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2.
Artículo en Inglés | MEDLINE | ID: mdl-38082651

RESUMEN

Uroflowmetry is a non-invasive diagnostic test used to evaluate the function of the urinary tract. Despite its benefits, it has two main limitations: high intra-subject variability of flow parameters and the requirement for patients to urinate on demand. To overcome these limitations, we have developed a low-cost ultrasonic platform that utilizes machine learning (ML) models to automatically detect and record natural in-home voiding events, without any need for user intervention. This platform operates outside of human-audible frequencies, providing privacy-preserving, automatic uroflowmetries that can be conducted at home as part of daily routines. After evaluating several machine learning algorithms, we found that the Multi-layer Perceptron classifier performed exceptionally well, with a classification accuracy of 97.8% and a low false negative rate of 1.2%. Furthermore, even on lightweight SVM models, performance remains robust. Our results also showed that the voiding flow envelope, helpful for diagnosing underlying pathologies, remains intact even when using only inaudible frequencies.Clinical relevance- This classification task has the potential to be part of an essential toolkit for urology telemedicine. It is especially useful in areas that lack proper medical infrastructure but still host ubiquitous embedded privacy-preserving audio capture devices with Edge AI capabilities.


Asunto(s)
Algoritmos , Privacidad , Humanos , Micción , Redes Neurales de la Computación , Acústica
3.
Artículo en Inglés | MEDLINE | ID: mdl-38082693

RESUMEN

This work constitutes a first approach to automatically classify the urination medium for non-invasive sound based uroflowmetry tests. Often the voiding flow impacts the toilet wall (often made of ceramic) instead of the water. This causes a reduction in the amplitude of the recorded audio signal, and thus a reduction in the amplitude of the extracted envelope. Analysing the envelope alone, it is not possible to tell accurately if the reduction in the amplitude is due to a low voiding flow or an impact on the toilet walls. In this work, we carry out a study on the classification of sound uroflowmetry data depending on the medium where the urine impacts within the toilet: water or ceramic. In the analysis, a classification algorithm is proposed to identify the physical medium automatically based on the urination acoustics. The classification algorithm takes as input the frequency spectrum, the variance, and the kurtosis of the audio signal corresponding to a voiding event.Clinical relevance- Sound uroflowmetry has a strong correlation with the standard uroflowmetry. It is useful for the non-invasive detection of pathologies associated with the urinary tract as a support tool for information processing and screening. It consists of a characterization of the urinary flow patterns by capturing the sound generated when the urine stream impacts the water in the toilet. Identifying the medium which originates the sound is of paramount importance to better interpret the sound uroflowmetry.


Asunto(s)
Micción , Urodinámica , Sonido , Acústica , Agua
4.
Circ Res ; 133(12): 1022-1039, 2023 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-37961886

RESUMEN

BACKGROUND: The endocardium is a crucial signaling center for cardiac valve development and maturation. Genetic analysis has identified several human endocardial genes whose inactivation leads to bicuspid aortic valve formation and calcific aortic valve disease, but knowledge is very limited about the role played in valve development and disease by noncoding endocardial regulatory regions and upstream factors. METHODS: We manipulated Notch signaling in mouse embryonic endocardial cells by short-term and long-term coculture with OP9 stromal cells expressing Notch ligands and inhibition of Notch activity. We examined the transcriptional profile and chromatin accessibility landscape for each condition, integrated transcriptomic, transcription factor occupancy, chromatin accessibility, and proteomic datasets. We generated in vitro and in vivo models with CRISPR-Cas9-edited deletions of various noncoding regulatory elements and validated their regulatory potential. RESULTS: We identified primary and secondary transcriptional responses to Notch ligands in the mouse embryonic endocardium, and a NOTCH-dependent transcriptional signature in valve development and disease. By defining the changes in the chromatin accessibility landscape and integrating with the landscape in developing mouse endocardium and adult human valves, we identify potential noncoding regulatory elements, validated selected candidates, propose interacting cofactors, and define the timeframe of their regulatory activity. Additionally, we found cooperative transcriptional repression with Hippo pathway by inhibiting nuclear Yap (Yes-associated protein) activity in the endocardium during cardiac valve development. CONCLUSIONS: Sequential Notch-dependent transcriptional regulation in the embryonic endocardium involves multiple factors. Notch activates certain noncoding elements through these factors and simultaneously suppresses elements that could hinder cardiac valve development and homeostasis. Biorxviv: https://www.biorxiv.org/content/10.1101/2023.03.23.533882v1.full.


