ABSTRACT
BACKGROUND: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. PATIENTS AND METHODS: Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients' individual risk of event. RESULTS: ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status [diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS)]. At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression. CONCLUSIONS: The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway.
Subject(s)
Biomarkers, Tumor , Bone Neoplasms , Circulating Tumor DNA , Osteosarcoma , Humans , Osteosarcoma/genetics , Osteosarcoma/blood , Osteosarcoma/pathology , Osteosarcoma/surgery , Osteosarcoma/mortality , Osteosarcoma/diagnosis , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , Male , Female , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Bone Neoplasms/blood , Bone Neoplasms/surgery , Bone Neoplasms/mortality , Adult , Adolescent , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Prospective Studies , Young Adult , Child , DNA Copy Number Variations , Neoplasm Grading , Middle Aged , Whole Genome Sequencing , Progression-Free SurvivalABSTRACT
INTRODUCTION: Sleep-disordered breathing (SDB) and non-alcoholic fatty liver disease (NAFLD) are both common comorbidities in obese patients. Structured weight loss programs are effective and can reduce the incidence and severity of obesity-related comorbidities. The objective of the present analysis is to test whether weight loss induced alleviation of SDB is a predictor for improvement of NAFLD. METHODS: Obese participants underwent a standardized non-surgical 3 months weight reduction program (800 kilocalories per day with low carbohydrate and fat content). Abdominal sonography for NAFLD (grade 0 to 3) and monitoring for SDB (defined as apnea-hypopnea index [AHI] ≥ 15/h) were performed at baseline and after 3 months. Alleviation of SDB was defined as a shift from AHI≥ 15/h to <15/h. RESULTS: 48 patients (48% female, age 42 ± 12 years, body-mass index 40.3 ± 8.1 kg/m2, AHI 14 ± 17/h, 85% NAFLD grade ≥1) participated in the weight loss program. In contrast to the no SDB group, in patients with SDB weight loss of 27.1 ±0 .9 kg (8.4 ± 2.8 kg/m2) after three months was paralleled by a reduction in AHI (-22 ± 17/h), prevalence of SDB (from 31% to 13%), and oxidized low-density lipoprotein (-13 ± 11 U/l). In individuals with preexisting SDB NAFLD grade improved more (2 versus 1, p<0.001) and was at a lower degree at 3 months than in those without SDB (0 versus 1, p = 0.015). In multivariable analysis models, SDB at baseline was associated with improvement of NAFLD grade (B 0.908; 95% CI 0.125, 1.691; p = 0.024), independently of age, sex, and BMI (each p>0.05, respectively). Decreasing BMI (B 0.16 [95%-CI 0.08; 0.23], p<0.001) and alleviation of SDB (B 0.90 [95%-CI 0.21; 1.58], p = 0.012) were independently associated with improvement of NAFLD grade. CONCLUSION: Preexisting SDB and weight loss induced alleviation of SDB are predictors for improvement in NAFLD grade, independent of the extent of weight loss. SDB may contribute to the pathogenesis of NAFLD via SDB-induced oxidative stress and inflammation, but the causal mechanism remains unclear.
Subject(s)
Non-alcoholic Fatty Liver Disease , Sleep Apnea Syndromes , Humans , Female , Adult , Middle Aged , Male , Non-alcoholic Fatty Liver Disease/complications , Polysomnography , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/therapy , Sleep Apnea Syndromes/epidemiology , Obesity/complications , Weight LossABSTRACT
Veterinary and para-veterinary professionals working in the animal research sector are critical to ensure scientific quality and the humane care and use of animals. However, there are few focused education and training opportunities available for these professionals in South Africa. A survey of veterinarians working in animal research, undertaken by the South African Association for Laboratory Animal Science, identified the need for more advanced education and training opportunities beyond the routine Day 1 Skills currently provided for in undergraduate education. These could be broadly categorised into knowledge and skills relating to species-specific husbandry, procedures and clinical approaches, research-related biosecurity and biosafety, and study-specific ethical and animal welfare considerations. A subsequent workshop, attended by 85 veterinary and para-veterinary professionals in the animal research sector, identified 53 life-long learning needs, each with an associated learning outcome, for this professional community. These were grouped into five overarching themes: Personal development (9); Leadership and management skills (12); Education and training skills (5); Welfare, ethics and clinical skills (20); and Regulations and quality-assurance (7). Of the 53 learning outcomes, 14 were knowledge-based, ten were competencies, and 29 both knowledge and competence. These life-long learning opportunities, if available and implemented, will address important needs of veterinary and paraveterinary professionals in the animal research sector in South Africa. This would empower these professionals, assist in improving animal and human wellbeing, support high-quality ethical science, and maintain public confidence in the sector, thus enabling a more satisfactory career environment.
