The Story behind the Science: The discovery of CagA, the first tumorigenic bacterial protein.

In this article, we reconstruct the history of the science that led to the discovery of CagA, the protein that causes gastric cancer, where teams in the United States and Italy made independent observations that ultimately merged. We also honor the memory of Antonello Covacci, who played an important role in this discovery and passed away prematurely in 2023.

-specific TIGIT Treg are present in the blood of healthy subjects - a hurdle for vaccination?

poses an enormous burden of morbidity and mortality worldwide. Making an efficacious vaccine has however proven extremely challenging. Due to colonizing interactions, pre-existing -specific CD4 T cells are often found in the human population and yet a detailed characterization of their phenotypes and how they might in turn impact vaccine efficacy are thus far unknown.

PROMRIINE (PRe-operatory Magnetic Resonance Imaging is INEffective) Study: A Systematic Review and Meta-analysis of the Impact of Magnetic Resonance Imaging on Surgical Decisions and Clinical Outcomes in Women with Breast Cancer.

Background: The purpose of this study was to review and summarize the association between preoperative magnetic resonance imaging (MRI) and surgical outcomes in women with newly diagnosed invasive breast cancer from published randomized controlled trials (RCT).

Materials And Methods: Two independent researchers conducted a systematic review through a comprehensive search of electronic databases, including PubMed, Medline, Embase, Ovid, Cochrane Library, and Web of Science. If there was disagreement between the two reviewers, a third reviewer assessed the manuscript to determine whether it should be included for data extraction.

The Incidence of Skin and Soft Tissue Infections in the United States and Associated Healthcare Utilization Between 2010 and 2020.

Background: The number of patients with skin and soft tissue infections (SSTIs) in the United States appeared to be increasing well into the 21st century. However, no recent data have confirmed this trend.

Methods: This retrospective, observational cohort study used claims data over 11 years (2010-2020) from Optum's de-identified Clinformatics Data Mart Database.

Reverse development of vaccines against antimicrobial-resistant pathogens.

Vaccine R&D is typically a lengthy process taking >10 years. However, vaccines still fail in clinical development because of unreliable animal models or absent immunological correlates of protection. Without a correlate of protection, phase-1 and -2 studies of safety and immunogenicity can fail to predict phase-3 efficacy.

Vaccination with staphylococcal protein A protects mice against systemic complications of skin infection recurrences.

Skin and soft tissue infections (SSTIs) are the most common diseases caused by (), which can progress to threatening conditions due to recurrences and systemic complications. Staphylococcal protein A (SpA) is an immunomodulator antigen of , which allows bacterial evasion from the immune system by interfering with different types of immune responses to pathogen antigens. Immunization with SpA could potentially unmask the pathogen to the immune system, leading to the production of antibodies that can protect from a second encounter with , as it occurs in skin infection recurrences.

The immune evasion roles of protein A and impact on vaccine development.

While () bacteria are part of the human commensal flora, opportunistic invasion following breach of the epithelial layers can lead to a wide array of infection syndromes at both local and distant sites. Despite ubiquitous exposure from early infancy, the life-long risk of opportunistic infection is facilitated by a broad repertoire of virulence proteins. These proteins play a key role in inhibiting development of a long-term protective immune response by mechanisms ranging from dysregulation of the complement cascade to the disruption of leukocyte migration.

Early breast cancer: concept and therapeutic review.

Objective: Breast cancer treatment has evolved significantly over the years, both in terms of local and systemic approaches. Halsted's radical mastectomy gave way to modified mastectomies and to conservative surgeries, along with breast reconstruction and repair. Although the use of new drugs has directly increased the survival of patients submitted to adjuvant or neoadjuvant systemic therapies, the de-escalation of drugs may also be beneficial in numerous cases.

How well are Brazilian mastologists (breast surgeons) trained in breast reconstruction and oncoplastic surgery? A study of the impact of a breast reconstruction and oncoplastic surgery improvement course.

Introduction: The breasts are a female symbol, impacts self-image and self-esteem. Breast reconstructive and oncoplastic surgeries have an important role in minimizing injuries. In Brazil less than a third of public health system (SUS) users have access to immediate reconstructive surgery.

Dermoglandular advancement-rotation flap for conservative treatment of breast cancer - description of technique, objective and subjective assessments.

Objective: to describe and evaluate the dermoglandular advancement-rotation flap with no contralateral surgery as a technique for the conservative treatment of breast cancer when skin or a large proportion of gland requires resection.

Patients/methods: 14 patients with breast tumors with a mean size of 4.2 cm and need for skin resection.

Gene Expression Profiling of Staphylococcus aureus during Infection Informs Design of Stemless Leukocidins LukE and -D as Detoxified Vaccine Candidates.

Staphylococcus aureus is a clinically important bacterial pathogen that has become resistant to treatment with most routinely used antibiotics. Alternative strategies, such as vaccination and phage therapy, are therefore actively being investigated to prevent or combat staphylococcal infections. Vaccination requires that vaccine targets are expressed at sufficient quantities during infection so that they can be targeted by the host's immune system.

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study-The ARTHR-IS Study Group.

Introduction: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome.

Methods: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016.

Preoperative and perioperative risk factors, and risk score development for prosthetic joint infection due to Staphylococcus aureus: a multinational matched case-control study.

