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1.
Clin Radiol ; 78(4): e336-e341, 2023 04.
Article in English | MEDLINE | ID: mdl-36746724

ABSTRACT

AIM: To understand the attitudes of UK radiology trainees towards artificial intelligence (AI) in Radiology, in particular, assessing the demand for AI education. MATERIALS AND METHODS: A survey, which ran over a period of 2 months, was created using the Google Forms platform and distributed via email to all UK training programmes. RESULTS: The survey was completed by 149 trainee radiologists with at least one response from all UK training programmes. Of the responses, 83.7% were interested in AI use in radiology but 71.4% had no experience of working with AI and 79.9% would like to be involved in AI-based projects. Almost all (98.7%) felt that AI should be taught during their training, yet only one respondent stated that their training programme had implemented AI teaching. Respondents indicated that basic understanding, implementation, and critical appraisal of AI software should be prioritized in teaching. Of the trainees, 74.2% agreed that AI would enhance the job of diagnostic radiologists over the next 20 years. The main concerns raised were information technology/implementation and ethical/regulatory issues. CONCLUSION: Despite the current limited availability of AI-based activities and teaching within UK training programmes, UK trainees' attitudes towards AI are mostly positive with many showing interest in being involved with AI-based projects, activities, and teaching.


Subject(s)
Artificial Intelligence , Radiology , Humans , Radiology/education , Radiologists , Radiography , Surveys and Questionnaires
2.
Sleep Breath ; 27(4): 1443-1454, 2023 08.
Article in English | MEDLINE | ID: mdl-36449218

ABSTRACT

PURPOSE: Obstructive sleep apnea (OSA) is prevalent in the bariatric population. OSA should be recognized in patients undergoing bariatric surgery preoperatively to prevent peri- and post-operative complications. Lipid metabolism-related biomarkers are associated with OSA. Triglyceride metabolism is, among others, regulated by angiopoietin-like protein five (ANGPTL5). We aimed to evaluate the level of ANGPTL5 in patients with OSA of different severity levels before and after bariatric surgery. METHODS: We performed a single-center prospective cohort study including a consecutive series of patients who underwent bariatric surgery. We collected the clinical data, polysomnography (PSG) or polygraphy (PG) parameters, and plasma derived via venipuncture before and 6 to 12 months after surgery. Lipid profile, glucose levels, and ANGPTL5 levels were assessed. ANGPTL5 levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The study included 88 patients for analysis. The patients were divided into two subgroups: no or mild OSA (apnea-hypopnea index (AHI) < 15 events/hour, n = 57) and moderate-to-severe OSA (AHI ≥ 15 events/hour, n = 31). The ANGPTL5 level was higher in the moderate-to-severe OSA group (20.5 [15.6, 26.5] ng/mL) compared to the no or mild OSA group (16.3 [12.5, 19.4] ng/mL) (p = 0.008). A significant positive correlation was observed between ANGPTL5 and AHI (ρ = 0.256, p = 0.017), apnea index (AI) (ρ = 0.318, p = 0.003), and triglyceride levels (ρ = 0.240, p = 0.025). ANGPTL5 levels were reduced significantly after bariatric surgery in both moderate-to-severe OSA (15.6 [10.3, 18.7] ng/mL) and no or mild OSA (13.4 [9.2, 15.8] ng/mL) groups, though to a lower level in the group without or mild OSA. Post-surgery, the significant positive correlation between ANGPTL5 and AHI (ρ = 0.210, p = 0.047), AI (ρ = 0.230, p = 0.034), and triglyceride (ρ = 0.397, p < 0.001) remained. CONCLUSION: The data showed increased levels of ANGPTL5 in patients with moderate-to-severe OSA. Both AHI and ANGPTL5 levels decreased significantly after bariatric surgery. We also report an association between ANGPTL5 levels and OSA severity.


