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1.
Phys Chem Chem Phys ; 26(12): 9500-9509, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38450597

RESUMO

In the present work phenyl phosphine-protected Au9 nanoclusters were deposited onto (3-mercaptopropyl) trimethoxysilane (MPTMS) modified and unmodified mesoporous screen printed TiO2. The removal of the cluster ligands by annealing was applied to enhance the interaction between Au cluster cores and semiconductor surfaces in the creation of efficient photocatalytic systems. The heat treatment could lead to undesired agglomeration of Au clusters, affecting their unique properties as size specific clusters. To address this challenge, the semiconductor surfaces were modified by MPTMS. Characterization techniques confirm the effectiveness of the modification processes, and XPS demonstrates that S functionalized MTiO2 is more efficient than MTiO2 in increasing Au9 NCs adsorption by a factor of 10 and preventing Au cluster agglomeration even after annealing. Overall, this work contributes valuable insights into photocatalytic systems through controlled modification of semiconductor surfaces and Au nanocluster deposition.

2.
J Low Genit Tract Dis ; 27(3): 223-229, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37166026

RESUMO

OBJECTIVE: To test whether headset-delivered virtual reality (VR) content affects satisfaction and/or anxiety in women with cervical squamous intraepithelial lesions undergoing colposcopy and colposcopically guided cervical biopsy. METHODS: In this single-center, randomized trial, the authors measured overall satisfaction (100-mm visual analog scale) and situation-specific anxiety (STAI-S) in 247 women with suspected cervical squamous intraepithelial lesions wearing either no VR headset (arm 1, control) or a VR headset before (arm 2) or before and during colposcopy (arm 3). Secondary endpoints were pain, discomfort, and anxiety during colposcopy, heart rate, and 72-hour follow-up parameters: overall satisfaction, bleeding severity, bleeding duration, pain, and use of analgesics. Analysis was by intention to treat. RESULTS: Median values for overall satisfaction were 100 (interquartile range, 90-100) in controls (n = 83), 100 (95-100) in arm 2 (n = 82), and 100 (95-100) in arm 3 (n = 82), respectively ( p = .92). The median Δ of situational anxiety (baseline vs after colposcopy) was -8 (-13 to -3), -8 (-16.5 to -4), and -10 (-20.5 to -4.5), respectively ( p = .09). The secondary endpoints pain during colposcopy (20 [10-50] vs 20 [10-40] vs 30 [10-50]; p = .65), discomfort during colposcopy (30 [10-50] vs 30 [10-50] vs 20 [10-50]; p = .46), and anxiety during colposcopy (20 [0-50] vs 10 [0-40] vs 10 [0-30]; p = .44), were not different between arms. Follow-up data showed no improvement in the 2 VR arms compared with controls (overall satisfaction, p = .37; bleeding severity, p = .09; pain level, p = .89; duration of pain; p = .23; and use of analgesics; p = .39). Per-protocol analysis did not change the results. CONCLUSIONS: A VR headset showing a 360-degree surround vision film has no effect on satisfaction or anxiety in women undergoing colposcopy.


Assuntos
Lesões Intraepiteliais Escamosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Realidade Virtual , Humanos , Feminino , Gravidez , Colposcopia , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologia , Dor/etiologia , Ansiedade , Analgésicos
3.
Nervenarzt ; 94(10): 934-943, 2023 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-37140605

RESUMO

BACKGROUND: Malignant middle cerebral artery infarction is a potentially life-threatening disease. Decompressive hemicraniectomy constitutes an evidence-based treatment practice, especially in patients under 60 years of age; however, recommendations with respect to postoperative management and particularly duration of postoperative sedation lack standardization. OBJECTIVE: This survey study aimed to analyze the current situation of patients with malignant middle cerebral artery infarction following hemicraniectomy in the neurointensive care setting. MATERIAL AND METHODS: From 20 September 2021 to 31 October 2021, 43 members of the initiative of German neurointensive trial engagement (IGNITE) network were invited to participate in a standardized anonymous online survey. Descriptive data analysis was performed. RESULTS: Out of 43 centers 29 (67.4%) participated in the survey, including 24 university hospitals. Of the hospitals 21 have their own neurological intensive care unit. While 23.1% favored a standardized approach regarding postoperative sedation, the majority utilized individual criteria (e.g., intracranial pressure increase, weaning parameters, complications) to assess the need and duration. The timing of targeted extubation varied widely between hospitals (≤ 24 h 19.2%, ≤ 3 days in 30.8%, ≤ 5 days in 19.2%, > 5 days in 15.4%). Early tracheotomy (≤ 7 days) is performed in 19.2% and 80.8% of the centers aim for tracheotomy within 14 days. Hyperosmolar treatment is used on a regular basis in 53.9% and 22 centers (84.6%) agreed to participate in a clinical trial addressing the duration of postoperative sedation and ventilation. CONCLUSION: The results of this nationwide survey among neurointensive care units in Germany reflect a remarkable heterogeneity in the treatment practices of patients with malignant middle cerebral artery infarction undergoing hemicraniectomy, especially with respect to the duration of postoperative sedation and ventilation. A randomized trial in this matter seems warranted.


