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.

Pelvic examination: an iatrogenic cause of microscopic hematuria in women?

INTRODUCTION AND HYPOTHESIS: Microscopic hematuria (MH) in women is a common incidental finding that can trigger morbid and costly investigation. Identifying non-pathologic etiologies of MH may help limit unnecessary investigation. Our study aimed to determine whether pelvic examination (PE) increases the prevalence of MH in women. METHODS: Between May 2018 and October 2018, 157 women > 18 years of age and presenting to the Obstetrics and Gynecology private clinics at a tertiary care center were approached and asked to provide two urine samples: one before PE and one after. Samples were then analyzed to asses for the presence of MH. The McNemar test was used to evaluate whether the conversion from no MH to MH could be attributed to PE rather than to chance. An associated p < 0.05 was determined to be significant. Chi-square test was used to determine whether this conversion is influenced by age and menopausal status. RESULTS: Thirteen women (8.3%) had MH before PE. Of 144 participants with no initial MH, 22 (15.3%) had MH after PE. PE was significantly correlated with the conversion from no MH to MH (p = 0.002). The conversion from no MH to MH following PE was not correlated with age (p = 0.451) or menopausal status (p = 0.411). CONCLUSIONS: PE performed within an hour before urinalysis was found to be a risk factor for MH in women.

Non-tuberculous mycobacteria profiles and their anti-mycobacterial resistance at a major medical center in Lebanon.

INTRODUCTION: Infection with non-tuberculosis mycobacteria (NTM) has been on the rise globally causing a wide spectrum of respiratory and extrapulmonary infections in humans. Studies on these pathogens from the Middle-East including Lebanon are scarce. METHODOLOGY: This retrospective study addresses the approach used for investigation, speciation and antimicrobial resistance (AMR) profiles of recovered NTM isolates from respiratory sources at a major tertiary care center in Lebanon during two periods (2003-2007 and 2013-2017). Processing of specimens, culture and differentiation of recovered NTM isolates from Mycobacterium tuberculosis were done in-house according to standard procedures. Upon request, speciation and AMR testing were performed using molecular and broth dilution methods, respectively, at Mayo Medical Laboratories (Rochester, Minnesota, USA). RESULTS: Among 108 NTM analyzed isolates, 8 species were revealed during the two periods: M. simiae (51% vs 61%), M. avium complex (MAC) (6 % vs 12%) M. fortuitum (12% vs 5%), M. gordonae (6% vs 5%), M. abscessus (6% vs 7%), M. immunogenum (12% vs 0%), M. szulgai (4% vs 0%) and M. peregrinum (0% vs 2%). M. simiae isolates showed high susceptibility (93%-96%) to amikacin and clarithromycin, but high resistance to rifampin, ethambutol, ciprofloxacin, rifabutin, linezolid, trimethoprim/sulfamethoxazole and moxifloxacin. MAC isolates were only susceptible to clarithromycin (86%). M. abscessus isolates were uniformly susceptible to amikacin (100%). CONCLUSION: The revelaed different NTM species, with predominance of M.simiae and various AMR profiles provide a current epidemiologic database and help guiding the selection of appropriate empirical therapy once the clinical relevance is established.

Internal fixation of shaft humerus fractures by dynamic compression plate or interlocking intramedullary nail: a prospective, randomised study.

Compare the results of internal fixation of shaft of humerus fractures using dynamic compression plating (DCP) or antegrade interlocking intramedullary nail (IMN). Fifty patients with diaphyseal fracture of the shaft of the humerus and fulfilling the inclusion criterion were randomly assigned to one of the two groups. Twenty-five patients were managed with closed antegrade interlocking intramedullary nail, and 25 underwent open reduction and internal fixation using dynamic compression plating. The mean age of patients with IMN fixation was 37.28 years (SD 12.26) and 37.72 years (SD 12.70) for those who underwent plating. Road traffic accident was the most common mode of injury in both groups. There was a statistically significant difference between the two groups with respect to duration of hospital stay, operative time and blood loss. There was no significant difference between the two groups in terms of union or complications. The functional assessment at the end of 1 year between the two groups did not show any significant difference in outcome. Antegrade interlocking IMN and DCP fixation are comparable when managing diaphyseal shaft of humerus fractures with respect to union rates and complications. Although shoulder related complications are more in the IMN group, however, it is associated with shorter hospital stay, lesser operative time and less blood loss. This makes interlocking IMN an effective option in managing these fractures.