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BACKGROUND: Endovascular repair of aortic aneurysmal disease is established due to perceived advantages in patient survival, reduced postoperative complications, and shorter hospital lengths of stay. High spatial and contrast resolution 3D CT angiography images are used to plan the procedures and inform device selection and manufacture, but in standard care, the surgery is performed using image-guidance from 2D X-ray fluoroscopy with injection of nephrotoxic contrast material to visualise the blood vessels. This study aims to assess the benefit to patients, practitioners, and the health service of a novel image fusion medical device (Cydar EV), which allows this high-resolution 3D information to be available to operators at the time of surgery. METHODS: The trial is a multi-centre, open label, two-armed randomised controlled clinical trial of 340 patient, randomised 1:1 to either standard treatment in endovascular aneurysm repair or treatment using Cydar EV, a CE-marked medical device comprising of cloud computing, augmented intelligence, and computer vision. The primary outcome is procedural time, with secondary outcomes of procedural efficiency, technical effectiveness, patient outcomes, and cost-effectiveness. Patients with a clinical diagnosis of AAA or TAAA suitable for endovascular repair and able to provide written informed consent will be invited to participate. DISCUSSION: This trial is the first randomised controlled trial evaluating advanced image fusion technology in endovascular aortic surgery and is well placed to evaluate the effect of this technology on patient outcomes and cost to the NHS. TRIAL REGISTRATION: ISRCTN13832085. Dec. 3, 2021.
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Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Análisis Costo-Beneficio , Nube Computacional , Procedimientos Endovasculares/métodos , Implantación de Prótesis Vascular/efectos adversos , Resultado del Tratamiento , Estudios Retrospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoAsunto(s)
Aneurisma de la Aorta Abdominal , Endofuga , Procedimientos Endovasculares , Tomografía Computarizada por Rayos X , Humanos , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Endofuga/diagnóstico por imagen , Endofuga/etiología , Tomografía Computarizada por Rayos X/métodos , RadiómicaRESUMEN
OBJECTIVE: This study aimed to assess the quality of patient information material regarding elective abdominal aortic aneurysm (AAA) repair on the internet using the Modified Ensuring Quality Information for Patients (MEQIP) tool. METHODS: A qualitative assessment of internet based patient information was performed. The 12 most used search terms relating to AAA repair were identified using Google Trends, with the first 10 pages of websites retrieved for each term searched. Duplicates were removed, and information for patients undergoing elective AAA were selected. Further exclusion criteria were marketing material, academic journals, videos, and non-English language sites. The remaining websites were then MEQIP scored independently by two reviewers, producing a final score by consensus. RESULTS: A total of 1 297 websites were identified, with 235 (18.1%) eligible for analysis. The median MEQIP score was 18 (interquartile range [IQR] 14, 21) out of a possible 36. The highest score was 33. The 99th percentile MEQIP scoring websites scored > 27, with four of these six sites representing online copies of hospital patient information leaflets, however hospital sites overall had lower median MEQIP scores than most other institution types. MEQIP subdomain median scores were: content, 8 (IQR 6, 11); identification, 3 (IQR 1, 3); and structure, 7 (IQR 6, 9). Of the analysed websites, 77.9% originated from the USA (median score 17) and 12.8% originated in the UK (median score 22). Search engine ranking was related to website institution type but had no correlation with MEQIP. CONCLUSION: When assessed by the MEQIP tool, most websites regarding elective AAA repair are of questionable quality. This is in keeping with studies in other surgical and medical fields. Search engine ranking is not a reliable measure of quality of patient information material regarding elective AAA repair. Health practitioners should be aware of this issue as well as the whereabouts of high quality material to which patients can be directed.
