Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients.

Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (α=0.05). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.

Exploratory Assessment of Galectin-1, -3, and -9 in Non-Small Cell Lung Cancer.

Galectins play a pivotal role in lung cancer oncogenic pathways, influencing apoptosis, angiogenesis, and tumor metastasis. Biomarkers that diagnose, prognose, and guide cancer treatment are crucial, with galectins having the biomarker potential for non-small cell lung cancer (NSCLC). Using enzyme-linked immunosorbent assay (ELISA), we assessed serum galectin-1, -3, and -9 levels in NSCLC patients. A retrospective chart review was performed to examine patient demographics, cancer stage, tumor biology, cancer treatment, and patient outcomes. Galectin levels were then compared across these factors. In this exploratory analysis, galectin-3 levels were significantly lower in patients with squamous cell lung cancer (p = 0.0019) and in patients exposed to chemotherapy (p = 0.0375). Galectin-1 levels were significantly lower in patients with previous metastasis but had no correlation with future metastasis. Abnormal galectin-1 levels were significantly correlated with decreased overall survival (OS) in NSCLC (p = 0.0357) and specifically in patients with surgically resectable NSCLC (p = 0.0112). However, abnormal galectin-1 levels were not found to correlate with decreased OS in multivariable analysis (p = 0.0513). These findings may have clinical implications as galectin-3 inhibitors are in trials for NSCLC. Additionally, they suggest that galectin-1 has potential as a prognostic marker for surgically resectable NSCLC.

Oncology Nurses Can Build Patient-Centered Outcomes Research Partnerships.

Nurses can inform and lead patient-centered outcomes research (PCOR) projects that address care-related questions prioritized by patients. However, PCOR projects may fail to materialize because time constraints create barrier.

Pattern Analysis of Serum Galectins-1, -3, and -9 in Breast Cancer.

Galectins have been shown to have roles in cancer progression via their contributions to angiogenesis, metastasis, cell division, and the evasion of immune destruction. This study analyzes galectin-1, -3, and -9 serum concentrations in breast cancer patients through enzyme-linked immunosorbent assay (ELISA) against the characteristics of the patient and the tumor such as stage, molecular subtype, and receptor expression. Galectin-9 was found to be statistically significantly increased in HER2-enriched tumors and reduced in patients with hormone-receptor-positive tumors. Galectin-1 was found to be statistically significantly increased in the serum of patients who had undergone hormonal, immunotherapy, or chemotherapy. These findings provide insight into the changes in galectin levels during the progress of cancer, the response to treatment, and the molecular phenotype. These findings are valuable in the further understanding of the relationships between galectin and tumor biology and can inform future research on therapeutic targets for galectin inhibitors and the utility of galectin biomarkers.

Comprehensive and User-Analytics-Friendly Cancer Patient Database for Physicians and Researchers.

Nuanced cancer patient care is needed, as the development and clinical course of cancer is multifactorial with influences from the general health status of the patient, germline and neoplastic mutations, co-morbidities, and environment. To effectively tailor an individualized treatment to each patient, such multifactorial data must be presented to providers in an easy-to-access and easy-to-analyze fashion. To address the need, a relational database has been developed integrating status of cancer-critical gene mutations, serum galectin profiles, serum and tumor glycomic profiles, with clinical, demographic, and lifestyle data points of individual cancer patients. The database, as a backend, provides physicians and researchers with a single, easily accessible repository of cancer profiling data to aid-in and enhance individualized treatment. Our interactive database allows care providers to amalgamate cohorts from these groups to find correlations between different data types with the possibility of finding "molecular signatures" based upon a combination of genetic mutations, galectin serum levels, glycan compositions, and patient clinical data and lifestyle choices. Our project provides a framework for an integrated, interactive, and growing database to analyze molecular and clinical patterns across cancer stages and subtypes and provides opportunities for increased diagnostic and prognostic power.

Tixagevimab-Cilgavimab: COVID-19 Pre-Exposure Prophylaxis.