ABSTRACT
Education and training is essential for laboratory animal caretakers (LACs), but there are no courses available in South Africa. A national workshop was thus held to collaboratively establish the learning outcomes (LOs) for the education and training (E&T) of LACs. Eighty-five stakeholders from 30 institutions took part in small group discussions interspersed with plenary sessions to draw up the consensus LOs. One-hundred-and-twenty LOs were identified, grouped into the following three main themes and 15 topics: 1) Focus on animals (animal care and husbandry, animal ethics, animal welfare, basic biology, environment); 2) Focus on humans (administration, health and safety, lifelong learning, professionalism, psychological wellbeing); and 3) Focus on systems (biosecurity, equipment, jurisprudence, logistics, and quality management). This E&T framework provides a foundation for a career path in the laboratory animal science field. The psychological (i.e. mental and emotional) wellbeing of LACs forms a noteworthy component of the focus on humans, since working with research animals is stressful and coping mechanisms are needed in order to promote compassion satisfaction and prevent compassion fatigue and burnout. Approximately 75% of the LOs are knowledge-based, while 25% are competencies in practical skills. It is recommended that competencies should be assessed by direct observation of practical/procedural skills, where competence in a procedure or practical task is assessed against predetermined criteria. These LOs are published with the intent that they will promote animal and human wellbeing, support ethical science, maintain public confidence, and in so doing, contribute to a just and civilised society.
ABSTRACT
SARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; androgen receptor activation increases TMPRSS2 levels in various tissues, most notably prostate. We show here that treatment with the antiandrogen enzalutamide-a well-tolerated drug widely used in advanced prostate cancer-reduces TMPRSS2 levels in human lung cells and in mouse lung. Importantly, antiandrogens significantly reduced SARS-CoV-2 entry and infection in lung cells. In support of this experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2, including in specific lung cell types targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.
Subject(s)
Androgen Antagonists/pharmacology , Benzamides/pharmacology , COVID-19 Drug Treatment , Nitriles/pharmacology , Phenylthiohydantoin/pharmacology , Serine Endopeptidases/metabolism , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/chemical synthesis , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/metabolism , COVID-19/virology , Down-Regulation/drug effects , Female , Humans , Lung/metabolism , Lung/virology , Male , Mice , SARS-CoV-2/drug effects , Serine Endopeptidases/geneticsABSTRACT
Diet-induced obesity and metabolic syndrome are associated with the onset of gastrointestinal diseases, such as hepatic steatosis and gut inflammation. Prior research shows that a proprietary soil-derived organic mineral complex (OMC) prevents hyperglycemia, endotoxemia, and liver injury in rats fed a high-fat diet (HFD) for 10 weeks. The aim of this study was to further examine the effects of OMC on the liver and gastrointestinal health of these rats. Six-week-old male Sprague-Dawley rats (n = 36) were divided into two dietary groups: Chow or HFD fed for 10 weeks. Animals were further divided (n = 6/group) and administered 0, 0.6, or 3.0 mg/mL OMC in their drinking water. The 10-week HFD resulted in significant liver fat accumulation. Both OMC doses prevented hepatic increases in the glycation end product Nε-(carboxymethyl)lysine (CML) induced by HFD (p < 0.05). Low-dose OMC was associated with higher expression of occludin in the small intestine of rats fed either diet (two-way ANOVA, p < 0.042). Linear discriminant analysis (LDA) effect size (LEfSe) indicated significant differences in fecal microbial composition of untreated HFD-fed rats in comparison to untreated Chow rats at 10 weeks (LDA score > 2.0 : 18). After 10 weeks, untreated HFD-fed rats were also more abundant in bacteria associated with obesity and metabolic disease in comparison to corresponding week 0 samples (LDA score > 2.0 : 31), 10-week untreated Chow (LDA > 2.0 : 18), or 10-week OMC-treated HFD-fed rats (0.6 mg/mL; LDA > 2.0 : 80, 3.0 mg/mL; LDA > 2.0 : 8). Low-dose OMC prevented the HFD-induced increase in the Firmicutes-to-Bacteroidetes (F/B) ratio (p < 0.0416). Study animals treated with OMC exhibited no significant changes in the gut microbiota at week 10, although gut inflammatory biomarkers were not significantly altered by diet or OMC treatment. These results indicate that OMC supplementation ameliorates glycosylation reactions and modifies HFD-induced alterations in the intestinal microbiota.
