Metastases to Both Parotid Glands Six and Twelve Years after Resection of Renal Cell Carcinoma

Metastases of renal cell carcinoma (RCC) involving the parotid gland are very rare. We present to our knowledge the first case of a 74-year-old woman with metastases of an RCC which affected both parotid glands six and twelve years following curative therapy

Einsatz von Instrumenten bei der klinischen Untersuchung in deutschen HNO-Abteilungen und Privatpraxen heutzutage

Background: The classical forehead reflector as traditionally used by ear, nose, and throat (ENT) physicians for the ENT examination is now iconic for doctors in general. It is unknown which instruments are currently used in Germany to clinically examine ENT patients. Therefore, this study aims to present results of a survey about commonly used instruments. Materials and methods: An evaluation of 321 questionnaires from ENT doctors working in general and university hospitals (172) and in private practices (149) was performed. Results: The ENT mirror examination is nowadays carried out with a self-illuminating headlamp with battery and/or light guide cable. Approximately 20% of respondents also use a forehead mirror. The microscope is used by 90% of doctors to examine the ears; a rigid endoscope was used in 53.3% to examine the larynx, epipharynx (41.1%), and the nose/sinuses (34.6%). Flexible endoscopes and otoscopes are used only rarely. Conclusion: The self-illuminating headlamp, which is more often wireless in eastern Germany, has largely replaced the classical forehead reflector, with which doctors younger than 40 years were no longer trained. At least some organs are also examined very regularly with the microscope or rigid endoscope. The flexible endoscope and otoscope are used much less frequently overall, mainly by younger physicians and ENT doctors working in hospitals. The diagnostic potential of flexible endoscopy may be compromised by the outpatient remuneration structures in Germany

Duration of deafness impacts auditory performance after cochlear implantation: A meta‐analysis

Objective: Hearing loss is a highly disabling condition. Cochlear implantation is an established remedy if conventional hearing aids have failed to alleviate the level of disability. Unfortunately, cochlear implant (CI) performance varies dramatically. This study aims to examine the effects of duration of deafness (DoD) prior to cochlear implantation and the postoperative duration of implant experience with resulting hearing performance in postlingually deaf patients. Methods: A systematic literature review and two meta-analyses were conducted using the search terms cochlear implant AND duration deafness. Included studies evaluate the correlation between the DoD and auditory performance after cochlear implantation using monosyllabic and sentence tests. Correlation coefficients were determined using Pearson's correlation and Spearman rho. Results: A total of 36 studies were identified and included data on cochlear implantations following postlingual deafness and postoperative speech testing of hearing outcomes for 1802 patients. The mean age ranged from 44 to 68 years with a DoD of 0.1 to 77 years. Cochlear implant use varied from 3 months to 14 years of age. Speech perception, which was assessed by sentence and monosyllabic word perception, was negatively correlated with DoD. Subgroup analyses revealed worse outcomes for longer DoD and shorter postoperative follow-up. Conclusion: DoD is one of the most important factors to predict speech perception after cochlear implantation in postlingually deaf patients. The meta-analyses revealed a negative correlation between length of auditory deprivation and postoperative sentence and monosyllabic speech perception. Longer DoD seems to lead to worse CI performance, whereas more experience with CI mitigates the effect

Carcinoma of Unknown Primary and the 8th Edition TNM Classification for Head and Neck Cancer

Objective: In the 8th Edition TNM Classification for Head and Neck Cancer, the classification for carcinoma of unknown primary (CUP) changed in addition to oropharyngeal carcinomas. The current classification considers extranodal extension (ENE), determination of p16 (surrogate marker for human papillomavirus), and detection of Epstein-Barr virus (EBV). The aim of this study was to investigate the influence of the new classification on the prognosis of p16-positive and p16-negative CUP and the impact of EBV proof. Methods: Clinical and pathological data from patients with CUP of the head and neck between 2009 and 2018 were evaluated. The 7th (UICC7) and 8th (UICC8) edition of the Union for International Cancer Control staging system were applied and compared. Results: There were 97 patients treated, 26.8% women and 73.2% men. The average age at initial diagnosis was 64.6 years. Of which, 58.8% had a documented history of smoking, 37.1% were positive for p16, 4.1% were positive for EBV, and 66% had ENE. Most of the patients were at stage III/IVa (78.4% according to UICC7). According to UICC8, p16+ patients were mainly at stage I (86.1%), and p16- at stage IVb (56.1%). P16 status (P = .002), ENE (P = .001), nodal category (TNM7, P < .001), UICC stage (TNM7, P < .001) and UICC stage (TNM8, P < .001) had a significant impact on survival in the univariate analysis. The 8th TNM classification resulted in a downstaging of p16-positive CUP syndromes and an upstaging of p16-negative syndromes. Conclusion: The 8th TNM classification shows the lower UICC stage in p16-positive CUP syndromes. The prognostic significance for survival has improved from the 7th to the 8th TNM classification. LEVEL OF EVIDENCE USING THE 2011 OCEBM: Level 3

