Critical Limb Ischaemia in Octogenarians: Treatment Outcomes Compared With Younger Patients.

Objective: A growing proportion of patients with chronic limb threatening ischaemia (CLTI) are elderly, the most challenging for management decisions. The aim was to study the patient profile and outcome of CLTI in octogenarian patients, comparing them with younger patients. Methods: Retrospective cohort of consecutive patients hospitalised for CLTI with infrainguinal disease in a Spanish centre (2013-2020). Data on age, comorbidity, anatomical characteristics, and treatment were gathered. Patients were stratified according to age (<80 and ≥80 years). The primary outcomes were overall survival and limb salvage (LS), analysed using Kaplan-Meier and Cox regression. Results: : A total of 512 patients were enrolled: 305 were <80 years old with mean age 69.7 ± standard deviation (SD) 8.2 years, and 207 were ≥80 years old with mean age 85.3 ± SD 3.6 years. Smoking and diabetes mellitus were more frequent in younger patients (78.0% vs. 45.4%, p < .001; 68.5% vs. 59.5%, p = .037 respectively). Older patients had a higher prevalence of heart and kidney disease (70.5% vs. 57.0%, p = .002; 39.6% vs. 24.3%, p < .001, respectively). The arterial disease was femoropopliteal or tibial in 68.9% and 31.1% in patients <80 years and 58.9% and 41.1% in patients ≥80 years (p = .021). In younger patients, conservative treatment was indicated in 18.0%, endovascular treatment (ET) in 41.6%, and open or hybrid surgery (OS) in 40.3%; in patients ≥80 years these were 36.9%, 37.4%, and 25.7%, respectively (p <. 001). Mean follow up was 23.3 ± SD 17.4 months. One and two year overall survival was 85.4% and 73.0% in younger patients and 64.1% and 51.3% in patients ≥80 years (p < .001). LS was 83.7% and 79% at the same times in younger patients and 75.3% and 72.1% in older ones (p = .045). In younger patients ET led to worse LS than OS (p = .005) but not in older patients (p = .29). Conclusion: Patients ≥80 years with CLTI have higher comorbidity and lower life expectancy and receive conservative treatment more frequently than younger patients. ET and OS are associated with similar survival and LS in these older patients.

Increased let-7d-5p in non-alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis.

BACKGROUND AND AIMS: The molecular mechanisms driving non-alcoholic fatty liver disease (NAFLD) are poorly understood; however, microRNAs might play a key role in these processes. We hypothesize that let-7d-5p could contribute to the pathophysiology of NAFLD and serve as a potential diagnostic biomarker. METHODS: We evaluated let-7d-5p levels and its targets in liver biopsies from a cross-sectional study including patients with NAFLD and healthy donors, and from a mouse model of NAFLD. Moreover, the induction of let-7d-5p expression by fatty acids was evaluated in vitro. Further, we overexpressed let-7d-5p in vitro to corroborate the results observed in vivo. Circulating let-7d-5p and its potential as a NAFLD biomarker was determined in isolated extracellular vesicles from human plasma by RT-qPCR. RESULTS: Our results demonstrate that hepatic let-7d-5p was significantly up-regulated in patients with steatosis, and this increase correlated with obesity and a decreased expression of AKT serine/threonine kinase (AKT), insulin-like growth factor 1 (IGF1), IGF-I receptor (IGF1R) and insulin receptor (INSR). These alterations were corroborated in a NAFLD mouse model. In vitro, fatty acids increased let-7d-5p expression, and its overexpression decreased AKT, IGF-IR and IR protein expression. Furthermore, let-7d-5p hindered AKT phosphorylation in vitro after insulin stimulation. Finally, circulating let-7d-5p significantly decreased in steatosis patients and receiver operating characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker. CONCLUSIONS: Our results highlight the emerging role of let-7d-5p as a potential therapeutic target for NAFLD since its overexpression impairs hepatic insulin signalling, and also, as a novel non-invasive biomarker for NAFLD diagnosis.

Implication of miR-155-5p and miR-143-3p in the Vascular Insulin Resistance and Instability of Human and Experimental Atherosclerotic Plaque.

