European Society for Organ Transplantation (ESOT) Consensus Statement on the Use of Non-invasive Biomarkers for Cardiothoracic Transplant Rejection Surveillance.

While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field's incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.

Thrombotic microangiopathy in patients with malignant hypertension.

BACKGROUND: Thrombotic microangiopathy (TMA) is a complication of malignant hypertension (mHTN) attributed to high blood pressure (BP). However, no studies have investigated in patients with mHTN of different aetiologies whether the presence of TMA is associated with specific causes of mHTN. METHODS: We investigated the presence of TMA (microangiopathic haemolytic anaemia and thrombocytopenia) in a large and well-characterized cohort of 199 patients with mHTN of different aetiologies [primary HTN 44%, glomerular diseases 16.6%, primary atypical haemolytic uraemic syndrome (aHUS) 13.1%, renovascular HTN 9.5%, drug-related HTN 7%, systemic diseases 5.5%, endocrine diseases 4.5%]. Outcomes of the study were kidney recovery and kidney failure. RESULTS: Patients with TMA [40 cases (20.1%)] were younger, were more likely female and had lower BP levels and worse kidney function at presentation. Their underlying diseases were primary aHUS (60%), drug-related mHTN (15%), glomerular diseases [all of them immunoglobulin A nephropathy (IgAN); 10%], systemic diseases (10%) and primary HTN (5%). The presence of TMA was 92.3% in primary aHUS, 42.9% in drug-related HTN, 36.4% in systemic diseases, 12.1% in glomerular diseases and 2.3% in primary HTN. No patient with renovascular HTN or mHTN caused by endocrine diseases developed TMA, despite BP levels as high as patients with TMA. A higher proportion of TMA patients developed kidney failure as compared with patients without TMA (56.4% versus 38.9%, respectively). CONCLUSIONS: The presence of TMA in patients with mHTN should guide the diagnosis towards primary aHUS, drug-related mHTN, some systemic diseases and IgAN, while it is exceptional in other causes of mHTN.

How do cultural factors influence the provision of end-of-life care? A narrative review.

BACKGROUND: Culture influences the way in which patients, families and professionals provide care and undergo decision-making at the end of life. OBJECTIVE: Therefore, our research questions were: How do cultural aspects influence the needs, perceptions, and experiences of patients and their families in end-of-life care? What implications does cultural diversity have for professionals who care for individuals at the end of life? METHODS: A narrative review was conducted between June and July 2022. Articles published between 2017 and 2022 in peer-reviewed journals were included. RESULTS: A total of 43 studies were included. Our findings were grouped into four themes: 1) places to die and preferences about healthcare interventions (e.g. parts of the immigrant population tend to receive more aggressive and invasive interventions); 2) advance care planning and verbalization of death (e.g. less use of ACP in some minority groups); 3) rituals and family involvement during healthcare; 4) professionals addressing multiculturalism in care at the end of life (e.g. lack of training in addressing the context of multiculturalism). CONCLUSIONS: These findings could contribute to making professionals more aware of cultural aspects that influence the process of death and highlight the need for further training in the handling of such situations.

Accuracy and Limitations of Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients with Positive Nodes.

Background: Axillary surgical management in patients with node-positive breast cancer at the time of diagnosis converted to negative nodes through neoadjuvant chemotherapy (NAC) remains unclear. Removal of more than two sentinel nodes (SLNs) in these patients may decrease the false negative rate (FNR) of sentinel lymph node biopsies (SLNBs). We aim to analyse the detection rate (DR) and the FNR of SLNB assessment according to the number of SLNs removed. Methods: A retrospective study was performed from October 2012 to December 2018. Patients with invasive breast cancer who had a clinically node-positive disease at diagnosis and with a complete axillary response after neoadjuvant chemotherapy were selected. Patients included underwent SLNB and axillary lymph node dissection (ALND) after NAC. The SLN was considered positive if any residual disease was detected. Descriptive statistics were used to describe the clinicopathologic features and the results of SLNB and ALND. The DR of SLNB was defined as the number of patients with successful identification of SLN. Presence of residual disease in ALND and negative SLN was considered false negative. Results: A total of 368 patients with invasive breast cancer who underwent surgery after complete NAC were studied. Of them, 85 patients met the eligibility criteria and were enrolled in the study. The mean age at diagnosis was 50.8 years. Systematic lymphadenectomy was performed in all patients, with an average of 10 lymph nodes removed. The DR of SLNB was 92.9%, and the FNR was 19.1. The median number of SLNs removed was 3, and at least, three SLNs were obtained in 42 patients (53.2%). When at least three sentinel nodes were removed, the FNR decreased to 8.7%. Conclusions: In this cohort, the SLN assessment was associated with an adequate DR and a high FNR. Removing three or more SLNs decreased the FNR from 19.1% to 8.7%. Complementary approaches may be considered for axillary lymph node staging after neoadjuvant chemotherapy. The study was approved by our institution's ethics committee (Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain) (https://clinicaltrials.gov/ct2/show/NCEI:20/0048).

