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1.
Gynecol Oncol ; 183: 25-32, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38490057

RESUMO

BACKGROUND: Before the era of immunotherapies and antibody-drug conjugates, there were limited chemotherapeutic options for patients with recurrent and metastatic cervical cancer. Combination therapies with cisplatin have shown some superiority over monotherapy. This study examined platinum-free treatment regimens, comparing a combination of topotecan and paclitaxel (TP) with topotecan and cisplatin (TC) in patients with recurrent or metastatic cervical cancer, with or without prior platinum-based treatment. METHODS: The AGO-Zervix-1 Study (NCT01405235) is a prospective, randomized phase III study in which patients were randomly assigned at a 1:1 ratio to treatment within the control arm with topotecan (0.75 mg/m2) on days 1-3 and cisplatin (50 mg/m2) on day 1 every 3 weeks and in the study arm topotecan (1.75 mg/m2) and paclitaxel (70 mg/m2) on days 1, 8, and 15 every 4 weeks or treatment. The primary study aim was overall survival; progression-free survival, toxicity, and quality of life were secondary aims. The interim and final analysis is here reported after recruitment of 173 of 312 planned patients. RESULTS: Median overall survival in the TP arm was 9.6 months, compared with 12.0 months in the TC arm (log-rank test, P = 0.33). Median progression-free survival rates were 4.4 months with TP and 4.2 months with TC (log-rank test, P = 0.47). Leukopenia and nausea/vomiting were more frequent in the cisplatin-containing arm. Otherwise, toxicity profiles were comparable. There were no differences in FACT-G-assessed quality of life. CONCLUSION: Platinum-based combination chemotherapy remains the standard of care chemotherapy regimen for patients with recurrent or metastatic cervical cancer.

2.
Transpl Int ; 36: 11331, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37680646

RESUMO

The European Society of Organ Transplantation (ESOT) strives to promote equity, diversity, and inclusion (EDI) across all its activities. We surveyed the transplant community's experiences and perspectives regarding EDI within ESOT as an organization and its educational activities, and research in general. A total of 299 respondents completed the questionnaire. About half agreed that ESOT's Executive Committee, Council, and Sections/Committees are diverse and inclusive (51%) and that ESOT promotes EDI in its live and digital educational activities (54%). Forty percent of respondents agreed that scientific and clinical trials in the field of transplantation are diverse and inclusive. Despite the wide distribution of the survey, most of the respondents self-identified as White and were either physician or surgeon. However, the results contribute a unique insight into the experiences and perspectives of the transplantation community regarding EDI. Whilst ESOT is committed to the principles of EDI, perceptions and the high number of proposals show the apparent need to prioritize efforts to embed EDI across ESOT and transplantation science. These data should constitute a starting point for change and provide guidance for future efforts to promote EDI within the transplantation community.


Assuntos
Transplante de Órgãos , Cirurgiões , Transplantes , Humanos , Diversidade, Equidade, Inclusão
3.
Nat Metab ; 4(5): 534-546, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35655026

RESUMO

Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor.


Assuntos
Fumaratos/farmacologia , Interferons , Macrófagos , Maleatos/farmacologia , Antivirais/metabolismo , Antivirais/farmacologia , Carboxiliases , Catálise , Humanos , Inflamação/metabolismo , Macrófagos/metabolismo , Estresse Oxidativo
4.
Geburtshilfe Frauenheilkd ; 81(6): 699-707, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34168382