Subject(s)
Bariatric Surgery , Sleep Apnea, Obstructive , Humans , Prospective Studies , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/surgery , Sleep Apnea, Obstructive/epidemiology , Polysomnography , Postoperative Complications
3.
Obes Surg ; 30(12): 5026-5032, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32880049

ABSTRACT

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is often the preferred conversion procedure for laparoscopic adjustable gastric banding (LAGB) poor responders. However, there is controversy whether it is better to convert in one or two stages. This study aims to compare the outcomes of one and two-stage conversions of LAGB to RYGB. METHODS: Retrospective review of a multicenter prospectively collected database. Data on conversion in one and two stages was compared. RESULTS: Eight hundred thirty-two patients underwent LAGB conversion to RYGB in seven specialized bariatric centers. Six hundred seventy-three (81%) were converted in one-stage. Patients in the two-stage group were more likely to have experienced technical complications, such as slippage or erosions (86% vs. 37%, p = 0.0001) and to have had a higher body mass index (BMI) (41.6 vs. 39.9 Kg/m2, p = 0.005). There were no differences in postoperative complications and mortality rates between the one-stage and two-stage groups (13.5% vs. 10.8%, and 0.7% vs. 0.0% respectively, p = ns). Mean final BMI and %total weight loss (%TWL) for the one-stage and the two-stage groups were 31.6 vs. 32.4 Kg/m2 (p = ns) and 30.4 vs. 26.8 (p = 0.017) after a mean follow-up of 33 months. Follow-up at 1, 3, and 5 years was 98%, 75%, and 54%, respectively. CONCLUSIONS: One-stage conversion of LAGB to RYGB is safe and effective. Two-stage conversion carries low morbidity and mortality in the case of band slippage, erosion, or higher BMI patients. These findings suggest the importance of patient selection when choosing the appropriate conversion approach.


Subject(s)
Gastric Bypass , Gastroplasty , Laparoscopy , Obesity, Morbid , Humans , Obesity, Morbid/surgery , Postoperative Complications/epidemiology , Postoperative Complications/surgery , Reoperation , Retrospective Studies , Treatment Outcome
4.
J Plast Reconstr Aesthet Surg ; 73(6): 1159-1165, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32173244

ABSTRACT

INTRODUCTION: Reimbursement of body-contouring surgery (BCS) is a worldwide problem: there is no objective instrument to decide which postbariatric patients should qualify for reimbursement. The British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) has developed a screening tool for this purpose. In this study, we used a modified version of this screening tool in a postbariatric population and describe which patients would qualify for reimbursement using this tool. METHODS: In this cross-sectional study postbariatric patients were asked to fill in an online questionnaire based on the BAPRAS screening tool with questions regarding complaints of overhanging skin and medical history. Weight loss data were extracted from a prospective database. The BODY-Q was added to assess patient-reported outcomes. RESULTS: Patients who wanted to undergo BCS (n = 90) had higher screening tool scores and lower BODY-Q scores compared to patients who did not want BCS (n = 24). In total, 25 patients (26%) qualified for reimbursement, these patients had higher weight loss (33.5% versus 29.2%, p = 0.008), lower BMI (27.3 kg/m2 versus 30.4 kg/m2, p = 0.014) and more medical (4.0 versus 2.0, p = 0.004) and psychological complaints (88% versus 61%, p = 0.009). There was a significant, negative correlation between the screening tool scores and almost all BODY-Q scales. CONCLUSIONS: Patients with a desire for BCS have more complaints of excess skin, which negatively impacts their well-being. With the modified BAPRAS screening tool, patients with the best weight (loss) and most medical and psychological complaints of excess skin qualified for referral and reimbursement of BCS.


Subject(s)
Bariatric Surgery , Body Contouring , Insurance, Health, Reimbursement , Adult , Body Contouring/economics , Cross-Sectional Studies , Female , Humans , Insurance Coverage/standards , Insurance Coverage/statistics & numerical data , Insurance, Health, Reimbursement/standards , Insurance, Health, Reimbursement/statistics & numerical data , Male , Middle Aged , Netherlands , Patient Reported Outcome Measures , Surveys and Questionnaires , Weight Loss
5.
Obes Surg ; 30(3): 924-930, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31792701

