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PURPOSE: To prove the utility of magnetic resonance (MR) imaging response as a surrogate end point of treatment efficacy and survival after yttrium-90 transarterial radioembolization (TARE) for colorectal liver metastases (CRLMs), and to investigate whether outcomes can be predicted at baseline using MR imaging or clinical variables. MATERIALS AND METHODS: A total of 50 (135) patients with TARE for CRLMs between August 2008 and January 2020 and peri-interventional MR imaging within defined timeframes were included for tumor segmentation. Pretreatment and posttreatment target tumor volumes were measured according to the volumetric Response Evaluation Criteria In Solid Tumors (vRECIST) and the quantitative European Association for the Study of the Liver (qEASL) criteria. Cox regression models were used to analyze the impact of MR morphologic response, vascularity at baseline, and clinical variables on patient survival. Logistic regression analyses were used to evaluate the predictors of MR morphologic response at baseline. RESULTS: The median survival was 337 days (95% confidence interval [CI], 243-431). As opposed to the vRECIST, the application of the qEASL criteria 3 months after the treatment allowed for a significant (P < .05) separation of the survival curves for partial response, stable disease, and progressive disease with a median survival of 412 days (95% CI, 57-767) in responders. High tumor burden and technetium-99m lung shunt significantly decreased the probability of survival. MR morphologic response was not predictable at baseline using imaging or clinical data. CONCLUSIONS: MR response according to the qEASL criteria outperformed the vRECIST in measuring the biologic impact of TARE and predicting patient survival. Baseline contrast enhancement did not predict MR response to treatment, which may reflect elevated dose requirements in tumors with a high proportion of viable tumor volume.
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Neoplasias Colorretais , Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Radioisótopos de Ítrio/efeitos adversos , Embolização Terapêutica/métodos , Imageamento por Ressonância Magnética/métodos , Resultado do Tratamento , Neoplasias Colorretais/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is an established method for pain relief. But electrical TENS currents are also a source of electromagnetic interference (EMI). Thus, TENS is considered to be contraindicated in implantable cardioverter-defibrillator (ICD) patients. However, data might be outdated due to considerable advances in ICD and cardiac resynchronization therapy (CRT) filtering and noise protection algorithm technologies. The aim of this pilot safety study was to re-evaluate the safety of TENS in patients with modern ICDs. METHODS AND RESULTS: One hundred and seven patients equipped with 55 different models of ICD/CRT with defibrillators from 4 manufacturers underwent a standardized test protocol including TENS at the cervical spine and the thorax, at 2 stimulation modes-high-frequency TENS (80â Hz) and burst-mode TENS (2â Hz). Potential interference monitoring included continuous documentation of ECG Lead II, intracardiac electrograms and the marker channel. Electromagnetic interference was detected in 17 of 107 patients (15.9%). Most frequent were: interpretations as a premature ventricular beats (VS/S) in 15 patients (14%), noise reversion in 5 (4.6%) which resulted in temporary asynchronous pacing in 3 (2.8%), interpretation as ventricular tachycardia/ventricular fibrillation in 2 (1.9%), and premature atrial beat in 2 (1.9%) patients. Electromagnetic interference occurrence was influenced by position (chest, P < 0.01), higher current intensity (P < 0.01), and manufacturer (P = 0.012). CONCLUSION: Overall, only intermittent and minor EMI were detected. Prior to the use of TENS in patients with ICDs, they should undergo testing under the supervision of a cardiac device specialist.
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Desfibriladores Implantáveis , Estimulação Elétrica Nervosa Transcutânea , Humanos , Manejo da Dor , Algoritmos , Fibrilação Ventricular , Fenômenos EletromagnéticosRESUMO
OBJECTIVES: This study aims to better characterize potential responders of Y-90-radioembolization at baseline through analysis of clinical variables and contrast enhanced (CE) MRI tumor volumetry in order to adjust therapeutic regimens early on and to improve treatment outcomes. METHODS: Fifty-eight HCC patients who underwent Y-90-radioembolization at our center between 10/2008 and 02/2017 were retrospectively included. Pre- and post-treatment target lesion volumes were measured as total tumor volume (TTV) and enhancing tumor volume (ETV). Survival analysis was performed with Cox regression models to evaluate 65% ETV reduction as surrogate endpoint for treatment efficacy. Univariable and multivariable logistic regression analyses were used to evaluate the combination of baseline clinical variables and tumor volumetry as predictors of ≥ 65% ETV reduction. RESULTS: Mean patients' age was 66 (SD 8.7) years, and 12 were female (21%). Sixty-seven percent of patients suffered from liver cirrhosis. Median survival was 11 months. A threshold of ≥ 65% in ETV reduction allowed for a significant (p = 0.04) separation of the survival curves with a median survival of 11 months in non-responders and 17 months in responders. Administered activity per tumor volume did predict neither survival nor ETV reduction. A baseline ETV/TTV ratio greater than 50% was the most important predictor of arterial devascularization (odds ratio 6.3) in a statistically significant (p = 0.001) multivariable logistic regression model. The effect size was strong with a Cohen's f of 0.89. CONCLUSION: We present a novel approach to identify promising candidates for Y-90 radioembolization at pre-treatment baseline MRI using tumor volumetry and clinical baseline variables. KEY POINTS: ⢠A decrease of 65% enhancing tumor volume (ETV) on follow-up imaging 2-3 months after Y-90 radioembolization of HCC enables the early prediction of significantly improved median overall survival (11 months vs. 17 months, p = 0.04). ⢠Said decrease in vascularization is predictable at baseline: an ETV greater than 50% is the most important variable in a multivariable logistic regression model that predicts responders at a high level of significance (p = 0.001) with an area under the curve of 87%.
