Neoadjuvant therapy for breast cancer

Objective: To evaluate the frequency of neoadjuvant therapy (NT) in women with stage I–III breast cancer in Italy and whether it is influenced by biological characteristics, screening history, and geographic area. Methods: Data from the High Resolution Study conducted in 7 Italian cancer registries were used; they are a representative sample of incident cancers in the study period (2009–2013). Included were 3546 women aged <85 years (groups <50, 50–69, 70–64, and 75+) with stage I–III breast cancer at diagnosis who underwent surgery. Women were classified as receiving NT if they received chemotherapy, target therapy, and/or hormone therapy before the first surgical treatment. Logistic models were built to test the association with biological and contextual variables. Results: Only 8.2% of women (290 cases) underwent NT; the treatment decreases with increasing age (14.5% in age <50 and 2.2% in age 75+), is more frequent in women with negative receptors (14.8%), HER2-positive (15.7%), and triple-negative (15.6%). The multivariable analysis showed the probability of receiving NT is higher in stage III (odds ratio [OR] 3.83; 95% confidence interval [CI] 2.83–5.18), luminal B (OR 1.87; 95% CI 1.27–2.76), triple-negatives (OR 1.88; 95% CI 1.15–3.08), and in symptomatic cancers (OR 1.98; 95% CI 1.13–3.48). Use of NT varied among geographic areas: Reggio Emilia had the highest rates (OR 2.29; 95% CI 1.37–3.82) while Palermo had the lowest (OR 0.41; 95% CI 0.24–0.68). Conclusions: The use of NT in Italy is limited and variable. There are no signs of greater use in hospitals with more advanced care

webPDBinder: a server for the identification of ligand binding sites on protein structures

The webPDBinder (http://pdbinder.bio.uniroma2.it/PDBinder) is a web server for the identification of small ligand-binding sites in a protein structure. webPDBinder searches a protein structure against a library of known binding sites and a collection of control non-binding pockets. The number of similarities identified with the residues in the two sets is then used to derive a propensity value for each residue of the query protein associated to the likelihood that the residue is part of a ligand binding site. The predicted binding residues can be further refined using conservation scores derived from the multiple alignment of the PFAM protein family. webPDBinder correctly identifies residues belonging to the binding site in 77% of the cases and is able to identify binding pockets starting from holo or apo structures with comparable performances. This is important for all the real world cases where the query protein has been crystallized without a ligand and is also difficult to obtain clear similarities with bound pockets from holo pocket libraries. The input is either a PDB code or a user-submitted structure. The output is a list of predicted binding pocket residues with propensity and conservation values both in text and graphical format

PIK3CA exon 20 mutations are associated with poor prognosis in breast cancer patients

OBJECTIVES: The phosphatidylinositol 3-kinase/AKT axis is an important cell-signaling pathway that mediates cell proliferation and survival, two biological processes that regulate malignant cell growth. The phosphatidylinositol 3-kinase CA gene encodes the p110α subunit of the phosphatidylinositol 3-kinase protein. There are phosphatidylinositol 3-kinase CA mutations in several types of human tumors, and they are frequently observed in breast cancer. However, these mutations have not been investigated in Brazilian breast cancer patients. METHODS: PCR-SSCP and direct DNA sequencing were performed to identify phosphatidylinositol 3-kinaseCA exon 9 and exon 20 mutations in 86 patients with sporadic breast cancer. The relationships between PIK3CA mutations and patient clinicopathological characteristics and survival were analyzed. The presence of the TP53 mutation was also examined. RESULTS: Twenty-three (27%) of the 86 primary breast tumors contained PIK3CA mutations. In exons 9 and 20, we identified the hotspot mutations E542K, E545K, and H1047R, and we identified two new missense mutations (I1022V and L1028S) and one nonsense (R992X) mutation. Phosphatidylinositol 3-kinase CA exon 20 mutations were associated with poor overall survival and TP53 gene mutations. CONCLUSIONS: Phosphatidylinositol 3-kinase CA mutations are common in tumors in Brazilian breast cancer patients, and phosphatidylinositol 3-kinase CA and TP53 mutations are not mutually exclusive. Phosphatidylinositol 3-kinase CA exon 20 mutations are associated with poor survival, and they may be useful biomarkers for identifying breast cancer patients with aggressive tumors and for predicting the response to treatment with PI3K pathway inhibitors

Rehabilitative good practices in the treatment of sarcopenia: a narrative review

ABSTRACT: To date, rehabilitative good practices that analyze all aspects of the rehabilitation management of the patient with sarcopenia are absent in the literature. The purpose of this article is to carry out research and evaluation of the evidence, good practice, and recommendations in the literature relating to the rehabilitative treatment of disabilities associated with sarcopenia. Bibliographic research was conducted on Medline, PEDro, Cochrane Database, and Google Scholar. All articles published in the last 10 yrs were analyzed. The results of this research generated three guidelines, eight meta-analyses, five systematic reviews, a Cochrane review, 17 reviews, and seven consensus conferences. From the analysis of the literature, it seems that most of the works agree in affirming that exercise and diet supplementation are the cornerstones of rehabilitation treatment of patients with sarcopenia. The practice of an adequate lifestyle received numerous high-grade recommendations in the included guidelines. Based on the data obtained, the rehabilitation management of the patient with sarcopenia must be personalized and must include exercise and nutritional supplementation. These factors are important in increasing the autonomy of the elderly essential for safe walking without neglecting stretching exercises that are important for flexibility and balance and coordination exercises

Gait analysis advancements: rehabilitation value and new perspectives from forensic application

The clinical and rehabilitation value of gait analysis is remarkable and indisputable and poised to grow as technological advancements unfold. This article aims to shed light on the advances in how gait is assessed, enabling those who have suffered an injury impairing their motor skills to be diagnosed more accurately and efficiently as well as to compare the hallmarks of rehabilitative and forensic gait analysis. The authors have conducted an analysis of relevant papers (published between 1967 and 2020) from a medicolegal perspective, cited in PubMed, MEDLINE, Cochrane Library, EMBASE, and available recommendations for the legal application of such techniques. Moreover, considering the use of gait analysis as a forensic tool, this study broadens the scope of research by including search engines, legal databases, and court filings (DeJure, Lexis Nexis, Justia) between 2000 and 2022. The instrumental assessment of movement (Gait Analysis) has come to constitute an essential analytical tool for the biomedical sector to objectively and accurately assess human movement and posture. The article is also aimed at elaborating differences and similarities between clinical and forensic gait analysis. When it comes to the forensic applicability of gait analysis and its evidentiary value, however, there is a pressing need for a review of its scientific basis. Therefore, it is necessary to conduct a thorough evaluation of its use in legal practice, as stressed in scientific literature and surveys. It is of utmost importance to highlight the procedural and assessment standards currently applied to forensic gait analysis, to evaluate its strengths and weaknesses, and to achieve standardized guidelines based on broad scientific consensus