Tixagevimab-cilgavimab is the only nonvaccine drug currently authorized in the United States for the prevention of COVID-19 infection in individuals who are moderately to severely immunocompromised or unable to receive COVI.

KIT Mutations Correlate with Higher Galectin Levels and Brain Metastasis in Breast and Non-Small Cell Lung Cancer.

To investigate a potential role for galectins as biomarkers that enable diagnosis or prognostication of breast or non-small cell lung cancer, the serum levels of galectins -1, -3, -7, -8, and -9 of cancer patients determined by ELISA assays were compared to the mutation status of 50 known cancer-critical genes, which were determined using multiplex PCR in tumors of the same patients. Mutations in the KIT proto-oncogene, which codes for the c-Kit protein, a receptor tyrosine kinase, correlated with higher levels of galectins -1, -3, -8, and -9 in breast cancer patients and galectin-1 in non-small cell lung cancer patients. Mutations in the KIT gene were more likely found in brain metastases from both of these primary cancers. The most common KIT mutation in our panel was p.M541L, a missense mutation in the transmembrane domain of the c-Kit protein. These results demonstrate an association between KIT oncogenic signaling and elevated serum galectins in patients with metastatic disease. Changes in protein trafficking and the glycocalyx composition of cancer cells may explain the observed alterations in galectin expression. This study can be useful for the targeted selection of receptor tyrosine kinase and galectin inhibitor anti-cancer treatments.

Hypofractionated Radiation: Understanding the Modality and Impact on Patient Outcomes 
.

Radiation therapy has been used as a method to treat cancer since the early 1900s (Gianfaldoni et al., 2017). As of 2020, radiation continues to be a common treatment modality received by 50%-70% of patients with cancer at some point during the course of treatment (Peng et al., 2020). Numerous advances in radiation technology have occurred since its initial discovery, yet the goal of radiation remains the same. While chemotherapy is a systemic treatment, radiation therapy is designed to locally treat a malignancy. Unlike chemotherapy, radiation uses high-energy photon beams (x-ray or gamma rays), or charged particles (electrons or protons), to target specific locations of the body (Gianfaldoni et al., 2017). The damage to the DNA of the cells in the targeted region leads to eventual cell death, while allowing healthy cells outside of the targeted field to remain unaffected. Although toxicities occur, patients often experience fewer side effects during radiation therapy compared to chemotherapy because of its targeted approach. Advances in technology have led to better opportunities for targeting smaller areas of the body, reducing the potential for side effects (Garibaldi et al., 2017). In addition, radiation can be divided into larger doses to be given once a day, or less often, and is sometimes used as a shorter course of treatment. This is known as hypofractionated radiation. This article will explain the differences in radiation therapy modalities, focusing on hypofractionation and its benefits to patients.

Increased Circulating Levels of Galectin Proteins in Patients with Breast, Colon, and Lung Cancer.

Galectins are proteins with high-affinity ß-galactoside-binding sites that function in a variety of signaling pathways through interactions with glycoproteins. The known contributions of galectins-1, -3, -7, -8, and -9 to angiogenesis, metastasis, cell division, and evasion of immune destruction led us to investigate the circulating levels of these galectins in cancer patients. This study compares galectin concentrations by enzyme-linked immunosorbent assay (ELISA) from each stage of breast, lung, and colon cancer. Galectins-1 and -7, which share a prototype structure, were found to have statistically significant increases in breast and lung cancer. Of the tandem-repeat galectins, galectin-8 showed no statistically significant change in these cancer types, but galectin-9 was increased in colon and lung cancer. Galectin-3 is the only chimera-type galectin and was increased in all stages of breast, colon, and lung cancer. In conclusion, there were significant differences in the galectin levels in patients with these cancers compared with healthy controls, and galectin levels did not significantly change from stage to stage. These findings suggest that further research on the roles of galectins early in disease pathogenesis may lead to novel indications for galectin inhibitors.

Preventing weight gain in adults: A systematic review and meta-analysis of randomized controlled trials.

