scholarly journals High levels of periostin correlate with increased fracture rate, diffuse MRI pattern, abnormal bone remodeling and advanced disease stage in patients with newly diagnosed symptomatic multiple myeloma

2016 ◽  
Vol 6 (10) ◽  
pp. e482-e482 ◽  
Author(s):  
E Terpos ◽  
D Christoulas ◽  
E Kastritis ◽  
T Bagratuni ◽  
M Gavriatopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Remodeling ◽  
Advanced Disease ◽  
Disease Stage ◽  
Fracture Rate ◽  
Newly Diagnosed ◽  
Advanced Disease Stage

scholarly journals Socio-demographic, clinical and health facility-related predictors of delayed HIV diagnosis among patients newly diagnosed with HIV in Northwest Ethiopia: a multilevel analysis

2020 ◽  
Author(s):  
Nurilign Abebe Moges ◽  
Yemane Berhane ◽  
Joshua Odunayo AKINYEMI ◽  
Micheal A. Okunlola ◽  
Olubukola Adeponle Adesina
Keyword(s):  
Health Facility ◽  
Advanced Disease ◽  
Northwest Ethiopia ◽  
Disease Stage ◽  
Newly Diagnosed ◽  
Hiv Diagnosis ◽  
Factors Associated ◽  
Multilevel Logistic Regression Analysis ◽  
Advanced Disease Stage ◽  
Facility Level

Abstract Background Ethiopia recently implemented the ‘test and treat’ strategy for all HIV-infected individuals receiving a diagnosis at the health facility level. However, the impact of this policy in terms of timely HIV diagnosis and factors associated with it were not evaluated. Therefore, this study aimed to determine the magnitude and predictors of delayed HIV diagnosis among newly diagnosed people living with HIV in the northwest, Ethiopia. Methods In this cross-sectional study, a total of 759 newly diagnosed patients were recruited consecutively. The multistage sampling technique was employed to select health facilities and all newly diagnosed patients were included. Delayed HIV diagnosis was defined when there is an established AIDS-defining clinical condition (WHO clinical stage III or IV), irrespective of CD4 count. Data were entered into Epi-Data version 3.5 and exported to STATA version 14 for further analysis. Taking into account the nested structure of the data, multilevel logistic regression analysis has been employed. Four models containing variables of interest were fitted. Multivariate multilevel logistic regression analysis was performed to estimate the adjusted odds ratios (AOR) at a 95% confidence interval (CI). Results A one-fourth of newly diagnosed HIV patients diagnosed at advanced disease stage. After controlling for other individual and health facility level factors, factors associated with delayed HIV diagnosis were: Patients who had completed secondary school or higher (AOR = 2.08, 95% CI = 1.06, 4.08), patients who presented to health facilities with HIV symptoms (AOR = 5.87, 95% CI = 3.57, 9.62), being non-working functional status (AOR = 4.80, 95% CI = 2.58, 8.92) and HIV diagnosis at hospitals (AOR = 2.16, 95% CI = 1.08, 4.31). Conclusion The magnitude of delayed HIV diagnosis was improved. In addition to individual-level factors, it is important to address health facility-related factors to improve earlier HIV diagnosis. Here, we recommend using both clinical and laboratory characteristics of a patient particularly, baseline CD4 count and viral load to identify patients diagnosed with advanced disease stage. Moreover, public health interventions are important targeted on factors associated with delayed HIV diagnosis.

scholarly journals Loss of cIAP1 in Endothelial Cells Limits Metastatic Extravasation through Tumor-Derived Lymphotoxin Alpha

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 599
Author(s):  
Lazaros Vasilikos ◽  
Kay Hänggi ◽  
Lisanne M. Spilgies ◽  
Samanta Kisele ◽  
Stefanie Rufli ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Advanced Disease ◽  
Disease Stage ◽  
Stromal Compartment ◽  
Tumor Load ◽  
Smac Mimetics ◽  
Advanced Disease Stage ◽  
Lymphotoxin Alpha ◽  
Open Question

In this study, we determined whether Smac mimetics play a role in metastasis, specifically in circulation, tumor extravasation and growth in a metastatic site. Reports suggest inducing the degradation of IAPs through use of Smac mimetics, alters the ability of the tumor cell to metastasize. However, a role for the immune or stromal compartment in affecting the ability of tumor cells to metastasize upon loss of IAPs has not been defined. To address this open question, we utilized syngeneic tumor models in a late-stage model of metastasis. Loss of cIAP1 in the endothelial compartment, rather than depletion of cIAP2 or absence of cIAP1 in the hematopoietic compartment, caused reduction of tumor load in the lung. Our results underline the involvement of the endothelium in hindering tumor cell extravasation upon loss of cIAP1, in contrast to the immune compartment. Endothelial specific depletion of cIAP1 did not lead to cell death but resulted in an unresponsive endothelium barrier to permeability factors causing a decrease in tumor cell extravasation. Surprisingly, lymphotoxin alpha (LTA), and not TNF, secreted by the tumor cells, was critical for the extravasation. Using TCGA, we found high LTA mRNA expression correlated with decreased survival in kidney carcinoma and associated with advanced disease stage. Our data suggest that Smac mimetics, targeting cIAP1/2, reduce metastasis to the lung by inhibiting tumor cell extravasation.

Malignant mesothelioma: prognostic variables in a registry of 180 patients, the Dana-Farber Cancer Institute and Brigham and Women's Hospital experience over two decades, 1965-1985.