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Aneurisma de la Aorta Abdominal , Información de Salud al Consumidor , Procedimientos Quirúrgicos Electivos , Internet , Educación del Paciente como Asunto , Aneurisma de la Aorta Abdominal/cirugía , Humanos , Procedimientos Quirúrgicos Electivos/normas , Educación del Paciente como Asunto/normas , Información de Salud al Consumidor/normas , Procedimientos Quirúrgicos Vasculares/normasRESUMEN
OBJECTIVE: Despite widespread use, long term outcomes for fenestrated endovascular aneurysm repair (FEVAR) are uncertain. This meta-analysis reports long term survival, freedom from re-intervention, target vessel patency, and one year sac regression after FEVAR. DATA SOURCES: Systematic review and meta-analysis to pool time to event data according to PRISMA guidelines. The study was registered with the international prospective register of systematic reviews (PROSPERO) (ID: CRD42023401468). REVIEW METHODS: Medline, Embase, and Cochrane databases were searched from 1992 - 2023; articles were independently screened by two authors. Publication of complete time to event data for any outcome of interest was an inclusion criterion. Raw Kaplan-Meier probabilities were directly extracted from published curves and pooled by random effects. Risk of bias was assessed using ROBINS I and certainty with GRADE. RESULTS: A total of 3 569 records were retrieved, 2 869 screened after duplicate removal, yielding 37 included studies (n = 4 371). The pooled mean age was 73.2 years (interquartile range [IQR] 72.2, 73.7) and 87.4% were male (95% confidence interval [CI] 85.8 - 88.9). Pooled Kaplan-Meier estimated probabilities of survival (n = 34 studies, n = 4 192 patients) at one, three, and five years were 91.6% (95% CI 90.2 - 92.9), 80.8% (95% CI 78.0 - 83.2), and 65.1% (95% CI 60.9 - 69.1). For freedom from re-intervention (n = 24, n = 3 211 patients) at one, three, and five years these were 90.2% (95% CI 87.3 - 92.7), 80.9% (95% CI 76.5 - 84.9), and 73.8% (95% CI 67.1 - 79.6). For target vessel patency (n = 13, n = 5805 target vessels) at one, three, and five years, these were 96.6% (95% CI 94.9 - 98.0), 94.5% (95% CI 91.7 - 96.7), and 93.1% (95% CI 89.3 - 96.0). Pooled estimate of sac regression (n = 8, n = 560) at one year was 40.2% (95% CI 28.9 - 52.7). Risk of bias was judged as moderate in 11 studies and low for the remaining 26. CONCLUSION: There are moderate to low certainty data supporting reasonable long term outcome estimates following fenestrated endovascular aneurysm repair. Beyond five years there is a lack of data in the literature.
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Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Masculino , Anciano , Femenino , Prótesis Vascular , Reparación Endovascular de Aneurismas , Implantación de Prótesis Vascular/efectos adversos , Aneurisma de la Aorta Abdominal/cirugía , Factores de Riesgo , Resultado del Tratamiento , Procedimientos Endovasculares/efectos adversos , Complicaciones Posoperatorias/cirugía , Diseño de PrótesisRESUMEN
OBJECTIVE: This study aimed to construct a decision aid to estimate the likelihood of independence with a prosthesis following rehabilitation for limb loss secondary to advanced ischaemia (acute or chronic limb threatening ischaemia) or diabetic foot disease (DFD). A secondary aim was to determine whether prosthetic independence is a surrogate marker of long term survival. METHODS: A retrospective cohort study of a prospectively maintained database of unilateral amputations due to ischaemia or DFD entering rehabilitation between 2007 and 2020 was performed. Predictors of independent prosthetic mobility (IPM) were used in construction of the IPM prediction model, which underwent bootstrap internal and criterion validation through correlation with predictors of other measures of function: Timed Up and Go (TUG) and two minute walk test. Kaplan-Meier and Cox regression analyses were performed to address the secondary aim. RESULTS: Of the 771 patients included, only 49.9% of amputees achieved IPM. Independent negative predictors of IPM were age > 75 years, female sex, higher amputation level, active malignancy, cerebrovascular disease, end stage renal disease, and cognitive impairment. The model yielded high discrimination (C statistic 0.778), and internal validation was demonstrated with bootstrapping (C statistic 0.778), confirming no over optimism. There was a strong correlation between IPM, TUG, and two minute distance and their predictors, confirming strong criterion validity. The IPM group had a median survival of 93.7 (80.7, 105) months, whereas the non-IPM group fared worse with a median survival of 56.6 (48.5, 66.7) months (p < .001). CONCLUSION: An internally validated decision aid for estimating the likelihood of independence with a prosthesis after major amputation was constructed. A strong association between female sex and poorer prosthetic mobility was observed. Prosthetic function was shown to be a surrogate marker of long term survival. Future research will involve external validation studies to confirm the generalisability of the decision aid in clinical practice.
