The prognostic value of vascular endothelial growth factors (VEGFs)-A and -B and their receptor, VEGFR-1, in invasive breast carcinoma

OBJECTIVES: Vascular endothelial growth factors A and B (VEGF-A and VEGF-B) play a major role in angiogenesis and activate VEGF receptor 1 (VEGFR-1). However, the clinicopathologic and clinical value of VEGF-B and VEGFR-1 in invasive breast carcinoma remains unclear. METHODS: We immunohistochemically examined the expression pattern of VEGF-A, VEGF-B and VEGFR-1 in 177 invasive breast carcinomas in relation to clinicopathological parameters, p53, c-erbB2 proteins expression and patients' survival. RESULTS: VEGF-A, VEGF-B and VEGFR-1 were immunodetected predominantly in the cytoplasm of the malignant cells. None of the studied markers correlated with any of the clinicopathological parameters, other than stromal VEGFR-1 which inversely correlated with PR (p=0.021). Cancerous VEGF-A and stromal VEGFR-1 were positively related to p53 (p=0.016 and p=0.033, respectively). Cancerous VEGF-B was positively associated with c-erbB-2 (p=0.045) and was found to exert an unfavorable impact on both disease-free and the overall survival of the node-positive patients (p=0.05 and p=0.029, respectively). Cancerous VEGFR-1 was recognized as being an independent poor prognostic indicator (p=0.037). CONCLUSION: These findings suggest that, while VEGF-B seems to be useful as a prognostic indicator only in node-positive patients, VEGFR-1 may be an independent poor prognosticator in patients with invasive breast carcinoma.     

Tyrosine kinase inhibitors in sarcoma treatment

Sarcomas are a group of rare mesenchymal malignant tumors that arise from transformed cells of the mesenchymal connective tissue, which are challenging to treat. The majority of sarcomas are soft tissue sarcomas (STSs; 75%) and this heterogeneous group of tumors is further comprised of gastrointestinal stromal tumors (~15%) and bone sarcomas (10%). Although surgery remains the current primary therapeutic approach for localized disease, recurrent, metastatic and refractory sarcomas require cytotoxic chemotherapy, which usually yields poor results. Therefore the efficiency of sarcoma treatment imposes a difficult problem. Furthermore, even though progress has been made towards understanding the underlying molecular signaling pathways of sarcoma, there are limited treatment options. The aim of the present study was therefore to perform a systematic literature review of the available clinical evidence regarding the role of tyrosine kinase inhibitors (TKIs) in patients with recurrent or refractory STSs and bone sarcomas over the last two decades. Tyrosine kinases are principal elements of several intracellular molecular signaling pathways. Deregulation of these proteins has been implicated in driving oncogenesis via the crosstalk of pivotal cellular signaling pathways and cascades, including cell proliferation, migration, angiogenesis and apoptosis. Subsequently, small molecule TKIs that target these proteins provide a novel potential therapeutic approach for several types of tumor by offering significant clinical benefits. Among the eligible articles, there were 45 prospective clinical trials, primarily multicentric, single arm, phase II and non-randomized. Numerous studies have reported promising results regarding the use of TKIs, mainly resulting in disease control in patients with STSs. The lack of randomized clinical trials demonstrates the ambiguous efficiency of various studied treatment options, which therefore currently limits the approved drugs used in clinical practice. Research both in clinical and preclinical settings is needed to shed light on the underlying molecular drivers of sarcomagenesis and will identify novel therapeutic approaches for pretreated patients.     

Patient contracts for chronic medical conditions: Scoping review

ObjectiveTo describe how and why patient contracts are used for the management of chronic medical conditions.Data sourcesA scoping review was conducted in the following databases: MEDLINE, Embase, AMED, PsycInfo, Cochrane Library, CINAHL, and Nursing & Allied Health. Literature from 1997 to 2017 was included.Study selectionArticles were included if they were written in English and described the implementation of a patient contract by a health care provider for the management of a chronic condition. Articles had to present an outcome as a result of using the contract or an intervention that included the contract.SynthesisOf the 7528 articles found in the original search, 76 met the inclusion criteria for the final review. Multiple study types were included. Extensive variety in contract elements, target populations, clinical settings, and cointerventions was found. Purposes for initiating contracts included behaviour change and skill development, including goal development and problem solving; altering beliefs and knowledge, including motivation and perceived self-efficacy; improving interpersonal relationships and role clarification; improving quality and process of chronic care; and altering objective and subjective health indices. How contracts were developed, implemented, and assessed was inconsistently described.ConclusionMore research is required to determine whether the use of contracts is accomplishing their intended purposes. Questions remain regarding their rationale, development, and implementation.     

Influence of Documented Lead Poisoning on Environmental Modification Programs in Newark,New Jersey

Data from the Newark, New Jersey Childhood Lead Poisoning Program suggest that the major consequence of the program has been early intervention rather than the amelioration of environmental contamination. During 1975 to 1976, the authors investigated housing for 253 black and Hispanic children with blood levels over 60 Mg/100 ml. Of these, 115 had moved or had given incorrect addresses and were lost to follow-up, 22 were in the same homes but did not make themselves available and in 16 instances, the houses were boarded up or had been destroyed by fire. Of the remaining 100 children, 31% suffered from symptoms potentially related to lead poisoning and 57% of the children were still living in the same dwelling in which the c h id was affected. Only one-fourth of the houses had been properly abated, i. e., the problem of environmental lead had been corrected, and one-fourth of the houses were not investigated at all by health authorities. These data support the concern that lead poisoning will not be effectively combated until the environmental issue is fully addressed.     

A new instrument for assessing the quality of studies on prevalence

There are numerous scientific articles of studies on the prevalence of disorders with non-standardised examination and diagnostic protocols. Because their quality is heterogeneous, a new instrument has been developed for the assessment of such studies. The new instrument is based mainly on statistical criteria. The points assigned for each of the main criteria according to the information gained from each paper are summed up to form a Total Quality Score (TQS). The interrater reliability of the instrument was tested by employing Kappa and Interrater Correlation Coefficient (ICC) statistics. The latter was assessed on the results of three independent investigators. The new quality instrument appeared to be easy to use, and the instructions were comprehensible. The ICC_(2,1) for the TQS ranged between 0.94 and 1.00 indicating almost perfect agreement between the investigators. The reliability of the new instrument enables its use for scientific review purposes. In this way, its validity will also be tested. The instrument could be adopted for assessment of scientific articles of studies on the prevalence of disorders in many, similar, scientific areas.