Systematic assessment of the quality of osteoporosis guidelines

Background  

Numerous agencies have developed clinical practice guidelines for the management of postmenopausal osteoporosis. The study objective was to conduct a systematic assessment of the quality of osteoporosis guidelines produced since 1998.     

Hepatic gene expression and prediction of therapy response in chronic hepatitis C patients

Chronic hepatitis C (HCV) infection remains a major health problem worldwide. The current standard of care is a combination of pegylated interferon-alpha and ribavirin. Considering the length of antiviral therapy, as well as its side effects and costs, accurate prediction of treatment response prior to initiation of treatment is critical. In addition to viral, demographic and environmental factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes of chronic HCV. The development of high-throughput technologies provides opportunities to define patterns of gene expression that are associated with certain disease outcomes and/or response to therapy. This article reviews genomics-based predictors of pre-treatment response to antiviral therapy.     

Monocyte adhesion and transmigration induce tissue factor expression: role of the mitogen-activated protein kinases

The expression of tissue factor (TF) by monocytes that have transmigrated across the endothelium to sites of extravascular inflammation acts both to focus and amplify the inflammatory response. Because clustering of the integrins responsible for endothelial adhesion and transmigration induces tyrosine phosphorylation and activation of the mitogen-activated protein (MAP) kinases, we postulated that transmigration might lead to monocyte activation and TF production. Monocytes were migrated across TNFalpha-primed ECV304 cells grown on fibronectin-coated Transwell chambers in response to FMLP (10(-8) M). After transmigration, monocytes showed a time-dependent increase in surface TF expression and biological procoagulant activity. TF expression was dependent on monocyte adhesion to ECV304 cells. Specifically, TF was not induced by FMLP treatment of suspended monocytes, by migration across fibronectin alone, or by soluble factors induced during migration, whereas monocyte-ECV304 adhesion was sufficient to stimulate TF. Antibodies against CD29 (beta1 integrin), but not against CD18 (beta2 integrin) or CD31 (PECAM-1), inhibited TF expression. Monocyte adhesion to ECV304 cells induced tyrosine phosphorylation of cellular proteins and specifically of the ERK and p38 MAP kinases. Tyrosine kinase inhibition with genistein (10 microg/mL) blocked transmigration, whereas selective ERK inhibition with PD98059 (50 microM) or p38 inhibition with SB203580 (20 microM) did not. However, both ERK and p38 inhibition dose dependently abolished TF expression. These studies suggest that an extravascular focus of infection or inflammation can promote both intravascular thrombosis and extravascular fibrin deposition during the process of adhesion and transmigration across the endothelial barrier. The selective inhibition of the mitogen-activated protein kinases may offer a novel therapeutic means of modulating this inflammatory sequence.     

Longitudinal morphological change of acetabular subchondral bone cyst after total hip arthroplasty in developmental dysplasia of the hip

Purpose

The purpose of this study is to clarify morphological changes of acetabular subchondral bone cyst after total hip arthroplasty for osteoarthritis secondary to developmental dysplasia of the hip.

Methods

Two hundred and sixty-one primary cementless total hip arthroplasties of 208 patients, 18 males, 190 females, were retrospectively reviewed. Morphological changes of subchondral bone cyst were evaluated by computed tomography (CT). The mean cross-sectional area of the cyst from CT scans at 3 months postoperatively and after 7–10 years (average 8.4 years) were compared.

Results

Acetabular subchondral bone cysts were found in 49.0% of all cases in preoperative CT scans. There was no cyst which was newly recognized in CT scan performed after postoperative 7–10 years. All the cross-sectional areas of the cysts evaluated in this study were reduced postoperatively.

Conclusions

This study revealed that acetabular subchondral bone cysts do not increase or expand after total hip arthroplasty and indicated that the longitudinal morphological change of acetabular bone cysts in patients of developmental dysplasia of the hip do not influence long-term implant fixation in total hip arthroplasty.

