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Introduction: Septic shock is associated with high mortality and hemodynamic impairment. The use of corticoids is a common therapeutic tool in critically ill patients. However, data on the mechanisms and prognostic ability of hemodynamic improvement by adjunctive steroids are rare. This study primarily aimed to evaluate short-term effects of hydrocortisone therapy on catecholamine requirement and hemodynamics derived from transpulmonary thermodilution (TPTD) in 30 critically ill patients with septic shock and a 28 days mortality rate of 50%. Methods: Hydrocortisone was administered with an intravenous bolus of 200â mg, followed by a continuous infusion of 200â mg per 24â h. Hemodynamic assessment was performed immediately before as well as 2, 8, 16, and 24â h after the initiation of corticoids. For primary endpoint analysis, we evaluated the impact of hydrocortisone on vasopressor dependency index (VDI) and cardiac power index (CPI). Results: Adjunctive hydrocortisone induced significant decreases of VDI from 0.41 (0.29-0.49) mmHg-1 at baseline to 0.35 (0.25-0.46) after 2â h (P < .001), 0.24 (0.12-0.35) after 8â h (P < .001), 0.18 (0.09-0.24) after 16â h (P < .001) and 0.11 (0.06-0.20) mmHg-1 after 24â h (P < .001). In parallel, we found an improvement in CPI from 0.63 (0.50-0.83) W/m2 at baseline to 0.68 (0.54-0.85) after 2â h (P = .208), 0.71 (0.60-0.90) after 8â h (P = .033), 0.82 (0.6-0.98) after 16â h (P = .004) and 0.90 (0.67-1.07) W/m2 after 24â h (P < .001). Our analyses revealed a significant reduction in noradrenaline requirement in parallel with a moderate increase in mean arterial pressure, systemic vascular resistance index, and cardiac index. As a secondary endpoint, our results showed a significant decrease in lung water parameters. Moreover, changes in CPI (ΔCPI) and VDI (ΔVDI) after 24â h of hydrocortisone therapy revealed accurate prognostic ability to predict 28 days mortality (AUC = 0.802 vs 0.769). Conclusion: Adjunctive hydrocortisone leads to a rapid decrease in catecholamine requirement and a substantial circulatory improvement in critically ill patients with septic shock.
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Choque Séptico , Humanos , Hidrocortisona/uso terapêutico , Termodiluição/métodos , Estado Terminal/terapia , Hemodinâmica , Norepinefrina , Vasoconstritores/uso terapêutico , Vasoconstritores/farmacologiaRESUMO
INTRODUCTION: The aim of this laboratory study is to objectively analyze the new hydrophobic, acrylic, enhanced monofocal intraocular lens Acunex Quantum (AN6Q) and compare it with the monofocal platform Acunex AN6. METHODS: Two IOL models were analyzed (Acunex Quantum AN6Q and Acunex AN6, Teleon Surgical, Spankeren, Netherlands), each having the same refractive power of + 22.0 D, on the optical bench with the OptiSpheric IOL PRO 2. The measurements followed the guidelines of the International Standard Organization with following parameters: ISO 2 cornea (+ 0,28 µ), ISO 11979/2, lens placement in situ in NaCl with 35° temperature, 546 nm and selection of different aperture sizes (3.0 mm vs 4.5 mm). The aberrations of each IOL were evaluated by the WaveMaster IOL 2, a high-resolution Shack-Hartmann sensor in reverse projection setup. An in-situ model eye was used according to ISO 11979 in NaCl (n = 1.337) with 546 nm, mask width 4.51. Zernike polynomials up to 10th order were determined by means of the measured wavefront that describe the optical properties of the IOL. RESULTS: Through frequency modulation transfer function (mean) at 50 lp/mm (AN6Q/AN6 centered) was 0.687/0.731 (3.0 mm aperture) and 0.400/0.509 (4.5 mm aperture). The SR (mean) was 0.592/0.809 (3.0 mm) and 0.332/0.372 (4.5 mm). The MTF (mean) at 50 lp/mm (AN6Q/AN6 decentered by 1 mm) was 0.413/0.478 (3.0 mm) and 0.257/0.229 (4.5 mm). The SR (mean) was 0.393/0.404 (3.0 mm) and 0.183/0.212 (4.5 mm). The MTF (mean) at 50 lp/mm (AN6Q/AN6 tilted by 5°) was 0.508/0.710 (3.0 mm) and 0.337/0.513 (4.5 mm). The SR (mean) was 0.508/0.760 (3.0 mm) and 0.235/0.2372 (4.5 mm). AN6Q showed MTF peak of 0.55 with an enlarged depth of power of about 2.5 D and two cusps in the MTF curve. The spherical aberration Z 4-0 was about -0.21 µm and the secondary spherical aberration Z 6-0 was about 0.16 µm. No other relevant aberration showed up. CONCLUSION: The new, enhanced monofocal AN6Q provides an extended range of focus with only slight decrease in contrast quality. Both types of the hydrophobic, acrylic Acunex IOL platform have its particular advantages in clinical settings and therefore its importance, respectively.
