Effect of Display Resolution on Time to Diagnosis with Virtual Pathology Slides in a Systematic Search Task

Performing diagnoses using virtual slides can take pathologists significantly longer than with glass slides, presenting a significant barrier to the use of virtual slides in routine practice. Given the benefits in pathology workflow efficiency and safety that virtual slides promise, it is important to understand reasons for this difference and identify opportunities for improvement. The effect of display resolution on time to diagnosis with virtual slides has not previously been explored. The aim of this study was to assess the effect of display resolution on time to diagnosis with virtual slides. Nine pathologists participated in a counterbalanced crossover study, viewing axillary lymph node slides on a microscope, a 23-in 2.3-megapixel single-screen display and a three-screen 11-megapixel display consisting of three 27-in displays. Time to diagnosis and time to first target were faster on the microscope than on the single and three-screen displays. There was no significant difference between the microscope and the three-screen display in time to first target, while the time taken on the single-screen display was significantly higher than that on the microscope. The results suggest that a digital pathology workstation with an increased number of pixels may make it easier to identify where cancer is located in the initial slide overview, enabling quick location of diagnostically relevant regions of interest. However, when a comprehensive, detailed search of a slide has to be made, increased resolution may not offer any additional benefit.     

Separation of lymphoid and myeloid blasts in the mixed blast crisis of chronic myelogenous leukemia: no evidence for Ig gene rearrangement in CALLA-positive blasts

Recent studies suggest that lymphoid blast crisis cells of chronic myelogenous leukemia (CML) expressing the common acute lymphoblastic leukemia antigen (CALLA) are B precursor cells, based on the demonstration of immunoglobulin (Ig) gene rearrangement similar to common acute lymphocytic leukemia. There is little evidence to suggest whether the cells with similar lymphoid characteristics in the mixed blast crisis of CML are also committed to B cell lineage. A patient in "mixed" blast crisis of CML was studied. On the basis of morphology, cytochemistry, and immunological studies, the blasts were classified as having either lymphoid or myeloid characteristics. A proportion of the leukemic blasts expressed CALLA, whereas others expressed My7 antigen. In order to characterize both populations of cell further, CALLA+ blasts and My7+ (myeloid) blasts were isolated by fluorescence-activated cell sorting. The My7+ cells were highly proliferative in cell culture blast colony assays, retained the Ph1 chromosome, and were indistinguishable from acute myelogenous leukemia blasts. The CALLA+ cells were also Ph1-chromosome positive, but in contrast, were poorly proliferative in vitro. Of particular note was their retention of germline configuration of Ig genes, thus distinguishing them from blasts in the lymphoid crisis of CML. We conclude that the lymphoid component in mixed blast crisis may represent a stage of differentiation prior to commitment to B lineage.     

Efficacy of a nicotine lozenge for smoking cessation

BACKGROUND: Since nicotine gum was introduced in the 1980s, nicotine replacement therapy has become the most widely used pharmacological smoking cessation treatment. Some smokers prefer acute oral forms, but many smokers reject chewing gum. We tested the safety and efficacy of a new nicotine polacrilex lozenge for smoking cessation. METHODS: Double-blind, placebo-controlled, randomized clinical trial with parallel arms testing 2- and 4-mg nicotine lozenges. Smokers (n = 1818) were assigned to a lozenge dose on the basis of nicotine dependence, assessed by time to the first cigarette of the day. Low-dependence smokers were randomized to receive the 2-mg nicotine (n = 459) or placebo (n = 458) lozenge; high-dependence smokers, the 4-mg nicotine (n = 450) or placebo (n = 451) lozenge. We assessed abstinence at 6, 12, 24, and 52 weeks and analyzed craving and withdrawal symptoms. RESULTS: Treatment with the nicotine lozenge resulted in significantly greater 28-day abstinence at 6 weeks, for the 2-mg (46.0% vs. 29.7%; odds ratio [OR], 2.10; 95% confidence interval [CI], 1.59-2.79; P<.001) and the 4-mg (48.7% vs. 20.8%; OR, 3.69; 95% CI, 2.74-4.96; P<.001) lozenges, compared with placebo. Significant treatment effects were maintained for a full year. Smokers who used more lozenges achieved significantly better treatment effects. Use of the active lozenge also resulted in reduced craving and withdrawal. Most adverse events were moderate and resembled those seen with nicotine gum. CONCLUSION: The nicotine lozenge is a safe and effective new treatment for smoking cessation in low- and high-dependence smokers.     