Prognostic Factors Predict Oncological Outcome in Older Patients With Head and Neck Cancer Undergoing Chemoradiation Treatment

Purpose: Older patients with head and neck cancer (HNC) represent a challenging group, as frailty and comorbidities need to be considered. This study aimed to evaluate the efficacy and side effects of curative and palliative (chemo) radiation ([C]RT) with regard to basic geriatric screening in older patients. Methods: This study included HNC patients aged >= 70 years who were treated with curative or palliative (C)RT. Clinicopathological data including Charlson Comorbidity Index (CCI), Karnofsky performance status (KPS), and treatment data were analyzed as predictors of overall survival (OS). Results: A total of 271 patients (median age, 74 years) were enrolled. The majority had UICC stage III/IV (90%) and underwent curative treatment (85.2%). A total of 144 (53.1%) patients received definitive and 87 (32.1%) had adjuvant (C)RT. Overall, 40 patients (14.8%) received palliative (C)RT. Median follow-up duration (curative setting) was 87 months, and the 2- and 5-year OS rates were 57.8 and 35.9%, respectively. Median OS was significantly different for age ≤75 vs. >75 years, CCI vs. ≥6, KPS ≥70 vs. <70%, Tx/T1/T2 vs. T3/T4, and adjuvant vs. definitive (C)RT, respectively. Age 70-75 years (p = 0.004), fewer comorbidities when CCI < 6 (p = 0.014), good KPS ≥70% (p = 0.001), and adjuvant (C)RT (p = 0.008) independently predicted longer survival. Palliative RT resulted in a median OS of 4 months. Conclusion: Older age, lower KPS, higher CCI, and definitive (C)RT are indicators of worse survival in older patients with HNC treated curatively. Without a comprehensive geriatric assessment in patients aged >75 years, the KPS and CCI can be useful tools to account for "fitness, vulnerability or frailty" to help in treatment decision-making

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients

Purpose: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. Methods: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019). Results: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age <= 60 years, HIV-PCR <= 50 copies, CD4 cells <= 200/mm(3), cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. Conclusions: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high

Predictive non-genetic parameters as the basis for an individualized treatment of head and neck diseases