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Lentes Intraoculares , Cloreto de Sódio , Olho Artificial , Humanos , Desenho de Prótese , Visão OcularRESUMO
PURPOSE: We conducted a patterns-of-care survey on chemoradiation for locoregionally confined anal cancer in Austria to evaluate areas of disagreement and to identify possible targets for further standardization. METHODS: An anonymous questionnaire comprising 38 questions was sent to all Austrian radiation oncology departments. Results were analyzed descriptively and compared to two international guidelines. RESULTS: The response rate was 93%. Work-up generally includes DRE, endoscopy, and cross-sectional imaging of chest/abdomen and pelvis. PET-CT is used by 38%. Screening for HIV and biopsies of suspicious lymph nodes are infrequently used. All centers perform IMRT, mainly with daily IGRT. Median doses to the primary are 54.7â¯Gy (T1-2) and 59.4â¯Gy (T3-4). Suspicious nodes receive a boost (median dose 54â¯Gy), while elective nodal areas are mainly treated with 45-50.4â¯Gy. Target delineation of elective nodal areas seems generally uniform, although disagreement exists regarding inclusion of the common iliac nodes. No agreement was found for OAR-delineation and dose constraints. Concurrent chemotherapy is mitomycin and 5FU/capecitabine. Supportive care beyond skin care is infrequently offered. Intensive follow-up is performed for at least 5 years. Treatment of T1N0 shows considerable disagreement. CONCLUSION: We found a high rate of agreement between the centers and concordance with major guidelines. PET-CT, routine HIV testing, and biopsies of suspicious LN seem underrepresented. The largest controversy regarding target volumes concerns inclusion of the common iliac nodes. Prescribed doses are generally in line with the recommendations or higher. OAR delineation, dose constraints, supportive care, and treatment of early anal cancer represent areas for further standardization.
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Neoplasias do Ânus , Radioterapia (Especialidade) , Radioterapia de Intensidade Modulada , Neoplasias do Ânus/patologia , Neoplasias do Ânus/radioterapia , Áustria/epidemiologia , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioterapia de Intensidade Modulada/métodos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Bilomas are defined collections of bile fluids mainly caused by iatrogenic injuries of the bile duct system. Owing to the infrequency of this disease, studies addressing bilomas are rare. METHODS: By using an endoscopic database, this retrospective study identified 32 patients with bilomas treated between 2004 to 2015, in order to analyse aetiology, clinical presentation, spectrum of pathogens, and resolution rate of bilomas. RESULTS: 65.6% of the study population (21/32) developed bilomas after surgery and 21.9% (7/32) after endoscopic retrograde cholangiography (ERC). Icterus, fever, and abdominal pain were the leading symptoms. 93.9% (46/49) of microbiological bile cultures revealed a positive microbiology. The predominant microorganisms were the group of Enterobacteriaceae (43.0%, 52/121), followed by Enterococcus spp. (32.2%, 39/121), and Candida spp. (9.1%, 11/121). Multiresistant bacteria like Enterobacteriaceae were isolated from one quarter of all patients. Single or multimodal treatment resulted in an overall complication rate of 4.8% (9/188). Clinical follow-up analysis showed a complete resolution rate of 78.3% for interventional therapy and 80% in the non-interventional group. CONCLUSIONS: Pathogen spectrum of bilomas mainly comprises the group of Enterobacteriacae and Enterococcus spp., with a high proportion of multiresistant bacteria. Different interventional approaches are available for biloma drainage, which seem to be safe and effective for most patients. TRIAL REGISTRATION: German Clinical Trials Register DRKS00015208 , retrospectively registered.