1988 ◽  
Vol 6 (1) ◽  
pp. 147-153 ◽  
Author(s):  
K Antman ◽  
R Shemin ◽  
L Ryan ◽  
K Klegar ◽  
R Osteen ◽  
...  
Keyword(s):  
Chest Pain ◽  
Advanced Disease ◽  
Performance Status ◽  
Randomized Study ◽  
Prolonged Survival ◽  
Disease Stage ◽  
Computer Search ◽  
Prognostic Variables ◽  
Dana Farber Cancer Institute ◽  
Advanced Disease Stage

All mesothelioma patients identified by a computer search of pathologic diagnoses at the Dana-Farber Cancer Institute (DFCI) between 1965 and 1985 were the subjects of this analysis. A total of 180 patients were identified, 136 with pleural and 37 with peritoneal mesothelioma. There were five pericardial and two testicular primaries. Of the two decades included in the study, later patients were significantly older, with a more advanced disease stage, and a lower performance status than those accrued early in the study. Factors at diagnosis associated with a significantly prolonged survival for all patients with mesothelioma included a 0 to 1 performance status, absence of chest pain, age less than 50 years, and epithelial histology. Factors at diagnosis associated with prolonged survival for the subset of patients with pleural mesothelioma included epithelial histology, 0 to 1 performance status, the absence of chest pain, an interval of greater than 6 months from onset of symptoms, and treatment with chemotherapy and pleuropneumonectomy. This last result must be interpreted with caution, since this was not a randomized study.

scholarly journals Effect of induction therapy with lenalidomide, doxorubicin and dexamethasone on bone remodeling and angiogenesis in newly diagnosed multiple myeloma

2019 ◽  
Vol 145 (2) ◽  
pp. 559-568
Author(s):  
Evangelos Terpos ◽  
Eirini Katodritou ◽  
Argiris Symeonidis ◽  
Flora Zagouri ◽  
Antonis Gerofotis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Remodeling ◽  
Induction Therapy ◽  
Newly Diagnosed

scholarly journals T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy

2020 ◽  
Author(s):  
Pascal Martin ◽  
Gisela E. Hagberg ◽  
Thomas Schultz ◽  
Klaus Harzer ◽  
Uwe Klose ◽  
...  
Keyword(s):  
Metachromatic Leukodystrophy ◽  
Advanced Disease ◽  
Magnetization Transfer ◽  
Brain Magnetic Resonance Imaging ◽  
Disease Stage ◽  
Magnetization Transfer Ratio ◽  
Water Fraction ◽  
Mri Protocol ◽  
Advanced Disease Stage ◽  
Multimodal Mri

Abstract Purpose T2-weighted signal hyperintensities in white matter (WM) are a diagnostic finding in brain magnetic resonance imaging (MRI) of patients with metachromatic leukodystrophy (MLD). In our systematic investigation of the evolution of T2-hyperintensities in patients with the late-infantile form, we describe and characterize T2-pseudonormalization in the advanced stage of the natural disease course. Methods The volume of T2-hyperintensities was quantified in 34 MRIs of 27 children with late-infantile MLD (median age 2.25 years, range 0.5–5.2 years). In three children with the most advanced clinical course (age >4 years) and for whom the T2-pseudonormalization was the most pronounced, WM microstructure was investigated using a multimodal MRI protocol, including diffusion-weighted imaging, MR spectroscopy (MRS), myelin water fraction (MWF), magnetization transfer ratio (MTR), T1-mapping and quantitative susceptibility mapping. Results T2-hyperintensities in cerebral WM returned to normal in large areas of 3 patients in the advanced disease stage. Multimodal assessment of WM microstructure in areas with T2-pseudonormalization revealed highly decreased values for NAA, neurite density, isotropic water, mean and radial kurtosis, MWF and MTR, as well as increased radial diffusivity. Conclusion In late-infantile MLD patients, we found T2-pseudonormalization in WM tissue with highly abnormal microstructure characterizing the most advanced disease stage. Pathological hallmarks might be a loss of myelin, but also neuronal loss as well as increased tissue density due to gliosis and accumulated storage material. These results suggest that a multimodal MRI protocol using more specific microstructural parameters than T2-weighted sequences should be used when evaluating the effect of treatment trials in MLD.

scholarly journals Angiogenesis-Related Cytokines, RANKL, and Osteoprotegerin in Multiple Myeloma Patients in relation to Clinical Features and Response to Treatment

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
K. Sfiridaki ◽  
C. A. Pappa ◽  
G. Tsirakis ◽  
P. Kanellou ◽  
M. Kaparou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Growth Factor ◽  
Serum Levels ◽  
Response To Treatment ◽  
Disease Stage ◽  
Vascular Endothelial ◽  
Newly Diagnosed ◽  
Plateau Phase ◽  
Endothelial Growth Factor ◽  
Hepatocyte Growth

An essential cytokine system for the osteoclast biology in multiple myeloma (MM) consists of the receptor of activator of NF-κB ligand (RANKL), its receptor (RANK), and the soluble decoy receptor, osteoprotegerin (OPG). Myeloma cells cause imbalance in OPG/RANKL interactions. We measured serum levels of OPG, soluble (s) RANKL, sRANKL/OPG ratio, markers of disease activity [LDH, CRP, interleukin-6 (IL-6),β2-microglobulin (B2M)], and angiogenic factors [hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], in 54 newly diagnosed MM patients and in 25 of them in plateau phase. All the above values were higher in MM patients compared to controls and decreased in plateau phase. sRANKL and RANKL/OPG were higher with advancing disease stage and skeletal grade. Significant correlations were found among RANKL and RANKL/OPG with HGF, LDH, VEGF, IL-6, and B2M. In conclusion, RANKL and OPG play significant roles in MM pathophysiology, as regulators of bone turnover and mediators of angiogenesis.

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