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1.
Int J Mol Sci ; 25(15)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39126005

RESUMO

Diagnosis of biliopancreatic cancers by the available serum tumor markers, imaging, and histopathological tissue specimen examination remains a challenge. Circulating cell-free DNA derived from matched pairs of secretin-stimulated duodenal fluid (DF) and plasma from 10 patients with biliopancreatic diseases and 8 control subjects was analyzed using AmpliSeq™ HD technology for Ion Torrent Next-Generation Sequencing to evaluate the potential of liquid biopsy with DF in biliopancreatic cancers. The median cfDNA concentration was greater in DF-derived than in plasma-derived samples. A total of 13 variants were detected: 11 vs. 1 were exclusive for DF relative to the plasma source, and 1 was shared between the two body fluids. According to the four-tier systems, 10 clinical tier-I-II (76.9%), 1 tier-III (7.7%), and 2 tier-IV (15.4%) variants were identified. Notably, the 11 tier-I-III variants were exclusively found in DF-derived cfDNA from five patients with biliopancreatic cancers, and were detected in seven genes (KRAS, TP53, BRAF, CDKN2A, RNF43, GNAS, and PIK3CA); 82% of the tier-I-III variants had a low abundance, with a VAF < 6%. The mutational profiling of DF seems to be a reliable and promising tool for identifying cancer-associated alterations in malignant cancers of the biliopancreatic tract.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Neoplasias Pancreáticas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Duodeno/metabolismo , Duodeno/patologia , Biomarcadores Tumorais/genética , Biópsia Líquida/métodos , Adulto , Ácidos Nucleicos Livres/genética , Neoplasias do Sistema Biliar/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Cromograninas
2.
Expert Rev Med Devices ; 21(7): 561-577, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38829122

RESUMO

INTRODUCTION: Endoscopic submucosal dissection (ESD) is a widely used technique to remove early neoplastic lesions. It was primarily used in the initial days to treat gastric lesions, but recently, the horizon of this endoscopic procedure has expanded, which has allowed us to manage other technically more complex locations, such as the colorectum. AREAS COVERED: There has been an exponential growth regarding the wide range of devices available in the market for performing colorectal ESD. As a result, the aim of this review is to highlight the indication of this endoscopic technique, which device is best suited for which indication, as well as future trajectories in this field. EXPERT OPINION: Although some devices have proven to be more advantageous than others in this area, very often the choice is still subjective, which is commonly attributed to individual preferences and experience. However, an accurate knowledge of the available tools and their functioning, with their pros and cons, is fundamental for any endoscopist venturing into the field of third space endoscopy. In this way, one can choose which device best suits a particular situation, along with simultaneously having the wealth of knowledge related to therapeutic armamentarium at our disposal in the endoscopy suite.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Ressecção Endoscópica de Mucosa/instrumentação , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Colorretais/cirurgia
5.
Int J Cancer ; 152(4): 725-737, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36305648

RESUMO

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.


Assuntos
Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Pré-Escolar , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/patologia , Metilação de DNA , Estudos de Casos e Controles , Estudos Prospectivos , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Biomarcadores Tumorais/metabolismo , Amianto/efeitos adversos , Marcadores Genéticos , Células Sanguíneas , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia
6.
Endosc Int Open ; 10(5): E616-E621, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35571479

RESUMO

Background and study aims Adenoma detection rate (ADR) is a well-accepted quality indicator of screening colonoscopy. In recent years, the added value of artificial intelligence (AI) has been demonstrated in terms of ADR and adenoma miss rate (AMR). To date, there are no studies evaluating the impact of AI on the performance of trainee endoscopists (TEs). This study aimed to assess whether AI might eliminate any difference in ADR or AMR between TEs and experienced endoscopists (EEs). Patients and methods We performed a prospective observational study in 45 subjects referred for screening colonoscopy. A same-day tandem examination was carried out for each patient by a TE with the AI assistance and subsequently by an EE unaware of the lesions detected by the TE. Besides ADR and AMR, we also calculated for each subgroup of endoscopists the adenoma per colonoscopy (APC), polyp detection rate (PDR), polyp per colonoscopy (PPC) and polyp miss rate (PMR). Subgroup analyses according to size, morphology, and site were also performed. Results ADR, APC, PDR, and PPC of AI-supported TEs were 38 %, 0.93, 62 %, 1.93, respectively. The corresponding parameters for EEs were 40 %, 1.07, 58 %, 2.22. No significant difference was found for each analysis between the two groups ( P  > 0.05). AMR and PMR for AI-assisted TEs were 12.5 % and 13 %, respectively. Sub-analyses did not show any significant difference ( P  > 0.05) between the two categories of operators. Conclusions In this single-center prospective study, the possible impact of AI on endoscopist quality training was demonstrated. In the future, this could result in better efficacy of screening colonoscopy by reducing the incidence of interval or missed cancers.

