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Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1-3. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)4-7. RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.
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Proteína C-Reactiva/genética , COVID-19/genética , Perfilación de la Expresión Génica/métodos , Macrófagos/metabolismo , SARS-CoV-2/aislamiento & purificación , Componente Amiloide P Sérico/genética , Células A549 , Adulto , Proteína C-Reactiva/metabolismo , COVID-19/epidemiología , COVID-19/virología , Línea Celular Tumoral , Células Cultivadas , Estudios de Cohortes , Células Endoteliales/metabolismo , Epidemias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Neutrófilos/metabolismo , Pronóstico , SARS-CoV-2/fisiología , Componente Amiloide P Sérico/metabolismoRESUMEN
BACKGROUND: Previous research has found associations between various non-genetic factors and breast cancer (BrCa) risk. This study summarises and appraises the credibility of the available evidence on the association between non-genetic factors and BrCa risk. METHODS: We conducted an umbrella review of meta-analyses. Medline, Scopus, and the Cochrane databases were systematically searched for meta-analyses examining non-genetic factors and BrCa incidence or mortality. The strength of the evidence was graded in four categories (i.e., weak, suggestive, highly suggestive, convincing). RESULTS: A total of 781 meta-analyses from 280 publications were evaluated and graded. We included exposures related to anthropometric measurements, biomarkers, breast characteristics and diseases, diet and supplements, environment, exogenous hormones, lifestyle and social factors, medical history, medication, reproductive history, and pregnancy. The largest number of examined associations was found for the category of diet and supplements and for exposures such as aspirin use and active smoking. The statistically significant (P-value < 0.05) meta-analyses were 382 (49%), of which 204 (53.4%) reported factors associated with increased BrCa risk. Most of the statistically significant evidence (n = 224, 58.6%) was graded as weak. Convincing harmful associations with heightened BrCa risk were found for increased body mass index (BMI), BMI and weight gain in postmenopausal women, oral contraceptive use in premenopausal women, increased androstenedione, estradiol, estrone, and testosterone concentrations, high Breast Imaging Reporting and Data System (BIRADS) classification, and increased breast density. Convincing protective factors associated with lower BrCa risk included high fiber intake and high sex hormone binding globulin (SHBG) levels while highly suggestive protective factors included high 25 hydroxy vitamin D [25(OH)D] levels, adherence to healthy lifestyle, and moderate-vigorous physical activity. CONCLUSIONS: Our findings suggest some highly modifiable factors that protect from BrCa. Interestingly, while diet was the most studied exposure category, the related associations failed to reach higher levels of evidence, indicating the methodological limitations in the field. To improve the validity of these associations, future research should utilise more robust study designs and better exposure assessment techniques. Overall, our study provides knowledge that supports the development of evidence-based BrCa prevention recommendations and guidance, both at an individual level and for public health initiatives. TRIAL REGISTRATION: PROSPERO CRD42022370675.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/epidemiología , Dieta , Suplementos Dietéticos , Estilo de Vida , Metaanálisis como Asunto , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: To summarize the epidemiologic evidence and assess the validity of claimed associations of inflammatory bowel diseases (IBDs) with overall and site-specific cancer risk. METHODS: We systematically searched PubMed, Embase, and Scopus from inception to May 10, 2021, to identify and comprehensively reanalyze the data of meta-analyses on associations between IBDs (ie, Crohn's disease [CD] and ulcerative colitis [UC]) and subsequent risk of cancer. The strength of epidemiologic evidence was graded as high, moderate, or weak, by applying prespecified criteria that included the random effects estimate, its 95% confidence interval, and P value, estimates of heterogeneity, small-study effects, and robustness to unmeasured confounding. RESULTS: This study critically appraised 277 estimates derived from 24 published meta-analyses and our own meta-analyses. The association between pediatric-onset IBDs and overall risk of cancer showed high epidemiologic evidence. Twenty associations (15 cancer types) demonstrated moderate evidence: any cancer (pediatric-onset UC), mouth to terminal ileum (CD), small bowel (CD/UC), colon (CD), rectum (CD/UC), colon-rectum (IBDs, pediatric-onset CD/UC), bile ducts and liver (CD/UC), liver (CD), intrahepatic cholangiocarcinoma (IBDs), bile ducts (CD), skin (CD), squamous cell carcinoma of the skin (CD), nonmelanoma skin cancer (UC), kidney (CD), and thyroid cancer (IBDs). Another 40 associations (23 cancer types) showed statistical significance; however, our confidence in these effect estimates was weak. No statistical significance was found regarding further 47 associations. CONCLUSIONS: Associations between IBDs and different types of malignancy showed varying levels of evidence and magnitude of risk. Further primary research investigating the impact of a consistent set of risk factors that are known to affect cancer risk is warranted. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021254996.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Neoplasias , Niño , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/epidemiología , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Metaanálisis como Asunto , Neoplasias/epidemiología , Neoplasias/etiologíaRESUMEN
INTRODUCTION: We assessed the prevalence and clinical outcomes of segmental colitis associated with diverticulosis (SCAD) in patients with newly diagnosed diverticulosis. METHODS: A 3-year international, multicenter, prospective cohort study was conducted involving 2,215 patients. RESULTS: SCAD diagnosis was posed in 44 patients (30 male patients; median age: 64.5 years; prevalence of 1.99%, 95% confidence interval, 1.45%-2.66%). Patients with SCAD types D and B showed worse symptoms, higher fecal calprotectin values, needed more steroids, and reached less likely complete remission. DISCUSSION: Although SCAD generally had a benign outcome, types B and D were associated with more severe symptoms and worse clinical course.