Assuntos
Craniectomia Descompressiva , Infarto da Artéria Cerebral Média , Humanos , Infarto da Artéria Cerebral Média/cirurgia , Craniectomia Descompressiva/métodos , Inquéritos e Questionários , Hospitais Universitários , Traqueotomia , Resultado do Tratamento
4.
BMC Cancer ; 22(1): 570, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597921

RESUMO

BACKGROUND/AIM: To develop and validate a nebulizer device for anti-cancer research on pressurized intraperitoneal aerosol supply in a preclinical peritoneal metastases (PM) rat model. MATERIAL AND METHODS: For aerosol generation, an ultrasonic nebulizer (USN) was modified. Aerosol analyses were performed ex-vivo by laser diffraction spectrometry (LDS). Intraperitoneal (IP) 99mtechnetium sodium pertechnetate (99mTc) aerosol distribution and deposition were quantified by in-vivo single photon emission computed tomography (SPECT/CT) and compared to liquid IP instillation of equivalent volume/doses of 99mTc with and without capnoperitoneum. PM was induced by IP injection of HCT116-Luc2 human colon cancer cells in immunosuppressed RNU rats. Tumor growth was monitored by bioluminescence imaging (BLI), 18F-FDG positron emission tomography (PET) and tissues examination at necropsy. RESULTS: The USN was able to establish a stable and reproducible capnoperitoneum at a pressure of 8 to 10 mmHg. LDS showed that the USN provides a polydisperse and monomodal aerosol with a volume-weighted diameter of 2.6 µm. At a CO2 flow rate of 2 L/min with an IP residence time of 3.9 s, the highest drug deposition efficiency was found to be 15 wt.-%. In comparison to liquid instillation, nebulization showed the most homogeneous IP spatial drug deposition. Compared to BLI, 18F-FDG-PET was more sensitive to detect smaller PM nodules measuring only 1-2 mm in diameter. BLI, 18F-FDG PET and necropsy analyses showed relevant PM in all animals. CONCLUSIONS: The USN together with the PM rat model are suitable for robust and species-specific preclinical pharmacological studies regarding intraperitoneal delivery of pressurized aerosolized drugs and cancer research.


Assuntos
Neoplasias do Colo , Neoplasias Peritoneais , Aerossóis , Animais , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/tratamento farmacológico , Fluordesoxiglucose F18 , Humanos , Nebulizadores e Vaporizadores , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/secundário , Ratos
5.
Arch Gynecol Obstet ; 305(2): 415-423, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34802113

RESUMO

PURPOSE: To compare resected cone mass and resection margin status when performing Large Loop Excision of the Transformation Zone (LLETZ) using video colposcopy (LLETZ-VC) versus a headlight (LLETZ-HL) in women with cervical dysplasia. METHODS: Prospective, randomised trial (monocentric) at a specialised cervical dysplasia unit in a University Hospital. Women with a biopsy-proven CIN2 + or persisting CIN1 or diagnostic LLETZ were recruited and randomised. LLETZ was performed either under video colposcopic vision or using a standard surgical headlight. The primary endpoint was resected cone mass. Secondary endpoints were the rate of involved margins, fragmentation of the specimen, procedure time, time to complete haemostasis (TCH), blood loss, pain, intra- and postoperative complications, and surgeon preference. RESULTS: LLETZ-VC and LLETZ-HL (109 women each) had comparable cone masses (1.57 [0.98-2.37] vs. 1.67 [1.15-2.46] grams; P = 0.454). TCH was significantly shorter in the LLETZ-VC arm (60 [41-95.2] vs. 90 [47.2-130.2] seconds; P = 0.008). There was no statistically significant difference in involved resection margins (6/87 [6.5%] vs. 16/101 [13.7%], P = 0.068) and postoperative complications (13/82 [13.7%] vs. 22/72 [23.4%], P = 0.085). Patient-reported outcomes favoured LLETZ-VC with a lower use of analgesics (6/80 [7.0%] vs. 17/87 [16.3%]; P = 0.049). However, LLETZ-VC was more difficult to perform with significantly lower ratings for handling (7 [5-9] vs. 9 [8-10]; P < 0.001) and general satisfaction (7.5 [5-9] vs. 10 [8-10]; P < 0.001). CONCLUSION: Intraoperative video colposcopy for LLETZ has minimal benefits at the cost of surgeons' satisfaction. CLINICAL TRIAL REGISTRATION: NCT04326049 (ClinicalTrials.gov).


Assuntos
Displasia do Colo do Útero , Neoplasias do Colo do Útero , Colposcopia/métodos , Feminino , Humanos , Gravidez , Estudos Prospectivos , Displasia do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/cirurgia
6.
Nervenarzt ; 92(6): 593-601, 2021 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-34046722