     

The keratin polypeptides of psoriatic epidermis

The polyacrylamide SDS electrophoretic pattern of protein extracted from the stratum corneum obtained by scraping the surface of involved skin of patients with psoriasis was different from that of uninvolved skin and normal controls. The pattern from superficial scales was similar to that of whole stratum corneum in the case of involved psoriatic epidermis but different in uninvolved and normal epidermis. These data indicate that the changes which are observed in the structural proteins during normal keratinization are not seen in involved psoriatic epidermis. In addition, the relative proportion of keratin polypeptides was different in involved psoriatic epidermis compared to normal skin. That these changes are not specific for psoriasis was shown by finding similar electrophoretic patterns with stratum corneum proteins from patients with other keratinizing disorders.     

Triple negative breast cancer in North of Morocco: clinicopathologic and prognostic features

Background

Triple Negative Breast Cancer (TNBC) is defined by a lack of estrogen and progesterone receptor gene expression and by the absence of overexpression on HER2. It is associated to a poor prognosis. We propose to analyze the clinicopathologic and prognostic characteristics of this breast cancer subtype in a Mediterranean population originated or resident in the North of Morocco.

Methods

We conducted a retrospective study of 279 patients diagnosed with breast cancer between January 2010 and January 2015. Clinicopathologic and prognostic features have been analyzed. Disease-Free Survival (DFS) and Overall Survival (OS) have been estimated.

Results

Of all cases, forty-nine (17.6 %) were identified as having triple negative breast cancer with a median age of 46 years. The average tumor size was 3.6 cm. The majority of patients have had invasive ductal carcinoma (91.8 %) and 40.4 % of them were grade III SBR. Nodal metastasis was detected in 38.9 % of the patients and vascular invasion was found in 36.6 % of them. About half of the patients had an early disease (53.1 %) and 46.9 % were diagnosed at an advanced stage. Patients with operable tumors (61.2 %) underwent primary surgery and adjuvant chemotherapy. Patients with no operable tumors (26.5 %) received neoadjuvant chemotherapy followed by surgery, and patients with metastatic disease (12.2 %) were treated by palliative chemotherapy. DFS and OS at 5 years were respectively 83.7 and 71.4 %. Among 49, twelve had recurrences, found either when diagnosing them or after a follow-up. Local relapse was 6.1 %. Lung and liver metastases accounted consecutively for 8.2 and 10.2 %. Bone metastases were found in 4.1 % and brain metastases in 2.1 % of the cases.

Conclusion

Our results are in accordance with literature data, particularly what concerning young age and poor prognosis among TNBC phenotype. Therefore, the identification of BRCA mutations in our population seems to be essential in order to better adapt management options for this aggressive form of breast cancer.

     

Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice

The outbreak of severe acute respiratory syndrome (SARS) in 2003 reinforces the potential of lethal pandemics of respiratory viral infections. The underlying mechanisms of SARS are still largely undefined. Long pentraxin PTX3, a humoral mediator of innate immunity, has been reported to have anti-viral effects. We examined the role of PTX3 in coronavirus murine hepatitis virus strain 1 (MHV-1)-induced acute lung injury, a previously reported animal model for SARS. PTX3-deficient mice (129/SvEv/C57BL6/J) and their wild-type (WT) littermates were intranasally infected MHV-1. These mice were also treated with recombinant PTX3. Effects of PTX3 on viral binding and infectivity were determined in vitro. Cytokine expression, severity of lung injury, leukocyte infiltration and inflammatory responses were examined in vivo. In PTX3 WT mice, MHV-1 induced PTX3 expression in the lung and serum in a time-dependent manner. MHV-1 infection led to acute lung injury with greater severity in PTX3-deficient mice than that in WT mice. PTX3 deficiency enhanced early infiltration of neutrophils and macrophages in the lung. PTX3 bound to MHV-1 and MHV-3 and reduced MHV-1 infectivity in vitro. Administration of recombinant PTX3 significantly accelerated viral clearance in the lung, attenuated MHV-1-induced lung injury, and reduced early neutrophil influx and elevation of inflammatory mediators in the lung. Results from this study indicate a protective role of PTX3 in coronaviral infection-induced acute lung injury.