Expanding active living after cancer to underserved cancer survivors and their caregivers.

BACKGROUND: Physical activity (PA) improves physical and psychological health in cancer survivors. This study evaluated Active Living After Cancer (ALAC), a community-based program to improve PA, physical function, and quality of life (QOL) in minority and medically underserved cancer survivors and their caregivers. METHODS: Participants completed 12 weekly ALAC sessions and assessments of PA, physical functioning, and QOL at baseline and follow-up (week 12). Paired samples t-tests were used to assess changes in outcomes over time. RESULTS: 540 cancer survivors (M age = 61.1 years, SD = 11.3) and 87 caregivers (M age = 62.3 years, SD = 13.1) were enrolled. Most were women (91.4%), Hispanic (61.1%) or non-Hispanic Black (19.3%), and medically underserved (86.4%). The percent of cancer survivors meeting PA recommendations increased from 28.9% to 60.2% (d = 0.75), and the number of sit-to-stand repetitions in a 30-second period increased from 12.3 to 14.3 (d = 0.39) from 0-12 weeks. Cancer survivors reported significant improvements in physical (T-score Δ = 1.7, d = 0.06) and mental (T-score Δ = 2.3, d = 0.31) health-related QOL. Caregivers also improved their PA, physical function, and QOL, and there were no statistically significant differences between breast and other cancer survivors and between cancer survivors and caregivers. CONCLUSIONS: The ALAC program demonstrated increased PA, physical function, and QOL in medically underserved cancer survivors and their caregivers. Furthermore, ALAC was successfully implemented by community partners and serves as a good model for reaching medically underserved cancer survivors and improving survivorship. Additional efforts are warranted to further extend reach, improve cancer survivorship, and reduce cancer health disparities among underserved cancer survivors.

Experimentally evolved Staphylococcus aureus shows increased survival in the presence of Pseudomonas aeruginosa by acquiring mutations in the amino acid transporter, GltT.

When cultured together under standard laboratory conditions Pseudomonas aeruginosa has been shown to be an effective inhibitor of Staphylococcus aureus. However, P. aeruginosa and S. aureus are commonly observed in coinfections of individuals with cystic fibrosis (CF) and in chronic wounds. Previous work from our group revealed that S. aureus isolates from CF infections are able to persist in the presence of P. aeruginosa strain PAO1 with a range of tolerances with some isolates being eliminated entirely and others maintaining large populations. In this study, we designed a serial transfer, evolution experiment to identify mutations that allow S. aureus to survive in the presence of P. aeruginosa. Using S. aureus USA300 JE2 as our ancestral strain, populations of S. aureus were repeatedly cocultured with fresh P. aeruginosa PAO1. After eight coculture periods, S. aureus populations that survived better in the presence of PAO1 were observed. We found two independent mutations in the highly conserved S. aureus aspartate transporter, gltT, that were unique to evolved P. aeruginosa-tolerant isolates. Subsequent phenotypic testing demonstrated that gltT mutants have reduced uptake of glutamate and outcompeted wild-type S. aureus when glutamate was absent from chemically defined media. These findings together demonstrate that the presence of P. aeruginosa exerts selective pressure on S. aureus to alter its uptake and metabolism of key amino acids when the two are cultured together.

Endocrine features of Langerhans cell histiocytosis in paediatric patients: A 30-year review.

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder characterised as an inflammatory myeloid neoplasia. Endocrine manifestations of LCH, particularly central diabetes insipidus (CDI), have been described from the 1940s, through case studies and small cohort analyses. There are limited Australian paediatric data described in recent literature. AIM: To document the incidence of endocrine features in paediatric patients with LCH, treated at a tertiary paediatric centre in Victoria, Australia. METHODS: Retrospective chart review of electronic medical records and oncology database of patients with LCH managed at a tertiary paediatric centre. Patients were excluded if a biopsy did not suggest LCH or if records were incomplete. RESULTS: One hundred seventy-one patients were identified and 141 records of patients diagnosed with LCH over the last 30 years were assessed for endocrinopathies, from diagnosis to last documented follow-up. Mean age at diagnosis was 5 years 8 months. Of these, 15% (n = 21) had CDI, 7% had growth hormone deficiency (GHD) (n = 10) and 8% (n = 11) had more than one endocrinopathy noted during follow-up. Forty percent (n = 57) were pre-pubertal at the time of audit or upon discharge from tertiary services. CONCLUSIONS: Ongoing pituitary assessment, in addition to CDI, is required to detect evolving deficiencies of GHD and gonadotropins as these can be subtle, late or missed. Close follow-up of growth and progression through puberty, even if discharged from tertiary care, is essential.