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Amputación Quirúrgica , Alta del Paciente , Humanos , Femenino , Anciano , Estudios Retrospectivos , Amputación Quirúrgica/efectos adversos , Procedimientos Quirúrgicos Vasculares , Biomarcadores , Isquemia , Extremidad Inferior/cirugíaRESUMEN
Bacterial microcompartments (BMCs) are proteinaceous organelle-like structures formed within bacteria, often encapsulating enzymes and cellular processes, in particular, allowing toxic intermediates to be shielded from the general cellular environment. Outside of their biological role they are of interest, through surface modification, as potential drug carriers and polyvalent antigen display scaffolds. Here we use a post-translational modification approach, using copper free click chemistry, to attach a SpyTag to a target protein molecule for attachment to a specific SpyCatcher modified BMC shell protein. We demonstrate that a post-translationally SpyTagged material can react with a SpyCatcher modified BMC and show its presence on the surface of BMCs, enabling future investigation of these structures as polyvalent antigen display scaffolds for vaccine development. This post-translational 'click' methodology overcomes the necessity to genetically encode the SpyTag, avoids any potential reduction in expression yield and expands the scope of SpyTag/SpyCatcher vaccine scaffolds to form peptide epitope vaccines and small molecule delivery agents.
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AIM: The aim of this study was to determine if there is an association between statin-use and prosthetic mobility and long-term survival in patients receiving rehabilitation after major amputation for lower limb arterial disease. METHODS: A retrospective analysis of prospectively maintained data (2008-2020) from a centre for rehabilitation was performed. Patients were grouped by statin-use status and sub-grouped by the combination of statin and antithrombotic drugs (antiplatelets or anticoagulants). Outcomes were prosthetic mobility (SIGAM score, timed-up-go and 2-min walking distance) and long-term survival. Regression, Kaplan-Meier and Cox-proportional hazard analyses were performed to test associations adjusted to confounders. RESULTS: Of 771 patients, 499 (64.7%) were on a statin before amputation or prescribed a statin peri-operatively. Rate of statin-use was significantly lower among female (53.3%) compared to male (68.2%) patients, P < 0.001. Statin-use was associated with significantly better prosthetic independence (53.1% vs 44.1%, P = 0.017), timed-up-go (mean difference of 4 s, P = 0.04) and long-term survival HR 0.59 (0.48-0.72, P < 0.001). Significance persisted after adjusting for confounding factors and in subgroup analyses. The combination of statin with antiplatelet was associated with the most superior survival, HR 0.51 (0.40-0.65, P < 0.001). Sensitivity analysis (exclusion of non-users of prosthesis) showed that statin-use remained a significant indicator of longer survival, maximally when combined with antiplatelet use HR 0.52 (0.39-0.68, P < 0.001). CONCLUSIONS: Statin-use is associated with better mobility and long-term survival in rehabilitees after limb loss, particularly when used in combination with antiplatelets. Significantly lower rates of statin-use were observed in female patients. Further research is warranted on gender disparities in statin-use and causality in their association with improved mobility and survival.
