Conventional Therapy In Patients Research Articles

Cost Comparison of Hematopoietic Stem Cell Transplantation and Conventional Therapy for Patients with Thalassemia Major in China

▪Background: The conventional treatment (CT) for beta- thalassemia major (TM) includes regular transfusion accompanied by iron-chelating therapy. However, this laborious treatment by given desferrioxamine (DFO) subcutaneously for 8 to12 hours per days, at least 5 days per week with/without deferiprone (DFP) has led to poor compliance, even though, the new medicine named deferasirox (DFX) has been introduced in China recent years. Nevertheless, the high cost makes it difficult to use widely for many families. Hematopoietic stem cell transplantation (HSCT) provides an alternative curative option for TM patients. To our knowledge, data from China has not been available in the literature on cost comparison between HSCT and CT.Aims: The principal aim of our study is to compare the lifetime undiscounted mean cost (UMC) of hematopoietic stem cell transplantation (HSCT) with UMC of conventional therapy (CT) in beta-thalassemia major (TM) patients and to investigate the relationship of the clinical features to cost outcomes of HSCT.Methods: We estimated UMC of 93 TM-HSCTs between 2011 and 2012 with a median age of 6 years (range, 3-16) and a median follow-up time of 3 years (range, 2.4 -3.8). The relationship between the UMC of HSCT and patient characteristics were analyzed. The UMC of 93 TM-HSCTs was compared with UMC of CT based on total 1526 TM patients. Age was used as matching variant, and the mean cost of each age was calculated, then cumulative cost was further adjusted for age in patients.Results: UMC of TM-HSCT was CNY (Chinese Yuan) 235,254/USD 37,664 (95% confidence interval (CI) CNY208, 081-262,719/USD 33,293-42,035) with mean hospital stay of 60.5 days (95% CI 49-71). UMC of 20 years of follow-up and total undiscounted lifetime (55 years) for patients underwent HSCT were CNY 345,317/USD55, 251 and CNY 465,975/USD 74,602 respectively. However, the corresponding costs of patients undergoing CT were CNY 2,101,488/ USD336, 238 and CNY 7,489,519/ USD1, 198,323 respectively. Patient characteristics were helpless to predict the costs. HLA-mismatched transplants increased significantly UMC of HSCT than matched transplants (USD 35,818 vs. USD 52,771; p<0.001). The development of GVHD were associated with higher costs (USD 63,933 vs. USD 44,547; p = 0.001).Conclusions: Cost comparison of HSCT and CT suggests that HSCT is an efficient and high cost-effective treatment for TM patients. Mismatched donor transplant increases the cost of HSCT.Keywords: hematopoietic stem cell transplantation, iron overload, cost analysis [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The effects of additional proprioceptive neuromuscular facilitation over conventional therapy in patients with adhesive capsulitis

Purpose: This study is performed to investigate the effectiveness of upper extremity and scapula Proprioceptive Neuromuscular Facilitation (PNF) techniques in adhesive capsulitis (AC). Methods: Thirty-six subjects were randomized into two groups. Control group (n=18) was treated with conventional physiotherapy applications consisting of hot-pack and ultrasound, and wall and wand exercises instructed as a home program; study group (n=18) was treated with upper ext remity and scapula PNF patterns besides conventional physiotherapy. Patients were treated five times a week, for a total of 15 sessions. Pain intensity was assessed on a visual analogue scale; postural deformities were evaluated by inspection. Range of shoulder movements (ROM) were measured by a universal goniometer. “Lateral Scapular Slide Test” and assessment of scapular po sition were used for evaluation of the scapula. Functional performance was assessed by Shoulder Pain and Disability Index (SPADI). Results: Intensity of pain during activity significantly decreased and ROM increased in both groups (p 0.05). Scapula position didn’t change after therapy in both groups (p>0.05). SPADI scores decreased in both groups (p<0.05). Discussion: This study showed that PNF patterns provide significant contribution to night pain and range of flexion and abduction movements in patients with AC. Including PNF applications in AC treatment program may provide better outcomes.