Experimentally Evolved Staphylococcus aureus Survives in the Presence of Pseudomonas aeruginosa by Acquiring Mutations in the Amino Acid Transporter, GltT.

Staphylococcus aureus and Pseudomonas aeruginosa are the most common bacterial pathogens isolated from cystic fibrosis (CF) related lung infections. When both of these opportunistic pathogens are found in a coinfection, CF patients tend to have higher rates of pulmonary exacerbations and experience a more rapid decrease in lung function. When cultured together under standard laboratory conditions, it is often observed that P. aeruginosa effectively inhibits S. aureus growth. Previous work from our group revealed that S. aureus from CF infections have isolate-specific survival capabilities when cocultured with P. aeruginosa. In this study, we designed a serial transfer evolution experiment to identify mutations that allow S. aureus to adapt to the presence of P. aeruginosa. Using S. aureus USA300 JE2 as our ancestral strain, populations of S. aureus were repeatedly cocultured with fresh P. aeruginosa strain, PAO1. After 8 coculture periods, S. aureus populations that survived better in the presence of PAO1 were observed. We found two independent mutations in the highly conserved S. aureus aspartate transporter, gltT, that were unique to evolved P. aeruginosa-tolerant isolates. Subsequent phenotypic testing demonstrated that gltT mutants have reduced uptake of glutamate and outcompete wild-type S. aureus when glutamate is absent from chemically-defined media. These findings together demonstrate that the presence of P. aeruginosa exerts selective pressure on S. aureus to alter its uptake and metabolism of key amino acids when the two bacteria are cultured together.

Promiscuous Enzymes for Residue-Specific Peptide and Protein Late-Stage Functionalization.

The late-stage functionalization of peptides and proteins holds significant promise for drug discovery and facilitates bioorthogonal chemistry. This selective functionalization leads to innovative advances in in vitro and in vivo biological research. However, it is a challenging endeavor to selectively target a certain amino acid or position in the presence of other residues containing reactive groups. Biocatalysis has emerged as a powerful tool for selective, efficient, and economical modifications of molecules. Enzymes that have the ability to modify multiple complex substrates or selectively install nonnative handles have wide applications. Herein, we highlight enzymes with broad substrate tolerance that have been demonstrated to modify a specific amino acid residue in simple or complex peptides and/or proteins at late-stage. The different substrates accepted by these enzymes are mentioned together with the reported downstream bioorthogonal reactions that have benefited from the enzymatic selective modifications.

Moving the needle on time to resuscitation: An EAST prospective multicenter study of vascular access in hypotensive injured patients using trauma video review.

BACKGROUND: Vascular access in hypotensive trauma patients is challenging. Little evidence exists on the time required and success rates of vascular access types. We hypothesized that intraosseous (IO) access would be faster and more successful than peripheral intravenous (PIV) and central venous catheter (CVC) access in hypotensive patients. METHODS: An EAST prospective multicenter trial was performed; 19 centers provided data. Trauma video review was used to evaluate the resuscitations of hypotensive (systolic blood pressure ≤90 mm Hg) trauma patients. Highly granular data from video recordings were abstracted. Data collected included vascular access attempt type, location, success rate, and procedural time. Demographic and injury-specific variables were obtained from the medical record. Success rates, procedural durations, and time to resuscitation were compared among access strategies (IO vs. PIV vs. CVC). RESULTS: There were 1,410 access attempts that occurred in 581 patients with a median age of 40 years (27-59 years) and an Injury Severity Score of 22 [10-34]. Nine hundred thirty-two PIV, 204 IO, and 249 CVC were attempted. Seventy percent of access attempts were successful but were significantly less likely to be successful in females (64% vs. 71%, p = 0.01). Median time to any access was 5.0 minutes (3.2-8.0 minutes). Intraosseous had higher success rates than PIV or CVC (93% vs. 67% vs. 59%, p < 0.001) and remained higher after subsequent failures (second attempt, 85% vs. 59% vs. 69%, p = 0.08; third attempt, 100% vs. 33% vs. 67%, p = 0.002). Duration varied by access type (IO, 36 [23-60] seconds; PIV, 44 [31-61] seconds; CVC 171 [105-298]seconds) and was significantly different between IO versus CVC ( p < 0.001) and PIV versus CVC ( p < 0.001) but not PIV versus IO. Time to resuscitation initiation was shorter in patients whose initial access attempt was IO, 5.8 minutes versus 6.7 minutes ( p = 0.015). This was more pronounced in patients arriving to the hospital with no established access (5.7 minutes vs. 7.5 minutes, p = 0.001). CONCLUSION: Intraosseous is as fast as PIV and more likely to be successful compared with other access strategies in hypotensive trauma patients. Patients whose initial access attempt was IO were resuscitated more expeditiously. Intraosseous access should be considered a first line therapy in hypotensive trauma patients. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study.