ABSTRACT

INTRODUCTION: A considerable number of patients experience some long-term weight regain after bariatric surgery. Body contouring surgery (BCS) is thought to strengthen post-bariatric surgery patients in their weight control and maintenance of achieved improvements in comorbidities. OBJECTIVES: To examine the impact of BCS on long-term weight control and comorbidities after bariatric surgery. METHODS: We performed a retrospective study in a prospective database. All patients who underwent primary Roux-en-Y gastric bypass (RYGB) and presented for preoperative consultation of BCS in the same hospital were included in the study. Linear and logistic mixed-effect model analyses were used to evaluate the longitudinal relationships between patients who were accepted or rejected for BCS and their weight loss outcomes or changes in comorbidities. RESULTS: Of the 1150 patients who underwent primary RYGB between January 2010 and December 2014, 258 patients (22.4%) presented for preoperative consultation of BCS. Of these patients, 126 patients eventually underwent BCS (48.8%). Patients who were accepted for BCS demonstrated significant better ∆body mass index (BMI) on average over time (- 1.31 kg/m2/year, 95% confidence interval (CI) -2.52 - -0.10, p = 0.034) and percent total weight loss (%TWL) was significantly different at 36 months (5.79, 95%CI 1.22 - 10.37, p = 0.013) and 48 months (6.78, 95%CI 0.93 - 12.63, p = 0.023) after body contouring consultation. Patients who were accepted or rejected did not differ significantly in the maintenance of achieved improvements in comorbidities. CONCLUSION: BCS could not be associated with the maintenance of achieved improvements in comorbidities after bariatric surgery, whereas it could be associated with improved weight loss maintenance at 36 and 48 months after body contouring consultation. This association should be further explored in a large longitudinal study.


Subject(s)
Bariatric Surgery , Body Contouring , Body Weight Maintenance/physiology , Obesity, Morbid/epidemiology , Obesity, Morbid/surgery , Adult , Bariatric Surgery/rehabilitation , Bariatric Surgery/statistics & numerical data , Body Contouring/methods , Body Contouring/statistics & numerical data , Body Mass Index , Comorbidity , Female , Humans , Longitudinal Studies , Male , Middle Aged , Postoperative Period , Reoperation/methods , Reoperation/statistics & numerical data , Retrospective Studies , Weight Loss/physiology
6.
Vascul Pharmacol ; 125-126: 106634, 2020.
Article in English | MEDLINE | ID: mdl-31866461

ABSTRACT

Despite the advent of new-generation drug-eluting stents, in-stent restenosis remains a significant problem in patients with coronary artery disease. In- stent restenosis is defined as the gradual re-narrowing of a stented coronary artery lesion due to arterial damage with subsequent local inflammation of the vessel wall and excessive growth of the vascular smooth muscle cells (vSMCs). Four-and-a-half LIM-domain protein 2 (FHL2) is a scaffold protein involved in regulating vSMC function and inflammation. Previously we have demonstrated that FHL2 prevents vSMC proliferation in a murine carotid artery ligation model. However, the effect of FHL2 on the inflammatory response of the vSMCs is not investigated. Therefore, we studied the inflammatory response in the vessel wall of FHL2-deficient (-KO) mice after carotid artery ligation. We found that circulating cytokines and local macrophage infiltration in the ligated carotid vessels were increased in FHL2-KO mice after carotid artery ligation. Moreover, FHL2-KO vSMCs showed increased secretion of cytokines such as SDF-1α and RANTES, and enhanced activation of the NFκB pathway. Finally, we found that blocking the NFκB signalling pathway abrogated this pro-inflammatory state in FHL2-KO vSMCs. Taken together, our results demonstrate that FHL2 decreases the inflammatory response of vSMCs through inhibition of the NFkB-signalling pathway.


Subject(s)
Carotid Artery Diseases/metabolism , Inflammation/metabolism , LIM-Homeodomain Proteins/metabolism , Muscle Proteins/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , NF-kappa B/metabolism , Transcription Factors/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Carotid Arteries/metabolism , Carotid Arteries/pathology , Carotid Artery Diseases/genetics , Carotid Artery Diseases/pathology , Carotid Artery Diseases/prevention & control , Cells, Cultured , Cytokines/blood , Disease Models, Animal , Inflammation/genetics , Inflammation/pathology , Inflammation/prevention & control , LIM-Homeodomain Proteins/deficiency , LIM-Homeodomain Proteins/genetics , Macrophages/metabolism , Macrophages/pathology , Mice, Knockout , Muscle Proteins/deficiency , Muscle Proteins/genetics , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/pathology , NF-kappa B/antagonists & inhibitors , NF-kappa B/genetics , Signal Transduction , Transcription Factors/deficiency , Transcription Factors/genetics
7.
Obes Rev ; 19(10): 1395-1411, 2018 10.
Article in English | MEDLINE | ID: mdl-29883059

