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1.
Ann Oncol ; 35(3): 276-284, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38061428

RESUMO

BACKGROUND: Persisting cancer-related fatigue impairs health-related quality of life (HRQoL) and social reintegration in patients with Hodgkin's lymphoma (HL). The GHSG HD18 trial established treatment de-escalation for advanced-stage HL guided by positron emission tomography after two cycles (PET-2) as new standard. Here, we investigate the impact of treatment de-escalation on long-term HRQoL, time to recovery from fatigue (TTR-F), and time to return to work (TTR-W). PATIENTS AND METHODS: Patients received European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and life situation questionnaires at baseline, interim, end of treatment, and yearly follow-up. TTR-F was defined as time from the end of chemotherapy until the first fatigue score <30. TTR-W was analyzed in previously working or studying patients and measured from the end of treatment until the first documented work or education. We compared duration of treatment on TTR-F and TTR-W using Cox proportional hazards regression adjusted for confounding variables. RESULTS: HRQoL questionnaires at baseline were available in 1632 (83.9%) of all randomized patients. Overall, higher baseline fatigue and age were significantly associated with longer TTR-F and TTR-W and male sex with shorter TTR-W. Treatment reduction from eight to four chemotherapy cycles led to a significantly shorter TTR-F [hazard ratio (HR) 1.41, P = 0.008] and descriptively shorter TTR-W (HR 1.24, P = 0.084) in PET-2-negative patients. Reduction from six to four cycles led to non-significant but plausible intermediate accelerations. The addition of rituximab caused significantly slower TTR-F (HR 0.70, P = 0.0163) and TTR-W (HR 0.64, P = 0.0017) in PET-2-positive patients. HRQoL at baseline and age were the main determinants of 2-year HRQoL. CONCLUSIONS: Individualized first-line treatment in patients with advanced-stage HL considerably shortens TTR-F and TTR-W in PET-2-negative patients. Our results support the use of response-adapted shortened treatment duration for patients with HL.


Assuntos
Doença de Hodgkin , Humanos , Masculino , Doença de Hodgkin/patologia , Qualidade de Vida , Retorno ao Trabalho , Fadiga/etiologia , Sobreviventes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
J Chem Phys ; 159(14)2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37815111

RESUMO

The dynamics of a tracer particle in a bath of quasi-hard colloidal spheres is studied by Langevin dynamics simulations and mode coupling theory (MCT); the tracer radius is varied from equal to up to seven times larger than the bath particles radius. In the simulations, two cases are considered: freely diffusing tracer (passive microrheology) and tracer pulled with a constant force (active microrheology). Both cases are connected by linear response theory for all tracer sizes. It links both the stationary and transient regimes of the pulled tracer (for low forces) with the equilibrium correlation functions; the velocity of the pulled tracer and its displacement are obtained from the velocity auto-correlation function and the mean squared displacement, respectively. The MCT calculations give insight into the physical mechanisms: At short times, the tracer rattles in its cage of neighbours, with the frequency increasing linearly with the tracer radius asymptotically. The long-time tracer diffusion coefficient from passive microrheology, which agrees with the inverse friction coefficient from the active case, arises from the transport of transverse momentum around the tracer. It can be described with the Brinkman equation for the transverse flow field obtained in extension of MCT, but cannot be recovered from the MCT kernel coupling to densities only. The dynamics of the bath particles is also studied; for the unforced tracer the dynamics is unaffected. When the tracer is pulled, the velocity field in the bath follows the prediction of the Brinkman model, but different from the case of a Newtonian fluid.