RESUMO

Background More and more information about complementary and integrative medicine is becoming available, especially among cancer patients. However, little is known about the use of herbal medicine by patients with gynecologic cancers. This study aimed to assess the use of herbal products by gynecologic cancer patients compared with healthy controls. Methods This cross-sectional study was conducted at the Department for Gynecology and Obstetrics of Erlangen University Hospital and included 201 patients with gynecologic cancer and 212 healthy controls. Use of herbal medicines was evaluated using a standardized questionnaire. Medical information on cancer patients was collected from hospital records. Group comparisons were done using a logistic regression model. Risk ratios were assessed using a Poisson regression model. Results Gynecologic cancer patients used herbal medicine significantly less often than healthy persons. 69% of gynecologic cancer patients and 81% of healthy participants reported using herbal products. 40% of cancer patients and 56% of healthy persons reported using plants for medicinal purposes. Motives of cancer patients for using herbal medicine included treatment of cancer-related symptoms. The major source of information for both groups was family and friends. Conclusions Although herbal medicine was used less by patients with gynecologic cancer, herbal products were used by both cancer patients and healthy individuals. To provide cancer patients with optimal therapy, oncologists should be informed about the herbal products used by their patients as this will allow them to take their patients' self-medication with herbal medicine into account. Counseling by oncologists on the use of herbal medicine should be encouraged.

5.
J Hosp Infect ; 110: 26-32, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33482298

RESUMO

BACKGROUND: Daily chlorhexidine bathing has been associated with a reduction in central line-associated bloodstream infections (CLABSI). In the setting of an already established CLABSI surveillance system and an implemented CLABSI prevention bundle, we analysed the effect of daily chlorhexidine bathing in ICU patients on CLABSI incidence and its causative pathogens. METHODS: This was a before-and-after study in intensive care units (ICUs) at a tertiary-care centre in Switzerland. Prospective surveillance of CLABSIs and their aetiologies was established. The intervention consisted of daily chlorhexidine bathing of ICU patients with a central venous catheter. A baseline period of 19 months was followed by an intervention period of 9 months. FINDINGS: A total of 5008 patients were included. In the baseline period a mean CLABSI rate of 2.45/1000 catheter days (95% confidence interval (CI) 1.93-3.07) was observed, followed by 1.00/1000 catheter days (95% CI 0.55-1.67; P<0.001) in the intervention period. Introduction of chlorhexidine bathing was independently associated with a reduced risk of CLABSI (adjusted odds ratio 0.47, 95% CI 0.26-0.84, P=0.011). We did not observe a significant change in aetiology except for an increase of Serratia marcescens in the intervention period. CONCLUSIONS: Introduction of daily chlorhexidine bathing resulted in a decline in CLABSI incidence on ICUs. Starting from a baseline CLABSI rate that can be considered standard in a high-income setting and several measures for CLABSI prevention implemented, chlorhexidine bathing proved helpful for a further reduction.


Assuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Clorexidina/uso terapêutico , Infecção Hospitalar , Sepse , Infecções Relacionadas a Cateter/prevenção & controle , Infecção Hospitalar/prevenção & controle , Humanos , Unidades de Terapia Intensiva , Estudos Prospectivos , Sepse/prevenção & controle , Suíça , Centros de Atenção Terciária
6.
Arch Gynecol Obstet ; 301(1): 289-294, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31858234

RESUMO

PURPOSE: Postmenopausal hormone therapy (HT) is known to affect the development of hormone-dependent endometrial carcinoma (type I EC). Several studies on breast and ovarian carcinoma have shown that HT influences the molecular profile and prognostic behavior of these tumors. This study aimed to investigate the influence of prior HT and other risk factors on the prognosis in a cohort of patients with invasive endometrial carcinoma (EC). METHODS: Among 525 patients diagnosed with EC between 1987 and 2010, 426 postmenopausal patients were identified. Information regarding HT was available in 287 of these patients, 78 of whom had a history of HT and 209 of whom did not. Both overall survival (OS) and progression-free survival (PFS) were analyzed. In addition to OS and PFS, risk factors such as age at diagnosis, postmenopausal HT, body mass index (BMI), diabetes mellitus, tumor stage, EC type (I or II), and recurrences were analyzed. RESULTS: Relative to HT alone, women with EC and a history of HT had a longer survival than those with no HT. However, the Cox proportional hazards model showed that it was not HT itself, but rather other characteristics in the HT group that were causally associated with longer survival. CONCLUSIONS: Age (the older, the worse) and tumor stage (the higher, the worse) were significant influences on overall survival. Patients with HT also had lower BMIs, less diabetes, more type I EC, and fewer recurrences in comparison with the non-HT group. With regard to the PFS, it made no difference whether the patient was receiving HT.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Terapia de Reposição de Estrogênios/efeitos adversos , Idoso , Estudos de Coortes , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Recidiva Local de Neoplasia , Prognóstico , Fatores de Risco , Taxa de Sobrevida
10.
Oncol Res Treat ; 41(11): 687-692, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30317238

