Pharmacogenomics in Lebanon: current status, challenges and opportunities.

Pharmacogenomics (PGx) research and applications are of utmost relevance in Lebanon considering its population genetic diversity. Moreover, as a country with regional leadership in medicine and higher education, Lebanon holds a strong potential in contributing to PGx research and clinical implementation. In this manuscript, we first review and evaluate the available PGx research conducted in Lebanon, then describe the current status of PGx practice in Lebanon while reflecting on the local and regional challenges, and highlighting areas for action, and opportunities to move forward. We specifically expand on the status of PGx at the American University of Beirut Faculty of Medicine and Medical Center as a case study and guide for the further development of local and regional comprehensive PGx research, teaching, and clinical implementation programs. We also delve into the status of PGx knowledge and education, and prospects for further advancement such as with online courses and certificates.

Patterns and predictors of positive multiplex polymerase chain reaction respiratory panel among patients with acute respiratory infections in a single center in Lebanon.

BACKGROUND: Infectious agents associated with community-acquired acute respiratory infections (ARIs) remain understudied in Lebanon. We aim to assess the microbiological profiles of ARIs by employing polymerase chain reaction (PCR) and identifying predictors of positive PCR results among patients admitted for ARI. METHODS AND RESULTS: We conducted a retrospective single-center study at the American University of Beirut Medical Center, including all respiratory PCR panels performed on pediatric (< 18) and adult (≥ 18) patients presenting with an ARI from January 2015 to March 2018, prior to the onset of the COVID-19 pandemic. We aimed to identify the epidemiological patterns of ARIs and the factors associated with positive PCRs in both adult and pediatric patients. Among 281 respiratory PCRs, 168 (59.7%) were positive for at least one pathogen, with 54.1% positive PCR for viruses, 7.8% for bacteria species, and 3.9% with virus-bacteria codetection. Almost 60% of the patients received antibiotics prior to PCR testing. PCR panels yielded more positive results in pediatric patients than in adults (P = 0.005). Bacterial detection was more common in adults compared to pediatrics (P < 0.001). The most common organism recovered in the entire population was Human Rhinovirus (RhV) (18.5%). Patients with pleural effusion on chest CT were less likely to have a positive PCR (95% Cl: 0.22-0.99). On multivariate analysis, pediatric age group (P < 0.001), stem cell transplant (P = 0.006), fever (P = 0.03) and UTRI symptoms (P = 0.004) were all predictive of a positive viral PCR. CONCLUSION: Understanding the local epidemiology of ARI is crucial for proper antimicrobial stewardship. The identification of factors associated with positive respiratory PCR enhances our understanding of clinical characteristics and potential predictors of viral detection in our population.

Biospecimen Repositories in Low- and Middle-Income Countries: Insights From an American University of Beirut and Memorial Sloan Kettering Collaboration.

PURPOSE: Biobanking helps source tissue and blood for studying cancer genomics. Access to biorepository resources in low- and middle-income countries is lacking. Memorial Sloan Kettering Cancer Center (MSK) and the American University of Beirut (AUB) established a joint tissue biorepository at AUB in Beirut, Lebanon. The undertaking encountered key challenges that were unanticipated. MATERIALS AND METHODS: Patients age 18 years or older were eligible for enrollment at AUB. After consent, biospecimens were obtained at the time of routine diagnostic and/or therapeutic interventions. Both normal and abnormal tissue and solid and/or liquid specimens were collected from varied body sites. Early on, declining consent was frequently observed, and this was highlighted for investigation to understand potential participants reasoning. RESULTS: Of 850 patients approached, 704 (70.8%) elected to consent and 293 (29.5%) declined participation. The number of declined consents led to an amendment permitting the documentation of reasons for same. Of 100 potential participants who declined to consent and to whom outreach was undertaken, 63% indicated lack of research awareness and 27% deferral to their primary physician or family member. A financial gain for AUB was cited as concern by 5%, cultural boundaries in 4%, and 1% expressed concern about confidentiality. Of the patients who elected to consent, 682 biospecimens were procured. CONCLUSION: The AUB-MSK biospecimen repository has provided a unique resource for interrogation. Patient participation rate was high, and analyses of those who elected not to consent (29%) provide important insights into educational need and the local and cultural awareness and norms.

