Preliminary Analysis of Gut Microbiome and Gastrointestinal Symptom Burden in Breast Cancer Patients Receiving Chemotherapy Compared to Healthy Controls.

BACKGROUND: Alterations in the naturally occurring bacteria of the gut, known as the gastrointestinal (GI) microbiome, may influence GI symptoms in women with breast cancer. OBJECTIVE: This work aims to describe GI symptom occurrence, duration, severity, and distress and measures of the GI microbiome among women with breast cancer receiving chemotherapy compared to age- and sex-matched healthy controls. INTERVENTIONS/METHODS: 22 women with breast cancer receiving chemotherapy and 17 healthy control women provided stool specimens and GI symptom data using the modified Memorial Symptom Assessment Scale (MSAS). The fecal microbiome was profiled by metagenomic sequencing of 16S Ribosomal RNA (rRNA). GI microbiome was compared between groups using alpha-diversity (Observed OTU number and Shannon index), beta-diversity (UniFrac distances), and relative abundance of select genera. RESULTS: GI symptoms with high symptom reports among breast cancer patients included nausea, diarrhea, flatulence, dry mouth, taste change, and poor appetite. Indices of differential abundance (beta diversity) significantly distinguished between breast cancer patients and healthy controls. Unique bacterial features differentiating the 2 groups were Prevotella_9, Akkermansia, Lachnospira, Lachnospiraceae_NK4A136, Lachnoclostridium, and Oscillibacter. CONCLUSIONS: Gut bacteria are associated with GI inflammation and mucus degradation, suggesting the potential role of the GI microbiome in GI symptom burden. Understanding the influence of GI bacteria on gut health and symptoms will help harness the enormous potential of the GI microbiome as a future diagnostic and therapeutic agent to reduce the symptom burden associated with chemotherapy.

Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria.

As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.

Longitudinal Subgrouping of Patients With Cancer Based on Symptom Experiences: An Integrative Review.

PROBLEM IDENTIFICATION: The purpose of this integrative review is to identify literature describing (a) subgrouping patients with cancer based on symptom experiences and their patterns of symptom changes over time and (b) methodologies of subgrouping patients with cancer based on symptom experiences. LITERATURE SEARCH: PubMed®, CINAHL®, and PsycINFO® were searched through January 2019. DATA EVALUATION: Studies were appraised for patterns of symptom change over time and methodologic approach using the QualSyst quality rating scale. SYNTHESIS: 11 studies met inclusion criteria. Clinical variables that influence symptom patterns were diverse. The most common clustering method was latent variable analysis (73%), and all studies collected symptom data prospectively using survey analysis to assess symptoms. IMPLICATIONS FOR PRACTICE: The majority of studies (91%) observed that the symptom experience within the group of patients with cancer changed over time. Identifying groups of patients with similar symptom experiences is useful to determine which patients need more intensive symptom management over the trajectory of cancer treatment, which is essential to improve symptoms and quality of life.

Multiple sclerosis patients have an altered gut mycobiome and increased fungal to bacterial richness.

Trillions of microbes such as bacteria, fungi, and viruses exist in the healthy human gut microbiome. Although gut bacterial dysbiosis has been extensively studied in multiple sclerosis (MS), the significance of the fungal microbiome (mycobiome) is an understudied and neglected part of the intestinal microbiome in MS. The aim of this study was to characterize the gut mycobiome of patients with relapsing-remitting multiple sclerosis (RRMS), compare it to healthy controls, and examine its association with changes in the bacterial microbiome. We characterized and compared the mycobiome of 20 RRMS patients and 33 healthy controls (HC) using Internal Transcribed Spacer 2 (ITS2) and compared mycobiome interactions with the bacterial microbiome using 16S rRNA sequencing. Our results demonstrate an altered mycobiome in RRMS patients compared with HC. RRMS patients showed an increased abundance of Basidiomycota and decreased Ascomycota at the phylum level with an increased abundance of Candida and Epicoccum genera along with a decreased abundance of Saccharomyces compared to HC. We also observed an increased ITS2/16S ratio, altered fungal and bacterial associations, and altered fungal functional profiles in MS patients compared to HC. This study demonstrates that RRMS patients had a distinct mycobiome with associated changes in the bacterial microbiome compared to HC. There is an increased fungal to bacterial ratio as well as more diverse fungal-bacterial interactions in RRMS patients compared to HC. Our study is the first step towards future studies in delineating the mechanisms through which the fungal microbiome can influence MS disease.

