Promising New Treatment For Patients Research Articles

Experience of using homeopathic ointment in the treatment of patients with anal itching

Introduction. Anal contact or conduction in the anal canal and rectum is a common condition in the coloproctological field, occurring in 5% of the population that affects this country. Treatment consists of hygiene and the use of topical steroids, antibacterial and antifungal agents. No generally accepted attitude towards a private person has been developed.Aim. To study the effectiveness of using homeopathic ointment in the treatment of patients with anal itching.Material and methods. A prospective comparative randomized study was conducted in a specialized advisory center of the Clinics of Samara State Medical University. The study included 96 patients with anal itching without fungal infection of the perianal skin and concomitant purulent pathology. In the main group (n = 46), treatment was carried out using homeopathic ointment in the perianal area 2–3 times a day for 14 days. In the control group (n = 50), treatment was carried out with topical steroid ointments 2–3 times a day for 14 days.Results and discussion. From the data obtained on the use of homeopathic ointment, it follows that it is not inferior in effectiveness to topical steroid ointments in reducing symptoms of the disease (Student’s t-test = 0.35; p > 0.05 and Student’s t-test = 0.28; p > 0.05), and by the number of relapses (χ2 = 0.535; p > 0.05).Conclusion. The use of homeopathic ointment for topical application appears to be a promising new treatment for patients with anal itching and is as effective as topical steroid ointments.

Middle meningeal artery embolization of septated chronic subdural hematomas.

Middle meningeal artery embolization (MMAE) has emerged as a promising new treatment for patients with chronic subdural hematomas (cSDH). Its efficacy, however, upon the subtype with a high rate of recurrence-septated cSDH-remains undetermined. From our prospective registry of patients with cSDH treated with MMAE, we classified patients based on the presence or absence of septations. The primary outcome was the rate of recurrence of cSDH. Secondary outcomes included a reduction in cSDH thickness, midline shift, and rate of reoperation. Among 80 patients with 99 cSDHs, the median age was 68 years (IQR 59-77) with 20% females. Twenty-eight cSDHs (35%) had septations identified on imaging. Surgical evacuation with burr holes was performed in 45% and craniotomy in 18.8%. Baseline characteristics between no-septations (no-SEP) and septations (SEP) groups were similar except for median age (SEP vs no-SEP, 72.5 vs. 65.5, p = 0.016). The recurrence rate was lower in the SEP group (SEP vs. no-SEP, 3 vs. 16.7%, p = 0.017) with higher odds of response from MMAE for septated lesions even when controlling for evacuation strategy and antithrombotic use (OR = 0.06, CI [0.006-0.536], p = 0.012). MMAE resulted in higher mean absolute thickness reduction (SEP vs. no-SEP, -8.2 vs. -4.8 mm, p = 0.016) with a similar midline shift change. The rate of reoperation did not differ (6.2 vs. 3.1%, p = 0.65). MMAE appears to be equal to potentially more effective in preventing the recurrence of cSDH in septated lesions. These findings may aid in patient selection.

Epidermal growth factor-like 7 is a novel therapeutic target in mantle cell lymphoma

Mantle cell lymphoma (MCL) is an aggressive, noncurative, mature B-cell lymphoma, with a median overall survival of 6-7 years. This underlines a need for effective therapeutic strategies to treat MCL better. Epidermal growth factor-like 7 (EGFL7) is a protein secreted by endothelial cells shown to play a critical role in angiogenesis. Our laboratory has previously demonstrated that EGFL7 supports the growth of leukemic blasts in patients with acute myeloid leukemia (AML); however, its role in MCL has not been investigated yet. In this study, we report that EGFL7 messenger RNA (mRNA) is increased in the cells of patients with MCL compared with cells from healthy controls, and patients with high EGFL7 are associated with lower overall survival rates. Furthermore, EGFL7 is increased in the plasma of patients with MCL compared with the plasma from healthy controls. We further show that EGFL7 binds to epidermal growth factor receptor (EGFR) and activates AKT signaling pathway in MCL cells and that blocking EGFL7 in MCL in patient and cell lines decreases cell growth and increases apoptosis in vitro. Finally, anti-EGFL7 treatment inhibits tumor size and prolongs survival in a mouse model of MCL. In conclusion, our study reveals a role for EGFL7 in MCL cell proliferation and highlights EGFL7 inhibition as a promising new treatment for patients with MCL.

CANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders – Results of a prospective, multicenter, randomized, double-blind, placebo controlled, phase IIIb superiority study

Preliminary data suggest that cannabis-based medicines might be a promising new treatment for patients with Tourette syndrome (TS)/chronic tic disorders (CTD) resulting in an improvement of tics, comorbidities, and quality of life. This randomized, multicenter, placebo-controlled, phase IIIb study aimed to examine efficacy and safety of the cannabis extract nabiximols in adults with TS/CTD (n = 97, randomized 2:1 to nabiximols:placebo). The primary efficacy endpoint was defined as a tic reduction of ≥ 25% according to the Total Tic Score of the Yale Global Tic Severity Scale after 13 weeks of treatment. Although a much larger number of patients in the nabiximols compared to the placebo group (14/64 (21·9%) vs. 3/33 (9·1%)) met the responder criterion, superiority of nabiximols could formally not be demonstrated. In secondary analyses, substantial trends for improvements of tics, depression, and quality of life were observed. Additionally exploratory subgroup analyses revealed an improvement of tics in particular in males, patients with more severe tics, and patients with comorbid attention deficit/hyperactivity disorder suggesting that these subgroups may benefit better from treatment with cannabis-based medication. There were no relevant safety issues. Our data further support the role of cannabinoids in the treatment of patients with chronic tic disorders.

Hematologic Responses and Cardiac Organ Improvement in Patients with Heavily Pretreated Cardiac Immunoglobulin Light Chain (AL) Amyloidosis Receiving Daratumumab

▪Introduction: In immunoglobulin light chain (AL) amyloidosis, cardiac involvement is the primary cause of premature death. Light chain suppression, with therapies targeting the underlying plasma cell clone producing amyloidogenic free light chains, has been difficult to achieve in a relapsed/refractory disease setting. Hematologic response is required to obtain a cardiac organ response, which is predictive of survival and is an important, if not primary, therapeutic goal. We have previously reported rapid and favorable hematologic response rates with the monoclonal anti-CD38 antibody daratumumab in a cohort of heavily pretreated relapsed/refractory AL patients. The aim of this study was to evaluate cardiac organ response following light chain suppressive therapy with daratumumab in patients with relapsed/refractory AL.Materials & Methods:Consecutive patients with biopsy-proven AL and cardiac involvement, followed at the Stanford University Amyloid Center, who received daratumumab were retrospectively evaluated for hematologic and cardiac organ response. In accordance with IRB approval, demographic and clinical information was obtained from medical records. Hematologic and cardiac organ response criteria were defined per consensus guidelines in AL (Comenzo et al, Leukemia 2012).Results: Twelve patients with previously treated AL with cardiac involvement received a median of 12 doses (range 5-18) of single agent daratumumab. The antibody was given intravenously at 16 mg/kg weekly for 8 weeks, followed by every other week infusion for 8 doses and then monthly infusions. The median patient age was 67 and 75% of patients were male. The median number of lines of prior therapy was 3; notably, none of the patients had previously achieved a hematologic complete response to prior therapy including high dose melphalan and autologous stem cell transplant in 2 patients. Ten of 12 patients (83%) achieved a partial hematologic response or better with daratumumab (3 complete responses (25%), 3 very good partial responses (25%), and 4 partial responses (33%)). Median NT-pro BNP was 2516 pg/mL prior to daratumumab therapy. Of all 12 treated patients, seven patients were evaluable for cardiac response based on baseline NT-proBNP >650 ng/L. Of these, 3 patients achieved a cardiac organ response by NT-pro BNP criteria (>30% reduction and >300 ng/l decrease). Two patients had cardiac progression by NT-pro BNP criteria (no echocardiographic progression was observed) despite hematologic response with one patient discontinuing therapy to pursue hospice care. Infusion reactions were observed in 8/12 patients with only 1 grade 3 infusion reaction.Conclusions: Daratumumab yielded rapid and significant hematologic responses in our retrospective single institution cohort of heavily pretreated AL patients. At a median daratumumab duration of therapy of only 4 months, evidence of cardiac organ improvement was observed. Daratumumab represents a well tolerated and exceptionally promising new treatment for patients with AL amyloidosis; larger prospective trials to evaluate this agent are warranted. DisclosuresLiedtke:Takeda: Consultancy, Research Funding; Prothena: Consultancy, Research Funding; Celgene: Research Funding; Amgen: Consultancy, Research Funding; Novartis: Research Funding; Gilead: Research Funding; Pfizer: Consultancy, Research Funding.

