Extracellular Vesicles from Adipose Tissue-Derived Stromal Cells Stimulate Angiogenesis in a Scaffold-Dependent Fashion.

BACKGROUND: The extracellular vesicles (EVs) secreted by adipose tissue-derived stromal cells (ASC) are microenvironment modulators in tissue regeneration by releasing their molecular cargo, including miRNAs. However, the influence of ASC-derived extracellular vesicles (ASC-EVs) on endothelial cells (ECs) and vascularisation is poorly understood. The present study aimed to determine the pro-angiogenic effects of ASC-EVs and explore their miRNA profile. METHODS: EVs were isolated from normoxic and hypoxic cultured ASC conditioned culture medium. The miRNA expression profile was determined by miRseq, and EV markers were determined by Western blot and immunofluorescence staining. The uptake dynamics of fluorescently labelled EVs were monitored for 24 h. ASC-EVs' pro-angiogenic effect was assessed by sprouting ex vivo rat aorta rings in left ventricular-decellularized extracellular matrix (LV dECM) hydrogel or basement membrane hydrogel (Geltrex®). RESULTS: ASC-EVs augmented vascular network formation by aorta rings. The vascular network topology and stability were influenced in a hydrogel scaffold-dependent fashion. The ASC-EVs were enriched for several miRNA families/clusters, including Let-7 and miR-23/27/24. The miRNA-1290 was the highest enriched non-clustered miRNA, accounting for almost 20% of all reads in hypoxia EVs. CONCLUSION: Our study revealed that ASC-EVs augment in vitro and ex vivo vascularisation, likely due to the enriched pro-angiogenic miRNAs in EVs, particularly miR-1290. Our results show promise for regenerative and revascularisation therapies based on ASC-EV-loaded ECM hydrogels.

Mechanisms modulating foam cell formation in the arterial intima: exploring new therapeutic opportunities in atherosclerosis.

In recent years, the role of macrophages as the primary cell type contributing to foam cell formation and atheroma plaque development has been widely acknowledged. However, it has been long recognized that diffuse intimal thickening (DIM), which precedes the formation of early fatty streaks in humans, primarily consists of lipid-loaded smooth muscle cells (SMCs) and their secreted proteoglycans. Recent studies have further supported the notion that SMCs constitute the majority of foam cells in advanced atherosclerotic plaques. Given that SMCs are a major component of the vascular wall, they serve as a significant source of microvesicles and exosomes, which have the potential to regulate the physiology of other vascular cells. Notably, more than half of the foam cells present in atherosclerotic lesions are of SMC origin. In this review, we describe several mechanisms underlying the formation of intimal foam-like cells in atherosclerotic plaques. Based on these mechanisms, we discuss novel therapeutic approaches that have been developed to regulate the generation of intimal foam-like cells. These innovative strategies hold promise for improving the management of atherosclerosis in the near future.

Increased plasma levels of N-terminal pro-B-type natriuretic peptide as biomarker for the diagnosis of cardioembolic ischaemic stroke.

BACKGROUND: Despite comprehensive study, the aetiology of stroke is not identified in 35% of cases. AIMS: We conducted a study to assess the diagnostic capacity of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the identification of ischaemic stroke of cardioembolic origin. The secondary purpose of the study was to evaluate the prognostic value of NT-proBNP for predicting 90-day all-cause mortality. METHODS: We designed a prospective observational study including patients hospitalised due to stroke between March 2019 and March 2020. Blood samples were collected on admission to the emergency department and serum NT-proBNP levels were determined. Statistical analysis was performed using a bivariate logistic regression model and receiver operating characteristic (ROC) and Kaplan-Meier curves. Statistical significance was established at p<.05. RESULTS: The study included 207 patients with first ischaemic stroke. Plasma NT-proBNP levels were significantly higher (p<.001) in the cardioembolic stroke group (2069pg/mL±488.5). ROC curves showed that NT-proBNP>499pg/mL was the optimum value for diagnosing cardioembolic ischaemic stroke (sensitivity, 82%; specificity, 80%). Moreover, plasma NT-proBNP levels>499pg/mL were independently associated with cardioembolic stroke (OR: 9.881; p=.001). Finally, NT-proBNP>1500pg/mL was useful for predicting 90-day mortality (sensitivity, 70%; specificity, 93%). CONCLUSIONS: NT-proBNP was independently associated with cardioembolic stroke and should be quantified in blood tests within 24h of stroke onset. High plasma levels (>499pg/mL) may indicate an underlying cardioembolic cause, which should be further studied, while NT-proBNP >1500pg/mL was associated with increased 90-day mortality.