ABSTRACT
OBJECTIVES: National and international guidelines recommend empiric first-line treatments of individuals infected with Helicobacter pylori without prior antimicrobial susceptibility testing. For this reason, knowledge of primary resistance to first-line antibiotics such as clarithromycin is essential. We assessed the primary resistance of H. pylori in Germany to key antibiotics by molecular genetic methods and evaluated risk factors for the development of resistance. METHODS: Gastric tissue samples of 1851 yet treatment-naïve H. pylori-positive patients were examined with real-time PCR or PCR and Sanger sequencing for mutations conferring resistance to clarithromycin, levofloxacin and tetracycline. Clinical and epidemiological data were documented and univariable and multivariable logistic regression analyses were conducted. RESULTS: Overall primary resistances were 11.3% (210/1851) to clarithromycin, and 13.4% (201/1497) to levofloxacin; resistance to tetracycline (2.5%, 38/1497) was as low as combined resistance to clarithromycin/levofloxacin (2.6%, 39/1497). Female sex and prior antimicrobial therapies owing to unrelated bacterial infections were risk factors for clarithromycin resistance (adjusted OR (aOR) 2.3, 95% CI 1.6-3.4; and 2.6, 95% CI 1.5-4.5, respectively); older age was associated with levofloxacin resistance (aOR for those ≥65 years compared with those 18-35 years: 6.6, 95% CI 3.1-14.2). CONCLUSIONS: Clarithromycin might still be recommended in first-line eradication therapies in yet untreated patients, but as nearly every tenth patient may carry clarithromycin-resistant H. pylori it may be advisable to rule out resistance ahead of treatment by carrying out susceptibility testing or prescribing an alternative therapy.
Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Helicobacter pylori/drug effects , Adolescent , Adult , Age Factors , Aged , Clarithromycin/pharmacology , Female , Germany/epidemiology , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Humans , Levofloxacin/pharmacology , Male , Microbial Sensitivity Tests , Middle Aged , Mutation , Risk Factors , Sex Factors , Tetracycline/pharmacology , Young AdultABSTRACT
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but aggressive form of skin cancer in which Merkel cell polyomavirus infection and chronic exposure to ultraviolet radiation are key risk factors. Immune checkpoint inhibition has revolutionized the treatment of locally advanced, inoperable and metastatic MCC. AIM: To outline the modern management of MCC based on advances in our understanding of MCC tumour biology and the development of immune checkpoint inhibitors, namely inhibitors of programmed cell death protein (PD)-1- and PD1 ligand 1 (PD-L1). METHODS: A review of the scientific literature listed in PubMed. RESULTS: First line therapy with the PD-L1 blocking antibody avelumab is associated with a response rate of 62%. In the second line setting, for example after chemotherapy, the response rate only reaches 33%. However, in patients who responded in the second line setting, 69% remained relapse free after 2 years. Treatment responses occurred on average after 6.1 weeks of therapy. First line treatment with pembrolizumab (anti-PD1 antibody) is associated with a 2-year survival rate of 69% and the median survival rate has not been reached. Whilst the various chemotherapy regimens are associated with similar response rates, these are typically short lived. DISCUSSION: Checkpoint inhibition offers an effective treatment option for patients with MCC. Avelumab is currently licensed as a treatment for metastatic disease. Chemotherapy remains an option to reduce tumor load, or in the context of resistance and/or contraindications to immune checkpoint therapy. Adjuvant and neoadjuvant use of checkpoint inhibition in MCC may represent a future treatment strategy pending the results of on-going clinical trials.