Disclosure of Diagnosis and Prognosis to Cancer Patients in Traditional Societies: A Qualitative Assessment from Lebanon

Background: The issue of when, how, and whether to disclose full information about cancer diagnosis and prognosis to patients is still debated in some parts of the world, including Lebanon. Despite formal academic emphasis on a larger autonomy for Lebanese patients in deciding the course of their disease, there has been no apparent impact on either clinical practices nor public expectations.  The topic of full disclosure is rarely if ever discussed in open fora, or in mass media channels in Lebanon. Subjects and Method: Seven key stakeholders were identified and interviewed regarding obstacles to spelling out clear guidelines within our national context. The interviews were transcribed and subsequently analyzed for recurrent patterns and concepts.Results: Senior oncologists interviewed generally favored gradual disclosure and most perceived a changing trend among both patients and physicians towards more disclosure. They also agreed on a need for the formal training of residents and fellows to better communicate bad news to patients. All the interviewed physicians attested to the benefits of candid disclosure in terms of patient psychology and overall wellbeing. They also mentioned that psychological services, which may facilitate the disclosure process, are greatly under-utilized in oncology. Lawyers highlighted the vagueness of the current Lebanese legislation regarding the obligation of truthful disclosure in comparison to laws in developed countries and the implications on patient autonomy. Conclusion: The study identified the need for improvements at various levels, including interventions to modify the expectations of the Lebanese public regarding cancer disclosure and to clarify existing legislative texts.Keywords: Ethics; Legislation; Middle-East; DisclosureCorrespondence: James Feghali. Faculty of Medicine, American University of Beirut (AUB), Lebanon, 1101 North Calvert Street, 610, Baltimore, Maryland, 21202. E-mail: [email protected]. Telephone: +1-(267)-595-9995.Journal of Epidemiology and Public Health (2019), 4(2): 109-116https://doi.org/10.26911/jepublichealth.2019.04.02.0

Comparison of Proteomic and Transcriptomic Profiles in the Bronchial Airway Epithelium of Current and Never Smokers

Although prior studies have demonstrated a smoking-induced field of molecular injury throughout the lung and airway, the impact of smoking on the airway epithelial proteome and its relationship to smoking-related changes in the airway transcriptome are unclear.Airway epithelial cells were obtained from never (n = 5) and current (n = 5) smokers by brushing the mainstem bronchus. Proteins were separated by one dimensional polyacrylamide gel electrophoresis (1D-PAGE). After in-gel digestion, tryptic peptides were processed via liquid chromatography/ tandem mass spectrometry (LC-MS/MS) and proteins identified. RNA from the same samples was hybridized to HG-U133A microarrays. Protein detection was compared to RNA expression in the current study and a previously published airway dataset. The functional properties of many of the 197 proteins detected in a majority of never smokers were similar to those observed in the never smoker airway transcriptome. LC-MS/MS identified 23 proteins that differed between never and current smokers. Western blotting confirmed the smoking-related changes of PLUNC, P4HB1, and uteroglobin protein levels. Many of the proteins differentially detected between never and current smokers were also altered at the level of gene expression in this cohort and the prior airway transcriptome study. There was a strong association between protein detection and expression of its corresponding transcript within the same sample, with 86% of the proteins detected by LC-MS/MS having a detectable corresponding probeset by microarray in the same sample. Forty-one proteins identified by LC-MS/MS lacked detectable expression of a corresponding transcript and were detected in <or=5% of airway samples from a previously published dataset.1D-PAGE coupled with LC-MS/MS effectively profiled the airway epithelium proteome and identified proteins expressed at different levels as a result of cigarette smoke exposure. While there was a strong correlation between protein and transcript detection within the same sample, we also identified proteins whose corresponding transcripts were not detected by microarray. This noninvasive approach to proteomic profiling of airway epithelium may provide additional insights into the field of injury induced by tobacco exposure

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

TN-RS: a novel scoring system predicts Gamma Knife Radiosurgery outcome for trigeminal neuralgia patients.

BACKGROUND: Gamma Knife Radiosurgery (GKRS) is an effective treatment option for medically refractory trigeminal neuralgia (TN). This study examines GKRS outcome in a large cohort of TN patients and highlights pretreatment factors associated with pain relief. METHODS: This is a single-center retrospective analysis of patients treated with GKRS for TN between 2011 and 2019. Pain relief was assessed at 1 year, and 2-3 years following GKRS. Multivariable analysis identified several factors that predicted pain relief. These predicting factors were applied to establish a pain relief scoring system. RESULTS: A total of 162 patients met inclusion criteria. At 1 year post-GKRS, the breakdown of Barrow Neurological Institute (BNI) score for pain relief was as follows: 77 (48%) score of I, 13 (8%) score of II, 37 (23%) score of III, 22 (14%) score of IV, and 13 (8%) score of V. Factors that were significantly associated with pain-free outcome at 1 year were: Typical form of TN (OR = 2.2 [1.1, 4.9], p = 0.049), No previous microvascular decompression (OR = 4.4 [1.6, 12.5], p = 0.005), Response to medical therapy (OR = 2.7 [1.1, 6.1], p = 0.018), and Seniority \u3e 60 years (OR = 2.8 [1.4, 5.5], p = 0.003). The term Trigeminal Neuralgia-RadioSurgery was used to create the TN-RS acronym representing the significant factors. A stepwise increase in the median predicted probability of pain-free outcome at 1 year from 3% for patients with a score of 0 to 69% for patients with a maximum score of 4. CONCLUSION: The TN-RS scoring system can assist clinicians in identifying patients that may benefit from GNRS for TN by predicting 1-year pain-free outcomes

Prediction of severity and subtype of fibrosing disease using model informed by inflammation and extracellular matrix gene index.

