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Tirzepatide is a new drug targeting glucagon-like peptide 1(GLP1) and gastric inhibitory polypeptide (GIP) receptors. This drug has demonstrated great potential in improving the clinical outcomes of patients with type 2 diabetes. It can lead to weight loss, better glycemic control, and reduced cardiometabolic risk factors. GLP1 receptor agonists have been proven effective antidiabetic medications with possible cardiovascular benefits. Even though they have been proven to reduce the risk of major adverse cardiovascular events, their effectiveness in treating heart failure is unknown. Unlike traditional GLP1 receptor agonists, tirzepatide is more selective for the GIP receptor, resulting in a more balanced activation of these receptors. This review article discusses the possible mechanisms tirzepatide may use to improve cardiovascular health. That includes the anti-inflammatory effect, the ability to reduce cell death and promote autophagy, and also its indirect effects through blood pressure, obesity, and glucose/lipid metabolism. Additionally, tirzepatide may benefit atherosclerosis and lower the risk of major adverse cardiac events. Currently, clinical trials are underway to evaluate the safety and efficacy of tirzepatide in patients with heart failure. Overall, tirzepatide's dual agonism of GLP1 and GIP receptors appears to provide encouraging cardiovascular benefits beyond glycemic control, offering a potential new therapeutic option for treating cardiovascular diseases and heart failure.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Hipoglucemiantes , Incretinas , Humanos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/farmacología , Animales , Resultado del Tratamiento , Incretinas/uso terapéutico , Incretinas/efectos adversos , Receptores de la Hormona Gastrointestinal/agonistas , Receptores de la Hormona Gastrointestinal/metabolismo , Transducción de Señal/efectos de los fármacos , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Sistema Cardiovascular/efectos de los fármacos , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/efectos adversos , Biomarcadores/sangre , Medición de Riesgo , Receptor del Péptido 2 Similar al Glucagón , Polipéptido Inhibidor GástricoRESUMEN
BACKGROUND: Cystinuria is a rare genetic disease characterized by impaired tubular transport of cystine. Clinical features of cystinuria mainly include nephrolithiasis and its complications, although cystinuric patients may present with other comorbidities. There are currently no data on bone features of patients with cystinuria. Our aim is to characterize bone mineral density (BMD) in cystinuria. METHODS: Our study included adult cystinuric patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 followed at 3 specialized outpatient clinics in Italy (Rome, Naples and Verona). Markers of bone turnover were analyzed in a centralized laboratory. Clinical, biochemical and dual-energy X-ray absorptiometry (DEXA) data were collected from September 2021 to December 2022. Linear regression models were used to evaluate statistically significant deviations from zero of Z-scores. RESULTS: Twenty-seven patients were included in the study. Mean (SD) age was 37 (15) years, 41% were women. Mean estimated glomerular filtration rate was 99 mL/min/1.73 m2. Serum parameters associated with bone turnover (parathyroid hormone, FGF23, calcium and phosphate) were all in the normal range, with only 4 patients showing mild hypophosphatemia. Prevalence of low bone mineral density, defined as Z-score ≤ - 2 at any site, was 15%. Average Z-scores were negative across most sites. CONCLUSIONS: Our study suggests that cystinuric patients have lower bone mineral density compared with individuals of the same sex and age, even when their kidney function is normal.
