Publications by authors named "Jessica Khoury"

11 Publications

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Speaking Softly and Listening Hard: The Process of Involving Young Voices from a Culturally and Linguistically Diverse School in Child Health Research.

Int J Environ Res Public Health 2021 05 28;18(11). Epub 2021 May 28.

Population Child Health, School of Women's and Children's Health, Faculty of Medicine, UNSW, Sydney 2031, Australia.

The involvement of young people in the planning of research continues to be rare, particularly for young people from culturally and linguistically diverse communities. This paper describes our experience in establishing a Youth Research Advisory Group (YRAG) in South West Sydney (SWS), including barriers and successful strategies. One hundred and fifteen students between school Years 7 and 12 (ages 11-18) took part in at least one of five sessions between 2019 and 2021. In total, we carried out 26 YRAG sessions, with between five and 30 students in each. Sessions focused on mapping the health priorities of the participants and co-developing research project proposals related to their health priorities. Our work with students revealed that their main areas of concern were mental health and stress. This led to material changes in our research strategy, to include "Mental Health" as a new research stream and co-develop new mental health-related projects with the students. Important strategies that enabled our research included maintaining flexibility to work seamlessly with organisational and individual preferences, and ensuring our processes were directed by the schools and-most importantly-the students themselves. Strategies such as maintaining an informal context, responding rapidly to student preference, and regularly renegotiating access enabled us to engage with the students to deepen our understanding of their experiences.
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http://dx.doi.org/10.3390/ijerph18115808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198054PMC
May 2021

PTEN R130Q Papillary Tumor of the Pineal Region (PTPR) with Chromosome 10 Loss Successfully Treated with Everolimus: A Case Report.

Curr Oncol 2021 Mar 20;28(2):1274-1279. Epub 2021 Mar 20.

Department of Pediatric Neurology, Faculty of Medicine, Lebanese University, Beirut P.O. Box 6573/14, Lebanon.

Papillary tumors of the pineal region (PTPR) can be observed among adults with poor prognosis and high recurrence rates. Standards of therapy involve total surgical excision along with radiation therapy, with no promising prospects for primary adjuvant chemotherapy, as long-term treatment options have not been explored. Chromosome 10 loss is characteristic of PTPR, and gene alterations are frequently encountered in a wide range of human cancers and may be treated with mTORC1 inhibitors such as everolimus. In parallel, there are no reports of treating PTPR with everolimus alone as a monopharmacotherapy. We report the case of a patient diagnosed with PTPR (grade III) characterized by a alteration with chromosome 10 loss that was treated with everolimus pharmacotherapy alone, resulting in an asymptomatic course and tumor regression, a rare yet notable phenomenon not described in the literature so far with potential to alter the management approach to patients with PTPR.
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http://dx.doi.org/10.3390/curroncol28020121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025816PMC
March 2021

Safety and efficacy of pazopanib as a second-line treatment and beyond for soft tissue sarcomas: A real-life tertiary-center experience in the MENA region.

Cancer Treat Res Commun 2021 11;26:100275. Epub 2020 Dec 11.

Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon. Electronic address:

Introduction: Sarcomas are uncommon malignancies. No advances have been recently achieved despite multiple efforts. Pazopanib is a safe and effective tyrosine kinase inhibitor used in managing soft tissue sarcomas (STS) after chemotherapy failure. However, its use is limited in developing countries and no efficacy data exist from our region. We aimed to study the efficacy of pazopanib in our population, characterized by response rates of patients with chemotherapy-refractory advanced STS receiving pazopanib. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity profile.

Materials And Methods: 15 patients (age≥18 year) diagnosed with advanced STS, refractory to first-line chemotherapy, receiving pazopanib as ≥second-line therapy in one tertiary center in Lebanon were included between January 1st, 2014 and October 31st, 2018. Patient and disease characteristics, disease evaluation, as well as tolerance to treatment, were extracted from charts retrospectively. Statistical analysis was done using SPSS version 24.

Results: The mean age was 48.6 [19-66] years. Eleven patients (73.3%) received pazopanib in second-line, whereas four patients (26.7%) received it in third-line. Thirteen patients (86.7%) progressed, and two patients (13.3%) had stable disease. The median PFS was three months [1-19] and the mean OS was 25.4 months [17.2-33.6]. Five patients required dose-reductions due to poor tolerance.

