共查询到20条相似文献,搜索用时 225 毫秒
1.
The aims of our investigation were to develop and optimize ciclopirox (CPX) nail lacquer using nonbiodegradable Eudragit RLPO (E-RLPO) as a film former and to assess its penetration efficiency across the human nail plate. Preliminary trials such as hydration enhancement factor (HEF), a retained drug in the nail plate, and SEM were studied to select the optimized permeation enhancer to be incorporated in the optimized lacquer formulation. A 33 full factorial design was built up to study the effect of three different factors, concentration of E-RLPO (10, 20, and 30%), Tween 80 (0.25, 0.5, and 1%), and triacetin (0, 10, and 30% of polymer weight). The studied responses were the drying time, water resistance, viscosity, and drug release up to 4 h. An ex vivo permeation study for the optimized formulations was carried out. The preliminary study aided the selection of 5% papain (endopeptidase enzyme) as a penetration enhancer; it showed the highest HEF of 15.27%, the highest amount of drug retained in the nail plate (886.2 μg/g). An ex vivo permeation study guided the selection of F4B (flux value of 3.79 μg/cm2/h) as optimized formulation. The optimized lacquer formula showed threefold increases in the permeation than the marketed CPX lacquer (Batrafen®). Confocal laser scanning microscopy revealed the higher intensity of the Rhodamine B dye across the nail plate in the case of the formula containing papain than the marketed formula without papain. Conclusively, an efficient and stable nail lacquer was developed for potential transungual delivery of CPX to target the drug to the nail bed and ensure efficiency against onychomycosis. 相似文献
2.
Avadhesh Singh Kushwaha Michael A. Repka S. Narasimha Murthy 《AAPS PharmSciTech》2017,18(8):2949-2956
The objective was to prepare a novel nail lacquer formulation to improve the ungual and trans-ungual delivery of apremilast for the potential treatment of nail psoriasis. Nail lacquer formulation was prepared using Eudragit® S 100 as a film-forming polymer and the mixture of ethanol, ethyl acetate, and water as a solvent system. As a result of high-throughput screening studies, dexpanthenol and salicylic acid were found to be the potential penetration enhancers. After 7 days of in vitro studies, the cumulative amount of apremilast delivered by the nail lacquer formulation across the nail plate was found to be ~3-fold (0.52 ± 0.07 μg/cm2) more compared to control (nail lacquer formulation without enhancers) (0.19 ± 0.02 μg/cm2). The cumulative amount of apremilast retained in the nail plate in the case of nail lacquer formulation was 1.26 ± 0.18 μg/mg which was found to be ~2-fold more compared to control (0.57 ± 0.07 μg/mg). Human subject studies were performed on the nails of thumb and index finger of six volunteers for 15 days. As a result, the cumulative amount of apremilast retained in the free distal edge of the nail plate in the case of nail lacquer was found to be ~2-fold (0.93 ± 0.14 μg/mg) more related to control (0.41 ± 0.04 μg/mg). As a conclusion, nail lacquer formulation was found to be capable of delivering a substantial amount of apremilast into the nail apparatus; thus, it can be a potential option for the treatment of nail psoriasis. 相似文献
3.
Alexandro Bonifaz Andrés Tirado-Sánchez María José Graniel Carlos Mena Adriana Valencia Rosa María Ponce-Olivera 《Mycopathologia》2013,175(3-4):249-254
Aim
Diaper dermatitis (DD) is an inflammatory irritating condition that is common in infants. Most cases are associated with the yeast colonization of Candida or diaper dermatitis candidiasis (DDC), and therefore, the signs and symptoms improve with antimycotic treatment. Sertaconazole is a broad-spectrum third-generation imidazole derivative that is effective and safe for the treatment for superficial mycoses, such as tineas, candidiasis, and pityriasis versicolor. Our goal was to assess the efficacy and safety of sertaconazole cream (2 %) in DDC.Materials and methods
Twenty-seven patients with clinical and mycological diagnosis of DDC were enrolled and treated with 2 daily applications for 14 days and were followed-up for 2 further weeks.Results
Three etiologic agents were isolated: Candida albicans in 88.8 %, Candida parapsilosis in 7.3 %, and Candida glabrata in 3.2 %. There was an average symptom reduction from 7.1 to 3.2 in the middle of treatment and to 1.2 and 0.4 units at the end of treatment and follow-up, respectively. The treatment evaluation at the end of the follow-up period showed a total clinical and mycological cure in 88.8 %, improvement in 3.7 %, and failure in 7.4 %. There was side effect (3.7 %) of skin irritation, but the drug was not discontinued.Conclusions
Based on its safety and effectiveness, sertaconazole cream may be considered a new alternative for DDC treatment. 相似文献4.