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Doenças dos Ductos Biliares/microbiologia , Bile/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças dos Ductos Biliares/diagnóstico , Doenças dos Ductos Biliares/terapia , Drenagem/métodos , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/terapia , Enterococcus/isolamento & purificação , Feminino , Humanos , Doença Iatrogênica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Endosonographically guided transgastric drainage is the first-line interventional therapy of walled-off necrosis and symptomatic pancreatic pseudocysts in necrotizing pancreatitis. Plastic stents or lumen apposing metal stents are commonly used. A possible complication of endoscopic therapy is stent migration. CASE REPORT: We report upon a 51-year-old man who presented with acute necrotizing pancreatitis. Transgastric necrosectomy was performed and 5 transmural double-pigtail stents (DPS) were left in situ to drain the residual retroperitoneal cavity. The patient recovered and 4 stents were endoscopically removed 5 weeks later on an outpatient basis, whereas the fifth stent was suspected to have passed spontaneously via the natural route. The asymptomatic patient presented 3 months later for follow-up computed tomography. The necrosis had healed but one DPS was seen beyond the gastric wall near the kidney. Transmural access to the stent could be achieved by an endosonographically guided puncture toward the proximal portion of the stent followed by placement of a hydrophilic guidewire alongside the stent. A new gastrostomy was created by using a 6F cystotome followed by wire-guided dilation with a 12â¯mm balloon. The stent could then be grasped with transmurally inserted rat-tooth forceps and repositioned across the gastrostomy site. The patient was given prophylactic antibiotics. After removal of the stent, the patient could be discharged. CONCLUSION: Herein, we present the successful endosonographically guided transmural removal of a retroperitoneally migrated plastic stent. Of note, in our patient we had to rely completely on endosonography and radiography for localization and targeting of the stent, since the former necrotic cavity had meanwhile completely healed.
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Endoscopia Gastrointestinal/métodos , Endoscopia/instrumentação , Endossonografia/métodos , Migração de Corpo Estranho/diagnóstico por imagem , Pancreatite Necrosante Aguda/etiologia , Pancreatite Necrosante Aguda/cirurgia , Stents/efeitos adversos , Irrigação Terapêutica/instrumentação , Drenagem , Endossonografia/instrumentação , Migração de Corpo Estranho/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pseudocisto Pancreático , Pancreatite Necrosante Aguda/diagnóstico , Resultado do TratamentoRESUMO
We demonstrate a plasmonic Mach-Zehnder (MZ) modulator with a flat frequency response exceeding 170 GHz. The modulator comprises two phase modulators exploiting the Pockels effect of an organic electro-optic material in plasmonic slot waveguides. We further show modulation at 100 GBd NRZ and 60 GBd PAM-4. The electrical drive signals were generated using a 100 GSa/s digital to analog converter (DAC). The high-speed and small-scale devices are relevant for next-generation optical interconnects.
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BACKGROUND: Esophageal bougination is a worldwide standard endoscopic procedure. Clinical methods and recommendations are based on clinical experiences only. Mechanical properties have never been described. Aim of the study was to establish a realistic ex vivo training model. Therefore, detailed assessment of relevant mechanical features of esophageal bougination should be evaluated ex vivo and in patient setting and correlated against. PATIENTS AND METHODS: A three-step concept was used to evaluate mechanical properties at stenosis level. First, insertion forces were evaluated in an ex vivo linear single stenosis model during steady mechanical insertion. Second, adding friction and properties of the pharynx and upper esophagus, the model was integrated in an artificial endoscopic training model (ELITE training model). Third, in vivo measurements were taken to correlate ex vivo data with parameters of a realistic patient setting. RESULTS: With the presented setup, we were able to assess insertion force and pressure levels in an artificial stricture using different sizes of commercially available standard bougies. In all models, there was a relevant increase in insertion force with higher stricture pressure levels. Insertion force levels in the ELITE model show higher levels compared to the linear stenosis model. Having regard to the maximum forces in patients, there is also a constant increase in mean insertion force according to higher bougie sizes, but lower forces were measured as in the ELITE model. DISCUSSION: The applied models are suitable to appraise mechanical properties of esophageal bougination in an ex vivo model and patient setting. Forces could be constituted reliable, significant increase was documented according to stenosis level and results were comparable to patient data. This was comparable to patient data. Further clinical evaluation in different kinds of stenosis is necessary.