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OBJECTIVE: To evaluate the long term outcomes of individuals who attended for transthoracic echocardiograms (TTEs) or lower limb arterial duplex scans (LLADS) and were opportunistically screened for abdominal aortic aneurysms (AAA). METHODS: Follow up of a prospective single centre pilot cohort study conducted between December 2012 and September 2014 at a tertiary vascular centre in the United Kingdom. Men and Women aged 65 and over were invited to undergo AAA screening when attending hospital for TTE or LLADS. Screening was performed by ultrasonographic examination of the abdomen at the end of their planned scans. AAA was defined as an abdominal aorta outer wall to outer wall anteroposterior diameter of 30 mm or more. Patients were excluded if they had a known AAA or previous abdominal aorta intervention. Follow up outcomes were evaluated in December 2020. RESULTS: 762 patients were enrolled in this study; 486 had TTE and 276 patients had LLADS. The overall incidence of AAA was 54 (7.1%) in the combined cohort, 25 (5.1%) in the TTE group, and 29 (10.5%) in the LLADS group. After a median 7.6 years, two of the 54 AAAs received intervention in the form of endovascular repair. Three others reached treatment threshold but were managed conservatively. The overall intervention rate was 3.7% of detected AAAs. Adjusted mortality rates in those with AAA vs. without was 64.8% and 36%, respectively (hazard ratio [HR] 2.02, p < .001). Diabetes (HR 1.35, p = .015) and older age (HR 1.18, p = .17) were the other factors associated with death. CONCLUSION: AAA is associated with a significantly increased mortality rate. Populations attending hospital for TTE or LLADS demonstrate a higher prevalence of AAA than population based screening; however, the proportion offered AAA intervention was low. Further research into opportunistic screening should target those more likely to undergo AAA repair, unless other interventions are demonstrated, to reduce the general increased mortality in AAA patients.
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Aneurisma de la Aorta Abdominal , Diabetes Mellitus , Masculino , Humanos , Femenino , Estudios Prospectivos , Proyectos Piloto , Ecocardiografía , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/epidemiología , Diabetes Mellitus/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVES: The aim of this study was to compare outcomes of major lower limb amputation (MLA) in patients with and without cancer and with cancer patients receiving palliation over amputation for their unsalvageable limb. METHODS: Cancer patients who underwent a major amputation or palliation between 2013 and 2018 were included. Comparison groups were cancer-MLA (active/managed cancers), non-cancer MLA (historic cancer or no cancer history) and cancer-palliation at presentation with unsalvageable limbs. Prospectively collected data was retrospectively analysed for outcomes including survival, postoperative complications, length of stay, suitability for rehabilitation and discharge destination. RESULTS: 262 (cancer and non-cancer) patients underwent MLA and 18 patients with cancer received palliation. Of those amputated, 26 (9.9%) had active or managed cancer, of which 12 were diagnosed in the 6 months before MLA. Cancer-MLA patients presented with more acute ischaemia compared to non-cancer patients. Median survival was significantly different between the cancer-MLA (14.1 [9.5 - 29.5, 95% CI] months), non-cancer MLA (57.7 [45 - 73.6, 95% CI] months) and cancer-palliation (.6 [.4 - 2.3, 95% CI] months) groups, P < .001. A significantly higher proportion of cancer-MLA patients (10/26, 38.5%) were deemed unsuitable for rehabilitation in post-operative assessment compared to non-cancer MLA (21/236, 8.9%) patients, P < .001. There was a variation in destinations of discharge, with a greater proportion of cancer-MLA patients (4/26, 15.4%) going to a nursing home compared to non-cancer MLA (10/236, 4.2%) patients, P = .016. CONCLUSION: Cancer is prevalent among vascular amputees, with a large proportion being occult diagnoses. Cancer is associated with poorer outcomes following amputation, but survival remains significantly better compared to palliation in cancer patients presenting with unsalvageable limbs.
