinct group of lymphomas displaying characteristics of both BL and DLBCL (high grade B‐cell lymphoma, HGBL) was introduced into the WHO classification. Histopathological discrimination of BL, DLBCL, and HGBL may be challenging. Data on the frequency of histopathological difficulties resulting in revision of the final diagnosis of BL/DLBCL/HGBL and its impact on the prognosis are limited. Methods: We assessed histopathological features and clinical outcomes of 66 patients with suspected diagnosis of BL at the reporting institution between 2010 and 2020. Results: The median age was 51 years (range 19‐82) and final histopathological diagnosis revealed BL (n = 40), DLBCL (n = 12), or HGBL (n = 14). Patients with DLBCL and HGBL were either treated with DLBCL‐directed (83.3% and 35.7%) or BL‐directed (16.7% and 64.3%) protocols. Patients in whom diagnosis was revised from DLBCL to BL after initiation of DLBCL‐directed treatment had a significantly inferior progression‐free survival (PFS) than patients initially diagnosed with BL (p = 0.045), thus resembling rather the prognosis of DLBCL/HGBL. There was no difference between patients with DLBCL and HGBL, respectively, regarding PFS and OS (p = 0.38 and p = 0.27). Conclusion: These results suggest that timely and precise histopathological diagnosis as well as reference histopathological review of the underlying lymphoma is critical to determine up‐front treatment strategies. Consequently, selection of more aggressive treatment protocols in case of difficulties with discrimination between DLBCL/HGBL/BL may be a reasonable approach. [ABSTRACT FROM AUTHOR]

Partial epithelial‐to‐mesenchymal transition (pEMT) contributes to cellular heterogeneity that is associated with nodal metastases and unfavorable clinical parameters in head and neck squamous cell carcinomas (HNSCCs). We developed a single‐cell RNA sequencing signature‐based pEMT quantification through cell type‐dependent deconvolution of bulk RNA sequencing and microarray data combined with single‐sample scoring of molecular phenotypes (Singscoring). Clinical pEMT‐Singscores served as molecular classifiers in multivariable Cox proportional hazard models and high scores prognosticated poor overall survival and reduced response to irradiation as independent parameters in large HNSCC cohorts [The Cancer Genome Atlas (TCGA), MD Anderson Cancer Centre (MDACC), Fred Hutchinson Cancer Research Center (FHCRC)]. Differentially expressed genes confirmed enhanced cell motility and reduced oxidative phosphorylation and epithelial differentiation in pEMThigh patients. In patients and cell lines, the EMT transcription factor SLUG correlated most strongly with pEMT‐Singscores and promoted pEMT, enhanced invasion, and resistance to irradiation in vitro. SLUG protein levels in HNSCC predicted disease‐free survival, and its peripheral expression at the interphase to the tumor microenvironment was significantly increased in relapsing patients. Hence, pEMT‐Singscores represent a novel risk predictor for HNSCC stratification regarding clinical outcome and therapy response that is partly controlled by SLUG. [ABSTRACT FROM AUTHOR]

Background: Primary central nervous system lymphoma (PCNSL) is a rare type of aggressive lymphoma of the central nervous system. Treatment strategies improved significantly over the past decades differ regionally but mainly consist of rituximab and high‐dosed methotrexate (MTX)‐based therapies. Methods: We assessed clinical outcomes of 100 patients with newly diagnosed PCNSL between 2010‐2020 at the University Hospital of Cologne, Germany. Results: Patients were 23‐88 years of age and either treated with MTX‐based regimens (PRIMAIN, MARTA, MATRix), individual regimens, or best supportive care, respectively. Overall response rates were generally high (66,7‐83,8%), but different organ toxicities required dose adjustments in most groups. Two‐year overall survival rates were 57,9% (PRIMAIN), 63,6% (MARTA), 65,4% (MATRix), and 37,5% (Other), respectively. Out of 9 patients suffering from relapse >12 months from primary diagnosis, 7 patients (77,8%) received methotrexate‐based salvage therapy with 2‐year overall survival of 4/6 patients (66,7%). Conclusion: Although a relevant proportion of patients are not eligible for clinical trials due to age, performance status, or comorbidities, these results prove feasibility of different MTX‐based treatment strategies in clinical routine. Even elderly patients displayed surprisingly favorable outcomes. However, with compromising organ toxicities, reduction of intensity should be part of strategies in future clinical trials. [ABSTRACT FROM AUTHOR]

