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1.
Transl Lung Cancer Res ; 13(7): 1505-1517, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39118890

RESUMEN

Background: Lung cancer is still the main cause of cancer death. In the last decades, significant innovations were introduced in non-small cell lung cancer (NSCLC) treatment and management improving patient outcomes. The discovery of immune checkpoint inhibitors and the detection of an increasing list of actionable genetic alterations are enabling a tailored approach. Herein, we assessed in a pragmatic retrospective study the rate of biomarker tests within a large pulmonary pathology-based unit (PPU) network of the Veneto region (Northern Italy). Methods: Each PPU of 7 hubs and spoke centers implemented a biomarker database with pathologic and clinical data of patients with NSCLC diagnosis over 24 months. Results: Out of 1,817 NSCLC cases, 51% were advanced and 49% early stage, with 72% being adenocarcinomas. Programmed death ligand 1 expression and epidermal growth factor receptor mutations were available in most samples, 91% and 78%, respectively. Only 36% of advanced stages received all 5 biomarker tests with an increased rate over time. Co-occurring molecular alterations were detected in 42 cases (2%): the prevalence was (n=17) 41% and (n=25) 59% in early and late-stage adenocarcinomas, respectively. Conclusions: In this real-world study, while most patients received at least one biomarker test, less than 50% had all 5 biomarkers. The screening appeared to increase over time especially with the progressive use of next generation sequencing. Our results confirm the importance of systematic biomarker testing including all NSCLCs based on the evidence of several genomic alterations also in early-stage disease whose analysis may become relevant as neo-adjuvant targeted therapies are available. Keywords: Non-small cell lung cancer (NSCLC); biomarkers; actionable targets; lung cancer.

2.
Comput Methods Programs Biomed ; 255: 108326, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39029416

RESUMEN

BACKGROUND AND OBJECTIVE: Researchers commonly use automated solutions such as Natural Language Processing (NLP) systems to extract clinical information from large volumes of unstructured data. However, clinical text's poor semantic structure and domain-specific vocabulary can make it challenging to develop a one-size-fits-all solution. Large Language Models (LLMs), such as OpenAI's Generative Pre-Trained Transformer 3 (GPT-3), offer a promising solution for capturing and standardizing unstructured clinical information. This study evaluated the performance of InstructGPT, a family of models derived from LLM GPT-3, to extract relevant patient information from medical case reports and discussed the advantages and disadvantages of LLMs versus dedicated NLP methods. METHODS: In this paper, 208 articles related to case reports of foreign body injuries in children were identified by searching PubMed, Scopus, and Web of Science. A reviewer manually extracted information on sex, age, the object that caused the injury, and the injured body part for each patient to build a gold standard to compare the performance of InstructGPT. RESULTS: InstructGPT achieved high accuracy in classifying the sex, age, object and body part involved in the injury, with 94%, 82%, 94% and 89%, respectively. When excluding articles for which InstructGPT could not retrieve any information, the accuracy for determining the child's sex and age improved to 97%, and the accuracy for identifying the injured body part improved to 93%. InstructGPT was also able to extract information from non-English language articles. CONCLUSIONS: The study highlights that LLMs have the potential to eliminate the necessity for task-specific training (zero-shot extraction), allowing the retrieval of clinical information from unstructured natural language text, particularly from published scientific literature like case reports, by directly utilizing the PDF file of the article without any pre-processing and without requiring any technical expertise in NLP or Machine Learning. The diverse nature of the corpus, which includes articles written in languages other than English, some of which contain a wide range of clinical details while others lack information, adds to the strength of the study.

3.
J Clin Med ; 13(13)2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38999229

RESUMEN

Background/Objectives: Chest X-ray (CXR) is currently the most used investigation for clinical follow-up after major noncardiac thoracic surgery. This study explores the use of lung ultrasound (LUS) as an alternative to CXR in the postoperative management of patients who undergo major thoracic procedures. Methods: The patients in our cohort were monitored with both a CXR and a lung ultrasonography after surgery and the day after chest drain removal. The LUS was performed by a member of the medical staff of our unit who was blinded to both the images and the radiologist's report of the CXR. Findings were compared between the two methods. Results: In the immediate postoperative evaluation, 280 patients were compared, finding general agreement between the two procedures at 84% (kappa statistic, 0.603). The LUS showed a sensibility of 84.1%, a specificity of 84.3%, a positive predictive value (PPV) of 60.9%, and a negative predictive value (NPV) of 94.8%. We evaluated 219 out of 280 patients in the postdrainage-removal setting due to technical issues. Concordance between the methods in the postdrainage-removal setting was 89% (kappa statistic, 0.761) with the LUS demonstrating an 82.2% sensibility, a 93.2% specificity, a PPV of 85.7%, and an NPV of 91.3%. Conclusions: The results of this study showed a substantial agreement between LUS and CXR, suggesting that the LUS could reduce the number of X rays in certain conditions. The high NPV allows for the exclusion of PNX and pleural effusion without the need to expose patients to radiation. Discrepancies were noted in cases of mild pneumothorax or modest pleural effusion, without altering the clinical approach.