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Carcinoma, Merkel Cell/drug therapy , Carcinoma, Merkel Cell/immunology , Skin Neoplasms/drug therapy , Skin Neoplasms/immunology , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Merkel Cell/pathology , Humans , Neoplasm Recurrence, Local , Skin Neoplasms/pathology , Treatment Outcome , Ultraviolet RaysABSTRACT
Pneumocystis jirovecii pneumonia (PcP) has for many years been reported mostly in human immunodeficiency virus-infected patients. Increasingly, it also affects other immunocompromised patients, e.g. after organ or allogeneic stem cell/bone marrow transplantation, patients with hematologic malignancies or autoimmune diseases. The diagnosis of PcP relies on a critical evaluation of clinical symptoms, risk factors, radiologic features and microbiological tests. High dose cotrimoxazole is the most effective therapeutic option. Rapid initiation is essential, since mortality is especially high in patients admitted to intensive care with respiratory failure. This article reviews the current epidemiology of PcP and highlights the diagnostic and therapeutic options. Recommendations for primary and secondary prophylaxis are summarized.
Subject(s)
HIV Infections/complications , Immunocompromised Host , Opportunistic Infections , Pneumocystis Infections/diagnosis , Pneumonia, Pneumocystis/diagnosis , Anti-Bacterial Agents/therapeutic use , Humans , Pneumocystis Infections/complications , Pneumocystis Infections/drug therapy , Pneumocystis carinii/isolation & purification , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/drug therapy , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic useABSTRACT
CD4+ regulatory T cells (Treg ) expressing the forkhead box protein 3 (FOXP3) transcription factor (Tregs ) are instrumental for the prevention of autoimmune diseases. There is increasing evidence that the human T regulatory population is highly heterogeneous in phenotype and function. Numerous studies conducted in human autoimmune diseases have shown that Treg cells are impaired either in their suppressive function, in number, or both. However, the contribution of the FOXP3+ Treg subpopulations to the development of autoimmunity has not been delineated in detail. Rare genetic disorders that involve deficits in Treg function can be studied to develop a global idea of the impact of partial or complete deficiency in a specific molecular mechanism involved in Treg function. In patients with reduced Treg numbers (but no functional deficiency), the expansion of autologous Treg cells could be a suitable therapeutic approach: either infusion of in-vitro autologous expanded cells, infusion of interleukin (IL)-2/anti-IL-2 complex, or both. Treg biology-based therapies may not be suitable in patients with deficits of Treg function, unless their deficit can be corrected in vivo/in vitro. Finally, it is critical to consider the appropriate stage of autoimmune diseases at which administration of Treg cellular therapy can be most effective. We discuss conflicting data regarding whether Treg cells are more effectual at preventing the initiation of autoimmunity, ameliorating disease progression or curing autoimmunity itself.