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Colitis , Divertículo , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Resultado del Tratamiento , Colitis/complicaciones , Colitis/epidemiología , Colitis/diagnóstico , Divertículo/complicacionesRESUMEN
We conducted a systematic review aiming to summarize the data on the current hemorrhage prediction models and evaluate their potential for generalized application in the neonatal population. The electronic databases PubMed and Scopus were searched, up to September 20, 2023, for studies that focused on development and/or validation of a prediction model for bleeding risk in neonates, and described the process of model building. Nineteen studies fulfilled the inclusion criteria for the present review. Eighteen bleeding risk prediction models in the neonatal population were identified, four of which were internally validated, one temporally and one externally validated. The existing prediction models for neonatal hemorrhage are mostly based on clinical variables and do not take into account the clinical course and hemostatic profile of the neonates. Most studies aimed at predicting the risk of intraventricular hemorrhage (IVH) reflecting the fact that IVH is the most frequent and serious bleeding complication in preterm neonates. A justification for the study sample size for developing the prediction model was given only by one study. Prediction and stratification of risk of hemorrhage in neonates is yet to be optimized. To this end, qualitative standards for model development need to be further improved. The assessment of the risk of bleeding incorporating platelet count, coagulation parameters, and a set of relevant clinical variables is crucial. Large, rigorous, collaborative cohort studies are warranted to develop a robust prediction model to inform the need for transfusion, which is a fundamental step towards personalized transfusion therapy in neonates.
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We aimed to investigate the hemostatic status of diseased neonates using nonactivated rotational thromboelastometry (ROTEM) assay (NATEM) assay and, in addition, to evaluate the discriminative power of NATEM parameters in predicting the risk of bleeding in critically ill neonates and compare it to that of EXTEM (extrinsically activated ROTEM) parameters. This cohort study included 158 consecutive, critically ill neonates with presumed sepsis, perinatal hypoxia, or respiratory distress syndrome. The EXTEM and NATEM assays were performed on the first day of disease onset. The neonatal bleeding assessment tool was used to record and assess clinical bleeding events on the day of ROTEM analysis. Several EXTEM and NATEM ROTEM parameters differed between neonates with and without clinical bleeding events, indicating a hypo-coagulable state in neonates with clinical bleeding. NATEM parameters had comparable predictive performance for clinical bleeding events with EXTEM parameters for clotting time, clot formation time (CFT), A10 (clot amplitude at 10minutes), maximum clot firmness, lysis index at 60minutes, and maximum clot elasticity (p>0.05). However, NATEM A20, A30, and α angle demonstrated better predictive ability than EXTEM A20, A30, and α angle, respectively (p<0.05). A NATEM CFT value ≥147seconds presented 95.2% sensitivity (95% confidence interval [CI]: 76.1-99.8%) and 65.6% specificity (95% CI: 57.1-73.5%) to detect neonates with clinical bleeding, while a NATEM A10 value ≤42mm had 80.8% sensitivity (95% CI: 71.8-85.9%) and 76.0% specificity (95% CI: 52.8-91.7%) to detect neonates with clinical bleeding events. The NATEM assay has shown remarkable sensitivity in predicting bleeding in critically ill neonates, exceeding EXTEM performance in some selected parameters. The incorporation of NATEM test parameters in predictive models for neonatal hemorrhage seems promising.