3.
BMC Cancer ; 22(1): 820, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35897060

RESUMO

BACKGROUND: Initial systemic therapy for patients with metastatic colorectal cancer (mCRC) is usually based on two- or three-drug chemotherapy regimens with fluoropyrimidine (5-fluorouracil (5-FU) or capecitabine), oxaliplatin and/or irinotecan, combined with either anti-VEGF (bevacizumab) or, for RAS wild-type (WT) tumors, anti-EGFR antibodies (panitumumab or cetuximab). Recommendations for patients who are not eligible for intensive combination therapies are limited and include fluoropyrimidine plus bevacizumab or single agent anti-EGFR antibody treatment. The use of a monochemotherapy concept of trifluridine/ tipiracil in combination with monoclonal antibodies is not approved for first-line therapy, yet. Results from the phase II TASCO trial evaluating trifluridine/ tipiracil plus bevacicumab in first-line treatment of mCRC patients and from the phase I/II APOLLON trial investigating trifluridine/ tipiracil plus panitumumab in pre-treated mCRC patients suggest favourable activity and tolerability of these new therapeutic approaches. METHODS: FIRE-8 ( NCT05007132 ) is a prospective, randomized, open-label, multicenter phase II study which aims to evaluate the efficacy of first-line treatment with trifluridine/tipiracil (35 mg/m2 body surface area (BSA), orally twice daily on days 1-5 and 8-12, q28 days) plus either the anti-EGFR antibody panitumumab (6 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm A] or (as control arm) the anti-VEGF antibody bevacizumab (5 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm B] in RAS WT mCRC patients. The primary objective is to demonstrate an improved objective response rate (ORR) according to RECIST 1.1 from 30% (control arm) to 55% with panitumumab. With a power of 80% and a two-sided significance level of 0.05, 138 evaluable patients are needed. Given an estimated drop-out rate of 10%, 153 patients will be enrolled. DISCUSSION: To the best of our knowledge, this is the first phase II trial to evaluate the efficacy of trifluridine/tipiracil plus panitumumab in first-line treatment of RAS WT mCRC patients. The administration of anti-EGFR antibodies rather than anti-VEGF antibodies in combination with trifluridine/tipiracil may result in an increased initial efficacy. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT) 2019-004223-20 . Registered October 22, 2019, ClinicalTrials.gov NCT05007132 . Registered on August 12, 2021.


Assuntos
Neoplasias Colorretais , Trifluridina , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Peso Corporal , Ensaios Clínicos Fase II como Assunto , Neoplasias Colorretais/patologia , Fluoruracila , Humanos , Estudos Multicêntricos como Assunto , Panitumumabe/uso terapêutico , Estudos Prospectivos , Pirrolidinas , Ensaios Clínicos Controlados Aleatórios como Assunto , Timina , Trifluridina/uso terapêutico
4.
HNO ; 70(2): 117-124, 2022 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-34347110

RESUMO

BACKGROUND: The aim of this study was to develop a shortened German version of the Singing Voice Handicap Index (SVHI). The SVHI is a one-dimensional instrument for self-assessment of a voice disorder in singers. The questionnaire developed in the USA comprises 36 items and has been available in a validated German version since 2013. METHODS: Bicentric data from a total of 200 patients formed the basis for item analysis and selection. Using corrected item-total correlations, 12 items were selected for the abridged version. The internal consistency was calculated. The SVHI-12 was subsequently validated in 97 vocal patients and 105 vocally healthy singers (control group) using the test-retest procedure. RESULTS: The SVHI-12 achieved a good internal consistency (Cronbach's alpha = 0.93) and a good test-retest reliability (intra-class correlation r = 0.88 ; p < 0.001). The patients had significantly higher overall scores (18 ± 13 vs. 7 ± 6) compared to the healthy control group. The SVHI-12 overall score correlated significantly positively with the severity of the voice disorder as reported by the patient (r = 0.68; p < 0.001). As a threshold value above which a voice can be described as disturbed, a total score > 7 points was calculated using receiver operating curve analysis. As an indication of a voice disorder, a sensitivity of 81% and a specificity of 71% is thus achieved (Youden index 0.523, area under the curve 0.827, 95% confidence interval 0.769-0.885). CONCLUSION: The shortened SVHI has similarly good psychometric characteristics to the original SVHI. With the SVHI-12, a valid and effective instrument for the detection of singing voice disorders is available for German-speaking countries.