Inseminate without hormonal treatment in dairy sheep farms: exploring the consequences on the sustainability of several contrasted production systems.

Alternatives to hormonal treatments (HTs) in dairy sheep reproduction management are being explored in response to increasing societal concerns regarding animal welfare and food safety. However, hormone-free reproduction implies higher variability in flock performances and additional constraints for timely synchronised artificial insemination (AI) in the flock, impacting the diffusion of genetic progress. The use of the male effect, a well-known practice to induce synchronised oestrus, combined with precision tools (e.g., heat detector), is a plausible way to implement AI without HT in dairy sheep farms. To date, the consequences of such alternative reproduction management on the whole farm sustainability remain unknown. To anticipate these potential impacts, a multiagent model (REPRIN'OV) was used to simulate dairy sheep farms' sustainability indicators (biotechnical, economic, environmental and workload). A reproduction management scenario, including the use of the male effect followed by AI on the adult ewes (HFAI), was simulated and compared to the current reproduction management of four case study farms (Early_conv, Late_conv, Early_org and Late_org). They were selected to represent the different agricultural models (Conventional or Organic) and reproduction seasons (Early - during spring, out of ewes' natural reproduction season - or Late -from early summer to the end of autumn) of the Roquefort Basin's farms in Southern France. Simulation results showed that the HFAI scenario had different consequences depending on the farm's production system type. A negative effect on most key sustainability indicators of the Conv farms was observed, as a significant reduction in the fertility rate, in the proportion of young ewes born from AI (-54% in both farms; P < 0.05) and in the flock's milk production were observed; while the workload and greenhouse gas (GHG) emissions were increased compared to the initial scenario. In the Org farms, HFAI had neutral to positive effects on most indicators as the fertility, milk production of the flock, workload during milking and GHG emissions were barely affected by this scenario, while an increase in the proportion of young ewes born from AI was observed (+39% and + 43% in each farm, respectively; P < 0.05), allowing a better farm gross margin. Still, the workload during lambing was increased in Early_org (+18%; P < 0.05), as Early farms, tended to be more negatively impacted by HFAI than Late ones. Overall, our simulation approach provides interesting elements to exchange with stakeholders on how to progress towards a socially acceptable reproduction management system, for the dairy sheep sector.

Uric acid and acute kidney injury in high-risk patients for developing acute kidney injury undergoing cardiac surgery: A prospective multicenter study.

PURPOSE: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN: Multicenter prospective international cohort study. SETTING: Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

Clinical-haematological changes and predictors of severity in acute food protein-induced enterocolitis syndrome reactions at oral food challenge: a multicentre observational study.

BACKGROUND: Oral food challenge (OFC) is the gold standard for diagnosis of acute Food Protein-Induced Enterocolitis Syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated. OBJECTIVE: To assess clinical-haematological changes and predictors of severity of FPIES reactions at OFC. METHODS: Observational multicentre prospective study. Children aged 0-18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centres in Spain and Italy. OFC Outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed based on published '2017 FPIES Consensus' criteria. Clinical characteristics were recorded, and full blood count was done at baseline, reaction onset and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC. RESULTS: 81 children had positive OFC (mild in 11% (9/81), moderate in 61% (49/81), severe in 28% (23/81)). Increase in neutrophils and reduction in eosinophils, basophils and lymphocytes was observed (P-value<0.05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not gender, age, culprit food, cumulative dose and previous reaction severity) was associated with reduced odds of severe reaction compared to giving multiple doses in a single day. CONCLUSION: Distinct haematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may associate a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES.

Circumferential Inferior Vena Cavectomy Without Caval Replacement in the Management of Renal Cell Carcinoma with Tumor Thrombus.

