Detroit Interventional Pain Assessment Scale: A Pain Score and Method for Measuring and Evaluating Post-Operative Pain Management-A Prospective Study.

Background and Objectives: Orthopedic surgeons commonly prescribe opioids, surpassing all medical specialties. Our objective was to develop a pain management scale that captures medication use, patient-reported pain scores, and helps orthopedic surgeons evaluate their post-operative prescribing practice. Materials and Methods: An IRB-approved prospective study followed 502 post-operative orthopedic surgery patients over a six-month period. All patients were surveyed in an orthopedic clinic at a Level 1 US Trauma Center, during a routine follow-up. Patient pain satisfaction was assessed using the validated Interventional Pain Assessment (IPA) scale, which uses three categories: 0 (no pain), 1 (tolerable pain), and 2 (intolerable pain). Daily narcotic use was translated to morphine milligram equivalents (MMEs) using the Michigan Automated Prescription System (MAPS) narcotics registry. When patient pain satisfaction and narcotic usage were combined, this scale was called the Detroit Interventional Pain Assessment (DIPA) scale. Results: The five classes based on common prescription and usage of narcotics in this cohort include the following: A (no pain medication), B (over-the-counter medication), C (occasional use of short-acting narcotics 1-30 MMEs), D (consistent/regular use of short-acting narcotics 31-79 MMEs), and E (long-duration or stronger short-acting narcotics 80+ MMEs). Patients were most satisfied with their pain management at six weeks (80.5%) and three months (75.65%), and least satisfied at two weeks (62.5%) and six months (60.9%). Additional information displayed on the DIPA graph revealed there was a significant decrease in the percentage of patients on narcotics at two weeks (65.2%) to six months (32.6%) at p < 0.001. Conclusions: The DIPA pain scale shows the relationship between patient pain perception and opioid prescription/usage, while also tracking prescriber tendencies. Providers were able to visualize their post-operative pain management progression at each designated clinic visit with corresponding alphabetical daily MME categories. In this study, results suggest that surgeons were not effective at managing the pain of patients at two weeks post-operative, which is attributed to an inadequate number of pain pills prescribed upon discharge. Overall, the DIPA graph signaled that better pain management interventions are necessitated in periods with lower efficiency scores.

Dietary Garcinol Arrests Pancreatic Cancer in p53 and K-ras Conditional Mutant Mouse Model.

Pancreatic cancer (PC) patients have poor prognosis and survival rate. Gemcitabine, the drug of choice has a dismal 15% response rate. Earlier, we reported that Garcinol alone and in combination with gemcitabine showed a dose-dependent favorable response on PC cell lines. This study probes the in vivo effects of dietary Garcinol on PC progression in transgenic PC mice (KPC; K-ras and p53 conditional mutant). KPC male mice were divided into: KC- Control diet; KGr-0.05% Garcinol diet; KGm-Gemcitabine injected; KGG - Garcinol diet + Gemcitabine injected groups. Changes in tumor progression, toxicity, or cell morphology were monitored by magnetic resonance imaging, Fore-stomach, and blood smear, respectively. Pancreatic Intraepithelial Neoplasia (mPanIN) grading with hematoxylin and eosin (H&E) staining was conducted on pancreas and validated by immunohistochemistry. The KGr group showed improved survival, no observable toxicity with marked reduction in papilloma formation in the fore-stomach, and a higher ratio of NK and NKT cells compared to Non-NK lymphocytes. Additionally, the KGr, KGm, and KGG groups showed reduction in tumor volumes and reduced number of advanced mouse PanIN3. Dietary Garcinol alone and in combination with gemcitabine retarded the progression of PC in transgenic PC mice, arresting the cancer in the earlier stages, improving prognosis and survival.

Detection of Cystic Fibrosis Serological Biomarkers Using a T7 Phage Display Library.