Knowledge and practices regarding malaria and the National Treatment Guidelines among public health workers in Equatorial Guinea.

BACKGROUND: In 2018, an estimated 228 million cases of malaria occurred worldwide. Countries are far from having achieved reasonable levels of national protocol compliance among health workers. Lack of awareness of treatment protocols and treatment resistance by prescribers threatens to undermine progress when it comes to reducing the prevalence of this disease. This study sought to evaluate the degree of knowledge and practices regarding malaria diagnosis and treatment amongst prescribers working at the public health facilities of Bata, Equatorial Guinea. METHODS: A cross-sectional survey was conducted in October-December 2017 amongst all public health professionals who attended patients under the age of 15 years, with suspected malaria in the Bata District of Equatorial Guinea. Practitioners were asked about their practices and knowledge of malaria and the National Malaria Treatment Guidelines. A bivariate analysis and a logistic regression model were used to determine factors associated with their knowledge. RESULTS: Among the 44 practitioners interviewed, 59.1% worked at a Health Centre and 40.9% at the District Hospital of Bata. Important differences in knowledge and practices between hospital and health centre workers were found. Clinical diagnosis was more frequently by practitioners at the health centres (p = 0.059), while microscopy confirmation was more frequent at regional hospital (100%). Intramuscular artemether was the anti-malarial most administrated at the health centres (50.0%), while artemether-lumefantrine was the treatment most used at the regional hospital (66.7%). Most practitioners working at public health facilities (63.6%) have a low level of knowledge regarding the National Malaria Treatment Guidelines. While knowledge regarding malaria, the National Malaria Treatment Guidelines and treatment resistances is low, it was higher amongst hospital workers than amongst practitioners at health centres. CONCLUSIONS: It is essential to reinforce practitioners' knowledge, treatment and diagnosis practices and use of the National Malaria Treatment Guidelines in order to improve malaria case management and disease control in the region. A specific malaria training programme ensuring ongoing updates training is necessary in order to ensure that greater experience does not entail obsolete knowledge and, consequently, inadequate diagnosis and treatment practices.

Heterogeneity of clinical management of low-grade gastric lymphoma of mucosa-associated lymphoid tissue. An audit of 198 patients in Spain.

INTRODUCTION: Cure of Helicobacter pylori infection in patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT) leads to long-term clinical remission in the initial stages. As it is a rare disease, its management in clinical practice remains largely unknown and heterogeneity of care remains a concern. The aim was to audit the management and evolution of a large series of low-grade gastric MALT lymphomas from thirteen Spanish hospitals. MATERIALS AND METHODS: Multicentre retrospective study including data on the diagnosis and follow-up of patients with gastric low-grade MALT lymphoma from January 1998 to December 2013. Clinical, biological and pathological data were analyzed and survival curves were drawn. RESULTS: One-hundred and ninety-eight patients were included. Helicobacter pylori was present in 132 (69%) patients and 103 (82%) in tumors confined to the stomach (stage EI) and was eradicated in 92% of patients. Chemotherapy was given in 90 (45%) patients and 43 (33%) with stage EI. Marked heterogeneity in the use of diagnostic methods and chemotherapy was observed. Five-year overall survival was 86% (89% in EI). Survival was similar in EI patients receiving aggressive treatment and in those receiving only antibiotics (p=0.577). DISCUSSION: Gastric MALT lymphoma has an excellent prognosis. We observed, however, a marked heterogeneity in the use of diagnostic methods or chemotherapy in early-stage patients.

Solvent-Controlled Spatial Distribution of SI-AGET-ATRP Grafted Polymers in Lignocellulosic Materials.