Assuntos
Canto , Distúrbios da Voz , Avaliação da Deficiência , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Distúrbios da Voz/diagnóstico , Qualidade da Voz
5.
Phys Rev Lett ; 127(8): 085501, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34477411

RESUMO

Direct correlation functions (DCFs), linked to the second functional derivative of the free energy with respect to the one-particle density, play a fundamental role in a statistical mechanics description of matter. This holds, in particular, for the ordered phases: DCFs contain information about the local structure including defects and encode the thermodynamic properties of crystalline solids; they open a route to the elastic constants beyond low temperature expansions. Via a demanding numerical approach, we have explicitly calculated for the first time the DCF of a solid: based on the fundamental measure concept, we provide results for the DCF of a hard sphere crystal. We demonstrate that this function differs at coexistence significantly from its liquid counterpart-both in shape as well as in its order of magnitude-because it is dominated by vacancies. We provide evidence that the traditional use of liquid DCFs in functional Taylor expansions of the free energy is conceptually wrong and show that the emergent elastic constants are in good agreement with simulation-based results.

6.
Arch Virol ; 166(10): 2789-2801, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34370094

RESUMO

Data mining and metagenomic analysis of 277 open reading frame sequences of bipartite RNA viruses of the genus Nepovirus, family Secoviridae, were performed, documenting how challenging it can be to unequivocally assign a virus to a particular species, especially those in subgroups A and C, based on some of the currently adopted taxonomic demarcation criteria. This work suggests a possible need for their amendment to accommodate pangenome information. In addition, we revealed a host-dependent structure of arabis mosaic virus (ArMV) populations at a cladistic level and confirmed a phylogeographic structure of grapevine fanleaf virus (GFLV) populations. We also identified new putative recombination events in members of subgroups A, B and C. The evolutionary specificity of some capsid regions of ArMV and GFLV that were described previously and biologically validated as determinants of nematode transmission was circumscribed in silico. Furthermore, a C-terminal segment of the RNA-dependent RNA polymerase of members of subgroup A was predicted to be a putative host range determinant based on statistically supported higher π (substitutions per site) values for GFLV and ArMV isolates infecting Vitis spp. compared with non-Vitis-infecting ArMV isolates. This study illustrates how sequence information obtained via high-throughput sequencing can increase our understanding of mechanisms that modulate virus diversity and evolution and create new opportunities for advancing studies on the biology of economically important plant viruses.


Assuntos
Genoma Viral/genética , Especificidade de Hospedeiro/genética , Nepovirus/genética , Evolução Molecular , Variação Genética , Metagenômica , Nepovirus/classificação , Fases de Leitura Aberta/genética , Filogenia , Filogeografia , Plantas/classificação , Plantas/virologia , RNA Viral/genética , Recombinação Genética
7.
Plant Dis ; 105(1): 14-26, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32840434

RESUMO

Pathogen-tested foundation plant stocks are the cornerstone of sustainable specialty crop production. They provide the propagative units that are used to produce clean planting materials, which are essential as the first-line management option of diseases caused by graft-transmissible pathogens such as viruses, viroids, bacteria, and phytoplasmas. In the United States, efforts to produce, maintain, and distribute pathogen-tested propagative material of specialty crops are spearheaded by centers of the National Clean Plant Network (NCPN). Agricultural economists collaborated with plant pathologists, extension educators, specialty crop growers, and regulators to investigate the impacts of select diseases caused by graft-transmissible pathogens and to estimate the return on investments in NCPN centers. Economic studies have proven valuable to the NCPN in (i) incentivizing the use of clean planting material derived from pathogen-tested foundation plant stocks; (ii) documenting benefits of clean plant centers, which can outweigh operating costs by 10:1 to 150:1; (iii) aiding the development of disease management solutions that are not only ecologically driven but also profit maximizing; and (iv) disseminating integrated disease management recommendations that resonate with growers. Together, economic studies have reinforced efforts to safeguard specialty crops in the United States through the production and use of clean planting material.