ABSTRACT

OBJECTIVE: The objective of this study is to systematically assess the quality of existing patient-reported outcome measures developed and/or validated for Quality of Life measurement in bariatric surgery (BS) and body contouring surgery (BCS). METHODS: We conducted a systematic literature search in PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Database Systematic Reviews and CENTRAL identifying studies on measurement properties of BS and BCS Quality of Life instruments. For all eligible studies, we evaluated the methodological quality of the studies by using the COnsensus-based Standards for the selection of health Measurement INstruments checklist and the quality of the measurement instruments by applying quality criteria. Four degrees of recommendation were assigned to validated instruments (A-D). RESULTS: Out of 4,354 articles, a total of 26 articles describing 24 instruments were included. No instrument met all requirements (category A). Seven instruments have the potential to be recommended depending on further validation studies (category B). Of these seven, the BODY-Q has the strongest evidence for content validity in BS and BCS. Two instruments had poor quality in at least one required quality criterion (category C). Fifteen instruments were minimally validated (category D). CONCLUSION: The BODY-Q, developed for BS and BCS, possessed the strongest evidence for quality of measurement properties and has the potential to be recommended in future clinical trials.


Subject(s)
Bariatric Surgery/psychology , Body Contouring/psychology , Obesity/surgery , Quality of Life/psychology , Humans , Obesity/psychology , Outcome Assessment, Health Care , Reproducibility of Results
8.
Surg Obes Relat Dis ; 14(7): 1020-1025, 2018 07.
Article in English | MEDLINE | ID: mdl-29703507

ABSTRACT

BACKGROUND: One third of bariatric surgery patients have an apnea-hypopnea index (AHI)>15/hr, representing moderate and severe forms of obstructive sleep apnea (OSA). Treating these forms of OSA is recommended to reduce the risk of perioperative complications. The AHI derived from poly(somno)graphy [P(S)G] is the gold standard for OSA diagnosis. However, performing P(S)G in all patients scheduled for bariatric surgery is time consuming and expensive. An accurate and simple screening tool able to rule out moderate to severe OSA would reduce the number of patients needing mandatory P(S)Gs. OBJECTIVES: To assess the validity of a simple sleep monitor (Checkme Health Monitor) as a screening tool for OSA in bariatric surgery patients. SETTING: Obesity Center Amsterdam, OLVG-West, Amsterdam, the Netherlands METHODS: Patients scheduled for bariatric surgery were prospectively enrolled in this study. All patients underwent preoperative P(S)G and simultaneously used the Checkme to assess the oxygen desaturation index. The diagnostic performance of the Checkme for AHI ≥15/hr was assessed using receiver operating characteristic curve analysis. RESULTS: A total of 50 patients were analyzed. Sensitivity and negative predictive value were 100% and 100%, respectively, specificity and positive predictive value were 69% and 64%, respectively, for the optimal cutoff value of Checkme-3% oxygen desaturation index ≥9/hr for P(S)G-AHI ≥15. The area under the curve value expressed by the receiver operating characteristic curve was .95. CONCLUSION: The Checkme is valid for exclusion of moderate and severe OSA in bariatric surgery patients. The Checkme enables bariatric clinics not to perform P(S)G in all patients scheduled for bariatric surgery.


Subject(s)
Bariatric Surgery/methods , Obesity, Morbid/epidemiology , Polysomnography/instrumentation , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiology , Adult , Cohort Studies , Comorbidity , Female , Follow-Up Studies , Humans , Male , Middle Aged , Netherlands , Obesity, Morbid/diagnosis , Patient Selection , Pilot Projects , Preoperative Care , Prospective Studies , ROC Curve , Sensitivity and Specificity , Tertiary Care Centers , Treatment Outcome
9.
Rev Sci Instrum ; 87(11): 11D503, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27910640

ABSTRACT

The Hitomi Soft X-ray Spectrometer (SXS) was a pioneering non-dispersive imaging x-ray spectrometer with 5 eV FWHM energy resolution, consisting of an array of 36 silicon-thermistor microcalorimeters at the focus of a high-throughput soft x-ray telescope. The instrument enabled astrophysical plasma diagnostics in the 0.3-12 keV band. We introduce the SXS calibration strategy and corresponding ground calibration measurements that took place from 2012-2015, including both the characterization of the microcalorimeter array and measurements of the x-ray transmission of optical blocking filters.