Lenvatinib - A multikinase inhibitor for radioiodine-refractory differentiated thyroid cancer.

Lenvatinib, an oral multikinase inhibitor, was approved by the US Food and Drug Administration in February 2015. In a pivotal phase III study of 392 patients with progressive radioiodine-refractory thyroid cancer, the overall response rate of patients receiving lenvatinib was 64.8%, with complete response in four patients. The median progression-free survival was 18.3 months in the lenvatinib arm versus 3.6 months in patients receiving placebo. Median overall survival was not reached in either arm. Lenvatinib is a promising new treatment for patients with radioiodine (iodine-131)-refractory differentiated thyroid cancer.

Intratumoral Injection of TLR4 Agonist (G100) Leads to Tumor Regression of A20 Lymphoma and Induces Abscopal Responses

Background: Toll-like receptors (TLRs) are components of the innate immune system that recognize pathogen-associated molecular patterns present on bacterial, fungal, or viral pathogens. Glucopyranosyl lipid A (GLA) is a synthetic TLR4 agonist that activates dendritic cells (DC) and enhances antigen-specific Th1 cell responses.Scientific question: Can an oil-in-water emulsion of GLA (G100) induce an anti-tumor effect due to modulation of the tumor microenvironment?Results: In our A20 murine lymphoma tumor model, intratumoral (i.t) administration of G100 resulted in tumor regression in approximately 50% of the mice in a dose dependent manner with an optimal dose of 10-20 μg/mouse. Surviving mice remained tumor-free at three months post G100 treatment and were resistant to a secondary tumor challenge with A20 cells, but not with CT26 colon cancer cells or 4T1 breast cancer cells. The effect was CD8+ T cell mediated as CD8+ depletion resulted in a significant loss of the effect. To examine the potential systemic effect of G100 i.t. treatment, Balb/c mice were implanted bilaterally with A20 tumors. Injection of G100 into the ipsilateral tumor three times a week resulted in an abscopal effect on the contralaterally implanted, untreated tumor, as evidenced by reduced tumor growth. Furthermore, the potential synergy between G100 and immunomodulatory antibodies was investigated: mice with bilateral A20 tumors received intratumoral G100 alone, systemic anti-PD-1 mAb alone, or a combination of both agents. Mice receiving combination therapy showed best overall survival, as measured by regression or reduced growth of both treated and untreated tumors. In addition, injection of low doses of anti-CTLA4 and anti-OX40 mAbs together with G100, directly into the tumor, was able to cure mice with established disease.Significance: Immunomodulatory antibodies are currently under clinical development for cancer treatment. We show here that combining these antibodies with a TLR4 agonist is sufficient to trigger a systemic anti-tumor response able to eradicate tumor at a distant site. This anti-tumor immune response was long lasting, specific and required CD8+ T cells as the effect was lost in CD8+ T cell depleted mice.Impact: We recently published positive results of intra-tumoral CpG (TLR9 agonist) in combination with immunomodulatory antibodies (Marabelle, Levy, et al. JCI, 2013). Both anti-CTLA4 and anti-PD1 antibodies have been FDA approved, and anti-PD-L1 and anti-OX40 antibodies are currently in advanced clinical trials. Our results suggest that G100 alone or in combination with immunomodulatory mAbs may be a promising new treatment for patients with injectable sites of lymphoma. Clinical studies investigating intratumoral G100 are underway. DisclosuresOff Label Use: G100- a TLR4 agonist. Lu:Immune Design: Employment. Hewitt:Immune Design: Employment. Hsu:Immune Design: Employment. Meulen:Immune Design: Employment. Levy:Immune Design: Research Funding; Dynavax: Research Funding.

Cognitive-behavioural therapy augments the effects of deep brain stimulation in obsessive-compulsive disorder.