The Influence of Multiple Chronic Conditions on Symptom Clusters in People With Solid Tumor Cancers.

BACKGROUND: People with cancer who also have multiple chronic conditions (MCCs) experience co-occurring symptoms known as symptom clusters. OBJECTIVE: To describe MCC and symptom clusters in people with cancer and to evaluate the relationships between MCCs and symptom severity, symptom interference with daily life, and quality of life (QoL). METHODS: Weekly over a 3-week chemotherapy cycle, 182 adults with solid tumor cancer receiving chemotherapy completed measures of symptom severity, symptom interference with daily life, and QoL. Medical records reviewed to count number of MCCs in addition to cancer. Exploratory factor analysis was performed to identify symptom clusters. The relationships between the number of MCCs and the outcomes (symptom severity and symptom interference with daily life and QoL) at each time point were examined using the χ2 test. Longitudinal changes in outcomes were examined graphically. RESULTS: The number of MCCs ranged from 0 to 9, but most participants (62.1%) had 2 or fewer MCCs. Obesity was the most prevalent chronic condition. Four symptom clusters were identified: nutrition, neurocognitive, abdominal discomfort, and respiratory clusters. At each time point, no significant differences were found for MCCs and any outcome. However, symptom severity in all the symptom clusters, symptom interference with daily life, and QoL demonstrated a worsening in the week following chemotherapy. CONCLUSION: A majority of our sample had 2 or fewer MCCs, and MCCs did contribute to patient outcomes. Rather, timing of chemotherapy cycle had the greatest influence of patient outcomes. IMPLICATIONS FOR PRACTICE: Additional support on day 7 of chemotherapy treatment is needed for people with MCCs.

The role of spirituality in symptom experiences among adults with cancer.

PURPOSE: Adults with cancer experience symptoms such as pain, fatigue, depression, and sleep disturbance, which can impede quality of life. Research suggests that addressing spirituality may be one route to support holistic symptom management. The purpose of this study is to explore how spirituality relates to common cancer-related symptoms (including severity, distress, and interference) among a sample of adults with cancer. METHODS: This is a secondary analysis of data from N = 200 solid tumor cancer patients undergoing chemotherapy. Symptom experiences were assessed with a modified version of the Memorial Symptom Assessment Scale and the M. D. Anderson Symptom Inventory-Interference Subscale. Spirituality was assessed using a subset of items from the Fox Simple Quality of Life Scale. A series of ordinal and linear regressions were used to examine the relationship between spirituality and symptom severity, symptom-related distress, and symptom interference across four cancer-related symptoms (pain, fatigue, depression, and sleep disturbance). RESULTS: Higher spirituality trended toward an association with lower pain severity, although results were not significant (p < .058). Higher spirituality was significantly associated with lower severity of fatigue (p < .003), depression (p < .006), and sleep disturbance (p < .004). Spirituality was not significantly associated with any of the four symptom-related distress outcomes. Higher spirituality was significantly associated with lower overall symptom interference (p < .004). DISCUSSION: This study highlights the role of spirituality in the experience of cancer-related symptoms. Additional research is needed among more diverse samples of people with cancer. This foundational work could lead to the development of symptom management interventions that incorporate aspects of spirituality.

Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer.