An Effective and Well Tolerated Strategy of Bladder Preservation Therapy in Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer

BackgroundThe purpose of this study was to determine the feasibility and clinical effectiveness of concurrent weekly carboplatin chemotherapy in conjunction with definite radiation with or without adjuvant chemotherapy in the treatment of muscle-invasive bladder cancer. Patients and MethodsBetween April 2010 and December 2013, 30 patients with muscle-invasive bladder cancer were evaluated retrospectively in this study. Concurrent chemoradiotherapy (CCRT) with weekly carboplatin was initiated. CCRT was followed by 2 courses of carboplatin and gemcitabine limited to patients with Eastern Cooperative Oncology Group performance status < 3 and age < 80 years. ResultsThirty patients were treated and all completed the CCRT protocol. Seven of 8 patients (88%) achieved a pathological complete response (pCR) with CCRT alone, and 18 of 22 patients (82%) treated with CCRT followed by adjuvant chemotherapy had a pCR. The median follow-up was 23.2 (range, 8.3-40.7) months. The median progression-free survival was 15.9 months for the CCRT group, and not sufficient to evaluate CCRT followed by adjuvant chemotherapy. The median overall survival with CCRT was 18.8 months, and had not yet been reached for CCRT with adjuvant chemotherapy. The protocol was well tolerated for adverse events. ConclusionOur study has shown that concomitant chemotherapy using weekly carboplatin in the management of muscle-invasive bladder cancer is feasible and well tolerated, even in older patients. Additional adjuvant chemotherapy with 2 cycles of carboplatin and gemcitabine should be encouraged in physically fit patients. These results provide a basis for randomized studies to compare this approach with conventional therapy for patients who wish to preserve the bladder.

The Effects of Additional Proprioceptive Neuromuscular Facilitation Over Conventional Therapy In Patients With Adhesive Capsulitis

Purpose: This study is performed to investigate the effectiveness of upper extremity and scapula Proprioceptive Neuromuscular Facilitation (PNF) techniques in adhesive capsulitis (AC). Methods: Thirty-six subjects were randomized into two groups. Control group (n=18) was treated with conventional physiotherapy applications consisting of hot-pack and ultrasound, and wall and wand exercises instructed as a home program; study group (n=18) was treated with upper ext remity and scapula PNF patterns besides conventional physiotherapy. Patients were treated five times a week, for a total of 15 sessions. Pain intensity was assessed on a visual analogue scale; postural deformities were evaluated by inspection. Range of shoulder movements (ROM) were measured by a universal goniometer. “Lateral Scapular Slide Test” and assessment of scapular po sition were used for evaluation of the scapula. Functional performance was assessed by Shoulder Pain and Disability Index (SPADI). Results: Intensity of pain during activity significantly decreased and ROM increased in both groups (p<0.05). While increase amounts of shoulder flexion and abduction ROMs were higher in the PNF group (p<0.05), there was no difference between groups in internal and external rotation move ments. Although, night pain significantly decreased in the study group (p<0.05), it remained unc hanged in the control group (p>0.05). Scapula position didn’t change after therapy in both groups (p>0.05). SPADI scores decreased in both groups (p<0.05). Discussion: This study showed that PNF patterns provide significant contribution to night pain and range of flexion and abduction movements in patients with AC. Including PNF applications in AC treatment program may provide better outcomes.

Abstract 2400: Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for targeted sequencing in a prospective randomized trial for personalized treatment in all tumor type: The SHIVA study