7.
Nutr Metab Cardiovasc Dis ; 32(3): 684-691, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34991937

RESUMO

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant disease that leads to cardiovascular (CV) disease. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-I) demonstrated efficacy in low-density lipoprotein cholesterol (LDL-C) reduction and in prevention of CV events. The aim of our study is to evaluate the relationship between LDL receptor (LDLR) mutations and response to PCSK9-I therapy. METHODS AND RESULTS: We evaluated total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in consecutive patients with FH before PCSK9-I treatment and after 12 (T12w) and 36 (T36w) weeks of treatment. We evaluated LDL-C target achievement according to different mutations in LDLR. Eighty FH subjects (mean age:54 ± 13.3 years), 39 heterozygous (He) with defective LDLR gene mutations, 30 He with null mutations and 11 compound-He or homozygous (Ho) were recruited. At baseline, 69 subjects were under maximal lipid lowering therapy (MLLT) and 11 subjects had statin-intolerance. From baseline to T36w we observed an overall 51% reduction in LDL-C. We found no difference in LDL-C changes between subjects with He-defective mutation and He-null mutations both at T12w (p = 1.00) and T36w (p = 0.538). At T36w, LDL-C target was achieved in 59% of He-defective mutations subjects and in 36% of He-null mutations subgroup (p = 0.069), whereas none of compound-He/Ho-FH achieved LDL-C target. CONCLUSIONS: After 36 weeks there were no differences in response to PCSK9-I therapy between different groups of He-FH subjects. Response to PCSK9-I was significantly lower in carriers of compound-He/Ho mutations. Registration number for clinical trials: NCT04313270 extension.


Assuntos
Hiperlipoproteinemia Tipo II , Pró-Proteína Convertase 9 , Adulto , Idoso , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , Pessoa de Meia-Idade , Mutação , Inibidores de PCSK9 , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/uso terapêutico , Receptores de LDL/genética
8.
Int J Mol Sci ; 24(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36614110

RESUMO

Achalasia is an esophageal smooth muscle motility disorder with unknown pathogenesis. Taking into account our previous results on the downexpression of miR-200c-3p in tissues of patients with achalasia correlated with an increased expression of PRKG1, SULF1, and SYDE1 genes, our aim was to explore the unknown biological interaction between these genes and human miR-200c-3p and if this relation could unravel their functional role in the etiology of achalasia. To search for putative miR-200c-3p binding sites in the 3'-UTR of PRKG1, SULF1 and SYDE1, a bioinformatics tool was used. To test whether PRKG1, SULF1, and SYDE1 are targeted by miR-200c-3p, a dual-luciferase reporter assay and quantitative PCR on HEK293 and fibroblast cell lines were performed. To explore the biological correlation between PRKG1 and miR-200c-3p, an immunoblot analysis was carried out. The overexpression of miR-200c-3p reduced the luciferase activity in cells transfected with a luciferase reporter containing a fragment of the 3'-UTR regions of PRKG1, SULF1, and SYDE1 which included the miR-200c-3p seed sequence. The deletion of the miR-200c-3p seed sequence from the 3'-UTR fragments abrogated this reduction. A negative correlation between miR-200c-3p and PRKG1, SULF1, and SYDE1 expression levels was observed. Finally, a reduction of the endogenous level of PRKG1 in cells overexpressing miR-200c-3p was detected. Our study provides, for the first time, functional evidence about the PRKG1 gene as a direct target and SULF1 and SYDE1 as potential indirect substrates of miR-200c-3p and suggests the involvement of NO/cGMP/PKG signaling in the pathogenesis of achalasia.