Fibrosis is a chronic disease with heterogeneous clinical presentation, rate of progression, and occurrence of comorbidities. Systemic sclerosis (scleroderma, SSc) is a rare rheumatic autoimmune disease that encompasses several aspects of fibrosis, including highly variable fibrotic manifestation and rate of progression. The development of effective treatments is limited by these variabilities. The fibrotic response is characterized by both chronic inflammation and extracellular remodeling. Therefore, there is a need for improved understanding of which inflammation-related genes contribute to the ongoing turnover of extracellular matrix that accompanies disease. We have developed a multi-tiered method using Naïve Bayes modeling that is capable of predicting level of disease and clinical assessment of patients based on expression of a curated 60-gene panel that profiles inflammation and extracellular matrix production in the fibrotic disease state. Our novel modeling design, incorporating global and parametric-based methods, was highly accurate in distinguishing between severity groups, highlighting the importance of these genes in disease. We refined this gene set to a 12-gene index that can accurately identify SSc patient disease state subsets and informs knowledge of the central regulatory pathways in disease progression

Disclosure of Diagnosis and Prognosis to Cancer Patients in Traditional Societies: A Qualitative Assessment from Lebanon

Background: The issue of when, how, and whether to disclose full information about cancer diagnosis and prognosis to patients is still debated in some parts of the world, including Lebanon. Despite formal academic emphasis on a larger autonomy for Lebanese patients in deciding the course of their disease, there has been no apparent impact on either clinical practices nor public expectations. The topic of full disclosure is rarely if ever discussed in open fora, or in mass media channels in Lebanon. Subjects and Method: Seven key stakeholders were identified and interviewed regarding obstacles to spelling out clear guidelines within our national context. The interviews were transcribed and subsequently analyzed for recurrent patterns and concepts. Results: Senior oncologists interviewed generally favored gradual disclosure and most perceived a changing trend among both patients and physicians towards more disclosure. They also agreed on a need for the formal training of residents and fellows to better communicate bad news to patients. All the interviewed physicians attested to the benefits of candid disclosure in terms of patient psychology and overall wellbeing. They also mentioned that psychological services, which may facilitate the disclosure process, are greatly under-utilized in oncology. Lawyers highlighted the vagueness of the current Lebanese legislation regarding the obligation of truthful disclosure in comparison to laws in developed countries and the implications on patient autonomy. Conclusion: The study identified the need for improvements at various levels, including interventions to modify the expectations of the Lebanese public regarding cancer disclosure and to clarify existing legislative texts

Differential DNA Methylation Landscape in Skin Fibroblasts from African Americans with Systemic Sclerosis

The etiology and reasons underlying the ethnic disparities in systemic sclerosis (SSc) remain unknown. African Americans are disproportionally affected by SSc and yet are underrepresented in research. The aim of this study was to comprehensively investigate the association of DNA methylation levels with SSc in dermal fibroblasts from patients of African ancestry. Reduced representation bisulfite sequencing (RRBS) was performed on primary dermal fibroblasts from 15 SSc patients and 15 controls of African ancestry, and over 3.8 million CpG sites were tested for differential methylation patterns between cases and controls. The dermal fibroblasts from African American patients exhibited widespread reduced DNA methylation. Differentially methylated CpG sites were most enriched in introns and intergenic regions while depleted in 5' UTR, promoters, and CpG islands. Seventeen genes and eleven promoters showed significant differential methylation, mostly in non-coding RNA genes and pseudogenes. Gene set enrichment analysis (GSEA) and gene ontology (GO) analyses revealed an enrichment of pathways related to interferon signaling and mesenchymal differentiation. The hypomethylation of DLX5 and TMEM140 was accompanied by these genes' overexpression in patients but underexpression for lncRNA MGC12916. These data show that differential methylation occurs in dermal fibroblasts from African American patients with SSc and identifies novel coding and non-coding genes

Insulin-Like Growth Factor-Binding Protein-5 Induces Pulmonary Fibrosis and Triggers Mononuclear Cellular Infiltration

We have recently shown that insulin-like growth factor-binding protein (IGFBP)-5 is overexpressed in idiopathic pulmonary fibrosis lung tissues and increases collagen and fibronectin deposition. Here, we further examined the effect of IGFBP-5 in vivo by intratracheal administration of replication-deficient adenovirus expressing human IGFBP-5 (Ad5), IGFBP-3 (Ad3), or no cDNA (cAd) to wild-type mice. Increased cellular infiltration and extracellular matrix deposition were observed in mice after Ad5 administration compared with Ad3 and cAd. Mononuclear cell infiltration consisted predominantly of T lymphocytes at day 8. By day 14, the number of infiltrating T cells decreased, whereas that of B cells and monocytes/macrophages increased. IGFBP-5 also induced migration of peripheral blood mononuclear cells in vitro, suggesting that in vivo mononuclear cell infiltration may be the direct result of IGFBP-5 expression. α-Smooth muscle actin and Mucin-1 co-localized in cells of mice treated with Ad5, suggesting that IGFBP-5 induced epithelial-mesenchymal transition. In addition, exogenous IGFBP-5 induced α-smooth muscle actin expression in primary fibroblasts and epithelial-mesenchymal transition of pulmonary epithelial cells in vitro. In conclusion, our results suggest that overexpression of IGFBP-5 in mouse lung results in fibroblast activation, increased extracellular matrix deposition, and myofibroblastic changes. Thus, the IGFBP-5-induced fibrotic phenotype in vivo may represent a novel model to better understand the pathogenesis of fibrosis