BACKGROUND: Though the gut microbiome has been associated with efficacy of immunotherapy (ICI) in certain cancers, similar findings have not been identified for microbiomes from other body sites and their correlation to treatment response and immune related adverse events (irAEs) in lung cancer (LC) patients receiving ICIs. METHODS: We designed a prospective cohort study conducted from 2018 to 2020 at a single-center academic institution to assess for correlations between the microbiome in various body sites with treatment response and development of irAEs in LC patients treated with ICIs. Patients must have had measurable disease, ECOG 0-2, and good organ function to be included. Data was collected for analysis from January 2019 to October 2020. Patients with histopathologically confirmed, advanced/metastatic LC planned to undergo immunotherapy-based treatment were enrolled between September 2018 and June 2019. Nasal, buccal and gut microbiome samples were obtained prior to initiation of immunotherapy +/- chemotherapy, at development of adverse events (irAEs), and at improvement of irAEs to grade 1 or less. RESULTS: Thirty-seven patients were enrolled, and 34 patients were evaluable for this report. 32 healthy controls (HC) from the same geographic region were included to compare baseline gut microbiota. Compared to HC, LC gut microbiota exhibited significantly lower α-diversity. The gut microbiome of patients who did not suffer irAEs were found to have relative enrichment of Bifidobacterium (p = 0.001) and Desulfovibrio (p = 0.0002). Responders to combined chemoimmunotherapy exhibited increased Clostridiales (p = 0.018) but reduced Rikenellaceae (p = 0.016). In responders to chemoimmunotherapy we also observed enrichment of Finegoldia in nasal microbiome, and increased Megasphaera but reduced Actinobacillus in buccal samples. Longitudinal samples exhibited a trend of α-diversity and certain microbial changes during the development and resolution of irAEs. CONCLUSIONS: This pilot study identifies significant differences in the gut microbiome between HC and LC patients, and their correlation to treatment response and irAEs in LC. In addition, it suggests potential predictive utility in nasal and buccal microbiomes, warranting further validation with a larger cohort and mechanistic dissection using preclinical models. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03688347 . Retrospectively registered 09/28/2018.

Post-treatment head and neck cancer survivors' approaches to self-management: A qualitative study.

PURPOSE: Post-treatment head and neck cancer (HNC) survivors contend with distinct, long-term challenges related to cancer treatments that impact their day-to-day lives. Alongside follow-up cancer care, they also must be responsible for the daily management of often intrusive physical and psychological symptoms, as well as maintaining their health and a lifestyle to promote their well-being. The purpose of this study was to identify HNC survivors' approaches toward engagement in self-management activities. METHODS: Post-treatment HNC survivors (N=22) participated in the study through purposeful sampling. Participants were eligible if they 1) had a history of upper aerodigestive tract cancer; 2) completed their most recent primary treatment (i.e. chemotherapy, radiation, and surgery) more than eighteen months prior and had no evidence of HNC, and 3) could speak in English. A semi-structured interview was used. Data was analyzed using content analysis. RESULTS: We identified three approaches that survivors took towards self-management activities: taking charge, living with it, and engaging as needed. Our results showed that taking charge is when survivors take an active role in evaluating their health and taking action subsequently; as needed represents engaging in self-management as necessary; and living with it reflects adapting to the symptoms and side effects without managing them. CONCLUSIONS: We propose self-management approaches as a novel mechanism to understand the relationship between survivors' characteristics and health preferences and their self-management. It is important for clinicians to highlight the variation in individuals 'self-management approaches as they work to identify tailored patient-centered strategies that compliment specific patient needs.

An integrated model of multimorbidity and symptom science.

BACKGROUND: Prevalence and complexity of persons with multiple chronic conditions (MCC), also known as multimorbidity, are shifting clinical practice from a single disease focus to one considering MCC and symptoms. Although symptoms are intricately bound to concepts inherent in MCC science, symptoms are largely ignored in multimorbidity research and literature. PURPOSE: Introduce an Integrated Model of Multimorbidity and Symptom Science. METHODS: Critical integrative review and synthesis process. FINDINGS: The model comprises three primary domains: 1. Contributing/ Risk Factors; 2. Symptom/Disease/Treatment Interactions; and 3. Patient Outcomes. DISCUSSION: The model highlights the multilevel nature of contributing factors and the recursive interactions among multiple etiologies, conditions, symptoms, therapies, and outcomes.