PURPOSE OF REVIEW: Renal cell carcinoma presents a unique proclivity for vascular involvement giving rise to a peculiar form of locally advanced disease so-called tumor thrombus. To date, the only curative strategy for these cases remains surgery, which should aim to remove every vestige of macroscopic disease. Most of the preexisting literature advocates opening the vena cava to allow tumor thrombus removal and subsequent venous suture closure. However, inferior vena cava circumferential resection (cavectomy) without caval replacement is possible in the majority of cases since progressive occlusion facilitates the development of a collateral venous network aimed at maintaining cardiac preload. RECENT FINDINGS: Radical nephrectomy with tumor thrombectomy remains a surgical challenge not exempt of operative complications even in experienced hands. In opposition to what traditional cavotomy and thrombus withdrawal can offer, circumferential cavectomy without caval replacement would provide comparable or even better oncologic control, decrease the likelihood of operative bleeding, and prevent the development of perioperative pulmonary embolism. This review focuses on the rationale of circumferential IVC resection without caval replacement and the important technical aspects of this approach in cases of renal cell carcinoma with vascular involvement. We also include an initial report on the surgical outcomes of a contemporary series of patients managed under this approach at our center.

[A descriptive overview of cases of congenital cytomegalovirus at a tertiary hospital between 2017 and 2023]. / Descriptivo de los casos de citomegalovirus congénitos en un hospital terciario entre 2017-2023.

OBJECTIVE: Cytomegalovirus infection (CMV) is the most common congenital infection in developed countries. The aim of our study was to describe the features of the children that have congenital CMV infection at our hospital for the last 6 years. METHODS: A retrospective descriptive study was designed that included all the children with CMV congenital infection that were diagnosed at tertiary hospital of Madrid Community between 2017 and 2023. RESULTS: Twenty-two children were included. 54.5% have a prenatal diagnosis, 50% of them were in the third trimester, 25% at first trimester and 25% at the second. 22.7% were preterm. CMV was isolated in all the samples with CV more than 1000 copies/ml. When CMV was made in blood, 11/22 (50%) had a high CV. Only one newborn had a high CV at CRL. 44% have affectation at transfontanellar ultrasound evidenced by vasculopathy (62%), intraventricular hemorrhage (IVH) or periventricular calcifications (20%). 68% were asymptomatic, al though 20% had a retarded intrauterine growth (RIG) at birth or clinical features or analytical were objectified (neutropenia, thrombocytopenia, cholestasis). 33% got treatment with val ganciclovir and 33% had sequelae (hearing loss). CONCLUSIONS: CMV congenital infection is still a severe public health issue in developed countries. Most of the cases are mild or asymptomatic even though we should have high clinical suspicion with compatible symptoms and consistent maternal history in order to make an early diagnosis and treatment to prevent or reduce sequelae.

Afectación ocular como primera y única manifestación del síndrome de Bardet-Biedl: presentación de un caso / Ocular impairment as the first and only manifestation of Bardet–Biedl syndrome: A case report

El síndrome de Bardet-Biedl (SBB) es una ciliopatía que se asocia principalmente a distrofia retiniana, disfunción renal, polidactilia posaxial, obesidad, déficit cognitivo e hipogonadismo. Los síntomas vinculados a la distrofia retiniana no suelen aparecer hasta la primera década de vida, por lo que la detección tiende a retrasarse. La afectación ocular puede ser la forma inicial de manifestación de este síndrome, incluso puede ser la única, por lo que se debería tener en cuenta en el diagnóstico diferencial de una ambliopía en un niño que no mejora a pesar del correcto cumplimiento del tratamiento. Se presenta un caso de baja agudeza visual (AV) en una paciente pediátrica como manifestación inicial que lleva al diagnóstico del SBB y que es, además, el único síntoma que exhibe hasta la fecha, a pesar de tratarse de una enfermedad multisistémica.(AU)

Bardet–Biedl syndrome is a ciliopathy mainly associated with retinal dystrophy, renal dysfunction, post-axial polydactyly, obesity, cognitive deficit and hypogonadism. The symptoms associated with retinal dystrophy do not usually appear until the first decade of life, so the diagnosis is usually delayed. Ocular involvement may be the initial form of manifestation of this syndrome, it may even be the only one, so it should be taken into account in the differential diagnosis of amblyopia in a child who does not improve despite correct compliance with treatment. A case of low visual acuity in a pediatric patient is presented as an initial manifestation that leads to the diagnosis of Bardet–Biedl syndrome, and which is also the only symptom that the patient presents to date, despite being a multisystem disease.(AU)

Biomarkers of Bipolar Disorder in Late Life: An Evidence-Based Systematic Review.