4.
Clin Nutr ESPEN ; 63: 635-641, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39053696

RESUMEN

BACKGROUND AND AIMS: Patients undergoing pancreatic resection are commonly malnourished. It is still unclear whether nutritional scores reliably predict postoperative outcomes after pancreatic resection. This study evaluated whether five commonly used preoperative nutritional screening scores predicted severe complications and length of stay. METHODS: Patients scheduled for pancreatic resection (pancreatoduodenectomy, distal and total pancreatectomy) at a national referral center for pancreatic surgery from September 2022 to June 2023 were prospectively screened for malnutrition with MNA, MUST, SGA, SNAQ, and NRS2002 scores. Postoperative complications were classified using the Clavien-Dindo classification. #NCT05608538. RESULTS: Three hundred patients were enrolled, including 168 pancreatoduodenectomies (56%), 102 distal pancreatectomies (34%), and 30 total pancreatectomies (10%). Final pathology revealed malignancy in 203 cases (67.7%). When applying the scores, the proportion of patients malnourished or at risk of malnutrition ranged from 21.7% for SGA to 79.3% for NRS2002. After adjusting for selected confounders, only an MNA <17 was associated with severe postoperative complications (OR 8.39, 95%CI [1.95-32.31], p = 0.01). MNA, SGA, and SNAQ predicted the length of stay (all p < 0.01), while MNA and SGA also correlated with a higher probability of having a greater heterogeneity in the length of stay (p = 0.04 and 0.002, respectively). DISCUSSION: We promote using MNA to detect malnourished patients at risk of severe postoperative complications and longer hospitalization after pancreatic surgery. SGA and SNAQ may also have value in predicting patients who will be hospitalized longer. More prospective studies will be needed to corroborate these findings.

5.
J Clin Med ; 13(11)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38892873

RESUMEN

Background: Institutionalized individuals with dysphagia are particularly at risk for malnutrition. This study investigated two texture-modified models for patients with dysphagia, as follows: (i) traditional homemade pureed food (PF) and (ii) homogenized meals obtained from dehydrated and rehydrated instantaneous preparations (IPs). Methods: A retrospective pilot study was performed. It included patients affected by medium-severity dysphagia admitted to the nursing home "Sacra Famiglia" Institute of Cocquio Trevisago, Varese. The patients were aged 41-81 years old and all had complex disabilities. They underwent anthropometric and biochemical parameter assessments at baseline, as well as at two months and four months follow-up. Results: The study involved 30 patients, 15 received the IP meal. The comparison between the baseline and the follow-up did not show significant anthropometric and biochemical parameter differences. Conversely, the IP group reported significantly higher levels of consumption and satisfaction, evaluated using a modified Chernoff scale based on three levels of smiles, than the PF group. Conclusions: The present findings provide promising indications to improve the diet of patients affected by dysphagia, since meal satisfaction is a relevant factor that has been shown to be associated with better patient mood, motivation to eat, and adherence to prescribed diet.