In the current quest for the design of advanced complex materials, the functionalization of biological materials having hierarchical structures has been of high interest. In the case of lignocellulosic materials, various modification techniques have allowed one to obtain materials with outstanding properties. However, the control over the spatial distribution of the modification inside the wood scaffold, which is an important parameter to obtain the desired properties, has yet to be understood. In this study, the use of solvents with different wood-swelling capabilities is proposed to control the spatial polymer-modification distribution inside the hierarchical wood structure. Wood cubes were functionalized via SI-AGET-ATRP using solvents with different wood-swelling capabilities. Spectroscopic (Raman and FTIR) and electron microscopy techniques showed that a good wood-swelling solvent as reaction media can transport the polymerization initiator molecule into the cell wall, allowing it to react with all the available -OH groups in the wood structure. Conversely, the use of a bad wood-swelling solvent limits the reaction to the available -OH groups at the lumen/cell wall interface. The subsequently added polymers grow from the available initiator sites and therefore show similar spatial distribution. This diffusion limitation is visible not only at the microscopic level (cellular structure) but also at the macroscopic level (over the length of the sample).

[Biology and mechanobiology of the intervertebral disc]. / Biología y mecanobiología del disco intervertebral.

The intervertebral disc (IVD) is noted for its low cell content, and being the largest avascular structure of human body. The low amount of cells in the disc have to adapt to an anaerobic metabolism with low oxygen pressure and acidic pH. Apart from surviving in an adverse microenvironment, they are exposed to a high level of mechanical stress. The biological adaptation of cells to acidosis and hyperosmolarity conditions are regulated by mechanoproteins, which are responsible for converting a mechanical signal into a cellular response, thus modifying its gene expression. Mechanobiology helps us to better understand the pathophysiology of IVD and its potential biological repair.

[Prevalence of subjective memory complaints: Population study in Spain]. / Prevalencia de quejas subjetivas de memoria: estudio poblacional en España.

INTRODUCTION: Subjective memory complaints (SMC) might be an early sign of further deterioration in cognitive functions. However, no population studies have been published covering all Spain to determine the SMC prevalence. The objective of the present study was to determine the SMC prevalence in the general population residing in Spain >50 years of age and also which related actions were done. MATERIALS AND METHODS: Interviews were conducted with a nationally representative sample >50 years of age using an online/computer assisted web interview (CAWI) questionnaire. The survey consisted of 34 items divided into two blocks. Presence of SMC was considered when in question 1 the subject answered that "Yes" he had some memory problem. RESULTS: Two thousand three hundred people (53.7% women; 23.9% ≥75 years old) were interviewed. 31% answered that they considered they had a memory problem (no differences between sexes, mean time with memory problems of 3.0 years). A higher prevalence of SMC was observed in ≥75 years old (44%). 90% did not include any specific foods in their diet for their memory problems, neither were taking any pharmaceuticals, diet supplements or nutritional supplements (92%). 78% of those interviewed with SMC have not consulted health professionals for their memory problems. CONCLUSIONS: SMC are considerably prevalent in our environment affecting almost a third of people ≥50 years of age. Most of the interviewees with SMC did not go to health professionals to manage their SMC.

High-Flow Nasal Cannula Therapy as an Adjuvant Therapy for Respiratory Support during Endoscopic Techniques: A Narrative Review.

High-flow nasal cannula (HFNC) is a respiratory support technique that delivers a controlled concentration of oxygen with high flow, heat, and humidity via the nasal pathway. As it has many physiological effects, its use has increased for a variety of clinical indications; however, there is limited guidance on using HFNC as a respiratory support tool during endoscopic procedures. We conducted a narrative review to evaluate the effect of HFNC as an adjuvant tool during fiberoptic bronchoscopy (FOB), upper gastrointestinal tract endoscopy, and surgical procedures in adults. A search of the PubMed and Cochrane databases were performed. Approximately 384 publications were retrieved, and 99 were selected (93 original works and 6 case reports with a literature review). In patients who underwent FOB, HFNC appears to be superior to conventional oxygen therapy (COT) in preventing hypoxaemia. In contrast, for gastrointestinal endoscopy, the current evidence is insufficient to recommend HFNC over COT in a cost-effective manner. Finally, in surgical procedures such as laryngeal microsurgery or thoracic surgery, HFNC has been shown to be a safe and effective alternative to orotracheal intubation. As the results are heterogeneous, we advocate for the need for more quality studies to understand the effectiveness of HFNC during endoscopic procedures.