RESUMO

Like other uterine sarcomas, low-grade endometrial stromal sarcomas (LG-ESS) are a very rare tumor entity. In the past, research studies therefore discussed the various different types of the disease in combination. In addition, the classification of endometrial stromal tumors presented difficulties for quite some time so that in earlier studies it was not always possible to precisely distinguish between LG-ESS, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. For LG-ESS, surgery with hysterectomy and adnexectomy is the first-line treatment. The benefits of lymphadenectomy and tumor debulking are unclear. Endocrine therapy with gestagens and aromatase inhibitors is under discussion to provide adjuvant treatment for patients with advanced stages of the disease. As radiotherapy only provides locoregional control, and in view of the usually good prognosis of patients with LG-ESS, its benefits need to be weighed against its side effects. In the case of recurrence, repeat surgery is the first choice. Further research studies viewing LG-ESS as a distinct entity are needed in order to improve treatment options for patients with LG-ESS.


Assuntos
Neoplasias do Endométrio/terapia , Endométrio/patologia , Recidiva Local de Neoplasia/terapia , Sarcoma do Estroma Endometrial/terapia , Antineoplásicos Hormonais/uso terapêutico , Quimioterapia Adjuvante/métodos , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Endométrio/cirurgia , Feminino , Humanos , Histerectomia/métodos , Excisão de Linfonodo/métodos , Gradação de Tumores , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Radioterapia Adjuvante/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação/métodos , Salpingo-Ooforectomia/métodos , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/patologia
11.
J Viral Hepat ; 25(11): 1384-1394, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29888837

RESUMO

Chronic hepatitis D is caused by coinfection of hepatitis B and hepatitis D virus. While HDV is the dominant virus over HBV in the majority of cases, mechanisms and consequences of viral dominance are largely unknown. We aimed to investigate associations between viral dominance patterns and patients' characteristics and inflammatory features; 109 HDV-infected patients treated with PEG-IFNa-2α within the international multicentre, prospective HIDIT-2 trial were studied. Patients were classified as D- or B-dominant if the viral load of one virus exceeded that of the other virus by more than 1log10 . Otherwise, no viral dominance (ND) was described. We used Luminex-based multiplex technology to study 50 soluble immune mediators (SIM) in pretreatment samples of 105 HDV RNA-positive patients. Dominance of HDV was evident in the majority (75%) of cases. While only 7% displayed B-dominance, 17% showed nondominance. D-dominance was associated with downregulation of 4 interleukins (IL-2ra, IL-13, IL-16 and IL-18) and 5 chemokines/cytokines (CTACK (CCL27), MCP-1 (CCL2), M-CSF, TRAIL and ICAM-1) while no analyte was increased. In addition, D-dominance could be linked to a delayed HDV RNA response to pegylated interferon as patients with B-dominance or nondominance showed higher early HDV RNA responses (61% at week 12) than D-dominant patients (11%; P < .001). In conclusion, this study revealed unexpected effects of viral dominance on clinical and immunological features in chronic hepatitis delta patients. Individualizing PEG-IFNa-2α treatment duration should consider viral dominance. Overall, our findings suggest an activated but exhausted IFN system in D-dominant patients.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/fisiologia , Hepatite D Crônica/tratamento farmacológico , Hepatite D Crônica/virologia , Vírus Delta da Hepatite/fisiologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Ensaios Clínicos como Assunto , Citocinas/sangue , DNA Viral/sangue , Feminino , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite D Crônica/imunologia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/imunologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Adulto Jovem
12.
Reprod Health ; 15(1): 37, 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29499716