6.
J Clin Med ; 13(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38892983

RESUMEN

Background: Quality-of-life metrics are increasingly important for oncological patients alongside traditional endpoints like mortality and disease progression. Statistical tools such as Win Ratio, Win Odds, and Net Benefit prioritize clinically significant outcomes using composite endpoints. In randomized trials, Win Statistics provide fair comparisons between treatment and control groups. However, their use in observational studies is complicated by confounding variables. Propensity score (PS) matching mitigates confounding variables but may reduce the sample size, affecting the power of win statistics analyses. Alternatively, PS matching can stratify samples, preserving the sample size. This study aims to assess the long-term impact of these methods on decision making, particularly in colorectal cancer patients. Methods: A motivating example involves a cohort of patients from the ReSARCh observational study (2016-2021) with locally advanced adenocarcinoma of the rectum, situated up to 12 cm from the anal verge. These patients underwent either a watch-and-wait approach (WW) or trans-anal local excision (LE). Win statistics compared the effects of WW and LE on a composite outcome (overall survival, recurrence, presence of ostomy, and rectum excision). For matched win statistics, we used robust inference techniques proposed by Matsouaka et al. (2022), and for stratified win statistics, we applied the method proposed by Dong et al. (2018). A simulation study assessed the coverage probability of matched and stratified win statistics in balanced and unbalanced groups, calculating how often the confidence intervals included the true values of WR, NB, and WO across 1000 simulations. Results: The results suggest a better efficacy of the LE approach when considering efficacy outcomes alone (WR: 0.47 (0.01 to 1.14); NB: -0.16 (-0.34 to 0.02); and WO: 0.73 (0.5 to 1.05)). However, when QoL outcomes are included in the analyses, the estimates are closer to 1 (WR: 0.87 (0.06 to 2.06); WO: 0.93 (0.61 to 1.4)) and to 0 (NB: -0.04 (-0.25 to 0.17)), indicating a negative impact of the treatment effect of LE regarding the presence of ostomy and the excision of the rectum. Moreover, based on the simulation study, our findings underscore the superior performance of matched compared to stratified win statistics in terms of coverage probability (matched WR: 97% vs. stratified WR: 33.3% in a high-imbalance setting; matched WR: 98% vs. stratified WR: 34.4% in a medium-imbalance setting; and matched WR: 99.2% vs. stratified WR: 37.4% in a low-imbalance setting). Conclusions: In conclusion, our study sheds light on the interpretation of the results of win statistics in terms of statistical significance, providing insights into the application of pairwise comparison in observational settings, promoting its use to improve outcomes for cancer patients.

8.
JAMA Netw Open ; 7(5): e2413208, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38805230

RESUMEN

This cross-sectional study assesses the accuracy, sensitivity, and specificity of a large language model used to process unstructured, non-English emergency department (ED) data in medical records.


Asunto(s)
Servicio de Urgencia en Hospital , Heridas y Lesiones , Humanos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Heridas y Lesiones/clasificación , Heridas y Lesiones/epidemiología , Procesamiento de Lenguaje Natural , Masculino , Femenino , Adulto
9.
Eur J Pediatr ; 183(7): 2945-2954, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38625387

RESUMEN

Down syndrome is one of the most common genetic diseases, generally associated with an increased probability of congenital heart diseases. This increased risk contributes to escalated levels of morbidity and mortality. In this study, we sought to analyze nationwide data of pediatric and adult patients with Down syndrome and congenital heart disease over a 15-year period. Data obtained from the hospital discharge form between 2001 and 2016 of patients diagnosed with Down syndrome in Italy and at least one congenital heart disease were included. Information on 12362 admissions of 6527 patients were included. Age at first admission was 6.2 ± 12.8 years and was a predictor of mortality (HR = 1.51, 95% CI 1.13-2.03, p = 0.006). 3923 (60.1%) patients underwent only one admission, while 2604 (39.9%) underwent multiple (> 1) admissions. There were 5846 (47.3%) admissions for cardiac related symptoms. Multiple admissions (SHR: 3.13; 95% CI: 2.99, 3.27; P < 0.01) and cardiac admissions (SHR: 2.00; 95% CI: 1.92, 2.09; P < 0.01) were associated with an increased risk of additional potential readmissions. There was an increased risk of mortality for patients who had cardiac admissions (HR = 1.45, 95% CI: 1.08-1.94, p = 0.012), and for those who underwent at least 1 cardiac surgical procedure (HR = 1.51, 95% CI 1.13-2.03, p = 0.006). CONCLUSIONS: A younger age at first admission is a predictor for mortality in patients with Down syndrome and congenital heart disease. If patients undergo more than one admission, the risk of further readmissions increases. There is a pivotal role for heart disease in influencing the hospitalization rate and subsequent mortality. WHAT IS KNOWN: • Down syndrome individuals often face an increased risk of congenital heart diseases. • Congenital heart diseases contribute significantly to morbidity and mortality in Down syndrome patients. WHAT IS NEW: • This study analyzes nationwide data covering a 15-year period of pediatric and adult patients in Italy with Down syndrome and congenital heart disease. • It identifies a younger age at first admission as a predictor for mortality in these patients, emphasizing the criticality of early intervention. • Demonstrates a correlation between multiple admissions, particularly those related to cardiac issues, and an increased risk of further readmissions, providing insights into the ongoing healthcare needs of these individuals.