Weight gain prevention is a global public health priority to address escalating adiposity in adults. This review evaluates the efficacy of weight gain prevention trials targeting adults aged 18-50 years and adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Trials of any duration from inception to May 2020 that evaluated a weight gain prevention intervention (using either prescriptive diet, prescriptive physical activity, prescriptive diet, and/or physical activity or non-prescriptive lifestyle) and included weight or body mass index (weight [kg]/height [m2 ]) were eligible. Twenty-nine trials across 34 publications (participants n = 37,407) were included. Intervention resulted in less weight gain compared with controls (-1.15 kg [95% CI -1.50, -0.80 kg] p < 0.001). Subgroup analysis demonstrated greater effectiveness with prescriptive (-1.60 kg [95% CI -2.00, -1.19] p < 0.001) compared with non-prescriptive (-0.81 kg [95% CI 1.10, -0.53] p < 0.001) intervention types. Interventions had greatest impact in healthy weight (18.5-24.9 kg/m2 ) (-0.82 kg [95% CI -1.5, -0.50] p < 0.001) or overweight (25.0-29.9 kg/m2 ) (-1.48 kg [95% CI -1.85, -1.12] p < 0.001) compared with obese populations (≥30.0 kg/m2 ) (-0.56 kg [95% CI -1.40, 0.27] p = 0.19). These findings demonstrate that lifestyle intervention prevents cumulative weight gain in non-obese adults, with future research required to inform cost-effectiveness and implementation feasibility.

Rising to the Occasion During the COVID-19 Pandemic.

Nurses across specialties continue to play a key role in the response to the COVID-19 pandemic. Oncology nurses are no exception. In response to COVID-19 and other healthcare issues, nurses have established core competencies. These core competencies allow us to mentor others if we simply step up and take the lead.

Convalescent Plasma: Education and Administration Implications.

Convalescent plasma has emerged as a treatment that merits consideration for COVID-19-positive patients requiring hospitalization. With millions of cases of COVID-19 being reported worldwide, nurses across specialties are caring for infected patients and are often the primary patient educators about convalescent plasma treatment. Keeping abreast of current clinical guidelines and evidence-based practice allows nurses to identify patients who should be considered for treatment, understand the administration guidelines, and be aware of the toxicity profile to provide safe and high-quality care to patients. The purpose of this article is to provide information on convalescent plasma as a treatment for COVID-19.

Efficacy of therapeutic plasma exchange in the treatment of penn class 3 and 4 cytokine release syndrome complicating COVID-19.

OBJECTIVES: Cytokine release syndrome (CRS) is a potentially severe complication of COVID-19 most commonly resulting in respiratory failure. This ten-patient study was designed to determine the efficacy of therapeutic plasma exchange (TPE) in improving oxygenation and in reducing the cytokine load in a critically ill subset of patients. METHODS: Five single volume plasma exchanges over eight days within a 14-day study period. In mechanically ventilated patients, oxygenation was measured via the PaO2/FiO2 (P/F) ratio and the oxygenation index (OI) daily for 14 days. Supplemental oxygen requirements were tracked daily for non-ventilated patients. RESULTS: Non-ventilated patients were liberated from supplemental oxygen after TPE. The response was rapid with an 87% average reduction in oxygenation requirements following and average time to return to room air of 5.25 days. All mechanically ventilated patients demonstrated improvement in oxygenation with a 78% average improvement in the P/F ratio and a 43% improvement in OI. C-reactive protein (CRP) and serum levels of IL-6, IL-8, IL-10, TNFα, IFNγ and GM-CSF, were measured daily with immediate post TPE levels drawn on days 1, 2, 4, 6 and 8. All patients demonstrated significant reductions in CRP, IL-6, IL-10 and TNFα. CONCLUSIONS: In the majority of patients with Penn class 3 and 4 CRS complicating COVID-19, TPE demonstrated a prompt improvement in oxygenation and reduction in cytokine load without compromising patient safety. As this pilot study was envisioned to be hypothesis generating, expanded trials using TPE alone and in conjunction with novel pharmacologic agents are warranted. REGISTRATION: ClinicalTrials.gov NCT04374149.