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Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Embolização Terapêutica/métodos , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Masculino , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento , Radioisótopos de Ítrio/uso terapêuticoRESUMO
OBJECTIVE: Motor cortical dysfunction has been shown to be reversible in patients with unilateral atherosclerotic disease after cerebral revascularization. Moyamoya vasculopathy (MMV) is a rare bilateral stenoocclusive cerebrovascular disease. The aim of this study was to analyze the corticospinal excitability and the role of bypass surgery in restoring cortical motor function in patients by using navigated transcranial magnetic stimulation (nTMS). METHODS: Patients with bilateral MMV who met the criteria for cerebral revascularization were prospectively included. Corticospinal excitability, cortical representation area, and intracortical inhibition and facilitation were assessed by nTMS for a small hand muscle (first dorsal interosseous) before and after revascularization. The clinically and/or hemodynamically more severely affected hemisphere was operated first as the leading hemisphere. Intra- and interhemispheric differences were analyzed before and after direct or combined revascularization. RESULTS: A total of 30 patients with bilateral MMV were examined by nTMS prior to and after revascularization surgery. The corticospinal excitability was higher in the leading hemisphere compared with the non-leading hemisphere prior to revascularization. This hyperexcitability was normalized after revascularization as demonstrated in the resting motor threshold ratio of the hemispheres (preoperative median 0.97 [IQR 0.89-1.08], postoperative median 1.02 [IQR 0.94-1.22]; relative effect = 0.61, p = 0.03). In paired-pulse paradigms, a tendency for a weaker inhibition of the leading hemisphere was observed compared with the non-leading hemisphere. Importantly, the paired paradigm also demonstrated approximation of excitability patterns between the two hemispheres after surgery. CONCLUSIONS: The study results suggested that, in the case of a bilateral chronic ischemia, a compensation mechanism between both hemispheres seemed to exist that normalized after revascularization surgery. A potential role of nTMS in predicting the efficacy of revascularization must be further assessed.
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Revascularização Cerebral , Transtornos Cerebrovasculares , Doença de Moyamoya , Potencial Evocado Motor , Mãos , Humanos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Estimulação Magnética TranscranianaRESUMO
In the original publication of this article [1], the authors missed that reverse coding was necessary for the item "Do you work separate from your colleagues?" before calculating the scale 'social relations'. So they corrected the analysis accordingly. The results with the revised scale show that there are no longer any significant differences between nurses and physicians with regard to this scale.
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The underlying genetic mechanisms and early pathological events of children with primary cardiomyopathy (CMP) are insufficiently characterized. In this study, we aimed to characterize the mutational spectrum of primary CMP in a large cohort of patients ≤18 years referred to a tertiary center. Eighty unrelated index patients with pediatric primary CMP underwent genetic testing with a panel-based next-generation sequencing approach of 89 genes. At least one pathogenic or probably pathogenic variant was identified in 30/80 (38%) index patients. In all CMP subgroups, patients carried most frequently variants of interest in sarcomere genes suggesting them as a major contributor in pediatric primary CMP. In MYH7, MYBPC3, and TNNI3, we identified 18 pathogenic/probably pathogenic variants (MYH7 n = 7, MYBPC3 n = 6, TNNI3 n = 5, including one homozygous (TNNI3 c.24+2T>A) truncating variant. Protein and transcript level analysis on heart biopsies from individuals with homozygous mutation of TNNI3 revealed that the TNNI3 protein is absent and associated with upregulation of the fetal isoform TNNI1. The present study further supports the clinical importance of sarcomeric mutation-not only in adult-but also in pediatric primary CMP. TNNI3 is the third most important disease gene in this cohort and complete loss of TNNI3 leads to severe pediatric CMP.