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Background and Objectives: An extracellular vesicle is part of a class of submicron particles derived from cells, mediating cellular crosstalk through microRNA (miRNA). MiRNA is a group of RNA molecules, each of which consists of 15-22 nucleotides and post-transcriptionally modulates gene expression. The complementary mRNAs-onto which the miRNAs hybridize-are involved in processes such as implantation, tumor suppression, proliferation, angiogenesis, and metastasis that define the entire tumor microenvironment. The endometrial biopsy is a standard technique used to recognize cellular atypia, but other non-invasive markers may reduce patient discomfort during the use of invasive methods. The present study aims to examine the distribution and the regulation of the differentially expressed miRNAs (DEMs) and EV-derived substances in women with endometrial cancer. Materials and Methods: We systematically searched the PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect databases in April 2023, adopted the string "Endometrial Neoplasms AND Exosomes", and followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We selected all the studies that included patients with endometrial cancer and that described the regulation of miRNA molecules in that context. The differences in molecule expression between patients and controls were evaluated as significant when the proteins had a fold change of ±1.5. Results: Seventeen records fulfilled the inclusion criteria: a total of 371 patients and 273 controls were analyzed. The upregulated molecules that had the widest delta between endometrial cancer patients and controls-relative expression ≥ 1 > 3 log2(ratio)-were miR-20b-5p, miR-204-5p, miR-15a-5p, and miR-320a. In particular, miR-20b-5p and miR-204-5p were extracted from both serum and endometrial specimens, whereas miR-15a-5p was only isolated from plasma, and miR-320a was only extracted from the endometrial specimens. In parallel, the most downregulated miRNA in the endometrial cancer patients compared to the healthy subjects was miR-320a, which was found in the endometrial specimens. Conclusions: Although their epigenetic regulation remains unknown, these upregulated molecules derived from EVs are feasible markers for the early detection of endometrial cancer. The modulation of these miRNA molecules should be assessed during different treatments or if recurrence develops in response to a targeted treatment modality.
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Neoplasias Endometriales , MicroARNs , Femenino , Humanos , Implantación del Embrión , Neoplasias Endometriales/genética , Neoplasias Endometriales/terapia , Endometrio/patología , Epigénesis Genética , MicroARNs/genética , Microambiente TumoralRESUMEN
In this review, we have summarized the existing knowledge of ulcerative colitis (UC) markers based on current literature, specifically, the roles of potential new biomarkers, such as circulating, fecal, genetic, and epigenetic alterations, in UC onset, disease activity, and in therapy response. UC is a complex multifactorial inflammatory disease. There are many invasive and non-invasive diagnostic methods in UC, including several laboratory markers which are employed in diagnosis and disease assessment; however, colonoscopy remains the most widely used method. Common laboratory abnormalities currently used in the clinical practice include inflammation-induced alterations, serum autoantibodies, and antibodies against bacterial antigens. Other new serum and fecal biomarkers are supportive in diagnosis and monitoring disease activity and therapy response; and potential salivary markers are currently being evaluated as well. Several UC-related genetic and epigenetic alterations are implied in its pathogenesis and therapeutic response. Moreover, the use of artificial intelligence in the integration of laboratory biomarkers and big data could potentially be useful in clinical translation and precision medicine in UC management.
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Colitis Ulcerosa , Humanos , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/genética , Inteligencia Artificial , Inflamación , Biomarcadores , Epigénesis Genética , Índice de Severidad de la Enfermedad , HecesRESUMEN
BACKGROUND: As diagnostic and prognostic models developed by traditional statistics perform poorly in real-world, artificial intelligence (AI) and Big Data (BD) may improve the supply chain of heart transplantation (HTx), allocation opportunities, correct treatments, and finally optimize HTx outcome. We explored available studies, and discussed opportunities and limits of medical application of AI to the field of HTx. METHOD: A systematic overview of studies published up to December 31st, 2022, in English on peer-revied journals, have been identified through PUBMED-MEDLINE-WEB of Science, referring to HTx, AI, BD. Studies were grouped in 4 domains based on main studies' objectives and results: etiology, diagnosis, prognosis, treatment. A systematic attempt was made to evaluate studies by the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD). RESULTS: Among the 27 publications selected, none used AI applied to BD. Of the selected studies, 4 fell in the domain of etiology, 6 in the domain of diagnosis, 3 in the domain of treatment, and 17 in that of prognosis, as AI was most frequently used for algorithmic prediction and discrimination of survival, but in retrospective cohorts and registries. AI-based algorithms appeared superior to probabilistic functions to predict patterns, but external validation was rarely employed. Indeed, based on PROBAST, selected studies showed, to some extent, significant risk of bias (especially in the domain of predictors and analysis). In addition, as example of applicability in the real-world, a free-use prediction algorithm developed through AI failed to predict 1-year mortality post-HTx in cases from our center. CONCLUSIONS: While AI-based prognostic and diagnostic functions performed better than those developed by traditional statistics, risk of bias, lack of external validation, and relatively poor applicability, may affect AI-based tools. More unbiased research with high quality BD meant for AI, transparency and external validations, are needed to have medical AI as a systematic aid to clinical decision making in HTx.