Cystic fibrosis (CF) is an autosomal recessive disorder affecting the cystic fibrosis transmembrane conductance regulator (CFTR). CF is characterized by repeated lung infections leading to respiratory failure. Using a high-throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL) cells and leukocytes of sarcoidosis patients. This library was biopanned to obtain 1070 potential antigens. A microarray platform was constructed and immunoscreened with sera from healthy (n = 49), lung cancer (LC) (n = 31) and CF (n = 31) subjects. We built 1,000 naïve Bayes models on the training sets. We selected the top 20 frequently significant clones ranked with student t-test discriminating CF antigens from healthy controls and LC at a False Discovery Rate (FDR) < 0.01. The performances of the models were validated on an independent validation set. The mean of the area under the receiver operating characteristic (ROC) curve for the classifiers was 0.973 with a sensitivity of 0.999 and specificity of 0.959. Finally, we identified CF specific clones that correlate highly with sweat chloride test, BMI, and FEV1% predicted values. For the first time, we show that CF specific serological biomarkers can be identified through immunocreenings of a T7 phage display library with high accuracy, which may have utility in development of molecular therapy.

Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota in sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. Granulomatous inflammation in sarcoidosis may affect multiple organs, including the lungs, skin, CNS, and the eyes, leading to severe morbidity and mortality. The underlying mechanisms for sustained inflammation in sarcoidosis are unknown. We hypothesized that metabolic changes play a critical role in perpetuation of inflammation in sarcoidosis. 1H nuclear magnetic resonance (NMR)-based untargeted metabolomic analysis was used to identify circulating molecules in serum to discriminate sarcoidosis patients from healthy controls. Principal component analyses (PCA) were performed to identify different metabolic markers and explore the changes of associated biochemical pathways. Using Chenomx 7.6 NMR Suite software, we identified and quantified metabolites responsible for such separation in the PCA models. Quantitative analysis showed that the levels of metabolites, such as 3-hydroxybutyrate, acetoacetate, carnitine, cystine, homocysteine, pyruvate, and trimethylamine N-oxide were significantly increased in sarcoidosis patients. Interestingly, succinate, a major intermediate metabolite involved in the tricyclic acid cycle was significantly decreased in sarcoidosis patients. Application of integrative pathway analyses identified deregulation of butanoate, ketone bodies, citric cycle metabolisms, and transmethylation. This may be used for development of new drugs or nutritional modification.

Delta-tocotrienol suppresses Notch-1 pathway by upregulating miR-34a in nonsmall cell lung cancer cells.

MicroRNAs (miRNAs) are small noncoding RNAs that play critical roles in regulating various cellular functions by transcriptional silencing. miRNAs can function as either oncogenes or tumor suppressors (oncomirs), depending on cancer types. In our study, using miRNA microarray, we observed that downregulation of the Notch-1 pathway, by delta-tocotrienol, correlated with upregulation of miR-34a, in nonsmall cell lung cancer cells (NSCLC). Moreover, re-expression of miR-34a by transfection in NSCLC cells resulted in inhibition of cell growth and invasiveness, induction of apoptosis and enhanced p53 activity. Furthermore, cellular mechanism studies revealed that induction of miR-34a decreased the expression of Notch-1 and its downstream targets including Hes-1, Cyclin D1, Survivin and Bcl-2. Our findings suggest that delta-tocotrienol is a nontoxic activator of mir-34a which can inhibit NSCLC cell proliferation, induce apoptosis and inhibit invasion, and thus offering a potential starting point for the design of novel anticancer agents.

Inhibition of cell growth and induction of apoptosis in non-small cell lung cancer cells by delta-tocotrienol is associated with notch-1 down-regulation.

Lung cancer is the leading cause of death among all cancers. Non-small cell lung cancer accounts for 80% of lung cancer with a 5-year survival rate of 16%. Notch pathway, especially Notch-1 is up-regulated in a subgroup of non-small cell lung cancer patients. Since Notch-1 signaling plays an important role in cell proliferation, differentiation, and apoptosis, down-regulation of Notch-1 may exert anti-tumor effects. The objective of this study was to investigate whether delta-tocotrienol, a naturally occurring isoform of Vitamin E, inhibits non-small cell lung cancer cell growth via Notch signaling. Treatment with delta-tocotrienol resulted in a dose and time dependent inhibition of cell growth, cell migration, tumor cell invasiveness, and induction of apoptosis. Real-time RT-PCR and western blot analysis showed that antitumor activity by delta-tocotrienol was associated with a decrease in Notch-1, Hes-1, Survivin, MMP-9, VEGF, and Bcl-XL expression. In addition, there was a decrease in NF-κB-DNA binding activity. These results suggest that down-regulation of Notch-1, via inhibition of NF-κB signaling pathways by delta-tocotrienol, could provide a potential novel approach for prevention of tumor progression in non-small cell lung cancer.