PURPOSE OF REVIEW: Review the current evidence on biomarkers for bipolar disorder in the older adults. We conducted a systematic search of PubMed MEDLINE, PsycINFO, and Web of Science databases using the MeSH search terms "Biomarkers", "Bipolar Disorder", "Aged" and and "Aged, 80 and over". Studies were included if they met the following criteria: (1) the mean age of the study population was 50 years old or older, (2) the study included patients with bipolar disorder, and (3) the study examined one type of biomarkers or more including genetic, neuroimaging, and biochemical biomarkers. Reviews, case reports, studies not in English and studies for which no full text was available were excluded. A total of 26 papers were included in the final analysis. RECENT FINDINGS: Genomic markers of bipolar disorder in older adults highlighted the implication of serotonin metabolism, while the expression of genes involved in angiogenesis was dysregulated. Peripheral blood markers were mainly related with low grade inflammation, axonal damage, endothelial dysfunction, and the dysregulation of the HPA axis. Neuroanatomical markers reflected a dysfunction of the frontal cortex, a loss of neurones in the anterior cingulate cortex and a reduction of the hippocampal volume (in patients older than 50 years old). While not necessarily limited to older adults, some of them may be useful for differential diagnosis (neurofilaments), disease staging (homocysteine, BDNF) and the monitoring of treatment outcomes (matrix metalloproteinases). Our review provides a comprehensive overview of the current evidence on biomarkers for bipolar disorder in the older adults. The identification of biomarkers may aid in the diagnosis, treatment selection, and monitoring of bipolar disorder in older adults, ultimately leading to improved outcomes for this population. Further research is needed to validate and further explore the potential clinical utility of biomarkers in this population.

Prevalence and management of urinary incontinece after pelvic organ prolapse surgery (sacrocolpopexy). A literature review.

INTRODUCTION: Stress urinary incontinence (SUI) is frequently associated with pelvic organ prolapse (POP) and may occur after its surgical treatment. AIM: To determine the incidence, risk factors and management of SUI during and after POP surgery through a review of the available literature. MATERIALS AND METHOD: Narrative literature review on the incidence and management of SUI after POP surgery after search of relevant manuscripts indexed in PubMed, EMBASE and Scielo published in Spanish and English between 2013 and 2023. RESULTS: Occult SUI is defined as visible urine leakage when prolapse is reduced in patients without SUI symptoms. De novo SUI develops after prolapse surgery without having previously existed. In continent patients, the number needed to treat (NNT) to prevent one case of de novo SUI is estimated to be 9 patients and about 17 to avoid repeat incontinence surgery. In patients with occult UI, the NNT to avoid repeat incontinence surgery is around 7. Patients with POP and concomitant SUI are the group most likely to benefit from combined surgery with a more favorable NNT (NNT 2). CONCLUSION: Quality studies on combined surgery for treatment SUI and POP repair are lacking. Continent patients with prolapse should be warned of the risk of de novo SUI, although concomitant incontinence treatment is not currently recommended. Incontinence surgery should be considered on an individual basis in patients with prolapse and SUI.

Trichiasis removal using dermatological punch: A case report.

Entropion, a common malposition of the eyelid, can lead to trichiasis and corneal damage. This article presents a clinical case in which, following initial surgery to correct entropion, the use of a dermatological punch was chosen to definitively eliminate persistent trichiasis. This relatively unknown yet effective approach proved to be a quick and straightforward alternative with positive outcomes, emphasizing the importance of considering innovative approaches to recurrent challenges in clinical practice.

Ocular impairment as the first and only manifestation of Bardet-Biedl syndrome: A case report.