Abstract Rationale: The noninvasive biomarker circulating cell-free tumor DNA (ctDNA) has the potential to enable noninvasive diagnostic tests for personalized medicine in providing similar molecular information as that derived from invasive tumor biopsies. The ongoing large multicentric randomized histology-independent phase II trial (SHIVA, NCT01771458) compares molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with any type of refractory cancer. The screening phase consists of the invasive biopsy of metastatic tumor tissue and downstream analysis using Ion Torrent's Ampliseq hotspot cancer panel. We evaluated whether ctDNA analysis would identify the same mutations as those obtained through invasive biopsy. Patients and methods: de novo detection of somatic mutations using ctDNA in 34 patients covering 18 different tumor types, scanning ∼50 genes and more than 2500 mutations with a multiplexed next generation sequencing panel. Results: In 27 patients, 27 of 28 actionable mutations identified in metastasis biopsies (96%) were detected in matched ctDNA. Among these 27 patients, two additional mutations were found in ctDNA only. In the seven other patients, mutation detection from metastasis biopsy failed due to inadequate biopsy material, but was successful in all plasma DNA samples providing three more potential actionable mutations. Conclusion; These results suggest that ctDNA analysis is a cheaper, safer and quicker alternative to invasive biopsy of metastasis, irrespective of cancer type and metastatic site, for multiplexed mutation detection in selecting personalized therapies based on the patient's tumor genetic content. Citation Format: Jean-Yves Pierga, Charles Decraene, Virginie Bernard, Maud Kamal, Anthony Blin, Quentin Leroy, Thomas Rio Frio, Gaëlle Pierron, Céline Callens, Ivan Bieche, Adrien Saliou, Jordan Madic, Etienne Rouleau, François-Clément Bidard, Olivier Lantz, Marc-Henri Stern, Ronald Lebofsky, Christophe Le Tourneau. Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for targeted sequencing in a prospective randomized trial for personalized treatment in all tumor type: The SHIVA study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2400. doi:10.1158/1538-7445.AM2015-2400

Prevention Of Coronary Heart Disease And Stroke Complications In Type 2 Diabetes Mellitus: An Observational, Prospective Study

Abstract Background and Aims: We assessed the effect of intensive therapy on modifiable cardiovascular (CV) risk factors and CV risk as compared to conventional therapy in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Material and Methods: This was an observational, prospective study, conducted in Romania. During 1-year follow-up period the enrolled participants received either multi-factorial pharmacotherapy associated with intensive therapeutic education (Intensive group), or conventional therapy (Control group). Current analysis included data (anthropometric measurements, blood pressure and biochemical parameters) recorded at months (M) 0, 6 and 12. CV risk was calculated at M1 and M12 using the UK Prospective Diabetes Study Risk Engine. Results: 138 patients aged 57.02±10.05 years were included in this analysis (69 in each group). At M6 and M12 a significant improvement of the majority of the modifiable risk factors in the Intensive group compared to the Control group was observed. At M12, coronary heart disease (CHD)/fatal-CHD risks were significantly lower in the Intensive (7.5%/3.1%) than in the Control (17.95%/10.3%) group (p&lt;0.05). A similar trend was observed for the stroke/fatal-stroke risks. Conclusions: CHD/fatal-CHD and stroke/fatal-stroke risk burden decreased in newly diagnosed diabetic patients following multi-factorial pharmacotherapy association with intensive lifestyle changes during 1-year follow-up.

Randomized phase II trial comparing molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer: Results of the SHIVA trial.

11113 Background: Non-randomized studies suggested that selecting molecularly targeted agents (MTAs) based on the molecular profile of pts’ tumors, independently of tumor location and histology, improves outcome. We evaluated this histology-agnostic approach in pts who have failed standard of care therapy. Methods: Eligible pts underwent a biopsy of a metastatic site in order to establish the molecular profile of their tumor. Pts for whom a molecular alteration was identified and matched a MTA according to a pre-specified treatment algorithm (Table), were stratified according to the molecular pathway and randomly allocated to matching MTA or treatment at physician’s choice (TPC). MTAs were only allowed outside their licensed indication and if not previously given. The primary end point was PFS. Results: Among 741 included pts, 195 were randomized. 82, 89 and 24 pts were allocated to the HT, PI3K and RTK/MAPK subgroups. G3/4 AEs rates were 43% and 35% in the MTA and TPC arms. ORR was 4.1% in the MTA arm vs...