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Pierna , Neoplasias , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias/complicaciones , Neoplasias/diagnóstico , Amputación QuirúrgicaRESUMEN
Chinese hamster ovary (CHO) cells are the leading mammalian cell host employed to produce complex secreted recombinant biotherapeutics such as monoclonal antibodies (mAbs). Metabolic selection marker technologies (e.g. glutamine synthetase (GS) or dihydrofolate reductase (DHFR)) are routinely employed to generate such recombinant mammalian cell lines. Here we describe the development of a selection marker system based on the metabolic requirement of CHO cells to produce proline, and that uses pyrroline-5-carboxylase synthetase (P5CS) to complement this auxotrophy. Firstly, we showed the system can be used to generate cells that have growth kinetics in proline-free medium similar to those of the parent CHO cell line, CHOK1SV GS-KO™ grown in proline-containing medium. As we have previously described how engineering lipid metabolism can be harnessed to enhance recombinant protein productivity in CHO cells, we then used the P5CS selection system to re-engineer lipid metabolism by over-expression of either sterol regulatory element binding protein 1 (SREBF1) or stearoyl CoA desaturase 1 (SCD1). The cells with re-engineered proline and lipid metabolism showed consistent growth and P5CS, SCD1 and SREBF1 expression across 100 cell generations. Finally, we show that the P5CS and GS selection systems can be used together. A GS vector containing the light and heavy chains for a mAb was super-transfected into a CHOK1SV GS-KO™ host over-expressing SCD1 from a P5CS vector. The resulting stable transfectant pools achieved a higher concentration at harvest for a model difficult to express mAb than the CHOK1SV GS-KO™ host. This demonstrates that the P5CS and GS selection systems can be used concomitantly to enable CHO cell line genetic engineering and recombinant protein expression.
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Transient gene expression (TGE) in mammalian cells is a method of rapidly generating recombinant protein material for initial characterisation studies that does not require time-consuming processes associated with stable cell line construction. High TGE yields are heavily dependent on efficient delivery of plasmid DNA across both the plasma and nuclear membranes. Here, we harness the protein nucleoside diphosphate kinase (NDPK-A) that contains a nuclear localisation signal (NLS) to enhance DNA delivery into the nucleus of CHO cells. We show that co-expression of NDPK-A during transient expression results in improved transfection efficiency in CHO cells, presumably due to enhanced transportation of plasmid DNA into the nucleus via the nuclear pore complex. Furthermore, introduction of the Epstein Barr Nuclear Antigen-1 (EBNA-1), a protein that is capable of inducing extrachromosomal maintenance, when coupled with complementary oriP elements on a transient plasmid, was utilised to reduce the effect of plasmid dilution. Whilst there was attenuated growth upon introduction of the EBNA-1 system into CHO cells, when both NDPK-A nuclear import and EBNA-1 mediated technologies were employed together this resulted in enhanced transient recombinant protein yields superior to those generated using either approach independently, including when expressing the complex SARS-CoV-2 spike (S) glycoprotein.
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The timing of carotid endarterectomy (CEA) for symptomatic ipsilateral carotid artery stenosis has evolved in practice over time. Key landmark trials outlined the benefit of performing CEA in the recently symptomatic carotid artery stenosis, defined as revascularisation within 6 months of the index neurological event. Further evidence and sub-analysis demonstrate that performing CEA within 2 weeks of symptoms has the maximal benefit in reducing stroke free survival and is associated with a safe perioperative complication profile. This has translated into guideline recommendations and widespread clinical practice. The case for performing urgent CEA (within 48 hours of index neurological event) over early CEA (within 2 weeks) has been put forward and studied. Data examining perioperative complications for urgent CEA are mostly derived from retrospective single series studies. A moderate balance exists in the literature for the safety and risk of urgent CEA. Although many studies present acceptable perioperative stroke and mortality rates associated with urgent CEA, evidence still exists that the perioperative complications may not be insignificant. This is particularly the case if the presenting neurology is a stroke, rather than a transient ischaemic attack (TIA) or amaurosis fugax. This should be contextualised in the practice of modern aggressive medical therapy with dual antiplatelets and statins, with evidence suggesting a reduction in recurrent ischaemic events prior to surgical intervention. Careful patient selection, presenting neurology and medical therapy is likely to be a key feature in considering urgent CEA versus early CEA.
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The data presented in this article relates to the manuscript entitled 'Engineering of Chinese hamster ovary cell lipid metabolism results in an expanded ER and enhanced recombinant biotherapeutic protein production', published in the Journal Metabolic Engineering [1]. In the article here, we present data examining the overexpression of the lipid metabolism modifying genes SCD1 and SREBF1 in CHO cells by densitometry of western blots and by using mass spectrometry to investigate the impact on specific lipid species. We also present immunofluorescence data at the protein level upon SCD1 and SREBF1 overexpression. The growth profile data during batch culture of control CHO cells and CHO cells engineered to overexpress SCD1 and SREBF1 during batch culture are also reported. Finally, we report data on the yields of model secretory recombinant proteins produced from control, SCD1 or SREBF1 engineered cells using a transient expression systems.