Comparison between the accuracy of chest computerized tomography vs. reverse transcriptase polymerase chain reaction in a tertiary care center in Lebanon; along with their correlation to mortality, morbidity and symptoms in COVID-19 patients.

Objectives: Chest Computerized Tomography has been widely used in COVID patients' assessment. Hence the question arises as to whether there is any correlation between the Ct value and findings on Chest CT scan or clinical presentation of the patient. We wanted to test the hypothesis of whether low Ct values (≤30) in RT-PCR were associated with a high mortality rate, CT scan findings, or with comorbidities such as immunosuppression and lung disease. Methods: The radiographic records and RT-PCR Ct values of 371 COVID patents diagnosed at the American University of Beirut Medical Center were reviewed. Results: We found out that the sensitivity of chest CT scan compared to RT-PCR, the gold standard, turned out to be 74% (95% CI 69-79%). Specificity, on the other hand was 33% (95% CI 16-55%). The positive predictive value of CT was 94% (95% CI 91-97%) and the negative predictive value was 8% (95% CI 4-16%). low Ct values in RT-PCR were not associated with a higher mortality rate (p-value = 0.416). There was no significant positive association between low Ct value and suspicious CT scan findings (typical and indeterminate for COVID-19), with a p-value of 0.078. There was also no significant association between low Ct value and immunosuppression (p-value = 0.511), or lung disease (p-value =0.06). CT scan findings whether suspicious or not for COVID-19 infection, were not shown to be significantly associated with respiratory symptoms of any kind.No association was found between a history of lung disease, immunosuppression and suspicious CT scan findings for COVID-19. Conclusion: As long as this pandemic exists, nucleic acid testing was and remains the gold standard of COVID-19 diagnosis worldwide and in our community as it has a superior diagnostic accuracy to CT scan and higher sensitivity (94% vs 74%).

The Impact of an Educational Video in Arabic Language on Patients' Knowledge and Attitudes Towards Genetic Testing for Cancer Therapy.

Rapid advances in cancer genetics are paving the way towards personalized cancer management, and genetic testing is now an important decision-making tool. Despite the advantages, genetic testing adds a layer of complexity in the management which is difficult to communicate with patients. The variability health literacy among patients may restrict their engagement in genetic procedures. Improving the language and presentation of genomic concepts can influence patients' risk assessment and willingness to undergo testing. The study aimed to compare the knowledge and attitudes of cancer patients presenting to oncology clinics at The American University of Beirut Medical Center before and after watching a short educational video that clarifies the concepts of genetic mutations, genetic testing technique, and its purposes.Twenty-nine adult patients presenting to the oncology clinics and due to receive somatic or germline genetic testing filled a questionnaire which assesses their knowledge and attitudes before and after the educational video was played. The majority of patients had poor baseline knowledge before the intervention. After watching the video, the percentage of patients with poor knowledge decreased to a minimum of 3.4% and a maximum of 39% for each concept. Mean score for attitude questions also increased significantly. Effective patient education and counseling programs in the patients' native language prior to genetic testing can increase knowledge, decrease hesitancy, and improve clinical decision making. A short educational video is an example of a simple intervention towards an inclusive approach in patient care all over the world.

Sequence-based allelic variations and frequencies for 22 autosomal STR loci in the Lebanese population.

This is the first study that characterizes the sequence-based allelic variations of 22 autosomal Short Tandem Repeat (aSTR) loci in a population dataset collected from Lebanon. Genomic DNA extracts from 195 unrelated Lebanese individuals were amplified with PowerSeq 46GY System Prototype. Targeted amplicons were subjected to DNA library preparation and sequenced on the Verogen MiSeq FGx Sequencing System. Raw FASTQ data files were processed by STRait Razor v3. Sequence strings were annotated according to the considerations of the DNA Commission of the International Society for Forensic Genetics (ISFG) and tabulated herein with their respective allelic frequencies and GeneBank accession and version numbers. The sequenced Lebanese dataset resulted in 429 distinct allelic sequences as compared to the 236 alleles identified by length only. The increase in the number of alleles was observed at 18 out of 22 aSTR loci and was attributed to the sequence variations residing in both the STR repeat motifs and flanking regions. The study uncovered 25 novel aSTR allelic sequences across 12 loci for which GenBank records did not previously exist in the STRSeq BioProject, PRJNA380127. For a concordance check, the length-based allelic calls derived from the full sequences were compared to those genotyped using capillary electrophoresis (CE) methods. Population genetic parameters relevant to the evaluation of forensic DNA evidence were assessed for the sequence-based data and compared to the parameters generated from the length-based information. Using the sequence-based data, Analysis of MOlecular VAriance (AMOVA), genetic distances, and population genetic structure were evaluated for 1231 individuals sampled from the Lebanese and four U.S. populations (African American, Asian, Caucasian, and Hispanic). The results were tabulated and visualized in a population tree, multidimensional scaling scatter plots, and bar plots. This newly established sequence-based database for the Lebanese population can be beneficial for extending NGS applicability to casework or paternity testing and assessing the strength of evidence for NGS-STR profiles. The described novel sequence variants at certain loci can further help in the effort to characterize the sequence diversity of STR markers from different populations around the world.