(1) Background: Cardiovascular diseases (CVDs) are the main cause of death in developed countries, being atherosclerosis, a recurring process underlying their apparition. MicroRNAs (miRNAs) modulate the expression of their targets and have emerged as key players in CVDs; (2) Methods: 18 miRNAs were selected (Pubmed and GEO database) for their possible role in promoting atherosclerosis and were analysed by RT-qPCR in the aorta from apolipoprotein E-deficient (ApoE-/-) mice. Afterwards, the altered miRNAs in the aorta from 18 weeks-ApoE-/- mice were studied in human aortic and carotid samples; (3) Results: miR-155-5p was overexpressed and miR-143-3p was downregulated in mouse and human atherosclerotic lesions. In addition, a significant decrease in protein kinase B (AKT), target of miR-155-5p, and an increase in insulin-like growth factor type II receptor (IGF-IIR), target of miR-143-3p, were noted in aortic roots from ApoE-/- mice and in carotid plaques from patients with advanced carotid atherosclerosis (ACA). Finally, the overexpression of miR-155-5p reduced AKT levels and its phosphorylation in vascular smooth muscle cells, while miR-143-3p overexpression decreased IGF-IIR reducing apoptosis in vascular cells; (4) Conclusions: Our results suggest that miR-155-5p and miR-143-3p may be implicated in insulin resistance and plaque instability by the modulation of their targets AKT and IGF-IIR, contributing to the progression of atherosclerosis.

Embedding Wound Hygiene into a proactive wound healing strategy.

FOREWORD. WOUND HYGIENE: THE NEXT STAGE: Since a panel published the first consensus document on Wound Hygiene in March 2020, there has been a flurry of activity in support of this newly established concept in proactive wound healing.1 The document concluded that all wounds, particularly hard-to-heal ones, will benefit from Wound Hygiene, which should be initiated at the first referral, following a full holistic assessment to identify the wound aetiology and comorbidities, and then implemented at every dressing change until full healing occurs.1 The consensus has since been bolstered by educational webinars; competency-based skills training and support; development of international Wound Hygiene ambassadors; a survey of 1478 respondents, published in July 2021;2 and a case study supplement, published in January 2022, featuring a range of wound types, anatomies and underlying conditions on the improvements in wound-healing progress that can be achieved.3 Wound Hygiene has gained its own identity and is now a term in and of itself, that encompasses a 4-step protocol of care. It is an antibiofilm approach that is increasingly being used across wound care. The results of the survey2 were particularly encouraging for seeing how far Wound Hygiene has come, and how quickly: More than half (57.4%) had heard of the concept of Wound Hygiene Of those, 75.3% have implemented Wound Hygiene Overall, following implementation of Wound Hygiene, 80.3% of respondents reported improved healing rates.2 However, the top three barriers identified by the survey-lack of confidence, competence and research data-show that there is more to be done to support Wound Hygiene in practice.2 As a result, a consensus panel of international key opinion leaders convened virtually in the summer of 2021 to discuss what has been done so far, the outputs of the survey, and ideas for addressing the unmet needs identified by the results. The result is this publication, which represents an addendum to the initial consensus document, broadening support for implementation of Wound Hygiene. This document will reflect on the reasons Wound Hygiene has been successful in its first two years of implementation, reiterating its DNA: Do not wait to treat hard-to-heal wounds Use a simple 4-step approach Enable all healthcare professionals to implement and use Wound Hygiene. The document will also discuss the evolution of the Wound Hygiene concept, focusing on how and when to implement Wound Hygiene on all tissue types of hard-to-heal wounds, and proposing what these are. The panel has expanded the framework in which Wound Hygiene is used, with the ultimate objective of introducing the concept of 'embedding Wound Hygiene intro a proactive wound healing strategy.' Key inefficiencies are often observed along the journeys of people living with hard-to-heal wounds. The limited number of specialised healthcare professionals and the resulting delays in reaching them may increase the likelihood of a hard-to-heal wound developing. In a world where so much is happening so quickly that we may, at times, feel powerless to drive change, the panel wants to provide further guidance to propel the use of Wound Hygiene. The concept of Wound Hygiene is resonating, and the panel wants you to know that in whatever region you work, in whatever area of clinical practice, you are enabled to make this change. Wielding the 4-step Wound Hygiene protocol consistently is a key action every healthcare professional in every care setting can take to tackle the global wound care crisis. Wound Hygiene has taken off-now, where do we want to land? In a place where Wound Hygiene is practised on all wounds, at every stage, until healing. The panel once again recognises that the community of global healthcare providers should consider their local standards and guidelines when applying the recommendations of this document. To this end, the panel has created a flexible 3-phase framework that situates Wound Hygiene as integral to proactive wound healing. The panel hopes you will continue to implement Wound Hygiene and see the benefits it can bring to people living with wounds, as well as those who care for them.

