The Pathology of Type II Modic Changes: Fat Deposition or Osteosclerosis? A Study Using CT Scan

Study Design. A retrospective cross-sectional study of type II Modic changes (MCs). Objective. To evaluate the CT values of type II MCs and determine their relationship with disc degeneration. Methods. 124 type II MCs from 66 patients' MRI and CT were included and analyzed. Disc degeneration adjacent to MCs was evaluated based on Pfirrmann classification. CT values of bone marrow area and endplate from MC regions, adjacent non-MC regions, and L1 vertebra were measured. CT value changes (ΔCT value) were defined as MCs' CT value minus non-MCs'. According to the types of variables, paired t-test, signed-rank test, two-way ANOVA, and Friedman test were used. Results. The CT value of MCs was significantly higher than that of non-MCs at both bone marrow area and endplate (P

https://ift.tt/2Jf527e

Cost Effectiveness of Pharmacological Treatments for Asthma: A Systematic Review

Abstract

Objective

The objective of this article was to summarize the findings of all the available studies on alternative pharmacological treatments for asthma and assess their methodological quality, as well as to identify the main drivers of the cost effectiveness of pharmacological treatments for the disease.

Methods

A systematic review of the literature in seven electronic databases was conducted in order to identify all the available health economic evidence on alternative pharmacological treatments for asthma published up to April 2017. The reporting quality of the included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.

Results

A total of 72 studies were included in the review, classified as follows: medications for acute asthma treatment (n = 5, 6.9%); inhaled corticosteroids (ICS) administered alone or in conjunction with long-acting β-agonists (LABA) or tiotropium for chronic asthma treatment (n = 38, 52.8%); direct comparisons between different combinations of ICS, ICS/LABA, leukotriene receptor antagonists (LTRA), and sodium cromoglycate for chronic asthma treatment (n = 14, 19.4%); and omalizumab for chronic asthma treatment (n = 15, 20.8%). ICS were reported to be cost effective when compared with LTRA for the management of persistent asthma. In patients with inadequately controlled asthma taking ICS, the addition of long-acting β-agonist (LABA) preparations has been demonstrated to be cost effective, especially when combinations of ICS/LABA containing formoterol are used for both maintenance and reliever therapy. In patients with uncontrolled severe persistent allergic asthma, omalizumab therapy could be cost effective in a carefully selected subgroup of patients with the more severe forms of the disease. The quality of reporting in the studies, according to the CHEERS checklist, was very uneven. The main cost-effectiveness drivers identified were the cost or rate of asthma exacerbations, the cost or rate of the use of asthma medications, the asthma mortality risk, and the rate of utilization of health services for asthma.

Conclusions

The present findings are in line with the pharmacological recommendations for stepwise management of asthma given in the most recent evidence-based clinical practice guidelines for the disease. The identified reporting quality of the available health economic evidence is useful for identifying aspects where there is room for improvement in future asthma cost-effectiveness studies.

https://ift.tt/2LVGS3A

Cancers, Vol. 10, Pages 178: p53 and the Viral Connection: Back into the Future ‡

Cancers, Vol. 10, Pages 178: p53 and the Viral Connection: Back into the Future ‡

Cancers doi: 10.3390/cancers10060178

Authors: Ronit Aloni-Grinstein Meital Charni-Natan Hilla Solomon Varda Rotter

The discovery of the tumor suppressor p53, through its interactions with proteins of tumor-promoting viruses, paved the way to the understanding of p53 roles in tumor virology. Over the years, accumulating data suggest that WTp53 is involved in the viral life cycle of non-tumor-promoting viruses as well. These include the influenza virus, smallpox and vaccinia viruses, the Zika virus, West Nile virus, Japanese encephalitis virus, Human Immunodeficiency Virus Type 1, Human herpes simplex virus-1, and more. Viruses have learned to manipulate WTp53 through different strategies to improve their replication and spreading in a stage-specific, bidirectional way. While some viruses require active WTp53 for efficient viral replication, others require reduction/inhibition of WTp53 activity. A better understanding of WTp53 functionality in viral life may offer new future clinical approaches, based on WTp53 manipulation, for viral infections.