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Enfermedad Crítica , Tromboelastografía , Recién Nacido , Humanos , Estudios de Cohortes , Pruebas de Coagulación Sanguínea , Hemorragia/diagnósticoRESUMEN
The frequency of red blood cell (RBC) transfusions is high in total joint arthroplasties, and the hemorrhagic risk is associated with both surgery- and patient-related factors. This study aims to assess the ability of rotational thromboelastometry (ROTEM) to identify patients at high risk for transfusion and excessive bleeding. A prospective observational study was conducted including 206 patients who underwent total knee or hip arthroplasties. Assessment of the coagulation status was performed preoperatively and immediately postoperatively using ROTEM analysis and conventional coagulation tests. The number of RBC transfusions and the postoperative hemoglobin drop were recorded. ROTEM findings were compared between transfused and nontransfused patients, and also between patients with and without excessive bleeding. Higher values of postoperative FIBTEM maximum clot firmness (MCF) were associated with lower risks of transfusion (odds ration [OR]: 0.66, 95% confidence interval [CI]: 0.57-0.78, p<0.001) and excessive bleeding (OR: 0.58, 95% CI: 0.36-0.94, p=0.028). A postoperative FIBTEM MCF value ≤10mm had 80.1% (95% CI: 73.1-85.9%) sensitivity with 75.5% (95% CI: 60.4-87.1%) specificity to predict transfusion requirements, and 70.5% (95% CI: 63.6-76.8%) sensitivity with 88.8% (95% CI: 51.7-99.7%) specificity to predict excessive bleeding. The estimated average probability of transfusion in patients with FIBTEM MCF values of 0 to 4mm is 86.3%. ROTEM assay demonstrated high predictive ability for transfusion and excessive bleeding. Identification of patients at risk for transfusion could allow blood banks to ensure adequate blood supply, while also more intense blood-salvaging strategies could be implemented in these patients.
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Hemorragia , Tromboelastografía , Humanos , Pruebas de Coagulación Sanguínea , Transfusión Sanguínea , ArtroplastiaRESUMEN
BACKGROUND AND AIMS: Adenoma detection rate (ADR) is still the main surrogate outcome parameter of screening colonoscopy, but most studies include mixed indications, and basic ADR is quite variable. We therefore looked at the control groups in randomized ADR trials using advanced imaging or mechanical methods to find out whether indications or other factors influence ADR levels. METHODS: Patients in the control groups of randomized controlled trials (RCTs) on ADR increase using various methods were collected based on a systematic review; this control group had to use high-definition white-light endoscopy performed between 2008 and 2021. Random-effects meta-analysis was used to pool ADR in control groups and its 95% confidence interval (CI) according to clinical (indication and demographic), study setting (tandem/parallel, number of centers, sample size), and technical (type of intervention, withdrawal time) parameters. Interstudy heterogeneity was reported with the I2 statistic. Multivariable mixed-effects meta-regression was performed for potentially relevant variables. RESULTS: From 80 studies, 25,304 patients in the respective control groups were included. ADR in control arms varied between 8.2% and 68.1% with a high degree of heterogeneity (I2 = 95.1%; random-effect pooled value, 37.5%; 95% CI, 34.6â40.5). There was no difference in ADR levels between primary colonoscopy screening (12 RCTs, 15%) and mixed indications including screening/surveillance and diagnostic colonoscopy; however, fecal immunochemical testing as an indication for colonoscopy was an independent predictor of ADR (odds ratio [OR], 1.6; 95% CI, 1.1-2.4). Other well-known parameters were confirmed by our analysis such as age (OR, 1.038; 95% CI, 1.004-1.074), sex (male sex: OR, 1.02; 95% CI, 1.01-1.03), and withdrawal time (OR, 1.1; 95% CI, 1.0-1.1). The type of intervention (imaging vs mechanical) had no influence, but methodologic factors did: More recent year of publication and smaller sample size were associated with higher ADR. CONCLUSIONS: A high level of variability was found in the level of ADR in the control groups of RCTs. With regards to indications, only fecal immunochemical test-based colonoscopy studies influenced basic ADR, and primary colonoscopy screening appeared to be similar to other indications. Standardization for variables related to clinical, methodologic, and technical parameters is required to achieve generalizability and reproducibility.