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Inteligencia Artificial , Trasplante de Corazón , Humanos , Macrodatos , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Anticancer treatments are improving the prognosis of patients fighting cancer. However, anticancer treatments may also increase the cardiovascular (CV) risk by increasing metabolic disorders. Atherosclerosis and atherothrombosis related to anticancer treatments may lead to ischemic heart disease (IHD), while direct cardiac toxicity may induce non-ischemic heart disease. Moreover, valvular heart disease (VHD), aortic syndromes (AoS), and advanced heart failure (HF) associated with CV risk factors and preclinical CV disease as well as with chronic inflammation and endothelial dysfunction may also occur in survivors of anti-carcer treatments. METHODS: Public electronic libraries have been searched systematically looking at cardiotoxicity, cardioprotection, CV risk and disease, and prognosis after cardiac surgery in survivors of anticancer treatments. RESULTS: CV risk factors and disease may not be infrequent among survivors of anticancer treatments. As cardiotoxicity of established anticancer treatments has been investigated and is frequently irreversible, cardiotoxicity associated with novel treatments appears to be more frequently reversible, but also potentially synergic. Small reports suggest that drugs preventing HF in the general population may be effective also among survivors of anticancer treatments, so that CV risk factors and disease, and chronic inflammation, may lead to indication to cardiac surgery in survivors of anticancer treatments. There is a lack of substantial data on whether current risk scores are efficient to predict prognosis after cardiac surgery in survivors of anticancer treatments, and to guide tailored decision-making. IHD is the most common condition requiring cardiac surgery among survivors of anticancer treatments. Primary VHD is mostly related to a history of radiation therapy. No specific reports exist on AoS in survivors of anticancer treatments. CONCLUSIONS: It is unclear whether interventions to dominate cancer- and anticancer treatment-related metabolic syndromes, chronic inflammation, and endothelial dysfunction, leading to IHD, nonIHD, VHD, HF, and AoS, are as effective in survivors of anticancer treatments as in the general population. When CV diseases require cardiac surgery, survivors of anticancer treatments may be a population at specifically elevated risk, rather than affected by a specific risk factor.
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BRCA1 and BRCA2 are onco-suppressor genes involved in the DNA repair mechanism. The presence of BRCA1/2 mutations confers a higher risk of developing several cancer types. To date, the FDA approved various PARP inhibitors to treat selected BRCA1/2 mutated oncologic patients. At first, PARP inhibitors were approved for patients with ovarian and breast cancers, and subsequently for metastatic pancreatic adenocarcinoma and metastatic castration-resistant prostate cancer after the treatment with chemotherapy. The current guidelines for BRCA testing are very heterogeneous between the different types of tumors regarding the diagnostic algorithm and the type of sample to analyze, such as the blood for the germline mutations and the tumoral tissue for the somatic mutations. Few data have currently been described regarding the detection of BRCA1/2 somatic mutations in formalin-fixed paraffin-embedded (FFPE) samples. In this review, we propose an overview of the BRCA mutations in FFPE samples of several cancers, including breast, ovarian, fallopian tube, primary peritoneal, prostate, and pancreatic cancer. We summarize the types and the frequency of BRCA mutations, the guidelines approved for the test, the molecular assays used for the detection and the PARP inhibitors approved for each tumor type.