Das zunehmende Wissen über die Komplexität von biologischen Systemen machen in der Medizin neue Diagnostik- und Therapieansätze möglich. Erkrankungen im Kopf-Hals-Bereich sind häufig Erkrankungen mit multifaktoriellen Ursachen. Simple lineare Empfehlungen können daher nicht gegeben werden. Für eine effiziente Behandlung komplexer Erkrankungen ist es notwendig, die Faktoren in der Entstehung und Therapie zu differenzieren und den Stellenwert zu bestimmen. Für individualisierte Therapien werden prädiktive Parameter benötigt, um das Ansprechen und individuelle Risiken einer Therapie abzuschätzen. Dazu werden klinische Parameter und Biomarker verwendet. Diese werden wiederum in genetische und nicht genetische prädiktive Parameter unterschieden. Um zu verdeutlichen, dass neben genetischen Untersuchungen weitere Verfahren verfügbar und notwendig sind, um eine individuelle Therapie bei Kopf-Hals-Erkrankungen (KHE) zu gestalten, werden in der vorliegenden Arbeit die eigenen Beobachtungsstudien und Metaanalysen vorgestellt. Die Studien untersuchen Kopf-Hals-Plattenepithelkarzinome (KH-PECA) sowie Komplikationen nach endotrachealen Intubationen und Tonsillektomien. Beispielhaft werden die in den Studien untersuchten nicht genetischen prädiktiven Parameter vier Verfahren zugeordnet. Dabei wird die Relevanz der nicht genetischen prädiktiven Parameter bei der auf den Defekt zugeschnittenen individualisierten Therapie der KHE sowie ihr Bezug für die evidenzbasierte Medizin erläutert. Die vorliegende Arbeit zeigt, dass neben genetischen prädiktiven Parametern eine Vielzahl von nicht genetischen prädiktiven Parametern notwendig ist, um eine individuelle Therapie zu gestalten. Mit Genetik allein lassen sich Krankheiten und ihre Behandlung nicht ausreichend beschreiben. Während die Suche nach genetischen Prädiktoren nur einen Aspekt, möglicherweise die Grundlage der Krankheitsentstehung und ihrer Behandlung beleuchtet, stellen insbesondere bei komplexen Erkrankungen die nicht genetischen prädiktiven Parameter eine Möglichkeit für eine wesentlich größere Anzahl von Aspekten bei der Behandlung zur Verfügung. Bei bestimmten Entitäten von KHE (z.B. Frakturen) haben allein nicht genetische Faktoren Einfluss auf das Therapieansprechen. Bei bestimmten Erkrankungen, z.B. bei HPV-Infektionen und KH-PECA, kann eine Kombination von genetischen und nicht genetischen, einschließlich epigenetischen Markern die Sicherheit von Entscheidungen verbessern. Die zunehmende pathophysiologische Aufklärung der genetischen Veränderungen (Big Data) muss bei der präventiven, diagnostischen und therapeutischen Betrachtung berücksichtigt werden. Doch erst in Folge der intelligenten Verlängerung der individuellen genetischen Suszeptibilität kann durch die vier Verfahren zur Erfassung von nicht genetischen prädiktiven Parametern eine individualisierte Behandlung erfolgen. Das „gefühlte“ Wissen kann so auf eine evidenzbasierte Grundlage gestellt werden. Ein validiertes Nomogramm kann entwickelt werden, das das Wissen des Arztes in der Diskussion mit Patienten und Krankenkassen unterstützt. Die resultierenden Behandlungsempfehlungen sollten abschließend auf die ethische Richtigkeit für den individuellen Patienten geprüft werden.Our increasing knowledge about complex biological systems makes new diagnostic and therapeutic approaches possible in medicine. Diseases of the head and neck region frequently have multifactorial causes. To effectively treat complex diseases, it is necessary to differentiate factors in the pathogenesis and therapy, and to determine their value. For individualized therapies, predictive parameters are needed to assess their response and individual risks. Clinical parameters and biomarkers are used for this purpose. They are distinguished in each genetic and non-genetic predictive parameter. In addition to genetic investigations, further methods are available and necessary to form an individual therapy for head and neck diseases. We therefore present our own observation studies and meta-analyses. The studies investigated head and neck squamous cell carcinoma (HNSCC) and complications following endotracheal intubation and tonsillectomies. The predictive, none- genetic parameters of the investigated studies are assigned to four procedures. The manuscript discusses the relevance of predictive non-genetic parameters for individualized head and neck disease therapy according to the individual defect and the impact on evidence-based medicine. The present manuscript shows that, in addition to predictive genetic parameters, a large number of predictive non-genetic parameters are necessary to form an individual therapy. Genetics alone do not adequately describe diseases and their treatment. The search for genetic predictors is only one aspect, possibly the basis of disease development and its treatment. In complex diseases particularly, the predictive non-genetic parameters allow for a substantially greater number of treatment aspects. In certain types of head and neck diseases (e.g., fractures), only non-genetic parameters affect the response to treatment. For certain diseases, e.g. HPV infections and HNSCC, a combination of genetic and non-genetic parameters, including epigenetic markers, can improve the safety of decisions. The increasing pathophysiological elucidation of genetic changes (big data) has to be considered in preventive, diagnostic and therapeutic decisions. However, only the intelligent extension of individual genetic susceptibility using the four methods of detecting predictive non-genetic parameters helps to perform an individualized treatment. The "felt" knowledge can thus be placed on an evidence-based basis. A validated nomogram can be developed supporting the doctor's knowledge in discussion with patients and health insurers. The resulting treatment recommendations should be examined for ethical accuracy with the individual patient