Asunto(s)
Endocardio , Vía de Señalización Hippo , Animales , Ratones , Humanos , Endocardio/metabolismo , Proteómica , Factores de Transcripción/metabolismo , Cromatina/genética , Cromatina/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Regulación del Desarrollo de la Expresión Génica
5.
Artículo en Inglés | MEDLINE | ID: mdl-37898359

RESUMEN

OBJECTIVE: To assess differences in the five year abdominal aortic aneurysm (AAA) sac regression rate after endovascular aneurysm repair (EVAR) in patients with and without diabetes mellitus (DM). METHODS: An international prospective registry (Europe, USA, Brazil, Australia, and New Zealand) of patients treated with the GORE EXCLUDER endograft. All scheduled EVARs for infrarenal AAA between 2014 and 2016 with complete five year imaging follow up were included. Emergency procedures, ancillary proximal procedures, and inflammatory and infectious aetiologies were excluded. Descriptive and inferential statistics, and Cox proportional hazards survival models were used. A control group of patients without DM with similar age and comorbidities was selected using propensity scores, matched in a 1:2 scheme. RESULTS: A total of 2 888 patients (86.1% male; mean age 73.5 ± 8 years) was included, of whom 545 (18.9%) had DM. Patients with DM had higher rates of hypertension (89.2% vs. 78.4%), dyslipidaemia (76.0% vs. 60.7%), coronary artery disease (52.3% vs. 37.9%), and chronic renal impairment (20.9% vs. 14.0%) (all p < .001). The mean pre-procedural AAA diameter was 58.1 ± 10 mm. Five years post-EVAR, the type 1A endoleak rate was 1.1% (0.6% DM vs. 1.2% non-DM), the endograft related re-intervention rate was 7.3% (6.2% vs. 7.6%), the major adverse cardiovascular event (MACE) rate was 1.4% (1.1% vs. 1.5%), and aortic related mortality rate was 1.0% (0.6% vs. 1.2%), without statistically significant differences between groups. The overall five year mortality rate was higher in diabetics (36.3% vs. 30.5%; hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.07 - 1.58; p = .001). No statistically significant differences were found in sac regression rate (≥ 5 mm) between diabetics and non-diabetics 70.0% vs. 73.1%; HR 0.88, 95% CI 0.75-1.04; p = .131. These differences remained statistically non-significant after excluding patients performed out of instructions for use (p = .61) and patients with types 1, 2 or 3 endoleaks (p = .39). CONCLUSION: The paradoxical relationship between DM and AAA does not appear to result in differences in post-EVAR sac regression rates. However, even when controlling for other comorbidities, patients with DM undergoing EVAR may have a higher five year mortality rate.

6.
Vascular ; : 17085381231193453, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37526918

RESUMEN

OBJECTIVES: Several predictive models exist for estimating the postoperative risks of abdominal aortic aneurysm (AAA) repair, although no particular tool has seen widespread use. We present the results of a multicenter, historic cohort study comparing the predictive capacity of the psoas muscle area (PMA), radiodensity (PMD), and lean muscle area (LMA) as surrogate markers of sarcopenia, over short- and long-term outcomes after AAA repair, compared to the mFI-5 and American Society of Anesthesiologists (ASA) scales. METHODS: Retrospective review was conducted of all consecutive AAA elective repair cases (open or endovascular) in three tertiary-care centers from 2014 to 2019. Cross-sectional PMA, PMD, and LMA at the mid-body of the L3 vertebra were measured by two independent operators in the preoperative computed tomography. Receiver operating characteristic (ROC) curves were used to determine optimal cutoff values. Bivariate analysis, logistic regression, and Cox's proportional hazards models were built to examine the relationship between baseline variables and postoperative mortality, long-term mortality, and complications. RESULTS: 596 patients were included (mean age 72.7 ± 8 years, 95.1% male, 66.9% EVAR). Perioperative mortality was 2.3% (EVAR 1.2% vs open repair 4.6%, p = .015), and no independent predictors could be identified in the multivariate analysis. Conversely, an age over 74 years old (OR 1.84 95%CI 1.25-2.70), previous heart diseases (OR 1.62 95%CI 1.13-2.32), diabetes mellitus (OR 1.61 95%CI 1.13-2.32), and a PMD value over 66 HU (OR 0.58 95%CI 0.39-0.84) acted as independent predictors of long-term mortality in the Cox's proportional hazards model. Heart diseases (congestive heart failure or coronary artery disease), serum creatinine levels over 1.05 mg/dL, and an aneurysm diameter over 60 mm were independent predictors of major complications. CONCLUSION: Surrogate markers of sarcopenia had a poor predictive profile for postoperative mortality after AAA repair in our sample. However, PMD stood out as an independent predictor of long-term mortality. This finding can guide future research and should be confirmed in larger datasets.

