Initial experience in implementing quantitative DCE-MRI to predict breast cancer therapy response in a multi-center and multi-vendor platform setting.

Quantitative dynamic contrast-enhanced (DCE) MRI as a promising method for the prediction of breast cancer response to neoadjuvant chemotherapy (NAC) has been demonstrated mostly in single-center and single-vendor platform studies. This preliminary study reports the initial experience in implementing quantitative breast DCE-MRI in multi-center (MC) and multi-vendor platform (MP) settings to predict NAC response. MRI data, including B mapping, variable flip angle (VFA) measurements of native tissue R (R), and DCE-MRI, were acquired during NAC at three sites using 3T systems with Siemens, Philips, and GE platforms, respectively.

Datopotamab-deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes.

Incidence of cough from acute exposure to fine particulate matter (PM2.5) in Madagascar: A pilot study.

Prolonged exposure to fine particulate matter (PM2.5) is a known risk to respiratory health, causing chronic lung impairment. Yet, the immediate, acute effects of PM2.

Tuberculosis treatment monitoring tests during routine practice: study design guidance.

Scope: The current tools for tuberculosis (TB) treatment monitoring, smear microscopy and culture, cannot accurately predict poor treatment outcomes. Research into new TB treatment monitoring tools (TMTs) is growing, but data are unreliable. In this article, we aim to provide guidance for studies investigating and evaluating TB TMT for use during routine clinical care.

A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma.

Background: ONC201 is a small molecule that can cause nonapoptotic cell death through loss of mitochondrial function. Results from the phase I/II trials of ONC201 in patients with refractory solid tumors demonstrated tumor responses and prolonged stable disease in some patients.

Methods: This single-arm, open-label, phase II clinical trial evaluated the efficacy of ONC201 at the recommended phase II dose (RP2D) in patients with recurrent or refractory metastatic breast or endometrial cancer.

First-in-human phase 1 clinical trial of anti-core 1 O-glycans targeting monoclonal antibody NEO-201 in treatment-refractory solid tumors.

Background: NEO201 is a humanized IgG1 monoclonal antibody (mAb) generated against tumor-associated antigens from patients with colorectal cancer. NEO-201 binds to core 1 or extended core 1 O-glycans expressed by its target cells. Here, we present outcomes from a phase I trial of NEO-201 in patients with advanced solid tumors that have not responded to standard treatments.

Phase I Study and Cell-Free DNA Analysis of T-DM1 and Metronomic Temozolomide for Secondary Prevention of HER2-Positive Breast Cancer Brain Metastases.

Purpose: Preclinical data showed that prophylactic, low-dose temozolomide (TMZ) significantly prevented breast cancer brain metastasis. We present results of a phase I trial combining T-DM1 with TMZ for the prevention of additional brain metastases after previous occurrence and local treatment in patients with HER2+ breast cancer.

Patients And Methods: Eligible patients had HER2+ breast cancer with brain metastases and were within 12 weeks of whole brain radiation therapy (WBRT), stereotactic radiosurgery, and/or surgery.

Multicomponent strategy with decentralised molecular testing for tuberculosis in Uganda: a cost and cost-effectiveness analysis.

Background: Decentralised molecular testing for tuberculosis could reduce missed diagnoses and losses to follow-up in high-burden settings. The aim of this study was to evaluate the cost and cost-effectiveness of the Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) study strategy, a multicomponent strategy including decentralised molecular testing for tuberculosis, in Uganda.

Methods: We conducted a costing and cost-effectiveness analysis nested in a pragmatic cluster-randomised trial of onsite (decentralised) versus hub-and-spoke (centralised) testing for tuberculosis with Xpert MTB/RIF Ultra (Xpert) in 20 community health centres in Uganda.

Neurologic complications of breast cancer.

Breast cancer is a heterogeneous disease with unique neurologic complications that can arise from central nervous system (CNS) involvement or secondary to treatments themselves. As progress is made, with more targeted therapies and combinations available, particularly in the realm of human epidermal growth factor receptor 2 (HER2)-positive disease, the role of these new agents in patients with CNS disease is gradually evolving, although intracranial efficacy itself is lagging. At the same time, both systemic and local standard therapies pose clinical challenges regarding neurologic complications, such as peripheral neuropathy and cognitive changes.

Standard error estimation in meta-analysis of studies reporting medians.

We consider the setting of an aggregate data meta-analysis of a continuous outcome of interest. When the distribution of the outcome is skewed, it is often the case that some primary studies report the sample mean and standard deviation of the outcome and other studies report the sample median along with the first and third quartiles and/or minimum and maximum values. To perform meta-analysis in this context, a number of approaches have recently been developed to impute the sample mean and standard deviation from studies reporting medians.