Effect of proinflammatory cytokines on the expression of human β2-defensin in the intestinal mucosa – In-vitro study in a model system with the human epithelial cell line HT-29

Einleitung: Bei Morbus Crohn sind eine gestörte intestinale Mukosabarriere, eine zelluläre, zytokinvermittelte Immunantwort gegen die kommensale Flora und eine gestörte Defensin-Homöostase bekannt. Das transkriptionell regulierte humane β2-Defensin (HBD-2) wird von Epithelzellen gebildet und durch bisher nicht ausreichend bekannte Mechanismen induziert. In einem Modell mit der Adenokarzinom-Zelllinie HT-29 wird der Einfluss proinflammatorischer Zytokine auf die HBD-2-Expression auf Transkriptions- und Translationsebene analysiert. Methodik: HT-29-Zelllen wurden mit humanen rekombinanten Zytokinen kultiviert. Die HBD-2-mRNA wurde mit semiquantitativer Polymerasekettenreaktion (PCR) zunächst abgeschätzt. Als standardisiertes Screening-Verfahren für Darmbiopsien wurde eine quantitative TaqMan-PCR etabliert. Als absolute Standards wurden cDNA-Abschnitte für HBD-2 und Glyceraldehyd-3-phosphat- Dehydrogenase in den Vektor pCR2.1 kloniert. Ein HBD-2-spezifischer Western- blot wurde mit rekombinantem HBD-2 und einem Fusionsprotein aus HBD-2 und der Glutathion-S-Transferase (GST) etabliert. Auf der Basis des Vektors pEGFP wurden rekombinante HBD-2-Fusionsproteine mit dem Enhanced Green Fluorescent Protein (EGFP) für die Sekretion bzw. intrazelluläre Expression hergestellt. Die Expression von HBD-2-EGFP durch transfizierte Zellen wurde durchflusszytometrisch über EGFP bestimmt und im HBD-2-spezifischen Western- blot nachgewiesen. Ergebnisse: Interleukin (IL)-1β, nicht aber Tumornekrosefaktor-α, IL-6 bzw. IL-17 induzierte die Expression von HBD-2-mRNA. Obwohl der hochsensitive Western-blot reproduzierbar 1.5 pMole HBD-2 darstellte und die Fusionsproteine HBD-2-EGFP und HBD-2-GST spezifisch nachgewiesen wurden, konnte HBD-2 aus menschlichem Darmgewebe bzw. bei mit IL- 1β-inkubierten HT-29-Zellen nicht gezeigt werden. Wurde rekombinantes HBD-2 gemeinsam mit zellulären Proteinen aufgetragen, waren mindestens 70 pMole HBD-2 für den Nachweis notwendig; Mengen die nach Induktion mit IL-1β bzw. in Darmproben nicht erreicht wurden. Für eine Anreicherung durch Immunpräzipitation von HBD-2 aus Kulturüberständen oder Zelllysaten war der im Western-blot verwendete Antikörper nicht geeignet. Bei einer Transfektionseffizienz um 70% in HT-29 und primären Zellen wurde unter der Kontrolle des HBD-2-Signals exprimiertes HBD-2-EGFP mit einer Größe von ~38 kDa sowohl in Lysaten aus 1×10^5 Zellen als auch aus Kulturüberständen direkt gezeigt. Schlussfolgerung: Die auf Transkriptionsebene in der Zelllinie HT-29 gezeigte Induktion der HBD-2-Expression durch proinflammatorisches IL-1β unterstützt die Annahme, dass die Defensinproduktion nicht nur direkt durch Bakterien, sondern auch indirekt über zellproduzierte Zytokine reguliert wird. Mittels TaqMan-PCR kann die HBD-2-mRNA in Darmbiopsien quantifiziert werden. Die Sensitivität des Western-blots gestattet keinen unmittelbaren Proteinnachweis aus solchen Proben. Mit dem Modell konstitutiv durch transfizierte epitheliale Zellen exprimierter HBD-2-EGFP-Fusionsproteine können Methoden zur Anreicherung und Darstellung des HBD-2-Proteins aus Zelllysaten und Zellkulturüberständen etabliert werden. Die hier bereitgestellten Methoden gestatten den Nachweis von Defensinen auf mRNA- und Proteinebene und können auf Proben menschlicher Darmepithelien übertragen werden.Background: Altered intestine mucosal barrier and cellular cytokine-mediated immune responses against commensal flora as well as a disordered homoeostasis of defensins are hallmarks in Crohn’s disease. Transcriptionally regulated human β2-defensin (HBD)-2 is expressed and