7.
JAMA Cardiol ; 8(8): 721-731, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37405741

RESUMEN

Importance: Nonsyndromic bicuspid aortic valve (nsBAV) is the most common congenital heart valve malformation. BAV has a heritable component, yet only a few causative genes have been identified; understanding BAV genetics is a key point in developing personalized medicine. Objective: To identify a new gene for nsBAV. Design, Setting, and Participants: This was a comprehensive, multicenter, genetic association study based on candidate gene prioritization in a familial cohort followed by rare and common association studies in replication cohorts. Further validation was done using in vivo mice models. Study data were analyzed from October 2019 to October 2022. Three cohorts of patients with BAV were included in the study: (1) the discovery cohort was a large cohort of inherited cases from 29 pedigrees of French and Israeli origin; (2) the replication cohort 1 for rare variants included unrelated sporadic cases from various European ancestries; and (3) replication cohort 2 was a second validation cohort for common variants in unrelated sporadic cases from Europe and the US. Main Outcomes and Measures: To identify a candidate gene for nsBAV through analysis of familial cases exome sequencing and gene prioritization tools. Replication cohort 1 was searched for rare and predicted deleterious variants and genetic association. Replication cohort 2 was used to investigate the association of common variants with BAV. Results: A total of 938 patients with BAV were included in this study: 69 (7.4%) in the discovery cohort, 417 (44.5%) in replication cohort 1, and 452 (48.2%) in replication cohort 2. A novel human nsBAV gene, MINDBOMB1 homologue MIB1, was identified. MINDBOMB1 homologue (MIB1) is an E3-ubiquitin ligase essential for NOTCH-signal activation during heart development. In approximately 2% of nsBAV index cases from the discovery and replication 1 cohorts, rare MIB1 variants were detected, predicted to be damaging, and were significantly enriched compared with population-based controls (2% cases vs 0.9% controls; P = .03). In replication cohort 2, MIB1 risk haplotypes significantly associated with nsBAV were identified (permutation test, 1000 repeats; P = .02). Two genetically modified mice models carrying Mib1 variants identified in our cohort showed BAV on a NOTCH1-sensitized genetic background. Conclusions and Relevance: This genetic association study identified the MIB1 gene as associated with nsBAV. This underscores the crucial role of the NOTCH pathway in the pathophysiology of BAV and its potential as a target for future diagnostic and therapeutic intervention.


Asunto(s)
Enfermedad de la Válvula Aórtica Bicúspide , Transducción de Señal , Ubiquitina-Proteína Ligasas , Receptores Notch/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Estudios de Asociación Genética , Humanos
8.
Rev. logop. foniatr. audiol. (Ed. impr.) ; 43(2): [100302], Abr-Jun 2023. tab
Artículo en Español | IBECS | ID: ibc-221019

RESUMEN

Introducción: La esclerosis múltiple es una enfermedad desmielinizante de origen autoinmune que afecta al sistema nervioso central. Entre los daños que ocasiona se encuentran las alteraciones del habla, lo que compromete la capacidad comunicativa de las personas con esta enfermedad, disminuyendo así su calidad de vida. Objetivo: Analizar cómo influyen los trastornos de habla de las personas con esclerosis múltiple en las medidas de calidad de vida. Material y método: Participaron 45 personas con esclerosis múltiple, 14 (31.11%) con alteraciones del habla y 31 (68.88%) sin ellas. A todos se les pasó el Protocolo de Evaluación del Habla (PEH) y 2pruebas de calidad de vida (QoL-Dys y FAMS). Resultados: No se observaron diferencias en la calidad de vida general entre los participantes con y sin alteraciones del habla, pero sí en los ítems referidos a los índices de tristeza y depresión y en la prueba de calidad de vida específica respecto al habla. Conclusiones: Las personas con esclerosis múltiple muestran una reducción del tiempo máximo de fonación independientemente de que tengan o no disartria. Cuando esta está presente, la percepción que tienen sobre su calidad de vida se ve más afectada, especialmente respecto a las reacciones percibidas de terceras personas y a los índices de tristeza y depresión.(AU)