RESUMO

BACKGROUND AND OBJECTIVE: Telemedical stroke networks improve stroke care and provide access to time-dependent acute stroke treatment in predominantly rural regions. The aim is a presentation of data on its utility and regional distribution. METHODS: The working group on telemedical stroke care of the German Stroke Society performed a survey study among all telestroke networks. RESULTS: Currently, 22 telemedical stroke networks including 43 centers (per network: median 1.5, interquartile range, IQR, 1-3) as well as 225 cooperating hospitals (per network: median 9, IQR 4-17) operate in Germany and contribute to acute stroke care delivery to 48 million people. In 2018, 38,211 teleconsultations (per network: median 1340, IQR 319-2758) were performed. The thrombolysis rate was 14.1% (95% confidence interval 13.6-14.7%) and transfer for thrombectomy was initiated in 7.9% (95% confidence interval 7.5-8.4%) of ischemic stroke patients. Financial reimbursement differs regionally with compensation for telemedical stroke care in only three federal states. CONCLUSION: Telemedical stroke care is utilized in about 1 out of 10 stroke patients in Germany. Telemedical stroke networks achieve similar rates of thrombolysis and transfer for thrombectomy compared with neurological stroke units and contribute to stroke care in rural regions. Standardization of network structures, financial assurance and uniform quality measurements may further strengthen the importance of telestroke networks in the future.


Assuntos
Consulta Remota , Acidente Vascular Cerebral , Telemedicina , Alemanha , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Terapia Trombolítica
7.
Pneumologie ; 75(10): 753-760, 2021 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-34428830

RESUMO

Health status and quality of life are impaired in patients with idiopathic pulmonary fibrosis (IPF) and idiopathic non-specific interstitial fibrosis (iNSIP). In Germany exists only the K-BILD questionnaire for patients with ILD 1 in a professional translation by Kreuter et al. 2 This questionnaire focuses on the main problems in patients with progressive lung fibrosis in a limited manner. Therefore a new quality of life questionnaire for patients with idiopathic pulmonary fibrosis was developed and linguistically validated. METHODS: The linguistic validation of our questionnaire was carried out in a multistage process in collaboration with the developer of the questionnaire and bilingual, professional translators. Review by the developers and back translations as well as clinical assessment by IPF- and iNSIP-patients ensured that the translated questionnaire reflected the intention of the original English version of our questionnaire.Cross-validation was carried out with the St. Georges Respiratory Questionnaire (SGRQ). RESULTS: The new questionnaire concerning the health status was composed in English and German language. The questions cover five scales (sensitivity, selectivity and symptoms like breathlessness and cough and a visual analog scale on general health status) with 23 items. CONCLUSIONS: The results show that the FFB maps the special needs of the patients with IPF and iNSIP well and can support clinical and scientific questions and can be helpful in monitoring the clinical course.


Assuntos
Fibrose Pulmonar Idiopática , Qualidade de Vida , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Idioma , Linguística , Inquéritos e Questionários
8.
BMC Cancer ; 20(1): 1122, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213407

RESUMO

BACKGROUND: Peritoneal metastasis (PM) in patients with breast (BC) and endometrial cancer (EC) is rare and treatment options are limited. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) has demonstrated efficacy against PM from various cancers, but its efficacy in BC/EC patients is unknown. METHODS: Retrospective cohort study of patients with PM from BC/EC undergoing PIPAC with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Data were collected within an international prospective PIPAC registry. Study outcomes were microscopic tumor regression grade (TRG), survival, adverse events (CTCAE), and quality of life (QoL). RESULTS: 150 PIPAC procedures in 44 patients (BC/EC = 28/16; mean age 58.8 ± 10.1 and 63.2 ± 10.1 years, respectively) were analyzed. The mean number of PIPACs per patient was 3 (range 0-9) and 3.5 (range 0-10), respectively. Primary/secondary non-access occurred in 4/3 of 150 (5%) procedures. PIPAC induced objective tumor regression as demonstrated by repetitive PM biopsies in 73% (32/44) of patients. Peri- and postoperative CTCAE grade 3 and 4 complications were observed in 12/150 (8%) of procedures. No grade 5 event was observed. After a median follow up of 5.7 (IQR 2.7-13.0) months, overall median survival was 19.6 (95% CI: 7.8-31.5) months (from first PIPAC). QoL indicators (general health, nausea, fatigue, constipation, pain, dyspnea, social, cognitive, emotional, and physical functioning) all improved or were maintained throughout PIPAC treatments. CONCLUSIONS: Repetitive intraperitoneal chemotherapy with PIPAC is feasible and safe in patients with PM from BC and EC. PIPAC induces significant histological regression of PM while maintaining QoL.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias Peritoneais/secundário , Aerossóis , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Am J Obstet Gynecol ; 223(1): 101.e1-101.e8, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31981505