Asunto(s)
Síndrome de Down , Cardiopatías Congénitas , Hospitalización , Humanos , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/mortalidad , Femenino , Masculino , Italia/epidemiología , Hospitalización/estadística & datos numéricos , Niño , Adolescente , Preescolar , Lactante , Adulto , Adulto Joven , Estudios Retrospectivos , Recién Nacido , Readmisión del Paciente/estadística & datos numéricos , Persona de Mediana Edad , Factores de Riesgo
10.
J Clin Med ; 13(5)2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38592081

RESUMEN

Background: Cardiovascular magnetic resonance (CMR) has emerged as the most accurate, non-invasive method to support the diagnosis of clinically suspected myocarditis and as a risk-stratification tool in patients with cardiomyopathies. We aim to assess the diagnostic and prognostic role of CMR at diagnosis in patients with myocarditis. Methods: We enrolled consecutive single-center patients with 2013 ESC consensus-based endomyocardial biopsy (EMB)-proven or clinically suspected myocarditis undergoing CMR at diagnosis. The pre-specified outcome was defined as NYHA class > I and echocardiographic left ventricular ejection fraction (LVEF) < 50% at follow-up. Results: We included 207 patients (74% male, median age 36 years; 25% EMB-proven). CMR showed the highest sensitivity in myocarditis with infarct-like presentation. Patients with EMB-proven myocarditis were more likely to have diffuse LGE and right ventricular LGE (p < 0.001), which was also more common among patients with arrhythmic presentation (p = 0.001). The outcome was met in 17 patients at any follow-up time point, more commonly in those with larger biventricular volumes (p < 0.001), CMR-based diagnosis of dilated cardiomyopathy (p < 0.001), and ischemic LGE (p = 0.005). Higher biventricular systolic function (p < 0.001) and greater LGE extent (p = 0.033) at diagnosis had a protective effect. Conclusions: In our single-center cohort of rigorously defined myocarditis patients, higher biventricular systolic function and greater LGE extent on CMR at diagnosis identified patients with better functional class and higher left ventricular ejection fraction at follow-up. Conversely, larger biventricular volumes, CMR-based DCM features, and the presence of an ischemic LGE pattern at diagnosis were predictors of worse functional class and LV systolic dysfunction at follow-up. Larger prospective studies are warranted to extend our findings to multi-center cohorts.

11.
Eur J Heart Fail ; 26(5): 1175-1185, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38629741

RESUMEN

AIMS: Standardized immunosuppressive therapy (IS) had been previously investigated in biopsy-proven (BP) lymphocytic myocarditis with heart failure (HF). This study evaluated efficacy and safety of tailored IS in BP immune-mediated myocarditis, irrespective of histology and clinical presentation. METHODS AND RESULTS: Consecutive BP myocarditis patients treated with long-term tailored IS on top of optimal medical therapy (OMT), were compared with OMT non-IS controls using propensity-score weighting. The primary outcome was a composite of death or heart transplant, the secondary outcome was a composite of biventricular function, New York Heart Association (NYHA) class variation, and relapse. IS was managed by a multidisciplinary Cardioimmunology Team, involved a safety checklist and active patients' education. Ninety-one IS patients were compared with 267 non-IS patients. IS patients more frequently had systemic immune-mediated diseases (35% vs. 9.7%), lower baseline echocardiographic left ventricular ejection fraction (35% vs. 43%), lower right ventricular fractional area change (34% vs. 41%) and higher frequency of active lymphocytic, eosinophilic and giant cell myocarditis (71% vs. 58%, 12% vs. 1.1%, and 6.6% vs. 1.5%, respectively). At 5-year follow up, no difference was observed in the primary outcome (survival rate 93% in IS vs. 87% in non-IS), but IS patients had a higher relapse rate. Thus, IS patients, with a lower biventricular function and a higher risk profile at baseline, presented similar biventricular function and NYHA class to non-IS patients at follow-up. Minor adverse drug reactions occurred in 13% of patients, all resolved with therapy switch. CONCLUSIONS: Prolonged tailored IS is effective and safe in BP immune-mediated myocarditis irrespective of histology and clinical presentation.


