Hypofractionated radiation therapy for invasive breast cancer: From moderate to extreme protocols

Adjuvant irradiation is the standard treatment after breast conservative surgery. Normofractionated regimen with an overall treatment time of 5 to 6 weeks is often considered as a limiting factor for irradiation compliance. In order to answer this issue, moderate and more recently extreme hypofractionated protocols appeared. We report here oncological outcomes and toxicity of hypofractionated breast irradiation. After defining the frame of moderate and extreme hypofractionated breast irradiations based on overall treatment time, patient selection criteria were listed. According to their levels of proof, the results of moderate and extreme hypofractionated breast irradiation were analysed. Overall treatment time for moderate hypofractionated breast irradiation ranged from 3 to 4 weeks, while for extreme hypofractionated breast irradiation, it was less than 1 week. For moderate hypofractionated breast irradiation, whole breast irradiation was currently performed with or without lymph node irradiation. Moderate hypofractionated breast irradiation has proven to be as safe and as efficient as normofractionated breast irradiation with level IA evidence. For extreme hypofractionated breast irradiation, phase III randomized trials confirmed that accelerated partial breast irradiation was non-inferior in terms of local control compared to normofractionated whole breast irradiation (with external beam radiation therapy and multicatheter brachytherapy), with similar acute and late toxicity. While the use of intraoperative breast irradiation remains under debate, new very accelerated partial breast irradiation (overall treatment time not exceeding 2 days) protocols emerged with encouraging results. Accelerated partial breast irradiation is warranted for extreme hypofractionated breast irradiation and is indicated for low-risk breast cancers. Moderate and extreme hypofractionated breast irradiation regimens are validated and can be routinely proposed according to patient selection criteria.     

Fibrous dysplasia of the jaws: Integrating molecular pathogenesis with clinical,radiological, and histopathological features

Fibrous dysplasia is a non‐neoplastic developmental process that affects the craniofacial bones, characterized by painless enlargement as a result of bone substitution by abnormal fibrous tissue. Postzygotic somatic activating mutations in the GNAS1 gene cause fibrous dysplasia and have been extensively investigated, as well as being helpful in the differential diagnosis of the disease. Fibrous dysplasia may involve one (monostotic) or multiple bones (polyostotic), sporadically or in association with McCune‐Albright syndrome, Jeffe‐Lichenstein syndrome, or Mazabreud syndrome. This review summarizes the current knowledge on fibrous dysplasia, emphasizing the value of integrating the understanding of its molecular pathogenesis with the clinical, radiological, and histopathological features. In addition, we address important aspects related to the differential diagnosis and patient management.     

Strategies to enhance transductional efficiency of adenoviral-based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie-adenovirus receptor (CAR). We explored CAR-independent transduction to fibroblasts and keratinocytes using a panel of CAR-independent fiber-modified Ads to determine enhancement of infectivity. These fiber-modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber-modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, alpha upsilon integrin, syndecan-1, and glypican-1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of alpha upsilon integrin, syndecan-1 and glypican-1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan-1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber-modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.     

Experimental arthritis induced by a clinical Mycoplasma fermentans isolate

Background  

Mycoplasma fermentans has been associated with rheumatoid arthritis. Recently, it was detected in the joints and blood of patients with rheumatoid arthritis, but it is not clear yet how the bacteria enter the body and reach the joints. The purpose of this study was to determine the ability of M. fermentans to induce experimental arthritis in rabbits following inoculation of the bacteria in the trachea and knee joints.     

Quantitative diagnostic performance of myocardial perfusion SPECT with attenuation correction in women.

Attenuation correction (AC) for myocardial perfusion SPECT (MPS) had not been evaluated separately in women despite specific considerations in this group because of breast photon attenuation. We aimed to evaluate the performance of AC in women by using automated quantitative analysis of MPS to avoid any bias. METHODS: Consecutive female patients--134 with a low likelihood (LLk) of coronary artery disease (CAD) and 114 with coronary angiography performed within less than 3 mo of MPS--who were referred for rest-stress electrocardiography-gated 99mTc-sestamibi MPS with AC were considered. Imaging data were evaluated for contour quality control. An additional 50 LLk studies in women were used to create equivalent normal limits for studies with AC and with no correction (NC). An experienced technologist unaware of the angiography and other results performed the contour quality control. All other processing was performed in a fully automated manner. Quantitative analysis was performed with the Cedars-Sinai myocardial perfusion analysis package. All automated segmental analyses were performed with the 17-segment, 5-point American Heart Association model. Summed stress scores (SSS) of > or =3 were considered abnormal. RESULTS: CAD (> or =70% stenosis) was present in 69 of 114 patients (60%). The normalcy rates were 93% for both NC and AC studies. The SSS for patients with CAD and without CAD for NC versus AC were 10.0 +/- 9.0 (mean +/- SD) versus 10.2 +/- 8.5 and 1.6 +/- 2.3 versus 1.8 +/- 2.5, respectively; P was not significant (NS) for all comparisons of NC versus AC. The SSS for LLk patients for NC versus AC were 0.51 +/- 1.0 versus 0.6 +/- 1.1, respectively; P was NS. The specificity for both NC and AC was 73%. The sensitivities for NC and AC were 80% and 81%, respectively, and the accuracies for NC and AC were 77% and 78%, respectively; P was NS for both comparisons. CONCLUSION: There are no significant diagnostic differences between automated quantitative MPS analyses performed in studies processed with and without AC in women.     

Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32

Some MCP SNP and aHUS-associated MCP mutation