Fishing for litter, accidental catch in bottom trawl nets along the Catalan coast, Northwestern Mediterranean.

The seafloor of the Mediterranean Sea accumulates marine litter (ML), an area where bottom trawlers operate and can accidentally catch the litter from the seafloor. This study aims to describe and quantify the ML caught by bottom trawlers along the Catalan coast (NW Mediterranean Sea) and estimate the potential of the bottom trawl fleet to extract ML from the area as a Fishing for Litter (FFL) initiative to tackle the ML issue. Marine litter was collected from commercial trawlers and was classified as metal, plastic, rubber, textile, wood, and other waste and weighed (kg) from 305 hauls performed during three years (2019-2021) from 9 different ports at 3 different depths. ML was present in 97 % of the hauls, with plastic being the most abundant material. The composition varied according to zone, port and depth, with the highest densities found in highly urbanized areas (13.75 ± 3.25 kg km-2), which mainly contained plastics (74.3 %). The port of Barcelona had the highest presence of plastics (23.62 ± 6.49 kg km-2), mainly wet wipes. Regarding depth, the continental shelf had the highest density of ML, with 12.24 ± 2.40 kg km-2. The potential ML removal (t year-1) was calculated using fishing effort (hours). It is estimated that the bottom trawlers may potentially remove 237 ± 36 t year-1 of ML in the Catalan coast. FFL initiatives should be part of a multidisciplinary approach to tackle marine litter, which must include prevention, monitoring, and cleaning actions.

A Pictorial Exploration of Mammary Paget Disease: Insights and Perspectives.

Mammary Paget disease (MPD) is a rare condition primarily affecting adult women, characterized by unilateral skin changes in the nipple-areolar complex (NAC) and frequently associated with underlying breast carcinoma. Histologically, MPD is identified by large intraepidermal epithelial cells (Paget cells) with distinct characteristics. Immunohistochemical profiles aid in distinguishing MPD from other skin conditions. Clinical evaluation and imaging techniques, including magnetic resonance imaging (MRI), are recommended if MPD is suspected, although definitive diagnosis always requires histological examination. This review delves into the historical context, epidemiology, pathogenesis, clinical manifestations, and diagnosis of MPD, emphasizing the need for early detection. The classification of MPD based on pathogenesis is explored, shedding light on its varied presentations. Treatment options, including mastectomy and breast-conserving surgery, are discussed with clear guidelines for different scenarios. Adjuvant therapies are considered, particularly in cases with underlying breast cancer. Prognostic factors are outlined, underlining the importance of early intervention. Looking to the future, emerging techniques, like liquid biopsy, new immunohistochemical and molecular markers, and artificial intelligence-based image analysis, hold the potential to transform MPD diagnosis and treatment. These innovations offer hope for early detection and improved patient care, though validation through large-scale clinical trials is needed.

Diagnostic clues for hyalinizing trabecular tumor on fine needle aspiration cytology.

Objectives: The hyalinizing trabecular tumor (HTT) is a rare benign neoplasm of the thyroid gland. This neoplasm has overlapping cytological features with Papillary Thyroid Carcinoma, Medullary Carcinoma and Follicular Neoplasm with Nuclear Features of Papillary Carcinoma. This can lead to misdiagnosis of malignancy in fine needle aspiration (FNA) cytology specimens with unnecessary total thyroidectomy. The aim of this study is to determine if there are some cytological features that could help us to suspect HTT on FNA specimens and avoid radical surgery. Material and Methods: With this purpose we have collected 6 cases diagnosed of HTT in Hospital Clínico San Carlos of Madrid (Spain) in the last 10 years and reviewed the cytological specimens. Result: We conclude that the presence of hyaline material in FNA specimens of HTT is a constant feature being a diagnostic clue. We must be cautious not to confuse it with dense colloid or amyloid material, the latter seen in Medullary Carcinoma. Papillary architecture and fibrovascular cores are not present in a HTT. Special stains as ki-67, calcitonin and Congo Red staining could help us in achieving the correct diagnosis. Conclusion: We feel the cytopathologists must be aware of the distinguishing features of this lesion, mainly the typical hyaline material to achieve a proper diagnosis and be able to reduce unnecessary aggressive management of these patients.

Self-Harm on the Internet Among Adolescents: Prevalence and Association With Depression, Anxiety, Family Cohesion, and Social Resources.