Asunto(s)
Inmunosupresores , Miocarditis , Puntaje de Propensión , Humanos , Miocarditis/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Inmunosupresores/uso terapéutico , Biopsia/métodos , Adulto , Resultado del Tratamiento , Estudios Retrospectivos , Miocardio/patología , Estudios de Seguimiento , Ecocardiografía/métodos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/tratamiento farmacológico , Volumen Sistólico/fisiología
12.
EuroIntervention ; 20(8): e504-e510, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38629420

RESUMEN

The treatment of coronary artery disease (CAD) in patients with severe aortic valve stenosis (AVS) eligible for transcatheter aortic valve implantation (TAVI) is not supported by clinical evidence, and the role of physiology over anatomy as well as the timing of coronary intervention are not defined. FAITAVI (ClinicalTrials.gov: NCT03360591) is a nationwide prospective, open-label, multicentre, randomised controlled study comparing the angiography-guided versus the physiology-guided coronary revascularisation strategy in patients with combined significant CAD and severe AVS undergoing TAVI. Significant CAD will be defined as coronary stenosis ≥50%, as assessed by visual estimation in vessels ≥2.5 mm. Physiology will be tested by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). The study will be conducted at 15 sites in Italy. In the angiography arm, percutaneous coronary intervention (PCI) will be performed either before TAVI, during the TAVI procedure - before or after the valve implantation - or within 1 month±5 days of the valve implantation, left to the operator's decision. In the physiology arm, FFR and iFR will be performed before TAVI, and PCI will be indicated for FFR ≤0.80, otherwise the intervention will be deferred. In case of borderline values (0.81-0.85), FFR and iFR will be repeated after TAVI, with PCI performed when needed. With a sample size of 320 patients, the study is powered to evaluate the primary endpoint (a composite of death, myocardial infarction, stroke, major bleeding, or ischaemia-driven target vessel revascularisation). TAVI indication, strategy and medical treatment will be the same in both groups. After discharge, patients will be contacted at 1, 6, 12 and 24 months after the procedure to assess their general clinical status, and at 12 months for the occurrence of events included in the primary and secondary endpoints. FAITAVI is the first randomised clinical trial to investigate "optimal" percutaneous coronary intervention associated with TAVI in patients with severe AVS and CAD.


Asunto(s)
Estenosis de la Válvula Aórtica , Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Intervención Coronaria Percutánea , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Estudios Prospectivos , Resultado del Tratamiento , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto
13.
Ann Cardiothorac Surg ; 13(2): 146-154, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38590988

RESUMEN

The onset of atrial fibrillation (AF) has a direct association with left atrial appendage (LAA) function, as demonstrated by recent studies demonstrating the link between left atrial (LA) wall fibrosis, impaired contractility, and the development of AF. Non-valvular AF (NVAF) affects almost 30 million people worldwide, with this number expected to increase in the next 20 years. It is the main cause of ischemic stroke, with significant subsequent economic and social impact. Currently, the mainstay of stroke prevention in patients with NVAF is oral anticoagulation (OAC), which reduces the incidence of ischemic events at the stake of increased hemorrhagic events. Despite the introduction and widespread use of direct oral anticoagulants (DOACs), which almost completely replaced vitamin K antagonists (VKAs), the adherence to OAC is still low, hindering the efficacy of stroke prevention. Percutaneous LAA occlusion (LAAO) is now indicated (class IIB) in patients with NVAF at increased ischemic risk who cannot undergo OAC. Recently published data demonstrated that a reduced dose of DOAC after percutaneous LAAO is superior to long-term dual antiplatelet therapy (DAPT) for stroke prevention in the mid-term. One of the possible pitfalls of percutaneous LAAO is postprocedural peri-device leaks (PDLs) that have been associated with increased thromboembolic events. According to LAAOS III results, surgical LAAO during cardiac surgery brings a 33% reduction in risk of stroke at five years, independently from the OAC regimen with a high rate of complete appendage occlusion. The combination of surgical LAAO and reduced dose DOAC might ensure adequate embolic prevention, lowering the hemorrhagic risk. The present manuscript aims to describe the rationale and design of the Minimally Invasive Left Atrial Appendage Occlusion Plus REduced Dose DOAC To Prevent Stroke In Patients With Atrial Fibrillation Randomized Clinical Trial (LAAO-PlusRE).