11.
Clin Pharmacol Ther ; 100(1): 21-3, 2016 07.
Article in English | MEDLINE | ID: mdl-27060214

ABSTRACT

Is the European Union (EU) regulatory framework concerning pregnant women and women at risk of becoming pregnant fit for the purpose? This article discusses improvements in how medicines should be developed and monitored for safe and effective use by pregnant women and women at risk of becoming pregnant.


Subject(s)
Drug Design , Drug and Narcotic Control , Drug-Related Side Effects and Adverse Reactions/prevention & control , European Union , Female , Humans , Pregnancy , Risk
12.
Ned Tijdschr Geneeskd ; 160: A9285, 2016.
Article in Dutch | MEDLINE | ID: mdl-27071358

ABSTRACT

BACKGROUND: Soft tissue swelling of the leg is a relatively uncommon occurrence in children, and is often benign. In adults, 1% of malignancies originate in soft tissue, whereas for children the figure is 8%. Based on medical history and physical examination alone, it is difficult to differentiate between benign and malignant soft tissue tumours. CASE DESCRIPTION: A 15-year-old girl presented to her GP with a swelling in the left thigh, without alarming symptoms. The GP suspected the lesion to be benign and she was asked to return if the swelling increased in size. Five months later, when the lesion was excised, it proved to be a granular cell tumour. The second case concerns a 12-year-old boy who presented to his GP with a swelling of the lateral malleolus, which had developed after impact against a door five years ago. The boy was referred to the surgical department where after excision it was shown to be a dermatofibrosarcoma protuberans. CONCLUSION: In paediatric cases when diagnosis is inconclusive, including cases involving possible growth of the swelling, suspicions raised during physical examination, or unusually lengthy recovery after trauma, awareness is important. Imaging diagnostics or even tissue excision with histopathology may be indicated to allow the correct diagnosis to be made.


Subject(s)
Dermatofibrosarcoma/diagnosis , Edema/diagnosis , Granular Cell Tumor/diagnosis , Adolescent , Child , Female , Humans , Leg/pathology , Male , Physical Examination , Thigh/pathology
13.
Colloids Surf B Biointerfaces ; 141: 365-373, 2016 May 01.
Article in English | MEDLINE | ID: mdl-26878287

ABSTRACT

The role of biomaterials surface in controlling the interfacial biological events leading to implant integration is of key importance. In this study, the effects of NiTi surfaces treated by plasma electrolytic oxidation (PEO) on human umbilical vein endothelial cells (HUVECs) have been investigated. The changes in NiTi surface morphology and chemistry were assessed by SEM, XPS and cross-section TEM/EDX analyzes whereas the effects of the resultant surfaces on in vitro endothelialization and cell junction proteins have been evaluated by life/dead staining, SEM, cells counting, qPCR and immunofluorescence. The findings indicated that the PEO-treated NiTi, with a microporous morphology and oxide dominated surface chemistry, supports viability and proliferation of HUVECs. Numerous thin filopodia probing the microporous surface assisted cells attachment. In addition, claudin-5 and occludin have been upregulated and expression of vascular endothelial-cadherin was not suppressed on PEO-treated NiTi relative to the reference electropolished surfaces. The results of this study suggest that novel NiTi surfaces may be developed using the PEO process, which can be of benefit to atherosclerosis treatment.


