23 research outputs found
Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma
Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection
Low inâhospital mortality rate in patients with COVIDâ19 receiving thromboprophylaxis: data from the multicentre observational STARTâCOVID Register
Abstract
COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre,
Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in
the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease,and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate
was 18.3%. Heparin use was independently associated with survival in patients aged ⼠59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years
Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both
Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPDâ+âHF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPDâ+âHF. Patients with COPDâ+âHF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPDâ+âHF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPDâ+âHF for all causes (pâ=â0.010), respiratory causes (pâ=â0.006), cardiovascular causes (pâ=â0.046) and respiratory plus cardiovascular causes (pâ=â0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population
Efficient synthesis of 3,5-dicarbamoyl-1,4-dihydropyridines from pyridinium salts. Key molecules in understanding NAD(P)+/NAD(P)H pathways
3,5-Dicarbamoyl-1,4-dihydropyridines were prepared in high yields using a green protocol by reductionof the corresponding pyridinium salts in aqueous buffered sodium dithionite solutions. The pH value is a fundamental parameter for the reduction step and depends on the nature of substituent groups at positions 1, 3, and 5 of the pyridinium salts. These 3,5-dicarbamoyl dihydropyridines show a lower tendency towardsoxidation and a higher stability than N-benzyl-3-carbamoyl- 1,4-dihydropyridine at low pH values
Dynamic-shared pharmacophore approach as tool to design new allosteric PRC2 inhibitors, targeting EED binding pocket
Abstract: The Polycomb Repressive complex 2
(PRC2) maintains a repressive chromatin state and silences
many genes, acting as methylase on histone tails. This
enzyme was found overexpressed in many types of cancer.
In this work, we have set up a Computer-Aided Drug Design
approach based on the allosteric modulation of PRC2. In
order to minimize the possible bias derived from using a
single set of coordinates within the protein-ligand complex,
a dynamic workflow was developed. In details, molecular
dynamic was used as tool to identify the most significant
ligand-protein interactions from several crystallized protein
structures. The identified features were used for the
creation of dynamic pharmacophore models and docking
grid constraints for the design of new PRC2 allosteric
modulators. Our protocol was retrospectively validated
using a dataset of active and inactive compounds, and the
results were compared to the classic approaches, through
ROC curves and enrichment factor. Our approach suggested
some important interaction features to be adopted for
virtual screening performance improvemen
Epithelioid haemangioendothelioma arising in the nasal cavity
We report here the case of an epithelioid haemangioendothelioma (EHE) arising in the nasal cavity which is, to the best of our knowledge, the first ever described example in the world literature in that particular site. The patient is a 23-year-old male who presented with repeated episodes of epistaxis from the nasal cavity and with a 1.5 cm reddish, polypoid, smooth, spontaneously bleeding nodule in the right middle meatus. This lesion was histologically diagnosed as epithelioid haemangioendothelioma. Immunohistochemically the neoplasm displayed striking positivity for CD31, CD34 and vimentin. A surgical approach was performed by 'facial degloving', removing the right inferior turbinate, the anterior two-thirds of the middle turbinate and the medial wall of the ethmoid bone. After 12 months follow-up the patient is disease-free, without any local or distant recurrence
A new family of Jumonji C domain-containing KDM inhibitors inspired by natural product Purpurogallin
Aberrant epigenetic modifications are involved in cancer development. Jumonji C
domain-containing histone lysine demethylases (KDMs) are found mainly up-regulated
in breast, prostate, and colon cancer. Currently, growing interest is focusing on the
identification and development of new inhibitors able to block the activity of KDMs
and thus reduce tumor progression. KDM4A is known to play a role in several
cellular physiological processes, and was recently found overexpressed in a number
of pathological states, including cancer. In this work, starting from the structure of
purpurogallin 9aa, previously identified as a natural KDM4A inhibitor, we synthesized
two main sets of compound derivatives in order to improve their inhibitory activity
against KDM4A in vitro and in cells, as well as their antitumor action. Based on
the hypothetical biogenesis of the 5-oxo-5H-benzo[7]annulene skeleton of the natural
product purpurogallin (Salfeld, 1960; Horner et al., 1961; DĂźrckheimer and Paulus,
1985; Tanaka et al., 2002; Yanase et al., 2005) the pyrogallol and catechol units were
first combined with structural modifications at different positions of the aryl ring using
enzyme-mediated oxidative conditions, generating a series of benzotropolone analogs.
Two of the synthetic analogs of purpurogallin, 9ac and 9bc, showed an efficient inhibition
(50 and 80%) of KDM4A in enzymatic assays and in cells by increasing levels of its specific
targets, H3K9me3/2 and H3K36me3. However, these two compounds/derivatives did
not induce cell death. We then synthesized a further set of analogs of these two
compounds with greater structural diversification. The most potent of these analogs,
9bf, displayed the highest KDM4A inhibitory enzymatic activity in vitro (IC50 of 10.1 and
24.37ÎźM) in colon cancer cells, and the strongest antitumor action in several solid and
hematological human cancer cell lines with no toxic effect in normal cells. Our findings
suggest that further development of this compound and its derivatives may lead to the
identification of new therapeutic antitumor agents acting through inhibition of KDM4A.Associazione Italiana per la Ricerca sul Cancro | Ref. AIRC-17217Regione Campania | Ref. iCURE (CUP B21c17000030007)Regione Campania | Ref. FASE 2: IDEAL (CUP B63D18000560007)Xunta de Galicia | Ref. ED431C 2017/61Xunta de Galicia | Ref. ED-431G/02-FEDEREuropean Commission | Ref. FP7-BLUEPRINT (282510)European Commission | Ref. Ocean Medicine #690944Ministero Italiano dellâUniversitĂ | Ref. PRIN-20152TE5PKEuropean Commission | Ref. SAF2016-77620-R-FEDE