14.
Front Nutr ; 11: 1346455, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476598

RESUMEN

Introduction: Over the last years, many Mediterranean countries, including Italy, have witnessed a shift away from the Mediterranean Diet, thus contributing to the high rates of overweight and obesity. The survey "Adherence to Mediterranean Diet in Italy (ARIANNA)" aimed to evaluate the Adherence to Mediterranean Diet (AMD) and its main determinants in the Italian population. Materials and methods: This study started on March 2023 and was addressed to adults aged ≥17 years, born and resident in Italy, proficient in Italian. Data are collected electronically through a voluntary, anonymous and self-administered questionnaire on the project website. Univariate and then multivariate logistic regressions were performed to evaluate associations between AMD and demographic characteristics, socio-economic status, health status, and lifestyle. Results: On a total of 3,732 completed questionnaires, the 87.70% of the respondents was female and the 71.28% was 17-40 years old. The 83.82% of the respondents had medium AMD, 11.33% low and only 4.85% high. The multivariate analysis revealed that being male (p < 0.001), aged >40 years (p < 0.05), workers (p ≤ 0.001), and unemployed (p < 0.05), determined the probability of having a lower AMD. Vegans and vegetarian's diets positively contributed to a higher AMD (p < 0.001). Discussion: These results highlighted a medium AMD in the Italian adult participants and suggested the necessity to implement tailored public health intervention strategies to improve food habits.

15.
Stroke ; 55(4): 963-971, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38465650

RESUMEN

BACKGROUND: Thrombosis is linked to neutrophil release of neutrophil extracellular traps (NETs). NETs are proposed as a mechanism of resistance to thrombolysis. This study intends to analyze the composition of thrombi retrieved after mechanical thrombectomy, estimate the age and organization of thrombi, and evaluate associations with the use of thrombolysis, antiplatelets, and heparin. METHODS: This retrospective observational study involved 72 samples (44 from cerebral and 28 coronary arteries), which were stained with hematoxylin and eosin, anti-NE (neutrophil elastase) antibody, and anti-histone H2B (histone H2B) antibody, representing different components in NET formation, all detectable during the later stages of NETosis, for histochemical and digital quantification of NET content. The histological and morphological evaluations of the specimens were correlated, through univariate and mediation analyses, with clinical information and therapy administered before intervention. RESULTS: The results demonstrated that the composition of cerebral and coronary thrombi differs, and there were significantly more lytic cerebral thrombi than coronary thrombi (66% versus 14%; P=0.005). There was a considerably higher expression of NETs in the cerebral thrombi as testified by the higher expression of H2B (P=0.031). Thrombolysis was remarkably associated with higher NE positivity (average marginal effect, 6.461 [95% CI, 0.7901-12.13]; P=0.02555), regardless of the origin of thrombi. There was no notable association between the administration of antiaggregant therapy/heparin and H2B/NE amount when adjusted for the thrombus location. Importantly, the age of the thrombus was the only independent predictor of NET content without any mediation of the thrombolytic treatment (P=0.014). CONCLUSIONS: The age of the thrombus is the driving force for NET content, which correlates with impaired clinical outcomes. The therapy that is currently administered does not modify NET content. This study supports the need to investigate new pharmacological approaches added to thrombolysis to prevent NET formation or enhance their disruption, such as recombinant human DNase I (deoxyribonuclease I).


Asunto(s)
Trampas Extracelulares , Trombosis , Humanos , Trampas Extracelulares/metabolismo , Neutrófilos/metabolismo , Trombosis/tratamiento farmacológico , Trombosis/metabolismo , Histonas/metabolismo , Terapia Trombolítica , Heparina
16.
Heart Rhythm ; 21(6): 725-732, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38309449