Subject(s)
Coated Materials, Biocompatible/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Nickel/pharmacology , Titanium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Antigens, CD/genetics , Antigens, CD/metabolism , Cadherins/genetics , Cadherins/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Claudin-5/genetics , Claudin-5/metabolism , Coated Materials, Biocompatible/chemistry , Electrolysis , Electrolytes/chemistry , Gene Expression/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/ultrastructure , Humans , Microscopy, Confocal , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Nickel/chemistry , Occludin/genetics , Occludin/metabolism , Oxidation-Reduction , Photoelectron Spectroscopy , Reverse Transcriptase Polymerase Chain Reaction , Surface Properties , Titanium/chemistry
15.
Allergy ; 70(12): 1531-44, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26222912

ABSTRACT

BACKGROUND: Asthma is an inflammatory disease that involves airway hyper-responsiveness and mucus hypersecretion. The LIM-only protein FHL2 is a crucial modulator of multiple signal transduction pathways and functions as a scaffold in specific protein-protein interactions. OBJECTIVE: We sought to investigate the role of FHL2 in airway inflammation. METHODS: Allergic airway inflammation was induced in WT and FHL2-knock out (FHL2-KO) mice with ovalbumin (OVA). Lung tissue, bronchoalveolar lavage fluid (BALF) and draining lymph node cells were analysed for inflammation. FHL2 loss and gain of function studies were performed in lung epithelial cells. RESULTS: FHL2-deficient mice challenged with OVA show significantly reduced airway inflammation as evidenced by reduced infiltration of inflammatory cells including eosinophils, dendritic cells, B cells and T cells. Furthermore, mucus production was decreased in FHL2-KO mice. In BALF, the levels of IL-5, IL-13, eotaxin-1 and eotaxin-2 were significantly lower in FHL2-KO mice. In addition, draining lymph node cells from FHL2-KO mice show reduced levels of IL-5 and IL-13. Consistent with this, OVA-specific serum IgG and IgE levels were reduced in FHL2-KO mice. We also found that phosphorylation of ERK1/2 is markedly attenuated in FHL2-KO lung. Knock-down of FHL2 in human lung epithelial cells resulted in a striking decrease in ERK1/2 phosphorylation and mRNA levels of inflammatory cytokines and MUC5AC, whereas FHL2 overexpression exhibited opposite effects. Finally, the SNP rs4851765 shows an association with the severity of bronchial hyper-responsiveness. CONCLUSION: These results highlight functional involvement of FHL2 in airway inflammation and identify FHL2 as a novel gene associated with asthma severity in human.


Subject(s)
Asthma/genetics , LIM-Homeodomain Proteins/metabolism , Muscle Proteins/metabolism , Pneumonia/genetics , Respiratory Hypersensitivity/genetics , Transcription Factors/metabolism , Animals , Asthma/metabolism , Blotting, Western , Disease Models, Animal , Genetic Predisposition to Disease/genetics , Genotype , Humans , LIM-Homeodomain Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle Proteins/genetics , Oligonucleotide Array Sequence Analysis , Pneumonia/metabolism , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Respiratory Hypersensitivity/metabolism , Transcription Factors/genetics
17.
Cancer Gene Ther ; 22(3): 154-62, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25633483

ABSTRACT

Effective immunotherapeutic strategies require the ability to generate a systemic antigen-specific response capable of impacting both primary and metastatic disease. We have built on our oncolytic vaccinia a granulocyte-macrophage colony-stimulating factor (GM-CSF) strategy by adding recombinant tumor antigen to increase the response in the tumor microenvironment and systemically. In the present study, orthotopic growth of a syngeneic HER2/neu-overexpressing mammary carcinoma in FVB/N mice (NBT1) was associated with increased Gr1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs) both systemically and in the tumor microenvironment. This MDSC population had inhibitory effects on the HER2/neu-specific Th1 immune response. VVneu and VVGMCSF are recombinant oncolytic vaccinia viruses that encode HER2/neu and GM-CSF, respectively. Naive FVB mice vaccinated with combined VVneu and VVGMCSF given systemically developed systemic HER2/neu-specific immunity. NBT1-bearing mice became anergic to systemic immunization with combined VVneu and VVGMCSF. Intratumoral VVGMCSF failed to result in systemic antitumor immunity until combined with intratumoral VVneu. Infection/transfection of the tumor microenvironment with combined VVGMCSF and VVneu resulted in development of systemic tumor-specific immunity, reduction in splenic and tumor MDSC and therapeutic efficacy against tumors. These studies demonstrate the enhanced efficacy of oncolytic vaccinia virus recombinants encoding combined tumor antigen and GM-CSF in modulating the microenvironment of MDSC-rich tumors.