secreted by epithelial cells but the mechanism of its induction is not fully understood. Here the effect of proinflammatory cytokines on HBD-2 expression in the human adenocarcinoma cell line HT-29 as a model for human intestinal epithelial cells was studied at transcriptional and at protein level. Methods: HT-29 cells were incubated with recombinant human pro-inflammatory cytokines. In a semiquantitative approach, cellular HBD-2-mRNA levels were estimated after specific polymerase chain reaction (PCR). For standardized screening of HBD-2 expression in intestinal biopsies, a quantitative TaqMan-PCR was established using cDNA segments of HBD-2 and glyceraldehyde-3-phosphate-dehydrogenase cloned into the vector pCR2.1 as absolute standards. An HBD-2-specific western-blot was established with recombinant HBD-2 and a fusion protein of HBD-2 with the glutathione-S-transferase (GST). Using the vector pEGFP-HBD-2 was fused to the enhanced green fluorescent protein (EGFP) for secretion or for intracellular expression of the fusion protein. The expression of HBD-2-EGFP by transfected cells was monitored by flow cytometry of EGFP and by HBD-2-specific western- blot. Results: Interleukin (IL)-1β, but not tumor necrosis factor-α, IL-6 or IL-17, induced HBD-2 mRNA in HT-29 cells. Although the highly sensitive western-blot reproducibly detected 1.5 pmoles HBD-2 as validated with the recombinant HBD-2 as well as the fusion proteins HBD-2-EGFP and HBD-2-GST, the western-blot did not show HBD-2 in primary human ileum cells or IL-1β-treated HT-29 cells. Against the background of cellular proteins, 70 pmoles recombinant HBD-2 were necessary to be detected by western-blot; amounts not obtained by induction of HBD-2 expression in HT-29 cells by IL-1β or in intestinal biopsies. The HBD-2-specific antibodies used for Western-blot did not enrich HBD-2 from cell culture supernants or cell lysates in an immunoprecipitation approach. If transfected with the vector pHBD-2-EGFP, 70% of the HT-29 or primary cells expressed HBD-2-EGFP with a size of ~38 kDa and the fusion protein was detected in lysates from 1×10^5 cells as well as from cell culture supernantants. Conclusions: The induction of HBD-2-specific mRNA by IL-1β supports the hypothesis, that defensin production might not only be regulated by exogenous triggers like bacteria but also by cell derived cytokines. At transcriptional level HBD-2 expression in intestinal biopsies can be quantified by TaqMan-PCR. The sensitivity of the western-blot is not sufficient for direct detection of the HBD-2 protein. The model of constitutive expression of a secreted HBD-2-EGFP fusion protein by transfected epithelial cells can help to establish methods for reproducible enrichment and detection the HBD-2 protein from cell lysates as well as from cell culture supernants. The methods provided here allow to assess the quantitative limits for the detection of defensins at transcriptional and translational level and to be used for biopsy samples of the human intestine

Розробка політики безпеки інформації інформаційно-телекомунікаційної системи приватного підприємства ТОВ «ТБ «ГОЛДФРУКТ»»

Корнієвський А. О Розробка політики безпеки інформації інформаційно-телекомунікаційної системи приватного підприємства ТОВ «ТБ «ГОЛДФРУКТ»»: кваліфікаційна робота бакалавра / Корнієвський Антон Олегович . – Дніпро, 2020. – 91 с.У роботі наведено основні відомості про підприємство. Виконано обстеження інформаційної системи, фізичного середовища, середовище користувачів. Описано технологію обробки інформації та функціональний профіль захисту. Виконано категоріювання інформації, що обробляється в ІТС та визначено основні загрози та вразливості, їх джерела та складено модель порушника. Розроблено положення політики безпеки