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Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular , Toma de Decisiones Clínicas , Técnicas de Apoyo para la Decisión , Procedimientos Endovasculares , Tiempo de Internación , Selección de Paciente , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Femenino , Estado de Salud , Humanos , Masculino , Alta del Paciente , Readmisión del Paciente , Complicaciones Posoperatorias/etiología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The study aimed to assess the cumulative radiation exposure from preoperative, periprocedural, and follow-up imaging to patients who underwent common endovascular deep venous interventions for acute and chronic central venous outflow obstructive diseases; namely, deep vein thrombosis (DVT) thrombolysis, unilateral chronic iliofemoral venous stenting, and inferior vena cava (IVC) reconstruction in a single center. METHODS: Patients who had DVT thrombolysis of upper extremity (UE) DVT and lower extremity (LE) DVT, unilateral chronic iliofemoral venous stenting, and endovascular IVC reconstruction between May 1, 2012, and July 31, 2017, in a single unit were retrospectively reviewed. Demographic data, anatomic DVT, imaging, technical details of the index procedure, follow-up, and radiation exposure measured in dose-length product, dose-area product (DAP), and fluoroscopy time (FT) from related computed tomography scans and interventions were analyzed. Mann-Whitney U tests were performed to assess for significance of differences between subgroups. A P value of less than .05 was considered significant. RESULTS: In total, 20 UE DVT thrombolysis, 91 LE DVT thrombolysis, 56 unilateral chronic iliofemoral venous stenting, and 39 endovascular IVC reconstruction patients were included in the study, with the following median ages: 39 years (range, 20-67 years), 44 years (range, 15-78 years), 45 years (range, 20-80 years), and 35 years (range, 18 -73 years), respectively. The median cumulative DAP for the index DVT thrombolysis was 9.2 Gycm2 (range, 0.2-176.0 Gycm2) for LE DVT and 2.0 Gycm2 (range, 0.1-11.7 Gycm2) for UE DVT (P < .0001). The median cumulative FT for the index thrombolysis was 981 seconds (range, 20-4890 seconds) and 837 seconds (range, 19-2895 seconds) for LE DVT and UE DVT, respectively (P = .18). For unilateral chronic iliofemoral venous stenting, the median cumulative DAP and FT were 32.4 Gycm2 (range, 0.1-289.6 Gycm2) and 660 seconds (range, 246-4200 seconds), respectively. Meanwhile, the median cumulative DAP and FT for the endovascular IVC reconstruction were 60.8 Gycm2 (range, 2.5-269.1 Gycm2) and 2846 seconds (range, 836-11682 seconds), respectively. The median DAP for secondary procedures during follow-up was 6.6 Gycm2 (range, 0.8 186.5 Gycm2), 1.9 Gycm2 (range, 0.2-111.7 Gycm2), and 24.3 Gycm2 (range, 0.2-157.5 Gycm2) for LE DVT thrombolysis, unilateral chronic iliofemoral venous stenting, and endovascular IVC reconstruction, respectively. CONCLUSIONS: Patient radiation exposure for endovascular deep venous interventions for central venous outflow obstruction measured in DAP and FT seemed to be less than and at most similar to anatomically comparable arterial interventions in the literature. However, these patients were usually much younger than those with arterial diseases and may need secondary interventions involving further radiation exposure in their lifetime.