Assuntos
Agricultura , Produtos Agrícolas , Estados Unidos
8.
Skeletal Radiol ; 49(5): 765-772, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31822941

RESUMO

PURPOSE: To compare the diagnostic performance of different reconstruction algorithms of single-source dual-energy computed tomography (DECT) for the detection of bone marrow lesions (BML) in patients with vertebral compression fracture using MRI as the standard of reference. MATERIAL AND METHODS: Seventeen patients with an age over 50 who underwent single-source DECT of the spine were included. The raw data (RD) were reconstructed using filtered back-projection (FBP) and iterative reconstruction (IR) with three iteration levels (IR1-IR3). Bone marrow images were generated using a three-material decomposition (3MD) and a two-material decomposition (2MD) algorithm and an RD-based approach. Three blinded readers scored the images for image quality and the presence of bone marrow lesions (BML). Only vertebrae with height loss were included. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The different reconstructions were compared using Dunn's multiple comparison test. RESULTS: Thirty-nine vertebrae were included. IR(1-3) showed superior sensitivity (87.5%) compared to FBP (75%) using 3MD but was comparable to RD (83.3%). All 2MD images were inferior (sensitivity < 38%). The image quality score was significantly higher for 3MD-IR(1-3) compared to 3MD-FBP (p < 0.0001) and all 2MD data sets (p < 0.03). This pattern was also supported by the SNR and CNR measurements. RD showed no significant improvement compared to IR. CONCLUSION: The image quality of bone marrow images acquired with DECT can be improved by using IR compared with FBP. RD-based reconstruction does not offer significant improvement over image data-based reconstruction. 2MD algorithms are not suitable for BML detection.


Assuntos
Algoritmos , Doenças da Medula Óssea/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Radiográfica a Partir de Emissão de Duplo Fóton , Reprodutibilidade dos Testes , Estudos Retrospectivos
9.
Ann Oncol ; 30(8): 1329-1334, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132094

RESUMO

BACKGROUND: The prognosis of Hodgkin lymphoma (HL) is excellent rendering research into treatment complications highly important. An important complication of cancer and its treatment is thrombosis. Thrombotic events are regularly observed in HL patients but precise information on incidence and risk factors is lacking and the value of prophylactic anticoagulation unclear. PATIENTS AND METHODS: Thus, we comprehensively studied thrombotic events in 5773 patients from the German Hodgkin Study Group (GHSG) HD13-15 trials in early-favorable, intermediate and advanced HL. We estimated the incidence of and identified risk factors for thrombotic events. Additionally, we provide detailed data on the time course and characteristics of thrombotic events. RESULTS: A total of 193 thrombotic events occurred for an incidence of 3.3%. Out of these, 175 (90.7%) were venous thromboses, 3 (1.5%) newly emerging post-thrombotic syndromes and 15 (7.8%) arterial thromboses. There were 11 (0.7%) events in early-favorable, 27 (1.3%) in early-unfavorable and 155 (7.3%) in advanced patients, the latter incidence being significantly higher (P < 0.001). The most common locations were deep vein thrombosis of the arm (46.3%) and leg (24.6%). Most venous thrombotic events occurred during chemotherapy (78.9%). We observed 59 (30.6%) catheter-associated events and a descriptively increased risk of venous thrombotic events in patients with oral contraception use during treatment (6.8% versus 3.9%). In advanced HL, the incidence of venous thrombotic events was increased upon treatment with BEACOPP-14 (9.4%, P = 0.0079) compared with 5.1% with 6×BEACOPPesc and 5.7% with 8×BEACOPPesc. Among commonly applied risk factors, including the Khorana score, only age and smoking were prognostic. CONCLUSIONS: The incidence of thrombotic events in advanced stage HL is comparable to other high-risk cancer patients, especially if treated with dose-dense regimens. Additional risk factors are higher age and smoking. Selected HL patients could benefit from prophylactic anticoagulation, however, further interventional studies are needed before general recommendations can be made.