Are Perceived Stress and Cytokine Genotypes Clinically Feasible as Predictors of Psychoneuroimmune Symptoms in Advanced Cancer?

CONTEXT: Genetic variability and perceived stress have been identified as likely predictors of psychoneuroimmune (PNI) symptoms in patients with cancer. In the clinical setting, the ability to identify the patients at greatest risk of development of severe PNI symptoms continues to be elusive. OBJECTIVE: To evaluate the feasibility of cytokine genes and perceived stress scores as clinical predictors of PNI symptom severity in patients with a new diagnosis of advanced cancer compared with cancer-free controls (CFCs). DESIGN: Patients with advanced-stage cancer beginning chemotherapy and CFCs completed questionnaires at 6 time points during 24 weeks and provided blood samples for genotyping. MAIN OUTCOME MEASURES: Associations between single-nucleotide polymorphisms in cytokine genotypes and perceived stress scores with PNI symptom severity were evaluated using bivariate analysis. RESULTS: Forty-two participants were recruited (21 patients with cancer and 21 CFCs). Patients with cancer and CFCs were demographically similar and had similar allele frequencies for 15 of 16 single-nucleotide polymorphisms. Cancer-affected patients reported higher perceived stress and PNI symptom severity. Associations were found between several single-nucleotide polymorphisms and PNI symptoms, but no clear pattern emerged across time. Perceived stress was associated with PNI symptom severity for memory problems and fatigue at all 6 time points. CONCLUSION: Perceived stress performed better than cytokine genotypes as a clinical predictor of PNI symptoms in this small-scale study. Assessing perceived stress is an easy and low-cost approach that can be used to identify patients at high risk of PNI symptom development.

Postdoctoral Opportunities for Nursing PhD Graduates: A Resource Guide.

Before completing a nursing PhD program, doctoral students are encouraged to seek out and apply for a position in one of many, often highly competitive postdoctoral programs. These programs include the more traditional National Institutes of Health (NIH) funded experiences, such as the T32, as well as the nontraditional institution funded positions, including the associate faculty role. Graduates often need guidance on which postdoctoral programs are available, the resources each program offers to promote development of the applicant's program of research, the disadvantages of each program, and what each program uses as benchmarks for success. This article summarizes both traditional and nontraditional postdoctoral positions including the T32, F32, F99/K00, T90/R90, research supplements, associate faculty, research associate, and hospital-affiliated postdoctoral positions. This article updates previous papers describing postdoctoral opportunities and offers a starting place to aide PhD students planning their postgraduate activities in seeking and evaluating these positions.

Systematic Review of Nonpharmacologic Approaches for the Management of Gastrointestinal Symptoms.

PROBLEM IDENTIFICATION: To summarize and critique the literature for nonpharmacologic complementary approaches to manage gastrointestinal (GI) symptoms attributed to chemotherapy. LITERATURE SEARCH: A literature search was conducted using CINAHL®, MEDLINE®, and PsycINFO® from database inception through January 2018. DATA EVALUATION: Studies were independently appraised by each author regarding inclusion eligibility and summary of GI symptom outcomes and the nonpharmacologic complementary intervention. SYNTHESIS: 57 studies met inclusion criteria. GI symptoms most commonly evaluated as a chemotherapy outcome were nausea and vomiting and nausea alone. GI symptoms infrequently evaluated as outcomes included diarrhea, anticipatory nausea, and dysgeusia. Ten GI symptoms associated with chemotherapy were not evaluated by any study. Nonpharmacologic interventions included 15 different interventions. IMPLICATIONS FOR RESEARCH: Studies evaluating nonpharmacologic interventions for managing chemotherapy-related GI symptoms have been growing but tend to focus on nausea and vomiting to the exclusion of other relevant GI symptoms. Studies evaluating nonpharmacologic effects on other GI symptoms may make great strides in reducing patient symptom burden.

Distress-Based Gastrointestinal Symptom Clusters and Impact on Symptom Interference and Quality of Life in Patients with a Hematologic Malignancy Receiving Chemotherapy.