Background and purpose: The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease. Methods: This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months). Results: Fecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group. Conclusions: Subjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms. Clinical trial registration: ClinicalTrial.gov, identifier: NCT03671785.

Down the Rabbit Hole: Evaluation of Internet Information Quality in Parathyroid and Thyroid Surgery.

INTRODUCTION: Patients often discuss information obtained from Internet sources during clinic visits, which can be of variable quality and depth. We sought to review and assess information on the Internet regarding common operations within endocrine surgery. METHODS: Using Google's search engine, the top 100 websites from the search phrase "parathyroid surgery," and the top 100 websites from the phrase "thyroid surgery" were identified. Each website was evaluated for accessibility, accuracy, and completeness of information about gland hormone function, associated disease processes, and surgery itself. Results were stratified based on the website type, and bivariate analysis was performed to determine accuracy by category. Presence of author credentials, last webpage update, and presence of advertisements were also assessed. Inter-rater reliability was calculated for each variable. RESULTS: For parathyroid surgery, at least two-thirds of all websites included information about surgery, hormone function, and disease processes. For thyroid surgery, 71% of websites included procedure information, but only 52% included information about hormone function and 56% about disease processes. Less than 30% of all websites included advertisements and less than 25% listed author credentials or provided references. Academic or research-affiliated sources were most likely to have zero inaccuracies, but 44% of all websites had at least one potential inaccuracy. Inter-rater reliability achieved at least moderate agreement (>0.41) for 56% of variables. CONCLUSIONS: There is a wide array of information available to patients online, and accuracy varies based on multiple factors including the type of website. Endocrine surgeons and related practitioners must be cognizant of this fact when discussing treatment plans with patients.

Active Living After Cancer: Adaptation and evaluation of a community-based physical activity program for minority and medically underserved breast cancer survivors.

BACKGROUND: An expanding body of research documents the benefits of physical activity for cancer survivors' physical functioning and quality of life, but few successful models provide community-based physical activity programs to cancer survivors. This report presents an evaluation of Active Living After Cancer, an evidence-based physical activity program for breast cancer survivors, adapted for community delivery to minority and medically underserved survivors. METHODS: Survivors were recruited from health care and community settings. The program consisted of 12 weekly group sessions providing training in cognitive and behavioral skills for behavior change, brief physical activity, and cancer survivorship-related content. At the baseline and follow-up, participants completed assessments of their physical activity, quality of life, and physical functioning (6-minute walk and 30-second sit-to-stand test). At follow-up, they also completed questionnaires to measure program content mastery and satisfaction. RESULTS: The outcome analysis included 127 participants. Physical activity and quality of life (mental and physical) improved from the baseline to follow-up (all P < .01). Physical functioning improved, with increases in sit-to-stand repetitions (mean, 12.5 at the baseline vs 14.9 at the follow-up; P < .01) and 6-minute walk distances (mean, 428 m at the baseline vs 470 m at the follow-up; P < .01). CONCLUSIONS: The results highlight the effectiveness of an evidence-based program adapted for community-based delivery to minority and medically underserved breast cancer survivors. The program could be delivered to improve outcomes in diverse survivor populations. LAY SUMMARY: Physical activity in breast cancer survivors is related to better quality of life and longer cancer-free survival. However, there are few community-based programs to help breast cancer survivors to become more physically active. The Active Living After Cancer program was adapted from an evidence-based program and delivered in community-based settings to minority and medically underserved breast cancer survivors. It consisted of 12 weekly group sessions in which participants learned skills to increase their physical activity. The program participants increased their physical activity and improved their mental and physical well-being and physical functioning.