Introduction: Multiple sclerosis is a demyelinating disease of autoimmune origin that affects the central nervous system. Among the damages it causes are the alterations of speech, which compromises the communicative capacity of people with this disease, thus decreasing their quality of life. Objective: To analyze how speech disorders of people with multiple sclerosis influence quality of life measures. Material and method: 45 people with multiple sclerosis participated, 31 (68.88%) with no speech alterations and 31 (68,88%) with them. A speech assessment protocol (PEH), and 2quality of life test (QoL-Dys and FAMS) were applied to all the participants. Results: There are no differences in the general quality of life between participants with and without speech alterations, but there are differences in the items related to the rates of sadness and depression; and in the specific quality of life test regarding speech. Conclusions: People with multiple sclerosis show a reduction in maximum phonation time regardless of whether or not they have dysarthria. When this is present, their perception of their quality of life is more affected, especially with regard to the perceived reactions and the levels of sadness and depression.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Calidad de Vida , Esclerosis Múltiple , Trastornos del Habla , Disartria , Fonación , Afasia , Aflicción , Depresión , España , Trastornos de la Comunicación , Audiología , Fonoaudiología
9.
Rev. argent. radiol ; 87(2): 54-65, jun. 2023. graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1449415

RESUMEN

Resumen El síndrome linfoproliferativo postrasplante (SLPT o PTLD por sus siglas en inglés, posttransplantation lymphoproliferative disorder) consiste en un grupo heterogéneo de enfermedades linfoproliferativas que ocurren en el marco de la inmunosupresión postrasplante, que pueden abarcar desde una simple hiperplasia linfoidea hasta un linfoma maligno de alto grado, con eventual evolución fatal. Se estima su desarrollo entre el 1 y el 20% de los pacientes trasplantados. Los principales factores asociados con el desarrollo de SLPT son el grado de inmunosupresión y el virus de Epstein Barr (VEB). La mayoría suceden dentro del primer año postrasplante, pero el riesgo de desarrollarlo continúa hasta los 10 años. Su presentación es variable, puede ser asintomático o con manifestaciones inespecíficas (fiebre, linfadenopatías), lo que dificulta su diagnóstico desde el punto de vista clínico. Por este motivo, los métodos de imagen cumplen un rol fundamental en su diagnóstico, siendo la tomografía computada (TC) el más utilizado. Se deberá sospechar desde las imágenes en todo paciente trasplantado con afección nodal, principalmente en retroperitoneo y mesenterio; y/o extranodal, como el tracto gastrointestinal, órganos y el sistema nervioso central. El objetivo del presente trabajo consiste en realizar una revisión sobre el SLPT mediante las imágenes y conocer la importancia de su sospecha y diagnóstico.


Abstract Post-transplantation lymphoproliferative disease (PTLD) is a heterogeneous group of lymphoproliferative diseases in behave of posttransplant immunosuppression, which ranges from relatively benign lymphoid hyperplasia to poorly differentiated lymphoma, affecting different organs with fatal evolution, eventually. PTLD constitutes a disease with an increasing incidence and detection, estimating its development between 1 and 20% of transplant patients. Although it is based on a multifactorial etiology, the main factors associated with the development of PTLD are the degree of immunosuppression and the Epstein Barr virus (EBV). Most cases of this disorder occur during the first year posttransplant, however, the risk of developing is included in the next 5 to 10 years. The clinical presentation is variable, and the patient may be asymptomatic, or with nonspecific manifestations such as fever, lymphadenopathy, or digestive symptoms, making it difficult to diagnose this entity from clinical suspicion. Imaging plays a fundamental role in diagnosis of PTLD, with the computed tomography (CT) being the most widely used. Findings can mimic those lymphoproliferative processes in patients with no transplant and should be suspect in every transplant patient with nodal affection, such as retroperitoneum and mesenteric¸ or extranodal compromise, like gastrointestinal tract, solid organs, and central nervous system. The aim of this paper is to revise all about the PTLD trough different imaging methods and to know the importance of its suspicion and diagnosis.