Efficacy of RetroNectin-Activated Cytokine-Induced Killer Cell Therapy in Metastatic Brain Tumor Patients

Background: The aim of this study was to investigate the clinical efficacy of RetroNectin-activated cytokine-induced killer cell (R-CIK) therapy following conventional therapies in patients with metastatic brain tumors. Methods: This study included 20 patients with metastatic brain tumors. Patients received R-CIK therapy following conventional therapies (including chemotherapy and target therapy). Progression-free survival (PFS), overall survival (OS), and prognostic factors were evaluated. Results: Of the 4 breast cancer patients in our cohort, 2 remained alive and 2 died. Of the 14 non-small cell lung cancer (all adenocarcinoma) patients, 3 had a partial response, 8 had stable disease, and 3 had progressive disease after receiving R-CIKs. The overall response rate was 21.4% (3/14), and the disease control rate was 78.6% (11/14). The median PFS and OS were 7.7 months (95% confidence interval (CI) 3-16.5 months) and 12.6 months (95% CI 6-21 months), respectively. Conclusion: R-CIKs combined with conventional therapies could improve the prognosis of metastatic brain tumor patients, especially of those with adenocarcinoma of the lung.

Role of electrical stimulation added to conventional therapy in patients with idiopathic facial (Bell) palsy.

The aim of this study was to determine the efficacy of electrical stimulation when added to conventional physical therapy with regard to clinical and neurophysiologic changes in patients with Bell palsy. This was a randomized controlled trial. Sixty patients diagnosed with Bell palsy (39 right sided, 21 left sided) were included in the study. Patients were randomly divided into two therapy groups. Group 1 received physical therapy applying hot pack, facial expression exercises, and massage to the facial muscles, whereas group 2 received electrical stimulation treatment in addition to the physical therapy, 5 days per week for a period of 3 wks. Patients were evaluated clinically and electrophysiologically before treatment (at the fourth week of the palsy) and again 3 mos later. Outcome measures included the House-Brackmann scale and Facial Disability Index scores, as well as facial nerve latencies and amplitudes of compound muscle action potentials derived from the frontalis and orbicularis oris muscles. Twenty-nine men (48.3%) and 31 women (51.7%) with Bell palsy were included in the study. In group 1, 16 (57.1%) patients had no axonal degeneration and 12 (42.9%) had axonal degeneration, compared with 17 (53.1%) and 15 (46.9%) patients in group 2, respectively. The baseline House-Brackmann and Facial Disability Index scores were similar between the groups. At 3 mos after onset, the Facial Disability Index scores were improved similarly in both groups. The classification of patients according to House-Brackmann scale revealed greater improvement in group 2 than in group 1. The mean motor nerve latencies and compound muscle action potential amplitudes of both facial muscles were statistically shorter in group 2, whereas only the mean motor latency of the frontalis muscle decreased in group 1. The addition of 3 wks of daily electrical stimulation shortly after facial palsy onset (4 wks), improved functional facial movements and electrophysiologic outcome measures at the 3-mo follow-up in patients with Bell palsy. Further research focused on determining the most effective dosage and length of intervention with electrical stimulation is warranted.

Allogeneic hematopoietic stem cell transplantation for non-malignant hematological disorders

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a geno-identical matched sibling (MSD) is one of the most successful therapies in patients with non-malignant hematological disorders. This study included 273 patients with severe aplastic anemia (SAA), 152 patients with B-Thalassemia major (BTM), 31 patients with Fanconi’s anemia (FA), 20 patients with congenital immunodeficiency diseases (ID), and 13 patients with inherited metabolic disorders (IMD) allografted from a MSD. In SAA, the 8-year overall survival (OS) of the whole group patients was 74%. OS was significantly better in patients conditioned with fludarabine and cyclophosphamide (Flu/Cy) than in those who received cyclophosphamide and antithymocyte globulin (Cy/ATG) (p=0.021). Acute graft-versus-host disease (aGVHD) grade II–IV occurred in 15% while chronic GVHD (cGVHD) occurred in 28%. In BTM, the 12-year disease-free survival (DFS) of the whole group of BTM patients was 72.4%. DFS was 74% for peripheral blood stem cell (PBSC) group compared to 64% in the BM stem cell group. The incidence of graft rejection was significantly lower in patients who received PBSC than in those who received BM (9% vs 25%) (p=0.036). AGVHD grade II–IV and cGVHD occurred in 15% and 12% of the whole group of BTM patients respectively. In FA, the 5-year OS was 64.5%. Graft rejection occurred in 10% of patients. Grade II–IV aGVHD occurred in 16% while cGVHD occurred in 4%. In ID, the 5-year OS was 62%. Graft rejection occurred in two (10%) patients. Three patients (15%) developed grade II–IV aGVHD, 2 of them progressed to secondary cGVHD. In IMD, OS was 46% at 5years. Graft rejection occurred in 8% of patients. AGVHD grade II–IV occurred in 15% while cGVHD occurred in 14%. In conclusion, Allo-HSCT provides a higher DFS rate over conventional therapies for patients with non-malignant hematological disorders with prolonged survival.

