Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

Magnetic resonance elastography with guided pressure waves

Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.     

Review of the renal endpoints used in cardiovascular safety clinical trials in type 2 diabetes mellitus patients and their importance in primary care

Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes mellitus (T2DM). Furthermore, CKD confers a considerable increase in the risk of cardiovascular (CV) morbidity and mortality. In line with the need to improve knowledge in this field, this article aims to describe the renal endpoints used in the different cardiovascular outcome trials (CVOTs). The objective is to better know the renal variables used in the different CVOTs in order to optimize the implementation of advances in the prevention of progressive diabetic kidney disease in patients with T2DM in clinical practice.     

Periodization in Anterior Cruciate Ligament Rehabilitation: A Novel Framework

More than 250,000 anterior cruciate ligament (ACL) injuries occur each year in the USA, and approximately 65% of these injuries undergo reconstructive surgery. Appropriate rehabilitation after ACL reconstruction can yield predictably good outcomes, with return to previous levels of activity and high knee function. At present, periodization is used at all levels of sports training. Whether conceptualized and directed by coaches, or by athletes themselves, competitors structure their training in a cyclic fashion, enabling athletes to best realize their performance goals. In practical application, sport physical therapists use periodization: postoperative “protocols” serve as rudimentary forms of periodization, albeit implemented over shorter time frames than that typically employed in preparation for competition. An ACL injury should not be considered a “simple” musculoskeletal pathology with only local mechanical or motor dysfunctions. Together with the psychological trauma and reduction in physical capacity, there is a cascade of events, including neurological insult to the central nervous system and reduction in afferences to the sensorimotor system. Rehabilitation should consider all these issues, and periodization would allow to better define and to plan aims and objectives to return athletes to their sport. Technological resources including advanced neuroimaging methods, virtual reality for injury risk screening and return to sport assessment, and interactive artificial reality-based neuromuscular training methods offer new approaches and tools to address this important biomedical problem. The cost and availability of many of these technologies will continue to decrease, providing greater availability, scientific rigor, and ultimately, utility for cost-effective and data-driven assessments.     

What is the relapse after Le Fort I maxillary advancement in cleft lip and palate patients? A systematic review

Oral and Maxillofacial Surgery - Le Fort I osteotomy is the most common procedure for maxillary advancement in cleft patients, and a significant relapse is expected in the postoperative period....     

Aortitis no infecciosa: experiencia con tocilizumab en un hospital comarcal

ObjectivesDescribe patients with noninfectious aortitis and their response to treatment in a regional hospital.MethodsReview of patients with noninfectious aortitis, diagnostic technique used and immunosuppressive therapy received.ResultsWe report 8 patients (7 women and one man) diagnosed with aortitis by positron emission tomography (PET). The mean age was 69 years (interquartile range [IQR] 62-72.2). Three months of treatment with tocilizumab improved symptoms, erythrocyte sedimentation rate and C-reactive protein level (P < .001 and P < .012, respectively) in the 6 patients in whom it was used.ConclusionsTocilizumab was an effective and safe treatment in those patients diagnosed with aortitis refractory to steroids and conventional immunosuppressive therapy.