Elevated expression of cyclooxygenase-2 is a negative prognostic factor for overall survival in intrahepatic cholangiocarcinoma

The production of prostaglandins is regulated by cyclooxygenases (COXs), which also have a role in tumour development and progression in various human malignancies, including cholangiocarcinoma. Limited information is available of the correlation of COX-2 protein expression and prognosis in intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to determine the clinical significance of COX-2 expression in ICC. In addition the correlation of COX-2 expression and apoptosis/proliferation was analysed. COX-2 expression was determined immunohistochemically in 62 resected ICCs. Proliferation was assessed using Ki67-immunohistochemistry, and apoptosis was measured with the TdT-mediated dUTP nick-end-labelling technique. COX-2 was identified as an independent prognostic factor (P = 0.028) in resected ICC by survival analysis. High levels of COX-2 expression were found to be associated both with reduced apoptosis and increased proliferation of tumour cells. This study demonstrates the independent prognostic value of the COX-2 expression in resected ICC, thus, offering a potential additional adjuvant therapeutic approach with COX-2 inhibitors

Short- and long-term outcomes of single bare metal stent versus drug eluting stent in nondiabetic patients with a simple de novo lesion in the middle and large vessel

<p>Abstract</p> <p>Objective</p> <p>This study was aimed to investigate the short- and long-term outcomes of percutaneous coronary intervention (PCI) between single bare metal stent (BMS) and single drug eluting stent (DES) in nondiabetic patients with a simple de novo lesion in the middle and large vessel.</p> <p>Methods</p> <p>Two hundred and thirty-five consecutive patients with a simple de novo lesion in the middle and large vessel were treated with BMS or DES in our hospital from Apr. 2004 to Dec. 2004.</p> <p>The inclusion criteria: a simple de novo lesion in the middle and large vessel, stent diameter ≥ 3.0 mm, stent length ≤ 18 mm, the exclusion criteria: diabetes mellitus, left main trunk disease and left ventricular ejection fraction ≤ 30%. Of them, there were 150 patients in BMS group and 85 patients in DES group, and the rates of lost to follow up were 6.7% and 1.2% respectively.</p> <p>Results</p> <p>BMS group had lower hypercholesteremia rate (22.0% vs 38.8%) and higher proportion of TIMI grade 0 (12% vs 1.2%) than DES group (all P < 0.05), but both groups had similar stent length (16.16 ± 2.81 mm vs 16.06 ± 2.46 mm) and stent diameter (3.85 ± 3.07 mm vs 3.19 ± 0.24 mm) after procedure, in-segment restenosis rate (0% vs 1.2%) and target lesion revascularization (TLR, 2.0% vs 2.4%) at 6-month follow-up (all P > 0.05). No difference was found in TLR (1.3% vs 1.2%, P = 1.00) and recurrent myocardial infarction (Re-MI) (0% vs 1.2%, P = 0.36), cardiac death (0.7% vs 1.2%, P = 1.00) between 1- and 3-year. So were TLR (6.0% vs 5.9%, P = 0.97), Re-MI (0% vs 2.4%, P = 0.06), cardiac death (2.0% vs 3.5%, P = 0.48) and major adverse cardiac events (MACE, 8.7% vs 10.6%, P = 0.63), cardiac death-free cumulative survival (98.7% vs 97.7%, P = 0.56), TLR-free cumulative survival (94.0% vs 94.1%, P = 0.98) and Re-MI-free cumulative survival (100% vs 97.7%, P = 0.06) at 3-year follow-up.</p> <p>Conclusion</p> <p>The single BMS has similar efficacy and safety to single DES in nondiabetic patients with a simple de novo lesion in the middle and large vessel at short- and long-term follow-up.</p

Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions

<p>Abstract</p> <p>Background</p> <p>Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied.</p> <p>Methods</p> <p>In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses.</p> <p>Results</p> <p>Under normoxic conditions, a half maximal inhibitory concentration (IC₅₀) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was 2.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions.</p> <p>Conclusion</p> <p>Our results suggest that BA is capable of improving the effects of tumor therapy in human malignant glioma cells, particularly under hypoxic conditions. Further investigations are necessary to characterize its potential as a radiosensitizer.</p