Implementation of Wound Hygiene in clinical practice: early use of an antibiofilm strategy promotes positive patient outcomes.

Non-healing wounds are devastating for patients, potentially causing long-term morbidity and an impaired quality of life. They also incur a huge health economic burden for health-care services. Understanding of the causes of non-healing wounds has increased significantly. While the need to address the underlying aetiology has always been acknowledged, the role of biofilm in delaying or preventing healing is now accepted. There is a consensus on the need to debride the wound to remove biofilm and then prevent its reformation, to kickstart healing. The potential benefits of incorporating an antibiofilm component within the wound bed preparation framework are clear. However, such a strategy needs to be flexible enough so that it can be implemented by all practitioners, regardless of their expertise or specialty. Wound Hygiene does this. This supplement describes the Wound Hygiene protocol, and includes a selection of case studies on different wound types, demonstrating its ease of use and effectiveness in clinical practice.

Encuesta sobre la higiene de las heridas: conocimiento, implementación, obstáculos y resultados.

OBJETIVO: Se ha desarrollado una encuesta para comprender el conocimiento y la implementación actual del concepto de higiene de las heridas un año después de su difusión. También se analizaron los obstáculos para su implementación y los resultados. MÉTODO: La revista Journal of Wound Care (JWC), con la colaboración de ConvaTec, desarrolló una encuesta de 26 preguntas, compuesta por respuestas de opción múltiple y texto libre, que distribuyó globalmente por correo electrónico y en línea; la encuesta estuvo abierta unas 12 semanas. Debido a la naturaleza exploratoria de la investigación, se utilizó una técnica de muestreo no probabilístico. Los autores analizaron los resultados de la encuesta para sacar conclusiones de los datos. RESULTADOS: Un total de 1478 participantes dio su consentimiento para el uso de sus datos combinados anonimizados. Casi el 90% era de Estados Unidos o el Reino Unido. La mayoría se desempeñaba como especialista en el cuidado de las heridas y estaba distribuido equitativamente entre centros de atención primaria y hospitales de agudos. El 66,6% había trabajado en el área de cuidado de las heridas durante más de 8 años. Los encuestados trabajaban con una amplia variedad de tipos de heridas. Más de la mitad (57,4%) había oído hablar del concepto de higiene de las heridas, y entre ellos, el 75,3% la había implementado; el 78,7% respondió que la aplicaba "siempre", mientras que el 20,8% lo hacía "a veces". Los tres principales obstáculos para su adopción fueron la confianza (39,0%), el deseo de que haya más estudios sobre la higiene de las heridas (25,7%) y la competencia (24,8%). En general, tras la implementación de la higiene de las heridas, el 80,3% informó que las tasas de cicatrización de sus pacientes habían mejorado. CONCLUSIÓN: Los encuestados estuvieron totalmente de acuerdo en que la implementación de la higiene de las heridas es un método exitoso para el tratamiento del biofilm y un componente fundamental para mejorar las tasas de cicatrización en heridas de difícil cicatrización. Sin embargo, los obstáculos para su adopción e implementación demuestran que se necesitan cursos integrales de educación y capacitación, apoyo institucional para los cambios de política, protocolos, y más estudios clínicos para promover la higiene de las heridas.

Concerted regulation of non-alcoholic fatty liver disease progression by microRNAs in apolipoprotein E-deficient mice.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is constantly increasing, and altered expression of microRNAs (miRNAs) fosters the development and progression of many pathologies, including NAFLD. Therefore, we explored the role of new miRNAs involved in the molecular mechanisms that trigger NAFLD progression and evaluated them as biomarkers for diagnosis. As a NAFLD model, we used apolipoprotein E-deficient mice administered a high-fat diet for 8 or 18 weeks. We demonstrated that insulin resistance and decreased lipogenesis and autophagy observed after 18 weeks on the diet are related to a concerted regulation carried out by miR-26b-5p, miR-34a-5p, miR-149-5p and miR-375-3p. We also propose circulating let-7d-5p and miR-146b-5p as potential biomarkers of early stages of NAFLD. Finally, we confirmed that circulating miR-34a-5p and miR-375-3p are elevated in the late stages of NAFLD and that miR-27b-3p and miR-122-5p are increased with disease progression. Our results reveal a synergistic regulation of key processes in NAFLD development and progression by miRNAs. Further investigation is needed to unravel the roles of these miRNAs for developing new strategies for NAFLD treatment. This article has an associated First Person interview with the joint first authors of the paper.