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Cardiomiopatias/genética , Sequenciamento de Nucleotídeos em Larga Escala , Troponina I/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Família , Feminino , Feto/patologia , Regulação da Expressão Gênica , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Mutação/genética , Linhagem , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/genéticaRESUMO
Expansions of donor pools have a controversial impact on healthcare expenditures. The aim of this study was to investigate the emerging costs of expanded criteria donor (ECD) kidney transplantations (KT) and to identify independent risk factors for increased transplant-related costs. We present a retrospective explorative analysis of hospital costs and reimbursements of KTs performed between 2012 and 2016 in a German university hospital. A total of 174 KTs were examined, including 92 (52.9%) ECD organ transplantations. The ECD group comprised 43 (24.7%) 'old-for-old' transplantations. Median healthcare costs were 19 570 (IQR 18 735-27 405) in the standard criteria donor (SCD) group versus 25 478 (IQR 19 957-29 634) in the ECD group (+30%; P = 0.076). 'Old-for-old' transplantations showed the highest healthcare expenditures [26 702 (19 570-33 940)]. Irrespective of the allocation group, transplant-related costs increased significantly in obese (+6221; P = 0.009) and elderly recipients (+6717; P = 0.019), in warm ischaemia time exceeding 30 min (+3212; P = 0.009) and in kidneys with DGF or surgical complications (+8976 and +10 624; both P < 0.001). Transplantation of ECD organs is associated with incremental costs, especially in elderly and obese recipients. A critical patient selection, treatment of obesity before KT and keeping warm ischaemia times short seem to be crucial, in order to achieve a cost-effective KT regardless of the allocation group.
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Transplante de Rim/economia , Obtenção de Tecidos e Órgãos , Adulto , Idoso , Feminino , Humanos , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To revise the German guidelines and recommendations for ensuring Good Epidemiological Practice (GEP) that were developed in 1999 by the German Society for Epidemiology (DGEpi), evaluated and revised in 2004, supplemented in 2008, and updated in 2014. METHODS: The executive board of the DGEpi tasked the third revision of the GEP. The revision was arrived as a result of a consensus-building process by a working group of the DGEpi in collaboration with other working groups of the DGEpi and with the German Association for Medical Informatics, Biometry and Epidemiology, the German Society of Social Medicine and Prevention (DGSMP), the German Region of the International Biometric Society (IBS-DR), the German Technology, Methods and Infrastructure for Networked Medical Research (TMF), and the German Network for Health Services Research (DNVF). The GEP also refers to related German Good Practice documents (e.g. Health Reporting, Cartographical Practice in the Healthcare System, Secondary Data Analysis). RESULTS: The working group modified the 11 guidelines (after revision: 1 ethics, 2 research question, 3 study protocol and manual of operations, 4 data protection, 5 sample banks, 6 quality assurance, 7 data storage and documentation, 8 analysis of epidemiological data, 9 contractual framework, 10 interpretation and scientific publication, 11 communication and public health) and modified and supplemented the related recommendations. All participating scientific professional associations adopted the revised GEP. CONCLUSIONS: The revised GEP are addressed to everyone involved in the planning, preparation, execution, analysis, and evaluation of epidemiological research, as well as research institutes and funding bodies.
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Estudos Epidemiológicos , Guias como Assunto , Alemanha , Humanos , Sociedades MédicasRESUMO
BACKGROUND: Promoting patient and occupational safety are two key challenges for hospitals. When aiming to improve these two outcomes synergistically, psychosocial working conditions, leadership by hospital management and supervisors, and perceptions of patient and occupational safety climate have to be considered. Recent studies have shown that these key topics are interrelated and form a critical foundation for promoting patient and occupational safety in hospitals. So far, these topics have mainly been studied independently from each other. The present study investigated hospital staffs' perceptions of four different topics: (1) psychosocial working conditions, (2) leadership, (3) patient safety climate, and (4) occupational safety climate. We present results from a survey in two German university hospitals aiming to detect differences between nurses and physicians. METHODS: We performed a cross-sectional study using a standardized paper-based questionnaire. The survey was conducted with nurses and physicians to assess the four topics. The instruments mainly consisted of scales of the German version of the COPSOQ (Copenhagen Psychosocial Questionnaire), one scale of the Copenhagen Burnout Inventory (CBI), scales to assess leadership and transformational leadership, scales to assess patient safety climate using the Hospital Survey on Patient Safety Culture (HSPSC), and analogous items to assess occupational safety climate. RESULTS: A total of 995 completed questionnaires out of 2512 distributed questionnaires were returned anonymously. The overall response rate was 39.6%. The sample consisted of 381 physicians and 567 nurses. We found various differences with regard to the four topics. In most of the COPSOQ and the HSPSC-scales, physicians rated psychosocial working conditions and patient safety climate more positively than nurses. With regard to occupational safety, nurses indicated higher occupational risks than physicians. CONCLUSIONS: The WorkSafeMed study combined the assessment of the four topics psychosocial working conditions, leadership, patient safety climate, and occupational safety climate in hospitals. Looking at the four topics provides an overview of where improvements in hospitals may be needed for nurses and physicians. Based on these results, improvements in working conditions, patient safety climate, and occupational safety climate are required for health care professionals in German university hospitals - especially for nurses.
