Clinical and translational pharmacology of drugs for the prevention and treatment of bone metastases and cancer-induced bone loss.

Bone disease is a frequent event in cancer patients, both due to cancer spread to bone and to cancer therapies. Bone is the organ most frequently affected by metastatic disease when considering the two most frequent cancers in the Western world (breast and prostate cancers). Bone metastases can have a substantial detrimental effect on patients' quality of life, as well as significant morbidity due to complications collectively known as skeletal-related events (SREs), which include hypercalcaemia, pathological fractures, spinal cord compression, and need of radiotherapy or surgery to the bone. These have been successfully mitigated with the development of bone-targeted agents (BTAs; bisphosphonates and denosumab), focused on inhibiting osteoclast activity. The potential direct antitumour effect of bisphosphonates, as well as the impact of osteoclast inhibition with subsequent decrease in bone metabolism, have also propelled investigation on the role of BTAs in preventing cancer relapse in bone. In this review, the authors aimed to discuss the role of BTAs in the treatment and prevention of bone metastases, as well as their potential value in preventing cancer treatment-induced bone loss (CTIBL). The review will focus on breast and prostate cancers, with the aim of providing the most relevant clinical data emerging from bench to bedside translational research in the field of cancer-induced bone disease.

RegaDB: community-driven data management and analysis for infectious diseases.

SUMMARY: RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyse patient data, including viral genetic sequences. Moreover, RegaDB provides researchers with a mechanism to collect data in a uniform format and offers them a canvas to make newly developed bioinformatics tools available to clinicians and virologists through a user friendly interface. AVAILABILITY AND IMPLEMENTATION: Source code, binaries and documentation are available on http://rega.kuleuven.be/cev/regadb. RegaDB is written in the Java programming language, using a web-service-oriented architecture.

Mutations selected in HIV-2-infected patients failing a regimen including atazanavir.

OBJECTIVES: To investigate mutations selected in viruses from HIV-2-infected patients failing a highly active antiretroviral treatment (HAART) regimen including atazanavir/ritonavir. METHODS: Twenty-eight HIV-2-infected patients previously exposed to atazanavir/ritonavir and failing therapy were studied. The protease (PR) gene was amplified and sequenced, and mutations emerging under atazanavir/ritonavir selective pressure were reported. RESULTS: The I50L mutation emerged in 4 out of 28 HIV-2-infected patients failing a HAART regimen including atazanavir/ritonavir. Besides I50L, four PR mutations previously associated with protease inhibitor resistance (I54L, I64V, V71I and I82F) and six PR mutations of unknown impact (V10I, E37D, S43T, K45R, I75V and F85L) in HIV-2 were also identified in this small group of patients. CONCLUSIONS: Several mutations were associated with virological failure of a regimen including atazanavir/ritonavir in HIV-2-infected patients, including I50L for the first time. It should be included in HIV-2 algorithms for interpretation of genotypic resistance data, and taken into account when making therapeutic decisions for HIV-2-infected patients.

360 Health Analysis (H360)-A Comparison of Key Performance Indicators in Breast Cancer Management across Health Institution Settings in Portugal.

BACKGROUND: The increased focus on quality indicators (QIs) and the use of clinical registries in real-world cancer studies have increased compliance with therapeutic standards and patient survival. The European Society of Breast Cancer Specialists (EUSOMA) established QIs to assess compliance with current standards in breast cancer care. METHODS: This retrospective study is part of H360 Health Analysis and aims to describe compliance with EUSOMA QIs in breast cancer management in different hospital settings (public vs. private; general hospitals vs. oncology centers). A set of key performance indicators (KPIs) was selected based on EUSOMA and previously identified QIs. Secondary data were retrieved from patients' clinical records. Compliance with target KPIs in different disease stages was compared with minimum and target EUSOMA standards. RESULTS: A total of 259 patient records were assessed. In stages I, II, and III, 18 KPIs met target EUSOMA standards, 5 met minimum standards, and 8 failed to meet minimum standards. Compliance with KPIs varied according to the type of hospital (particularly regarding diagnosis) and disease stage. Although small differences were found in KPI compliance among institutions, several statistical differences were found among treatment KPIs according to disease stage, particularly in stage III. CONCLUSIONS: This study represents the first assessment of the quality of breast cancer care in different hospital settings in Portugal and shows that, although most QIs meet EUSOMA standards, there is room for improvement. Differences have been found across institutions, particularly between oncology centers and general hospitals, in diagnosis and compliance with KPIs among disease stages. Stage III showed the greatest variability in compliance with treatment KPIs, probably related to the lower specificity of the guidelines in this disease stage.

360 Health Analysis (H360) - A Proposal for an Integrated Vision of Breast Cancer in Portugal.

H360 aims to provide a comprehensive picture of breast cancer management in Portugal by retrieving real-world data from 10 Portuguese hospitals and deriving a snapshot from the medical interpretation of evidence-based data to patient perspective on the quality and effectiveness of medical care provided. This article reviews evidence on breast cancer clinical practice and quality of care and disease management in Portugal. A review of evidence on breast cancer clinical practice and quality of care over the last 10 years was performed in PubMed using the query "Organization and Administration"[Mesh] AND "breast cancer"[All Fields] NOT "Review" [ptyp]. National cancer initiatives relevant for quality of care and national and international guidelines and consensus were analyzed. Retrieved results showed that breast cancer incidence is still increasing, including in Portugal. Studies investigating disease outcomes seek to derive improvements to clinical practice and better financial resource allocation. Setting performance measures (KPIs) in institutions treating cancer is not a reality in Portugal yet, but has potential to leverage the quality of clinical performance. A multidisciplinary approach within one health structure is also desirable. More investment in clinical (including academic) research is key to optimize the quality of care. Implementation of clinical practice guidelines (largely based on ESMO guidelines in Portugal) is crucial to improve patient outcomes. Not less importantly, quality of life is a treatment goal on its own in breast cancer care. Breast cancer remains a health challenge and a multidimensional, 360-degree appraisal, beyond the exclusively clinical perspective, may provide new insights towards an optimal patient-centered approach.

Phase Angle as a Marker of Muscular Strength in Breast Cancer Survivors.

BACKGROUND: accurate prognostic tools are relevant for decision-making in cancer care. Objective measures, such as bioelectrical impedance (BI), have the potential to improve prognostic accuracy for these patients. This cross-sectional study aimed to investigate whether phase angle (PhA) derived from the electrical properties of the body tissues is a predictor of muscular strength in breast cancer survivors (BCS). METHODS: a total of 41 BCS (age 54.6 ± 9.2 years) were evaluated. PhA, obtained at frequency 50 kHz, was assessed with BI spectroscopy, and muscular strength with a handgrip dynamometer. Moderate-to-vigorous physical activity (MVPA) was assessed using the International Physical Activity Questionnaire (IPAQ). Measurements were performed in the morning after an overnight fast. RESULTS: linear regression analysis showed that PhA accounted for 22% (r2 = 0.22) of muscular strength variance. PhA remained a borderline predictor of muscular strength variance independently of age and MVPA. CONCLUSIONS: the findings of this study suggest that PhA is a significant predictor of maximal forearm isometric strength and a potential indicator of disease-related functionality in BCS.

HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen.

To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.