Conclusion: Conclusions cannot be drawn due to small patient numbers. However, given the 3-month PFS, 13% of patients maintaining stable disease, and tolerable safety profile, it is reasonable to incorporate pazopanib in STS treatment. More focused studies with larger patient populations need to be done in Lebanon.
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http://dx.doi.org/10.1016/j.ctarc.2020.100275DOI Listing
December 2020

Impact of Commercialized Genomic Tests on Adjuvant Treatment Decisions in Early Stage Breast Cancer Patients.

J Oncol 2020 28;2020:9238084. Epub 2020 Nov 28.

Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon.

Introduction: Advances in genomic techniques have been valuable in guiding decisions regarding the treatment of early breast cancer (EBC) patients. These multigene assays include Oncotype DX, Prosigna, and Endopredict. There has generally been a tendency to overtreat or undertreat patients, and having reliable prognostic factors could significantly improve rates of appropriate treatment administration. In this study, we showcase the impact of genomic tests on adjuvant treatment decisions in EBC patients.

Materials And Methods: This is a retrospective study that includes EBC patients treated between December 2016 and February 2018. The physician's choice of treatment was recorded before and after obtaining the results of the genomics tests. Baseline demographics and pathological data were collected from medical records.

Results: A total of 75 patients were included. Fifty patients underwent Oncotype DX genomic analysis, 11 patients underwent Prosigna analysis, and 14 patients underwent Endopredict analysis. A total of 21 physicians' plans (28%) were initially undecided and then carried out after obtaining genomic test results. 13 patients were planned to undergo endocrine therapy alone, while 8 were planned to undergo both endocrine therapy and chemotherapy. Treatment was changed in 26 patients (34.67%). The decision to deescalate therapy was taken in 19 patients (25.33%). The decision to escalate treatment was made in 7 patients (9.33%).

Conclusion: Our study demonstrates the importance of genomics testing, as it assisted physicians in avoiding unnecessary adjuvant chemotherapy in 25.33% of patients, thus reducing side effects of chemotherapy and the financial burden on patients.
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http://dx.doi.org/10.1155/2020/9238084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719508PMC
November 2020

Correlation of genetic alterations by whole-exome sequencing with clinical outcomes of glioblastoma patients from the Lebanese population.

PLoS One 2020 25;15(11):e0242793. Epub 2020 Nov 25.

Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.

Introduction: Glioblastoma (GBM) is an aggressive brain tumor associated with high degree of resistance to treatment. Given its heterogeneity, it is important to understand the molecular landscape of this tumor for the development of more effective therapies. Because of the different genetic profiles of patients with GBM, we sought to identify genetic variants in Lebanese patients with GBM (LEB-GBM) and compare our findings to those in the Cancer Genome Atlas (TCGA).

Methods: We performed whole exome sequencing (WES) to identify somatic variants in a cohort of 60 patient-derived GBM samples. We focused our analysis on 50 commonly mutated GBM candidate genes and compared mutation signatures between our population and publicly available GBM data from TCGA. We also cross-tabulated biological covariates to assess for associations with overall survival, time to recurrence and follow-up duration.

Results: We included 60 patient-derived GBM samples from 37 males and 23 females, with age ranging from 3 to 80 years (mean and median age at diagnosis were 51 and 56, respectively). Recurrent tumor formation was present in 94.8% of patients (n = 55/58). After filtering, we identified 360 somatic variants from 60 GBM patient samples. After filtering, we identified 360 somatic variants from 60 GBM patient samples. Most frequently mutated genes in our samples included ATRX, PCDHX11, PTEN, TP53, NF1, EGFR, PIK3CA, and SCN9A. Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). EGFR and NF1 mutations were associated with the frontal lobe and temporal lobe in our LEB-GBM cohort, respectively.

Conclusions: Our WES analysis confirmed the similarity in mutation signature of the LEB-GBM population with TCGA cohorts. It showed that 1 out of the 50 commonly GBM candidate gene mutations is associated with decreased overall survival among the Lebanese cohort. This study also highlights the need for studies with larger sample sizes to inform clinicians for better prognostication and management of Lebanese patients with GBM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242793PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688136PMC
January 2021

Fertility in Breast Cancer Survivors in the Middle East: A Retrospective Study.

Breast 2020 Aug 29;52:58-63. Epub 2020 Apr 29.

Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.

Introduction: By the time they complete breast cancer therapy, many young patients are still of childbearing age. We aim to estimate the incidence of pregnancies in women who completed treatment and examine the percentage of patients who received fertility counseling before initiation of therapy.

Material And Methods: Electronic health records of breast cancer patients between 2008 and 2014 at AUBMC were screened for exclusion criteria of having metastatic disease or known infertility, still receiving therapy, and being above 42 years at diagnosis. Data about therapy and tumor characteristics was obtained for the included survivors who were interviewed as well via telephone for information about fertility preservation counseling, pregnancy occurrence, and delivery.

Results: 451 breast cancer patients were identified. 39 patients remained after application of exclusion criteria. 30.76% (n = 12) wanted more children at the time of diagnosis. 10.25% (n = 4) of all 39 patients treated for breast cancer achieved one or more pregnancy after a median time of 3.83 years after completion of therapy. 25% (n = 3) of women who wanted more children at diagnosis (n = 12) were able to conceive. 23.07% (n = 9) of patients discussed fertility with their primary oncologist prior to treatment initiation. 35.89% (n = 14) of patients were aware of fertility preservation technique availability, but none of these patients used one.

Conclusions: The observed rate of pregnancy is comparable to the literature. There is a lack in fertility counseling of breast cancer patients, and the rate of use of fertility preservation techniques is very low despite prior knowledge about their availability.
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http://dx.doi.org/10.1016/j.breast.2020.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377329PMC
August 2020

Demographics and outcomes of meningioma patients treated at a tertiary care center in the Middle East.

Clin Neurol Neurosurg 2020 08 20;195:105846. Epub 2020 Apr 20.

Department of Surgery, American University of Beirut Medical Center, Lebanon. Electronic address:

Objective: Meningioma is the most common intracranial primary brain tumor. Risk factors such as age and exposure to radiation as well as prognostic factors such as grade, location, and extent of surgical resection have been reported in the literature worldwide; however, to our knowledge, data from the Middle East is still warranted. In this study, we aim to identify the characteristics, risk factors and outcomes of meningioma patients treated at a multidisciplinary regional referral center in the Middle East.

Patients And Methods: This is a retrospective chart review with a prospective follow up of outcomes. It included patients diagnosed with meningioma between January 2005 and December 2015 at the American University of Beirut Medical Center. Patient's demographics, risk factors and outcomes were first retrospectively collected. Then, we conducted phone calls to all included alive patients to update their disease status and outcomes.

Results: One-hundred and ninety-five patients were included. 69 % had grade I tumors and around 31 % with grades II and III meningiomas. The means of the overall survival and progression free survival (PFS) were 198 and 126 months, respectively. The residence area (city vs. countryside), occupation, alcohol use, oral contraceptive use, family history of meningioma, previous head trauma, radiation exposure for head/brain imaging, cell phone use, and finally, the tumor Ki-67 protein level did not correlate with the survival outcomes. The meningioma grade and extent of resection were significant predictors of the PFS on the univariate analysis, whereas, in the multivariate analysis only previous radiotherapy was significant in prolonging PFS.

Conclusion: In our study cohort, that included around 30 % grades II and III tumors, previous radiotherapy use was the only significant prognostic factor for longer PFS in patients diagnosed with meningioma. Future prospective studies should be conducted to evaluate genetic and molecular factors that could possibly be linked to meningioma grade and prognosis in our population of Middle Eastern patients.
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http://dx.doi.org/10.1016/j.clineuro.2020.105846DOI Listing
August 2020

Chemogenomic Screen for Imipenem Resistance in Gram-Negative Bacteria.

mSystems 2019 Nov 19;4(6). Epub 2019 Nov 19.