Intraperitoneal Monocytes plus IFNs as a Novel Cellular Immunotherapy for Ovarian Cancer: Mechanistic Characterization and Results from a Phase I Clinical Trial.

Purpose: Ovarian cancer is the most lethal gynecologic cancer and intrinsically resistant to checkpoint immunotherapies. We sought to augment innate immunity, building on previous work with IFNs and monocytes.

Patients And Methods: Preclinical experiments were designed to define the mechanisms of cancer cell death mediated by the combination of IFNs α and γ with monocytes.

Making cough count in tuberculosis care.

Cough assessment is central to the clinical management of respiratory diseases, including tuberculosis (TB), but strategies to objectively and unobtrusively measure cough are lacking. Acoustic epidemiology is an emerging field that uses technology to detect cough sounds and analyze cough patterns to improve health outcomes among people with respiratory conditions linked to cough. This field is increasingly exploring the potential of artificial intelligence (AI) for more advanced applications, such as analyzing cough sounds as a biomarker for disease screening.

Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline.

Purpose: This guideline provides updated evidence-based recommendations addressing recent developments in the management of patients with brain metastases, including advanced radiation therapy techniques such as stereotactic radiosurgery (SRS) and hippocampal avoidance whole brain radiation therapy and the emergence of systemic therapies with central nervous system activity.

Methods: The American Society for Radiation Oncology convened a task force to address 4 key questions focused on the radiotherapeutic management of intact and resected brain metastases from nonhematologic solid tumors. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality.

Biomarkers That Correlate with Active Pulmonary Tuberculosis Treatment Response: a Systematic Review and Meta-analysis.

Current WHO recommendations for monitoring treatment response in adult pulmonary tuberculosis (TB) are sputum smear microscopy and/or culture conversion at the end of the intensive phase of treatment. These methods either have suboptimal accuracy or a long turnaround time. There is a need to identify alternative biomarkers to monitor TB treatment response.

Tuberculosis in times of COVID-19.

The COVID-19 pandemic has caused widespread disruptions to tuberculosis (TB) care and service delivery in 2020, setting back progress in the fight against TB by several years. As newer COVID-19 variants continue to devastate many low and middle-income countries in 2021, the extent of this setback is likely to increase. Despite these challenges, the TB community can draw on the comprehensive approaches used to manage COVID-19 to help restore progress and mitigate the impact of COVID-19 on TB.

Actinobacillus utilizes a binding protein-dependent ABC transporter to acquire the active form of vitamin B.

Bacteria require high-efficiency uptake systems to survive and proliferate in nutrient-limiting environments, such as those found in host organisms. ABC transporters in the bacterial plasma membrane provide a mechanism for transport of many substrates. In this study, we examine an operon containing a periplasmic binding protein in Actinobacillus for its potential role in nutrient acquisition.

Can we predict the severe course of COVID-19 - a systematic review and meta-analysis of indicators of clinical outcome?

Background: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19.

Methods: This systematic review was registered at PROSPERO under CRD42020177154.

A novel blood-based assay for treatment monitoring of tuberculosis.

Objectives: A novel 3-gene host transcriptional signature (GBP5, DUSP3 and KLF2) has been validated for tuberculosis (TB) treatment monitoring using laboratory-based RNA sequencing platforms. The signature was recently translated by Cepheid into a prototype cartridge-based test that can be run on the GeneXpert instrument. In this study, we prospectively evaluated the change in the expression of the cartridge-based 3-gene signature following treatment initiation among pulmonary TB patients who were microbiologically cured at the end of treatment.

Facility-based directly observed therapy (DOT) for tuberculosis during COVID-19: A community perspective.

Facility-based directly observed therapy (DOT) has been the standard for treating people with TB since the early 1990s. As the commitment to promote a people-centred model of care for TB grows, the use of facility-based DOT has been questioned as issues of freedom, privacy, and human rights have been raised. The disruptions caused by the COVID-19 pandemic and ensuing lockdown measures have fast-tracked the need to find alternative methods to provide treatment to people with TB.

"Triple-Negative Breast Cancer Central Nervous System Metastases From the Laboratory to the Clinic".

Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers and has an incidence as high as 50% of brain metastases once patients develop advanced disease. The lack of targeted and effective therapies, characteristic of this subtype of breast cancer, is especially evident once central nervous system (CNS) metastases occur. Compared with other subtypes of breast cancer, TNBC patients have the shorter interval from diagnosis to development of brain metastases and the shorter overall survival once they occur, a median of 4 to 6 months.

HER2-positive breast cancer brain metastasis: A new and exciting landscape.

Background: Brain metastases (BrM) incidence is 25% to 50% in women with advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Radiation and surgery are currently the main local treatment approaches for central nervous system (CNS) metastases. Systemic anti-HER2 therapy following a diagnosis of BrM improves outcomes.