Deep brain stimulation (DBS) is a promising new treatment for patients with treatment-refractory obsessive-compulsive disorder (OCD). However, since most DBS patients only show a partial response, the treatment still needs to be improved. In this study we hypothesized that cognitive-behavioural therapy (CBT) could optimize the post-operative management in DBS and we evaluated the efficacy of CBT as augmentation to DBS targeted at the nucleus accumbens. A total of 16 patients with treatment-refractory OCD were treated with DBS targeted at the nucleus accumbens. After stabilization of decline in OCD symptoms, a standardized 24-week CBT treatment programme was added to DBS in an open-phase trial of 8 months. Changes in obsessive-compulsive, anxiety and depressive symptoms were evaluated using the Yale-Brown Obsessive Compulsive Scale, Hamilton Anxiety Scale and Hamilton Rating Scale for Depression. Following the addition of CBT to DBS, a significant decrease in obsessive-compulsive symptoms was observed, but not in anxiety and depressive symptoms. In a subsequent double-blind phase, in which stimulation was discontinued, OCD symptoms returned to baseline (relapse) and anxiety and depressive symptoms worsened (rebound) compared with baseline. The results of this explorative study suggest that a combined treatment of accumbens DBS and CBT may be optimal for improving obsessive-compulsive symptoms in treatment-refractory OCD. However, a subsequent randomized controlled trial is necessary to draw firm conclusions. It seems that DBS results in affective changes that may be required to enable response prevention in CBT. This may indicate that DBS and CBT act as two complementary treatments.

Pudendal Nerve Stimulation for Bowel Dysfunction in Complete Cauda Equina Syndrome

Pudendal nerve stimulation (PNS) aims to maximize afferent or efferent stimulation from the sacral plexus. We hypothesized this may be a promising new treatment for patients with bowel dysfunction in complete cauda equina syndrome (CES). Thirteen patients with complete CES [8 constipation predominant (group 1) and 5 incontinence predominant (group 2)] had a 3-week trial of PNS. Patients who showed a 50% or more improvement in symptoms during the trial phase proceeded to permanent neurostimulator implantation. Five (63%) of the 8 patients in group 1 showed a 50% or more improvement in bowel symptoms during the trial phase and were permanently implanted. The mean Cleveland Clinic constipation score, sense of incomplete evacuation (%), and straining during defecation (%) improved from 17 ± 3.2 to 10 ± 4.5, 94 ± 18% to 30 ± 35%, and 81 ± 23% to 44 ± 38%, respectively. All 5 patients in group 2 showed a 50% or more reduction in incontinent episodes during the trial phase. The mean St Mark's score, ability to defer defecation, and the number of incontinent episodes per week improved from 18 ± 1.0 to 3.8 ± 2.5, 2.2 ± 1.8 to 11 ± 5.5 minutes, and 9.4 ± 10.7 to 0.4 ± 0.5 episodes, respectively, per week. During a median follow-up of 12 (10-22) months of permanent implantation, one patient lost efficacy at 6 months due to lead migration and another required removal and reimplantation of the neurostimulator due to wound infection. PNS is an effective treatment in the short term for bowel dysfunction in some patients with complete CES.

Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial

IntroductionTo evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed.MethodsThirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety.ResultsThere was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50 ± 27 to 108 ± 73 mL/minute (mean ± SEM) for the AP group; and from 40 ± 37 to 65 ± 30 mL/minute for placebo; P = 0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial.ConclusionsThe improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI.Trial Registrationwww.clinicaltrials.gov: NCTNCT00511186

Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients.

Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+ KLK4 + cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian cancer immunotherapy.

Azacitidine for treatment of patients with myelodysplastic syndromes (MDS): practical recommendations of the German MDS Study Group

Myelodysplastic syndromes (MDS) are a group of common bone marrow disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and a substantial risk of progression to acute myeloid leukemia (AML). For many years, the main treatment option for MDS was best supportive care which alleviates symptoms, but has no effect on the natural course of the disease. Recently, demethylating agents have become available as a promising new treatment for patients with MDS. In two randomized clinical trials, the demethylating agent azacitidine has demonstrated a reduced risk of transformation to AML, improvement of peripheral blood values, an improved quality of life, and a definite survival advantage compared to conventional care regimens for patients with International Prognostic Scoring System score of intermediate-2 or high-risk MDS. This review aims to provide practical recommendations for the use of azacitidine and the management of its side effects in patients with MDS, assuring safe administration and best efficacy of treatment.