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Adenoma , Neoplasias Colorrectales , Masculino , Humanos , Grupos Control , Colonoscopía/métodos , Adenoma/diagnóstico por imagen , Tamizaje Masivo , Oportunidad Relativa , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodosRESUMEN
BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aimed to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPtical diagnosis Training to Improve dysplasia Characterization in Inflammatory Bowel Disease (OPTIC-IBD). METHODS: We designed a web-based learning module that includes surveillance principles, optical diagnostic methods, approach to characterization, and classifications of colonic lesions using still images and videos. We invited gastroenterologists from Canada, Italy, and the United Kingdom with a wide range of experience. Participants reviewed 24 educational videos of IBD colonic lesions, predicted histology, and rated their confidence. The primary endpoint was to improve accuracy in detecting dysplastic lesions after training on the platform. Furthermore, participants were randomized 1:1 to get additional training or not, with a final assessment occurring after 60 days. Diagnostic performance for dysplasia and rater confidence were measured. RESULTS: A total of 117 participants completed the study and were assessed for the primary endpoint. Diagnostic accuracy improved from 70.8% to 75.0% (P = .002) after training, with the greatest improvements seen in less experienced endoscopists. Improvements in both accuracy and confidence were sustained after 2 months of assessment, although the group randomized to receive additional training did not improve further. Similarly, participants' confidence in characterizing lesions significantly improved between before and after the course (P < .001), and it was sustained after 2 months of assessment. CONCLUSIONS: The OPTIC-IBD training module demonstrated that an online platform could improve participants' accuracy and confidence in the optical diagnosis of dysplasia in patients with IBD. The training platform can be widely available and improve endoscopic care for people with IBD. (Clinical trial registration number: NCT04924543.).
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BACKGROUND: This study aimed to explore the hemostatic profile of neonates with necrotizing enterocolitis (NEC) using Rotational Thromboelastometry (ROTEM) and to investigate if ROTEM parameters have the capacity to play a role in the differentiation of NEC from sepsis at the disease onset. METHODS: This observational study included 62 neonates (mean gestational age 31.6 weeks and mean birth weight 1620g) hospitalized in a neonatal intensive care unit. The neonates were categorized in three groups: neonates with NEC (Bell stage II and above), neonates with sepsis and healthy neonates and they were matched 1:1:1 with regards to gestational age, delivery mode, and sex. Clinical, laboratory data as well as measurements of ROTEM parameters at disease onset were recorded. RESULTS: ROTEM parameters differed between neonates with NEC and neonates with sepsis, indicating that NEC results in accelerated clot formation and higher clot strength compared to sepsis. The EXTEM CFT and A10 parameters demonstrated the highest diagnostic performance for NEC in terms of discrimination between NEC and sepsis (AUC, 0.997; 95% CI: 0.991-1.000 and 0.973; 95% CI: 0.932-1.000, respectively). CONCLUSIONS: Neonates with NEC manifested accelerated clot formation and higher clot strength compared to septic and healthy neonates, as these were expressed by ROTEM parameters. IMPACT: This work reports data on the hemostatic profile of neonates with necrotizing enterocolitis (NEC) using Rotational Thromboelastometry (ROTEM) and the capacity of ROTEM parameters in differentiating of NEC from sepsis at the disease onset. Neonates with NEC present acceleration of coagulation and exhibit a hypercoagulable profile, as this is expressed by ROTEM parameters, in comparison to septic and healthy neonates. ROTEM parameters demonstrated a good diagnostic capacity in differentiating NEC from sepsis at the disease onset.
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Autoimmune diseases comprise a very heterogeneous group of disorders characterized by disruptive immune responses against self-antigens, chronic morbidity and increased mortality. The incidence and prevalence of major autoimmune conditions are particularly high in the western world, at northern latitudes, and in industrialized countries. This study will mainly focus on five major autoimmune conditions, namely type 1 diabetes, multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, and autoimmune thyroid disorders. Epidemiological and experimental evidence suggests a protective role of sunlight exposure on the etiology of major autoimmune conditions mediated by the endogenous production of vitamin D and nitric oxide. A historical perspective shows how the rise of anthropogenic air pollutants is temporally associated with dramatic increases in incidence of these conditions. The scattering caused by ambient particulate matter and the presence of tropospheric ozone can reduce the endogenous production of vitamin D and nitric oxide, which are implicated in maintaining the immune homeostasis. Air pollutants have direct detrimental effects on the human body and are deemed responsible of an increasingly higher portion of the annual burden of human morbidity and mortality. Air pollution contributes in systemic inflammation, activates oxidative pathways, induces epigenetic alterations, and modulates the function and phenotype of dendritic cells, Tregs, and T-cells. In this review, we provide epidemiological and mechanistic insights regarding the role of UV-mediated effects in immunity and how anthropic-derived air pollution may affect major autoimmune conditions through direct and indirect mechanisms.