K. A. Mol B. M. Rahel F. Eerens S. Aydin R. P. Th. Troquay J. G. Meeder 《Netherlands heart journal》2013,21(10):449-455
Objectives
Analysis of the first results of off-site percutaneous coronary interventions (PCI) and fractional flow reserve (FFR) measurements at VieCuri Medical Centre for Northern Limburg in Venlo.Background
Off-site PCI is accepted in the European and American Cardiac Guidelines as the need for PCI increases and it has been proven to be a safe treatment option for acute coronary syndrome.Methods
Retrospective cohort study reporting characteristics, PCI and FFR specifications, complications and 6-month follow-up for all consecutive patients from the beginning of off-site PCI in Venlo until July 2012. If possible, the data were compared with those of Medical Centre Alkmaar, the first off-site PCI centre in the Netherlands.Results
Of the 333 patients, 19 (5.7 %) had a procedural complication. At 6 months, a major adverse cardiovascular event (MACE) occurred in 43 (13.1 %) patients. There were no deaths or emergency surgery related to the PCI or FFR procedures. There was no significant difference in occurrence of a MACE or adverse cerebral event between the Alkmaar and Venlo population in the 30-day follow-up.Conclusion
This study demonstrates off-site PCI at VieCuri Venlo to have a high success rate. Furthermore, there was a low complication rate, low MACE and no procedure-related mortality. 相似文献5.
M. W. A. van Geldorp H. J. Heuvelman A. P. Kappetein J. J. V. Busschbach J. J. M. Takkenberg A. J. J. C. Bogers 《Netherlands heart journal》2013,21(1):28-35
Background
Although symptomatic patients with severe aortic stenosis have a high disease burden and guidelines recommend aortic valve replacement, many are treated conservatively. This study describes to what extent quality of life is changed by aortic valve replacement relative to conservative treatment.Methods
This observational study followed 132 symptomatic patients with severe aortic stenosis who were subjected to an SF-36v2TM Health Survey.Results
At baseline 84 patients were treated conservatively, 48 were referred for aortic valve replacement. In the conservatively treated group 15 patients died during a mean follow-up of 18 months (Kaplan-Meier survival was 85 % and 72 % at one and 2 years respectively) and 22 patients crossed over to the surgical group. Of the resulting 70 patients in the surgical group 3 patients died during a mean follow-up of 11 months (survival 95 % at 1 year). Physical functioning, vitality and general health improved significantly 1 year after aortic valve replacement. In conservatively treated patients physical quality of life deteriorated over time while general health, vitality and social functioning showed a declining trend. Mental health remained stable in both groups.Conclusions
Aortic valve replacement improves physical quality of life, general health and vitality in patients with symptomatic severe aortic stenosis. Besides having a low life expectancy, conservatively treated patients experience deterioration of physical quality of life. Health surveys such as the SF-36v2TM can be valuable tools in monitoring the burden of disease for an individual patient and offer additional help in treatment decisions. 相似文献6.
T. Yetgin M. M. J. M. van der Linden A. G. de Vries P. C. Smits R. van Mechelen S. C. Yap E. Boersma F. Zijlstra R.-J. M. van Geuns 《Netherlands heart journal》2014,22(1):20-27
Background
Medical discharge management of acute coronary syndromes (ACS) remains suboptimal outside randomised trials and constitutes an essential quality benchmark for ACS. We sought to evaluate the rates of key guideline-recommended pharmacological agents after ACS and characteristics associated with optimal treatment at discharge.Methods
The Rijnmond Collective Cardiology Research (CCR) registry is an ongoing prospective, observational study in the Netherlands that aims to enrol 4000 patients with ACS. We examined discharge and 1-month follow-up medication use among the first 1000 patients enrolled in the CCR registry. Logistic regression was performed to identify patient and hospital characteristics associated with collective guideline-recommended pharmacotherapy at hospital discharge.Results
At discharge, 94 % of patients received aspirin, 100 % thienopyridines, 80 % angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers, 87 % β-blockers, 96 % statins, and 65 % the combination of all 5 agents. ST-segment elevation myocardial infarction, hypertension, hypercholesterolaemia, and enrolment in an interventional centre were positive independent predictors of 5-drug combination therapy at discharge. Negative independent predictors were unstable angina and advanced age.Conclusion
Current data from the CCR registry reflect a high quality of care for ACS discharge management in the Rotterdam-Rijnmond region. However, potential still remains for further optimisation. 相似文献7.