Distinct effects of human glioblastoma immunoregulatory molecules programmed cell death ligand-1 (PDL-1) and indoleamine 2,3-dioxygenase (IDO) on tumour-specific T cell functions

Immunotherapy is a promising new treatment for patients suffering from glioma, in particular glioblastoma multiforme (GBM). However, tumour cells use different mechanisms to escape the immune responses induced by the treatment. As many other tumours, gliomas express or secrete several immunosuppressive molecules that regulate immune cell functions. In this study, we first analysed FasL, HLA-G, IDO, PDL-1 and TGF-β1, - β2 and -β3 expression by transcriptomic microarray analysis in a series of 20 GBM samples and found respectively 15%, 60%, 85%, 30%, 70%, 80% and 35% of positive specimens. mRNA expression was then confirmed in 10 GBM primary cell lines and 2 immortalised cell lines U251 and U87MG. Furthermore, the protein expression of PDL-1, IDO activity and TGF-β2 secretion were found on most of the untreated GBM primary cell lines. Remarkably, treatment with IFN-γ increased the PDL-1 cell surface expression and the IDO activity, but reduced the TGF-β2 secretion of GBM cell lines. We finally analysed the immunosuppressive effects of IDO, PDL-1 and TGF-β1-3 by measuring IFN-γ production and cell cytotoxicity activity of tumour antigen-specific T cells. PDL-1 partially affected the IFN-γ production of antigen-specific T cells in response to GBM primary cell lines, and IDO inhibited lymphocyte proliferation induced by lectins. None of these molecules directly affected the T cell cytotoxicity function. Due to the functional role of PDL-1 and IDO molecules expressed by GBM cells, one could expect that blocking these molecules in the immunotherapy strategies would reinforce the efficiency of these treatments of GBM patients.

Continuous Aortic Flow Augmentation in a Chronic Heart Failure Patient With Peripheral Arterial Disease

Continuous Aortic Flow Augmentation in a Chronic Heart Failure Patient With Peripheral Arterial Disease

Effect of tadalafil on blood flow, pain, and function in chronic cold Complex Regional Pain Syndrome: a randomized controlled trial

BackgroundThis double-blind, randomized, controlled trial investigated the effect of the phosphodiesterase-5 inhibitor tadalafil on the microcirculation in patients with cold Complex Regional Pain Syndrome (CRPS) in one lower extremity.MethodsTwenty-four patients received 20 mg tadalafil or placebo daily for 12 weeks. The patients also participated in a physical therapy program. The primary outcome measure was temperature difference between the CRPS side and the contralateral side, determined by measuring the skin temperature with videothermography. Secondary outcomes were: pain measured on a Visual Analogue Scale, muscle force measured with a MicroFet 2 dynamometer, and level of activity measured with an Activity Monitor (AM) and walking tests.ResultsAt the end of the study period, the temperature asymmetry was not significantly reduced in the tadalafil group compared with the placebo group, but there was a significant and clinically relevant reduction of pain in the tadalafil group. Muscle force improved in both treatment groups and the AM revealed small, non-significant improvements in time spent standing, walking, and the number of short walking periods.ConclusionTadalafil may be a promising new treatment for patients that have chronic cold CRPS due to endothelial dysfunction, and deserves further investigation.Trial RegistrationThe registration number in the Dutch Trial Register is ISRCTN60226869.

AZD6140: a promising new treatment for patients with acute coronary syndromes

AZD6140: a promising new treatment for patients with acute coronary syndromes

Pasireotide (SOM230): Development, mechanism of action and potential applications

Pasireotide (SOM230) is a multi-receptor ligand somatostatin analogue with high binding affinity for somatostatin receptor subtypes sst(1,2,3) and sst(5). Pasireotide potently suppresses GH, IGF-I and ACTH secretion, indicating potential efficacy in acromegaly and Cushing's disease. The prolonged inhibition of hormone secretion by pasireotide in animal models and expression of multiple sst receptors in carcinoid tumors suggests that pasireotide may have clinical advantages over octreotide in patients with carcinoid tumors. Direct and indirect antitumor activity has been observed in vitro with pasireotide, including sst receptor-mediated apoptosis and antiangiogenesis, suggesting a possible role for pasireotide in antineoplastic therapy. In summary, preclinical evidence, as well as preliminary results from clinical studies suggests that pasireotide is a promising new treatment for patients with symptoms of metastatic carcinoid tumors refractory or resistant to octreotide, de novo or persistent acromegaly, and that pasireotide has the potential to be the first directed medical therapy for Cushing's disease.