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Contaminantes Atmosféricos , Contaminación del Aire , Enfermedades Autoinmunes , Humanos , Rayos Ultravioleta , Óxido Nítrico , Material Particulado , Enfermedades Autoinmunes/etiología , Vitamina DRESUMEN
Surgical resection of malignant bone tumors is associated with a high risk of venous thromboembolism (VTE). The purpose of this study was to evaluate the association between rotational thromboelastometry (ROTEM) parameters and VTE following oncologic resections, and to evaluate their prognostic capacity for this complication. A prospective observational study was conducted including 113 patients who underwent surgical resection of malignant bone tumors. ROTEM analysis and conventional coagulation studies were performed preoperatively and on the 2nd postoperative day, while patients were followed for the development of VTE. Logistic regression was used to assess the association between ROTEM parameters and occurrence of VTE. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were calculated as measures of discrimination and predictive accuracy. Fourteen patients (12.4%) developed symptomatic VTE. Development of VTE was associated with shortened INTEM CFT (Odds Ratio [OR] 0.90, 95% Confidence Interval [CI] 0.84 - 0.96, p = 0.004), higher INTEM A10 (OR 1.21, 95% CI 1.07 - 1.36, p = 0.002), higher INTEM MCF (OR 1.22, 95% CI 1.08 - 1.37, p = 0.001) and higher INTEM LI60 (OR 2.10, 95% CI 1.38 - 3.21, p = 0.001). An INTEM LI60 value indicative of fibrinolysis shutdown (≥ 98%) had the best predictive accuracy for VTE (AUC = 0.887, 95% CI 0.824 - 0.951, sensitivity = 100%, specificity = 67.0%), higher than that of D-dimer levels (p = 0.028). ROTEM parameters were promising predictors of symptomatic VTE. Fibrinolysis shutdown as reflected by ROTEM LI60 and high D-dimer levels can aid the identification of high-risk patients. Future studies should evaluate whether the addition of ROTEM findings to an expanded risk-assessing model can improve the predictive capacity and provide better guidance in thromboprophylaxis.
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Trastornos de la Coagulación Sanguínea , Neoplasias Óseas , Tromboembolia Venosa , Humanos , Pronóstico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiología , Fibrinólisis , Anticoagulantes , Tromboelastografía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Neoplasias Óseas/complicacionesRESUMEN
Purpose: In modern breast cancer treatment, a growing role has been observed for breast reconstruction together with an increase in clinical indications for postmastectomy radiotherapy (PMRT). Choosing the optimum type of reconstructive technique is a clinical challenge. We therefore conducted a national multicenter study to analyze the impact of PMRT on breast reconstruction. Methods: We conducted a retrospective case-control multicenter study on women undergoing breast reconstruction. Data were collected from 18 Italian Breast Centres and stored in a cumulative database which included the following: autologous reconstruction, direct-to-implant (DTI), and tissue expander/immediate (TE/I). For all patients, we described complications and surgical endpoints to complications such as reconstruction failure, explant, change in type of reconstruction, and reintervention. Results: From 2001 to April 2020, 3116 patients were evaluated. The risk for any complication was significantly increased in patients receiving PMRT (aOR, 1.73; 95% CI, 1.33-2.24; p < 0.001). PMRT was associated with a significant increase in the risk of capsular contracture in the DTI and TE/I groups (aOR, 2.24; 95% CI, 1.57-3.20; p < 0.001). Comparing type of procedures, the risk of failure (aOR, 1.82; 95% CI, 1.06-3.12, p=0.030), explant (aOR, 3.34; 95% CI, 3.85-7.83, p < 0.001), and severe complications (aOR, 2.54; 95% CI, 1.88-3.43, p < 0.001) were significantly higher in the group undergoing DTI reconstruction as compared to TE/I reconstruction. Conclusion: Our study confirms that autologous reconstruction is the procedure least impacted by PMRT, while DTI appears to be the most impacted by PMRT, when compared with TE/I which shows a lower rate of explant and reconstruction failure. The trial is registered with NCT04783818, and the date of registration is 1 March, 2021, retrospectively registered.