A Systematic Review and Meta-analysis of Peri-Procedural Outcomes in Patients Undergoing Carotid Interventions Following Thrombolysis.

OBJECTIVE: To evaluate the safety of carotid artery stenting (CAS) and carotid endarterectomy (CEA) after thrombolytic therapy (TT). DATA SOURCES: Medline, Scopus, and Cochrane databases. REVIEW METHODS: Systematic review and meta-analysis of studies involving patients who underwent CEA/CAS after TT. RESULTS: In 25 studies (n = 147 810 patients), 2 557 underwent CEA (n = 2 076) or CAS (n = 481) following TT. After CEA, the pooled peri-procedural stroke/death rate was 5.2% (95% confidence interval [CI] 3.3 - 7.5) and intracranial haemorrhage (ICH) was 3.4% (95% CI 1.7 - 5.6). After CAS, the pooled peri-procedural stroke/death rate was 14.9% (95% CI 11.9 - 18.2) and ICH was 5.5% (95% CI 3.7 - 7.7). In case control studies comparing CEA outcomes in patients receiving TT vs. no TT, peri-procedural death/stroke was non-significantly higher after TT (4.3% vs. 1.5%; odds ratio [OR] 2.34, 95% CI 0.74 - 7.47), but ICH was significantly higher after TT (2.2% vs. 0.12%; OR 7.82, 95% CI 4.07 - 15.02), as was local haematoma formation (3.6% vs. 2.26%; OR 1.17, 95% CI 1.17 - 2.33). In case control studies comparing CAS outcomes in patients receiving TT vs. no TT, peri-procedural stroke/death was significantly higher after TT (5.2% vs. 1.5%; OR 8.49, 95% CI 2.12 - 33.95) as was ICH (5.4% vs. 0.7%; OR 7.48, 95% CI 4.69 - 11.92). Meta-regression analysis demonstrated an inverse association between the time interval from intravenous (IV) TT to undergoing CEA and the risk of peri-procedural stroke/death (p = .032). Peri-operative stroke/death was 13.0% when CEA was performed three days after TT and 10.6% when performed four days after TT, with the risk reducing to within the currently accepted 6% threshold after six-seven days had elapsed. CONCLUSION: Peri-procedural ICH and local haematoma were significantly more frequent in patients undergoing CEA after TT (vs. no TT), although there were no randomised comparisons. Peri-procedural hazards were also significantly higher for CAS after TT. The inverse relationship between timing to CEA and peri-procedural stroke/death mandates careful patient selection and suggests that it may be safer to defer CEA for six-seven days after TT.

Outcomes of Small Incidental Abdominal Aortic Aneurysms in Octogenarian and Nonagenarian Patients in Northern Spain.

OBJECTIVE: Greater population life expectancy and consistent improvement in diagnostic techniques have increased the diagnosis of abdominal aortic aneurysms (AAAs) in the elderly population. The aim was to study the natural history of small (< 55 mm) incidental AAAs in octogenarian and nonagenarian patients to assess the need for follow up and/or invasive treatment. METHODS: This was a retrospective analysis of a prospective registry. Patients ≥ 80 years old at the time of diagnosis of a < 55 mm AAA in 1988-2018 were selected. Clinical and anatomical characteristics were registered. Patients were divided in three groups: 30 - 39 mm, 40 - 49 mm, and 50 - 54 mm AAA. The outcome variables were aorto-iliac rupture, AAA reaching a surgical threshold (≥ 55 mm), and death. A descriptive statistical analysis was performed and life tables, Kaplan-Meier curves, and uni- and multivariable Cox regression were used. RESULTS: Three hundred and ten patients were included, 256 (82.6%) men, with mean index age of 84.5 years (standard deviation [SD] 3.5), and median follow up of 37.9 months (interquartile range [IQR] 18.2 - 65.4). Eighteen (5.8%) AAAs ruptured; four of these patients were operated on and only one survived. Sixty-two (20%) AAA reached a surgical size; eight were repaired electively, with 0% early mortality. The survival rates were 81%, 70%, and 38% at one, two, and five years. The rupture rates were 1%, 2%, and 6% and the AAAs reaching surgical threshold were 1%, 4%, and 19% for the same time periods. AAA size < 40 mm was an independent protective factor from rupture (0.13; 95% confidence interval [CI] 0.03 - 0.48), reaching surgical threshold (0.08; 95% CI 0.04 - 0.16) and death (0.63; 95% CI 0.42 - 0.95). CONCLUSION: The risk of late rupture of small incidental AAA diagnosed in octogenarian and nonagenarian patients is very small, especially when the AAA is < 40 mm in diameter. In contrast, global mortality is high. Conservative management seems sensible, with strict selection of the patients who would benefit from follow up and eventual repair.