Subject(s)
Autoimmune Diseases/immunology , Forkhead Transcription Factors/immunology , Inflammation/immunology , T-Lymphocytes, Regulatory/immunology , Anemia, Pernicious/immunology , Animals , Autoimmune Diseases/genetics , Autoimmune Diseases/therapy , Autoimmunity , CTLA-4 Antigen/deficiency , CTLA-4 Antigen/genetics , CTLA-4 Antigen/immunology , Cell- and Tissue-Based Therapy/methods , Diabetes Mellitus, Type 1/congenital , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Diarrhea/genetics , Diarrhea/immunology , Forkhead Transcription Factors/genetics , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/immunology , Humans , Immune System Diseases/congenital , Immune System Diseases/genetics , Immune System Diseases/immunology , Immunotherapy/methods , Interleukin-2/immunology , Mice , Models, Immunological , T-Lymphocytes, Regulatory/classificationABSTRACT
BACKGROUND AND PURPOSE: Low-grade glioma (LGG) is a very common brain tumor in pediatric patients typically associated with a very good prognosis. This prognosis makes it imperative that the risk of long-term treatment-related side effects be kept at an absolute minimum. Proton therapy (PRT) provides a radiation technique that has the potential to further reduce the genesis of radiogenic impairment. MATERIALS AND METHODS: We retrospectively assessed 74 patients with LGG who underwent PRT. Conventional three-dimensional photon and PRT plans were generated after contouring structures of neurogenesis, crucial neuronal structures, and areas susceptible to secondary malignancies. Target volume coverage was evaluated using the homogeneity index (HI) and inhomogeneity coefficient (IC). Results were compared using the Wilcoxon-signed rank test, with p < 0.05 being statistically significant. RESULTS: Target volume coverage was comparable for the photon and proton plans. Overall, we could show an essential reduction in maximal, mean, and integral doses in critical neurologic structures, areas of neurogenesis, and structures of neurocognitive function. The study indicated specifically how contralaterally located structures could be spared with PRT. CONCLUSION: PRT is a highly conformal radiation technique offering superior dosimetric advantages over conventional radiotherapy by allowing significant dose reduction for organs at risk (OAR) that are essential for neurologic function, neurocognition, and quality of life, thus demonstrating the potential of this technique for minimizing long-term sequelae.
Subject(s)
Brain Neoplasms/radiotherapy , Glioma/radiotherapy , Proton Therapy/methods , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Conformal/methods , Adolescent , Adult , Brain Neoplasms/pathology , Child , Child, Preschool , Cranial Irradiation/methods , Female , Glioma/pathology , Humans , Male , Middle Aged , Neoplasm Grading , Organs at Risk/radiation effects , Proton Therapy/adverse effects , Radiation Protection/methods , Radiotherapy, Conformal/adverse effects , Retrospective Studies , Treatment Outcome , Young AdultSubject(s)
Ear Neoplasms/genetics , Ear Neoplasms/therapy , Ear, External , Genotype , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/therapy , Phenotype , Rhabdoid Tumor/genetics , Rhabdoid Tumor/therapy , SMARCB1 Protein/genetics , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Ear Neoplasms/pathology , Gene Expression Regulation, Neoplastic/genetics , Humans , Maintenance Chemotherapy/methods , Male , Nasopharyngeal Neoplasms/pathology , Neoplasm Staging , Rhabdoid Tumor/pathology , Treatment OutcomeABSTRACT
PURPOSE: The prognosis for high-grade glioma (HGG) patients is poor; thus, treatment-related side effects need to be minimized to conserve quality of life and functionality. Advanced techniques such as proton radiation therapy (PRT) and volumetric-modulated arc therapy (VMAT) may potentially further reduce the frequency and severity of radiogenic impairment. MATERIALS AND METHODS: We retrospectively assessed 12 HGG patients who had undergone postoperative intensity-modulated proton therapy (IMPT). VMAT and 3D conformal radiotherapy (3D-CRT) plans were generated and optimized for comparison after contouring crucial neuronal structures important for neurogenesis and neurocognitive function. Integral dose (ID), homogeneity index (HI), and inhomogeneity coefficient (IC) were calculated from dose statistics. Toxicity data were evaluated. RESULTS: Target volume coverage was comparable for all three modalities. Compared to 3D-CRT and VMAT, PRT showed statistically significant reductions (p < 0.05) in mean dose to whole brain (-20.2 %, -22.7 %); supratentorial (-14.2 %, -20,8 %) and infratentorial (-91.0 %, -77.0 %) regions; brainstem (-67.6 %, -28.1 %); pituitary gland (-52.9 %, -52.5 %); contralateral hippocampus (-98.9 %, -98.7 %); and contralateral subventricular zone (-62.7 %, -66.7 %, respectively). Fatigue (91.7 %), radiation dermatitis (75.0 %), focal alopecia (100.0 %), nausea (41.7 %), cephalgia (58.3 %), and transient cerebral edema (16.7 %) were the most common acute toxicities. CONCLUSION: Essential dose reduction while maintaining equal target volume coverage was observed using PRT, particularly in contralaterally located critical neuronal structures, areas of neurogenesis, and structures of neurocognitive functions. These findings were supported by preliminary clinical results confirming the safety and feasibility of PRT in HGG.