Machine-Based, Self-guided Home Therapy for Individuals With Severe Arm Impairment After Stroke

Background. Few therapeutic options exist for the millions of persons living with severe arm impairment after stroke to increase their dose of arm rehabilitation. This study compared self-guided, high-repetition home therapy with a mechanical device (the resonating arm exerciser [RAE]) to conventional therapy in patients with chronic stroke and explored RAE use for patients with subacute stroke. Methods. A total of 16 participants with severe upper-extremity impairment (mean Fugl-Meyer [FM] score = 21.4 ± 8.8 out of 66) >6 months poststroke were randomized to 3 weeks of exercise with the RAE or conventional exercises. The primary outcome measure was FM score 1 month posttherapy. Secondary outcome measures included Motor Activity Log, Visual Analog Pain Scale, and Ashworth Spasticity Scale. After a 1-month break, individuals in the conventional group also received a 3-week course of RAE therapy. Results. The change in FM score was significant in both the RAE and conventional groups after training (2.6 ± 1.4 and 3.4 ± 2.4, P = .008 and .016, respectively). These improvements were not significant at 1 month. Exercise with the RAE led to significantly greater improvements in distal FM score than conventional therapy at the 1-month follow-up (P = .02). In a separate cohort of patients with subacute stroke, the RAE was found feasible for exercise. Discussion. In those with severe arm impairment after chronic stroke, home-based training with the RAE was feasible and significantly reduced impairment without increasing pain or spasticity. Gains with the RAE were comparable to those found with conventional training and also included distal arm improvement.

De Novo Mutation Detection from Ctdna Correlates with Variants Detected on Metastasis of Patients with Any Kind of Refractory Cancer from the Shiva Trial

ABSTRACT Aim: The ability to perform molecular analyses on circulating tumor DNA (ctDNA) is a promising non-invasive tool to determine tumor genomic alterations. Liquid biopsies may provide information when the biopsy is not available, and address tumor heterogeneity. Multiple sampling and ctDNA analysis over time allows identification of emerging predictive biomarkers and collection of pharmacodynamic data. The aim of this study was to assess whether targeted sequencing on ctDNA permits the detection of the same mutations observed on solid tumor from the same patient. Methods: SHIVA is a multicentric randomized proof-of-concept phase II trial comparing molecularly targeted therapy based on tumor molecular profiling of a mandatory biopsy of a metastatic site versus conventional therapy in patients with any type of refractory cancer (Le Tourneau et al., BJC 2014). The molecular profile within SHIVA is performed on a mandatory biopsy and includes mutation analyses using AmpliSeq cancer panel (Life Technologies®). Blood samples for ctDNA analyses are taken before starting treatment, between day 7 and day 15, at first tumor evaluation, and at disease progression. The same approach was applied here to ctDNA before treatment and mutational profiles were compared to those from tumor biopsies. The bioinformatics analysis was done in a blinded manner. Results: ctDNA analysis was done on 19 patients including 3 patients with tumor biopsy not eligible for analysis. The mutation(s) identified from the solid tumor biopsy was confirmed in all corresponding blood samples (16/16) and 1 mutation was identified de novo in a patient whose tumor biopsy was uninformative. Tumor types included breast (5), lung (3), ovary (2), cervix (2) among others. Median ctDNA amount was 37 ng/mL [range: 7- 423]. Conclusions: Our results suggest that targeted sequencing of ctDNA across a panel of genes can reliably detect tumor sample mutations de novo without any a priori information from the tumor biopsy. Further analyses on ctDNA from different time points of the patient's treatment will give more insight into the potential of liquid biopsies to follow up disease progression and response to treatment. Disclosure: All authors have declared no conflicts of interest.