Frequency and mutational spectrum of PIK3CA gene mutations in breast cancer patients: Largest and first report from Lebanon.

The PIK3CA pathway is one of the most frequently altered pathways in human cancers, especially in breast cancer with approximately 40% of HR+/HER2- advanced breast cancer cases exhibiting mutations in the PIK3CA gene. While the mutations can occur across the entire gene, the most common are observed in exon 9 corresponding to the helical domain, and in exon 20 encompassing the kinase domain. This study constitutes the first attempt at determining the frequency and mutational spectrum in Lebanese breast cancer patients. For this purpose, DNA samples from 280 breast cancer patients from across Lebanon were screened for PIK3CA mutations using the Therascreen® PIK3CA RGQ Real-time PCR assay. In line with previous reports, 38.57% of cases were positive for at least one PIK3CA mutation, among which approximately 59% were in exon 9 and 37% in exon 20. However, PIK3CA mutations are breast cancer are heterogeneous whereby 20% of known PIK3CA mutants might not be detected by compact PCR based assays. Thus, the adoption of comprehensive Next Generation Sequencing based panels to decipher the complete clinical, molecular and immunohistochemical profile of breast cancer tumor requires further investigation.

Using comprehensive genomic and functional analyses for resolving genotype-phenotype mismatches in children with suspected CMMRD in Lebanon: an IRRDC study.

Constitutional mismatch repair deficiency (CMMRD) is an aggressive and highly penetrant cancer predisposition syndrome. Because of its variable clinical presentation and phenotypical overlap with neurofibromatosis, timely diagnosis remains challenging, especially in countries with limited resources. Since current tests are either difficult to implement or interpret or both we used a novel and relatively inexpensive functional genomic assay (LOGIC) which has been recently reported to have high sensitivity and specificity in diagnosing CMMRD. Here we report the clinical and molecular characteristics of nine patients diagnosed with cancer and suspected to have CMMRD and highlight the challenges with variant interpretation and immunohistochemical analysis that led to an uncertain interpretation of genetic findings in 6 of the 9 patients. Using LOGIC, we were able to confirm the diagnosis of CMMRD in 7 and likely exclude it in 2 patients, resolving ambiguous result interpretation. LOGIC also enabled predictive testing of asymptomatic siblings for early diagnosis and implementation of surveillance. This study highlights the varied manifestations and practical limitations of current diagnostic criteria for CMMRD, and the importance of international collaboration for implementing robust and low-cost functional assays for resolving diagnostic challenges.

The under investigated facet of the COVID-19 pandemic: Molecular analysis of secondary bacterial infections at a COVID dedicated intensive care unit within a tertiary care center in Lebanon.

Background: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Secondary bacterial infections are associated with unfavorable outcomes in respiratory viral infections. This study aimed at determining the prevalence of secondary bacterial infections in COVID-19 patients admitted at a tertiary medical center in Lebanon. Methodology: From May till November, 2020, a total of 26 Gram-negative isolates were recovered from 16 patients during the course of their COVID-19 infection with Escherichia coli being the most prevalent. The isolates were assessed for their antimicrobial susceptibility by broth microdilution against 19 antimicrobial agents from different classes. Whole genome sequencing of 13 isolates allowed the mining of antimicrobial resistance (AMR) determinants as well as mobile genetic elements and sequence types (ST). Finally, broth microdilution with three different efflux pump inhibitors [theobromine, conessine and PheArg-ß-naphthylamide (PAßN)] was done. Results: Antimicrobial susceptibility testing showed that out of the 26 Gram-negative isolates, 1 (4%) was extensively drug resistant and 14 (54%) were multi-drug resistant (MDR). Whole genome sequencing results revealed a plethora of AMR determinants among the 13 sequenced isolates. Moreover, the 9 Enterobacterales and 4 Pseudomonas aeruginosa sequenced isolates belonged to 9 and 2 different ST, respectively. Using a variety of efflux pump inhibitors we demonstrated that only PAßN had a significant effect when combined with levofloxacin, and the latter regained its activity against two P. aeruginosa isolates. Conclusion: The identification of carbapenem and colistin resistant Gram-negative bacilli causing secondary bacterial infections in critical patients diagnosed with COVID-19 should be of high concern. Additionally, it is crucial to monitor and track AMR, post-COVID pandemic, in order to better understand the effect of this disease on AMR exacerbation.