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Competência Clínica , Estenose Esofágica/cirurgia , Cirurgia Endoscópica por Orifício Natural/educação , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos AnatômicosRESUMO
Background and Objectives: Exposure to recreational noise is becoming increasingly important due to a change in leisure behavior amongst children and adolescents. The aim of this pilot study was to assess exposure of 6th grade pupils to recreational noise from portable listening devices (PLD). Furthermore, preventive measures to reduce recreational noise exposure should be identified. Methods: In "Ohrkan Kids", 38 Bavarian pupils aged 11 to 14 were interviewed regarding their music listening behavior using a standardized questionnaire. In addition, measurements of commonly used volume settings on the children's portable listening devices were carried out. Furthermore, the German Social Accident Insurance (DGUV), health insurance companies as well as health and education ministries of the German federal states were surveyed regarding their activities in the prevention of recreational noise exposure. Results: Based on the questionnaire data for weekly usage, 10 out of 31 children (32.3%) exceeded the upper exposure value of 85 dB recommended by labor protection law. Taking actually measured values, 9 out of 31 children (29%) exceeded this level. The DGUV and some federal states carry out specific projects for the prevention of recreational noise exposure. Conclusion: The large number of children with hazardous music consumption indicates that measures for the prevention of noise-induced hearing loss are already required for 11 to 14 year olds. To maximize the number of children addressed, age-appropriate and target-group-specific preventive measures are needed. As there are only few studies which examined the effectiveness of awareness campaigns for the prevention of recreational noise, any future prevention projects should be evaluated with an increased focus on estimating their effectiveness.
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Exposição Ambiental/prevenção & controle , Exposição Ambiental/estatística & dados numéricos , Perda Auditiva/epidemiologia , Perda Auditiva/prevenção & controle , Ruído/efeitos adversos , Recreação , Estudantes/estatística & dados numéricos , Adolescente , Criança , Exposição Ambiental/análise , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Música , Projetos Piloto , Prevalência , Fatores de RiscoRESUMO
We demonstrate a silicon-organic hybrid (SOH) Mach-Zehnder modulator (MZM) generating four-level amplitude shift keying (4ASK) signals at symbol rates of up to 64 GBd both at room temperature and at an elevated temperature of 80°C. The measured line rate of 128 Gbit/s corresponds to the highest value demonstrated for silicon-based MZM so far. We report bit error ratios of 10-10 (64 GBd BPSK), 10-5 (36 GBd 4ASK), and 4 × 10-3 (64 GBd 4ASK) at room temperature. At 80 °C, the respective bit error ratios are 10-10, 10-4, and 1.3 × 10-2. The high-temperature experiments were performed in regular oxygen-rich ambient atmosphere.
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OBJECTIVE: Prognosis of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. Novel therapeutic approaches are of great interest to improve the effects of radiochemotherapy. We evaluated the effects of tyrosine kinase inhibitor neratinib on HNSCC cell lines CAL27, SCC25 and FaDu as a single agent and in combination with irradiation and chemotherapy. METHODS: Effects of neratinib were evaluated in HNSCC cell lines CAL27, SCC25 and FaDu. Effect on cell viability of neratinib and combination with cisplatin and irradiation was measured using CCK-8 assays and clonogenic assays. Western blot analysis was performed to distinguish the effect on epithelial growth factor receptor and HER2 expression. Apoptosis was evaluated by flow cytometry analysis. RESULTS: Growth inhibition was achieved in all cell lines, whereas combination of cisplatin and neratinib showed greater inhibition than each agent alone. Apoptosis was induced in all cell lines. Combination of neratinib with irradiation or cisplatin showed significantly increased apoptosis. In clonogenic assays, significant growth inhibition was observed in all investigated cell lines. CONCLUSION: Neratinib, as a single agent or in combination with chemo-irradiation, may be a promising treatment option for patients with head and neck cancer.