BACKGROUND: Using the internet to search for information or share images about self-harm is an emerging risk among young people. The aims of this study were (a) to analyze the prevalence of different types of self-harm on the internet and differences by sex and age, and (b) to examine the relationship of self-harm on the internet with intrapersonal factors (i.e., depression and anxiety) and interpersonal factors (i.e., family cohesion and social resources). METHOD: The sample consisted of 1,877 adolescents (946 girls) between 12 and 17 years old (Mage = 13.41, SD = 1.25) who completed self-report measures. RESULTS: Approximately 11% of the participants had been involved in some type of self-harm on the internet. The prevalence was significantly higher among girls than boys and among adolescents older than 15 years old. Depression and anxiety increased the risk of self-harm on the internet, whereas family cohesion decreased the probability of self-harm on the internet. CONCLUSIONS: Self-harm on the internet is a relatively widespread phenomenon among Spanish adolescents. Prevention programs should include emotional regulation, coping skills, and resilience to reduce engagement in this behavior.

Feasibility and Long-Term Compliance to Continuous Positive Airway Pressure Treatment in Adults With Down Syndrome, a Genetic Form of Alzheimer's Disease.

Background: Down syndrome (DS) is a genetic form of Alzheimer's disease (AD) with a high prevalence of obstructive sleep apnea (OSA). These characteristics place the DS population as an optimal model to study the relationship between sleep and AD and to design clinical trials of preventive sleep therapies for AD. Regrettably, OSA treatment with continuous positive airway pressure (CPAP) is often neglected in adults with DS. In both clinical practice and research trials, it is usually presumed that these patients will not adapt to or tolerate the therapy. Study Objective: We aimed to evaluate the feasibility and long-term CPAP compliance in this population and their capacity to be enrolled in CPAP research studies. Methods: We prospectively compared the CPAP compliance of 17 OSA patients with DS and 19 age and sex matched OSA euploid patients. CPAP management and follow-up schedules were prescribed according to the habitual clinical practice. We compared group differences in tolerance, objective, and subjective hours of nightly CPAP usage at the 1st, 3rd, 6th, 12th, 24th, and 36th month visits. Good compliance was defined as at least 4 h use per night. We also investigated predictive factors of long-term CPAP compliance. Results: The percentage of DS subjects with good CPAP compliance (81.2 vs. 78.9%) and the objective CPAP use (5 vs. 6 h, p = 0.92) did not differ from the control group (CG). Subjective CPAP compliance was significantly higher in OSA patients with DS than in controls in all the follow-up visits (8 vs. 6.75 h, p = 0.001). The DS group had a significantly higher number of visits (9 vs. 5; p = 0.021) and mask changes (2.5 vs. 2; p = 0.05) than controls. Objective hours of CPAP use at the first follow-up visit predicted long-term CPAP compliance (p < 0.005). Conclusion: CPAP treatment is feasible and has good long-term compliance in OSA patients with DS. It should be recommended to improve health and prevent comorbidities. The DS population is indeed suitable to participate in longitudinal preventive sleep clinical trials for AD.

[Intermediate Respiratory Care Units: Questions and Answers]. / Unidades de Cuidados Respiratorios Intermedios: preguntas y respuestas.

The intermediate respiratory care units (UCRI) are areas of monitoring and specialized care of patients with acute or chronic-exacerbated respiratory failure, whose severity does not require admission to an intensive care unit, but which due to their complexity cannot be treated in conventional hospitalization. Although the COVID-19 pandemic has proven its usefulness in the management of critical respiratory patients, the historical trajectory of the UCRI comes from many years ago, in which its cost-effectiveness has been demonstrated by far. This document presents a series of questions and answers on the history of the UCRI, in addition to the criteria for admission, infrastructure, human and technical resources, and the types of existing Units. Within the UCRI year 2021-2022 designated by the Spanish Society of Pneumology and Thoracic Surgery, any scientific dissemination linked to the in-depth knowledge of these units is timely, where multidisciplinarity and the work of professionals related to the care of critical respiratory patients converge.

Long-Term Effect of Noninvasive Ventilation on Diaphragm in Chronic Respiratory Failure.