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Adenocarcinoma , Neoplasias Ováricas , Neoplasias Pancreáticas , Femenino , Humanos , Masculino , Proteína BRCA1/genética , Formaldehído , Mutación/genética , Neoplasias Ováricas/patología , Neoplasias Pancreáticas/genética , Adhesión en Parafina , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Genes BRCA1 , Genes BRCA2 , Neoplasias PancreáticasRESUMEN
Hereditary cancer syndromes predispose to several types of cancer due to inherited pathogenic variants in susceptibility genes. We describe the case of a 57-year-old woman, diagnosed with breast cancer, and her family. The proband belongs to a family with a suspected tumor syndrome, due to other cancer cases in her family from the paternal and maternal sides. After oncogenetic counseling, she was subjected to mutational analysis with an NGS panel analyzing 27 genes. The genetic analysis showed two monoallelic mutations in low penetrance genes, c.1187G>A (p.G396D) in MUTYH and c.55dup (p.Tyr19Leufs*2) in BRIP1. One of the mutations was inherited from the maternal side and the other from the paternal side, suggesting two different cancer syndrome types in the family. MUTYH mutation was related to the onset of cancers on the paternal side, as confirmed by the occurrence of the same mutation in the proband's cousin. BRIP1 mutation was found in the proband's mother, indicating that it was related to the cancer cases observed on the maternal side, including breast cancer and sarcoma. Advances in NGS technologies have allowed the identification of mutations in families with hereditary cancers in genes other than those related to a specific suspected syndrome. A complete oncogenetic counseling, together with molecular tests that enable a simultaneous analysis of multiple genes, is essential for the identification of a correct tumor syndrome and for clinical decision-making in a patient and his/her family. The detection of mutations in multiple susceptibility genes allows the initiation of early risk-reducing measures for identified mutation carriers among family members and to include them in a proper surveillance program for specific syndromes. Moreover, it may enable an adapted treatment for the affected patient, permitting personalized therapeutic options.
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Neoplasias de la Mama , Síndromes Neoplásicos Hereditarios , Humanos , Masculino , Femenino , Persona de Mediana Edad , Predisposición Genética a la Enfermedad , Mutación , Síndromes Neoplásicos Hereditarios/genética , Neoplasias de la Mama/genética , FamiliaRESUMEN
AIMS: The aims of this study were to evaluate parathormone (PTH) levels in people with diabetic foot ulcers (DFU) and investigate the relationship between PTH levels and osteomyelitis (OM) in this population. MATERIALS AND METHODS: Eighty-eight patients were admitted for DFU in a tertiary-care centre from October 2021 to May 2022. OM was diagnosed by clinical, laboratory, and radiological evaluations. Laboratory measurements and clinical parameters were collected from medical records. Participants in the study were divided into two groups according to the diagnosis of OM (patients with OM, group 1 [n = 54] and patients without OM, group 2 [n = 34]). RESULTS: Compared with group 2, patients in group 1 were younger and had a longer duration of diabetes. Erythrocyte sedimentation rate and fibrinogen were significantly higher in group 1 compared with group 2. PTH levels were significantly lower (group 1 vs. group 2, median [interquartile range] 16.2 (11.6, 31.0) vs. 23.7 (17.0, 38.1), p = 0.008) and alkaline phosphatase was significantly higher (97.0 (79.0, 112.0) vs. 88.0 (63.0, 107.0), p = 0.031) in group 1. In multiple linear regression analysis, the only independent predictors of PTH concentrations were alkaline phosphatase levels (ß-coefficient 0.441, p < 0.001) and the presence of OM (ß-coefficient -0.290, p = 0.038). CONCLUSIONS: In a population of patients with diabetes and OM admitted to a tertiary university centre, PTH levels were lower as compared with diabetic individuals without OM. The OM and alkaline phosphatase levels were independent predictors of PTH levels in this selected population.