Suppression of the xCT-CD44v antiporter system sensitizes triple-negative breast cancer cells to doxorubicin.

The xCT antiporter is known to be upregulated in 30% of triple-negative breast cancer (TNBC) cell lines. The xCT-CD44 variant (CD44v) system regulates the levels of reactive oxygen species (ROS) in cancer cells and promotes tumor growth. Here, the role of this antiporter system in relation to chemotherapy was evaluated. MDA-MB-231 and MDA-MB-436 cells were transfected with lentiviral vectors expressing short hairpin RNA against xCT or CD44v. Following doxorubicin treatment, cellular proliferation was monitored, ROS were measured, and intracellular levels of cysteine and glutathione (GSH) were determined using liquid chromatography-mass spectrometry. A TNBC orthotopic tumor model was used to evaluate the impact of xCT-CD44v inhibition on doxorubicin efficacy in vivo. Doxorubicin treatment of TNBC cells caused increased expression of xCT through upregulation of CD44v. Consequently, the intracellular uptake of cystine increased, enabling rapid synthesis of GSH, and neutralization of doxorubicin-induced ROS. Suppression of xCT or CD44v impaired the defense against drug-induced oxidative stress, thereby sensitizing cells to doxorubicin. The importance of the xCT-CD44v in supporting tumor growth during doxorubicin treatment was also demonstrated in an in vivo tumor model of TNBC. These findings suggest that the antiporter system could serve as a target for increasing the anticancer efficacy of conventional therapy in patients with TNBC.

Bidirectional and multi-user telerehabilitation system: clinical effect on balance, functional activity, and satisfaction in patients with chronic stroke living in long-term care facilities.

BackgroundThe application of internet technology for telerehabilitation in patients with stroke has developed rapidly.ObjectiveThe current study aimed to evaluate the effect of a bidirectional and multi-user telerehabilitation system on balance and satisfaction in patients with chronic stroke living in long-term care facilities (LTCFs).MethodThis pilot study used a multi-site, blocked randomization design. Twenty-four participants from three LTCFs were recruited, and the participants were randomly assigned into the telerehabilitation (Tele) and conventional therapy (Conv) groups within each LTCF. Tele group received telerehabilitation but the Conv group received conventional therapy with two persons in each group for three sessions per week and for four weeks. The outcome measures included Berg Balance Scale (BBS), Barthel Index (BI), and the telerehabilitation satisfaction of the participants.SettingA telerehabilitation system included “therapist end” in a laboratory, and the “client end” in LTCFs. The conventional therapy was conducted in LTCFs.ResultsTraining programs conducted for both the Tele and Conv groups showed significant effects within groups on the participant BBS as well as the total and self-care scores of BI. No significant difference between groups could be demonstrated. The satisfaction of participants between the Tele and the Conv groups also did not show significant difference.ConclusionsThis pilot study indicated that the multi-user telerehabilitation program is feasible for improving the balance and functional activity similar to conventional therapy in patients with chronic stroke living in LTCFs.

