Detection of Adenocarcinoma of the Colon on 18 F-Fluciclovine PET/CT.

ABSTRACT: An 85-year-old man with prostate cancer and de novo bone metastases was treated with hormonal therapy with resolution of bone lesions, improved primary disease, and improved serum tumor markers. Although on hormonal therapy, biochemical recurrence prompted performance of 18 F-fluciclovine PET/CT. Fluciclovine PET/CT revealed primary prostate cancer progression with incidental note of avid foci in the colon for which colonoscopy was recommended. Colonoscopy with biopsy was performed with pathology revealing primary colon adenocarcinoma. Before reinitiation of prostate cancer therapy, segmental colon resection was performed with pathology positive for additional sites of colon cancer.

Topical Noneuphoric Phytocannabinoid Elixir 14 Reduces Inflammation and Mitigates Burn Progression.

INTRODUCTION: Thermal injuries are caused by exposure to a wide variety of agents including heat, electricity, radiation, chemicals, and friction. Early intervention can decrease injury severity by preventing excess inflammation and mitigating burn wound progression for improved healing outcomes. Previous studies have demonstrated that cannabinoids can trigger anti-inflammatory responses and promote wound closure. Therefore, the purpose of this study was to investigate whether a topical application of Noneuphoric Phytocannabinoid Elixir 14 (NEPE14) containing a full complement of phytocannabinoids (< 0.3% delta-9-tetrahydrocannabinol or cannabidiol) and other phytochemicals would mitigate burn wound progression in the treatment of deep partial-thickness burn wounds. METHODS: Deep partial-thickness burns were created on the dorsum of four anesthetized pigs and treated with NEPE14, Vehicle control, Silverlon, or gauze. The burns were assessed on postburn days 4, 7, and 14. Assessments consisted of digital photographs, Laser-Speckle imagery (blood perfusion), MolecuLight imagery (qualitative bacterial load), and biopsies for histology and immunohistochemistry (interleukin six and tumor necrosis factor-α). RESULTS: Topical treatment with NEPE14 significantly (P < 0.001) decreased inflammation (interleukin six and tumor necrosis factor-α) in comparison to control groups. It was also demonstrated that the reduction in inflammation led to mitigation of burn wound progression. In terms of wound healing and presence of bacteria, no statistically significant differences were observed. CONCLUSIONS: Topical treatment of deep partial-thickness burns with NEPE14 decreased wound inflammation and mitigated burn wound progression in comparison to control treatments.

Prevalence of malnutrition comparing the GLIM criteria, ESPEN definition and MST malnutrition risk in geriatric rehabilitation patients: RESORT.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) has developed new criteria for the diagnosis of malnutrition. This study aimed 1) to determine and compare malnutrition prevalence and risk using the GLIM criteria, European Society for Clinical Nutrition and Metabolism (ESPEN) definition of malnutrition and the Malnutrition Screening Tool (MST) in patients admitted to subacute geriatric rehabilitation wards, 2) to explore the agreement of malnutrition prevalence determined by each definition, and 3) to determine the accuracy of the MST against the GLIM criteria and ESPEN definition as references. METHODS: Geriatric rehabilitation patients (n = 444) from the observational, longitudinal REStORing health of acutely unwell adulTs (RESORT) cohort in Melbourne, Australia were included. The GLIM criteria, ESPEN definition and MST were applied. Accuracy was determined by the sensitivity, specificity and Area Under the Curve (AUC). RESULTS: According to the GLIM criteria, the overall prevalence of malnutrition was 52.0%. The ESPEN definition diagnosed 12.6% of patients as malnourished and the MST identified 44.4% of patients at risk for malnutrition. Agreement was low; 7% of patients were malnourished and at risk for malnutrition according to all three definitions. The accuracy of the MST compared to the GLIM criteria was fair (sensitivity 56.7%, specificity 69.0%) and sufficient (AUC 0.63); MST compared to the ESPEN definition was fair (sensitivity 60.7%, specificity 58.0%) and poor (AUC 0.59). CONCLUSIONS: According to the GLIM criteria, half of geriatric rehabilitation patients were malnourished, whereas the prevalence was much lower applying the ESPEN definition. This highlights the need for further studies to determine diagnostic accuracy of the GLIM criteria compared to pre-existing validated tools.

Association of Prescription Opioid Exposure and Patient Factors With Prolonged Postoperative Opioid Use in Opioid-Naïve Patients.

The purpose of this research study was to identify factors associated with prolonged postoperative opioid use in opioid-naïve patients in 2 domains: specific patient characteristics and exposure through postoperative opioid prescriptions. A retrospective analysis was conducted of electronic medical records of opioid-naïve adult orthopedic surgical patients at a large academic medical center from January 1, 2012, through December 31, 2017. In this cohort, 4% continued to refill opioid prescriptions more than 90 days after their surgical procedure. Prolonged use was associated with an initial prescription that had an oral morphine milligram equivalent above 675. Receipt of opioid prescription refills was a significant predictor for receiving additional opioid prescriptions over time. Multivariate logistic regression indicated that the independent predictors of prolonged postoperative opioid use were alcohol abuse, black race, Medicaid insurance, and the following comorbidities: diabetes, mood disorder, hypertension, and chronic kidney disease. To decrease the rate of prolonged postoperative opioid use, clinical changes can be investigated, including collaborative perioperative pain management strategies using nonopioid pain control methods; perioperative patient screening; education of patients and clinicians; and close postoperative follow-up, especially in the most vulnerable populations.

