Genetic counseling and genetic testing for pathogenic germline mutations among high-risk patients previously diagnosed with breast cancer: a traceback approach.

Genetic counseling and testing are more accessible than ever due to reduced costs, expanding indications and public awareness. Nonetheless, many patients missed the opportunity of genetic counseling and testing due to barriers that existed at that time of their cancer diagnoses. Given the identified implications of pathogenic mutations on patients' treatment and familial outcomes, an opportunity exists to utilize a 'traceback' approach to retrospectively examine their genetic makeup and provide consequent insights to their disease and treatment. In this study, we identified living patients diagnosed with breast cancer (BC) between July 2007 and January 2022 who would have been eligible for testing, but not tested. Overall, 422 patients met the eligibility criteria, 282 were reached and invited to participate, and germline testing was performed for 238, accounting for 84.4% of those invited. The median age (range) was 39.5 (24-64) years at BC diagnosis and 49 (31-75) years at the date of testing. Genetic testing revealed that 25 (10.5%) patients had pathogenic/likely pathogenic (P/LP) variants; mostly in BRCA2 and BRCA1. We concluded that long overdue genetic referral through a traceback approach is feasible and effective to diagnose P/LP variants in patients with history of BC who had missed the opportunity of genetic testing, with potential clinical implications for patients and their relatives.

Molecular Characteristics of Colistin Resistance in Acinetobacter baumannii and the Activity of Antimicrobial Combination Therapy in a Tertiary Care Medical Center in Lebanon.

(1) Background: Infections with pan-drug-resistant (PDR) bacteria, such as A. baumannii, are becoming increasingly common, especially in healthcare facilities. In this study, we selected 15 colistin-resistant clinical A. baumannii isolates from a hospital in Beirut, Lebanon, to test combination therapies and determine their sequence types (STs) and the mechanism of colistin resistance using whole-genome sequencing (WGS). (2) Methods: Antimicrobial susceptibility testing via broth microdilution against 12 antimicrobials from different classes and growth rate assays were performed. A checkerboard assay was conducted on PDR isolates using six different antimicrobials, each in combination with colistin. Genomic DNA was extracted from all isolates and subjected to WGS. (3) Results: All isolates were resistant to all tested antimicrobials with the one exception that was susceptible to gentamicin. Combining colistin with either meropenem, ceftolozane-tazobactam, or teicoplanin showed synergistic activity. Sequencing data revealed that 67% of the isolates belonged to Pasteur ST2 and 33% to ST187. Furthermore, these isolates harbored a number of resistance genes, including blaOXA-23. Mutations in the pmrC gene were behind colistin resistance. (4) Conclusions: With the rise in antimicrobial resistance and the absence of novel antimicrobial production, alternative treatments must be found. The combination therapy results from this study suggest treatment options for PDR ST2 A. baumannii-infected patients.

Seroprevalence of Human Brucellosis among Syrian Refugees in Jordan, 2022.