Assuntos
Proteína Quinase Dependente de GMP Cíclico Tipo I , Acalasia Esofágica , MicroRNAs , Humanos , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Quinase Dependente de GMP Cíclico Tipo I/metabolismo , Acalasia Esofágica/genética , Células HEK293 , MicroRNAs/genética , MicroRNAs/metabolismo
10.
Clin Genet ; 100(5): 529-541, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34297352

RESUMO

Familial hypercholesterolemia (FH) is the most common genetic disease caused by variants in LDLR, APOB, PCSK9 genes; it is characterized by high levels of LDL-cholesterol and premature cardiovascular disease. We aim to perform a retrospective analysis of a genetically screened population (528 unrelated patients-342 adults and 186 children) to evaluate the biochemical and clinical correlations with the different genetic statuses. Genetic screening was performed by traditional sequencing and some patients were re-analyzed by next-generation-sequencing. Pathogenic variants, mainly missense in the LDLR gene, were identified in 402/528 patients (76.1%), including 4 homozygotes, 17 compound heterozygotes and 1 double heterozygotes. A gradual increase of LDL-cholesterol was observed from patients without pathogenic variants to patients with a defective variant, to patients with a null variant and to patients with two variants. Six variants accounted for 51% of patients; a large variability of LDL-cholesterol was observed among patients carrying the same variant. The frequency of pathogenic variants gradually increased from unlikely FH to definite FH, according to the Dutch Lipid Clinic Network criteria. Genetic diagnosis can help prognostic evaluation of FH patients, discriminating between the different genetic statuses or variant types. Clinical suspicion of FH should be considered even if few symptoms are present or if LDL-cholesterol is only mildly increased.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Fenótipo , Adulto , Alelos , Substituição de Aminoácidos , Biomarcadores , Criança , Éxons , Feminino , Frequência do Gene , Estudos de Associação Genética/métodos , Testes Genéticos/métodos , Testes Genéticos/normas , Genótipo , Humanos , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , Mutação , Melhoria de Qualidade , Curva ROC , Receptores de LDL/genética , Receptores de LDL/metabolismo
11.
J Clin Med ; 10(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920796

RESUMO

Worldwide population ageing is partly due to advanced standard of care, leading to increased incidence and prevalence of geriatric syndromes such as frailty and disability. Hence, the age at the onset of acute coronary syndromes (ACS) keeps growing as well. Moreover, ageing is a risk factor for both frailty and cardiovascular disease (CVD). Frailty and CVD in the elderly share pathophysiological mechanisms and associated conditions, such as malnutrition, sarcopenia, anemia, polypharmacy and both increased bleeding/thrombotic risk, leading to a negative impact on outcomes. In geriatric populations ACS is associated with an increased frailty degree that has a negative effect on re-hospitalization and mortality outcomes. Frail elderly patients are increasingly referred to cardiac rehabilitation (CR) programs after ACS; however, plans of care must be tailored on individual's clinical complexity in terms of functional capacity, nutritional status and comorbidities, cognitive status, socio-economic support. Completing rehabilitative intervention with a reduced frailty degree, disability prevention, improvement in functional state and quality of life and reduction of re-hospitalization are the goals of CR program. Tools for detecting frailty and guidelines for management of frail elderly patients post-ACS are still debated. This review focused on the need of an early identification of frail patients in elderly with ACS and at elaborating personalized plans of care and secondary prevention in CR setting.

12.
Clin Res Hepatol Gastroenterol ; 45(5): 101711, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33930589

RESUMO

Inverted colonic diverticulum (ICD) is a rare intraluminal lesion occurring in about 0.7-1.7% of people, often endoscopically indistinguishable from polyps. Some unspecific endoscopic features may assist to distinguish polypoid ICD from true polyps. This differentiation bears relevance for the therapeutic approach, as colonic polyps require snare polypectomy, a practice which may be associated with colonic perforation in case of true ICD. The endoscopist, therefore, should be aware of the likelihood of detecting these lesions during colonoscopy. A close inspection and a gentle probing could assist in a correct diagnosis and avoid risky procedures such as biopsy or polypectomy. Rarely, a neoplasm arising over an ICD and its treatment has been described. We reported two cases, one of which with dysplasia, and their treatment, and reviewed all the ICD endoscopic cases so far reported in the literature, remarking the possibility of finding pedunculated ICDs or neoplasm arising over an ICD.