RESUMEN

BACKGROUND: Atrial fibrillation (AF) is common in patients with cardiac amyloidosis (CA) and is a significant risk factor for heart failure hospitalization and thromboembolic events. OBJECTIVE: This study was designed to investigate the atrial electrofunctional predictors of incident AF in CA. METHODS: A multicenter, observational study was conducted in 4 CA referral centers including sinus rhythm patients with light-chain (AL) and transthyretin (ATTR) CA undergoing electrocardiography and cardiac magnetic resonance imaging. The primary end point was new-onset AF occurrence. RESULTS: Overall, 96 patients (AL-CA, n = 40; ATTR-CA, n = 56) were enrolled. During an 18-month median follow-up (Q1-Q3, 7-29 months), 30 patients (29%) had incident AF. Compared with those without AF, patients with AF were older (79 vs 73 years; P = .001). They more frequently had ATTR (87% vs 45%; P < .001); electrocardiographic interatrial block (IAB), either partial (47% vs 21%; P = .011) or advanced (17% vs 3%; P = .017); and lower left atrial ejection fraction (LAEF; 29% vs 41%; P = .004). Age (hazard ratio [HR], 1.059; 95% CI, 1.002-1.118; P = .042), any type of IAB (HR, 2.211; 95% CI, 1.03-4.75; P = .041), and LAEF (HR, 0.967; 95% CI, 0.936-0.998; P = .044) emerged as independent predictors of incident AF. Patients exhibiting any type of IAB, LAEF <40%, and age >78 years showed a cumulative incidence for AF of 40% at 12 months. This risk was significantly higher than that carried by 1 (8.5%) or none (7.6%) of these 3 risk factors. CONCLUSION: In patients with CA, older age, IAB on 12-lead electrocardiography, and reduced LAEF on cardiac magnetic resonance imaging are significant and independent predictors of incident AF. A closer screening for AF is advisable in CA patients carrying these features.


Asunto(s)
Fibrilación Atrial , Cardiomiopatías , Electrocardiografía , Humanos , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/epidemiología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/complicaciones , Masculino , Femenino , Anciano , Incidencia , Cardiomiopatías/fisiopatología , Cardiomiopatías/diagnóstico , Cardiomiopatías/epidemiología , Cardiomiopatías/etiología , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/diagnóstico por imagen , Factores de Riesgo , Estudios de Seguimiento , Imagen por Resonancia Cinemagnética/métodos , Amiloidosis/epidemiología , Amiloidosis/fisiopatología , Amiloidosis/diagnóstico , Amiloidosis/complicaciones
19.
J Am Coll Cardiol ; 83(8): 797-807, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38383094

RESUMEN

BACKGROUND: In recent years, it has become evident that arrhythmogenic cardiomyopathy (ACM) displays a wide spectrum of ventricular involvement. Furthermore, the influence of various clinical phenotypes on the prognosis of the disease is currently being assessed. OBJECTIVES: The purpose of this study was to evaluate the impact of phenotypic expression in ACM on patient outcomes. METHODS: We conducted an analysis of 446 patients diagnosed with ACM. These patients were categorized into 3 groups based on their phenotype: arrhythmogenic right ventricular cardiomyopathy (ARVC) (right-dominant ACM), arrhythmogenic left ventricular cardiomyopathy (ALVC) (left-dominant ACM), and biventricular arrhythmogenic cardiomyopathy (BIV). We compared clinical, instrumental, and genetic findings among these groups and also evaluated their outcomes RESULTS: Overall, 44% of patients were diagnosed with ARVC, 23% with ALVC, and 33% with BIV forms. Subjects showing with ARVC and BIV phenotype had a significantly higher incidence of life-threatening ventricular arrhythmias compared with ALVC (P < 0.001). On the other hand, heart failure, heart transplantation, and death caused by cardiac causes were more frequent in individuals with BIV forms compared to those with ALVC and ARVC (P < 0.001). Finally, patients with an ALVC phenotype had a higher incidence of hot phases compared with those with ARVC and BIV forms (P = 0.013). CONCLUSIONS: The comparison of ACM phenotypes demonstrated that patients with right ventricular involvement, such as ARVC and BIV forms, exhibit a higher incidence of life-threatening ventricular arrhythmias. Conversely, ACM forms characterized by left ventricular involvement, such as ALVC and BIV, show a higher incidence of heart failure, heart transplantation, and hot phases.


Asunto(s)
Displasia Ventricular Derecha Arritmogénica , Cardiomiopatías , Insuficiencia Cardíaca , Humanos , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/genética , Arritmias Cardíacas/diagnóstico , Cardiomiopatías/genética , Insuficiencia Cardíaca/epidemiología , Fenotipo
20.
Ann Clin Microbiol Antimicrob ; 23(1): 16, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38360651

RESUMEN

BACKGROUND: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.


Asunto(s)
Antibacterianos , Neutropenia Febril , Humanos , Niño , Antibacterianos/uso terapéutico , Incidencia , Teorema de Bayes , Hospitales Pediátricos , Combinación Piperacilina y Tazobactam , Pruebas de Sensibilidad Microbiana , Bacterias , Italia , Neutropenia Febril/tratamiento farmacológico
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