Sander Kelderman Bianca Heemskerk Harm van Tinteren Rob R. H. van den Brom Geke A. P. Hospers Alfonsus J. M. van den Eertwegh Ellen W. Kapiteijn Jan Willem B. de Groot Patricia Soetekouw Rob L. Jansen Edward Fiets Andrew J. S. Furness Alexandra Renn Marcin Krzystanek Zoltan Szallasi Paul Lorigan Martin E. Gore Ton N. M. Schumacher John B. A. G. Haanen James M. G. Larkin Christian U. Blank 《Cancer immunology, immunotherapy : CII》2014,63(5):449-458
Introduction
Ipilimumab, a cytotoxic T lymphocyte-associated antigen-4 blocking antibody, has improved overall survival (OS) in metastatic melanoma in phase III trials. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a ‘real world’ population of patients treated with ipilimumab to identify markers for treatment benefit.Methods
Patients with advanced cutaneous melanoma were treated in the Netherlands (NL) and the United Kingdom (UK) with ipilimumab at 3 mg/kg. Baseline characteristics and peripheral blood parameters were assessed, and patients were monitored for the occurrence of adverse events and outcomes.Results
A total of 166 patients were treated in the Netherlands. Best overall response and disease control rates were 17 and 35 %, respectively. Median follow-up was 17.9 months, with a median progression-free survival of 2.9 months. Median OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (LDH) was demonstrated to be the strongest predictive factor for OS. These findings were validated in an independent cohort of 64 patients from the UK.Conclusion
In both the NL and UK cohorts, long-term benefit of ipilimumab treatment was unlikely for patients with baseline serum LDH greater than twice the upper limit of normal. In the absence of prospective data, clinicians treating melanoma may wish to consider the data presented here to guide patient selection for ipilimumab therapy. 相似文献8.
Aims
To examine the effect of renal denervation (RDN) on 24?h ambulatory blood pressure (ABP) with a standard radiofrequency ablation catheter (RF catheter).Methods
Seventy-five patients with resistant hypertension received bilateral RDN with an RF catheter (6 RF applications, 1 minute each, 8–12 watts). Seventy patients fulfilled inclusion criteria with mean systolic ABP ≥140 mmHg (mean 165/89) despite treatment with ≥3 antihypertensive drugs (mean 5.9) including a diuretic, and were further analysed for ABP changes. Follow-up at 1/3/6/12 months comprised biochemical evaluations and ABP measurement. At 6/12 months, duplex sonography of the renal arteries was additionally performed.Results
At 1/3/6/12 months we observed a significant reduction in systolic ABP of ?15/?17/?18/?15 mmHg (n = 55/53/57/50; non-parametric Friedman test, p < 0.001) and diastolic ABP of ?6/?9/?10/?7 mmHg (p < 0.001). Of the patients, 70?%/64?% showed a systolic ABP reduction of ≥10 mmHg, and 77?%/70?% of ≥5 mmHg at 6/12-month follow-up. Two patients (2.7?%) developed renal artery stenosis (>70?%) with subsequent stenting without complications. Logistic regression analysis with systolic ABP reduction ≥10 mmHg at 12 months follow-up as criterion revealed that only the mean baseline systolic ABP was significant, OR = 2.174.Conclusions
RDN with a standard RF catheter can be used safely to reduce mean ABP in resistant hypertension as shown in long-term follow-up.9.