Rapid size dependent deletion of foreign gene sequences inserted into attenuated HIV-1 upon infection in vivo: implications for vaccine development

Live attenuated HIV vaccines offer a means to introduce exogenous sequences into the viral genome to target the virus elimination in vivo. Foreign genes inserted into the nef region of HIV-1 NL4-3 were found to be rapidly deleted following virus infection and/or replication, in a size dependent manner, in the human fetal Thymus/Liver implants of severe combined immunodeficient mouse (SCID-hu) model. When the murine heat stable antigen (HSA) of 283 bp was substituted into HIV-1 nef region, the viral loads in vivo were comparable to the negative control nef attenuated HIV-1, and the reporter HSA gene was not deleted upon infection. However, the murine Thy1.2 gene (505 bp) substituted into the nef attenuated HIV-1, upon infection and replication, deleted 441 bp in vitro and 437 bp in vivo, of the inserted Thy1.2 gene. When the enhanced green fluorescence protein (eGFP) gene (720 bp) was substituted for nef, virus replication was aborted in vivo in the Thy/Liv implants, as seen by the background levels of viral loads, comparable to mock infected implants, and the eGFP gene was deleted. When the herpes simplex virus thymidine kinase gene, HSV-TK (1.15 kbp), or HSA gene, was substituted into the viral vpr gene, TK but not HSA gene was deleted, upon infection in vitro. Moreover, NL-TKI reporter virus with both intact nef and vpr genes shows deletion of TK gene both in vitro and in vivo. Excision of foreign genes occurred within the exogenous segments but not in the viral own regions. These results suggest that larger "suicide" genes introduced via HIV-1 can be deleted upon infection. However, smaller size nucleotide sequences or genes (approximately 300 bp) inserted in place of viral nef or vpr gene may be used to target the virus or its components, for attack and elimination in vivo, and thus have implications for the development of live attenuated HIV vaccines.     

Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia

Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial.     

The immediate effect of osteopathic cervical spine mobilization on median nerve mechanosensitivity: A triple-blind,randomized, placebo-controlled trial

Background

Neurodynamics is a clinical medium for testing the mechanical sensitivity of peripheral nerves which innervate the tissues of both the upper and lower limb. Currently, there is paucity in the literature of neurodynamic testing in osteopathic research, and where there is research, these are often methodologically flawed, without the appropriate comparators, blinding and reliability testing.

Cardiac rehabilitation and its effects on cognition in patients with coronary artery disease and heart failure

Introduction: Cardiac rehabilitation program is an evidence-based intervention and established model of exercise delivery following myocardial infarction and heart failure. Although it forms an important part of recovery and helps to prevent future events and complications, there has been little focus on its potential cognitive benefits.

Areas covered: Coronary artery disease and heart failure are common heart problems associated with significant morbidity and mortality, and cognitive decline is commonly seen in affected individuals. Cognitive impairment may influence patient self-management by reducing medication adherence, rendering patients unable to make lifestyle modifications and causing missed healthcare visits. Cognitive assessment in cardiac rehabilitation as an outcome measure has the potential to improve clinical, functional and behavioral domains as well as help to reduce gaps in the quality of care in these patients.

Expert commentary: Limited evidence at present has shown that cardiac rehabilitation and exercise has potential in preventing cognitive decline. Cardiac prehabilitation, a rehabilitation-like program delivered before cardiac surgery, may also play a role in preventing postoperative cognitive dysfunction, but needs future research studies to support it.