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Diabetes Mellitus , Pie Diabético , Osteomielitis , Humanos , Pie Diabético/diagnóstico , Pie Diabético/epidemiología , Hormona Paratiroidea , Fosfatasa Alcalina , Osteomielitis/complicaciones , Osteomielitis/diagnósticoRESUMEN
Purpose: To assess the qualitative relationship between liquid biopsy and conventional tissue biopsy. As a secondary target, we evaluated the relationship between the liquid biopsy results and the T stage, N stage, M stage, and compared to grading. Methods: The Local Ethics Committee of the "Università degli Studi della Campania Luigi Vanvitelli", with the internal resolution number 24997/2020 of 12.11.2020, approved this spontaneous prospective study. According to the approved protocol, patients with lung cancer who underwent Fine-Needle Aspiration Cytology (FNAC), CT-guided biopsy, and liquid biopsy were enrolled. A Yates chi-square test was employed to analyze differences in percentage values of categorical variables. A p-value < 0.05 was considered statistically significant. Data analysis was performed using the Matlab Statistic Toolbox (The MathWorks, Inc., Natick, MA, USA). Results: When a genetic mutation is present on the pathological examination, this was also detected on the liquid biopsy. ROS1 and PDL1 mutations were found in 2/29 patients, while EGFR Exon 21 was identified in a single patient. At liquid biopsy, 26 mutations were identified in the analyzed samples. The mutations with the highest prevalence rate in the study populations were: ALK (Ile1461Val), found in 28/29 patients (96.6%), EML4 (Lys398Arg), identified in 16/29 (55.2%) patients, ALK (Asp1529Glu), found in 14/29 (48.3%) patients, EGFR (Arg521Lys), found in 12/29 (41.4%) patients, ROS (Lys2228Gln), identified in 11/29 (37.9%) patients, ROS (Arg167Gln) and ROS (Ser2229Cys), identified in 10/29 (34.5%) patients, ALK (Lys1491Arg) and PIK3CA (Ile391Met), identified in 8/29 (27.6%) patients, ROS (Thr145Pro), identified in 6/29 (20.7%) patients, and ROS (Ser1109Leu), identified in 4/29 (13.8%) patients. No statistically significant differences can be observed in the mutation rate between the adenocarcinoma population and the squamous carcinoma population (p > 0.05, Yates chi-square test). Conclusions: We showed that, when a genetic mutation was detected in pathological examination, this was always detected by liquid biopsy, demonstrating a very high concordance rate of genomic testing between tissues and their corresponding mutations obtained by liquid biopsy, without cases of false-negative results. In addition, in our study, liquid biopsy highlighted 26 mutations, with the prevalence of ALK mutation in 96.6% of patients, supporting the idea that this approach could be an effective tool in cases with insufficient tumor tissue specimens or in cases where tissue specimens are not obtainable.
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Big Data, and the derived analysis techniques, such as artificial intelligence and machine learning, have been considered a revolution in the modern practice of medicine. Big Data comes from multiple sources, encompassing electronic health records, clinical studies, imaging data, registries, administrative databases, patient-reported outcomes and OMICS profiles. The main objective of such analyses is to unveil hidden associations and patterns. In cardiac surgery, the main targets for the use of Big Data are the construction of predictive models to recognize patterns or associations better representing the individual risk or prognosis compared to classical surgical risk scores. The results of these studies contributed to kindle the interest for personalized medicine and contributed to recognize the limitations of randomized controlled trials in representing the real world. However, the main sources of evidence for guidelines and recommendations remain RCTs and meta-analysis. The extent of the revolution of Big Data and new analytical models in cardiac surgery is yet to be determined.
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Macrodatos , Procedimientos Quirúrgicos Cardíacos , Humanos , Inteligencia Artificial , Procedimientos Quirúrgicos Cardíacos/métodos , Aprendizaje Automático , Registros Electrónicos de SaludRESUMEN
Hereditary prostate cancer (HPCa) has the highest heritability of any cancer in men. Interestingly, it occurs in several hereditary syndromes, including breast and ovarian cancer (HBOC) and Lynch syndrome (LS). Several gene mutations related to these syndromes have been identified as biomarkers in HPCa. The goal of this study was to screen for germline mutations in susceptibility genes by using a multigene panel, and to subsequently correlate the results with clinical and laboratory parameters. This was undertaken in 180 HBOC families, which included 217 males with prostate cancer (PCa). Mutational analysis was further extended to 104 family members of mutated patients. Screening of HBOC families revealed that 30.5% harbored germline mutations in susceptibility genes, with 21.6% harboring pathogenic variants (PVs) and 8.9% having variants of uncertain significance (VUS). We found PVs at similar frequency in BRCA1 and BRCA2 genes (8.8% and 9.4%, respectively), while 0.56% of PVs were present in well-established susceptibility genes PALB2, TP53 and RAD51C. Moreover, 0.56% of monoallelic PVs were present in MUTYH, a gene whose function in tumorigenesis in the context of PCa is still unclear. Finally, we reported double heterozygosity (DH) in BRCA1/2 genes in a single family, and found double mutation (DM) present in BRCA2 in a separate family. There was no significant difference between the mean age of onset of PCa in HBOC families with or without germline mutations in susceptibility genes, while the mean survival was highest in mutated patients compared to wild type. Furthermore, PCa is the second most recurrent cancer in our cohort, resulting in 18% of cases in both mutated and non-mutated families. Our investigation shows that PVs were located mostly in the 3' of BRCA1 and BRCA2 genes, and in BRCA2, most PVs fell in exon 11, suggesting a mutation cluster region relating to risk of HPCa. A total of 65 family members inherited the proband's mutation; of these, 24 developed cancer, with 41 remaining unaffected.
