Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.     

Collaborating toward equity in Pennsylvania: The Age-Friendly Care,PA project

Objective

To collaboratively implement the age-friendly health systems framework, known as the 4Ms: What Matters, Medication, Mentation, and Mobility, at The Primary Health Network (PHN), a federally qualified health center.

Data Sources

Data were collected from PHN electronic medical records (EMRs) for individuals over age 65 from December 30, 2019 to December 24, 2021 and from Project ECHO© attendance and evaluation surveys.

Study Design

The telementoring educational program, Project ECHO©, was used to engage PHN health care professionals working in rural areas of Pennsylvania to incorporate the 4Ms into their practice starting with the annual wellness visit (AWV). Project ECHO© was launched at three primary care sites. After 18 months, it was then disseminated to an additional 18 sites creating pilot and comparison groups. Outcomes included codesigned patient process metrics using EMR data and project ECHO© participant data.

Data Collection Methods

EMR data were generated by system reports created by PHN's quality assurance program manager. Project ECHO© data were collected and managed using REDCap electronic data capture tools. Outcomes were aggregated, analyzed for trends over time, and compared between groups.

Principal Findings

All nine process outcomes increased from baseline to follow-up at the three initial sites, ranging from 4% to 43% g. At year two, the three initial sites had higher rates on AWVs (pilot 24%, comparison 12%; p < 0.0001), Advance Care Planning (New on file, pilot 8%, comparison 2%; Discussed with patient, pilot 18%, comparison 13%; Patient declined, pilot 0%, comparison 0%; p = 0.0001), Dementia Screening (pilot 24%, comparison 12%; p < 0.0001), Fall Risk Management (pilot 43%, comparison 10%; p < 0.0001), and Mobility Goal (pilot 19%, comparison 9%; p < 0.0001); and lower rates on High-Risk Medication Elimination (pilot 54%, comparison, 63%, p < 0.02).

Conclusions

Access to high-quality geriatric care for rural older adults can be improved by increasing health care professionals' knowledge of the 4Ms, beginning with its incorporation into the AWV.     

Bioimpedance as a measure of fluids in patients with septic shock. A prospective observational study

Background

Septic shock is often treated with aggressive fluid resuscitation leading to profound fluid overload. The assessment of fluid status relies on suboptimal measures making treatment difficult. Bioelectrical impedance analysis is an alternative but the validity is unclear. The aim of this study was to determine the validity of bioelectrical impedance analysis for fluid measures in patients with septic shock.

Methods

Single-center, prospective observational cohort study. We included adult ICU patients with septic shock. We evaluated the agreement between measures on the left and right side of the patient and measures 1 h apart by two bioelectrical impedance devices. Results are presented as Bland Altman plots with 95% Limits of Agreements (LoA) and as correlations between bioelectrical impedance analysis results and clinical markers of fluids.

Results

Forty-nine patients were included. The agreement between measures on the left and the right side of the patient and after 1 h was overall without bias, but with wide LoA's. Fluid overload 1 h apart showed the most narrow 95% LoA (−2.4–2.9 L). The same wide limits of agreements were observed when comparing devices. For example, total body water with 95% LoA of −14.8 –16.7 L. Correlations between bioelectrical impedance analysis and clinical measures were low but statistically significant.

Conclusions

In patients with septic shock bioelectrical impedance analysis had no systematic errors or bias, but wide limits of agreement, indicating that the devices have a large and uncorrectable random error. Fluid status by bioelectrical impedance analysis is not sufficiently accurate to guide treatment in this group of patients.     

Therapeutic augmentation of NO-sGC-cGMP signalling: lessons learned from pulmonary arterial hypertension and heart failure

Heart Failure Reviews - The nitric oxide (NO)–guanylate cyclase (GC)–cyclic guanosine monophosphate (cGMP) pathway plays an important role in cardiovascular, pulmonary and renal...     

Psychosocial outcomes of group prenatal care

Journal of Public Health - Group prenatal care provides an alternative model of prenatal care that allows for collaboration with peers, education, discussion, and self-management training in...     

Effects of Wenyang Zhenshuai Granules on the Expression of Key Mitochondrial Autophagy Proteins in the Doxorubicin-Induced Model of H9c2 Cardiomyocyte Injury

Bulletin of Experimental Biology and Medicine - This study aimed to explore the effects of Wenyang Zhenshuai granules (WZG) on the morphology of cardiomyocytes, cell viability, and the expression...     

RNA sequencing steps toward the first line

• DNA is the sequence that codes for proteins.
• Messenger RNA is transcribed from the DNA sequence of genes and translated into protein.
• It can be difficult to predict how a change in the DNA sequence will affect messenger RNA and protein quantity and quality.
• DNA translocation changes can cause the joining of sequences from two different genes or different parts of the same gene.
• DNA sequencing is often used clinically to predict how DNA changes might affect proteins.
• Alternatively, RNA sequencing can be used as a more direct measure of the effect of DNA changes on the protein products.
• This sequencing is important for identifying changes in cancer that may indicate response to targeted therapy, prognosis, or diagnosis.