Genomic surveillance of SARS-CoV-2 in COVID-19 vaccinated healthcare workers in Lebanon.

BACKGROUND: The emergence of SARS-CoV-2 variants including the Delta and Omicron along with waning of vaccine-induced immunity over time contributed to increased rates of breakthrough infection specifically among healthcare workers (HCWs). SARS-CoV-2 genomic surveillance is an important tool for timely detection and characterization of circulating variants as well as monitoring the emergence of new strains. Our study is the first national SARS-CoV-2 genomic surveillance among HCWs in Lebanon. METHODS: We collected 250 nasopharyngeal swabs from HCWs across Lebanon between December 2021 and January 2022. Data on the date of positive PCR, vaccination status, specific occupation, and hospitalization status of participants were collected. Extracted viral RNA from nasopharyngeal swabs was converted to cDNA, library prepped using the coronaHIT method, followed by whole genome sequencing on the Illumina NextSeq 500 platform. RESULTS: A total of 133 (57.1%) samples belonging to the Omicron (BA.1.1) sub-lineage were identified, as well as 44 (18.9%) samples belonging to the BA.1 sub-lineage, 28 (12%) belonging to the BA.2 sub-lineage, and only 15 (6.6%) samples belonging to the Delta variant sub-lineage B.1.617.2. These results show that Lebanon followed the global trend in terms of circulating SARS-CoV-2 variants with Delta rapidly replaced by the Omicron variant. CONCLUSION: This study underscores the importance of continuous genomic surveillance programs in Lebanon for the timely detection and characterization of circulating variants. The latter is critical to guide public health policy making and to timely implement public health interventions.

Thrombotic Microangiopathy in the Setting of Colorectal Cancer: A Therapeutic Challenge with a Bad Prognosis.

While most cases of thrombotic microangiopathic hemolytic anemias are idiopathic, some can occur in the setting of a malignancy. Differentiating both conditions is crucial to initiate the appropriate treatment. In this case report and literature review, we discuss the occurrence of a thrombotic microangiopathy in a 61-year-old male patient with a treatment-refractory metastatic colorectal cancer invading his bone marrow. Plasmapheresis does not constitute the mainstay of treatment in this setting, as targeting the primary disease is the ultimate management. Treating the condition of our patient has been challenging as multiple lines of treatments of his primary disease had been exhausted. The discrepancy in KRAs status obtained between PCR and later NGS offered a new treatment line with Cetuximab. In this article, we will discuss the different factors that differentiate between idiopathic and cancer-induced microangiopathy. We will emphasize on the fact that the treatment of the primary disease constitutes the most important step in the treatment of cancer-induced thrombotic microangiopathy. We will also raise several explanations to target the disagreement in KRAS status obtained by the different technical modalities.

Haploidentical stem cell transplantation with post-transplant cyclophosphamide challenges and outcome from a tertiary care center in Lebanon.

This letter describes the experience of the American University of Beirut Medical Center in Lebanon with haploidentical stem cell transplant (haplo-SCT) for hematological malignancies in adult patients. Haplo-SCT made it possible through universal and rapid donor availability for most of the adult patients with leukemia or lymphoma not only in the Middle East but also globally. Moreover, the use of post-transplant cyclophosphamide (PTCy) and reduced intensity conditioning (RIC) regimens when indicated improved the outcome and decreased the toxicity of haploidentical stem cell transplant.RIC regimens also allowed its use in the elderly population. Patients from throughout the Middle East come to our center, the American university of Beirut Medical Center, to receive this transformative type of stem cell transplant. In this paper, we discuss the results of haplo-SCT with PTCy done on adult patients with hematological malignancies in our center from 2015 to 2021. The results are encouraging and show that haplo-SCT should be considered more often in the Middle Eastern countries. The subgroup analysis showed the importance of achieving complete remission of the disease prior to transplant to improve outcomes in our center. There is a paucity of literature on the outcomes of haplo-SCT in the Middle East which may contribute to the limited number of centers that offer this type of SCT. Herein, we aim to fill this gap in the hopes of encouraging the implementation of this potentially curative modality of treatment to a larger extent in the Middle East.