PURPOSE: Home non-invasive ventilation (NIV) is recommended in patients with COPD and hypercapnic chronic respiratory failure (HCRF). The mechanism by it can improve alveolar ventilation during spontaneous breathing is not yet completely explained. Our aim is to evaluate the impact of on diaphragm muscle function in a series of patients with HCRF. PATIENTS AND METHODS: Observational, longitudinal, prospective study of a series of patients with very severe chronic obstruction to airflow treated with home high imntensity NIV (HINIV). Patients underwent a baseline and after 12 months assessment including adherence to treatment, quality of life, respiratory function tests and diaphragmatic ultrasound. SPSS v.26 software was used for statistical analysis. RESULTS: We studied 30 patients, 63% male, the mean age was 60.8 (±6.4) years old. Patients had a severe obstructive ventilatory pattern [FEV1 21.8 (±6.1)%] and hypercapnia [pCO2 56.4 (±7.2) mmHg]. After 12 months of HINIV, we observed significant increases in FVC of 9.2% (p = 0.002), FEV1 of 3.5% (p = 0.04), MIP of 9.4% (p = 0.006), and 6-minute-walking test (6MWT) of 31.9 m (p = 0.001), as well as decreases in paCO2 of 12.5 mmHg (p = 0.001), HCO3 of 4.7 mmol/L (p = 0.001) and BODE index from 7 to 6. Diaphragmatic ultrasound demonstrated an increase in the thickening fraction of 14% (p = 0.002). Respiratory symptoms (p = 0.04), physical function (p = 0.03), and sleep (p = 0.04) also improved. CONCLUSION: In patients with HCRF due to very severe chronic obstruction to airflow, long-term HINIV can improve respiratory performance by improving the function of the diaphragmatic musculature. Larger multicenter clinical trials are needed to confirm the results suggested in this study.

Coexistence of transmural and lateral wavefront progression of myocardial infarction in the human heart.

INTRODUCTION AND OBJECTIVES: According to the wavefront phenomenon described in the late 1970s, myocardial infarction triggered by acute coronary occlusion progresses with increasing duration of ischemia as a transmural wavefront from the subendocardium toward the subepicardium. However, whether wavefront progression of necrosis also occurs laterally has been disputed. We aimed to assess the transmural and lateral spread of myocardial damage after acute myocardial infarction in humans and to evaluate the impact of metoprolol on these. METHODS: We assessed myocardial infarction in the transmural and lateral dimensions in a cohort of 220 acute ST-segment elevation myocardial infarction (STEMI) patients from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction). The patients underwent cardiac magnetic resonance imaging at 5 to 7 days and 6 months post-STEMI. RESULTS: On day 5 to 7 post-STEMI cardiac magnetic resonance, there was a strong linear correlation between the transmural and lateral extent of infarction (delayed gadolinium enhancement) (r=-0.88; P<.001). Six months after STEMI, myocardial scarring (delayed gadolinium enhancement) was significantly less extensive in the transmural and lateral dimensions, suggesting that infarct resorption occurs in both. Furthermore, progression in both directions occurred both in patients receiving metoprolol and control patients, implying that myocardial salvage occurs both in the transmural and the lateral direction. CONCLUSIONS: Our findings challenge the assumption that irreversible injury does not spread laterally. A "circumferential" or multidirectional wavefront would imply that cardioprotective therapies might produce meaningful salvage at lateral borders of the infarct. This trial was registered at ClinicalTrial.gov (Identifier: NCT01311700).

Effect of mesenchymal stem cells combined with chondroitin sulfate in an in vitro model of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease affecting the whole joint structure. The specific molecules responsible for the inflammatory processes involved in the development of OA have been the focus of many studies. Adipose tissue-derived mesenchymal stem cells (ASCs) constitute a promising cell-based therapy which could be used as an alternative to or in combination with drug therapies. Chondroitin sulfate (CS) plays a protective role in the joint by decreasing concentrations of pro-inflammatory cytokines and therefore has an important part in moderating chondrocyte metabolism. The aim of this study is to use an in vitro model of OA to evaluate the combined effectiveness of CS and ASCs as a treatment. We give a detailed discussion of the roles of cytokines and other key molecules involved in OA. In addition, we report the effects of treating inflamed chondrocytes with ASCs and CS on the expression of specific cartilage genes. Findings show that both treatments reduced expression of all genes associated with the pro-inflammatory cytokines we analyzed. However, we saw no increase in the expression of the specific genes encoding for cartilage matrix proteins, such as collagen type II and aggrecan. This study shows the effectiveness of combining ASCs and CS in the treatment of OA.