RESUMO

BACKGROUND: Daysy is a fertility monitor that uses the fertility awareness method by tracking and analyzing the individual menstrual cycle. In addition, Daysy can be connected to the application DaysyView to transfer stored personal data from Daysy to a smartphone or tablet (IOS, Android). This combination is interesting because as it is shown in various studies, the use of apps is increasing patients´ focus on their disease or their health behavior. The aim of this study was to investigate if by the additional use of an App and thereby improved usability of the medical device, it is possible to enhance the typical-use related as well as the method-related pregnancy rates. RESULT: In the resultant group of 125 women (2076 cycles in total), 2 women indicated that they had been unintentionally pregnant during the use of the device, giving a typical-use related Pearl-Index of 1.3. Counting only the pregnancies which occurred as a result of unprotected intercourse during the infertile (green) phase, we found 1 pregnancy, giving a method-related Pearl-Index of 0.6. Calculating the pregnancy rate resulting from continuous use and unprotected intercourse exclusively on green days, gives a perfect-use Pearl-Index of 0.8. CONCLUSION: It seems that combining a specific biosensor-embedded device (Daysy), which gives the method a very high repeatable accuracy, and a mobile application (DaysyView) which leads to higher user engagement, results in higher overall usability of the method.


Assuntos
Fertilidade/fisiologia , Aplicativos Móveis , Detecção da Ovulação/métodos , Taxa de Gravidez , Smartphone/estatística & dados numéricos , Adulto , Feminino , Humanos , Gravidez , Estudos Retrospectivos
13.
Eur J Cancer ; 90: 122-129, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29306769

RESUMO

BACKGROUND: Immune checkpoint therapy has dramatically changed treatment options in patients with metastatic melanoma. However, a relevant part of patients still does not respond to treatment. Data regarding the prognostic or predictive significance of preexisting immune responses against tumour antigens are conflicting. Retrospective data suggested a higher clinical benefit of ipilimumab in melanoma patients with preexisting NY-ESO-1-specific immunity. PATIENTS AND METHODS: Twenty-five patients with previously untreated or treated metastatic melanoma and preexisting humoural immune response against NY-ESO-1 received ipilimumab at a dose of 10 mg/kg in week 1, 4, 7, 10 followed by 3-month maintenance treatment for a maximum of 48 weeks. Primary endpoint was the disease control rate (irCR, irPR or irSD) according to immune-related response criteria (irRC). Secondary endpoints included the disease control rate according to RECIST criteria, progression-free survival and overall survival (OS). Humoural and cellular immune responses against NY-ESO-1 were analysed from blood samples. RESULTS: Disease control rate according to irRC was 52%, irPR was observed in 36% of patients. Progression-free survival according to irRC was 7.8 months, according to RECIST criteria it was 2.9 months. Median OS was 22.7 months; the corresponding 1-year survival rate was 66.8%. Treatment-related grade 3 AEs occurred in 36% with no grade 4-5 AEs. No clear association was found between the presence of NY-ESO-1-specific cellular or humoural immune responses and clinical activity. CONCLUSION: Ipilimumab demonstrated clinically relevant activity within this biomarker-defined population. NY-ESO-1 positivity, as a surrogate for a preexisting immune response against tumour antigens, might help identifying patients with a superior outcome from immune checkpoint blockade. CLINICAL TRIAL INFORMATION: NCT01216696.