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Pessoal de Saúde/psicologia , Liderança , Segurança do Paciente , Gestão da Segurança , Adulto , Idoso , Esgotamento Profissional , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVEMoyamoya vasculopathy (MMV) is a steno-occlusive cerebrovascular disease that can be treated by a surgical revascularization. All the revascularization techniques influence the blood supply of the scalp, with a risk for wound healing disorders. The authors' aim was to analyze the wound healing process in the patients who underwent a direct or combined bypass surgery with a focus on different skin incisions.METHODSThe authors retrospectively identified all the patients with MMV who were treated surgically in their institution. Subsequently, they analyzed demographic data, clinical symptoms, surgical treatment, and detailed history of complications. Based on the evolution of their surgical techniques and the revascularization strategy to be used, the authors applied the following skin incisions: linear incision, curved incision, incomplete Y incision, and complete Y incision. Group comparisons regarding wound healing disorders were performed with significance testing using Fisher's exact test.RESULTSThe authors identified 172 patients with MMV (61.6% moyamoya disease, 7% unilateral moyamoya disease, 29.7% moyamoya syndrome, and 1.7% unilateral moyamoya syndrome), of whom 124 underwent bilateral operations. One-quarter of the patients were juveniles. A total of 236 hemispheres were included in the analysis, of which 27.9% were treated by a combined procedure with encephalomyosynangiosis. Overall, 5.1% major and 1.7% minor wound complications occurred. The overall wound complication rate was lower in direct revascularization compared to combined revascularization (3% vs 15.2%). The lowest incidence of wound healing disorders was found in the linear incision group for the parietal superficial temporal artery branch (1.6%), followed by the incomplete Y incision group for the frontal branch of the superficial temporal artery (3.8%) in the direct bypass group. In the combined revascularization cohort, major or minor wound disorders appeared in 14.3% and 4.8%, respectively, in the complete Y incision group and in 4.2% (for both major and minor) in the curved incision group. The complete Y incision caused significantly more wound healing disorders compared to the remaining incision types (17.1% vs 3.1%, p = 0.007).CONCLUSIONSWound healing disorders are one of the major complications of revascularization surgery. Their incidence depends on the revascularization strategy and skin incision applied, with a complete Y incision giving the worst results.
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Revascularização Cerebral/efeitos adversos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Ferida Cirúrgica/diagnóstico por imagem , Cicatrização/fisiologia , Adolescente , Adulto , Revascularização Cerebral/tendências , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Ferida Cirúrgica/complicações , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND AIMS: This study examined differences in personality, psychological distress, and stress coping in inflammatory bowel disease (IBD) depending on type of disease and disease activity. We compared patients suffering from Crohn's disease (CD) and ulcerative colitis (UC) with controls. While the literature is replete with distinctive features of the pathogenesis of IBD, the specific differences in psychological impairments are not well studied. METHODS: In this German national multicenter study, participants were recruited from 32 centers. Two hundred ninety-seven questionnaires were included, delivering vast information on disease status and psychological well-being based on validated instruments with a total of 285 variables. RESULTS: CD patients were more affected by psychological impairments than patients suffering from UC or controls. Importantly, patients with active CD scored higher in neuroticism (pâ<â0.01), psychological distress (pâ<â0.001) and maladaptive stress coping (escape, pâ=â0.03; rumination, pâ<â0.03), but less need for social support (pâ=â0.001) than controls. In contrast, patients suffering from active UC showed psychological distress (pâ<â0.04) and maladaptive coping (avoidance, pâ<â0.03; escape, pâ=â0.01). Patients in remission seemed to be less affected. In particular, patients with UC in remission were not inflicted by psychological impairments. The group of CD patients in remission however, showed insecurity (pâ<â0.01) and paranoid ideation (pâ=â0.04). CONCLUSIONS: We identified specific aspects of psychological impairment in IBD depending on disease and disease activity. Our results underscore the need for psychological support and treatment particularly in active CD.