RESUMO

BACKGROUND: Application of acetic acid to the cervix followed by colposcopic assessment with or without colposcopically directed biopsy is the standard test used to detect dysplastic lesions of the cervix. However, there is no evidence-based common standard defining how exactly to perform this test. OBJECTIVE: To prospectively define the optimal timing for the colposcopic assessment of acetowhite lesions. MATERIALS AND METHODS: Consecutive women referred to our colposcopy unit were recruited. Using a standardized colposcopy protocol, we recorded the most severe colposcopic lesion 1, 3, and 5 minutes after application of acetic acid (primary study end point). The time to first appearance of the most severe colposcopic lesion, highest staining intensity, and fading of the most severe colposcopic lesion were video documented (secondary study end points, assessed independently by 3 raters). Results were compared using parametric and nonparametric tests. RESULTS: A total of 300 women were included. After 1 minute, 290 of 300 patients (96.7%) were diagnosed with the most severe colposcopic lesion. This proportion did not improve after 3 minutes (290/300 [96.7%]) or after 5 minutes (233/264 [88.3%]). The proportion of minor and major changes continuously declined over time from 142 in 300 (47.3%; 1 minute) to 107 in 264 (40.5%; 5 minutes) and from 110 in 300 (36.7%) to 91 in 264 (34.5%), respectively. The median time until the first appearance of the most severe colposcopic lesion was 13.5 (interquartile range, 3-27.25) seconds and was significantly lower in high-grade squamous intraepithelial lesion (7 [interquartile range, 1-20] seconds) compared to low-grade squamous intraepithelial lesion (19 [interquartile range, 9-39.5] seconds; P < .001). We observed fading of acetowhite lesions in 78% of cases, occurring at a median of 191 (interquartile range, 120-295) seconds after application of acetic acid. Fading started earlier in high-grade squamous intraepithelial lesion compared to low-grade squamous intraepithelial lesion (179.5 [interquartile range, 110- 253.25] versus 212.5 [interquartile range, 146.5-300]; P = .044). Overall, the net difference between colposcopic assessments at 3 minutes versus at 1 minute was 1 more high-grade squamous intraepithelial lesion and 1 less low-grade squamous intraepithelial lesion. CONCLUSION: It is reasonable to conclude that the best time to identify lesions is 1 minute after the application of acetic acid. Continued evaluation for up to 3 minutes may be considered reasonable for an optimal high-grade squamous intraepithelial lesion yield. However, fading of acetowhite lesions is common, especially in high-grade squamous intraepithelial lesions, and supports a recommendation of not prolonging colposcopy beyond 3 minutes.


Assuntos
Ácido Acético/administração & dosagem , Colo do Útero/patologia , Colposcopia/métodos , Ácido Acético/farmacologia , Adulto , Idoso , Colo do Útero/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Adulto Jovem
10.
Am J Obstet Gynecol ; 223(6): 888.e1-888.e9, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32585223

RESUMO

BACKGROUND: Loop electrosurgical excision procedure may be performed under local anesthesia or general anesthesia, and practice patterns differ worldwide. No randomized head-to-head comparison has been published to confirm or refute either practice. OBJECTIVE: This study aimed to compare loop electrosurgical excision procedure under local anesthesia vs general anesthesia regarding patient satisfaction and procedure-related outcomes such as rates of involved margins, complications, pain, and blood loss. STUDY DESIGN: Consecutive women referred to our colposcopy unit were recruited. Loop electrosurgical excision procedure was performed under local anesthesia with 4 intracervical injections of bupivacaine hydrochloride 0.5% or under general anesthesia with fentanyl, propofol, and a laryngeal mask with sevoflurane maintenance. The primary endpoint was patient satisfaction assessed on the day of surgery and 14 days thereafter using a Likert scale (score 0-100) and a questionnaire. Secondary endpoints included rates of involved margins, procedure-related complications, pain, blood loss, and surgeon preference. Results were compared using nonparametric and chi-square tests. RESULTS: Between July 2018 and February 2020, we randomized 208 women, 108 in the local anesthesia arm and 100 in the general anesthesia arm. In the intention-to-treat analysis, patient satisfaction did not differ between the study groups directly after surgery (Likert scale 100 [90-100] vs 100 [90-100]; P=.077) and 14 days thereafter (Likert scale 100 [80-100] vs 100 [90-100]; P=.079). In the per-protocol analysis, women in the local anesthesia arm had significantly smaller cone volumes (1.11 cm3 [0.70-1.83] vs 1.58 cm3 [1.08-2.69], respectively; P<.001), less intraoperative blood loss (Δhemoglobin, 0.2 g/dL [-0.1 to 0.4] vs 0.5 g/dL [0.2-0.9]; P<.001), and higher satisfaction after 14 days (100 [90-100] vs 100 [80-100]; P=.026), whereas surgeon preference favored general anesthesia (90 [79-100] vs 100 [90-100], respectively; P=.001). All other secondary outcomes did not differ between groups (resection margin status R1, 6.6% vs 2.1% [P=.26]; cone fragmentation, 12.1% vs 6.3% [P=.27]; procedure duration, 151.5 seconds [120-219.5] vs 180 seconds [117-241.5] [P=.34]; time to complete hemostasis, 60 seconds [34-97] vs 70 seconds [48.25-122.25] [P=.08]; complication rate, 3.3% vs 1.1% [P=.59]). In a multivariate analysis, parity (P=.03), type of transformation zone (P=.03), and cone volume (P=.02) and not study group assignment, age, body mass index, and degree of dysplasia independently influenced the primary endpoint. CONCLUSION: Loop electrosurgical excision procedure under local anesthesia is equally well tolerated and offers patient-reported and procedure-related benefits over general anesthesia, supporting the preferred practice in some institutions and refuting the preferred practice in others.


