Podcasts about background patients

J Am Coll Cardiol 1995;26:57-65.Background Patients with diabetes have higher short- and long-term rates of mortality following acute myocardial infarction (AMI). Possible explanations for this include increased fatty acid metabolism, compromising glycolysis in ischemic and nonischemic areas as well as impairment of platelet and fibrinolytic function. This led to the theory that both processes could be improved with insulin infusion. Small studies at the time provided conflicting results. The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) trial sought to test the hypothesis that rapid improvement of metabolic control in diabetic patients with AMI by means of insulin-glucose infusion would decrease early mortality and that continued good metabolic control would improve subsequent prognosis.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Patients admitted to the CCUs of 19 Swedish hospitals with suspected AMI within the preceding 24 hours with a blood glucose level >11 mmol/l (198 mg/dl) with or without a previous history of diabetes mellitus. Exclusion criteria included inability to participate for reasons of health, refusal to give consent, residence outside the catchment area or enrollment in other studies.Baseline characteristics There were 1,240 patients who met inclusion criteria and 50% were excluded, mainly due to inability or unwillingness to participate. Compared to those enrolled, excluded patients were older (72 years of age) and more were women. The majority of those enrolled were men (62%) at an average age of 68 years. Nearly 40% had a history of previous MI and 22% had congestive heart failure. The mean time from the onset of symptoms to randomization was 13 hours. More than 80% of patients were non-insulin dependent. The average HbA1c at randomization was 8% and the blood glucose was 279 mg/dl.Procedures Patients randomized to insulin therapy were started on an insulin-glucose infusion at 30 ml/h and blood glucose was checked after 1 hour. The infusion rate was adjusted according to protocol. The infusion was continued until stable normoglycemia was attained for ≥24 hours. Subcutaneous administration of insulin was given immediately after cessation of the infusion, according to a multidose regimen, with the aim of maintaining normoglycemia. Serum potassium was measured immediately before the infusion and then after 6, 12, and 24 hr and was checked immediately in patients who developed any kind of clinically significant arrhythmia. Control patients were treated according to standard coronary care unit practice and did not receive insulin unless it was deemed clinically indicated.Endpoints The primary endpoint was all-cause mortality at 3 months. The investigators hypothesized that the insulin-glucose infusion followed by multidose subcutaneous insulin for 3 months would reduce the mortality rate by 30%, from a 35% mortality rate in the control group (35/100 to 24.5/100). Based on that assumption, a sample size of 600 was needed to demonstrate the expected mortality reduction with a 5% significance level and power of 80%.Results 620 patients were randomized, 306 to the intervention group and 314 to the control group. The blood glucose level was significantly lower in the insulin group 24 hours after randomization (173 mg/dl vs 211 mg/dl; p

Background: Patients diagnosed for a serous ovarian borderline tumor (s-BOT) typically present with an excellent clinical outcome. However there have been controversies concerning the prognostic impact of so-called implants, an extra ovarian spread occurring alongside the s-BOT in certain cases. It remains obscure whether these implants actually resemble metastasis owning the same genetic pattern as the ovarian primary or whether they develop independently. Methods: The current study, in the aim of further clarifying the genetic origin of implants, assessed BRAF/KRAS hot spot mutations and the p53/p16(INK4a) immunophenotype of s-BOTs and corresponding implants (n = 49) of 15 patients by pyro-sequencing and immunostaining, respectively. Results: A significant proportion of both s-BOTs and implants showed KRAS or BRAF mutation and though p16(INK4a) was found to be abundantly expressed, p53 immunoreactivity was rather low. When genotypes of BRAF/KRAS mutated s-BOTs and corresponding implants were compared no patient presented with a fully matching mutation profile of s-BOTs and all corresponding implants. Conclusions: The current study reveals genetic heterogeneity of s-BOTs and implants, as none of the markers examined showed constant reciprocity. Hence, our findings may assist to explain the different clinical presentation of s-BOTs and implants and might encourage to applying more individualized follow up protocols.

Background: Patients with B cell malignancies refractory to allogeneic stem cell transplantation (SCT) can be treated by subsequent immunotherapy with donor lymphocyte infusions (DLI). But unlike myeloid leukemia, B cell leukemia and lymphoma are less sensitive to allogeneic adoptive immunotherapy. Moreover, the beneficial graft-versus-lymphoma (GVL) effect may be associated with moderate to severe graft-versus-host disease (GVHD). Thus, novel therapeutic approaches augmenting the anti-tumor efficacy of DLI and dissociating the GVL effect from GVHD are needed. The anti-CD20 x anti-CD3 trifunctional bispecific antibody (trAb) FBTA05 may improve the targeting of tumor cells by redirecting immune allogeneic effector cells while reducing the risk of undesirable reactivity against normal host cells. Hence, FBTA05 may maximize GVL effects by simultaneously decreasing the incidence and severity of GVHD. Methods/Design: Based on this underlying treatment concept and on promising data taken from preclinical results and a small pilot study, an open-label, non-randomized, uncontrolled, dose-escalating phase I/II-study is conducted to evaluate safety and preliminary efficacy of the investigational antibody FBTA05 in combination with DLI for patients suffering from rituximab-and/or alemtuzumab-refractory, CD20-positive low-or high-grade lymphoma after allogeneic SCT. During the first trial phase with emphasis on dose escalation a maximum of 24 patients distributed into 4 cohorts will be enrolled. For the evaluation of preliminary efficacy data a maximum of 12 patients (6 patients with low-grade lymphoma and/or Chronic Lymphocytic Leukemia (CLL) / 6 patients with high-grade or aggressive lymphoma) will attend the second phase of this clinical trial. Discussion: Promising data (e. g. induction of cellular immunity; GVL predominance over GVHD; achievement of partial or complete responses; prolongation of time-to-progression) obtained from this phase I/II trial would represent the first milestone in the clinical evaluation of a novel immunotherapeutic concept for treatment-resistant low- and high-grade lymphoma and NHL patients in relapse.

Background: Patients with nonallergic rhinitis with eosinophilia syndrome (NARES) show typical symptoms of persistent allergic rhinitis (PAR). The aim of the present study was to compare nasal cytokine patterns between NARES and PAR. Methods: Nasal secretions of 31 patients suffering from NARES, 20 patients with PAR to house dust mite and 21 healthy controls were collected using the cotton wool method and analyzed for interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 beta (MIP-1 beta) by Bio-Plex Cytokine Assay as well as eosinophil cationic protein (ECP) and tryptase by UniCAP-FEIA. Results: NARES and PAR presented elevated levels of tryptase, while ECP was markedly increased solely in NARES compared to both the controls and PAR. Elevated levels of IL-1 beta, IL-17, IFN-gamma, TNF-alpha and MCP-1 were found in NARES compared to the controls as well as PAR. MIP-1 beta was elevated in NARES and PAR, while IL-4, IL-6 and G-CSF showed increased levels in NARES, and IL-5 was elevated in PAR only. Conclusions: In patients with NARES and PAR, eosinophils and mast cells appear to be the pivotal cells of inflammation, reflected by high levels of tryptase and ECP as well as IL-5 and GM-CSF as factors for eosinophil migration and survival. The elevated levels of proinflammatory cytokines in NARES may indicate the chronic, self-perpetuating process of inflammation in NARES which seems to be more pronounced than in PAR. IL-17 might be a factor for neutrophilic infiltration or be responsible for remodeling processes in NARES. Copyright (C) 2012 S. Karger AG, Basel

Background: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. Patients and Methods: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. Results: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombo-cytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. Conclusion: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2). Copyright (c) 2008 S. Karger AG, Basel.