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Adaptação Psicológica , Colite Ulcerativa/psicologia , Doença de Crohn/psicologia , Pacientes/psicologia , Estresse Psicológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Personalidade , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND AND HYPOTHESIS: Nonoperative treatment is standard for most diaphyseal clavicle fractures, but recent studies have demonstrated improved outcomes with operative treatment of displaced fractures. The objectives of this diagnostic study were to assess agreement of orthopaedic surgeons regarding their treatment preferences for diaphyseal clavicle fractures and to compare them with recent recommendations. Interobserver and intraobserver agreement in treatment decisions were hypothesized to be only slight. METHODS: Anonymized case vignettes of 50 acute diaphyseal clavicle fractures including medical history, physical examination findings, and radiographs were independently reviewed by 32 orthopaedic surgeons from the United States. Four treatment options were offered and decisions were compared with current treatment recommendations. Interobserver agreement was calculated using Fleiss' kappa coefficient. Average intraobserver agreement for surgeons who completed a retest review (minimum interval of 8 weeks) was calculated. RESULTS: Thirty-two surgeons completed the first round of reviewing and 27 completed the retest (mean interval, 22 weeks). Interobserver agreement was overall fair (kappa = 0.36) and moderate (kappa = 0.56) when operative options were compared with nonoperative options. Median intraobserver agreement was 74% for the 4 treatment options offered and 84% in deciding on operative vs. nonoperative means. Concordance with recent recommendations for operative vs. nonoperative treatment was seen in 91% of decisions (median). DISCUSSION AND CONCLUSIONS: Recent recommendations appear to have been adopted by a selected subgroup of U.S. orthopaedic surgeons, showing a surprisingly high median concordance of 91% in this study. However, only fair to moderate interobserver and intraobserver agreement was present, leaving potential for improvement.
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Clavícula/lesões , Fraturas Ósseas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Clavícula/diagnóstico por imagem , Competência Clínica , Tomada de Decisões , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Inquéritos e Questionários , Tomografia Computadorizada por Raios X/métodos , Adulto JovemRESUMO
Background: Due to modern therapies, survival in metastatic renal cell carcinoma (mRCC) has been significantly prolonged. Nevertheless, patients suffering from advanced disease often present with severe symptoms. Early integration of palliative care into anti-cancer treatment has been shown to improve quality of life and may even prolong survival. Therefore, it is recommended to offer palliative care to patients with complex symptoms at the beginning of an advanced disease stage. To our knowledge, so far, no study has been conducted to examine the role of palliative care in patients with mRCC. Objectives: This study aimed to assess the symptom burden and quality of life before and after an inpatient palliative care treatment. Design: The study design is a retrospective observational study. Methods: We included patients with mRCC, who were admitted to our palliative care unit between 2011 and 2017 due to severe symptoms. The symptom burden was assessed at admission, throughout treatment, and at discharge. The evaluation consisted of the palliative care base assessment and daily documentation of relevant symptoms. Results: We evaluated 110 hospitalizations of 58 RCC patients. On average, patients were admitted to the palliative care unit 7 years after initial diagnosis (range 1-305 months). The median age was 70.5 years, 69% of the patients were male, 3% female. The main causes for admission were pain (52%) and dyspnea (26%), and the most frequent patient-reported symptoms were fatigue/exhaustion (87%), weakness (83%), and need for assistance with activities of daily living (83%). Multidisciplinary palliative care treatment led to a significant reduction in the median minimal documentation system (MIDOS) symptom score (15.6-9.9, p < 0.001), the median numeric pain rating scale (3-0, p < 0.001), and a significant reduction in mean ratings of the distress thermometer (5.5-3.1, p = 0.016). Conclusion: Our analysis shows that the integration of palliative care treatment is effective throughout the disease in mRCC and could measurably reduce the symptom burden in our patient population. Palliative care should not be equated with end-of-life care but should rather be integrated throughout advanced disease, particularly as soon as a cure is impossible.