Introduction: Brucellosis is prevalent in Mediterranean countries. The aim of this study was to determine the seroprevalence of brucellosis and associated factors among Syrian refugees in Jordan. Methods: A cross-sectional study was conducted among adult Syrian refugees who attended the Public Health Lab (PHL) in Al Mafraq governorate, during the period of May-June 2022 to obtain a health certificate, which is legally required to receive governmental authorization for employment in Jordan. Blood samples were obtained from participants and a serum specimen was tested for the presence of IgG antibodies against Brucella using enzyme-linked immunosorbent assay (ELISA) IgG kits (Vircell Microbiologists, Granada, Spain). Results: A total of 1562 Syrian refugees were enrolled in the study. Their ages ranged between 18 and 74 years, with a median age of 30 years at presentation. The majority were males (75.9%, n = 1186) and 24.1% (n = 376) were females. The Brucella ELISA IgG results were positive for 149 persons, with an overall seroprevalence rate of 9.5% (95% confidence interval: 8.0%-11.0%). Having animal-related occupations, residing outside refugee camps, consuming unpasteurized milk, handling animals or their tissues, and slaughtering animals within 6 months of study inclusion were significantly higher among the seropositive group. In the multivariate analysis, IgG-positive persons were 13 times more likely to report being diagnosed with brucellosis (OR = 13.1, 95% CI: 6.1-28.3; p ≤ 0.001). In addition, they were more likely to reside in the city of Al Mafraq, as opposed to a refugee camp (OR = 1.9, 95% CI: 1.1-3.2; p = 0.025) and to have handled animals within 6 months of study inclusion (OR = 3.1, 95% CI: 1.1-8.9; p = 0.035). Conclusions: In conclusion, one-tenth of adult Syrian refugees were tested positive for Brucella ELISA IgG. Being diagnosed with brucellosis, residing in the city of Al Mafraq, as opposed to a refugee camp, and handling animals within 6 months of study inclusion were significantly associated with being positive for Brucella ELISA IgG. This study illustrates the need for improved brucellosis control measures via comprehensive vaccination of animals and enhanced laboratory detection and surveillance capacities, in addition to emphasizing the need for increased awareness sessions among Syrian refugees on the safe use and preparation of dairy products and safety practices of handling animals and their tissues.

Quality of Life of Family Caregivers of Critically Ill Patients With Cancer Before and After Intensive Care Unit Admission Measured by EQ-5D 3-Level: A Longitudinal Prospective Cohort Study.

OBJECTIVES: Admission to the Intensive Care Unit (ICU) is considered a distress journey with an increased demand and cost for informal caregiving. This study aimed to generate utility values through assessing the quality of life (QoL) of family caregivers using the EQ-5D-3L measure before and after ICU admission of their family members. METHODS: A 1-year prospective cohort study (January 2017 to February 2018) was conducted at a comprehensive cancer center in Jordan. Caregivers of adult patients who were in the ICU for ≥ 24 hours were included. The QoL was assessed using the EQ-5D-3L instrument. Caregivers' health profiles were described, and single summary index value for their health status were calculated before ICU admission and were compared with 1-week, 1-month, and 3-month utility index scores after ICU discharge. Predictors of the change of caregivers' QoL were also reported. RESULTS: During the study period, 126 caregivers completed the QoL assessment at baseline. The mean age ± SD of the cohort was 55 years ± 14, and 52% were males. The mean utility scores ± SD were 0.70 ± 0.32, 0.73 ± 0.29, 0.71 ± 0.31, and 0.78 ± 0.31 at baseline, 1 week, 1 month, and 3 months after discharge, respectively. A significant relationship between the patient's Acute Physiology and Chronic Health Evaluation (APACHE II) score and the change in caregiver's utility score index after 3 months was reported. CONCLUSIONS: Improvement in caregivers' QoL has been seen 3 months after ICU discharge. Patients' APACHE II score at baseline is a predictor of the change of caregivers' QoL 3 months after discharge.

Differences in clinicopathological characteristics, treatment, and survival outcomes between older and younger breast cancer patients.

In developing countries, breast cancer is diagnosed at a much younger age. In this study we investigate the dichotomies between older and young breast cancer patients in our region. The study involved two cohorts; older patients (≥ 65 years, n = 553) and younger ones (≤ 40 years, n = 417). Statistical models were used to investigate the associations between age groups, clinical characteristics and treatment outcomes. Compared to younger patients, older patients were more likely to present with advanced-stage disease (20.6% vs. 15.1%, p = .028). However, among those with non-metastatic disease, younger patients tended to have more aggressive pathological features, including positive axillary lymph nodes (73.2% vs. 55.6%, p < .001), T-3/4 (28.2% vs. 13.8%, p < .001) and HER2-positive disease (29.3% vs. 16.3%, p < .001). The 5-year overall survival (OS) rate was significantly better for the younger (72.1%) compared to the older (67.6%), p = .035. However, no significant difference was observed in disease-free survival (DFS) between the two groups.In conclusion, younger patients with breast cancer present with worse clinical and pathological features, albeit a better OS rate. The difference in DFS between the two groups was not insignificant, suggesting that older women were more likely to die from non-cancer related causes.