Antipneumococcal Activity of Ertapenem Compared with Gatifloxacin in a Temperature-Sensitive Murine Model of Acute Pneumonia

Fluoroquinolone-resistance among pneumococci is low; however the number of solates with a single ParC mutation has increased. Consequently, more potent agents are needed to minimize resistance selection. We investigated the efficacy of ertapenem versus gatifloxacin in a temperature-sensitive mouse model of pneumonia caused by a wildtype Streptococcus pneumoniae strain (A66) and an isogenic mutant with a ParC mutation (R222). Treatment started at 24 h and lasted for 5 days. Temperature was used to assess disease progression before and during treatment. Of mice infected with either strain and treated at an early stage of infection, 79-94% of those given ertapenem survived compared with 56-61% given gatifloxacin. If treated at a later stage, the results were similar for ertapenem (71-84%) but were considerably lower for gatifloxacin (17-33%). Ertapenem was as bactericidal as gatifloxacin against A66 (94-100% vs 92-100%) but was superior to gatifloxacin against R222 (95-100% vs 50-77%). Ertapenem is a promising new treatment for patients with pneumococcal pneumonia, including those at risk of infection with a fluoroquinolone-resistant strain.

Safety and feasibility of percutaneous autologous skeletal myoblast transplantation in the coil-infarcted swine myocardium

Introduction Autologous skeletal myoblast transplantation (ASMT) for myocardial regeneration is a promising new treatment for patients with congestive heart failure secondary to myocardial infarction (MI). However, non-surgical delivery could broaden the utility of this approach. The present study was designed to evaluate the safety and feasibility of transplanting autologous skeletal myoblast (ASM) via endovascular delivery into the infarcted swine myocardium. Methods Seven female Yorkshire swine successfully underwent induced left ventricular MI. ASM biopsies were obtained from the hind limb of each animal and myoblasts were expanded in vitro. In a pilot experiment, ASM were labeled with iridium and short-term retention and biodistribution was determined 2 h after ASM delivery via the MyoStar™ needle-injection catheter inserted through the femoral artery. At 30 days post-infarction, the remaining animals were divided into three groups containing 2 animals each for percutaneous catheter delivery into the infarcted zone: group 1 control animals were injected with media only, group 2 and 3 animals were injected with approximately 300 × 10 6 and 600 × 10 6 ASM, respectively. Sixty days post-transplantation, the swine hearts were harvested. Results During the 60-day period between transplantation and harvest, no adverse events were recorded, and continuous rhythm monitoring revealed no arrhythmias. In the small sampling size, myocardial function assessments revealed a trend toward improvement in the treatment groups with respect to ejection fraction, viability, and cardiac index. However, histology of treated swine hearts identified no skeletal muscle cells. Discussion Percutaneous ASMT into an infarcted swine myocardium is feasible and safe, and may contribute to overall improved heart function.

A phase I clinical trial of a BDCA-1+ blood dendritic cell preparation loaded with control and tumour-associated antigens, for immune therapy of metastatic refractory prostate cancer

2599 Background: In vitro loaded dendritic cells (DC) are a promising new treatment for patients with prostate cancer. Blood DC (BDC) preparations may be an attractive alternative to the more commonly used monocyte-derived DC (MoDC) in terms of performance, logistics, cost and regulatory issues. In preclinical studies, we have shown that CD1c+ BDC can be isolated from prostate cancer patients with equivalent numerical and functional integrity compared to healthy donors, justifying their use as a platform for immunotherapy. Methods: We have validated a procedure for the isolation of CD1c+ BDC by positive immunoselection using the CliniMACS system that is suitable for clinical use. BDC isolated from HLA-A*0201+ patients are pulsed with PSA-3, PSMA-2, PAP-5, and influenza matrix protein (FMP) peptides. Patients receive 3 i.d. or i.v. injections at monthly intervals. Results: We are currently investigating cell yields, purity and functionality of this cell preparation. Approximately 0.12% of mononuclear cells obtained by leukapheresis are recovered with greater than 80% purity. Conclusions: Our data shows that sufficient BDCA-1+ BDC can be isolated using this system for a vaccine regimen. A Phase I trial to establish safety and efficacy in prostate cancer patients is currently underway. No significant financial relationships to disclose.