Tobacco Screening and Use in Hospitalized Adolescents at a Children's Hospital.

OBJECTIVES: With this study, we aim to evaluate inpatient adolescent screening for tobacco, as well as the relationship between tobacco and other substance use, tobacco types used, and cessation interventions. METHODS: A retrospective chart review of inpatient hospital admissions of adolescents aged ≥13 years to a tertiary care, freestanding, urban children's hospital in 2018 was performed. Tobacco use-related variables were entered into a multiple logistic regression model in which the adjusted odds ratios were determined. Variables found to be significant in bivariate analysis were included as covariates in the model by using SAS 9.4 software (SAS Institute, Inc, Cary, NC). RESULTS: There were 4412 admissions of adolescents aged ≥13 years during the study period, of which 370 (8.4%) adolescents were screened for tobacco use by physicians. Significant factors associated with being screened included age 16 to 18 years, white race, and admission to the pediatric hospital medicine service. There were 93 (25.1%) tobacco users identified, of whom the majority reported concomitant caretaker use (78.6%), alcohol use (52.7%), and marijuana use (70.8%). The most commonly reported tobacco type used was cigarettes at 50.5%. Cessation intervention was documented in 8 tobacco users. CONCLUSIONS: Tobacco use screening of hospitalized adolescents aged ≥13 years was performed infrequently and was not standardized among physicians. Tobacco use was identified in 25.1% of those screened, and cessation interventions were inconsistently performed. This study suggests a need for universal, standardized tobacco use screening in inpatient adolescents and identifies a missed opportunity for treatment of tobacco dependence.

Genotypic and Phenotypic Diversity of Staphylococcus aureus Isolates from Cystic Fibrosis Patient Lung Infections and Their Interactions with Pseudomonas aeruginosa.

Staphylococcus aureus has recently overtaken Pseudomonas aeruginosa as the most commonly recognized bacterial pathogen that infects the respiratory tracts of individuals with the genetic disease cystic fibrosis (CF) in the United States. Most studies of S. aureus in CF patient lung infections have focused on a few isolates, often exclusively laboratory-adapted strains, and how they are killed by P. aeruginosa Less is known about the diversity of S. aureus CF patient lung isolates in terms of both their virulence and their interaction with P. aeruginosa To begin to address this gap, we recently sequenced 64 clinical S. aureus isolates and a reference isolate, JE2. Here, we analyzed the antibiotic resistance genotypes, sequence types, clonal complexes, spa types, agr types, and presence/absence of other known virulence factor genes of these isolates. We hypothesized that virulence phenotypes of S. aureus, namely, toxin production and the mucoid phenotype, would be lost in these isolates due to adaptation in the CF patient lung. In contrast to these expectations, we found that most isolates can lyse both rabbit and sheep blood (67.7%) and produce polysaccharide (69.2%), suggesting that these phenotypes were not lost during adaptation to the CF lung. We also identified three distinct phenotypic groups of S. aureus based on their survival in the presence of nonmucoid P. aeruginosa laboratory strain PAO1 and its mucoid derivative. Altogether, our work provides greater insight into the diversity of S. aureus isolates from CF patients, specifically the distribution of important virulence factors and their interaction with P. aeruginosa, all of which have implications in patient health.IMPORTANCEStaphylococcus aureus is now the most frequently detected recognized pathogen in the lungs of individuals who have cystic fibrosis (CF) in the United States, followed closely by Pseudomonas aeruginosa When these pathogens are found to coinfect the CF lung, patients have a significantly worse prognosis. While P. aeruginosa has been rigorously studied in the context of bacterial pathogenesis in CF, less is known about S. aureus Here, we present an in-depth study of 64 S. aureus clinical isolates from CF patients, for which we investigated genetic diversity utilizing whole-genome sequencing, virulence phenotypes, and interactions with P. aeruginosa We found that S. aureus isolated from CF lungs are phylogenetically diverse; most retain known virulence factors and vary in their interactions with P. aeruginosa (i.e., they range from being highly sensitive to P. aeruginosa to completely tolerant to it). Deepening our understanding of how S. aureus responds to its environment and other microbes in the CF lung will enable future development of effective treatments and preventative measures against these formidable infections.

Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.

BACKGROUND: Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI). AIMS: To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema. METHODS: In a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied. RESULTS: Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema. CONCLUSIONS: The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product. TRIAL REGISTRATION: ClinicalTrials.gov NCT02449174.

Creation and validation of a simulator for corneal rust ring removal.

OBJECTIVE: To create and validate a simulation model for corneal rust ring removal. METHODS: Rust rings were created on cadaveric eyes with the use of small particles of metal. The eyes were mounted on suction plates at slit lamps and the trainees practiced rust ring removal. An inexperienced cohort of medical students and first year ophthalmology residents (n=11), and an experienced cohort of senior residents and faculty (n=11) removed the rust rings from the eyes with the use of a burr. Rust ring removal was evaluated based on removal time, percentage of rust removed and incidence of corneal perforation. A survey was administered to participants to determine face validity. RESULTS: Time for rust ring removal was longer in the inexperienced group at 187±93 seconds (range of 66-408 seconds), compared to the experienced group at 117±54 seconds (range of 55-240 seconds) (p=0.046). Removal speed was similar between groups, at 4847±4355 pixels/minute and 7206±5181 pixels/minute in the inexperienced and experienced groups, respectively (p=0.26). Removal percentage values were similar between groups, at 61±15% and 69±18% (p=0.38). There were no corneal perforations. 100% (22/22) of survey respondents believed the simulator would be a valuable practice tool, and 89% (17/19) felt the simulation was a valid representation of the clinical correlate. CONCLUSION: The corneal rust ring simulator presented here is a valid training tool that could be used by early trainees to gain greater comfort level before attempting rust ring removal on a live patient.

Neurocognitive dysfunction in HIV-infected youth: investigating the relationship with immune activation.

BACKGROUND: HIV-infected individuals are at increased risk of neurocognitive impairment compared to the general population. Studies suggest that, despite combination antiretroviral therapy (cART), HIV infection causes immune activation which results in neural damage; however, few data exist in HIV-infected youth. METHODS: HIV-infected youth 8-26-years-old on cART with virological suppression were prospectively enrolled along with healthy controls. Neurocognitive performance was assessed by age-appropriate Wechsler Intelligence Scales. Soluble and cellular markers of T-lymphocyte and monocyte activation were measured by ELISA and flow cytometry, respectively. RESULTS: 45 HIV-infected subjects and 21 controls were enrolled. Markers of T-cell and monocyte activation were higher in the HIV-infected subjects compared to controls, but proportions of inflammatory and patrolling monocytes were similar. Although there were no significant differences in neurocognitive scores between the HIV-infected and control groups, scores were low-average for four of five testing domains for the HIV-infected subjects and average for all five in the controls, and % of HIV-infected subjects with scores classified as 'low average' or below was higher than in the controls. Variables most associated with neurocognitive performance among HIV-infected subjects included activated CD4+ T-cells (% CD4+CD38+HLA-DR), monocyte activation (soluble CD14), HIV duration, age and sex. CONCLUSIONS: HIV-infected youth on cART with virological suppression show subtle evidence of neurocognitive impairment compared to healthy controls, and increased immune activation appears to play a role. Additional studies are needed to develop strategic interventions beyond cART to potentially improve neurocognitive performance and/or minimize further impairment in this vulnerable population. ClinicalTrials.gov Identifier: NCT01523496.

Anomalous vertebral artery origins: the first and second reports of two variants.

We present two cases of aberrant origins of vertebral arteries. Case 1 is of a patient undergoing evaluation of an infrarenal aortic aneurysm stent graft. Computed tomography (CT) angiogram revealed an aberrant right vertebral artery that subsequently joined a second right vertebral artery that had the typical origin off the right subclavian artery. This represents an unusual anatomic variation not previously reported in the literature. Case 2 is of a patient being evaluated for thoracic aorta injury. CT angiogram of the chest revealed a five-vessel aortic arch with aberrant origin of the bilateral vertebral arteries distal to the left subclavian artery.