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Síndrome de Cáncer de Mama y Ovario Hereditario , Neoplasias de la Próstata , Masculino , Humanos , Femenino , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Predisposición Genética a la Enfermedad , Recurrencia Local de Neoplasia , Mutación de Línea Germinal , Neoplasias de la Próstata/genéticaRESUMEN
In the present study, immunogenicity data in 61 vaccinated healthcare workers (HCWs) either infection naïve (naïve HCWs) or with infection of Delta and/or Omicron COVID-19 (experienced HCWs) were evaluated up to 270 days after the second dose of BNT162b2 vaccine and up to 90 days after a booster dose. A decrease in antibody levels at 270 days following administration of the second dose (p = 0.0335) was observed, although values did not fall below the positivity threshold (33.8 BAU/ml). After booster vaccination, antibody levels increased after 30 days (p = 0.0486), with much higher values than after first and second vaccination. Antibody levels then decreased at 60 and 90 days after the booster dose. A comparison between mean antibody levels of naïve and experienced HCWs revealed higher values in experienced HCWs, resulting from both natural and vaccination-induced immunity. A total of 14.7% of HCWs contracted the Omicron virus variant after the vaccine booster, although none showed severe symptoms. These results support that a booster dose results in a marked increase in antibody response that subsequently decreases over time.
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COVID-19 , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Personal de Salud , Vacunas contra Hepatitis B , Humanos , SARS-CoV-2RESUMEN
BACKGROUND: Pectoral muscle removal is a fundamental preliminary step in computer-aided diagnosis systems for full-field digital mammography (FFDM). Currently, two open-source publicly available packages (LIBRA and OpenBreast) provide algorithms for pectoral muscle removal within Matlab environment. PURPOSE: To compare performance of the two packages on a single database of FFDM images. METHODS: Only mediolateral oblique (MLO) FFDM was considered because of large presence of pectoral muscle on this type of projection. For obtaining ground truth, pectoral muscle has been manually segmented by two radiologists in consensus. Both LIBRA's and OpenBreast's removal performance with respect to ground truth were compared using Dice similarity coefficient and Cohen-kappa reliability coefficient; Wilcoxon signed-rank test has been used for assessing differences in performances; Kruskal-Wallis test has been used to verify possible dependence of the performance from the breast density or image laterality. RESULTS: FFDMs from 168 consecutive women at our institution have been included in the study. Both LIBRA's Dice-index and Cohen-kappa were significantly higher than OpenBreast (Wilcoxon signed-rank test P < 0.05). No dependence on breast density or laterality has been found (Kruskal-Wallis test P > 0.05). CONCLUSION: Libra has a better performance than OpenBreast in pectoral muscle delineation so that, although our study has not a direct clinical application, these results are useful in the choice of packages for the development of complex systems for computer-aided breast evaluation.
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Neoplasias de la Mama , Músculos Pectorales , Algoritmos , Densidad de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Mamografía/métodos , Músculos Pectorales/diagnóstico por imagen , Intensificación de Imagen Radiográfica/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Reproducibilidad de los ResultadosRESUMEN
Objective: In the light of the current COVID-19 epidemic and the availability of effective vaccines, this study aims to identify factors associated with non-response to anti-SARS-CoV-2 vaccines as immunological alteration associated with immune rheumatic diseases (IRD) and immunosuppressive medications may impair the response to vaccination. Methods: Volunteers in the health profession community with IRD, age, and sex-matched controls (CTRL) who underwent vaccination with two doses of BNT162b2 were recruited for this study. Anti-Trimeric Spike protein antibodies were assayed eight ± one weeks after the second vaccine dose. Univariate and logistic regression analyses were performed to identify factors independently associated with non-response and low antibody titers. Results: Samples were obtained from 237 IRD patients (m/f 73/164, mean age 57, CI 95% [56-59]): 4 autoinflammatory diseases (AI), 62 connective tissue diseases (CTD), 86 rheumatoid arthritis (RA), 71 spondylarthritis (SpA) and 14 vasculitis (Vsc). 232 CTRL were recruited (m/f 71/161, mean age 57, CI 95% [56-58]). Globally, IRD had a lower seroconversion rate (88.6% vs 99.6%, CI 95% OR [1.61-5.73], p<0.001) and lower antibody titer compared to controls (median (IQR) 403 (131.5-1012) versus 1160 (702.5-1675), p<0.001). After logistic regression, age, corticosteroid (CCS), Abatacept and Mycophenolate Mofetil (MMF) use were associated with non-response. Lower antibody titer was associated with the use of MMF, ABA, CCS, Rituximab, tumor necrosis factor inhibitor, JAK inhibitors, and higher age. Conclusion: The response to anti-SARS-CoV-2 vaccines is often impaired in IRD patients under treatment and may pose them at higher risk of severe COVID-19. Specific vaccination protocols are desirable for these patients.