Challenges of genetic diagnosis of inborn errors of metabolism in a major tertiary care center in Lebanon.

Background: Inborn errors of metabolism are rare genetic disorders; however, these are prevalent in countries with high consanguinity rates, like Lebanon. Patients are suspected, based on a combination of clinical and biochemical features; however, the final confirmation relies on genetic testing. Using next generation sequencing, as a new genetic investigational tool, carries several challenges for the physician, the geneticist, and the families. Methods: In this retrospective study, we analyzed the clinical, biochemical, and genetic profile of inborn errors of metabolism suspected patients, seen at a major tertiary care center in Lebanon, between 2015 and 2018. Genetic testing was performed using next generation sequencing. Genotype-phenotype correlation and diagnostic yield of each testing modality were studied. Results: Out of 211 patients genetically tested, 126 were suspected to have an inborn error of metabolism. The diagnostic yield of next generation sequencing reached 64.3%. Single gene testing was requested in 53%, whole exome sequencing in 36% and gene panels in 10%. Aminoacid disorders were mostly diagnosed followed by storage disorders, organic acidemias and mitochondrial diseases. Targeted testing was performed in 77% of aminoacid and organic acid disorders and half of suspected storage disorders. Single gene sequencing was positive in 75%, whereas whole exome sequencing diagnostic yield for complex cases, like mitochondrial disorders, reached 49%. Good clinical and biochemical correlation allowed the interpretation of variants of unknown significance and negative mutations as well as therapeutic management of most patients. Conclusion: Tailoring the choice of test modality, by next generation sequencing, to the category of suspected inborn errors of metabolism may lead to rapid diagnosis, shortcutting the cost of repeated testing. Whole exome sequencing as a first-tier investigation may be considered mainly for suspected mitochondrial diseases, whereas targeted sequencing can be offered upon suspicion of a specific enzyme deficiency. Timing and modality of gene test remain challenging, in view of the cost incurred by families.

Heritable cancer predisposition testing in pediatric cancer patients excluding retinoblastoma in a middle-income country.

Resource-limited settings often have financial barriers to genetic testing for heritable cancer. This retrospective study investigated the pattern of heritable cancer predisposition testing in a middle-income country over the period 2014-2021, excluding retinoblastoma. After establishing a specific fund in 2019, rate of tests increased from 1.1% to 10.9% of new diagnoses. Most common testing was for constitutional mismatch repair deficiency (CMMRD), rhabdoid predisposition syndrome, TP53 (tumor protein 53) mutation, and hereditary cancer panel. Of 33 patients, 13 (39%) tested positive, 12 (36%) negative, and eight (24%) had variants of unknown significance. Positivity rate was 43% for a clinical phenotype and 44% for a tumor type indication.

Safety and Efficacy of Elective Switch from Nilotinib to Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia.

The treatment of newly diagnosed chronic phase chronic myeloid leukemia (CML) with nilotinib has resulted in a higher rate of major molecular (MMR) and complete cytogenetic response (CCyR) at 12 months compared to imatinib but at a higher cumulative cost and increased risk of serious adverse events. To maintain long-term efficacy and minimize both toxicity and costs, we aimed at evaluating in a prospective single-center trial the efficacy and safety of a response-directed switch from nilotinib to imatinib after 12 months in patients newly diagnosed with chronic phase CML. Thirteen adult patients were enrolled. Twelve patients started on nilotinib 300 mg twice daily. Eleven patients completed one year of nilotinib and were switched to imatinib 400 mg daily as per protocol. At 3 months, all patients achieved a complete hematologic response, with 7 (58%) patients had early molecular response. At 12 months, all patients achieved CCyR, of whom 5 (42%) and 4 (33%) patients achieved MMR and MR4.5, respectively. Three (27%) patients switched back to nilotinib after 18, 24, and 51 months respectively: 1 patient because of loss of CCyR after 18 months, and 2 patients because of imatinib intolerance. At last follow-up, all patients (n = 12) were alive and in MMR, 6 (50%) of them in continuous MR4.5. These findings suggest that response directed switch from nilotinib to imatinib at 12 months is capable of maintaining long-term response, with manageable side effects. This approach warrants further exploration with larger prospective trials. Clinical trial registration: Clinicaltrials.gov identifier: NCT01316250, https://clinicaltrials.gov/ct2/results?cond=&term=NCT01316250&cntry=&state=&city=&dist=. .