https://ift.tt/2xLHO7E

Cancers, Vol. 10, Pages 179: Allogeneic Hematopoietic Cell Transplantation for Older Adults with Acute Myeloid Leukemia

Cancers, Vol. 10, Pages 179: Allogeneic Hematopoietic Cell Transplantation for Older Adults with Acute Myeloid Leukemia

Cancers doi: 10.3390/cancers10060179

Authors: Jodi J. Lipof Kah Poh Loh Kristen O'Dwyer Jane L. Liesveld

Acute myeloid leukemia (AML) is a disease that affects adults aged 65 years and above, and survival in this population is poor. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for these patients but is underutilized due to frequent comorbidities and perceived higher risk of treatment-related mortality and non-relapse mortality. Increasing data supports the utility of allo-HCT in fit older patients after intensive chemotherapy resulting in improvement of outcomes. With the development of reduced intensity and non-myeloablative conditioning regimens that are associated with lower rates of treatment-related toxicity and mortality, this has allowed more older patients with AML to receive allo-HCT. In this review, we provide some guidance on appropriate selection of older patients as transplant candidates, benefits and risks associated with allo-HCT, conditioning regimen choice, and stem cell transplant sources as they relate to the conduct of stem cell transplantation in older patients.

https://ift.tt/2LVeuOV

Fludarabine and rituximab with escalating doses of lenalidomide followed by lenalidomide/rituximab maintenance in previously untreated chronic lymphocytic leukaemia (CLL): the REVLIRIT CLL-5 AGMT phase I/II study

Abstract

Despite recent advances, chemoimmunotherapy remains a standard for fit previously untreated chronic lymphocytic leukaemia patients. Lenalidomide had activity in early monotherapy trials, but tumour lysis and flare proved major obstacles in its development. We combined lenalidomide in increasing doses with six cycles of fludarabine and rituximab (FR), followed by lenalidomide/rituximab maintenance. In 45 chemo-naive patients, included in this trial, individual tolerability of the combination was highly divergent and no systematic toxicity determining a maximum tolerated dose was found. Grade 3/4 neutropenia (71%) was high, but only 7% experienced grade 3 infections. No tumour lysis or flare > grade 2 was observed, but skin toxicity proved dose-limiting in nine patients (20%). Overall and complete response rates after induction were 89 and 44% by intention-to-treat, respectively. At a median follow-up of 78.7 months, median progression-free survival (PFS) was 60.3 months. Minimal residual disease and immunoglobulin variable region heavy chain mutation state predicted PFS and TP53 mutation most strongly predicted OS. Baseline clinical factors did not predict tolerance to the immunomodulatory drug lenalidomide, but pretreatment immunophenotypes of T cells showed exhausted memory CD4 cells to predict early dose-limiting non-haematologic events. Overall, combining lenalidomide with FR was feasible and effective, but individual changes in the immune system seemed associated with limiting side effects. clinicaltrials.gov (NCT00738829) and EU Clinical Trials Register (www.clinicaltrialsregister.eu, 2008-001430-27)

https://ift.tt/2JrTJMh

Oxidation of 1-N2-etheno-2′-deoxyguanosine by singlet molecular oxygen results in 2′-deoxyguanosine: a pathway to remove exocyclic DNA damage?

Authors: Martinez, Glaucia Regina / Brum, Hulyana / Sassaki, Guilherme Lanzi / de Souza, Lauro Mera / Loureiro, Ana Paula de Melo / de Medeiros, Marisa Helena Gennari / Di Mascio, Paolo


https://ift.tt/2J7iLNz

Frontmatter

https://ift.tt/2rp4OTq