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Artritis Reumatoide , COVID-19 , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Vacunas , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Humanos , Persona de Mediana Edad , Vacunación , Vacunas/farmacologíaRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer death worldwide; most of cases are sporadic, however about 5% to 10% report a hereditary predisposition. Several hereditary syndromes have been associated with familial pancreatic cancer (FPC) onset, including hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), Familial atypical multiple mole melanoma (FAMMM), Familial adenomatous polyposis (FAP), Li-Fraumeni syndrome (LFS), Peutz-Jeghers syndrome (PJS), and Hereditary pancreatitis (HP).The aim of this study was to determine the mutational status of a cohort of 56 HBOC families, 7 LS families, 3 FAP and FAMMM families, and 1 LFS family with at least one case of PDAC. Mutation analysis of BRCA1/2, ATM, CHEK2, PALB2, RAD51C, RAD51D, NBN, CDH1, TP53, MLH1, MSH2, MSH6, and PMS2 genes, showedmutation in BRCA1/2, MLH1, and APC genes. We founda high mutation rate in patients belong HBOC and LS families, with a percentage of 28.6% in both syndromes and prevalence in HBOC of BRCA2 mutations with one case of double mutation in BRCA2 gene. In FAP family, we found a pathogenic mutation in APC gene in 1/3 families. We observed an early onset of PDAC and a lower survival in PDAC patients belonging to mutated families, while no evidence of possible pancreatic cancer cluster regions was found. Moreover, we identified a novel BRCA2 germline mutation, c.5511delT (p.Phe1837LeufsX3), not reported in any database, that segregated with disease in HBOC patients. Mutational analysis was extended to family membersof mutated patients, both healthy and cancer affected, which revealed 23 unaffected family members that inherited the proband's mutation. Although correlative by its nature, the presence of a BRCA mutation in PDAC patients may have benefits in terms of optimized treatment and longer outcome.
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Poliposis Adenomatosa del Colon , Carcinoma Ductal Pancreático , Neoplasias Colorrectales Hereditarias sin Poliposis , Síndrome de Cáncer de Mama y Ovario Hereditario , Neoplasias Pancreáticas , Poliposis Adenomatosa del Colon/genética , Proteína de la Poliposis Adenomatosa del Colon , Proteína BRCA1/genética , Proteína BRCA2 , Carcinoma Ductal Pancreático/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Femenino , Genes APC , Células Germinativas , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Humanos , Homólogo 1 de la Proteína MutL/genética , Mutación , Neoplasias Pancreáticas/genética , Fenotipo , Neoplasias PancreáticasRESUMEN
It is well-known that the Coronavirus Disease 2019, which is caused by the beta-coronavirus severe acute respiratory syndrome (SARS-CoV-2), emerged in December 2019 followed by an outbreak first reported in Wuhan, China. Thus far, vaccination appears to be the only way to bring the pandemic to an end. In the present study, immunogenicity data was evaluated using LIAISON® SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A) among a sample of 52 vaccinated healthcare workers, five of whom were previously infected with SARS-CoV-2 and 47 who were seronegative, over a time span of ≤90 days following the second dose of the BNT162b2 mRNA vaccine. The test detects antibodies against the Trimeric complex (S1, S2 and receptor binding domain). The overall mean value of the serum levels of IgG antibodies to SARS-CoV-2 30 days following the second dose of the vaccine was 1,901.8 binding arbitrary unit (BAU)/ml, after 60 days the mean value declined to 1,244.9 BAU/ml. The antibody levels then reached a plateau, as confirmed by the antibody test carried out 90 days following the second dose, which revealed a mean value of 1,032.4 BAU/ml (P<0.0001). A higher level was observed at all three times in male subjects compared with female subjects, and in younger male participants compared with female participants, although these differences did not reach a statistically significant level. Similarly, no significant difference was found in antibody values at different times according to age. After the second dose of the vaccine, two subjects were infected with SARS-CoV-2, and an increase in antibody values in the third assay was observed in both individuals.