Yanjuan Zhu Haibo Zhang Yong Li Jianping Bai Lirong Liu Yihong Liu Yanchun Qu Xin Qu 《Cancer immunology, immunotherapy : CII》2013,62(10):1629-1635
Purpose
To assess the activity and safety of postoperative adjuvant immunotherapy with transfusion of cytokine-induced killer (CIK) cells combined with chemotherapy in patients with colorectal cancer.Methods
We retrospectively studied 96 consecutive patients with colorectal cancer who were treated with resection between January 2010 and December 2012 as well as adjuvant chemotherapy. Twenty-one of these patients accepted at least 1 cycle of CIK cell transfusion for immunotherapy (CIK group). Disease free survival (DFS), immune cells and treatment related side effects were assessed. The patients were followed up until May 2013.Results
By the end of follow-up, 10 patients (10.42 %) had died. Eighteen patients (18.75 %) had withdrawn. All the patients in the CIK group are still alive, and only 1 patient had withdrawn. Patients in the CIK group had significantly longer DFS than those in the control group [HR = 0.28, 95 % CI (0.09, 0.91), p = 0.034]. The 2-year DFS rates of patients in the CIK group and the control group were 59.65 ± 24.80 % and 29.35 ± 6.39 %, respectively. The CD4+/CD8+ ratios were significantly lower during the period of chemotherapy than those before chemotherapy (p = 0.0038), while the ratios were significantly higher during the period of CIK cell transfusion than those before CIK therapy (p = 0.0484). There were no immediate adverse reactions to the CIK cell transfusions.Conclusion
Adjuvant transfusion of CIK cells prolongs DFS in patients with colorectal cancer. 相似文献10.
R. Jansen P. A. M. Kracht M. J. Cramer W. J. Tietge L. A. van Herwerden R. J. M. Klautz J. Kluin S. A. J. Chamuleau 《Netherlands heart journal》2013,21(11):487-496
Purpose
Exercise echocardiography can assess the dynamic component of mitral valve (MV) disease and may therefore be helpful for the clinical decision-making by the heart team. The purpose of this study is to determine the role of exercise echocardiography in the management of disproportionately symptomatic or otherwise atypical patients with mitral regurgitation (MR) and stenosis (MS) in clinical practice.Methods
Data of 14 MR and 14 MS patients, including echocardiograms at rest, were presented retrospectively to an experienced heart team to determine treatment strategy. Subsequently, exercise echo data were provided whereupon once again the treatment strategy was determined. This resulted in: value of exercise echo by means of 1) alteration or 2) confirmation of treatment strategy or 3) no additional value.Results
During exercise the echocardiographic severity of MV disease increased in 9 (64 %) MR and 8 (57 %) MS patients. Based upon alteration or confirmation of the treatment strategy, the value of exercise echocardiography in the management of MR and MS was 86 % and 57 %, respectively.Conclusion
This study showed that physical exercise echo can have an important role in the clinical decision-making of challenging patients with MV disease. Exercise echocardiography had additional value to the treatment strategy in 71 % of these patients. 相似文献11.
M. Voskuil W. L. Verloop P. J. Blankestijn P. Agostoni P. R. Stella P. A. Doevendans 《Netherlands heart journal》2011,19(7-8):319-323
Background
In a subpopulation of patients with essential hypertension, therapeutic targets are not met, despite the use of multiple types of medication. In this paper we describe our first experience with a novel percutaneous treatment modality using renal artery radiofrequency (RF) ablation.Methods
Patients who were resistant to at least three types of antihypertensive medical therapy (office systolic blood pressure?≥?160 mmHg; n?=?9) or who did not tolerate medication (n?=?2) were selected. Between July and November 2010, a total of 11 patients received percutaneous RF treatment. Patients were followed up for 1 month after treatment. Urine and blood samples were taken to evaluate the effects on renal function and neurohumeral factors.Results
No periprocedural complications or adverse events during follow-up were noted. A reduction of mean office blood pressure was seen from 203/109?±?32/19 mmHg at baseline to 178/97?±?28/21 mmHg at 1 month follow-up (mean difference 25?±?12 mmHg, p?<?0.01). Also, we noted a significant decrease in aldosterone level (391?±?210 pmol/L versus 250?±?142 pmol/L; p?=?0.03), while there was no decrease in plasma renin activity (190?±?134 fmol/L/s versus 195?±?163 fmol/L/s; p?=?0.43). No change in renal function was noted.Conclusion
Catheter-based renal denervation seems an attractive novel minimally invasive treatment option in patients with resistant hypertension, with a low risk of serious adverse events. 相似文献12.