Assuntos
Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/imunologia , Proteínas de Membrana/imunologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Imunidade Humoral , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Neoplasias Cutâneas/mortalidade
14.
Eur J Cancer ; 69: 180-188, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27837710

RESUMO

AIM OF THE STUDY: A tumour-free pathological resection margin of ≥8 mm is considered state-of-the-art. Available evidence is based on heterogeneous cohorts. This study was designed to clarify the relevance of the resection margin for loco-regional control in vulvar cancer. METHODS: AGO-CaRE-1 is a large retrospective study. Patients (n = 1618) with vulvar cancer ≥ FIGO stage IB treated at 29 German gynecologic-cancer-centres 1998-2008 were included. This subgroup analysis focuses on solely surgically treated node-negative patients with complete tumour resection (n = 289). RESULTS: Of the 289 analysed patients, 141 (48.8%) had pT1b, 140 (48.4%) pT2 and 8 (2.8%) pT3 tumours. One hundred twenty-five (43.3%) underwent complete vulvectomy, 127 (43.9%) partial vulvectomy and 37 (12.8%) radical local excision. The median minimal resection margin was 5 mm (1 mm-33 mm); all patients received groin staging, in 86.5% with full dissection. Median follow-up was 35.1 months. 46 (15.9%) patients developed recurrence, thereof 34 (11.8%) at the vulva, after a median of 18.3 months. Vulvar recurrence rates were 12.6% in patients with a margin <8 mm and 10.2% in patients with a margin ≥8 mm. When analysed as a continuous variable, the margin distance had no statistically significant impact on local recurrence (HR per mm increase: 0.930, 95% CI: 0.849-1.020; p = 0.125). Multivariate analyses did also not reveal a significant association between the margin and local recurrence neither when analysed as continuous variable nor categorically based on the 8 mm cutoff. Results were consistent when looking at disease-free-survival and time-to-recurrence at any site (HR per mm increase: 0.949, 95% CI: 0.864-1.041; p = 0.267). CONCLUSIONS: The need for a minimal margin of 8 mm could not be confirmed in the large and homogeneous node-negative cohort of the AGO-CaRE database.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Procedimentos Cirúrgicos em Ginecologia/métodos , Margens de Excisão , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Vulvares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Alemanha , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carga Tumoral , Neoplasias Vulvares/patologia , Adulto Jovem
15.
J Surg Oncol ; 114(5): 613-618, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27378217

RESUMO

BACKGROUND AND OBJECTIVES: Chylous ascites, an accumulation of milky-white lymph fluid in the peritoneal cavity, is a rare complication following retroperitoneal lymphadenectomy. This study evaluated the appearance and management of chylous ascites following lymphadenectomy for gynecological malignancies. METHODS: A total of 931 patients who underwent lymphadenectomy for gynecological malignancies at Erlangen University Hospital between 2002 and 2013 were reviewed retrospectively. RESULTS: Chylous ascites occurred postoperatively in 28 of the 931 patients (3.0%). All patients with chylous ascites had undergone combined systematic para-aortic and pelvic lymphadenectomy (SAPL). Patients with chylous ascites had a larger mean number of lymph nodes removed (51.9 vs. 40.0, P = 0.002) and the proportion of laparoscopic SAPLs was significantly higher (20/28; 71.4%) in comparison with open surgery (8/28; 28.6%) (P < 0.0001). Additional parameters, such as the number of positive lymph nodes, were not significantly associated with the occurrence of chylous ascites. Conservative management was sufficient to resolve chylous ascites in all observed cases, with a mean time to resolution of 8 days. CONCLUSIONS: Postoperative chylous ascites was more frequently observed in patients with laparoscopic SAPL in comparison with open SAPL and was strongly associated with a larger mean number of removed lymph nodes. J. Surg. Oncol. 2016;114:613-618. © 2016 Wiley Periodicals, Inc.