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Procedimientos Endovasculares , Síndrome de May-Thurner/terapia , Síndrome Postrombótico/terapia , Dosis de Radiación , Exposición a la Radiación , Radiografía Intervencional , Terapia Trombolítica , Procedimientos Quirúrgicos Vasculares , Insuficiencia Venosa/terapia , Trombosis de la Vena/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Femenino , Humanos , Masculino , Síndrome de May-Thurner/diagnóstico por imagen , Auditoría Médica , Persona de Mediana Edad , Seguridad del Paciente , Síndrome Postrombótico/diagnóstico por imagen , Exposición a la Radiación/efectos adversos , Radiografía Intervencional/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Stents , Terapia Trombolítica/efectos adversos , Procedimientos Quirúrgicos Vasculares/efectos adversos , Insuficiencia Venosa/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagen , Adulto JovenRESUMEN
Chinese hamster ovary (CHO) cell expression systems have been exquisitely developed for the production of recombinant biotherapeutics (e.g. standard monoclonal antibodies, mAbs) and are able to generate efficacious, multi-domain proteins with human-like post translational modifications at high concentration with appropriate product quality attributes. However, there remains a need for development of new CHO cell expression systems able to produce more challenging secretory recombinant biotherapeutics at higher yield with improved product quality attributes. Amazingly, the engineering of lipid metabolism to enhance such properties has not been investigated even though the biosynthesis of recombinant proteins is at least partially controlled by cellular processes that are highly dependent on lipid metabolism. Here we show that the global transcriptional activator of genes involved in lipid biosynthesis, sterol regulatory element binding factor 1 (SREBF1), and stearoyl CoA desaturase 1 (SCD1), an enzyme which catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids, can be overexpressed in CHO cells to different degrees. The amount of overexpression obtained of each of these lipid metabolism modifying (LMM) genes was related to the subsequent phenotypes observed. Expression of a number of model secretory biopharmaceuticals was enhanced between 1.5-9 fold in either SREBF1 or SCD1 engineered CHO host cells as assessed under batch and fed-batch culture. The SCD1 overexpressing polyclonal pool consistently showed increased concentration of a range of products. For the SREBF1 engineered cells, the level of SREBF1 expression that gave the greatest enhancement in yield was dependent upon the model protein tested. Overexpression of both SCD1 and SREBF1 modified the lipid profile of CHO cells and the cellular structure. Mechanistically, overexpression of SCD1 and SREBF1 resulted in an expanded endoplasmic reticulum (ER) that was dependent upon the level of LMM overexpression. We conclude that manipulation of lipid metabolism in CHO cells via genetic engineering is an exciting new approach to enhance the ability of CHO cells to produce a range of different types of secretory recombinant protein products via modulation of the cellular lipid profile and expansion of the ER.
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Técnicas de Cultivo Celular por Lotes , Productos Biológicos/metabolismo , Retículo Endoplásmico , Metabolismo de los Lípidos/genética , Ingeniería Metabólica , Animales , Células CHO , Cricetulus , Retículo Endoplásmico/enzimología , Retículo Endoplásmico/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Estearoil-CoA Desaturasa/biosíntesis , Estearoil-CoA Desaturasa/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/biosíntesis , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genéticaRESUMEN
INTRODUCTION: Short stay endovascular aneurysm repair pathways (SS-EVAR) provide potential advantages to both healthcare providers and patients. However, these benefits must be carefully balanced against the inherent risks to patient safety and tariff penalties associated with unplanned readmissions. EVIDENCE ACQUISITION: A literature review was performed using the databases MEDLINE, Embase and Cochrane Library up until March 2019. Search terms used included "endovascular aneurysm repair," "aneurysm repair," "EVAR," "abdominal aortic aneurysm," "day case," "short stay," "fast track," and "ambulatory." EVIDENCE SYNTHESIS: Nine relevant articles (including one prior review on the topic) were identified. This early data suggests that SS-EVAR is associated with good patient satisfaction and modest cost savings for healthcare providers. Patient selection, preoperative preparation and supported discharge with early follow-up are essential components of a SS-EVAR pathway. Increasingly, SS-EVAR tends to be delivered via bilateral percutaneous access and loco-regional anesthesia. Over 70% of patients enrolled onto SS-EVAR pathways successfully complete them. Long procedures with excessive blood loss are associated with pathway non-completion. All serious complications occur within 6 hours of the procedure and the mortality (0-1%), morbidity (8-58%) and readmission rates (0-6%) associated with SS-EVAR remains acceptably low. SS-EVAR pathways can be safely and effectively implemented in both teaching and non-teaching hospitals. CONCLUSIONS: Short-stay EVAR pathways are safe and acceptable to patients. With appropriate selection of motivated patients, successful expedited discharge can be achieved with limited readmissions, thus facilitating increased resource efficiency and cost savings for healthcare providers.