Subject(s)
Astrocytoma/radiotherapy , Brain Neoplasms/radiotherapy , Glioblastoma/radiotherapy , Proton Therapy/methods , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/methods , Adult , Brain Injuries/etiology , Brain Injuries/prevention & control , Cranial Irradiation/adverse effects , Cranial Irradiation/methods , Female , Humans , Male , Middle Aged , Organs at Risk/radiation effects , Proton Therapy/adverse effects , Radiation Exposure , Radiation Injuries/etiology , Radiation Injuries/prevention & control , Radiation Protection/methods , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies , Treatment OutcomeABSTRACT
Background and Purpose Coil embolization of ruptured and unruptured aneurysms has emerged as a widely accepted alternative to clipping. Unfortunately, coil-embolized aneurysms need a long-term imaging follow-up to confirm the stability of the occlusion status. We investigated whether contrast-enhanced time-of-flight (ToF) magnetic resonance angiography (MRA) (gadolinium [Gd]-ToF) provides any diagnostic benefit over conventional ToF MRA (nonenhanced [NE]-ToF) in this context. Material and Methods From October 2013 to January 2015, all patients who were regularly scheduled for their follow-up after coil embolization were examined with Gd-ToF and NE-ToF angiography. The general visibility of the occlusion result was compared between the two MRAs as well as with the last digital subtraction angiography (DSA) available. Subgroups of interest (follow-up after stent-assisted coil embolization, cases with already known aneurysm remnants) were also analyzed. Results A total of 70 patients (44 female) harboring 74 treated aneurysms were examined. The reproducibility of the DSA result in terms of therapeutic relevance was 100%. In 10 of 74 cases (14%), the aneurysm status was more difficult to judge in the NE-ToF images (p = 0.02), and the visualization of small vessels was significantly better in the Gd-ToF (p = 0.003). NE-ToF did not fail to show any aneurysm remnants but were more difficult to depict in 35% of the cases (p = 0.09). Regarding the aneurysms that were coiled with stent assistance, there was no significant difference in terms of the visualization (p = 0.1). Conclusion Gd-ToF angiography is in general not superior to NE- ToF for the follow-up of coil-embolized aneurysms.
Subject(s)
Angiography, Digital Subtraction/methods , Cerebral Angiography/methods , Embolization, Therapeutic/methods , Intracranial Aneurysm/diagnostic imaging , Magnetic Resonance Angiography/methods , Adult , Aged , Female , Follow-Up Studies , Gadolinium , Humans , Image Processing, Computer-Assisted , Intracranial Aneurysm/therapy , Male , Middle Aged , Treatment OutcomeABSTRACT
Background: In Germany some 2 000 children and adolescent are diagnosed with cancer every year. Curing rates are increasing and therewith also the number of survivors is growing. Survivors frequently suffer from long-term effects of the disease and its treatment, but long-term follow-up care shows deficits. Method: The Network for oncological advisory service (NOF) started in 11/2013, researching and building up a network of available support in Lower Saxony. A telephone hotline was installed in 01/2014 in order to advice survivors on their problems. At the same time, an interview study on survivors needs was conducted throughout Germany. Results: In the first 2 years, the NOF gave advice to 79 patients. Whilst enquiries of medical or psychological nature were transferred to the cooperation partner, requests on psychosocial and social legal issues are being deled by the NOF due to lack of appropriate partners. The evaluation of 25 interviews shows key issues in long-term after-care: (1) transition from acute therapy to everyday life, (2) problems due to pediatric cancer and therapy, (3) patients perception of own disposition, (4) social reactions towards survivors, (5) structure of long-term follow-up care, (6) information flow. Conclusion: Many survivors suffer from long-term effects of cancer and treatment. The lack of available contact person and being in limbo between cured and simultaneously affected by the cancer treatment and chronic diseases is perceived as being problematic. This translates to various requirements on a patient-oriented long-term care, mainly in the psychosocial field.