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Antineoplásicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinolinas/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Terapia Combinada , Citometria de Fluxo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , HumanosRESUMO
We report a case of a previously healthy 52-year-old man who presented with fever and liver lesions suspicious for metastatic disease, which proved subsequently to be abscesses. Further workup revealed a gastrointestinal stromal tumor (GIST) in the gastric corpus as entry port to Streptococcus intermedius-associated bacteremia and liver abscesses. After antibiotic treatment and surgical resection of the tumor, the patient recovered well. This unusual case indicates that gastrointestinal stromal tumors can remain undetected until they cause a life threatening infection. A review of recent literature pertaining to GIST and liver abscesses follows.
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Bacteriemia/microbiologia , Neoplasias Gastrointestinais/microbiologia , Tumores do Estroma Gastrointestinal/microbiologia , Abscesso Hepático Piogênico/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus intermedius/isolamento & purificação , Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Diagnóstico Diferencial , Neoplasias Gastrointestinais/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Abscesso Hepático Piogênico/prevenção & controle , Masculino , Pessoa de Meia-Idade , Penicilina G/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus intermedius/efeitos dos fármacos , Resultado do TratamentoRESUMO
Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy.
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Endoscopia Gastrointestinal/normas , Pancreatectomia/normas , Testes de Função Pancreática/normas , Pancreatite/diagnóstico , Pancreatite/terapia , Guias de Prática Clínica como Assunto , Doença Crônica , Alemanha , Humanos , Estados UnidosRESUMO
Children with chronic illness or disabilities and their families require more support than healthy families. The working group "custodial and psychosocial supply" defined 4 theses to figure out deficits and targets of family support: 1) my child is different; 2) my child is not devisable; 3) my child needs strong helpers; and 4) my child needs safety.Based on these theses, a questionnaire for parents was designed of which 20 were sent to 34 parent initiatives in Germany each, for distribution to a random sample of member families.499/680 questionnaires were returned of which 419 could be included in the analysis. Less than 50% of the parents felt adequately and timely informed about their child's condition, and support for coping with the child's diagnosis was rarely given. Less than half of the parents reported to have been informed about the options for support within the German social system, and less than 15% were aware of instructions for clearing houses on care and support. About a third of the parents reported needs for managing family, siblings or household, but only a third of these had been offered organised and structured family support. More than 50% of the families reported restraints in participating in social life: such restraints were associated with problems in partnership and loss of friends. Half of the parents felt restraints of the family income because of their child's condition.There is need for improvement of the psychosocial condition of families with chronically ill or disabled children by better, more and timely information about the child's clinical condition, access to the social support system and availability of support services.
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Doença Crônica/epidemiologia , Doença Crônica/psicologia , Crianças com Deficiência/psicologia , Crianças com Deficiência/estatística & dados numéricos , Pais/psicologia , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Recently, fibroblast growth factor receptor 1 (FGFR1) was discovered in squamous cell carcinomas (SCC) of the lung with FGFR1 amplification described as a promising predictive marker for anti-FGFR inhibitor treatment. Only few data are available regarding prevalence, prognostic significance and clinico-pathological characteristics of FGFR1-amplified and early-stage non-small cell lung carcinomas (NSCLC). We therefore investigated the FGFR1 gene status in a large number of well-characterised early-stage NSCLC. METHODS: FGFR1 gene status was evaluated using a commercially available fluorescent in situ hybridisation (FISH) probe on a tissue microarray (TMA). This TMA harbours 329 resected, formalin-fixed and paraffin-embedded, nodal-negative NSCLC with a UICC stage I-II. The FISH results were correlated with clinico-pathological features and overall survival (OS). RESULTS: The prevalence of an FGFR1 amplification was 12.5% (41/329) and was significantly (P<0.0001) higher in squamous cell carcinoma (SCC) (20.7%) than in adenocarcinoma (2.2%) and large cell carcinoma (13%). Multivariate analysis revealed significantly (P=0.0367) worse 5-year OS in patients with an FGFR1-amplified NSCLC. CONCLUSIONS: FGFR1 amplification is common in early-stage SCC of the lung and is an independent and adverse prognostic marker. Its potential role as a predictive marker for targeted therapies or adjuvant treatment needs further investigation.