K. Kraaier A. H. Starrenburg R. M. Verheggen J. van der Palen M. F. Scholten 《Netherlands heart journal》2013,21(4):191-195
Background
Implantable cardioverter defibrillators (ICDs) are designed to deliver shocks or antitachycardia pacing (ATP) in the event of ventricular arrhythmias. During follow-up, some ICD recipients experience the sensation of ICD discharge in the absence of an actual discharge (phantom shock). The aim of this study was to evaluate the incidence and predictors of phantom shocks in ICD recipients.Methods
Medical records of 629 consecutive patients with ischaemic or dilated cardiomyopathy and prior ICD implantation were studied.Results
With a median follow-up of 35 months, phantom shocks were reported by 5.1 % of ICD recipients (5.7 % in the primary prevention group and 3.7 % for the secondary prevention group; p=NS). In the combined group of primary and secondary prevention, there were no significant predictors of the occurrence of phantom shocks. However, in the primary prevention group, phantom shocks were related to a history of atrial fibrillation (p=0.03) and NYHA class <III (p=0.05). In the secondary prevention group, there were no significant predictors for phantom shocks.Conclusion
Phantom shocks occur in approximately 5 % of all ICD recipients. In primary prevention patients, a relation with a history of atrial fibrillation and NYHA class <III were significant predictors for the occurrence of phantom shocks. In the secondary prevention patients, no significant predictors were found. 相似文献13.
David A. Smith Paul Conkling Donald A. Richards John J. Nemunaitis Thomas E. Boyd Alain C. Mita Guillaume de La Bourdonnaye David Wages Alice S. Bexon 《Cancer immunology, immunotherapy : CII》2014,63(8):787-796
Background
IMO-2055 is a Toll-like receptor 9 (TLR9) agonist that potentially enhances the efficacy of antitumor agents through immune stimulation. The objective of this phase Ib dose-escalation trial (3 + 3 design) was to determine the recommended phase II dose (RP2D) of IMO-2055 when combined with erlotinib and bevacizumab in patients with advanced non-small cell lung cancer (NSCLC).Methods
Patients with stage 3/4 NSCLC and progressive disease (PD) following chemotherapy received IMO-2055 0.08, 0.16, 0.32, or 0.48 mg/kg once weekly plus erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks. Patients could receive treatment until PD or unacceptable toxicity.Results
Thirty-six patients were enrolled; 35 received at least one treatment dose. Two dose-limiting toxicities were observed across the dose range (Grade 3 dehydration and fatigue) with neither suggestive of a consistent toxicity pattern. IMO-2055 0.32 mg/kg was adopted as RP2D based on clinical and pharmacodynamic data. The most common treatment-emergent adverse events (TEAEs) were diarrhea (74 %), nausea (51 %), fatigue (51 %), rash (51 %), and injection-site reactions (49 %). Four patients experienced serious TEAEs considered to be study drug related. Five patients died, all due to PD. High-grade neutropenia and electrolyte disturbances previously reported with TLR9 agonists combined with platinum-based therapy were not observed in this study. Five of 33 patients evaluable for response (15 %) achieved partial response; another 20 (61 %) had stable disease, including 13 with stable disease ≥4 months.Conclusions
IMO-2055 demonstrated good tolerability and possible antitumor activity in combination with erlotinib and bevacizumab in heavily pretreated patients with advanced NSCLC. 相似文献14.
Pathogenic Dermatophytes Survive in Nail Lesions During Oral Terbinafine Treatment for Tinea Unguium
Tomoyuki Iwanaga Tsuyoshi Ushigami Kazushi Anzawa Takashi Mochizuki 《Mycopathologia》2017,182(7-8):673-679
Tinea unguium caused by dermatophyte species are usually treated with oral antimycotic, terbinafine (TBF). To understand the mechanisms of improvement and recalcitrance of tinea unguium by oral TBF treatment, a method of quantifying dermatophyte viability in the nail was developed, and the viability of dermatophytes was analyzed in toenail lesions of 14 patients with KOH-positive tinea unguium treated with oral TBF 125 mg/day for up to 16 weeks. Mycological tests, including KOH examination and fungal culture, and targeted quantitative real-time PCR for internal transcribed spacer (ITS) region, including rRNA, were demonstrated at the initial visit and after 8 and 16 weeks of treatment. Assays in eight patients showed that average ITS DNA amount significantly decreased, to 44% at 8 weeks and 36% at 16 weeks compared with 100% at initial visit. No significant difference was observed between at 8 and 16 weeks, despite the TBF concentration in the nail supposedly more than 10-fold higher than the minimum fungicidal concentration for dermatophytes. This finding suggests the pathogenic dermatophytes in nail lesions could survive in a dormant form, such as arthroconidia, during oral TBF treatment. Both antimycotic activity and nail growth are important factors in treatment of tinea unguium. 相似文献
15.