Objectives: We aim to identify the preoperative and perioperative risk factors associated with post-surgical Staphylococcus aureus prosthetic joint infections (PJI) and to develop and validate risk-scoring systems, to allow a better identification of high-risk patients for more efficient targeted interventions.

Methods: We performed a multicenter matched case-control study of patients who underwent a primary hip and knee arthroplasty from 2014 to 2016. Two multivariable models by logistic regression were performed, one for the preoperative and one for perioperative variables; predictive scores also were developed and validated in an external cohort.

Natural Human Immunity Against Staphylococcal Protein A Relies on Effector Functions Triggered by IgG3.

Staphylococcal protein A (SpA) is a multifunctional, highly conserved virulence factor of . By binding the Fc portion of all human IgG subclasses apart from IgG3, SpA interferes with antibody and complement deposition on the bacterial surface, impairing staphylococcal clearance by phagocytosis. Because of its anti-opsonic properties, SpA is not investigated as a surface antigen to mediate bacterial phagocytosis.

Dissecting the Human Response to Systemic Infections.

is a common human commensal and the leading cause of diverse infections. To identify distinctive parameters associated with infection and colonization, we compared the immune and inflammatory responses of patients with a diagnosis of invasive disease to healthy donors. We analyzed the inflammatory responses founding a pattern of distinctive cytokines significantly higher in the patients with invasive disease.

Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies.

is one of the most important human pathogens worldwide. Its high antibiotic resistance profile reinforces the need for new interventions like vaccines in addition to new antibiotics. Vaccine development efforts against have failed so far however, the findings from these human clinical and non-clinical studies provide potential insight for such failures.

Substantial Reduction in Adjuvant Chemotherapy With the Use of the 21-Gene Test to Manage Early Breast Cancer in a Public Hospital in Brazil.

Purpose: We evaluated the impact of 21-gene test results on treatment decisions for patients with early-stage breast cancer treated under the public health care system in Brazil, Sistema Único de Saúde.

Methods: Eligible patients treated at Hospital Pérola Byington and Santa Casa de Misericórdia de São Paulo in Brazil were required to have the following characteristics: postsurgery with hormone receptor-positive, human epidermal growth factor 2-negative, node-negative and node-positive, and T1/T2 breast cancer and patients with these characteristics were candidates for adjuvant systemic therapy. Treatment recommendations, chemotherapy plus hormonal therapy (CT + HT) or HT alone, were captured before and after 21-gene test results.

Virulence Gene Expression of in Human Skin.

is the main cause of human skin and soft tissue infections. However, pathogenicity within the skin is not fully characterized. Here, we implemented an cutaneous infection model using human skin explants and performed a time-course infection to study the gene expression profile of a large panel of virulence-related factors of USA300 LAC strain, by high-throughput RT-PCR.

Staphylococcal Protein A Induces Leukocyte Necrosis by Complexing with Human Immunoglobulins.

One of the defining features of Staphylococcus aureus is its ability to evade and impair the human immune response through expression of staphylococcal protein A (SpA). Herein, we describe a previously unknown mechanism by which SpA can form toxic immune complexes when in the presence of human serum, which leads to the loss of human leukocytes. Further, we demonstrate that these toxic complexes are formed specifically through SpA's interaction with intact human IgG and that, in the presence of purified IgG Fab and Fc fragments, SpA shows no such toxicity.

-Specific Tissue-Resident Memory CD4 T Cells Are Abundant in Healthy Human Skin.

The skin is an immunocompetent tissue that harbors several kinds of immune cells and a plethora of commensal microbes constituting the skin microbiome. is a prominent skin pathogen that colonizes a large proportion of the human population. We currently have an incomplete understanding of the correlates of protection against infection, however genetic and experimental evidence has shown that CD4 T cells play a key role in orchestrating a protective anti- immune response.

Staphylococcal protein A inhibits complement activation by interfering with IgG hexamer formation.

Immunoglobulin (Ig) G molecules are essential players in the human immune response against bacterial infections. An important effector of IgG-dependent immunity is the induction of complement activation, a reaction that triggers a variety of responses that help kill bacteria. Antibody-dependent complement activation is promoted by the organization of target-bound IgGs into hexamers that are held together via noncovalent Fc-Fc interactions.

The role of vaccines in combatting antimicrobial resistance.

The use of antibiotics has enabled the successful treatment of bacterial infections, saving the lives and improving the health of many patients worldwide. However, the emergence and spread of antimicrobial resistance (AMR) has been highlighted as a global threat by different health organizations, and pathogens resistant to antimicrobials cause substantial morbidity and death. As resistance to multiple drugs increases, novel and effective therapies as well as prevention strategies are needed.

Targeting Skin-Resident Memory T Cells via Vaccination to Combat Staphylococcus aureus Infections.

Tissue-resident memory T cells are important in adaptive immunity against many infections, rendering these cells attractive potential targets in vaccine development. Genetic and experimental evidence highlights the importance of cellular immunity in protection from Staphylococcus aureus skin infections, yet skin-resident memory T cells are, thus far, an untested component of immunity during such infections. Novel methods of generating and sampling vaccine-induced skin memory T cells are paralleled by discoveries of global, skin-wide immunosurveillance.