Assuntos
Anticoagulantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Trombose/epidemiologia , Administração Intravenosa/efeitos adversos , Administração Intravenosa/instrumentação , Administração Oral , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Catéteres/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Feminino , Alemanha/epidemiologia , Doença de Hodgkin/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Trombose/induzido quimicamente , Trombose/prevenção & controle , Adulto Jovem
10.
HNO ; 67(1): 36-44, 2019 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-30324556

RESUMO

BACKGROUND: Hearing-impairment can lead to a reduced quality of life and thus represents a vulnerability factor for mental disorders. OBJECTIVE: This study represents the first psychiatric analysis of subjective quality of life and depression in people with hearing-impairment in Germany. MATERIALS AND METHODS: The patient group included 30 hearing-impaired participants (27 women, 3 men) with a current or previous mental disorder and/or psychiatric/psychotherapeutic treatment (age: mean, M = 49.67 years; standard deviation, SD = 13.54 years). The control group consisted of 22 hearing-impaired participants (16 women, 6 men) without mental disorders or treatment (age: M = 52.41 years, SD = 17.30 years). Besides sociodemographic variables, we registered onset/extent of the various hearing-impairments and hearing aid provision. Both groups underwent extensive diagnostic assessment comprising subjective functional impairment (Sheehan Disability Scale, SDS), health-related quality of life (SF-36 Health Survey), and depressive symptoms (Beck Depression Inventory, BDI-II). RESULTS: Groups did not differ significantly in terms of sociodemographic variables such as age, gender, or intelligence. Participants of the patient group had a significantly greater subjective impairment, a lower quality of life, and more pronounced symptoms of depression. The invasiveness of the hearing aid (i. e., cochlear implant) as well as the timepoint of hearing-impairment onset (postlingually) appear to serve as vulnerability factors for mental health problems in this group. CONCLUSION: Our results indicate that besides delivering high-quality acoustic care, practitioners should continuously check patients' requirements for psychosocial treatment due to a loss of quality of life. The development of a specific psychotherapeutic treatment for hearing-impaired clients requires additional research focused on protective and vulnerability factors which may influence the emergence of mental disorders in these patients.


Assuntos
Depressão , Pessoas com Deficiência Auditiva/psicologia , Qualidade de Vida , Depressão/epidemiologia , Feminino , Alemanha , Auxiliares de Audição , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
11.
Ann Oncol ; 29(9): 1926-1931, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30010775

RESUMO

Background: Bone marrow (BM) involvement defines advanced-stage Hodgkin lymphoma and thus has impact on the assignment to treatment. Our aim was to evaluate whether the established BM biopsy may be omitted in patients if 18F-fluorodeoxyglucose positron emission tomography (PET) scanning is carried out during staging. Patients and methods: Our analysis set consisted of 832 Hodgkin lymphoma patients from the German Hodgkin Study Group trials HD16, HD17, and HD18 who underwent both PET scanning and BM biopsy before treatment. All PET studies were centrally reviewed and BM was categorized as showing focal involvement or not. Results: Taking BM biopsy as reference standard, baseline PET showed a negative predictive value of 99.9% [95% confidence interval (CI) 99.2% to 100%] with true-negative results in 702 of 703 cases. The sensitivity of PET for detecting BM involvement was 95.0% (95% CI 75.1% to 99.9%) as it could identify 19 out of 20 patients with positive BM biopsy. Moreover, PET found 110 additional subjects with focal BM lesions who would have been considered negative by biopsy. Conclusions: When compared with BM biopsy, PET was able to detect focal BM lesions in a large number of additional patients. This indicates that conventional BM biopsy may substantially underestimate the actual incidence of BM involvement. Given the high negative predictive value, baseline PET scanning can safely be used to exclude BM involvement in Hodgkin lymphoma. BM biopsy should be considered only in such patients in whom PET-detected lesions lead to a change of treatment protocol. Registered trials: The trials included in this analysis were registered at ClinicalTrials.gov: HD16-NCT00736320, HD17-NCT01356680, and HD18-NCT00515554.