L. R. A. Olde Nordkamp A. H. G. Driessen A. Odero N. A. Blom D. R. Koolbergen P. J. Schwartz A. A. M. Wilde 《Netherlands heart journal》2014,22(4):160-166
Introduction
Treating therapy-resistant patients with inherited arrhythmia syndromes can be difficult and left cardiac sympathetic denervation (LCSD) might be a viable alternative treatment option. We provide an overview of the indications and outcomes of LCSD in patients with inherited arrhythmia syndromes in the only tertiary referral centre in the Netherlands where LCSD is conducted in these patients.Methods
This was a retrospective study, including all patients with inherited arrhythmia syndromes who underwent LCSD in our institution between 2005 and 2013. LCSD involved ablation of the lower part of the left stellate ganglion and the first four thoracic ganglia.Results
Seventeen patients, 12 long-QT syndrome (LQTS) patients (71 %) and 5 catecholaminergic polymorphic ventricular tachycardia (CPVT) patients (29 %), underwent LCSD. Most patients (94 %) were referred because of therapy-refractory cardiac events. In 87 % the annual cardiac event rate decreased. However, after 2 years the probability of complete cardiac event-free survival was 59 % in LQTS and 60 % in CPVT patients. Two patients (12 %) had major non-reversible LCSD-related complications: one patient suffered from a Harlequin face post-procedure and one severely affected LQT8 patient died the day after LCSD due to complications secondary to an arrhythmic storm during the procedure.Conclusion
LSCD for inherited arrhythmia syndromes, which is applied on a relatively small scale in the Netherlands, reduced the cardiac event rate in 87 % of the high-risk patients who had therapy-refractory cardiac events, while the rate of major complications was low. Therefore, LSCD seems a viable treatment for patients with inherited arrhythmia syndromes without other options for therapy. 相似文献16.
H. Versteeg S. S. Pedersen M. H. Mastenbroek W. K. Redekop J. O. Schwab P. Mabo M. Meine 《Netherlands heart journal》2014,22(10):423-428
Background
Remote patient monitoring is a safe and effective alternative for the in-clinic follow-up of patients with cardiovascular implantable electronic devices (CIEDs). However, evidence on the patient perspective on remote monitoring is scarce and inconsistent.Objectives
The primary objective of the REMOTE-CIED study is to evaluate the influence of remote patient monitoring versus in-clinic follow-up on patient-reported outcomes. Secondary objectives are to: 1) identify subgroups of patients who may not be satisfied with remote monitoring; and 2) investigate the cost-effectiveness of remote monitoring.Methods
The REMOTE-CIED study is an international randomised controlled study that will include 900 consecutive heart failure patients implanted with an implantable cardioverter defibrillator (ICD) compatible with the Boston Scientific LATITUDE® Remote Patient Management system at participating centres in five European countries. Patients will be randomised to remote monitoring or in-clinic follow-up. The In-Clinic group will visit the outpatient clinic every 3–6 months, according to standard practice. The Remote Monitoring group only visits the outpatient clinic at 12 and 24 months post-implantation, other check-ups are performed remotely. Patients are asked to complete questionnaires at five time points during the 2-year follow-up.Conclusion
The REMOTE-CIED study will provide insight into the patient perspective on remote monitoring in ICD patients, which could help to support patient-centred care in the future. 相似文献17.
Ester Simeone Giusy Gentilcore Diana Giannarelli Antonio M. Grimaldi Corrado Caracò Marcello Curvietto Assunta Esposito Miriam Paone Marco Palla Ernesta Cavalcanti Fabio Sandomenico Antonella Petrillo Gerardo Botti Franco Fulciniti Giuseppe Palmieri Paola Queirolo Paolo Marchetti Virginia Ferraresi Gaetana Rinaldi Maria Pia Pistillo Gennaro Ciliberto Nicola Mozzillo Paolo A. Ascierto 《Cancer immunology, immunotherapy : CII》2014,63(7):675-683
Background
Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research.Patients and methods
Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12.Results
Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12).Conclusion
Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required. 相似文献18.