The blood–brain barrier (BBB) is a highly selective membrane composed predominantly of brain capillary endothelial cells expressing drug efflux transporters that prevent substrates from accessing the brain. Inflammation is associated with central nervous system diseases and can impair BBB permeability via several mechanisms, including altered transporter and cell junction expression. This can modify the brain's exposure to drugs. However, comprehensive genomic analysis of the impact of interleukin (IL)‐6, which plays a key role in the inflammatory response, on the BBB is lacking. In the present study, we analyzed the effects of exposure of hCMEC/D3 cells to 20 ng/mL IL‐6 for 72 h. We performed RNA sequencing and ABC transporter efflux assays. Physiologically based pharmacokinetics (PBPK) simulations were conducted to evaluate the potential impact of IL‐6 on the digoxin pharmacokinetics profile and brain exposure by decreasing BBB ABCB1 efflux activity. Exposure of hCMEC/D3 cells to IL‐6 triggered the deregulation of numerous genes involved in barrier permeability, such as cell junctions, focal adherens complex, and cell adhesion molecules. We observed mild modification of the mRNA expression and efflux activities of ABC transporters. PBPK simulation showed that, if we only consider the impact of IL‐6 on ABCB1 transporter, the modification of the digoxin pharmacokinetics profile and brain exposure is slight. IL‐6 slightly affected the gene expression levels and activities of ABC transporters on BBB cells, exhibiting a weaker effect than on hepatic cells. However, inflammation may cause other modifications, such as altered BBB permeability, that could modify drug pharmacokinetics. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinomas (HNSCCs) have poor clinical outcome owing to therapy resistance and frequent recurrences that are among others attributable to tumor cells in partial epithelial‐to‐mesenchymal transition (pEMT). We compared side‐by‐side software‐based and visual quantification of immunohistochemistry (IHC) staining of epithelial marker EpCAM and EMT regulator Slug in n = 102 primary HNSCC to assess optimal analysis protocols. IHC scores incorporated expression levels and percentages of positive cells. Digital and visual evaluation of membrane‐associated EpCAM yielded correlating scorings, whereas visual evaluation of nuclear Slug resulted in significantly higher overall scores. Multivariable Cox proportional hazard analysis defined the median EpCAM expression levels resulting from visual quantification as an independent prognostic factor of overall survival. Slug expression levels resulting from digital quantification were an independent prognostic factor of recurrence‐free survival, locoregional recurrence‐free survival, and disease‐specific survival. Hence, we propose to use visual assessment for the membrane‐associated EpCAM protein, whereas nuclear protein Slug assessment was more accurate following digital measurement. [ABSTRACT FROM AUTHOR]

Emissive media are often challenging to render: in thin regions where only few scattering events occur the emission is poorly sampled, while sampling events for emission can be disadvantageous due to absorption in dense regions. We extend the standard path space measurement contribution to also collect emission along path segments, not only at vertices. We apply this extension to two estimators: extending paths via scattering and distance sampling, and next event estimation. In order to do so, we unify the two approaches and derive the corresponding Monte Carlo estimators to interpret next event estimation as a solid angle sampling technique. We avoid connecting paths to vertices hidden behind dense absorbing layers of smoke by also including transmittance sampling into next event estimation. We demonstrate the advantages of our line integration approach which generates estimators with lower variance since entire segments are accounted for. Also, our novel forward next event estimation technique yields faster run times compared to previous next event estimation as it penetrates less deeply into dense volumes. [ABSTRACT FROM AUTHOR]

In photorealistic image synthesis the radiative transfer equation is often not solved by simulating every wavelength of light, but instead by computing tristimulus transport, for instance using sRGB primaries as a basis. This choice is convenient, because input texture data is usually stored in RGB colour spaces. However, there are problems with this approach which are often overlooked or ignored. By comparing to spectral reference renderings, we show how rendering in tristimulus colour spaces introduces colour shifts in indirect light, violation of energy conservation, and unexpected behaviour in participating media. Furthermore, we introduce a fast method to compute spectra from almost any given XYZ input colour. It creates spectra that match the input colour precisely. Additionally, like in natural reflectance spectra, their energy is smoothly distributed over wide wavelength bands. This method is both useful to upsample RGB input data when spectral transport is used and as an intermediate step for corrected tristimulus-based transport. Finally, we show how energy conservation can be enforced in RGB by mapping colours to valid reflectances. [ABSTRACT FROM AUTHOR]