BACKGROUND/SIGNIFICANCE: People with cancer can experience co-occurring related symptoms, labeled symptom clusters. Gastrointestinal (GI) symptoms are common side effects of chemotherapy, but little research has investigated GI symptom clusters. A further gap in symptom cluster research is the lack of studies reporting symptom clusters based on symptom distress ratings. PURPOSE: To identify distress-based GI symptom clusters and to investigate their relationship to symptom interference with daily life and quality of life (QoL). SUBJECTS: About 105 adults with hematologic malignancy receiving chemotherapy. METHODS: On Day 1 of a cycle of chemotherapy, participants completed a modified version of the Memorial Symptom Assessment Scale assessing 30 clinically relevant symptoms, the M.D. Anderson Symptom Inventory Symptom Interference with Daily Life subscale, and the Fox Simple Quality of Life Scale. Exploratory factor analysis was used to identify distress-based symptom clusters. Symptom clusters with ≥50% GI symptoms were labeled GI symptom clusters. Linear mixed modeling explored relationships between GI symptom clusters and symptom interference with daily life and QoL. RESULTS: Of the six distress-based symptom clusters found, the bloating cluster and appetite cluster were identified as GI symptom clusters. Both the bloating cluster and the appetite cluster were significantly related to symptom interference with daily life, but only the appetite cluster was significantly related to QoL. CONCLUSIONS: This research demonstrates the existence of distress-based GI symptom clusters and their relationship to symptom interference and QoL. Future work should explore predictors of distress-based symptom clusters and interventions to manage them.

Prevalence, Duration, Severity, and Distress of Chemotherapy-Related Gastrointestinal Symptoms in Patients With a Hematologic Malignancy.

PURPOSE/OBJECTIVES: To describe prevalence, duration, severity, and distress of chemotherapy-related gastrointestinal (GI) symptoms, and evaluate inclusion of clinically relevant GI symptom items on cancer symptom questionnaires.
. DESIGN: Longitudinal descriptive design.
. SETTING: Inpatient and outpatient hematology settings.
. SAMPLE: 105 adults with a hematologic malignancy receiving their third or subsequent cycle of chemotherapy. 
. METHODS: Participants completed weekly assessments of 19 GI symptoms during a three-week period of chemotherapy. Descriptive statistics were calculated to summarize GI symptom prevalence, duration, severity, and distress ratings at each week. Findings were compared to item content of 12 cancer multisymptom questionnaires identified in the literature.
. MAIN RESEARCH VARIABLES: GI symptom prevalence, duration, severity, and distress.
. FINDINGS: Participants reported an average of three to five GI symptoms at each time point that were typically experienced as mild to moderate in duration, severity, and distress. Only 3 of 11 clinically relevant GI symptoms were included on more than half of the cancer symptom questionnaires. 
. CONCLUSIONS: Patients receiving chemotherapy experience a moderate GI symptom burden across a wide range of potential GI symptoms.
. IMPLICATIONS FOR NURSING: Future research should include measures of clinically relevant GI symptoms that may be emerging with new cancer therapies and toxicity prevention protocols.

Pilot randomized controlled trial of a patient-controlled cognitive-behavioral intervention for the pain, fatigue, and sleep disturbance symptom cluster in cancer.