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Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/genética , Amplificação de Genes , Neoplasias Pulmonares/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Análise Serial de TecidosRESUMO
BACKGROUND AND PURPOSE: Merkel cell carcinoma (MCC) is a rare, but highly malignant tumor of the skin. In case of systemic disease, possible therapeutic options include irradiation or chemotherapy. The aim of this study was to evaluate whether the flavonoid resveratrol enhances the effect of radiotherapy or chemotherapy in MCC cell lines. MATERIALS AND METHODS: The two MCC cell lines MCC13 and MCC26 were treated with increasing doses of resveratrol. Combination experiments were conducted with cisplatin and etoposide. Colony forming assays were performed after sequential irradiation with 1, 2, 3, 4, 6, and 8 Gy and apoptosis was assessed with flow cytometry. Expression of cancer drug targets was analyzed by real-time PCR array. RESULTS: Resveratrol is cytotoxic in MCC cell lines. Cell growth is inhibited by induction of apoptosis. The combination with cisplatin and etoposide resulted in a partially synergistic inhibition of cell proliferation. Resveratrol and irradiation led to a synergistic reduction in colony formation compared to irradiation alone. Evaluation of gene expression did not show significant difference between the cell lines. CONCLUSION: Due to its radiosensitizing effect, resveratrol seems to be a promising agent in combination with radiation therapy. The amount of chemosensitizing depends on the cell lines tested.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/terapia , Quimiorradioterapia/métodos , Estilbenos/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Etoposídeo/administração & dosagem , Humanos , Resveratrol , Resultado do TratamentoRESUMO
BACKGROUND: Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. RESULTS: Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. CONCLUSION: Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity.
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Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Cisplatino/farmacologia , Neoplasias Otorrinolaringológicas/patologia , Venenos de Serpentes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células , Terapia Combinada , Regulação para Baixo/genética , Humanos , Integrinas/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/genética , Reação em Cadeia da Polimerase em Tempo Real , Ensaio Tumoral de Célula-TroncoRESUMO
BACKGROUND: Radial artery applanation tonometry technology can be used for continuous non-invasive measurement of arterial pressure (AP). The purpose of this study was to evaluate this AP monitoring technology in intensive care unit (ICU) patients in comparison with invasive AP monitoring using a radial arterial catheter. METHODS: In 24 ICU patients (German university hospital), AP values were simultaneously recorded on a beat-to-beat basis using radial artery applanation tonometry (T-Line system; Tensys Medical, San Diego, CA, USA) and a radial arterial catheter (contralateral arm). The primary endpoint of the study was to investigate the accuracy and precision of the non-invasively assessed AP measurements with the Bland-Altman method based on averaged 10 beat AP epochs (n=2993 10 beat epochs). RESULTS: For mean AP (MAP), systolic AP (SAP), and diastolic AP (DAP), we observed a bias (±standard deviation of the bias; 95% limits of agreement; percentage error) of +2 mm Hg (±6; -11 to +15 mm Hg; 15%), -3 mm Hg (±15; -33 to +27 mm Hg; 23%), and +5 mm Hg (±7; -9 to +19 mm Hg; 22%), respectively. CONCLUSIONS: In ICU patients, MAP and DAP measurements obtained using radial artery applanation tonometry show clinically acceptable agreement with invasive AP determination with a radial arterial catheter. While the radial artery applanation tonometry technology also allows SAP measurements with high accuracy, its precision for SAP measurements needs to be further improved.
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Pressão Arterial/fisiologia , Cuidados Críticos/métodos , Manometria/métodos , Monitorização Fisiológica/métodos , Artéria Radial/fisiologia , Adulto , Idoso , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Autoimmune pancreatitis (AIP) was first classified as a defined disease entity in 1995. It accounts for approximately 2 % of cases of chronic pancreatitis (western world prevalence 36-41/100,000 inhabitants) and AIP is diagnosed in 2.4 % of pancreas resection specimens. OBJECTIVES: Presentation of strategies for diagnosis and treatment with focus on differentiation of AIP and pancreatic carcinoma. METHODS: Selective literature research in PubMed regarding pathogenesis, diagnosis and treatment of AIP. RESULTS: Key characteristics of AIP are recurrent jaundice due to obstructed bile ducts, histological evidence of fibrosis, a lymphoplasmocytic or granulocytic infiltrate and the response to steroid therapy. There are two distinctive forms of AIP: type I or lymphoplasmocytic sclerosing pancreatitis and type II or idiopathic duct centric pancreatitis. The IgG4 positive AIP type I belongs to the group of IgG4-related systemic diseases. Diagnosis of AIP is established according to the international consensus diagnostic criteria (ICDC) or HISORt (mnemonic standing for histology, imaging, serology, other organ involvement and response to therapy) criteria. Differentiation from pancreatic adenocarcinoma can be challenging. The standard treatment consists of corticosteroids and in some cases azathioprine can be added. In refractory disease rituximab is a further option. Treatment is indicated in patients with jaundice, systemic manifestation or persistent pain. CONCLUSION: Although AIP is increasingly being identified, the differentiation from pancreatic adenocarcinoma still remains difficult and in cases of a suspicion of neoplasia, resection should be favored. It can successfully be treated conservatively with steroids and rituximab.