Genetic Biomarkers: Implications of Increased Understanding and Identification in Lung Cancer Management.

BACKGROUND: In the management of lung cancer, molecular profiling of the tumor is pivotal to defining a personalized treatment plan and is recommended for each patient. OBJECTIVES: The purpose of this article is to provide an update on genomic testing in lung cancer and the associated targeted treatment options. In addition, emerging biomarkers and mechanisms of resistance are discussed. METHODS: A comprehensive review of the CINAHL®, MEDLINE®, and PubMed® databases was performed. FINDINGS: Molecular tumor profiling has advanced treatment options for patients diagnosed with lung cancer. Knowledge about pathologic variants and inhibitory pathways have led to the development of targeted treatments for lung cancer. Based on a solid understanding of molecular biomarkers, testing protocols, testing results, and how biomarkers affect treatment decisions, nurses can best educate and support patients and family members as clinical care incorporates molecular profiling.

Postpartum Diet Quality: A Cross-Sectional Analysis from the Australian Longitudinal Study on Women's Health.

Reproductive-aged women are at high risk of developing obesity, and diet quality is a potential modifiable risk factor. There is limited research exploring diet quality and its association with time since childbirth. Using data from the Australian Longitudinal Study on Women's Health (ALSWH) survey 5 (2009) of women born between 1973-1978, who reported having previously given birth, we investigated the association between time since childbirth and diet quality, and differences in energy, macronutrients, micronutrient intake, and diet quality assessed by the dietary guideline index (DGI) in women stratified by time from last childbirth, early (0-6 months; n = 558) and late (7-12 months; n = 547), and all other women with children (>12 months post childbirth n = 3434). From this cohort, 8200 participants were eligible, of which 4539 participants completed a food frequency questionnaire (FFQ) and were included in this analysis. Overall, diet quality was higher in early and late postpartum women (mean DGI score 89.8 (SD 10.5) and mean DGI score 90.0 (SD 10.2), respectively) compared to all other women with children (>12 months post childbirth), mean DGI score 85.2 (SD 11.7), p < 0.001. Factors positively associated with diet quality included higher education, physical activity, health provider support, and vitamin and/or mineral supplement use. Conversely, increasing time from childbirth (>12 months), smoking compared with non-smoking and medium income level compared with no income was negatively associated with diet quality. A lower diet quality in women greater than 12 months post childbirth may be reflective of increased pressures, balancing childrearing and return to work responsibilities. This highlights the need to support women beyond the postpartum period to improve modifiable factors associated with weight gain, including diet quality, to optimize health and reduce chronic disease risk.

Diet Quality and Its Effect on Weight Gain Prevention in Young Adults: A Narrative Review.

Global environmental and societal changes have resulted in an increased consumption of energy-dense foods contributing to escalating obesity prevalence, with most rapid weight gain occurring in young adults. Diet is one major modifiable factor contributing to escalating obesity prevalence. Understanding overall diet quality of populations at high risk for weight gain and obesity development, including young adults, provides evidence of dietary intakes, dietary patterns, and associated behaviors, to inform the development of targeted interventions aimed at the prevention of weight gain. This narrative review synthesizes the current evidence of the association between diet quality and weight gain in young adults. Overall, there is a consistent direction of association between improved diet quality and reduced weight gain in adults. This demonstrates the potential of small improvements in diet quality over time as a probable contributor to minimizing weight gain in young adults. Future research evaluating environmental nutrition policies with associated change in diet quality and prospective weight change in population-based studies is warranted to determine their longer-term impact in improving overall diet quality as one strategy to halt escalating obesity prevalence rates.

Diet Quality in a Weight Gain Prevention Trial of Reproductive Aged Women: A Secondary Analysis of a Cluster Randomized Controlled Trial.