Assuntos
Carcinoma/cirurgia , Ascite Quilosa/etiologia , Neoplasias dos Genitais Femininos/cirurgia , Laparoscopia/efeitos adversos , Excisão de Linfonodo/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
16.
Am J Transplant ; 16(11): 3150-3162, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27273729

RESUMO

Experimentally, regulatory T cells inhibit rejection. In clinical transplantations, however, it is not known whether T cell regulation is the cause for, or an epiphenomenon of, long-term allograft survival. Here, we study naïve and alloantigen-primed T cell responses of clinical lung transplant recipients in humanized mice. The pericardiophrenic artery procured from human lung grafts was implanted into the aorta of NODrag-/- /IL-2rγc-/- mice reconstituted with peripheral blood mononuclear cells (PBMCs) from the respective lung recipient. Naïve or primed allogeneic PBMCs procured 21 days post-lung transplantation with or without enriching for CD4+ CD25high T cells were used. Transplant arteriosclerosis was assessed 28 days later by histology. Mice reconstituted with alloantigen-primed PBMCs showed significantly more severe transplant arteriosclerosis than did mice with naïve PBMCs (p = 0.005). Transplant arteriosclerosis was equally suppressed by enriching for autologous naïve (p = 0.012) or alloantigen-primed regulatory T cells (Tregs) (p = 0.009). Alloantigen priming in clinical lung recipients can be adoptively transferred into a humanized mouse model. Transplant arteriosclerosis elicited by naïve or alloantigen-primed PBMCs can be similarly controlled by potent autologous Tregs. Cellular therapy with expanded autologous Tregs in lung transplantation might be a promising future strategy.


Assuntos
Arteriosclerose/etiologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/imunologia , Isoantígenos/imunologia , Pneumopatias/imunologia , Transplante de Pulmão/efeitos adversos , Linfócitos T Reguladores/imunologia , Animais , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Pneumopatias/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Fenótipo , Transplantados , Transplante Homólogo
17.
J Viral Hepat ; 23(4): 305-15, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26852892

RESUMO

Hepatitis E is an inflammatory liver disease caused by infection with the hepatitis E virus (HEV). In tropical regions, HEV is highly endemic and predominantly mediated by HEV genotypes 1 and 2 with >3 million symptomatic cases per year and around 70 000 deaths. In Europe and America, the zoonotic HEV genotypes 3 and 4 have been reported with continues increasing new infections per year. So far, little is known about T-cell responses during acute HEV genotype 3 infection. Therefore, we did a comprehensive study investigating HEV-specific T-cell responses using genotypes 3- and 1-specific overlapping peptides. Additional cytokines and chemokines were measured in the plasma. In four patients, longitudinal studies were performed. Broad functional HEV-specific CD4(+) and CD8(+) T-cell responses were detectable in patients acutely infected with HEV genotype 3. Elevated of pro- and anti-inflammatory cytokine levels during acute HEV infection correlated with ALT levels. Memory HEV-specific T-cell responses were detectable up to >1.5 years upon infection. Importantly, cross-genotype HEV-specific T-cell responses (between genotypes 1 and 3) were measurable in all investigated patients. In conclusion, we could show for the first time HEV-specific T-cell responses during and after acute HEV genotype 3 infection. Our data of cross-genotype HEV-specific T-cell responses might suggest a potential role in cross-genotype-specific protection between HEV genotypes 1 and 3.


Assuntos
Genótipo , Vírus da Hepatite E/classificação , Vírus da Hepatite E/imunologia , Hepatite E/imunologia , Imunidade Heteróloga , Linfócitos T/imunologia , Adulto , Idoso , Alanina Transaminase/sangue , Reações Cruzadas , Citocinas/sangue , Feminino , Humanos , Memória Imunológica , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA
18.
Am J Transplant ; 16(5): 1371-82, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26602894

RESUMO

Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells.