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Introduction: Surgical procedures in children are among the most commonly performed procedures in otolaryngology. Perioperative safety and documentation of complications are becoming increasingly important. This study investigates perioperative complications in a clinical cohort of children with adenotonsillar hyperplasia undergoing adenotonsillectomy using the standardized Dindo-Clavien reporting system. Patients and Methods: Retrospective evaluation of 402 children who underwent adenotonsillectomy between 2009 and 2015. Patient parameters including all perioperative complications were investigated. Results: In the study, 124 complications were found (106 mild, 16 severe). According to the Dindo-Clavien classification, 93 grade I, 15 grade II, 5 grade III, 11 grade IV and 0 grade V complications were documented. Complications were associated with additional diagnoses (p = 0.001), long-term medication intake (p = 0.003), duration of hospitalization (p < 0.001) and duration of surgery (p < 0.001), undergoing tonsillotomy (p = 0.022) or tonsillectomy (p < 0.001), differences in ASA score (p = 0.005) and differences in OSA-18 score (p = 0.011). Severe complications, classified as grade III and IV, were associated with premature birth (p = 0.026), additional diagnoses (p = 0.017), long-term medication intake (p < 0.001) and differences in ASA score (p =< 0.001). Conclusion: The Dindo-Clavien classification is a standardized reporting system which can also be used for surgical procedures in children with adenotonsillar hyperplasia. The system shows associations with clinical parameters and thus can help to identify subgroups at risk of severe complications.
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The genus Pestivirus within the family Flaviviridae comprises highly relevant animal pathogens such as bovine viral diarrhoea virus 1 and 2 (BVDV-1 and -2) classified into the two species Pestivirus A and Pestivirus B, respectively. First described in 2004, HoBi-like pestiviruses (HoBiPeV) represent emerging bovine pathogens that belong to a separate species (Pestivirus H), but share many similarities with BVDV-1 and -2. Additionally, two giraffe pestivirus (GPeV) strains both originating from Kenya represent another distinct species (Pestivirus G), whose members replicate very efficiently in bovine cells. In this study, we investigated the role of bovine complement regulatory protein 46 (CD46bov), the receptor of BVDV-1 and -2, in the entry of HoBiPeV and GPeV. For this purpose, bovine CD46-knockout and CD46-rescue cell lines were generated by CRISPR/Cas9 technology and subsequent trans-complementation, respectively. Our results provide strong evidence that the impact of CD46bov differs between viruses belonging to Pestivirus H and viruses representing Pestivirus G: CD46bov revealed to be a major cellular entry factor for HoBiPeV strain HaVi-20. In contrast, GPeV strain PG-2 presented as largely independent of CD46bov, suggesting a different entry mechanism involving other molecular determinants which remain to be identified. In addition, we demonstrated that, similar to BVDV-1 and -2, virus isolates of both Pestivirus H and Pestivirus G are able to adapt to cell culture conditions by using heparan sulfate to enter the host cell. In conclusion, our findings show that different bovine pestiviruses use diverse mechanisms of host cell entry.
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Doença das Mucosas por Vírus da Diarreia Viral Bovina/metabolismo , Vírus da Diarreia Viral Bovina/fisiologia , Proteína Cofatora de Membrana/metabolismo , Receptores Virais/metabolismo , Animais , Doença das Mucosas por Vírus da Diarreia Viral Bovina/genética , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Bovinos , Linhagem Celular , Vírus da Diarreia Viral Bovina/classificação , Vírus da Diarreia Viral Bovina/genética , Proteína Cofatora de Membrana/genética , Receptores Virais/genética , Internalização do VírusRESUMO
OBJECTIVE: Cyberknife robotic radiosurgery (RRS) provides single-session high-dose radiotherapy of brain tumors with a steep dose gradient and precise real-time image-guided motion correction. Although RRS appears to cause more radiation necrosis (RN), the radiometabolic changes after RRS have not been fully clarified. 18F-FET-PET/CT is used to differentiate recurrent tumor (RT) from RN after radiosurgery when MRI findings are indecisive. We explored the usefulness of dynamic parameters derived from 18F-FET PET in differentiating RT from RN after Cyberknife treatment in a single-center study population. METHODS: We retrospectively identified brain tumor patients with static and dynamic 18F-FET-PET/CT for suspected RN after Cyberknife. Static (tumor-to-background ratio) and dynamic PET parameters (time-activity curve, time-to-peak) were quantified. Analyses were performed for all lesions taken together (TOTAL) and for brain metastases only (METS). Diagnostic accuracy of PET parameters (using mean tumor-to-background ratio >1.95 and time-to-peak of 20 min for RT as cut-offs) and their respective improvement of diagnostic probability were analyzed. RESULTS: Fourteen patients with 28 brain tumors were included in quantitative analysis. Time-activity curves alone provided the highest sensitivities (TOTAL: 95%, METS: 100%) at the cost of specificity (TOTAL: 50%, METS: 57%). Combined mean tumor-to-background ratio and time-activity curve had the highest specificities (TOTAL: 63%, METS: 71%) and led to the highest increase in diagnosis probability of up to 16% p. - versus 5% p. when only static parameters were used. CONCLUSIONS: This preliminary study shows that combined dynamic and static 18F-FET PET/CT parameters can be used in differentiating RT from RN after RRS.