Bardet-Biedl syndrome is a ciliopathy mainly associated with retinal dystrophy, renal dysfunction, post-axial polydactyly, obesity, cognitive deficit and hypogonadism. The symptoms associated with retinal dystrophy do not usually appear until the first decade of life, so the diagnosis is usually delayed. Ocular involvement may be the initial form of manifestation of this syndrome, it may even be the only one, so it should be taken into account in the differential diagnosis of amblyopia in a child who does not improve despite correct compliance with treatment. A case of low visual acuity in a pediatric patient is presented as an initial manifestation that leads to the diagnosis of Bardet-Biedl Syndrome, and which is also the only symptom that the patient presents to date, despite being a multisystem disease.

Satisfaction assessment study in patients (and their partners) with/without Peyronie's disease and penile prosthesis implantation.

INTRODUCTION AND OBJECTIVE: Among the many treatments for erectile dysfunction, implantation of a penile prosthesis has been associated with high patient satisfaction rates. However, patients with coexistent Peyronie's disease (PD) and refractory erectile dysfunction and/or severe deformities may show different results. The aim of our study was to assess and to compare the level of satisfaction, with an inflatable penile prosthesis (IPP), in men with/without coexistent PD. MATERIAL AND METHODS: A survey study based on a five-item satisfaction questionnaire was submitted to all those live patients implanted in the period 1992-2022 at our center (n=570) and their partners. Ninety-two percent of implants were inflatable devices. Surgeries were mainly performed by two surgeons. The main outcome measure used was the level of patient and partner satisfaction with sexual intercourse after IPP. RESULTS: Of the 570 eligible patients, 479 (84%) completed the survey (393 Non-PD: GROUP 1; 70 non-complex PD-Group 2; 16 complex PD). Eighty-six per cent of patients in Group 1 reported satisfactory sexual intercourse (very or moderately satisfied). Non-complex PD implanted patients (Group 2) reported a global 81% satisfactory sexual intercourse (very or moderately satisfied) (p>0.05). However, when we evaluated the PD subgroup of patients with severe PD who require incision/excision/grafting at the time of implant (Group 3: n=20), only 61% reported satisfactory sexual intercourse (p<0.01) with predominance of moderately satisfied patients over very satisfied: 78% vs. 22%). Additionally, 84% (Group 1), 80% (Group 2) and 54% (Group 3) of partners reported satisfactory intercourses, respectively (p<0.01). Overall, 84% of Group 1 implants and 79% of Group 2 reported that they would undergo the procedure again if the IPP failed (p>0.05; ns). Only 50% of Group 3 patients would do it again. With regard to cosmetic aspects, 48% of the Group 3 implant reported penile shortness or soft glans as the main causes of their dissatisfaction. Only 2.4% of total PP patients expressed difficulty in manipulating the device. CONCLUSION: The presence of PD alone may not impact PP patient and partner satisfaction, but patients with more severe baseline deformity who require incision/grafting may be less satisfied with outcomes including penile length and glans sensation.

Burnout Syndrome, Anxiety, and Depression in Dermatology Residents: A Cross-Sectional Study. / Síndrome de burnout, ansiedad y depresión en residentes de dermatología: un estudio transversal.

BACKGROUND AND OBJECTIVE: Burnout syndrome is a mental health disorder due to chronic occupational stress. Both burnout and associated comorbidities are prevalent among health care professionals, being medical residents a vulnerable group. Despite this, the scientific medical literature currently available on this issue in dermatology residents is scarce. The aim of this study was to analyze the prevalence of the burnout syndrome, anxiety, and depression in dermatology residents, and the associated risk factors. MATERIAL AND METHOD: This was a cross-sectional trial designed to include dermatology residents from Spain (from December 2022 through June 2023). A self-administered form was sent via online messaging applications, including validated scales to study professional quality of life, burnout syndrome, anxiety, and depression. RESULTS: A total of 48 dermatology residents were included in the study, 50% of whom (24/48) were women, with a mean age of 27 years (1.25). A total of 58.33% (28/48) of the residents had some degree of anxiety, 22.9% (11/48) some degree of depression, and 23.4% a moderate risk of burnout (11/48). Workload was the main risk factor associated with the 3 disorders studied, while managerial support or intrinsic motivation seem to play a protective role. CONCLUSIONS: Burnout syndrome and its comorbidities are both prevalent in dermatology residents in Spain and closely related to each other.