Assuntos
Medula Óssea/patologia , Doença de Hodgkin/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Adulto , Idoso , Biópsia/normas , Medula Óssea/diagnóstico por imagem , Ensaios Clínicos Fase III como Assunto , Conjuntos de Dados como Assunto , Feminino , Fluordesoxiglucose F18/administração & dosagem , Alemanha , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Padrões de Referência , Adulto Jovem
12.
Nature ; 488(7413): 603-8, 2012 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-22932384

RESUMO

Light-matter interactions are ubiquitous, and underpin a wide range of basic research fields and applied technologies. Although optical interactions have been intensively studied, their microscopic details are often poorly understood and have so far not been directly measurable. X-ray and optical wave mixing was proposed nearly half a century ago as an atomic-scale probe of optical interactions but has not yet been observed owing to a lack of sufficiently intense X-ray sources. Here we use an X-ray laser to demonstrate X-ray and optical sum-frequency generation. The underlying nonlinearity is a reciprocal-space probe of the optically induced charges and associated microscopic fields that arise in an illuminated material. To within the experimental errors, the measured efficiency is consistent with first-principles calculations of microscopic optical polarization in diamond. The ability to probe optical interactions on the atomic scale offers new opportunities in both basic and applied areas of science.

13.
Acta Chir Orthop Traumatol Cech ; 85(5): 319-324, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30383527

RESUMO

PURPOSE OF THE STUDY There is limited evidence on survival and complication rates in patients after total knee arthroplasty for posttraumatic osteoarthritis. The failure mechanisms leading to revision remain an issue of constant debate. The purpose of this study was to analyze the mid-term survival of primary total knee arthroplasties as well as to evaluate complications and failure mechanisms in patients with posttraumatic knee osteoarthritis. MATERIAL AND METHODS This retrospective study included 79 patients with an average age of 59 years at the time of primary total knee arthroplasty. A functional and radiographic assessment was obtained during outpatient clinical follow-up at 3 and 12 months postoperatively and yearly intervals after that. Survival rates were calculated using Kaplan-Meier analyses. The mean postoperative follow-up was 69 months. RESULTS At 69 month the revision-free survival rate was 88.6%. In nine cases (11.4%) a revision procedure was performed. The leading cause of revision was a periprosthetic infection (n = 6, 66.6%). An age of fewer than 55 years at the time of total knee arthroplasty had a significant influence on implant survival (p = 0.018) with superior survival in favor of the older patient population. At most recent follow-up, a mean Knee Society Score of 82 points and an average Function Score of 77 points were observed. CONCLUSIONS Periprosthetic joint infection is the primary failure mechanism leading to a revision in patients with total knee arthroplasty for posttraumatic osteoarthritis. Apart from the increased infection rate, total knee arthroplasties in patients with posttraumatic osteoarthritis revealed results that were comparable to patients with primary osteoarthritis. Key words:posttraumatic knee osteoarthritis, total knee replacement, survival, complications, revision, outcome.


Assuntos
Artroplastia do Joelho/efeitos adversos , Traumatismos do Joelho/cirurgia , Articulação do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Assistência ao Convalescente , Idoso , Artrite Infecciosa/complicações , Artroplastia do Joelho/mortalidade , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Taxa de Sobrevida
14.
Ann Oncol ; 28(6): 1352-1358, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28327958

RESUMO

BACKGROUND: Novel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of risk factors (RFs) for survival after ASCT. METHODS: In this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resulting prognostic score was then validated in an independent clinical sample (part II). RESULTS: In part I, we identified 656 patients treated for relapsed/refractory HL between 1993 and 2013 with a median follow-up of 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy [

Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Análise de Sobrevida , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Fatores de Risco
15.
Ann Oncol ; 28(6): 1359-1367, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28327908

RESUMO

BACKGROUND: Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. PATIENTS AND METHODS: We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards. RESULTS: Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status. CONCLUSION: Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT00003835.