Assuntos
Anestesia Geral/métodos , Anestesia Local/métodos , Colposcopia/métodos , Eletrocirurgia/métodos , Satisfação do Paciente , Displasia do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma in Situ/patologia , Adenocarcinoma in Situ/cirurgia , Adulto , Anestésicos Inalatórios/uso terapêutico , Anestésicos Intravenosos/uso terapêutico , Anestésicos Locais/uso terapêutico , Ansiedade , Atitude do Pessoal de Saúde , Perda Sanguínea Cirúrgica , Bupivacaína/uso terapêutico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Conização/métodos , Feminino , Fentanila/uso terapêutico , Ginecologia , Humanos , Máscaras Laríngeas , Margens de Excisão , Dor Pós-Operatória/fisiopatologia , Dor Processual , Complicações Pós-Operatórias , Hemorragia Pós-Operatória , Propofol/uso terapêutico , Sevoflurano/uso terapêutico , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/cirurgia , Cirurgiões , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia
11.
Pneumologie ; 74(5): 263-293, 2020 May.
Artigo em Alemão | MEDLINE | ID: mdl-32227328

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease. Diagnosis of IPF requires considerable expertise and experience. Since publication of the international IPF guideline in the year 2011 and Update 2018 several studies and technical advances occurred, which made a new assessment of the diagnostic process mandatory. In view of the antifibrotic drugs which have been approved for the treatment of IPF patients, the goal of this guideline is to foster early, confident and effective diagnosis of IPF. The guideline focusses on the typical clinical setting of an IPF patient and provides tools to exclude known causes of interstitial lung disease including standardised questionnaires, serologic testing and cellular analysis of bronchoalveolar lavage. High resolution computed tomography remains crucial in the diagnostic work-up. If it is necessary to obtain specimen for histology transbronchial lung cryobiopsy is the primary approach, while surgical lung biopsy is reserved for patients who are fit for it and in whom bronchoscopic diagnosis did not provide the information needed. Despite considerable progress, IPF remains a diagnosis of exclusion and multidisciplinary discussion remains the golden standard of diagnosis.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/terapia , Pulmão/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Biópsia , Humanos , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Doenças Pulmonares Intersticiais , Tomografia Computadorizada por Raios X
12.
BMC Cancer ; 19(1): 958, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619190

RESUMO

BACKGROUND: We analyzed the changes in permeability of endothelial cell layers after photon irradiation, with a focus on the metalloproteases ADAM10 and ADAM17, and on VE-cadherin, components crucial for the integrity of endothelial intercellular junctions, and their roles in the transmigration of cancer cells through endothelial cell monolayers. METHODS: Primary HUVEC were irradiated with 2 or 4 Gy photons at a dose rate of 5 Gy/min. The permeability of an irradiated endothelial monolayer for macromolecules and tumor cells was analyzed in the presence or absence of the ADAM10/17 inhibitors GI254023X and GW280264X. Expression of ADAM10, ADAM17 and VE-Cadherin in endothelial cells was quantified by immunoblotting and qRT. VE-Cadherin was additionally analyzed by immunofluorescence microscopy and ELISA. RESULTS: Ionizing radiation increased the permeability of endothelial monolayers and the transendothelial migration of tumor cells. This was effectively blocked by a selective inhibition (GI254023X) of ADAM10. Irradiation increased both, the expression and activity of ADAM10, which led to increased degradation of VE-cadherin, but also led to higher rates of VE-cadherin internalization. Increased degradation of VE-cadherin was also observed when endothelial monolayers were exposed to tumor-cell conditioned medium, similar to when exposed to recombinant VEGF. CONCLUSIONS: Our results suggest a mechanism of irradiation-induced increased permeability and transendothelial migration of tumor cells based on the activation of ADAM10 and the subsequent change of endothelial permeability through the degradation and internalization of VE-cadherin.


Assuntos
Proteína ADAM10/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Células Endoteliais/efeitos da radiação , Células Endoteliais da Veia Umbilical Humana/efeitos da radiação , Proteínas de Membrana/metabolismo , Proteólise/efeitos da radiação , Radiação Ionizante , Migração Transendotelial e Transepitelial/efeitos da radiação , Proteína ADAM10/antagonistas & inibidores , Proteína ADAM10/genética , Proteína ADAM17/antagonistas & inibidores , Proteína ADAM17/genética , Proteína ADAM17/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/genética , Linhagem Celular Tumoral , Dipeptídeos/farmacologia , Células Endoteliais/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Permeabilidade/efeitos da radiação , Radioterapia/efeitos adversos , Transdução de Sinais/efeitos da radiação , Migração Transendotelial e Transepitelial/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia
13.
Arch Gynecol Obstet ; 300(1): 117-126, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31093741

RESUMO

BACKGROUND: Acute colonic pseudo-obstruction or Ogilvie's syndrome (OS) is a rare form of postsurgical or posttraumatic complication. OS rarely occurs in the postoperative course of gynecologic and obstetric patients and is difficult to diagnose. CASE PRESENTATION: We present the case of an 83-years-old patient with carcinosarcoma of the uterus who developed OS with non-obstructive dilation of the right hemicolon and intraabdominal compression after total abdominal hysterectomy, omentectomy, and lymphadenectomy. Laparotomy with colonic decompression and abdominal dressing was performed. Subsequently, the patient developed pneumonia and peritonitis and died due to septic shock. SYSTEMATIC LITERATURE REVIEW: We identified 49 case reports and 10 case series describing 17 gynecologic (cervical cancer, n = 2; carcinosarcoma of the uterus, n = 1; benign gynecologic condition, n = 14) and 76 obstetric patients (cesarean section, n = 66; OS during pregnancy or after vaginal delivery, n = 10). Outcome data were available for 59 patients. First-line treatment was conservative in 22/59 (37%) cases, laparotomy with decompression or colon resection was performed in 20/59 (34%) cases, endoscopic decompression in 12/59 (20%) cases, and i.v. neostigmine in 4/59 (7%) cases. Resolution was achieved in 22/59 (37%) of patients. The most common second-line treatment was right hemicolectomy. Adverse events grade 3 and 4 were observed in 8/59 and 31/59 patients (together 66%), respectively, mortality was 3/59 (5%). CONCLUSION: OS is a rare postoperative complication of gynecologic and obstetric patients with a good prognosis, but a high morbidity. Pregnancy seems to be a predisposing factor for OS. Conservative treatment is a successful first-line approach.