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Aneurisma de la Aorta Abdominal/cirugía , Procedimientos Endovasculares , Ahorro de Costo , Procedimientos Quirúrgicos Electivos/economía , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/economía , Humanos , Tiempo de Internación , Readmisión del Paciente/estadística & datos numéricos , Selección de Paciente , Complicaciones Posoperatorias/epidemiologíaRESUMEN
INTRODUCTION: Transaxillary robotic thyroid surgery was pioneered in South Korea where cultural factors, anthropometry and remuneration favour this. Small thyroid nodules account for the majority of cases due to a national thyroid cancer screening programme. However, the technique has not been evaluated in the United Kingdom where larger thyroid nodules tend to undergo surgery in a patient population with a higher body mass index (BMI). METHODS: Long term prospective non-randomised study. Sixteen consecutive robotic hemithyroidectomy patients were compared to 16 open controls. RESULTS: There were no robotic conversions to open and no significant difference regarding pain, voice, or quality of life (QoL). In the robotic group, long term. scar cosmesis at 3 years was superior (p = 0.02) although the operative time was significantly longer (228 min vs. 85 min, p = 0.01). One patient had a transient recurrent laryngeal nerve paresis and another had temporary shoulder dysfunction. Both resolved in 4 weeks. DISCUSSION: This study highlights the considerable difference between a Western patient population compared to South East Asia. Despite this robotic thyroidectomy is feasible and safe in a UK population. CONCLUSIONS: Despite a low uptake in the UK compared to the Far East, robotic thyroidectomy represents a viable option for selected patients, achieving superior cosmesis compared with conventional thyroidectomy at the expense of time and cost. The key is careful patient selection. A randomised study is needed to establish the clinical efficacy compared to conventional surgery in this population.
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Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Robotizados/efectos adversos , Nódulo Tiroideo/cirugía , Tiroidectomía/efectos adversos , Adulto , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , Cicatriz , Comparación Transcultural , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Prospectivos , Calidad de Vida , República de Corea/etnología , Procedimientos Quirúrgicos Robotizados/métodos , Tiroidectomía/métodos , Resultado del Tratamiento , Reino Unido/etnologíaRESUMEN
INTRODUCTION: Various "scarless" approaches have been described for thyroid and parathyroid surgery. The objective of the current study was to investigate patients' perception of neck scar cosmesis, its impact on quality of life (QoL) and evaluate patient preference with regards to scar location. METHODS: 120 patients undergoing thyroid or parathyroid surgery were followed-up over a 5-year period (2008-2013). Validated tools were used to assess scar perception and its impact on QoL. These were evaluated against sex, age, ethnicity, operation type, histopathology, time following surgery and scar length. RESULTS: Mean follow-up was 2.6 ± 3.8 years. One of the most common post-operative problems was scar-related (n = 18). Caucasian patients and those with benign histology expressed a lower impact on QoL (p < 0.001, p = 0.038). Sex and scar length did not significantly affect patients' perception for scar cosmesis (p > 0.05). Clinicians tended to score scar cosmesis higher than patients (p = 0.02). Most participants (75%) expressed a clear preference for an extracervical "scar-less in the neck" approach. DISCUSSION: Scar-related issues are frequently reported following thyroid and parathyroid surgery. The negative impact, often underestimated by clinicians, is more apparent amongst Asian and Afro-Caribbean patients and can significantly impact on their QoL. This, combined with the lack of correlation between scar length and patient satisfaction, indicates the need to divert research from miniaturising neck scars to concealing them in extracervical sites. CONCLUSION: Patients prefer a scar-less in the neck approach when given the option. A prospective comparative study is required to compare the cervical and extracervical approaches.