CONTEXT: Pain, fatigue, and sleep disturbance commonly co-occur in patients receiving treatment for advanced cancer. OBJECTIVES: A pilot randomized controlled trial was conducted to assess initial efficacy of a patient-controlled cognitive-behavioral (CB) intervention for the pain, fatigue, and sleep disturbance symptom cluster. METHODS: Eighty-six patients with advanced lung, prostate, colorectal, or gynecologic cancers receiving treatment at a comprehensive cancer center were stratified by recruitment clinics (chemotherapy and radiation therapy) and randomized to intervention or control groups. Forty-three patients were assigned to receive training in and use of up to 12 relaxation, imagery, or distraction exercises delivered via an MP3 player for two weeks during cancer treatment. Forty-three patients were assigned to a waitlist control condition for the same two week period. Outcomes included symptom cluster severity and overall symptom interference with daily life measured at baseline (Time 1) and two weeks later (Time 2). RESULTS: Eight participants dropped out; 78 completed the study and were analyzed (36 intervention and 42 control subjects). Participants used the CB strategies an average of 13.65 times (SD=6.98). Controlling for baseline symptom cluster severity and other relevant covariates, it was found that the symptom cluster severity at Time 2 was lower in the intervention group (M(Adj)=2.99, SE=0.29) than in the waitlist group (M(Adj)=3.87, SE=0.36), F(1, 65)=3.57, P=0.032. Symptom interference with daily life did not differ between groups. No significant adverse events were noted with the CB intervention. CONCLUSION: Findings suggest that the CB intervention may be an efficacious approach to treating the pain, fatigue, and sleep disturbance symptom cluster. Future research is planned to confirm efficacy and test mediators and moderators of intervention effects.

Gastrointestinal symptom representation in cancer symptom clusters: a synthesis of the literature.

PURPOSE/OBJECTIVES: To review how gastrointestinal (GI)symptoms are represented within symptom clusters in patients with cancer receiving chemotherapy. DATA SOURCES: MedLINE, PsycINFO, and CINAHL. DATA SYNTHESIS: Forty-two symptom clusters containing a GI component emerged. Only four clusters were replicated in different samples; 38 were unique clusters. Thirteen different symptom measurement tools were used across the studies. Nineteen different GI symptoms were measured; however, many chemotherapy- or cancer-related GI symptoms known to be present in this population were missing or underrepresented. Twenty-one of the studies reviewed identified a symptom cluster that was primarily (50% or greater) composed of GI symptoms. CONCLUSIONS: GI symptoms are prevalent in symptom clusters, but those clusters often are inconsistent. One explanation for this finding may be that current symptom measurement tools do not fully address GI symptoms commonly experienced by patients receiving chemotherapy. IMPLICATIONS FOR NURSING: Future research should focus on using a comprehensive symptom assessment tool in a homogenous sample of participants who are receiving chemotherapy. Improved measurement of GI symptoms will advance symptom cluster research, which could impact assessment of chemotherapy-related symptoms and development of interventions for symptom clusters.

Mind-body treatments for the pain-fatigue-sleep disturbance symptom cluster in persons with cancer.

CONTEXT: Co-occurring pain, fatigue, and sleep disturbance comprise a common symptom cluster in patients with cancer. Treatment approaches that target the cluster of symptoms rather than just a single symptom need to be identified and tested. OBJECTIVES: To synthesize evidence regarding mind-body interventions that have shown efficacy in treating two or more symptoms in the pain-fatigue-sleep disturbance cancer symptom cluster. METHODS: A literature search was conducted using CINAHL, Medline, and PsychInfo databases through March 2009. Studies were categorized based on the type of mind-body intervention (relaxation, imagery/hypnosis, cognitive-behavioral therapy/coping skills training [CBT/CST], meditation, music, and virtual reality), and a preliminary review was conducted with respect to efficacy for pain, fatigue, and sleep disturbance. Mind-body interventions were selected for review if there was evidence of efficacy for at least two of the three symptoms. Forty-three studies addressing five types of mind-body interventions met criteria and are summarized in this review. RESULTS: Imagery/hypnosis and CBT/CST interventions have produced improvement in all the three cancer-related symptoms individually: pain, fatigue, and sleep disturbance. Relaxation has resulted in improvements in pain and sleep disturbance. Meditation interventions have demonstrated beneficial effects on fatigue and sleep disturbance. Music interventions have demonstrated efficacy for pain and fatigue. No trials were found that tested the mind-body interventions specifically for the pain-fatigue-sleep disturbance symptom cluster. CONCLUSION: Efficacy studies are needed to test the impact of relaxation, imagery/hypnosis, CBT/CST, meditation, and music interventions in persons with cancer experiencing concurrent pain, fatigue, and sleep disturbance. These mind-body interventions could help patients manage all the symptoms in the cluster with a single treatment strategy.