Tumor profiling of KRAS, BRAF, and NRAS gene mutations in patients with colorectal cancer: A Lebanese major center cohort study.

BACKGROUND: In the era of precision medicine, treatment schemes for advanced Colorectal (CRC) disease include monoclonal antibodies which block the epidermal growth factor receptor (EGFR) implicated in tumor proliferation, invasion, migration and neovascularization. Resistance to these agents has been correlated with activating downstream mutations in KRAS, BRAF and NRAS genes, among others, leading to constitutive activation of the EGFR axis bypassing EGFR blockade. The assessment of tumor RASandBRAFmutational status has thus become standard clinical practice. While multiple investigations reported roughly mutations rates of 40% in KRAS, 7% in NRAS and 5-15 % in BRAF, numbers vary across different populations with limited data specifically from the Middle East. METHODS: This is a retrospective observational Laboratory information system (LIS) chart review of all the patients with pathologically confirmed colorectal carcinoma (CRC) or metastatic CRC who underwent KRAS, NRAS and/or BRAF mutational analysis testing at the Molecular Diagnostics Laboratory of the American University of Beirut Medical Center (AUBMC) from January 2012 to December 2018, inclusive. Data retrieved included the results of mutation testing performed for KRAS, NRAS and BRAF genes, the age, gender, and tumor location for each patient. Analysis of the mutations was performed using polymerase chain reaction (PCR) hybridization StripAssay® (ViennaLab, Vienna, Austria). RESULTS: 130 (47.6%) out of 273 histologically confirmed CRC cases, had positive KRAS mutations, namely in codons 12 (82%), 13 (17%), 146 (1.5%), 117 (0.75%), or 61 (0.75%). Two patients had two concomitant mutations: 12 + 12 (different mutations) and 12 + 146. Of 203 CRC cases tested for NRAS mutations, 16 (7.8%) were found to be positive for a mutation in codon 12 (37.5%), 61 (37.5%), or 13 (12.5%). Two patients had two concomitant mutations: 12 + 13 and 59 + 61. Of 172 CRC cases tested for BRAF mutations, 2 (1.2 %) were positive for the V600E -. CONCLUSION: This retrospective study is the first to report the frequencies of KRAS, NRAS and BRAF gene mutations in a Lebanese CRC cohort diagnosed and managed at a tertiary care center. The frequencies of the studied somatic gene mutations were similar to previously reported cohorts in other populations however the rate of BRAF mutation was lower in this cohort than expected.

COVID-19 vaccination immune response in patients with solid organ and haematologic malignancies: call for active monitoring.

Vaccines against COVID-19 have demonstrated a remarkable efficacy in decreasing hospitalisations and deaths; however, clinical trials leading to vaccine approvals did not include immunocompromised individuals such as patients receiving antineoplastic therapies. Emerging data suggest that patients on active anti-cancer therapy may have a reduced immune response to COVID-19 vaccination compared to the general population and may be at greater risk of COVID-19 infection as measures to reduce transmission in the community are relaxed. We report preliminary data from the American University of Beirut Medical Center in Lebanon demonstrating relatively low seroconversion rates. Of 36 patients on active anti-cancer therapy who had received two doses of vaccine, 17% were negative for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) anti-spike IgG. These results highlight the importance of maintaining strict precautionary measures against COVID-19 in patients on immunosuppressive treatment. There is an urgent need for active monitoring of immune response post-vaccination in prospective studies involving populations from diverse resource settings.

Treatment-induced cerebral sinus venous thrombosis in childhood acute lymphoblastic malignancies: New risk factors to consider.

BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is one of the many side effects encountered during acute lymphoblastic leukemia (ALL) therapy. Due to the rarity of cases, lack of data, and consensus management, no recommendations exist to target the population at risk. METHODS: This is a retrospective chart review of 229 consecutive patients diagnosed with ALL with an age range of 1-21 years, treated at the Children's Cancer Center of Lebanon between October 2007 and February 2018. RESULTS: The incidence of CSVT was 10.5%. Using univariate analysis, increased risk of CSVT was observed with male gender, age >10 years, T-cell immunophenotype, intermediate/high-risk disease, maximum triglyceride (TG) level of >615 mg/dl, presence of mediastinal mass, and larger body surface area (BSA). With multivariate analysis, the only statistically significant risk factors were maximum TG level, BSA, presence of mediastinal mass, and risk stratification (intermediate/high risk). CONCLUSION: Our study was able to unveil TG level of >615 mg/dl, mediastinal mass, and a larger BSA as novel risk factors that have not been previously discussed in the literature.

Molecular prevalence of eight different sexually transmitted infections in a Lebanese major tertiary care center: impact on public health.

BACKGROUND: Sexually transmitted diseases (STD) are caused by a variety of pathogens transmitted by sexual activity. Untreated infections can cause major complications with a substantial high cost on health sector. With the development of molecular techniques, STD screening became easier with a high sensitivity and specificity. OBJECTIVES: In Lebanon, official data regarding STD trends are scarce. This study elucidates the STD molecular profile at a tertiary care center, American University of Beirut Medical Center (AUBMC), its distribution among gender and age groups, with a comparison to international studies. METHODS: A retrospective data analysis was conducted on all STD panels performed at AUBMC from January 2017 till December 2019 to determine the molecular prevalence of eight different sexually transmitted organisms. RESULTS: Our samples belonged to 248 females (41.5%) and 349 males (58.5%). Only 53.5% of the samples tested positive for one or more organisms. Ureaplasma urealyticum/parvum was found to be the most common pathogen (49.3%), followed by Gardenerella vaginalis (33.5%), Chlamydia trachomatis (5.36%), Mycoplasma genitalium (5.16%), Neisseria gonorrhea (2.5%), Herpes simplex virus (2.5%), and Trichomonas vaginalis (1.39%). Age was distributed between 5 and 80 years old. Regarding the pathogen's distribution among gender, Ureaplasma urealyticum/parvum, Herpes simplex virus, and Gardenerella vaginalis were more common in females, the rest was more detected in males. CONCLUSION: Data will be of great importance for clinicians, in terms of diagnosis and treatment. It will help adopting an evidence based STI control programs in Lebanon, and it is essential for future larger studies and sexual health awareness programs.

Sebaceous neoplasms: prevalence of HPV infection and relation to immunohistochemical surrogate markers.

BACKGROUND: Sebaceous neoplasms (SNs) and carcinomas (SCs) represent rare skin adnexal tumours. OBJECTIVES: To establish the prevalence of HPV in SNs, assess the relationship between HPV, p16 and p53 expression, and further elucidate the carcinogenetic course of SCs. MATERIALS & METHODS: A total of 113 resected SNs (five sebaceous adenomas, 10 sebaceomas and 98 SCs) from the Near-East were reviewed. Clinical information (age, gender, size and anatomical location), microscopic variables, and expression of several immunohistochemical markers (EMA, CK5/6, p63, p40, AR, p16 and p53) were documented. Cases were evaluated by fluorescently labelled PCR for HPV detection, followed by DNA microarray hybridization for subtype detection. RESULTS: HPV infection was detected in 9.4% of SNs: 28.6% sebaceous adenomas (HPV-16 and HPV-66), 9.1% sebaceomas (HPV-18) and 8.1% SCs. High-risk HPV types (HPV-16, -18, -52 and -66) constituted 90.9% of HPV infections. Histologically, HPV-positive SCs showed significantly milder cytologic atypia and patchy cellular necrosis. p16 was expressed in SNs irrespective of HPV status (20.0%, 33.3% and 65.5% of HPV-negative sebaceous adenomas, sebaceomas, and SCs, respectively), and p53 was abnormally expressed in 95.5% of HPV-negative SCs and all HPV-positive SCs. CONCLUSION: HPV infection is significantly present in benign and malignant SNs. HPV-positive SCs exhibit less cytologic atypia and necrosis than HPV-negative cases. p16 is not a surrogate marker of HPV infection in the SN setting. Further elucidation of various carcinogenic mechanisms in SCs will allow clinicians to single out the various populations at risk, optimize possible preventive strategies and develop targeted therapies.