10.
Front Neurol ; 14: 1149268, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37188309

RESUMEN

Fibromyalgia affects skeletal muscles presenting with muscle stiffness, pain, and fatigue. The exercise practice is wellstabilized and suggested for the reduction of symptoms. However, there are some gaps in the literature related to balance and neuromuscular performance in a strength training protocol. The aim of this study is to structure a protocol to verify the effects of strength training applied over a short period, on balance, neuromuscular performance, and fibromyalgia symptoms. Additionally, we intend to analyze the effects of a short period of cessation of training. Participants will be recruited through flyers, internet advertisements, clinical referrals, health professionals, and email outreach. Volunteers will be randomly assigned to the control group or experimental group. Before the training period, symptoms (Fibromyalgia Impact Questionnaire, Visual Analog Scale), balance (force plate), and neuromuscular performance (medicine ball throw and vertical jump) will be assessed. Participants in the experimental group will perform strength training twice a week (50 min each), on alternate days, for 8 weeks (16 sessions). Then, 4 weeks of detraining will be completed. This training program will be carried out online, using real-time videos, and the participants will be divided into two groups with different schedules. The Borg scale will be used to monitor perceived effort in each session. There is a gap in the literature about exercise prescriptions for fibromyalgia. The supervised online intervention enables a wide range of participation. The strength exercises used (without the use of external materials and/or machines) and load (few repetitions per set) represent a novelty to training programming. Moreover, this training program respects the limitations and individuality of the volunteers, providing exercise adaptations. With positive results, the present protocol could be an easy-to-apply guideline with clear instructions on the details related to exercise prescription. Also, ensure the effectiveness of a low-cost and feasible treatment, especially for fibromyalgia patients. Clinical trial registration: https://clinicaltrials.gov/, identifier: NCT05646641.

12.
Ann Vasc Surg ; 94: 316-322, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36868456

RESUMEN

BACKGROUND: Aortic infections are uncommon but life-threatening diseases. The material of choice for aortic reconstruction is still a matter of debate. The aim of this study is to examine the short- and mid-term outcomes in the treatment of abdominal aortic infections using self-made bovine pericardium tube grafts. METHODS: This retrospective, single-center study collected all patients who underwent in situ abdominal aortic reconstruction using self-made bovine pericardial tube grafts between February 2020 and December 2021 in a tertiary care center. Patient comorbidities, symptoms, radiological, bacteriological, and perioperative findings, as well as postoperative outcomes, were analyzed. RESULTS: Bovine pericardial aortic tube grafts were used in 11 patients (10 males, median age 68.7 years). Two patients presented with a native aortic infection, and 9 had graft infections (4 bypass grafts, 4 endografts, and a plurioperated patient who had undergone both endovascular and open procedures). There were 2 emergent surgeries due to infectious aneurysm ruptures. All patients were symptomatic, and the most frequent clinical finding was lumbar or abdominal pain (36%), followed by wound infection (27%), and fever (18%). Seven bifurcated and 4 straight pericardial tube grafts were needed. Purulent drainage was obtained around the previous graft or in the aneurysmal sac in 7 cases; intraoperative cultures were positive in 6 cases (gram + bacteria). Two patients died in the immediate postoperative period (perioperative mortality 18%; urgent procedures 50%; scheduled procedures 11%). One patient had a major complication due to bilateral severe acute respiratory syndrome coronavirus 2 pneumonia. There was 1 single reintervention to control hemostasis due to bleeding nongraft-related. The median follow-up was 14.1 months (3-24 months). CONCLUSIONS: Our preliminary experience in the treatment of abdominal aortic infections by in situ reconstruction with self-made bovine pericardial tube grafts shows promising results. These should be confirmed in the long term.


Asunto(s)
Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , COVID-19 , Procedimientos Endovasculares , Masculino , Humanos , Bovinos , Animales , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Aorta/cirugía , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Prótesis Vascular , Diseño de Prótesis
13.
Eur J Vasc Endovasc Surg ; 65(5): 720-727, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36731765