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Neoplasias de la Mama , Mamoplastia , Femenino , Humanos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/etiología , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/métodos , Mastectomía/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Mamoplastia/efectos adversos , Mamoplastia/métodosRESUMEN
INTRODUCTION: Tuberous breast deformity (TB) is a condition mostly characterized by breast stenosis, areolar widening and glandular asymmetry. The most accredited hypothesis describes an abnormal thickening of the fascia corporis that might influence an alteration in the glandular development, limiting the horizontal growth of breast parenchyma. Alterations in the extracellular matrix components (ECM) might be involved in the abnormal breast development. PATIENTS: The aim of our case control study is to use histological specimens to analyze qualitative and quantitative differences in collagen fibers, elastic fibers and vessel densities in TB and normal breasts of 20 patients using a software for digital pathology. RESULTS: The quantitative findings showed increasing concentrations of collagen fibers and decreasing elastic fibers in TB, compared to normal breasts. No difference was seen in vessel density among the two groups. The qualitative findings highlighted differences in the distribution of the ECM among the TB specimens. Collagen fibers showed a packed appearance rather a scattered distribution, while elastic fibers visibly presented a reduction and a focal distribution of their concentration. CONCLUSIONS: The study proposes a correlation between abnormalities in ECM concentrations and TB, resulting in a higher degree of fibrosis and in the characteristic stenotic and less elastic morphology of the deformity. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Mamoplastia , Humanos , Mamoplastia/métodos , Estudios de Cohortes , Estudios de Casos y Controles , Estudios Retrospectivos , Resultado del Tratamiento , Estética , Mama/cirugía , Pezones , Constricción Patológica , ColágenoRESUMEN
OBJECTIVE: To investigate the predictive value of the Diverticular Inflammation and Complication Assessment (DICA) classification and to develop and validate a combined endoscopic-clinical score predicting clinical outcomes of diverticulosis, named Combined Overview on Diverticular Assessment (CODA). DESIGN: A multicentre, prospective, international cohort study. SETTING: 43 gastroenterology and endoscopy centres located in Europe and South America. PARTICIPANTS: 2215 patients (2198 completing the study) at the first diagnosis of diverticulosis/diverticular disease were enrolled. Patients were scored according to DICA classifications. INTERVENTIONS: A 3-year follow-up was performed. MAIN OUTCOME MEASURES: To predict the acute diverticulitis and the surgery according to DICA classification. Survival methods for censored observation were used to develop and validate a novel combined endoscopic-clinical score for predicting diverticulitis and surgery (CODA score). RESULTS: The 3-year cumulative probability of diverticulitis and surgery was of 3.3% (95% CI 2.5% to 4.5%) in DICA 1, 11.6% (95% CI 9.2% to 14.5%) in DICA 2 and 22.0% (95% CI 17.2% to 28.0%) in DICA 3 (p<0.001), and 0.15% (95% CI 0.04% to 0.59%) in DICA 1, 3.0% (95% CI 1.9% to 4.7%) in DICA 2 and 11.0% (95% CI 7.5% to 16.0%) in DICA 3 (p<0.001), respectively. The 3-year cumulative probability of diverticulitis and surgery was ≤4%, and ≤0.7% in CODA A; <10% and <2.5% in CODA B; >10% and >2.5% in CODA C, respectively. The CODA score showed optimal discrimination capacity in predicting the risk of surgery in the development (c-statistic: 0.829; 95% CI 0.811 to 0.846) and validation cohort (c-statistic: 0.943; 95% CI 0.905 to 0.981). CONCLUSIONS: DICA classification has a significant role in predicting the risk of diverticulitis and surgery in patients with diverticulosis, which is significantly enhanced by the CODA score. TRIAL REGISTRATION NUMBER: NCT02758860.
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Enfermedades Diverticulares , Diverticulitis , Diverticulosis del Colon , Divertículo , Estudios de Cohortes , Colonoscopía , Enfermedades Diverticulares/diagnóstico , Diverticulitis/complicaciones , Diverticulitis/diagnóstico , Diverticulosis del Colon/diagnóstico , Divertículo/complicaciones , Humanos , Inflamación/complicaciones , Pronóstico , Estudios ProspectivosRESUMEN
OBJECTIVES: To investigate the agreement between the EXTEM and NATEM measurements. METHODS: In this retrospective observational study, EXTEM and NATEM analyses were performed on blood samples from 162 ill neonates, providing 324 paired measurements. The agreement between EXTEM and NATEM measurements was evaluated by the nonparametric spearman's rank correlation to assess the correlation between the paired measurements, by the Bland-Altman analysis for the graphical presentation of the agreement, and by the Deming regression model to assess the significance of the agreement. The agreement between the two methods for the detection of bleeding events was determined by kappa statistic. RESULTS: Strong correlations were found between EXTEM and NATEM measurements for A10, MCF. The Bland-Altman plots showed good agreement for A10, MCF, LI60, and alpha angle parameters, while CT showed a nearly linear slope indicating that bias increased with the mean. The highest agreement for bleeding events was found for the A10 parameter (κ = 0.70, p < .001), while the lowest for the CT parameter (κ = 0.36, p = .94). CONCLUSIONS: NATEM parameters that reflect clot firmness and fibrinolytic activity are strongly correlated with the corresponding EXTEM measurements with a good agreement between them, indicating that these two methods could be used interchangeably.