Axe des Maladies Infectieuses et Immunitaires du Centre de Recherche du CHU de Québec and Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, Québec, Canada

Carbapenem-resistant Gram-negative bacteria are considered a major threat to global health. Imipenem (IMP) is used as a last line of treatment against these pathogens, but its efficacy is diminished by the emergence of resistance. We applied a whole-genome screen in , , and isolates that were submitted to chemical mutagenesis, selected for IMP resistance, and characterized by next-generation sequencing. A comparative analysis of IMP-resistant clones showed that most of the highly mutated genes shared by the three species encoded proteins involved in transcription or signal transduction. Of these, the gene was one of the most prevalent and an strain disrupted for displayed a 4-fold increase in resistance to IMP. and also specifically shared several mutated genes, most involved in membrane/cell envelope biogenesis, and the contribution in IMP susceptibility was experimentally proven for amidases, transferases, and transglycosidases. differed from the two isolates with two different resistance mechanisms, with one involving mutations in the porin or, alternatively, in two-component systems. Our chemogenomic screen performed with the three species has highlighted shared and species-specific responses to IMP. Gram-negative carbapenem-resistant bacteria are a major threat to global health. The use of genome-wide screening approaches to probe for genes or mutations enabling resistance can lead to identification of molecular markers for diagnostics applications. We describe an approach called Mut-Seq that couples chemical mutagenesis and next-generation sequencing for studying resistance to imipenem in the Gram-negative bacteria , , and The use of this approach highlighted shared and species-specific responses, and the role in resistance of a number of genes involved in membrane biogenesis, transcription, and signal transduction was functionally validated. Interestingly, some of the genes identified were previously considered promising therapeutic targets. Our genome-wide screen has the potential to be extended outside drug resistance studies and expanded to other organisms.
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http://dx.doi.org/10.1128/mSystems.00465-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867876PMC
November 2019

Penicillin induces alterations in glutamine metabolism in Streptococcus pneumoniae.

Sci Rep 2017 11 6;7(1):14587. Epub 2017 Nov 6.

Centre de Recherche en Infectiologie du Centre de Recherche du CHU de Québec and Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, Québec, Canada.

Penicillin is a bactericidal antibiotic that inhibits the synthesis of the peptidoglycan by targeting penicillin-binding proteins. This study aimed to assess through transcriptional profiling the stress response of S. pneumoniae strains after exposure to lethal penicillin concentrations to understand further the mode of action of penicillin. Two experimental designs (time-course and dose-response) were used for monitoring the effect of penicillin on the transcriptional profile. The expression of some genes previously shown to be modulated by penicillin was altered, including ciaRH, pstS and clpL. Genes of the glnRA and glnPQ operons were among the most downregulated genes in the three strains. These genes are involved in glutamine synthesis and uptake and LC-MS work confirmed that penicillin treatment increases the intracellular glutamine concentrations. Glutamine conferred a protective role against penicillin when added to the culture medium. Glutamine synthetase encoded by glnA catalyses the transformation of glutamate and ammonium into glutamine and its chemical inhibition by the inhibitor L-methionine sulfoximine is shown to sensitize S. pneumoniae to penicillin, including penicillin-resistant clinical isolates. In summary, a combination of RNA-seq and metabolomics revealed that penicillin interferes with glutamine metabolism suggesting strategies that could eventually be exploited for combination therapy or for reversal of resistance.
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http://dx.doi.org/10.1038/s41598-017-15035-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673960PMC
November 2017

Narrative Exemplars and the Celebrity Spokesperson in Lebanese Anti-Domestic Violence Public Service Announcements.

J Health Commun 2016 08 21;21(8):935-43. Epub 2016 Jul 21.

b School of Journalism and Communication , University of Oregon , Eugene , Oregon , USA.

Domestic violence is a worldwide epidemic. This study examines the effects of narrative exemplars and a celebrity spokesperson in anti-domestic violence ads on Lebanese college students' attitudes and beliefs towards domestic violence and whether these effects are impacted by personal experience. The practical significance is derived from the high prevalence of domestic violence internationally, making it important to find ways to effectively use media to address this health-related issue that has huge consequences for the individual and society. This study adds to the theoretical understanding of narrative persuasion and media effects. Results indicated that narrative exemplars in anti-domestic violence ads promoting bystander awareness and intervention were more beneficial for people without relevant experience compared to people who know someone affected by domestic violence. Anti-domestic violence ads without narrative exemplars, but that also featured an emotional self-efficacy appeal targeting bystanders, were more effective for participants who know someone who had experienced domestic violence compared to participants without relevant experience. The presence of a celebrity spokesperson elicited more positive attitudes about the ad than a noncelebrity, but failed to directly affect relevant anti-domestic violence attitudes or beliefs. These results highlight the significance of formative audience research in health communication message design.
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http://dx.doi.org/10.1080/10810730.2016.1177146DOI Listing
August 2016
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