RESUMEN

OBJECTIVE: Aortic endografting and antegrade in situ laser fenestration of visceral arteries (LFEVAR) may be considered as an alternative to open surgery for the emergency repair of complex abdominal aortic aneurysms (AAA) in fragile patients. The aim of this article was to evaluate the midterm results of LFEVAR performed with polyester endografts. METHODS: From August 2015 to December 2020, all consecutive LFEVAR performed for non-deferrable treatment of complex AAA were analysed. Polyester endografts were deployed and subsequently fenestrated using an atherectomy laser probe; the fenestrations were enlarged using cutting and semicompliant balloons before implantation of balloon expandable bridging stents into the target vessels. Prospectively collected midterm survival, patency, and re-intervention rates were analysed. RESULTS: Forty four procedures were performed for 11 type 1a endoleaks, five thoraco-abdominal aneurysms, 20 pararenal aneurysms, four segmental renal artery (RA) preservations, three anastomotic aneurysms, and one aortic dissection. One hundred and eight laser fenestrations were performed (26 for the superior mesenteric artery [SMA], 13 for the coeliac trunk, 33 and 31 for the right and left RA, respectively). The median ischaemia duration was 7, 48, 48, and 45 minutes, respectively. The technical success rate was 97%, with no open surgical conversions. The 30 day mortality was 4.5% (n = 2). No spinal cord ischaemia events were observed nor early stent related complications. Kaplan-Meier overall survival at two years was 73%, the aortic related re-intervention free survival was 70%, and the stent related re-intervention free survival was 90.6%. Four target vessel thromboses were detected, of which three were rescued. Three type IIIc endoleaks, one RA false aneurysm, and one SMA stenosis, required re-intervention during a median follow up of 24.7 months. CONCLUSION: Antegrade LFEVAR is feasible, safe, and provides satisfactory early and midterm outcomes for non-deferrable treatment of aortic pathologies involving the visceral segment. Long term data are mandatory to confirm the usefulness of this promising off label technique.


Asunto(s)
Aneurisma de la Aorta Abdominal , Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Prótesis Vascular/efectos adversos , Arteria Renal/diagnóstico por imagen , Arteria Renal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Endofuga/etiología , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/complicaciones , Poliésteres , Resultado del Tratamiento , Stents/efectos adversos , Aneurisma de la Aorta Abdominal/cirugía , Rayos Láser , Diseño de Prótesis , Procedimientos Endovasculares/efectos adversos
14.
Circulation ; 147(1): 47-65, 2023 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-36325906

RESUMEN

BACKGROUND: The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered disease modeling and mechanistic understanding. Here, we show that 2 structural cardiac diseases, left ventricular noncompaction (LVNC) and bicuspid aortic valve, can be caused by a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) and cosegregating genes. METHODS: We used CRISPR-Cas9 gene editing to generate mice harboring a nonsense or a missense MIB1 mutation that are both found in LVNC families. We also generated mice separately carrying these MIB1 mutations plus 5 additional cosegregating variants in the ASXL3, APCDD1, TMX3, CEP192, and BCL7A genes identified in these LVNC families by whole exome sequencing. Histological, developmental, and functional analyses of these mouse models were carried out by echocardiography and cardiac magnetic resonance imaging, together with gene expression profiling by RNA sequencing of both selected engineered mouse models and human induced pluripotent stem cell-derived cardiomyocytes. Potential biochemical interactions were assayed in vitro by coimmunoprecipitation and Western blot. RESULTS: Mice homozygous for the MIB1 nonsense mutation did not survive, and the mutation caused LVNC only in heteroallelic combination with a conditional allele inactivated in the myocardium. The heterozygous MIB1 missense allele leads to bicuspid aortic valve in a NOTCH-sensitized genetic background. These data suggest that development of LVNC is influenced by genetic modifiers present in affected families, whereas valve defects are highly sensitive to NOTCH haploinsufficiency. Whole exome sequencing of LVNC families revealed single-nucleotide gene variants of ASXL3, APCDD1, TMX3, CEP192, and BCL7A cosegregating with the MIB1 mutations and LVNC. In experiments with mice harboring the orthologous variants on the corresponding Mib1 backgrounds, triple heterozygous Mib1 Apcdd1 Asxl3 mice showed LVNC, whereas quadruple heterozygous Mib1 Cep192 Tmx3;Bcl7a mice developed bicuspid aortic valve and other valve-associated defects. Biochemical analysis suggested interactions between CEP192, BCL7A, and NOTCH. Gene expression profiling of mutant mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes revealed increased cardiomyocyte proliferation and defective morphological and metabolic maturation. CONCLUSIONS: These findings reveal a shared genetic substrate underlying LVNC and bicuspid aortic valve in which MIB1-NOTCH variants plays a crucial role in heterozygous combination with cosegregating genetic modifiers.