Assuntos
Pseudo-Obstrução do Colo/diagnóstico , Doenças dos Genitais Femininos/etiologia , Doença Aguda , Idoso de 80 Anos ou mais , Pseudo-Obstrução do Colo/patologia , Feminino , Humanos
14.
Arch Gynecol Obstet ; 300(3): 651-660, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31338659

RESUMO

BACKGROUND: Chronic ectopic pregnancy (CEP) is a variant of ectopic pregnancy (EP) characterized by low or absent serum human chorionic gonadotropin (hCG) levels, resistance to methotrexate (MTX), and an adnexal mass with fibrosis, necrosis, and blood clots due to repeated and gradual fallopian tube wall disintegration. CEP may complicate the course of patients with EP and is difficult to diagnose. CASE PRESENTATION: The case of a 36-year-old woman with EP, low serum hCG levels, a small echogenic adnexal mass, and resistance to MTX is presented. Salpingectomy was performed and histology demonstrated CEP with fibrosis, necrosis, and a hematocele within degenerated chorionic villi. SYSTEMATIC LITERATURE REVIEW: In a database search, 19 case reports, 3 case-control studies, and 3 case series describing 399 patients with CEP were identified. Serum hCG was negative in 40/124 cases (32%) with reported levels of serum hCG. The most common presenting symptom was abdominal pain (284/399 [71%]), followed by irregular vaginal bleeding (219/399 [55%]), and fever (20/399 [5%]). 73/399 (18%) women were asymptomatic. An adnexal mass was seen in 144/298 (48%) cases with perioperative ultrasound examination and with a mean largest diameter of 6.8 cm. Data on treatment modalities and outcomes were available for 297 women. Of these, 89% underwent surgery as first-line therapy. Laparoscopy was performed in most cases. MTX was the first-line therapy in a minority of cases. Complete resolution was achieved by first-line therapy in 287/297 (97%) cases. Adverse events were reported in 218 patients with CEP. Among those, adverse events ≥ grade 3 were seen in 186/218 (85%) cases. There was no case of treatment-related mortality. CONCLUSION: CEP is a variant of EP with low or absent trophoblast activity. A prolonged clinical course is typical and surgery is the mainstay of treatment.


Assuntos
Dor Abdominal/etiologia , Febre/etiologia , Gravidez Ectópica , Salpingectomia , Hemorragia Uterina/etiologia , Doenças dos Anexos/diagnóstico por imagem , Doenças dos Anexos/cirurgia , Adulto , Estudos de Casos e Controles , Gonadotropina Coriônica/sangue , Feminino , Humanos , Gravidez , Complicações na Gravidez , Gravidez Ectópica/diagnóstico , Gravidez Ectópica/etiologia , Gravidez Ectópica/imunologia , Gravidez Ectópica/cirurgia , Útero/cirurgia
15.
Arch Gynecol Obstet ; 299(3): 791-800, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30656441

RESUMO

PURPOSE: The Internet has become a widely used source of healthcare information. Many Departments of Obstetrics and Gynecology use their websites for public relations purposes. It is, however, unclear, what relevant stakeholders such as patients, relatives of patients, physicians, and medical students expect of an Obstetrics and Gynecology Department's website. Therefore, we evaluated the opinions and expectations of the various stakeholders using a structured questionnaire. METHODS: We asked gynecologic patients, obstetric patients, relatives of patients, medical students, and physicians to fill in an anonymous questionnaire consisting of general facts about the informant, one open-ended question on expectations and wishes regarding the website, and 28 rating scale questions (7-step visual analog scale ranging from, not important' to, very important') covering the topics "website navigation" (4 questions), "first contact" (3 questions), "clinic processes" (7 questions), "facts and figures about the Department" (4 questions), "visual impressions" (5 questions), and "obstetrics-specific items" (5 questions). Questionnaires for physicians included four additional questions about the value of Department websites as an information tool for themselves and their patients. We used descriptive statistics to analyze the data. RESULTS: 1458 questionnaires were analyzed (gynecologic patients, n = 615 [42%]; obstetric patients, n = 479 [33%]; relatives of patients, n = 77 [5%]; medical students n = 238 [16%]; physicians, n = 41 [3%]). The number of circulated questionnaires was not recorded and thus, the response rate is unknown. 1304 (89%) respondents used the Internet as a regular source of health care information, 642 (44%) had previously searched an Obstetrics and Gynecology Department website. All respondents rated contact data and information about processes in the clinic highest; whereas, other issues such as medical facts, visual impressions, and website design issues were significantly less important. Pregnant women rated contact information and obstetric facts highest. 90% of physicians regularly used Department websites for patient referrals and rated contact information and medical team details most important. CONCLUSIONS: When designing a website of an Obstetrics and Gynecology Department, contact information and information about processes in the clinic should be displayed most prominently and be easily accessible. Subsections specifically targeted at obstetric patients and physicians should be provided.