Assuntos
Neoplasias do Colo/patologia , Recidiva Local de Neoplasia , Vitamina D/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/sangue , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Strahlenther Onkol ; 193(2): 100-108, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27678010

RESUMO

INTRODUCTION: Field design changed substantially from extended-field RT (EF-RT) to involved-field RT (IF-RT) and now to involved-node RT (IN-RT) and involved-site RT (IS-RT) as well as treatment techniques in radiotherapy (RT) of Hodgkin's lymphoma (HL). The purpose of this article is to demonstrate the establishment of a quality assurance program (QAP) including modern RT techniques and field designs within the German Hodgkin Study Group (GHSG). METHODS: In the era of modern conformal RT, this QAP had to be fundamentally adapted and a new evaluation process has been intensively discussed by the radiotherapeutic expert panel of the GHSG. RESULTS: The expert panel developed guidelines and criteria to analyse "modern" field designs and treatment techniques. This work is based on a dataset of 11 patients treated within the sixth study generation (HD16-17). CONCLUSION: To develop a QAP of "modern RT", the expert panel defined criteria for analysing current RT procedures. The consensus of a modified QAP in ongoing and future trials is presented. With this schedule, the QAP of the GHSG could serve as a model for other study groups.


Assuntos
Fidelidade a Diretrizes/estatística & dados numéricos , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/radioterapia , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Radioterapia (Especialidade)/normas , Radioterapia Conformacional/normas , Alemanha/epidemiologia , Fidelidade a Diretrizes/normas , Humanos , Prevalência , Radioterapia Conformacional/estatística & dados numéricos , Fatores de Risco , Integração de Sistemas , Resultado do Tratamento
17.
Strahlenther Onkol ; 193(2): 109-115, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27596217

RESUMO

INTRODUCTION: As part of the foundation of the German Hodgkin Study Group (GHSG) in 1978, a central radiotherapy (RT) reference centre was established to evaluate and to improve the quality of treatment. During the study generations, the quality assurance programs (QAP) were continued and adapted to the demands of each study. The purpose of this article is to demonstrate the results of the fifth study generation and to compare them to the previous findings. METHODS: With the start of the fourth GHSG study generation (HD10-12), a central prospective review of all diagnostic images was established to create an individual treatment plan for each early stage study patient. The quality of involved field RT was retrospectively evaluated by an expert panel of radiation oncologists. In the fifth study generation (HD13-15), the retrospective review of radiotherapy performed was refined and the results were compared with the findings of the fourth generation. RESULTS: The expert panel analyzed the RT planning and application of 1037 (28 %) patients (HD13 n = 465, HD14 n = 572). Simulation films were available in 85 % of cases and verification films in 87 %. RT was assessed as major violation in 46 % (HD13 = 38 %, HD14 = 52 %), minor violation in 9 % (HD13 = 9 %, HD14 = 9 %) and according to the protocol in 45 % (HD13 = 52 %, HD14 = 38 %). CONCLUSION: The value for QAP of RT within the GHSG trials is well known. Still there were several protocol violations. In the future, the QAP program has to be adapted to the requirements of "modern RT" in malignant lymphoma.