Tratamiento combinado de disfagia lusoria y estenosis carotídea ipsilateral concomitante / Combined treatment of dysphagia lusoria and concomitant ipsilateral carotid artery stenosis

INTRODUCCIÓN: la arteria subclavia aberrante es la anomalía más común del arco aórtico, aunque la clínica de disfagia lusoria aparece tan solo en el 0,5-2 % de los pacientes. No existe ningún consenso sobre su tratamiento. CASO CLÍNICO: se presenta el caso de una paciente de 86 años con clínica de disfonía y disfagia de 1,5-2 años de evolución que asocia una pérdida de peso de 10 kg en los últimos 6 meses. En el escáner realizado durante el estudio se encuentra una arteria subclavia aberrante no dilatada que comprime el esófago a su paso retrocardial. Además, la paciente presentaba una estenosis del 60 % de la arteria carótida ipsilateral que le había ocasionado un ictus 5 meses antes. Se realiza un bypass carótido-subclavio derecho con prótesis PTFE de 6 mm y en la misma intervención, tras el procedimiento anterior, se realiza una endarterectomía carotídea derecha y angioplastia quirúrgica. El posoperatorio transcurrió sin complicaciones. La paciente se mantuvo asintomática, sin eventos neurológicos; tampoco disfagia ni disfonía. Pudo retomar la ingesta normal de alimentos. En el CT de control a los 10 días se observó la arteria subclavia derecha trombosada sin compresión residual, por lo que no se consideró necesaria la exclusión de su origen con una endoprótesis torácica. DISCUSIÓN: aunque en un primer momento se consideró la posibilidad de realizar un tratamiento en dos tiempos (cirugía abierta y, posteriormente, endovascular torácico), el tratamiento quirúrgico combinado permitió tratar la disfagia lusoria, así como la estenosis carotídea sintomática ipsilateral, durante la misma intervención para no tener que someter a una paciente mayor a una cirugía excepcionalmente larga, además de omitir el uso de una endoprótesis torácica complementaria que finalmente no fue necesaria

INTRODUCTION: the aberrant subclavian artery is the most common variation of the aortic arch but symptoms of dysphagia lusoria appear only in 0,5-2 % of the patients. There is no consensus on its treatment. CASE REPORT: we hereby present the case of an 86 year-old woman who had suffered dysphonia and dysphagia for 1.5-2 years associating a loss of 10 kg of weight in the last 6 months. An angioCT scan revealed a non-dilated aberrant right subclavian artery which compressed of the retrocardial esophagus, and a 60 % stenosis of the right carotid artery, which had caused an ipsilateral minor stroke 5 months before. We performed a right carotid-subclavian bypass using a 6 mm ePTFE graft, followed by a right carotid endarterectomy and Dacron patch angioplasty in the same procedure. The postoperative period was uneventful, the patient remained asymptomatic, with no neurological symptoms, dysphagia or dysphonia, and resumed normal oral intake. Ten days after the procedure the control CT revealed a thrombosed right subclavian artery with no residual esophageal compression, so an additional endovascular occlusion of the subclavian origin was deemed unnecessary. DISCUSSION: although we first considered the possibility of performing a sequential hybrid treatment, with initial surgical bypass and secondary thoracic endovascular grafting, the combined open surgical technique allowed us to solve both the dysphagia lusoria and the symptomatic right carotid stenosis in one single procedure, and the complementary thoracic endografting was ultimately unnecessary