Subject(s)
Aftercare/organization & administration , Consultants , Hotlines/organization & administration , Interdisciplinary Communication , Intersectoral Collaboration , Long-Term Care/organization & administration , Patient Care Team/organization & administration , Referral and Consultation/organization & administration , Adolescent , Adult , Child , Evaluation Studies as Topic , Follow-Up Studies , Germany , Health Services Needs and Demand/organization & administration , Humans , Interview, Psychological , Patient Satisfaction , Pilot Projects , Survivors , Transitional Care/organization & administration , Young AdultABSTRACT
PURPOSE: Aim of the present study was to investigate the sensitivity of high resolution ultrasound (HRU), standard contrast-enhanced ultrasound (CEUS) and CEUS using a novel vascular endothelial growth factor receptor 2 (VEGFR2)-targeted contrast agent for the detection of hepatic metastases in a mouse model of colorectal cancer using clinical standard technology. MATERIALS AND METHODS: The human colon cancer cell line HT29, transfected with luciferase cDNA for in vivo bioluminescence monitoring, was injected intrasplenically into CB17.SCID mice. Mice were monitored weekly by bioluminescence and after 2 and 4.5 weeks by HRU and CEUS.âContrast media (untargeted BR1, targeted BR55) was applied and digital cine loops from the arterial phase (15â-â45âsec), portal venous phase (50â-â120âs) and late phases (3â-â5âmin, 1hour) of the whole liver were analyzed. Data were correlated with postmortem histopathology. RESULTS: Without contrast enhancement, lesions >â4âmm were reliably detected. After use of untargeted CEUS, lesions >â2âmm were reliably detected and enhanced rim vascularization and late-phase wash-out was shown. With BR55, lesions >â0.8âmm were reliably detected with excellent documentation of vascularization. A persistent contrast enhancement was seen >â30âmin after injection. Contrast-enhancement patterns with BR55 significantly correlated with CD31 (R2â=â0.74) and VEGFR2-immunohistochemistry (R2â=â0.66). CONCLUSION: Detection of metastases by HRU and CEUS was earlier and more accurate than monitoring via bioluminescence. In vivo monitoring of hepatic micrometastases can thus be performed without prior modification of cancer cells using standard technology.
Subject(s)
Colonic Neoplasms/diagnostic imaging , Contrast Media , Image Enhancement , Lipopeptides/administration & dosage , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Liver/diagnostic imaging , Molecular Imaging , Ultrasonography , Vascular Endothelial Growth Factor Receptor-2 , Animals , Female , HT29 Cells , Humans , Luminescent Measurements , Mice , Mice, Inbred Strains , Microbubbles , Neoplasm TransplantationABSTRACT
BACKGROUND: Leukoencephalopathy with calcifications and cysts (LCC or Labrune disease) is a relatively recently defined and exceptionally rare disease in which parenchymal cysts and calcifications within a widespread leukoencephalopathy can cause a broad spectrum of neurological symptoms. The cause of the disease is unknown. Manifestation is usually in childhood or adolescence, while onset in adulthood has been described in 19 cases. CASE PRESENTATION: Here we report a case of an adult-onset LCC of a Caucasian woman who became symptomatic at age 70 as confirmed by typical neuroimaging and neuropathological findings. After resection of left mesioparietal space-occupying cystic brain tissue the patient has so far remained clinically stable during one year of follow-up with a continuous treatment with glucocorticosteroids. CONCLUSION: To our knowledge this report of a patient who became symptomatic at age 70 represents the oldest age-at-onset case of LCC described so far.