Asunto(s)
Enfermedad de la Válvula Aórtica Bicúspide , Cardiomiopatías , Cardiopatías Congénitas , Células Madre Pluripotentes Inducidas , Humanos , Animales , Ratones , Cardiopatías Congénitas/complicaciones , Cardiomiopatías/etiología , Miocitos Cardíacos , Válvula Aórtica/diagnóstico por imagen , Factores de Transcripción , Proteínas Cromosómicas no Histona
15.
Minerva Anestesiol ; 89(7-8): 636-642, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36326773

RESUMEN

BACKGROUND: The best regional anesthesia plan with the best clinical results for Carotid endarterectomy (CEA) has not been defined yet. METHODS: Prospective multicentric observational study of two non-randomized matched cohorts including patients undergoing elective unilateral CEA (N.=100) between January-October 2021. Main outcomes were cerebral oximetry measurements, verbal numeric pain score assessment, peripheral nerve blockades and in-hospital stay. The main objective is to compare results achieved after carotid endarterectomy (CEA) performed under loco-regional blockade (LRB) versus general anesthesia (GA), in terms of intraoperative hemodynamic and neurologic variability. Patients undergoing LRB were performed under ultrasound (US) guidance and mild sedation. RESULTS: The LRB and GA groups showed no differences in comorbidities and risk factors. However, there was a significant difference in the intraoperative hemodynamic behavior due to the amount of vasoactive drugs used (0% vs. 16% for phenylephrine, P=0.006). The results showed neurological stability through the cerebral oximetry measurements during the procedure except for the left hemisphere de-clamp values, which were higher in the GA group (68.7±9.9 vs. 72.7±8.8; P=0.035). There were also significant differences in the verbal pain scale scores assessed 6 hours and 12 hours after the procedure; better pain control was evidenced in the LRB group (0[0-1] vs. 1[0-3], P=0.01; 1[0.5-2] vs. 0[0-2], P=0.01). An increased transient hypoglossal and laryngeal nerves blockade was observed in the LRB group (30% vs. 4%; P<0.001). The in-hospital length of stay was longer in the GA group (77.2±36.3 hours vs. 129.1±41.1 hours; P<0.001). CONCLUSIONS: Although the use of intermediate-deep cervical plexus blockade for CEA confers similar neurologic stability as GA does, there is a difference on the hemodynamic behaviour due to the differences in vasoactive drug consumption. Loco-regional techniques provide a better postoperative pain control and shorten in-hospital length of stay.


Asunto(s)
Anestesia de Conducción , Endarterectomía Carotidea , Humanos , Endarterectomía Carotidea/efectos adversos , Endarterectomía Carotidea/métodos , Circulación Cerebrovascular , Resultado del Tratamiento , Oximetría , Anestesia de Conducción/métodos , Anestesia General/efectos adversos , Ultrasonografía Intervencional/métodos , Dolor/etiología
17.
Eur Arch Otorhinolaryngol ; 280(2): 829-837, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36056169

RESUMEN

BACKGROUND: Surgical resection or radiotherapy (RT) are standard approaches for early-staged hypopharyngeal squamous cell carcinoma (HPSCC). Transoral laser microsurgery (TOLMS) seems to provide good oncological and functional results with few local complications. The aim of our study was to analyze the outcomes of TOLMS, with or without neck dissection or RT, in the treatment of HPSCC in a tertiary referral center. METHODS: A retrospective study was conducted in patients with early T-category (T1-T2) HPSCC treated by TOLMS. RESULTS: A total of 34 patients were included in the study. The series includes 17 (50%) T1 and 17 (50%) T2 classified tumors. The 5-year overall survival and disease-specific survival rates were 51% and 66%, respectively, with a 5-year local control rate of 92%. All patients reassumed oral diet and none of them had a tracheostomy at the end of the follow-up. CONCLUSIONS: TOLMS offers an effective treatment option in terms of oncologic control and function preservation in locally circumscribed HPSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Terapia por Láser , Humanos , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , Microcirugia/métodos , Neoplasias Hipofaríngeas/patología , Resultado del Tratamiento , Terapia por Láser/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/patología , Estadificación de Neoplasias , Neoplasias Laríngeas/cirugía
18.
J Thorac Dis ; 15(12): 6721-6729, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38249874