Assuntos
Quimerismo , Sobrevivência de Enxerto/imunologia , Isoantígenos/imunologia , Transplante de Pulmão , Linfócitos T Reguladores/efeitos da radiação , Animais , Feminino , Terapia de Imunossupressão , Masculino , Modelos Animais , Suínos , Porco Miniatura , Linfócitos T Reguladores/imunologia , Doadores de Tecidos , Tolerância ao Transplante , Transplante Homólogo , Irradiação Corporal Total
19.
Arch Gynecol Obstet ; 294(2): 343-51, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26711836

RESUMO

PURPOSE: There is low evidence regarding the optimal treatment in patients with uterine sarcomas and malignant mixed Mullerian tumors (MMMTs). This study provides an overview of experience at our center with patients diagnosed with uterine sarcoma and MMMT, in relation to the clinical management and outcome. METHODS: The medical records for 143 patients with low-grade endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and high-grade (undifferentiated) endometrial sarcoma (UES) and MMMT were reviewed. All available clinical and pathological data were collected and analyzed. Putative prognostic factors were entered into a multivariate analysis using a Cox proportional hazards ratio model, and survival data were calculated. RESULTS: The 5-year overall survival rates were significantly different between patients with ESS, LMS, and UES and MMMT (86 vs. 40 vs. 57 vs. 45 %; P < 0.001). The multivariate analysis showed that the patients' age, higher FIGO stage (III-IV), a history of smoking, prior pelvic radiation, diabetes, and residual tumor after surgery were associated with a poorer overall survival. Histological subtypes of LMS (HR 4.68; 95 % CI 1.35-16.17), UES (HR 1.21; 95 % CI 0.26-5.77) and MMMT (HR 1.63; 95 % CI 0.42-6.43) were also associated with a poorer overall survival than ESS (P = 0.008). Adjuvant therapies showed no associations with overall survival. CONCLUSIONS: Adjuvant therapy has so far not shown any overall survival benefit, and the focus is therefore on primary surgery. In future studies, the entities should be investigated separately in relation to prognostic factors and effective therapeutic management.


Assuntos
Tumores do Estroma Endometrial/patologia , Leiomiossarcoma/patologia , Tumor Mulleriano Misto/patologia , Sarcoma do Estroma Endometrial/patologia , Neoplasias Uterinas/patologia , Adulto , Idoso , Terapia Combinada , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Tumores do Estroma Endometrial/mortalidade , Tumores do Estroma Endometrial/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Leiomiossarcoma/mortalidade , Leiomiossarcoma/terapia , Pessoa de Meia-Idade , Tumor Mulleriano Misto/mortalidade , Tumor Mulleriano Misto/terapia , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Sarcoma/patologia , Sarcoma do Estroma Endometrial/mortalidade , Sarcoma do Estroma Endometrial/terapia , Taxa de Sobrevida , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/cirurgia
20.
BMC Cancer ; 15: 751, 2015 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-26487094

RESUMO

BACKGROUND: No screening programs are available for ovarian or endometrial cancer. One reason for this is the low incidence of the conditions, resulting in low positive predictive values for tests, which are not very specific. One way of addressing this problem might be to use risk factors to define subpopulations with a higher incidence. The aim of this study was to investigate the extent to which a medical history of endometriosis can serve as a risk factor for ovarian or endometrial cancer. METHODS: In a hospital-based case-control analysis, the cases represented patients with endometrial or ovarian cancer who were participating in studies aimed at assessing the risk for these diseases. The controls were women between the age of 40 and 85 who were invited to take part via a newspaper advertisement. A total of 289 cases and 1016 controls were included. Using logistic regression models, it was tested whether self-reported endometriosis is a predictor of case-control status in addition to age, body mass index (BMI), number of pregnancies and previous oral contraceptive (OC) use. RESULTS: Endometriosis was reported in 2.1 % of the controls (n = 21) and 4.8 % of the cases (n = 14). Endometriosis was a relevant predictor for case-control status in addition to other predictive factors (OR 2.63; 95 % CI, 1.28 to 5.41). CONCLUSION: This case-control study found that self-reported endometriosis may be a risk factor for endometrial or ovarian cancer in women between 40 and 85 years. There have been very few studies addressing this issue, and incorporating it into a clinical prediction model would require a more precise characterization of the risk factor of endometriosis.


Assuntos
Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Endometriose/complicações , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Fatores de Risco
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