Subject(s)
Calcinosis/diagnosis , Central Nervous System Cysts/diagnosis , Leukoencephalopathies/diagnosis , Aged , Calcinosis/therapy , Central Nervous System Cysts/therapy , Female , Glucocorticoids/therapeutic use , Humans , Leukoencephalopathies/therapy , Magnetic Resonance Imaging , Rare DiseasesSubject(s)
Ambulatory Care , Career Choice , Nurses, Community Health/supply & distribution , Pediatric Nursing , Schools, Nursing , Students, Nursing , Adolescent , Adult , Child , Child, Preschool , Female , Forecasting , Germany , Health Services Needs and Demand/trends , Humans , Infant , Male , Middle Aged , Nurses, Community Health/trends , Pediatric Nursing/education , Young AdultABSTRACT
BACKGROUND: In 2007 the children's right to specialised paediatric palliative home care became law in Germany. This claim should be met in Lower Saxony by the establishment of a comprehensive specialised paediatric home care (SPPHC). Since April 2010, a central office undertakes the coordination and administration throughout the federal state. Regional teams comprising nursing, medical and psychosocial specialists care for the children and adolescents suffering from complex conditions due to life-limiting conditions - subsidiary to regional health care providers. The aim of the study was to evaluate SPPHC in Lower Saxony. METHODOLOGY: From June 2012 to February 2013, semi-structured interviews were conducted with 20 parents of children aged from 3 to 18 years. The young patients fulfilled all criteria to be eligible for SPPHC. 13 of the families experienced SPPHC. 7 families did not utilise the specialised care, mostly because the palliative situation occurred before the implementation of specialised care. Data were analysed using content analysis (Mayring). Therefore, key aspects of paediatric palliative home care were summarised in main categories. The evaluation of parent's satisfaction with palliative home care was performed by an evaluation scheme developed for the main categories (very good - good - bad- very bad) and operated for every case. RESULTS: 6 dimensions of paediatric palliative home care were identified: (i) benefit of care, (ii) continuity of care, (iii) perception of care providers as a team, (iv) dealing with the issues death and dying/hospice and palliative, (v) care provider's communication/cooperation with parents, and (vi) parent's Information. As all parents clearly indicated a rating on the first 3 categories, these categories were selected for the evaluation of parent's satisfaction with the received home care. The evaluation revealed that parents experienced in SPPHC looked upon these 3 main categories more favourably than parents without the experience of SPPHC. As room for improvement, the respondents requested the extension of physician's presence and communication with the families as well as with each other, efforts to better meet the needs of psycho-social support of the families and to optimise follow up-care. CONCLUSION: The implementation of SAPPV was rated positively by the concerned families. In addition, options for improvement could be identified.
Subject(s)
Attitude to Health , Home Care Services/statistics & numerical data , Palliative Care/psychology , Palliative Care/statistics & numerical data , Parents/psychology , Patient Satisfaction/statistics & numerical data , Adolescent , Attitude to Death , Child , Child, Preschool , Continuity of Patient Care/statistics & numerical data , Female , Germany/epidemiology , Humans , Male , Quality Assurance, Health Care/statistics & numerical dataABSTRACT
Risk analysis is increasingly promoted as a tool to support science-based decisions regarding food safety. An online survey comprising 45 questions was used to gather information on the implementation of food safety risk analysis within the Latin American and Caribbean regions. Professionals working in food safety in academia, government, and private sectors in Latin American and Caribbean countries were contacted by email and surveyed to assess their individual knowledge of risk analysis and perceptions of its implementation in the region. From a total of 279 participants, 97% reported a familiarity with risk analysis concepts; however, fewer than 25% were able to correctly identify its key principles. The reported implementation of risk analysis among the different professional sectors was relatively low (46%). Participants from industries in countries with a long history of trade with the United States and the European Union, such as Mexico, Brazil, and Chile, reported perceptions of a higher degree of risk analysis implementation (56, 50, and 20%, respectively) than those from the rest of the countries, suggesting that commerce may be a driver for achieving higher food safety standards. Disagreement among respondents on the extent of the use of risk analysis in national food safety regulations was common, illustrating a systematic lack of understanding of the current regulatory status of the country. The results of this survey can be used to target further risk analysis training on selected sectors and countries.