Triple antiplatelet therapy for preventing vascular events: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Dual antiplatelet therapy is usually superior to mono therapy in preventing recurrent vascular events (VEs). This systematic review assesses the safety and efficacy of triple antiplatelet therapy in comparison with dual therapy in reducing recurrent vascular events.</p> <p>Methods</p> <p>Completed randomized controlled trials investigating the effect of triple versus dual antiplatelet therapy in patients with ischaemic heart disease (IHD), cerebrovascular disease or peripheral vascular disease were identified using electronic bibliographic searches. Data were extracted on composite VEs, myocardial infarction (MI), stroke, death and bleeding and analysed with Cochrane Review Manager software. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using random effects models.</p> <p>Results</p> <p>Twenty-five completed randomized trials (17,383 patients with IHD) were included which involving the use of intravenous (iv) GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban), aspirin, clopidogrel and/or cilostazol. In comparison with aspirin-based therapy, triple therapy using an intravenous GP IIb/IIIa inhibitor significantly reduced composite VEs and MI in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) (VE: OR 0.69, 95% CI 0.55-0.86; MI: OR 0.70, 95% CI 0.56-0.88) and ST elevation myocardial infarction (STEMI) (VE: OR 0.39, 95% CI 0.30-0.51; MI: OR 0.26, 95% CI 0.17-0.38). A significant reduction in death was also noted in STEMI patients treated with GP IIb/IIIa based triple therapy (OR 0.69, 95% CI 0.49-0.99). Increased minor bleeding was noted in STEMI and elective percutaneous coronary intervention (PCI) patients treated with GP IIb/IIIa based triple therapy. Stroke events were too infrequent for us to be able to identify meaningful trends and no data were available for patients recruited into trials on the basis of stroke or peripheral vascular disease.</p> <p>Conclusions</p> <p>Triple antiplatelet therapy based on iv GPIIb/IIIa inhibitors was more effective than aspirin-based dual therapy in reducing VEs in patients with acute coronary syndromes (STEMI and NSTEMI). Minor bleeding was increased among STEMI and elective PCI patients treated with a GP IIb/IIIa based triple therapy. In patients undergoing elective PCI, triple therapy had no beneficial effect and was associated with an 80% increase in transfusions and an eightfold increase in thrombocytopenia. Insufficient data exist for patients with prior ischaemic stroke and peripheral vascular disease and further research is needed in these groups of patients.</p

Improving the account record management of a customer success management team: An insider action research

Effective account records management is vital to the success of customer success managers (CSMs) in software companies. It enables better customer service, proactive issue resolution, collaboration, and data-driven decision-making. This study contributes to the knowledge base on the relevance of knowledge and performance management in improving account records practices by implementing two action research cycles to address inconsistent, inaccurate, and outdated records. The first cycle focused on improving process guidelines and process cascade. In contrast, the second cycle integrated account records management into the company\u27s performance management system. In addition, the ADKAR change management strategy was employed alongside force-field analysis and group dynamics concepts. They helped create awareness, impart knowledge and skills, and reinforce change for sustainability. The interventions improved account records\u27 accuracy, consistency, and timeliness, with team members benefiting from clearer guidelines and better compliance with processes. Although the specifics of this study may be unique to the organization, the broader context of action research applies to many organizations grappling with similar issues of inconsistent or outdated records. However, while the study focuses on account records management, it requires further research on whether the strategies implemented can be generalized to other business processes, as the effectiveness of the strategies may depend on the nature of the process, the organizational structure, and the culture of the organization. Nonetheless, this study highlights the importance of effective account records management in driving customer success. Further, it underscores the need for ongoing improvement efforts in this aspect

Autopercepção e condições de saúde bucal em gestantes

This study ev aluated oral health indic ators by determining the pr evalence of dental c aries, periodontal diseases, prosthetic conditions and need in pr egnant women; identifi ed self-perceived oral health status and evaluated association bet ween variables. A clinical examination was performed in fi fty pregnant women assisted in the Preventive Dentistry Clinic-FOAr-UNESP using traditional oral health indicators: DMFT, C ommunity Periodontal Index ( CPI) and pr osthetic c onditions. A semi-struc tured questionnair e was applied to identify oral health perception and to collect sociodemographic variables. For data analysis, pregnant women were allocated in three groups according to their oral health perception (good, fair, poor) and compared according to clinical variables by the Kruskal-Wallis and Dunn tests. DMFT was high, all of them showed periodontal changes, most do not use and do not r equire any type of prosthesis; 36% considered their oral appearance as good. There was signifi cant diff erence between groups for the DMFT index and prosthetic need. It may be concluded that despite dental caries experience of pregnant women was found to be high, the prosthetic need have been detected in most of them and the presence of calculus was observed in all the volunteers, the majority considered their oral health status satisfactory.O estudo avaliou indicadores de saúde bucal em gestantes por meio da determinação da prevalência de cárie dentária, periodont opatias, uso e necessidade de próteses; identifi cou a autopercepção de condições de saúde bucal e avaliou a associação entre as variávies. Exame clínico foi realizado em 50 gestantes atendidas na Clínica de Odont ologia Preventiva e Sanitária da FO Ar-UNESP utilizando indicadores tradicionais de saúde: IPC, CPO-D e avaliação protética. Um questionário semi-estruturado foi aplicado para identifi car a per cepção sobre a saúde bucal e c oletar variáveis sóciodemográfi cas. Para análise, três grupos foram formados segundo a percepção de saúde bucal: boa, regular, ruim, e comparados segundo as variáveis clínicas, pelos testes Kruskal-Wallis e Dunn. O CPO-D das gestantes foi considerado alto; todas apresentaram alterações periodontais; a maioria não utilizava e não necessitava de nenhum tipo de prótese; 36% das gestantes consideraram boa sua aparência bucal. Houve diferença signifi cativa entre os grupos para o índice CPOD e para nec essidade de pr ótese. Embora a experiência de cárie t enha sido alta, a nec essidade de pr ótese ter sido det ectada na maior par te da amostra e a pr esença de cálculo dental t enha sido obser vada em todas as voluntárias, a maioria considerou sua condição bucal satisfatória