Reproductive-aged women are at high risk for obesity development. Limited research exploring weight gain prevention initiatives and associated modifiable risk factors, including diet quality exists. In a secondary analysis of a 12 month, cluster randomized controlled trial for weight gain prevention in reproductive-aged women, we evaluated change in diet quality, macronutrient and micronutrient intake, predictors of change and associations with weight change at follow-up. Forty-one rural towns in Victoria, Australia were randomized to a healthy lifestyle intervention (n = 21) or control (n = 20). Women aged 18⁻50, of any body mass index and without conditions known to affect weight, were recruited. Diet quality was assessed by the Dietary Guideline Index (DGI) and energy, macronutrient, and micronutrient intake as well as anthropometrics (weight; kg) were measured at baseline and 12 months. Results were adjusted for group (intervention/control), town cluster, and baseline values of interest. Of 409 women with matched data at baseline and follow-up, 220 women were included for final analysis after accounting for plausible energy intake. At 12 months, diet quality had improved by 6.2% following the intervention, compared to no change observed in the controls (p < 0.001). Significant association was found between a change in weight and a change in diet quality score over time ß -0.66 (95%CI -1.2, -0.12) p = 0.02. The percentage of energy from protein (%) 0.009 (95%CI 0.002, 0.15) p = 0.01 and glycemic index -1.2 (95%CI -2.1, -0.24) p = 0.02 were also improved following the intervention, compared to the control group. Overall, a low-intensity lifestyle intervention effectively improves diet quality, with associated weight gain preventions, in women of reproductive age.

Exploring Diet Quality between Urban and Rural Dwelling Women of Reproductive Age.

Health disparities, including weight gain and obesity exist between urban and rural dwelling women. The primary aim was to compare diet quality in urban and rural women of reproductive age, and secondary analyses of the difference in macronutrient and micronutrient intake in urban and rural women, and the predictors of diet quality. Diet quality was assessed in urban (n = 149) and rural (n = 394) women by a modified version of the Dietary Guideline Index (DGI) energy, macronutrient and micronutrient intake from a food frequency questionnaire (FFQ) and predictors of diet quality. Diet quality did not significantly differ between urban and rural women (mean ± standard deviation (SD), 84.8 ± 15.9 vs. 83.9 ± 16.5, p = 0.264). Rural women reported a significantly higher intake of protein, fat, saturated fat, monounsaturated fat, cholesterol and iron and a higher score in the meat and meat alternatives component of the diet quality tool in comparison to urban women. In all women, a higher diet quality was associated with higher annual household income (>$Australian dollar (AUD) 80,000 vs. <$AUD80,000 p = 0.013) and working status (working fulltime/part-time vs. unemployed p = 0.043). Total diet quality did not differ in urban and rural women; however, a higher macronutrient consumption pattern was potentially related to a higher lean meat intake in rural women. Women who are unemployed and on a lower income are an important target group for future dietary interventions aiming to improve diet quality.

The Assessment of Diet Quality and Its Effects on Health Outcomes Pre-pregnancy and during Pregnancy.

Overweight and obesity pre pregnancy or during pregnancy is associated with an increased risk for maternal obstetric and fetal complications. Diet is one modifiable risk factor that women may be motivated to improve. General healthy eating guidelines, micronutrient sufficiency and macronutrient quantity and quality are important nutrition considerations pre and during pregnancy. With regards to specific nutrients, health authorities have recommendations for folate and/or iodine supplementation; but not consistently for iron and omega-3 despite evidence for their association with health outcomes. There are modest additional requirements for energy and protein, but not fat or carbohydrate, in mid-late pregnancy. Diet indices and dietary pattern analysis are additional tools or methodologies used to assess diet quality. These tools have been used to determine dietary intakes and patterns and their association with pregnancy complications and birth outcomes pre or during pregnancy. Women who may unnecessarily resist foods due to fear of food contamination from listeriosis and methylmercury may limit their diet quality and a balanced approached is required. Dietary intake may also vary according to certain population characteristics. Additional support for women who are younger, less educated, overweight and obese, from socially disadvantaged areas, smokers and those who unnecessarily avoid healthy foods, is required to achieve a higher quality diet and optimal lifestyle peri conception.