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Corticosteroides/uso terapêutico , Anticorpos Monoclonais Murinos/uso terapêutico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Azatioprina/uso terapêutico , Pancreatite/diagnóstico , Pancreatite/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Diagnóstico Diferencial , Reações Falso-Positivas , Humanos , Imunossupressores/uso terapêutico , RituximabRESUMO
AIM: To report a rare case of a spinal WHO grade I meningioma extending through intervertebral foramina C7 to D4 with an extensive mediastinal mass and infiltration of the vertebrae, and to discuss the malignant behavior of a tumor classified as benign. METHODS: (Clinical Presentation, Histology, and Imaging): A 54-year-old man suffered from increasing lower back pain with gait difficulties, weakness and numbness of the lower extremities, as well as urge incontinence. CT scan of the thorax and MRI scan of the spine revealed a large prevertebral tumor, which extended to the spinal canal and caused compression of the spinal cord at the levels of C7 to D4 leading to myelopathy with hyperintense signal alteration on T2-weighted MRI images. The signal constellation (T1 with and without contrast, T2, TIR) was highly suspicious for infiltration of vertebrae C7 to D5. Somatostatin receptor SPECT/CT with (111)In-DTPA-D: -Phe-1-octreotide detected a somatostatin receptor-positive mediastinal tumor with infiltration of multiple vertebrae, dura, and intervertebral foramina C7-D4, partially with Krenning score >2. Percutaneous biopsies of the mediastinal mass led to histopathological findings of WHO grade I meningioma of meningothelial subtype. RESULTS: (Therapy): C7 to D4 laminoplasty was performed, and the intraspinal, extradural part of the tumor was microsurgically removed. Postoperative stereotactic radiation therapy was done using the volumetric modulated arc therapy (VMAT) technique (RapidArc). No PRRNT with (90)Y-DOTA-TOC was done. CONCLUSIONS: Due to the rare incidence and complex presentation of this disease not amenable to complete surgical resection, an individualized treatment approach should be worked out interdisciplinarily. The treatment approach should be based not only on histology but also on clinical and imaging findings. Close clinical and radiological follow-up may be mandatory even for benign tumors.
Assuntos
Mediastino/patologia , Neoplasias Meníngeas/patologia , Meningioma/patologia , Terapia Combinada , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/terapia , Meningioma/terapia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The T-Line TL-200pro (TL-200pro) device (Tensys Medical, Inc., San Diego, CA, USA), based on radial artery tonometry, provides an arterial pressure (AP) waveform and beat-to-beat values of systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP). The aim of the study was to evaluate this non-invasive technique for continuous AP monitoring in medical intensive care unit (ICU) patients. METHODS: Arterial pressure measurements obtained using the TL-200pro technology were compared using Bland-Altman analysis with values measured directly from a femoral arterial catheter in 34 ICU patients. RESULTS: Arterial pressure values were analysed and compared in 4502 averaged 10-beat epochs. A bias of +0.72 mm Hg (95% limits of agreement -9.37 to +10.82 mm Hg) was observed for MAP. For SAP and DAP, there was a mean difference of -1.39 mm Hg (95% limits of agreement -18.74 to +15.96 mm Hg) and +4.36 mm Hg (95% limits of agreement -8.66 to +17.38 mm Hg), respectively. The percentage error for MAP, SAP, and DAP was 12%, 14%, and 21%, respectively. CONCLUSIONS: Arterial pressure measurement based on radial artery tonometry using the TL-200pro technology is feasible in medical ICU patients. The TL-200pro system is capable of providing MAP values with high accuracy (low mean difference) and precision (narrow limits of agreement) compared with MAP measured invasively using a femoral arterial catheter. The TL-200pro technology is promising for the measurement of SAP and DAP but further development is necessary to improve accuracy and precision.