Runmei Li Changli Wang Liang Liu Chunjuan Du Shui Cao Jinpu Yu Shizhen Emily Wang Xishan Hao Xiubao Ren Hui Li 《Cancer immunology, immunotherapy : CII》2012,61(11):2125-2133
Objective
Cytokine-induced killer (CIK) cells have the ability to kill tumor in vitro and in vivo. This study was designed to evaluate the clinical efficacy of CIK cell immunotherapy following regular chemotherapy in patients with non-small cell lung cancer (NSCLC) after surgery.Methods
A paired study, with 87 stage I–IV NSCLC patients in each group, was performed. Patients received either chemotherapy (arm 2) or chemotherapy in combination with autologous CIK cell immunotherapy (arm 1). Progression-free survival (PFS) and overall survival (OS) were evaluated.Results
Of the 87 paired patients, 50 had early-stage disease (stage I–IIIA) and 37 had advanced-stage disease (stage IIIB–IV). Among early-stage patients, the distribution of 3-year PFS rate and median PFS time showed no statistical difference between the two groups (p = 0.259 and 0.093, respectively); however, the 3-year OS rate and median OS time in arm 1 were significantly higher than those in arm 2 (82 vs. 66 %; p = 0.049 and 73 vs. 53 months; p = 0.006, respectively). Among the advanced-stage patients, the 3-year PFS and OS rates of arm 1 were significantly higher than those of arm 2 (6 vs. 3 %; p < 0.001 and 31 vs. 3 %; p < 0.001, respectively); the median PFS and OS times in arm 1 were also significantly longer than those in arm 2 (13 vs. 6 months; p = 0.001 and 24 vs. 10 months; p < 0.001, respectively). Multivariate analyses indicated that the frequency of CIK cell immunotherapy was significantly associated with prolonged PFS (HR = 0.91; 95 % CI 0.85–0.98; p = 0.012) and OS (HR = 0.83; 95 % CI, 0.74–0.93; p = 0.001) in the arm 1.Conclusions
The data suggested that CIK cell immunotherapy could improve the efficacy of conventional chemotherapy in NSCLC patients, and increased frequency of CIK cell treatment could further enhance the beneficial effects. A multi-center randomized trial is being carried out in our hospital to further validate these findings. 相似文献19.
M. A. Velders A. J. van Boven J. Brouwer P. C. Smits A. W. J. van ’t Hof C. J. de Vries M. Queré S. H. Hofma 《Netherlands heart journal》2014,22(4):167-173
Aims
Everolimus-eluting stents (EES) were superior to sirolimus-eluting stents (SES) in a dedicated myocardial infarction trial, a finding that was not observed in trials with low percentages of ST-elevation myocardial infarction (STEMI). Therefore, this study sought to investigate the influence of clinical presentation on outcome after EES and SES implantation.Methods
A pooled population of 1602 randomised patients was formed from XAMI (acute MI trial) and APPENDIX-AMI (all-comer trial). Primary outcome was cardiac mortality, MI and target vessel revascularisation at 2 years. Secondary endpoints included definite/probable stent thrombosis (ST). Adjustment was done using Cox regression.Results
In total, 902 EES and 700 SES patients were included, of which 44 % STEMI patients (EES 455; SES 257) and 56 % without STEMI (EES 447; SES 443). In the pooled population, EES and SES showed similar outcomes during follow-up. Moreover, no differences in the endpoints were observed after stratification according to presentation. Although a trend toward reduced early definite/probable ST was observed in EES compared with SES in STEMI patients, long-term ST rates were low and comparable.Conclusions
EES and SES showed a similar outcome during 2-year follow-up, regardless of clinical presentation. Long-term safety was excellent for both devices, despite wide inclusion criteria and a large sub-population of STEMI patients. 相似文献20.
L Rhoda Molife Li Yan Joanna Vitfell-Rasmussen Adriane M Zernhelt Daniel M Sullivan Philippe A Cassier Eric Chen Andrea Biondo Ernestina Tetteh Lillian L Siu Amita Patnaik Kyriakos P Papadopoulos Johann S de Bono Anthony W Tolcher Susan Minton 《Journal of hematology & oncology》2014,7(1):1-12