RESUMEN

Background: Open surgery remains the gold standard technique for the treatment of aortic arch pathologies, although endovascular techniques offer a new opportunity for patients deemed unfit for open repair. This paper assesses the early outcomes of patients treated with a double inner-branched arch endograft in a single, tertiary-care institution. Methods: All consecutive cases of elective endovascular arch repair from 2016 to 2022 were included in a prospective database. All procedures were performed using the custom-made Relay® (Terumo Aortic-Bolton Medical Inc., Sunrise, FL, USA) double inner-branched endograft; an extra-anatomical bypass was associated in all cases to preserve the patency of supra-aortic trunks. Comorbidities, periprocedural data, immediate results and follow-up complications were analyzed. Results: Twelve patients were treated during the study period [mean age 74±7 years, 100% male, 58% American Society of Anesthesiologists (ASA) risk ≥3]. Treated conditions included aneurysms (n=9), one pseudoaneurysm, one aortic ulcer and a type IA endoleak. The technical success rate was 100%. Early complications included respiratory insufficiency (n=3; 25%), stroke (n=1; 8.3%), acute coronary syndrome needing coronary stenting (n=1; 8.3%), and one perioperative death (n=1; 8.3%) secondary to an intracranial bleeding after coronary stenting. One patient required early reintervention due to retroperitoneal iliac access bleeding (n=1; 8.3%). During a median follow-up of 15.5 (range, 0-44) months, four patients suffered neurological events (two of them of cardioembolic origin), one reintervention was needed (subclavian anastomosis pseudoaneurysm), and a type IB endoleak was diagnosed. Overall mortality was of 17% (n=2), with an 83% overall survival at 2 years. The aortic-related death-free survival was 100%. Conclusions: Endovascular treatment of aortic arch pathology is feasible and shows promising early mortality and stroke rates in high-risk candidates. The main short and midterm goal should be minimizing neurological complications. A longer follow-up is mandatory to determine the effectiveness of the technique and to detect device related complications.

19.
Membranes (Basel) ; 12(11)2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36422137

RESUMEN

The globalization of the market and the increase of the global population that requires a higher demand of food products superimposes a big challenge to ensure food safety. In this sense, a common strategy to extend the shelf life and save life of food products is by avoiding bacterial contamination. For this, the development of antibacterial contact surfaces is an urgent need to fulfil the above-mentioned strategy. In this work, the role of MXene (Ti3C2Tx) in providing antibacterial contact surfaces was studied through the creation of composite films from polylactic acid (PLA), as the chosen polymeric matrix. The developed PLA/MXene films maintained the thermal and mechanical properties of PLA and also presented the attractive antibacterial properties of MXene. The composites' behaviour against two representative foodborne bacteria was studied: Listeria mono-cytogenes and Salmonella enterica (representing Gram-positive and Gram-negative bacteria, respectively). The composites prevented bacterial growth, and in the case of Listeria only 0.5 wt.% of MXene was necessary to reach 99.9999% bactericidal activity (six log reductions), while against Salmonella, 5 wt.% was necessary to achieve 99.999% bactericidal activity (five log reductions). Cy-totoxicity tests with fHDF/TER166 cell line showed that none of the obtained materials were cytotoxic. These results make MXene particles promising candidates for their use as additives into a polymeric matrix, useful to fabricate antibacterial contact surfaces that could prove useful for the food packaging industry.

20.
Healthcare (Basel) ; 10(10)2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36292433

RESUMEN

(1) Introduction: The aim was to describe the anesthetic and surgical technique of eversion carotid endarterectomy performed under intermediate-deep cervical block with sedation, and to analyze the intraoperative and postoperative results. (2) Material and Methods: Thirty cases of unilateral eversion carotid endarterectomy (n = 30), performed between 2019-2020 in a tertiary center under intermediate-deep ultrasound-guided cervical plexus block and sedation, were prospectively observed and analyzed. Hemodynamic (blood pressure, heart rate) and neurological (cerebral oximetry) variables were measured in four intraoperative phases: at the beginning of the operation, prior to carotid clamping, after unclamping and at the end of the operation. We assessed acute postoperative pain in a numerical rating scale at 6, 12 and 24 h, early and 30-day complications, and length of stay. (3) Results: Baseline mean arterial pressure values were 100.4 ± 18 mmHg, pre-clamping 95.8 ± 14 mmHg, post-clamping 94.9 ± 11 mmHg, and at the end of the operation 102.4 ± 16 mmHg. Cerebral oximetry values were 61.7 ± 7/62.7 ± 8, 68.5 ± 9.6/69.1 ± 11.7 and 68.1 ± 10/68.1 ± 10 for the left and right hemispheres at baseline, pre- and post-clamping, respectively. The pain assessment showed a score less than or equal to 3. The incidence of residual nerve block, early complications, and major complications in the first 30 days was 40%, 16.7% and 3.3%, respectively. (4) Conclusions: The combination of intermediate-deep cervical plexus block and low-dose sedation is an effective and safe alternative in awake eversion carotid endarterectomy.

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