Assuntos
Divertículo do Colo , Divertículo do Colo/diagnóstico , Divertículo do Colo/terapia , Endoscopia , Humanos
13.
Endosc Int Open ; 9(3): E388-E394, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33655038

RESUMO

Background and study aims The Paris classification of superficial colonic lesions has been widely adopted, but a simplified description that subgroups the shape into pedunculated, sessile/flat and depressed lesions has been proposed recently. The aim of this study was to evaluate the accuracy and inter-rater agreement among 13 Western endoscopists for the two classification systems. Methods Seventy video clips of superficial colonic lesions were classified according to the two classifications, and their size estimated. The interobserver agreement for each classification was assessed using both Cohen k and AC1 statistics. Accuracy was taken as the concordance between the standard morphology definition and that made by participants. Sensitivity analyses investigated agreement between trainees (T) and staff members (SM), simple or mixed lesions, distinct lesion phenotypes, and for laterally spreading tumors (LSTs). Results Overall, the interobserver agreement for the Paris classification was substantial (κ = 0.61; AC1 = 0.66), with 79.3 % accuracy. Between SM and T, the values were superimposable. For size estimation, the agreement was 0.48 by the κ-value, and 0.50 by AC1. For single or mixed lesions, κ-values were 0.60 and 0.43, respectively; corresponding AC1 values were 0.68 and 0.57. Evaluating the several different polyp subtypes separately, agreement differed significantly when analyzed by the k-statistics (0.08-0.12) or the AC1 statistics (0.59-0.71). Analyses of LSTs provided a κ-value of 0.50 and an AC1 score of 0.62, with 77.6 % accuracy. The simplified classification outperformed the Paris classification: κ = 0.68, AC1 = 0.82, accuracy = 91.6 %. Conclusions Agreement is often measured with Cohen's κ, but we documented higher levels of agreement when analyzed with the AC1 statistic. The level of agreement was substantial for the Paris classification, and almost perfect for the simplified system.

14.
Int J Colorectal Dis ; 36(7): 1561-1568, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33649902

RESUMO

PURPOSE: For superficial colonic lesions, the NICE and Kudo classifications are used in the in vivo prediction of histology and as guide to therapy. The NICE system derives information from unmagnified NBI endoscopic images. The Kudo one necessitates a magnification, but, as this tool is not commonly available, it is applied also to characterize unmagnified pictures to compare their diagnostic performances. METHODS: We conducted a prospective comparison of the NICE versus the Kudo classification for the differential diagnosis of colonic polyps taking histology as the gold standard. The inter-observer agreement for both classifications among 11 colonoscopists was also evaluated. Short unmagnified NBI videoclips of 64 colonic polyps were sent twice to the participants. In the first round, they classified the lesions according to the NICE classification; 4 months later, the same videos were assessed with the Kudo system. The diagnosis provided by the participants was grouped in non-neoplastic, non-invasive neoplasia, invasive neoplasia. RESULTS: Overall, the diagnostic accuracy was 82% (95%CI: 79-85) with the NICE system and 81% (95%CI: 78-84) with the Kudo one (ρ = 0.78). The accuracy of the NICE classification for non-neoplastic lesions was greater compared with the Kudo's (ρ = 0.03). Sensitivity sub-analyses revealed a higher ability of the NICE in distinguishing between neoplastic vs. non-neoplastic lesions (ρ = 0.01). The overall inter-rater agreement did not differ when the classifications were compared. CONCLUSION: The NICE and the Kudo classifications might be considered comparable. Our data could allow the use of the NBI Kudo classification even in those centers where magnification is not available.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Colo , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Humanos , Variações Dependentes do Observador , Estudos Prospectivos , Sensibilidade e Especificidade
15.
Panminerva Med ; 63(2): 122-132, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33565757

RESUMO

Atherosclerosis is a dynamic process driven by all cardiovascular risk factors that can be briefly divided into an early and a late phase. Inflammation is one of the fundamental substrates that initiates the atherosclerotic process in the early stages and promotes and maintains it in the final stages. In the last decades, clinical and experimental data have shown that inflammation is supported by mediators that respond to physical activity. The present review aimed at investigating the effect of physical exercise on inflammatory mediators, both the positive ones that have a proinflammatory effect (interleukin 6, c-reactive protein and tumor necrosis factor α, interferon γ, high-mobility group box-1), and the negative ones which have an anti-inflammatory effect (interleukin 10). Pooled data support the evidence that physical exercise can directly modulate the activity of inflammatory cytokines slowing down or preventing the formation of the atherosclerotic stage.