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Vacuna BNT162 , COVID-19 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , Femenino , Humanos , Masculino , Datos Preliminares , SARS-CoV-2 , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
Epidemiological evidence shows that diabetic patients have an increased cancer risk and a higher mortality rate. Glucose could play a central role in metabolism and growth of many tumor types, and this possible mechanism is supported by the high rate of glucose demand and uptake in cancer. Thus, growing evidence suggests that hyperglycemia contributes to cancer progression but also to its onset. Many mechanisms underlying this association have been hypothesized, such as insulin resistance, hyperinsulinemia, and increased inflammatory processes. Inflammation is a common pathophysiological feature in both diabetic and oncological patients, and inflammation linked to high glucose levels sensitizes microenvironment to tumorigenesis, promoting the development of malignant lesions by altering and sustaining a pathological condition in tissues. Glycemic control is the first goal of antidiabetic therapy, and glucose level reduction has also been associated with favorable outcomes in cancer. Here, we describe key events in carcinogenesis focusing on hyperglycemia as supporter in tumor progression and in particular, related to the role of a specific hypoglycemic drug class, sodium-glucose linked transporters (SGLTs). We also discuss the use of SGLT2 inhibitors as a novel potential cancer therapy. Our meta-analysis showed that SGLT-2 inhibitors were significantly associated with an overall reduced risk of cancer as compared to placebo (RR = 0.35, CI 0.33-0.37, P = 0. 00) with a particular effectiveness for dapaglifozin and ertuglifozin (RR = 0. 06, CI 0. 06-0. 07 and RR = 0. 22, CI 0. 18-0. 26, respectively). Network Medicine approaches may advance the possible repurposing of these drugs in patients with concomitant diabetes and cancer.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Animales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Reposicionamiento de Medicamentos , Epigénesis Genética , Glucosa/metabolismo , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/epidemiología , Hiperglucemia/genética , Incidencia , Neoplasias/epidemiología , Neoplasias/etiología , Neoplasias/genética , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The current management of breast cancer (BC) lacks specific noninvasive biomarkers able to provide an early diagnosis of the disease. Epigeneticsensitive signatures are influenced by environmental exposures and are mediated by direct molecular mechanisms, mainly guided by DNA methylation, which regulate the interplay between genetic and nongenetic risk factors during cancerogenesis. The inactivation of tumor suppressor genes due to promoter hypermethylation is an early event in carcinogenesis. Of note, targeted tumor suppressor genes are frequently hypermethylated in patientderived BC tissues and peripheral blood biospecimens. In addition, epigenetic alterations in triplenegative BC, as the most aggressive subtype, have been identified. Thus, detecting both targeted and genomewide DNA methylation changes through liquidbased assays appears to be a useful clinical strategy for early detection, more accurate risk stratification and a personalized prediction of therapeutic response in patients with BC. Of note, the DNA methylation profile may be mapped by isolating the circulating tumor DNA from the plasma as a more accessible biospecimen. Furthermore, the sensitivity to treatment with chemotherapy, hormones and immunotherapy may be altered by genespecific DNA methylation, suggesting novel potential drug targets. Recently, the use of epigenetic drugs administered alone and/or with anticancer therapies has led to remarkable results, particularly in patients with BC resistant to anticancer treatment. The aim of the present review was to provide an update on DNA methylation changes that are potentially involved in BC development and their putative clinical utility in the fields of diagnosis, prognosis and therapy.