Assuntos
Fidelidade a Diretrizes/estatística & dados numéricos , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/radioterapia , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Radioterapia Conformacional/normas , Alemanha/epidemiologia , Fidelidade a Diretrizes/normas , Humanos , Prevalência , Radioterapia (Especialidade)/normas , Radioterapia Conformacional/estatística & dados numéricos , Fatores de Risco , Integração de Sistemas , Resultado do Tratamento
18.
Pathologe ; 38(6): 529-534, 2017 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-28676898

RESUMO

BACKGROUND: Central collection of tissue blocks for pathological and translational research is particularly important in rare diseases. Transfer of tissue blocks from primary to central pathology is of crucial importance. OBJECTIVES: We aimed to answer the following questions: Has the transfer of tissue blocks sent for consultation or within clinical trials changed over the last 20 years? What are the reasons for reclaiming tissue blocks by the primary pathology and what actions would convince primary pathologists to leave the blocks in the reference pathology? MATERIAL AND METHODS: The first 100 biopsies of each year between 1995 and 2015 (n = 2100), as well as all tissue transfers within therapeutic studies (n = 1405, German Hodgkin Study Group, GHSG) between 1998 and 2015, were analyzed separately for block reclaims using the Department of Pathology database. A questionnaire evaluated the reasons for block reclaiming by the peripheral pathologists. RESULTS: There is a significant increase in block reclaims during the period analyzed among submissions for consultation as well as in clinical trials (linear regression, p = 0.0195 and p = 0.0107). The percentage of block reclaims does not differ between consultations and cases submitted upon request within clinical trials (p = 0.2404, t-test). A survey among pathologies that reclaim the block showed that their willingness to leave the block at the reference center would increase if the compatibility with accreditation guidelines (39.3%), a positive statement from professional associations (25%), or a formal confirmation of availability (53.6%) is provided. DISCUSSION: In particular, to improve research on rare diseases, it is desirable to point out the compatibility of central archiving in a designated center with accreditation guidelines.


Assuntos
Doença de Hodgkin/patologia , Linfonodos/patologia , Inclusão em Parafina , Alemanha , Humanos , Sistema de Registros , Inquéritos e Questionários
19.
Acta Chir Orthop Traumatol Cech ; 84(5): 341-346, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29351534

RESUMO

PURPOSE OF THE STUDY The postoperative outcomes of total hip replacement and hemiarthroplasty after femoral neck fractures in elderly patients were analysed to determine general and local complications as well as morbidity and mortality rates in order to detect risk profiles and assess the best individual treatment option. MATERIALS AND METHODS One hundred sixty-one femoral neck fractures among patients aged ≥ 65 years treated with cemented hemiarthroplasty (HA) or uncemented total hip arthroplasty (THA) between January 2005 and October 2013 were evaluated. In the presence of articular pathologies as well as a fracture type Garden III or IV, the indication for joint replacement was given. Criteria for performing hemiarthroplasty were previously limited mobility. Freely and fully mobilised patients and patients with manifested osteoarthritis received a cementless THA. A comparison of the observed complications was made, differentiating between general and surgery-specific hip-related complications. Furthermore, the mortality rates were analysed in relation to the respective surgical treatment. RESULTS Seventy cemented HA and ninety-one uncemented THA were performed. There was a high complication rate of approximately 19% in both surgical intervention groups. The patients were more likely to develop general complications (HA 12.8%; THA 10.8%) even though cardiopulmonary complications occurred more frequently in the cemented HA group. Four patients died after cemented hemiarthroplasty due to thromboembolic events (5.7% mortality rate), whereas no deaths occurred after total hip replacement. Surgery-specific complications rates were 7.8% in THA and 5.7% in HA patients. CONCLUSIONS THA in eldery patients with femoral neck fractures is associated with a higher complication rate, mostly of general medical entity. After cemented HA, our study reveals a high mortality rate due to thromboembolic events. For patients with multimorbidity in particular, these findings therefore suggest that uncemented THA should be considered to prevent lethal complications. Key words: femoral neck fracture; total hip arthroplasty; hemiarthroplasty; complications.


Assuntos
Artroplastia de Quadril/métodos , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia/métodos , Idoso , Artroplastia de Quadril/efeitos adversos , Cimentos Ósseos , Cimentação/efeitos adversos , Hemiartroplastia/efeitos adversos , Humanos , Complicações Pós-Operatórias , Análise de Sobrevida , Tromboembolia/etiologia
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