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Neoplasias Encefálicas , Lesões por Radiação , Radiocirurgia , Procedimentos Cirúrgicos Robóticos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Radioisótopos de Flúor , Humanos , Necrose/diagnóstico por imagem , Necrose/etiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , TirosinaRESUMO
Aim: The most suitable method for assessment of response to peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET) is still under debate. In this study we aimed to compare size (RECIST 1.1), density (Choi), Standardized Uptake Value (SUV) and a newly defined ZP combined parameter derived from Somatostatin Receptor (SSR) PET/CT for prediction of both response to PRRT and overall survival (OS). Material and Methods: Thirty-four NET patients with progressive disease (F:M 23:11; mean age 61.2 y; SD ± 12) treated with PRRT using either Lu-177 DOTATOC or Lu-177 DOTATATE and imaged with Ga-68 SSR PET/CT approximately 10-12 weeks prior to and after each treatment cycle were retrospectively analyzed. Median duration of follow-up after the first cycle was 63.9 months (range 6.2-86.2). A total of 77 lesions (2-8 per patient) were analyzed. Response assessment was performed according to RECIST 1.1, Choi and modified EORTC (MORE) criteria. In addition, a new parameter named ZP, the product of Hounsfield unit (HU) and SUVmean (Standard Uptake Value) of a tumor lesion, was tested. Further, SUV values (max and mean) of the tumor were normalized to SUV of normal liver parenchyma. Tumor response was defined as CR, PR, or SD. Gold standard for comparison of baseline parameters for prediction of response of individual target lesions to PRRT was change in size of lesions according to RECIST 1.1. For prediction of overall survival, the response after the first and second PRRT were tested. Results: Based on RECIST 1.1, Choi, MORE, and ZP, 85.3%, 64.7%, 61.8%, and 70.6% achieved a response whereas 14.7%, 35.3%, 38.2%, and 29.4% demonstrated PD (progressive disease), respectively. Baseline ZP and ZPnormalized were found to be the only parameters predictive of lesion progression after three PRRT cycles (AUC ZP 0.753; 95% CI 0.6-0.9, p 0.037; AUC ZPnormalized 0.766; 95% CI 0.6-0.9; p 0.029). Based on a cut-off-value of 1201, ZP achieved a sensitivity of 86% and a specificity of 67%, while ZPnormalized reached a sensitivity of 86% and a specificity of 76% at a cut-off-value of 198. Median OS in the total cohort was not reached. In univariate analysis amongst all parameters, only patients having progressive disease according to MORE after the second cycle of PRRT were found to have significantly shorter overall survival (median OS in objective responders not reached, in PD 29.2 months; p 0.015). Patients progressive after two cycles of PRRT according to ZP had shorter OS compared to those responding (median OS for responders not reached, for PD 47.2 months, p 0.066). Conclusions: In this explorative study, we showed that Choi, RECIST 1.1, and SUVmax-based response evaluation varied significantly from each other. Only patients showing progressive disease after two PRRT cycles according to MORE criteria had a worse prognosis while baseline ZP and ZPnormalized performed best in predicting lesion progression after three cycles of PRRT.
RESUMO
BACKGROUND: Anthracycline cardiomyopathy is of concern in children treated for acute myeloid leukaemia (AML), but there are few data on the incidence and natural history of cardiotoxicity after AML treatment in the United Kingdom, where regimens have included high anthracycline exposure. PROCEDURE: Prevalence and predictors of cardiotoxicity were retrospectively reviewed in 124 children treated on the MRC AML 10 and AML 12 trials in a single, large centre from November 1987 to September 2004. Subclinical cardiotoxicity was defined as a shortening fraction of less than 28% and clinical cardiomyopathy as evidence of heart failure, and both were classified as late cardiotoxicity 1 year after completing first line therapy. RESULTS: Cumulative survival was 61% at 10 years. The prevalence of early and late cardiotoxicity was 13.7% (95%-CI: 8.2-22.0%) and 17.4% (95%-CI: 10.9-26.8%), respectively. Early cardiotoxicity was a strong predictor (OR = 9.18; 95%-CI: 2.10-40.11; P < 0.005) and children who received salvage therapy following relapse showed a trend towards increased late cardiotoxicity (OR = 3.53; 95%-CI: 0.86-14.48; P < 0.08). Subclinical cardiotoxicity resolved spontaneously in all but one case, but clinical cardiomyopathy always required continuing therapy. Two children died of cardiomyopathy and six remained on medical therapy. CONCLUSIONS: Anthracycline cardiotoxicity remains a major concern for survivors of childhood AML and correlates with early cardiotoxicity and treatment intensity. Long-term follow-up is required to fully determine the outcome for children with subclinical cardiotoxicity.