The Impact of Patient Characteristics and Postoperative Opioid Exposure on Prolonged Postoperative Opioid Use: An Integrative Review.

OBJECTIVES: The United States is experiencing an opioid overdose crisis. Research suggests prolonged postoperative opioid use, a common complication following surgery, is associated with opioid misuse, which, in turn, is the greatest risk factor of heroin misuse. The objective of this review is to evaluate how postoperative opioid exposure relates to prolonged use and to identify factors that predict prolonged postoperative opioid use. DESIGN: An integrative review of the literature. DATA SOURCES: Electronic and hand searching methods were used in PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, and SCOPUS. Search terms included opioid, opiate, postoperative pain, drug administration, prescribing pattern, prescription, inappropriate prescribing, self-medication, patient-controlled analgesia, opioid-naïve patients, and prolonged opioid use. REVIEW/ANALYSIS METHODS: Data were synthesized by identifying themes reflecting the results of the review. A quality assessment of the articles was also conducted. RESULTS: Fourteen articles were included and two main themes emerged: (1) Surgery places opioid naïve patients at risk for prolonged opioid use and (2) Certain patient characteristics may be predictive of prolonged postoperative opioid use. CONCLUSIONS: Prolonged postoperative opioid use is related to factors in addition to prescribing practices. Researchers consistently found that patients who are already on opioids, benzodiazepines, or addicted to alcohol; who have mental health disorders, depressive symptoms, or a self-perceived risk of addiction; and patients with multiple co-morbidities are at greater risk of prolonged use; demographics were inconsistent. NURSING IMPLICATIONS: Studies are needed to determine the predicting characteristics of prolonged postoperative opioid use, the type of surgeries that place patients at most risk, and the effect postoperative exposure to opioids has on prolonged use. This information can be used to develop and implement protocols to prevent misuse among high-risk patients.

Re-examination of CD91 function in GRP94 (glycoprotein 96) surface binding, uptake, and peptide cross-presentation.

GRP94 (gp96)-peptide complexes can be internalized by APCs and their associated peptides cross-presented to yield activation of CD8(+) T cells. Investigations into the identity (or identities) of GRP94 surface receptors have yielded conflicting results, particularly with respect to CD91 (LRP1), which has been proposed to be essential for GRP94 recognition and uptake. To assess CD91 function in GRP94 surface binding and endocytosis, these parameters were examined in mouse embryonic fibroblast (MEF) cell lines whose expression of CD91 was either reduced via RNA interference or eliminated by genetic disruption of the CD91 locus. Reduction or loss of CD91 expression abrogated the binding and uptake of receptor-associated protein, an established CD91 ligand. Surface binding and uptake of an N-terminal domain of GRP94 (GRP94.NTD) was unaffected. GRP94.NTD surface binding was markedly suppressed after treatment of MEF cell lines with heparin, sodium chlorate, or heparinase II, demonstrating that heparin sulfate proteoglycans can function in GRP94.NTD surface binding. The role of CD91 in the cross-presentation of GRP94-associated peptides was examined in the DC2.4 dendritic cell line. In DC2.4 cells, which express CD91, GRP94.NTD-peptide cross-presentation was insensitive to the CD91 ligands receptor-associated protein or activated α(2)-macroglobulin and occurred primarily via a fluid-phase, rather than receptor-mediated, uptake pathway. These data clarify conflicting data on CD91 function in GRP94 surface binding, endocytosis, and peptide cross-presentation and identify a role for heparin sulfate proteoglycans in GRP94 surface binding.

Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control.

GRP94, the endoplasmic reticulum Hsp90, is a metazoan-restricted chaperone essential for early development in mammals, yet dispensable for mammalian cell viability. This dichotomy suggests that GRP94 is required for the functional expression of secretory and/or membrane proteins that enable the integration of cells into tissues. To explore this hypothesis, we have identified the Drosophila ortholog of GRP94, Gp93, and report that Gp93 is an essential gene in Drosophila. Loss of zygotic Gp93 expression is late larval-lethal and causes prominent defects in the larval midgut, the sole endoderm-derived larval tissue. Gp93 mutant larvae display pronounced defects in the midgut epithelium, with aberrant copper cell structure, markedly reduced gut acidification, atypical septate junction structure, depressed gut motility, and deficits in intestinal nutrient uptake. The metabolic consequences of the loss of Gp93-expression are profound; Gp93 mutant larvae exhibit a starvation-like metabolic phenotype, including suppression of insulin signaling and extensive mobilization of amino acids and triglycerides. The defects in copper cell structure/function accompanying loss of Gp93 expression resemble those reported for mutations in labial, an endodermal homeotic gene required for copper cell specification, and alpha-spectrin, thus suggesting an essential role for Gp93 in the functional expression of secretory/integral membrane protein-encoding lab protein target genes and/or integral membrane protein(s) that interact with the spectrin cytoskeleton to confer epithelial membrane specialization.

Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 signaling.

Macrophages are important mediators of chronic inflammation and are prominent in the synovial lining and sublining of patients with rheumatoid arthritis (RA). Recently, we demonstrated increased TLR2 and TLR4 expression and increased response to microbial TLR2 and TLR4 ligands in macrophages from the joints of RA. The current study characterized the expression of the 96-kDa heat shock glycoprotein (gp96) in the joints of RA and its role as an endogenous TLR ligand to promote innate immunity in RA. gp96 was increased in RA compared with osteoarthritis and arthritis-free control synovial tissues. The expression of gp96 strongly correlated with inflammation and synovial lining thickness. gp96 was increased in synovial fluid from the joints of RA compared with disease controls. Recombinant gp96 was a potent activator of macrophages and the activation was mediated primarily through TLR2 signaling. The cellular response to gp96 was significantly stronger with RA synovial macrophages compared with peripheral blood monocytes from RA or healthy controls. The transcription of TLR2, TNF-alpha, and IL-8, but not TLR4, was significantly induced by gp96, and the induction was significantly greater in purified RA synovial macrophages. The expression of TLR2, but not TLR4, on synovial fluid macrophages strongly correlated with the level of gp96 in the synovial fluid. The present study documents the potential role of gp96 as an endogenous TLR2 ligand in RA and provides insight into the mechanism by which gp96 promotes the chronic inflammation of RA, identifying gp96 as a potential new therapeutic target.

Self-reported sleep disturbance of patients with heart failure in Taiwan.

BACKGROUND: Western research studies have found that sleep disturbances reduced quality of life and daily functioning of patients with heart failure; however, information about sleep disturbance is lacking in Taiwanese people with heart failure. OBJECTIVES: The objective of this study was to investigate predictors of self-reported sleep disturbances in Taiwanese people with heart failure. The hypothesis was that health-related quality of life (HRQOL) could have significant effect on sleep disturbances, after controlling for demographics, heart failure characteristics, and health-related characteristics. METHODS: A cross-sectional, descriptive, correlational design was used. A purposive sample of 125 participants was recruited from the outpatient departments of two hospitals located in southern Taiwan. Participants were interviewed individually to complete the Pittsburgh Sleep Quality Index, Kansas City Cardiomyopathy Questionnaire, Charlson Comorbidity Index, and Perceived Health Scale instruments. RESULTS: Self-reported sleep disturbances were prevalent (74%) among people with heart failure in Taiwan. Five predictors were identified using hierarchical multiple regression analyses with forward methods, accounting for 26.9% of variance in sleep disturbances. They were education, New York Heart Association functional classification, perceived health, HRQOL social functioning, and physical symptoms. After controlling for demographics, heart failure characteristics, and health-related characteristics, the analysis showed that two variables of HRQOL accounted for 9.8% of the variance in sleep disturbances. DISCUSSION: The importance of ongoing screening for sleep disturbances in people with heart failure is highlighted based on the study findings about the prevalence of sleep disturbances among the participants in this study. Healthcare providers must understand the often multifactorial nature of sleep disturbances to achieve a better and more effective management.

Importance of arginine 20 of the swine vesicular disease virus 2A protease for activity and virulence.

A major virulence determinant of swine vesicular disease virus (SVDV), an Enterovirus that causes an acute vesicular disease, has been mapped to residue 20 of the 2A protease. The SVDV 2A protease cleaves the 1D-2A junction in the viral polyprotein, induces cleavage of translation initiation factor eIF4GI, and stimulates the activity of enterovirus internal ribosome entry sites (IRESs). The 2A protease from an attenuated strain of SVDV (Ile at residue 20) is significantly defective at inducing cleavage of eIF4GI and the activation of IRES-dependent translation compared to the 2A protease from a pathogenic strain (J1/73, Arg at residue 20), but the two proteases have similar 1D-2A cleavage activities (Y. Sakoda, N. Ross-Smith, T. Inoue, and G. J. Belsham, J. Virol. 75:10643-10650, 2001). Residue 20 has now been modified to every possible amino acid, and the activities of each mutant 2A protease has been analyzed. Selected mutants were reconstructed into full-length SVDV cDNA, and viruses were rescued. The rate of virus growth in cultured swine kidney cells reflected the efficiency of 2A protease activity. In experimentally infected pigs, all four of the mutant viruses tested displayed much-reduced virulence compared to the J1/73 virus but a significant, albeit reduced, level of viral replication and excretion was detected. Direct sequencing of cDNA derived from samples taken early and late in infection indicated that a gradual selection-reversion to a more efficient protease occurred. The data indicated that extensive sequence change and selection may introduce a severe bottleneck in virus replication, leading to a decreased viral load and reduced or no clinical disease.