Assuntos
Ginecologia/organização & administração , Obstetrícia/organização & administração , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Internet , Pessoa de Meia-Idade , Gravidez , Inquéritos e Questionários , Telemedicina , Adulto Jovem
16.
Arch Gynecol Obstet ; 299(6): 1567-1577, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30953184

RESUMO

PURPOSE: Calprotectin, a marker of acute and chronic inflammation, may play a role in pregnancy-associated disorders. We aimed to summarize available clinical data on calprotectin in pregnancy and to establish normal values of calprotectin during the course of pregnancy. METHODS: We performed a systematic review of the databases PubMed and Cochrane Central Register of Controlled Trials to identify experimental and clinical evidence assessing the role of calprotectin in pregnancy. In addition, we performed a prospective cohort study assessing serum and urine calprotectin throughout pregnancy. RESULTS: We identified 17 studies investigating 1638 pregnant women, 151 newborns, and 99 non-pregnant controls, measuring calprotectin in different compartments. Calprotectin was present in meconium and elevated in fecal samples of pregnant women with active inflammatory bowel disease. In women with pregnancy-induced hypertension, mild and severe preeclampsia (PE), calprotectin was significantly elevated in maternal plasma and serum, but not in fetal serum, amniotic fluid, and umbilical cord blood. For the cohort study, we recruited 196 pregnant women. PE and concomitant renal disease were present in 6/196 (3%) and 11/196 (5.6%) of women, respectively. Throughout pregnancy, median serum and urine levels of calprotectin largely exceed reported concentrations of the healthy non-pregnant population, but showed no significant variations between trimesters 1-3 and post-partum. Calprotectin in serum was correlated with systolic blood pressure and in urine with leukocytes and total protein. No significant differences were found in subgroup analyses of smokers vs. non-smokers, PE vs. none, and renal disease (kidney stones, reflux) vs. none. CONCLUSION: Calprotectin concentrations in amnion fluid and stools serve as potential indicators of inflammatory states during pregnancy. Urinary calprotectin concentrations are continuously high during pregnancy and show no significant variations between trimesters 1-3 and post-partum.


Assuntos
Biomarcadores/sangue , Complexo Antígeno L1 Leucocitário/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/farmacologia , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , Adulto Jovem
17.
Anaesthesist ; 68(1): 22-29, 2019 01.
Artigo em Alemão | MEDLINE | ID: mdl-30446808

RESUMO

BACKGROUND: No systematic study has previously been undertaken in Germany to ascertain why irreversible brain death determination (BDD) has not been carried out. OBJECTIVE: A comprehensive analysis of reasons for unperformed BDD in deceased patients with acute, severe brain damage could improve the identification of potential organ donors. METHOD: Using the Transplantcheck program of the German Organ Transplantation Foundation (DSO) an analysis of the data from 2016 was undertaken in participating hospitals in Saxony, Saxony-Anhalt and Thuringia (Region East of the DSO), regarding why a BDD was not initiated in deceased patients with primary or secondary brain damage. RESULTS: In 128 of the 144 Region East hospitals, 7889 deceased patients with primary or secondary brain damage were detected. In 7389 patients a BDD was out of the question for a variety of reasons. In 232 patients organ donation was not considered due to an advance directive. In 195 cases treatment was limited based on the patient's infaust neurological prognosis without the possibility of organ donation being discussed with relatives. In 73 cases initiation of BDD was indicated but not performed. CONCLUSION: The number of potential organ donors in Region East of the DSO could be significantly increased by identifying patients where BDD is indicated. By consistent evaluation of patients' wills in terms of organ donation before treatment is withdrawn in patients with poor neurological prognosis, additional potential organ donors could be identified. Furthermore, involving neurointensive care physicians in the care of all patients with brain damage could improve the prognostic assessment.


Assuntos
Transplante de Órgãos , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/organização & administração , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Encéfalo , Morte Encefálica , Lesões Encefálicas , Morte , Feminino , Alemanha , Humanos , Masculino , Estudos Retrospectivos
18.
Internist (Berl) ; 60(4): 345-361, 2019 04.
Artigo em Alemão | MEDLINE | ID: mdl-30887071

RESUMO

Fibrosing lung diseases describe a heterogeneous group of interstitial lung diseases (ILD) of highly variable etiology, but with a unifying terminal process of irreversible, fibroproliterative destruction of the alveolar surface, loss of compliance and progressive impairment of gas exchange. In view of the heterogeneity, the disastrous prognoses in some cases and the treatment consequences, a thorough differential diagnosis is essential in all patients. Antifibrotic therapies are currently only indicated in idiopathic pulmonary fibrosis (IPF). The only curative therapeutic option is lung transplantation. Therefore, suitable patients should be promptly evaluated.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Diagnóstico Diferencial , Humanos , Pulmão , Prognóstico
19.
BMC Cancer ; 18(1): 463, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29690864