Many-light methods approximate the light transport in a scene by computing the direct illumination from many virtual point light sources (VPLs), and render low-noise images covering a wide range of performance and quality goals. However, they are very inefficient at representing glossy light transport. This is because a VPL on a glossy surface illuminates a small fraction of the scene only, and a tremendous number of VPLs might be necessary to render acceptable images. In this paper, we introduce Rich-VPLs which, in contrast to standard VPLs, represent a multitude of light paths and thus have a more widespread emission profile on glossy surfaces and in scenes with multiple primary light sources. By this, a single Rich-VPL contributes to larger portions of a scene with negligible additional shading cost. Our second contribution is a placement strategy for (Rich-)VPLs proportional to sensor importance times radiance. Although both Rich-VPLs and improved placement can be used individually, they complement each other ideally and share interim computation. Furthermore, both complement existing many light methods, e.g. Lightcuts or the Virtual Spherical Lights method, and can improve their efficiency as well as their application for scenes with glossy materials and many primary light sources. [ABSTRACT FROM AUTHOR]

Background Carcinomas of the maxillary sinus are classified according to the Union Internationale Contre le Cancer (UICC)/American Joint Committee on Cancer (AJCC) TNM classification. The purpose of this study was to assess the prognostic significance of the UICC/AJCC TNM classification seventh edition, which was introduced in 2010. Methods One hundred thirteen patients with malignant tumors of the maxillary sinus were included in this study. The prognostic impact of the TNM classification and the UICC/AJCC seventh edition's stage grouping were analyzed in univariate and multivariate analysis. Results The UICC/AJCC stage grouping, the T classification, and the N classification had a significant impact on overall survival (OS) in univariate analysis ( p < .05). No significant differences were observed between the groups T4a and T4b ( p = .109). In multivariate analysis, the UICC/AJCC stage grouping ( p = .031), the N classification ( p = .014), and age ( p < .001) had a significant impact on OS. Conclusion Although UICC/AJCC stage grouping and the N classification provided a significant prediction of OS in univariate and multivariate analysis, T classification only influenced OS in univariate analysis. © 2014 Wiley Periodicals, Inc. Head Neck 37: 400-406, 2015 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To determine the prevalence and the morphometric characteristics of Killian's triangle and to examine their relationship with the anthropometric features of the person. Study Design: Prospective. Methods: The hypopharyngeal wall was examined on 47 human cadavers. After a standardized method of dissection, the muscular structures of the hypopharyngeal wall were demonstrated and the existence or absence of Killian's triangle was determined. The triangle was examined in regard to its morphometric characteristics. In addition, anthropometric examinations of the whole body and of the head and neck regions on these cadavers were done, and the results were compared with the features of Killian's dehiscence. Results: A triangle of Killian was present on 60% (9/15) of the males and on 34% (11/32) of the females. The mean height for the males was 7 mm and for the females 4 mm, and the width was on average 16 mm and 12 mm, respectively. The dimensions of the triangle were correlated significantly with the dimensions of the body and with the length and the descensus of the larynx. Conclusions: The frequency and the dimensions of Killian's triangle appear to be greater in males than in females. Furthermore, the morphometric characteristics of the dehiscence show a correlation with the anthropometric features of the person. These findings can be an explanation for the higher incidence of Zenker's diverticulum with men and for the geographical differences of the diverticulum's frequency. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]

Background. The epidermal growth factor receptor (EGFR) and the inhibitor of apoptosis protein survivin play important roles in the regulation of cellular proliferation and survival in squamous cell carcinomas. Their correlation in oropharyngeal squamous cell carcinoma (OSCC) has not been evaluated yet. Methods. In this multicenter study, we analyzed the expression of survivin and EGFR in tissue specimens from 73 selected patients with OSCC using immunohistochemistry. Results. Higher cytoplasmic survivin scores were significantly correlated with high scores of EGFR expression (p = .013). Nuclear survivin expression was associated with a poor overall survival rate with an estimated 3-year overall survival probability of 17.3% versus 87.4% for non-nuclear expression of survivin (p <.001). Multivariate analysis revealed that nuclear survivin expression was an independent negative prognostic factor (p = .008). Conclusion. Considering the strong impact of nuclear survivin expression on survival, the survivin expression should be prospectively evaluated to select patients with an increased risk for disease recurrence. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [ABSTRACT FROM AUTHOR]

The incidence of wound botulism is increasing dramatically among intravenous drug users. Efficient intensive care and early treatment with antitoxin is essential to avoid lethal courses. The clinical picture of botulism is of descending, symmetric, flaccid paralysis. Early symptoms include cranial nerve palsies resulting in blurred vision and diplopia, difficulty in focusing, ptosis, facial weakness, dysphagia, dysphonia, and dysarthria. Because patients presenting with dysarthria and dysphagia will often be seen by an ear, nose and throat specialist initially, this rare but upcoming neurologic disease must be considered in the differential diagnoses.