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Coagulación Sanguínea , Tromboelastografía , Enfermedad Crítica , Hemorragia/diagnóstico , Hemorragia/etiología , Humanos , Recién Nacido , Estudios Retrospectivos , Tromboelastografía/métodosRESUMEN
Aspergillus spp. osteoarticular infections are destructive opportunistic infections, while there is no clear consensus on their management. The purpose of this review is to investigate the current literature regarding Aspergillus spp. osteoarticular infections. An electronic search of the PubMed and Scopus databases was conducted considering studies that assessed osteoarticular infections from Aspergillus spp. We included only studies with biopsy proven documentation of positive cultures or histological findings for Aspergillus spp., and those with essential information for each case such as the anatomical location of the infection, the type of treatment (conservative, surgical, combination), the antifungal therapy, and the outcome. Overall, 148 studies from 1965 to 2021 including 186 patients were included in the review. One hundred and seven (57.5%) patients underwent surgical debridement in addition to antifungal therapy, while 79 (42.7%) patients were treated only conservatively. Complete infection resolution was reported in 107 (57.5%) patients, while partial resolution in 29 (15.5%) patients. Surgical debridement resulted in higher complete infection resolution rate compared to only antifungal therapy (70.0% vs. 40.5%, P < 0.001), while complete resolution rate was similar for antifungal monotherapy and combination/sequential therapy (58.3% vs. 54.5%; P = 0.76). Last, complete resolution rate was also similar for monotherapy with amphotericin B (58.1%) and voriconazole (58.6%; P = 0.95). The results of this study indicate that antifungal monotherapy has similar efficacy with combination/sequential therapy, while voriconazole has similar efficacy with amphotericin B. Moreover, surgical debridement of the infected focus results in better outcomes in terms of infection eradication compared to conservative treatment. LAY SUMMARY: Antifungal monotherapy has similar efficacy with combination/sequential therapy, and voriconazole has similar efficacy with amphotericin B for the treatment of Aspergillus spp. osteoarticular infections, while surgical debridement of the infected focus improves the infection eradication rate.
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Anfotericina B , Aspergilosis , Animales , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Aspergilosis/diagnóstico , Aspergilosis/tratamiento farmacológico , Aspergilosis/cirugía , Aspergilosis/veterinaria , Aspergillus , Pruebas de Sensibilidad Microbiana/veterinaria , Resultado del Tratamiento , Voriconazol/uso terapéuticoRESUMEN
The aim of the present study was to assess the coagulation profile in neonatal critical illness using rotational thromboelastometry (ROTEM), and to investigate its association with disease severity and its potential prognostic role in this clinical setting. Over a period of 67 months (July 2014-February 2020) 423 critically ill neonates with confirmed or suspected sepsis, perinatal hypoxia, or respiratory distress syndrome, hospitalized in our neonatal intensive care unit were included in the study. Demographic, clinical, and laboratory data were recorded on admission day and arterial blood was analyzed on ROTEM analyzer using the standard extrinsically activated rotational thromboelastometry assay (EXTEM). Neonatal illness severity scores (Modified NEOMOD [Neonatal Multiple Organ Dysfunction] and SNAPPE [Score for Neonatal Acute Physiology with Perinatal Extension]) were calculated at the same time as ROTEM analysis. Mortality during in-hospital stay was the main outcome measure. Multivariable analyses showed that a 10 mm decrease in EXTEM clot amplitude recorded at 10 minutes (A10) is significantly associated with a higher mortality (odds ratio [OR] = 1.69, 95% confidence interval [CI]: 1.33-2.08). Higher modified NEOMOD (OR = 1.36, 95% CI: 1.26-1.47) and higher SNAPPE scores (OR = 1.06, 95% CI: 1.04-1.08) were also associated with increased mortality. The CT and A10 variables demonstrated the best prognostic performance among the EXTEM parameters for mortality (area under the curve [AUC] = 0.78; 95% CI: 0.69-0.86 and AUC = 0.76; 95% CI: 0.66-0.85, respectively), showing an optimal cut-off CT ≥63 seconds and A10 ≤37 mm. Using optimal cut-off values of the EXTEM parameters for prediction of mortality, neonates with CT ≥63 seconds were 7.4 times more likely to die (OR = 7.40, 95% CI: 3.50-15.65), while neonates with A10 ≤37 mm were 5.8 times more likely to die (OR = 5.88, 95% CI: 2.94-12.50). An EXTEM hypocoagulable profile on disease onset was shown to be an independent risk factor for in-hospital mortality in neonatal critical illness.
Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Tromboelastografía , Enfermedad Crítica , Estudios Transversales , Humanos , Recién Nacido , PronósticoRESUMEN
BACKGROUND: Our aim was to investigate the role of thromboelastometry (ROTEM) parameters, including maximum clot elasticity (MCE) and platelet component (PLTEM MCE and PLTEM MCF), in early prediction of bleeding events in thrombocytopenic critically ill neonates. MATERIAL AND METHODS: This single-center, prospective cohort study included 110 consecutive thrombocytopenic neonates with sepsis, suspected sepsis, or hypoxia. On the first day of disease onset, ROTEM EXTEM and FIBTEM assays were performed and the neonatal bleeding assessment tool was used for the evaluation of bleeding events. RESULTS: Most EXTEM and FIBTEM ROTEM parameters significantly differed between neonates with (n = 77) and without bleeding events (n = 33). Neonates with bleeding events had significantly lower PLTEM MCE and PLTEM MCF values compared to those without bleeding events (P < .001). Platelet count was found to be strongly positively correlated with EXTEM A5 (Spearman's rho = 0.61, P < .001) and A10 (rho = 0.64, P < .001). EXTEM A10 demonstrated the best prognostic performance (AUC = 0.853) with an optimal cutoff value (≤37 mm) (sensitivity = 91%, specificity = 76%) for prediction of bleeding events in thrombocytopenic neonates. CONCLUSIONS: EXTEM A5 and EXTEM A10 were found to be strong predictors of hemorrhage, compared to most ROTEM variables quantifying clot elasticity and platelet component in thrombocytopenic critically ill neonates.
Asunto(s)
Enfermedad Crítica , Hemorragia/diagnóstico , Hemorragia/etiología , Pruebas de Función Plaquetaria , Tromboelastografía/métodos , Trombocitopenia/sangre , Trombocitopenia/complicaciones , Biomarcadores , Coagulación Sanguínea , Plaquetas/metabolismo , Femenino , Humanos , Recién Nacido , Masculino , Recuento de Plaquetas , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tromboelastografía/normas , Trombocitopenia/diagnóstico , Trombocitopenia/etiologíaRESUMEN
"Developmental hemostasis" refers to the dynamic process of gradual hemostatic maturation. Conventional coagulation tests seem to fail to accurately depict the in vivo hemostasis, while viscoelastic tests, thromboelastography (TEG), and rotational thromboelastometry (ROTEM) appear very promising as they provide insight more rapidly and accurately into the hemostatic potential. We systematically reviewed the literature in PubMed to examine the use of TEG and ROTEM in neonates. Our search yielded 34 studies, of which 18 concerned healthy neonates and 16 sick neonates. These viscoelastic tests have shown accelerated initiation of coagulation, increased clot strength, and increased fibrinolysis in healthy neonates compared to children and adults. Cord blood leads to a hypercoagulable state as compared to whole blood when testing is performed with TEG. Pre-term neonates have a more hypocoagulable profile, but balanced hemostasis, related to term neonates, that evolves to a more procoagulant phenotype over the first month of life. Critically ill neonates exhibit a more hypocoagulable profile as compared to healthy neonates. TEG and ROTEM have shown predictive value for bleeding events in critically ill neonates and neonates undergoing cardiopulmonary bypass or therapeutic hypothermia.Conclusion: TEG and ROTEM need to become part of the standard coagulation assessment in clinical settings in which hemostatic abnormalities are involved, as they seem to provide more rapid and accurate information regarding the hemostatic profile of the neonates. Their predictive value for bleeding events in critically ill neonates could lead to a more targeted therapy optimizing utilization of blood products. What is Known: ⢠Conventional coagulation tests seem to fail to accurately depict the in vivo hemostasis. ⢠TEG and ROTEM delineate more rapidly and accurately the hemostatic potential. What is New: ⢠TEG and ROTEM have shown predictive value for bleeding events. ⢠TEG and ROTEM may lead to a more targeted transfusion therapy optimizing utilization of blood products.