RESUMO

BACKGROUND: Radiogenic angiosarcoma of the breast (RASB) is a rare late sequela of local irradiation of the breast or chest wall after breast cancer. The prognosis of women with RASB is poor and there is no standardized therapy for this type of malignancy. CASE PRESENTATION: We present the case of a 54 year old woman with RASB (poorly differentiated angiosarcoma of the left breast; pT1, pNX, M0, L0, V0) and a history of invasive-ductal cancer of the left breast (pT1b, G2, pN0, ER positive, PR positive, HER-2/neu negative) treated in July 2012 with breast-conserving surgery, adjuvant chemotherapy with 6 cycles of epirubicin and cyclophosphamide, adjuvant irradiation of the left breast with 50 Gray, and adjuvant endocrine therapy with an aromatase inhibitor. In August 2016, a bilateral salpingo-oophorectomy was performed to remove a tumor of the left ovary, which was diagnosed as breast cancer recurrence. At the same time, a small, purple skin lesion of 1.2 cm in diameter was noted in the inner upper quadrant of the right breast. RASB was diagnosed by punch biopsy and the tumor was excised with clear margins. Imaging studies showed no evidence of further metastases. A systemic chemotherapy with 6 cycles of liposomal doxorubicin was initiated. Five months later, a local recurrence of RASB was diagnosed and mastectomy was performed. Six months later, the patient is alive with no evidence of disease. Three hundred seven cases of RASB were identified. The pooled incidence rate of RASB was 1/3754 women. The most common treatment of RASB was mastectomy in 83% of cases. Adjuvant radiotherapy or chemotherapy were rarely used with 6 and 4%, respectively, whereas in case of recurrence, chemotherapy was the mainstay of treatment, used in 58% of cases. Radiotherapy and repeated surgery were also common with 30 and 33% of cases, respectively. Overall, the prognosis of women with RASB was poor and the recurrence-free survival was short with a mean of 15.9 months. Mean overall survival was 27.4 months. CONCLUSION: RASB is a rare late complication of breast irradiation. The prognosis of women with RASB is poor. Surgery is the mainstay of treatment for localized disease while systemic chemotherapy and re-irradiation are appropriate for women with disseminated or recurrent RASB.


Assuntos
Neoplasias da Mama , Hemangiossarcoma , Segunda Neoplasia Primária , Radioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Biomarcadores , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/terapia , Terapia Combinada , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/epidemiologia , Hemangiossarcoma/etiologia , Hemangiossarcoma/terapia , Imuno-Histoquímica , Gradação de Tumores , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/terapia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos
20.
BMC Cancer ; 18(1): 442, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29669524

RESUMO

BACKGROUND: Patients with recurrent malignant epithelioid mesothelioma (MM) after surgery and standard chemotherapy with cisplatin and pemetrexed have limited treatment options. METHODS: We performed a retrospective cohort study of patients with recurrent MM undergoing Pressurized IntraPeritoneal/Thoracal Aerosol Chemotherapy (PIPAC/PITAC) with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Data were retrospectively collected in a prospective registry of patients undergoing PIPAC/PITAC. Study outcomes were microscopic tumor regression grade (TRG), survival and adverse events (v4.0 CTCAE). RESULTS: A total of 29 patients (m/f = 17/12) with MM with a mean age of 62.4 (range: 42 to 84) years were analyzed. A total of 74 PIPAC and 5 PITAC procedures were performed. The mean number of PIPAC applications was 2.5 (range: 0 to 10) per patient. Twenty patients (69%) had > 2 PIPAC procedure and were eligible for TRG analysis. TRG 1 to 4 was observed in 75% (15/20) of patients. Major regression (TRG 3) or complete regression (TRG 4) was observed in 20% and 10%, respectively. PIPAC induced significant tumor regression in 51.7% (15/29) of patients with a cumulative effect after repetitive PIPACs (PIPAC #1 vs. PIPAC #2: p = 0.001; PIPAC #1 vs. PIPAC #3: p = 0.001; PIPAC #1 vs. PIPAC #4: p = 0.001). Postoperative CTCAE grade 4 complications were observed in two patients (6.9%) who had cytoreductive surgery (CC2) and intraoperative PIPAC. One patient (3.4%) died due to postoperative kidney insufficiency. After a follow up of 14.4 (95% CI: 8.1 to 20.7) months after the last PIPAC/PITAC application, median overall survival was 26.6 (95% CI: 9.5 to 43.7) months (from the first application). CONCLUSION: After prior abdominal surgery and systemic chemotherapy, repetitive PIPAC applications are feasible and safe for patients with end-stage MM. Furthermore, PIPAC induces significant histological regression of malignant mesothelioma in the majority of patients. PITAC is feasible, but its safety and efficacy to control malignant pleural effusion remain unclear.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Infusões Parenterais , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Imageamento por Ressonância Magnética , Masculino , Mesotelioma/diagnóstico , Mesotelioma/mortalidade , Mesotelioma Maligno , Pessoa de Meia-Idade , Derrame Pleural Maligno/tratamento farmacológico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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