Assuntos
Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Cardiomiopatias/induzido quimicamente , Coração/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Cardiomiopatias/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Leucemia Mieloide Aguda/mortalidade , Masculino , Taxa de SobrevidaRESUMO
OBJECTIVES: Injury to major white matter pathways during language-area associated glioma surgery often leads to permanent loss of neurological function. The aim was to establish standardized tractography of language pathways as a predictor of language outcome in clinical neurosurgery. METHODS: We prospectively analyzed 50 surgical cases of patients with left perisylvian, diffuse gliomas. Standardized preoperative Diffusion-Tensor-Imaging (DTI)-based tractography of the 5 main language tracts (Arcuate Fasciculus [AF], Frontal Aslant Tract [FAT], Inferior Fronto-Occipital Fasciculus [IFOF], Inferior Longitudinal Fasciculus [ILF], Uncinate Fasciculus [UF]) and spatial analysis of tumor and tracts was performed. Postoperative imaging and the resulting resection map were analyzed for potential surgical injury of tracts. The language status was assessed preoperatively, postoperatively and after 3 months using the Aachen Aphasia Test and Berlin Aphasia Score. Correlation analyses, two-step cluster analysis and binary logistic regression were used to analyze associations of tractography results with language outcome after surgery. RESULTS: In 14 out of 50 patients (28%), new aphasic symptoms were detected 3 months after surgery. The preoperative infiltration of the AF was associated with functional worsening (cc = 0.314; p = 0.019). Cluster analysis of tract injury profiles revealed two areas particularly related to aphasia: the temporo-parieto-occipital junction (TPO; temporo-parietal AF, middle IFOF, middle ILF) and the temporal stem/peri-insular white matter (middle IFOF, anterior ILF, temporal UF, temporal AF). Injury to these areas (TPO: OR: 23.04; CI: 4.11 - 129.06; temporal stem: OR: 21.96; CI: 2.93 - 164.41) was associated with a higher-risk of persisting aphasia. CONCLUSIONS: Tractography of language pathways can help to determine the individual aphasia risk profile pre-surgically. The TPO and temporal stem/peri-insular white matter were confirmed as functional nodes particularly sensitive to surgical injuries.
Assuntos
Glioma , Idioma , Imagem de Tensor de Difusão , Glioma/diagnóstico por imagem , Glioma/cirurgia , Humanos , Vias Neurais , Medição de RiscoRESUMO
BACKGROUND: Stereotactic radiosurgery (SRS) is an effective treatment for trigeminal neuralgia (TN). Nevertheless, a proportion of patients will experience recurrence and treatment-related sensory disturbances. In order to evaluate the predictors of efficacy and safety of image-guided non-isocentric radiosurgery, we analyzed the impact of trigeminal nerve volume and the nerve dose/volume relationship, together with relevant clinical characteristics. METHODS: Two-hundred and ninety-six procedures were performed on 262 patients at three centers. In 17 patients the TN was secondary to multiple sclerosis (MS). Trigeminal pain and sensory disturbances were classified according to the Barrow Neurological Institute (BNI) scale. Pain-free-intervals were investigated using Kaplan Meier analyses. Univariate and multivariate Cox regression analyses were performed to identify predictors. RESULTS: The median follow-up period was 38 months, median maximal dose 72.4 Gy, median target nerve volume 25 mm3, and median prescription dose 60 Gy. Pain control rate (BNI I-III) at 6, 12, 24, 36, 48, and 60 months were 96.8, 90.9, 84.2, 81.4, 74.2, and 71.2%, respectively. Overall, 18% of patients developed sensory disturbances. Patients with volume ≥ 30 mm3 were more likely to maintain pain relief (p = 0.031), and low integral dose (< 1.4 mJ) tended to be associated with more pain recurrence than intermediate (1.4-2.7 mJ) or high integral dose (> 2.7 mJ; low vs. intermediate: log-rank test, χ2 = 5.02, p = 0.019; low vs. high: log-rank test, χ2 = 6.026, p = 0.014). MS, integral dose, and mean dose were the factors associated with pain recurrence, while re-irradiation and MS were predictors for sensory disturbance in the multivariate analysis. CONCLUSIONS: The dose to nerve volume ratio is predictive of pain recurrence in TN, and re-irradiation has a major impact on the development of sensory disturbances after non-isocentric SRS. Interestingly, the integral dose may differ significantly in treatments using apparently similar dose and volume constraints.