Efficacy of levosimendan vs.milrinone in decompensated heart failure patients

Objective To evaluate the short-term clinical efficacy and safety of administration of levosimendan or milrinone added to conventional therapy in patients with decompensated heart failure.Methods A total of 180 patients admitted due to heart failure [NYHA (New York Heart Association) class Ⅲ or Ⅳ] were randomly (random number) divided into control group,milrinone group and levosimendan group (n =60,each group).A continuous infusion of milrinone added to conventional therapy was administered for 72 hours in milrinone group,while administration of levosimendan for 24 hours in levosimendan group.The changes in left ventricular ejection fraction (LVEF),left ventricle end-diastolic diameter (LVDD) and B-type natriuretic peptide (BNP) plasma level were compared between before and after treatment,respectively,and comparisons of improvement in cardiac function (NYHA class) and hospital mortality were carried out among three groups.Patients were further followed up at 3 months after treatment.Results The LVEF in levosimendan group after treatment had significantly more increased than that in control group [(32.0±6.3)％ vs.(30.6 ±5.5)％,P =0.007].Compared BNP before treatment,the sums of BNP deducted were 444.0 (-74.0,1068.0) pg/mL,469.0 (141.5,1151.5) pg/mL and 936.5 (437.8,1566.8) pg/mL in control group,milrinone group and levosimendan group,respectively after treatment (all P ＜ 0.01).Moreover,the deduction in BNP was more dramatic in levosimendan group compared with control or milrinone group (t =3.256 or 2.665,P =0.004 or 0.026).After treatment for 5 days,the probability at least of achieving more effectively better improvement in NYHA class (cardiac function) in levosimendan group was 2.036 times that of control group (95％ CI:1.030-4.028,P =0.041).The incidence of combined end point events (death or readmission) in levosimendan group was significantly lower than that in milrinone group (50％ vs.70％,HR =0.573,95％ CI:0.358-0.917,P=0.020),while in hospital mortality,readmission or 3-month mortality incidence was similar among 3 groups (P ＞ 0.05).Conclusions The short-term clinical efficacy of levosimendan is superior to that of milrinone or conventional therapy in patients with decompensated heart failure. Key words: Heart failure; Levosimendan; Milrinone ; Treatment; Prognosis

Ciprofloxacin and probiotic Escherichia coli Nissle add-on treatment in active ulcerative colitis: A double-blind randomized placebo controlled clinical trial

Background and aimUlcerative colitis (UC) is a chronic inflammatory bowel disease. The probiotic bacterium Escherichia coli Nissle 1917 (EcN) has been used to maintain and induce clinical remission in UC. Our aim was to test the effect of Ciprofloxacin and/or orally administered EcN as add-on to conventional therapies in patients with active UC. Patients and methodsOur single center double-blinded randomized placebo controlled study included patients with a Colitis Activity Index (CAI) score of at least 6. Patients were randomized to Ciprofloxacin or placebo for 1week followed by EcN or placebo for 7weeks. All 4 treatments were given as add-on treatments. ResultsOne hundred subjects with active UC were recruited. In the per-protocol analysis we, surprisingly, found that in the group receiving placebo/EcN fewer patients, 54%, reached remission compared to the group receiving placebo/placebo, 89%, p<0.05. Among patients treated with Cipro/placebo and Cipro/EcN, 78% and 66% reached remission, respectively. Furthermore, the group receiving placebo/EcN had the largest number of withdrawals, 11 of 25 (44%), compared to 15 of 75 (20%) in any of the other groups, p<0.05. Indication of lack of mucosal healing was found in the group treated with placebo/Nissle, since only 4 (29%) of the 14 patients, who completed the study, reported no blood in stools at week 12 (p<0.02), compared to 63%, 67% and 65% in groups treated with Cipro/Nissle, Cipro/placebo and placebo/placebo, respectively. ConclusionsOur data suggest that there is no benefit in the use of E. coli Nissle as an add-on treatment to conventional therapies for active ulcerative colitis. Furthermore, treatment with E. coli Nissle without a previous antibiotic cure resulted in fewer patients reaching clinical remission.

Bioinformatics for precision medicine in oncology: principles and application to the SHIVA clinical trial.