Assuntos
Aterosclerose/prevenção & controle , Biomarcadores/sangue , Exercício Físico/fisiologia , Mediadores da Inflamação/sangue , Inflamação/sangue , Aterosclerose/sangue , Proteína C-Reativa/metabolismo , Proteína HMGB1 , Humanos , Interferon gama/sangue , Interleucina-6/sangue
16.
J Clin Med ; 11(1)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35011818

RESUMO

Atherogenic lipoproteins (particularly, very low-density lipoproteins, VLDL) are associated with subclinical atherosclerosis. The present study aims at evaluating whether routinely analysed lipid parameters are associated with carotid intima-media thickness, a proxy for subclinical atherosclerosis. Lipid parameters from 220 post-menopausal women undergoing ultrasound investigation of the carotid arteries were analysed. Forty-five percent of women showed subclinical atherosclerosis on carotid ultrasound. The mean carotid intima-media thickness was 1.26 ± 0.38 mm. The mean value of the non-HDL-C/HDL-C ratio was 3.1 ± 1.2. Univariate analysis showed a significant association between non-HDL-C/HDL-C ratio and intima-media thickness (r = 0.21, p = 0.001). After adjusting for cardiovascular risk factors (age, systolic blood pressure, smoking, body mass index Homeostasis model assessment: insulin resistance and high-sensitivity C-Reactive-Protein), multivariate analysis showed a significant association between non-HDL-C/HDL-C ratio and intima-media thickness (ß = 0.039, p = 0.04). Logistic regression analysis showed that the highest tertile of the non-HDL-C/HDL-C ratio was associated with the presence of carotid plaques (OR = 3.47, p = 0.003). Finally, a strong correlation between non-HDL-C/HDL-C ratio and cholesterol bound to VLDL (r = 0.77, p < 0.001) has been found. Non-HDL-C/HDL-C ratio is associated with the presence of carotid atherosclerosis in post-menopausal women and is strongly correlated to VLDL-C levels.

17.
Thromb Res ; 194: 229-236, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33213848

RESUMO

BACKGROUND: Treatment with protein convertase subtilisin kexin type 9 inhibitors (PCSK-9i) reduced cholesterol levels and cardiovascular events in patients with hypercholesterolemia. We assessed changes in lipid profile, oxidation markers and endothelial function in patients with familial hypercholesterolemia (FH) after a 12-week treatment with a PCSK-9i. METHODS: Patients with FH starting a treatment with PCSK-9i were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) (Lp(a)), small dense LDL (assessed by LDL score), 11-dehydro-thromboxane (11-TXB2), 8-isoprostaglandin-2alpha (8-iso-PGF2α), flow-mediated dilation (FMD) and reactive hyperaemia index (RHI) were evaluated before starting PCSK-9i treatment and after a 12-week treatment. RESULTS: Twenty-five subjects were enrolled (52% males, mean age 51.5 years). At the 12-week assessment, we observed a 38% median reduction in TC, 52% in LDL-C, 7% in Lp(a) and 46% in LDL score. In parallel, 11-TXB2 and 8-iso-PGF2α showed a reduction of 18% and 17%, respectively. FMD changed from 4.78% ± 2.27 at baseline to 10.6% ± 5.89 at 12 weeks (p < 0.001), with RHI changing from 2.37 ± 1.23 to 3.76 ± 1.36 (p < 0.001). A multivariate analysis showed that, after adjusting for potential confounders, change in LDL score was an independent predictor of changes in FMD (ß = -0.846, p = 0.015) and in 8-iso-PGF2α (ß = 0.778, p = 0.012). CONCLUSIONS: Small dense LDL reduction (assessed by LDL score) is related to changes in oxidation markers and endothelial function in patients with FH treated with PCSK-9i.


Assuntos
Anticolesterolemiantes , Hipercolesterolemia , Hiperlipidemias , Hiperlipoproteinemia Tipo II , LDL-Colesterol , Feminino , Humanos , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9
18.
Nutr Metab Cardiovasc Dis ; 30(6): 996-1004, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32402582