Subject(s)
Genes, erbB-2 , Mammary Neoplasms, Experimental/therapy , Oncolytic Virotherapy , Oncolytic Viruses/genetics , Vaccinia virus/genetics , Animals , Cancer Vaccines/therapeutic use , Cell Line, Tumor , Clonal Anergy , Female , Granulocyte-Macrophage Colony-Stimulating Factor , Mammary Neoplasms, Experimental/immunology , Mice, Transgenic , Myeloid Cells/physiology , Neoplasm Transplantation , T-Lymphocytes, Cytotoxic/immunology , Tumor Escape , Tumor Microenvironment/immunology , Vaccination
18.
Cell Tissue Bank ; 16(1): 1-17, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24789705

ABSTRACT

The successful transplantation of human materials such as organs, tissues and cells into patients does not only depend on the benefits, but also on the mitigation of risks. To gain insight into recent publications on risks associated with the process of transferring human materials from donor to recipient we performed a horizon scan by reviewing scientific literature and news websites of 2011 on this subject. We found there is ample information on how extended donor criteria, such as donor age, affect the survival rates of organs or patients. Interestingly, gender mismatch does not appear to be a major risk factor in organ rejection. Data on risks of donor tumor transmission was very scarce; however, risk categories for various tumor types have been suggested. In order to avoid rejection, a lot of research is directed towards engineering tissues from a patient's own tissues and cells. Some but not all of these developments have reached the clinic. Developments in the field of stem cell therapy are rapid. However, many hurdles are yet to be overcome before these cells can be applied on a large scale in the clinic. The processes leading to genetic abnormalities in cells differentiated from stem cells need to be identified in order to avoid transplantation of aberrant cells. New insights have been obtained on storage and preservation of human materials, a critical step for success of their clinical use. Likewise, quality management systems have been shown to improve the quality and safety of human materials used for transplantation.


Subject(s)
Patient Safety , Tissue Donors , Transplantation , Humans , Risk Assessment
19.
Science ; 345(6192): 64-8, 2014 Jul 04.
Article in English | MEDLINE | ID: mdl-24994647

ABSTRACT

Supermassive black holes in the nuclei of active galaxies expel large amounts of matter through powerful winds of ionized gas. The archetypal active galaxy NGC 5548 has been studied for decades, and high-resolution x-ray and ultraviolet (UV) observations have previously shown a persistent ionized outflow. An observing campaign in 2013 with six space observatories shows the nucleus to be obscured by a long-lasting, clumpy stream of ionized gas not seen before. It blocks 90% of the soft x-ray emission and causes simultaneous deep, broad UV absorption troughs. The outflow velocities of this gas are up to five times faster than those in the persistent outflow, and, at a distance of only a few light days from the nucleus, it may likely originate from the accretion disk.

20.
Neth Heart J ; 22(4): 167-73, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24522952

ABSTRACT

AIMS: Everolimus-eluting stents (EES) were superior to sirolimus-eluting stents (SES) in a dedicated myocardial infarction trial, a finding that was not observed in trials with low percentages of ST-elevation myocardial infarction (STEMI). Therefore, this study sought to investigate the influence of clinical presentation on outcome after EES and SES implantation. METHODS: A pooled population of 1602 randomised patients was formed from XAMI (acute MI trial) and APPENDIX-AMI (all-comer trial). Primary outcome was cardiac mortality, MI and target vessel revascularisation at 2 years. Secondary endpoints included definite/probable stent thrombosis (ST). Adjustment was done using Cox regression. RESULTS: In total, 902 EES and 700 SES patients were included, of which 44 % STEMI patients (EES 455; SES 257) and 56 % without STEMI (EES 447; SES 443). In the pooled population, EES and SES showed similar outcomes during follow-up. Moreover, no differences in the endpoints were observed after stratification according to presentation. Although a trend toward reduced early definite/probable ST was observed in EES compared with SES in STEMI patients, long-term ST rates were low and comparable. CONCLUSIONS: EES and SES showed a similar outcome during 2-year follow-up, regardless of clinical presentation. Long-term safety was excellent for both devices, despite wide inclusion criteria and a large sub-population of STEMI patients.

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