Precision medicine (PM) requires the delivery of individually adapted medical care based on the genetic characteristics of each patient and his/her tumor. The last decade witnessed the development of high-throughput technologies such as microarrays and next-generation sequencing which paved the way to PM in the field of oncology. While the cost of these technologies decreases, we are facing an exponential increase in the amount of data produced. Our ability to use this information in daily practice relies strongly on the availability of an efficient bioinformatics system that assists in the translation of knowledge from the bench towards molecular targeting and diagnosis. Clinical trials and routine diagnoses constitute different approaches, both requiring a strong bioinformatics environment capable of (i) warranting the integration and the traceability of data, (ii) ensuring the correct processing and analyses of genomic data, and (iii) applying well-defined and reproducible procedures for workflow management and decision-making. To address the issues, a seamless information system was developed at Institut Curie which facilitates the data integration and tracks in real-time the processing of individual samples. Moreover, computational pipelines were developed to identify reliably genomic alterations and mutations from the molecular profiles of each patient. After a rigorous quality control, a meaningful report is delivered to the clinicians and biologists for the therapeutic decision. The complete bioinformatics environment and the key points of its implementation are presented in the context of the SHIVA clinical trial, a multicentric randomized phase II trial comparing targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer. The numerous challenges faced in practice during the setting up and the conduct of this trial are discussed as an illustration of PM application.

Brain-blood amino acid correlates following protein restriction in murine maple syrup urine disease.

BackgroundConventional therapy for patients with maple syrup urine disease (MSUD) entails restriction of protein intake to maintain acceptable levels of the branched chain amino acid, leucine (LEU), monitored in blood. However, no data exists on the correlation between brain and blood LEU with protein restriction, and whether correction in blood is reflected in brain.MethodsTo address this question, we fed intermediate MSUD mice diets of 19% (standard) and 6% protein, with collection of sera (SE), striata (STR), cerebellum (CE) and cortex (CTX) for quantitative amino acid analyses.ResultsLEU and valine (VAL) levels in all brain regions improved on average 28% when shifting from 19% to 6% protein, whereas the same improvements in SE were on average 60%. Isoleucine (ILE) in brain regions did not improve, while the SE level improved 24% with low-protein consumption. Blood-branched chain amino acids (LEU, ILE, and VAL in sera (SE)) were 362-434 μM, consistent with human values considered within control. Nonetheless, numerous amino acids in brain regions remained abnormal despite protein restriction, including glutamine (GLN), aspartate (ASP), glutamate (GLU), gamma-aminobutyric acid (GABA), asparagine (ASN), citrulline (CIT) and serine (SER). To assess the specificity of these anomalies, we piloted preliminary studies in hyperphenylalaninemic mice, modeling another large neutral aminoacidopathy. Employing an identical dietary regimen, we found remarkably consistent abnormalities in GLN, ASP, and GLU.ConclusionsOur results suggest that blood amino acid analysis may be a poor surrogate for assessing the outcomes of protein restriction in the large neutral amino acidopathies, and further indicate that chronic neurotransmitter disruptions (GLU, GABA, ASP) may contribute to long-term neurocognitive dysfunction in these disorders.

Comparison between effectiveness of Maitland Compression Technique with Medial Glide and Conventional Therapy in Patients with Patellofemoral Osteoarthritis

Objective : To compare the effectiveness of maitland compression technique with medial glide and conventional therapy in patients with patellofemoral osteoarthritis. Study Design : Experimental study design. Subjects : 30 patients between the age group 45 yrs to 65 yrs having dominant patellofemoral osteoarthritis were selected as per the inclusion and exclusion criterion. Procedure : Using random sampling method the 30 subjects were divided into 2 equal groups with 15 patients each. Both the groups were given conventional physical therapy as a baseline treatment. Along with conventional therapy the experimental group received Maitland Compression technique with medial glide . 3 series of 15 compressions per session for 5 days per week., whereas the control group received only the conventional physical therapy. The study was performed for 3 weeks.Evaluation was done before starting the treatment and then after 3 weeks. Outcomes scores were evaluated using KOOS Scale and VAS scale . Result : Subjects receiving Maitland Compression Technique with Medial Glide showed significant reductions in pain and other symptoms with an improvement in quality of life.(t of KOOS =10.52 ,t of VAS = 8.064 ). Conclusion : The results supported the efficacy of Maitland Compression Technique with Medial Glide for rehabilitating the patients with Patellofemoral Osteoarthritis .These changes are clinically significant.

Tolvaptan more improved pleural effusion compared with conventional therapy in patients hospitalized due to heart failure

Tolvaptan more improved pleural effusion compared with conventional therapy in patients hospitalized due to heart failure