RESUMO

BACKGROUND AND AIM: Protein convertase subtilisin kexin type 9 (PCSK-9) inhibitors demonstrated efficacy in cholesterol reduction and in the prevention of cardiovascular events. We evaluated changes in lipid profile and carotid stiffness in patients with familial hypercholesterolemia during 12 weeks of treatment with a PCSK-9 inhibitor, Evolocumab®. METHODS AND RESULTS: Patients with familial hypercholesterolemia starting a treatment with Evolocumab® were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), small dense LDL (assessed by LDL score) and carotid stiffness were evaluated before starting treatment with Evolocumab® and during 12 weeks of treatment. Twenty-five subjects were enrolled (52% males, mean age 51.5 years). TC and LDL-C were reduced of 38% and 52%, respectively during treatment, with LDL score reduced of 46.1%. In parallel, carotid stiffness changed from 8.8 (IQR: 7.0-10.4) m/sec to 6.6 (IQR: 5.4-7.5) m/sec, corresponding to a median change of 21.4% (p < 0.001), with a significant increase in carotid distensibility (from 12.1, IQR: 8.73-19.3 kPA-1 × 10-3 at T0 to 21.8, IQR: 16.6-31.8 kPA-1 × 10-3 at T12w) corresponding to a median change of 62.8% (p < 0.001). A multivariate analysis showed that changes in LDL score were independently associated with changes in carotid stiffness (ß = 0.429, p = 0.041). CONCLUSION: Small dense LDL reduction, as assessed by LDL score, is associated with changes in carotid stiffness in patients with familial hypercholesterolemia treated with Evolocumab®.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Doenças das Artérias Carótidas/tratamento farmacológico , Artéria Carótida Primitiva/efeitos dos fármacos , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Rigidez Vascular/efeitos dos fármacos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/fisiopatologia , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/fisiopatologia , Regulação para Baixo , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
19.
J Clin Med ; 9(5)2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32403373

RESUMO

BACKGROUND: atherosclerotic process inexorably advances in patients reaching low-density lipoprotein cholesterol (LDL-C) targets. An attractive hypothesis is that lipoprotein particles (very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL)), could contribute to residual risk. The present study aims to investigate the relationship between carotid intima-media thickness (IMT) and different lipoprotein subfractions in a cohort of healthy postmenopausal women. METHODS: 75 postmenopausal women, at LDL-C target levels without overt cardiovascular disease, underwent biochemical analyses (including subfraction assay of plasma lipoproteins) and carotid ultrasound examination. RESULTS: a statistically significant correlation between VLDL and carotid IMT (p < 0.001) was found. No significant correlation was found between carotid IMT and LDL-C (p = 0.179), IDL-C (p = 0.815), high-density lipoprotein (HDL) (p = 0.855), and LDL score (p = 0.240). Moreover, IMT is significantly correlated to LDL particle diameter (p = 0.044). After adjusting for age, systolic blood pressure, body mass index, smoking habits, glucose plasma concentration, and Lipoprotein(a) (Lpa) levels, multivariate analysis showed that women in the third tertile of VLDL-C, compared with those in the first tertile, were significantly associated to the highest IMT (p = 0.04). CONCLUSIONS: in this cohort of postmenopausal women, VLDL-C was significantly associated to carotid IMT, independent of main cardiovascular risk factors. These findings pave the way for targeting circulating concentrations of VLDL-C to reduce cardiovascular events in patients with target LDL-C levels.

20.
Eur J Clin Invest ; : e13252, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323307

RESUMO

BACKGROUND: Acute obstructive colorectal cancer requires prompt decompression commonly by emergency surgery (ES). However, self-expanding metal stents (SEMS) have been increasingly used as a bridge-to-surgery (BTS) strategy. MATERIALS AND METHODS: In an 8-year period, consecutive patients with acute left-sided colonic obstruction, due to locally advanced colorectal cancer, underwent ES or SEMS implantation. We evaluated technical/clinical success of SEMS, adverse events, and overall (OS) and disease-free survival (DFS) of the two therapeutic options. RESULTS: Forty-five patients underwent ES (n = 23) or SEMS (n = 22). The two groups were comparable for sex, age, ASA score and cancer site/stage. Technical and clinical successes of SEMS were 100% and 72.7%, respectively. Clinical success correlated with neutrophil-lymphocyte ratio (NLR) at baseline (OR = 0.65, 95% CI 0.43-0.98, P = .04). SEMS allowed primary anastomosis in the 45.5% of cases (0% in ES). SEMS implantation allowed a higher rate of surgery carried out by a laparoscopic approach: 36.4% vs 13.0% in ES. Performance of a definitive stoma and complications were similar. Median OS (34 in SEMS; 45 in ES, P = .33) and DFS (36 in SEMS; 35 in ES, P = .35) did not differ between the two groups. At univariate analysis, DFS was positively associated with primary anastomosis (HR = 2.44, 95% CI 1.4-16.6, P = .04) and laparoscopic surgery (HR = 8.33, 95% CI 1.08-50, P = .04), and inversely associated with a NLR > 3.6 (HR = 0.59, 95% CI 0.16-0.92, P = .03). At multivariate analysis, no feature retained an independent predictive power. CONCLUSION: SEMS is an effective and safe procedure, equivalent to emergency surgery in terms of complications, OS and DFS, providing the chance of a primary anastomosis in the majority of patients.

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