Prolonged Neutropenia and Yellowish Discoloration of the Skin, But Not the Sclera, Following Excessive Turmeric Raw Root Ingestion.

The medicinal use of curcumin has gained popularity in recent years especially so among cancer patients undergoing chemotherapy. In this report, we describe the case of a 51-year-old female breast cancer patient who self-medicated on large amounts of turmeric root infusions while receiving chemotherapy. The patient presented with yellowish discoloration of her skin, but normal-colored sclera. She also had severe neutropenia, which persisted despite halting chemotherapy. When her white blood cell counts returned to normal, only after stopping her turmeric regimen, we determined that her neutropenia is associated with turmeric consumption making this the first report to establish this link. This report demonstrates that, as an alternative form of medication, curcumin consumption should still be monitored in cancer patients. We provide the visible sign of yellowish skin discoloration as a visible aid for healthcare providers in detecting turmeric consumption as a risk factor to be considered in differential diagnoses of unexplained neutropenia.

The epidemiology of meningococcal meningitis: multicenter, hospital-based surveillance of meningococcal meningitis in Iraq.

Objectives: Outbreaks of Neisseria meningitidis have reached alarming levels due to the pathogen's ability to cause severe complications, presenting as meningitis or septicemia. Our study reports the results of the first wide-scale surveillance of meningococcal meningitis in Iraq. Methods: The study included all consecutive cases of clinically suspected meningitis between June 2018 and May 2020 at 18 major hospitals around Iraq (n = 2314). Laboratory analysis of biological samples and real-time polymerase chain reaction tests were conducted to confirm bacterial etiology. Demographical and medical data were collected for statistical analysis. Results: In total, 370 patients were confirmed to have bacterial meningitis (215 had N. meningitidis, 154 had Streptococcus pneumoniae, and one case had Haemophilus influenzae type b). The most common N. meningitidis serogroup was B (77.7%), followed by W (18.1%) and X (4.2%). The annual incidence rate of N. meningitidis per 100 000 population was 0.86, with the highest being in Karbala (1.52 per 100 000 population). Cases of meningococcal meningitis were more likely to occur in children younger than 15 (OR = 3.526), and in the winter (OR = 1.474). Conclusions: Continuous surveillance of N. meningitidis is necessary in Iraq, and can only be achieved through improved detection methods. The incidence of meningococcal meningitis in Iraq warrants improved vaccination programs.

Effect of level of hormone-receptor expression on treatment outcomes of "triple-positive" early-stage breast cancer.

PURPOSE: Breast cancer that overexpresses the human epidermal growth factor receptor-2 (HER2) and both estrogen (ER) and progesterone (PR) receptors is recently recognized as a subtype (triple-positive) with distinctive behavior and response to treatment. In this study, we investigate the treatment outcomes and the beneficial effect of anti-HER2 treatment in relation to level of hormone-receptor (HR) expression. METHODS: Consecutive breast cancer patients with triple-positive disease, diagnosed, treated and followed at our institution between 2006 and 2016 were enrolled. Disease-free survival (DFS) was studied in relation to the level of HR-positivity. RESULTS: During the study period, a total of 312 were enrolled; median age (range) was 47 (20-83) years. Fifty (16.0%) of the enrolled patients received adjuvant chemotherapy without trastuzumab (cohort A). All remaining patients were treated with both chemotherapy and trastuzumab and were divided into two groups: Cohort B with both ER and PR scores ≥ 50% (n = 130, 41.7%) and Cohort C with ER and/or PR < 50% (n = 132, 42.3%). After a median follow-up of 47 months, 14 (28.0%), 30 (23.1%) and 20 (15.2%) patients in cohorts A, B, and C had an event in a form of local/system relapse or death while disease-free. The estimated 5-year DFS was 56.2%, 75.4%, and 80.8%, respectively, and at 7 year was 56.2%, 67.1%, and 78.0%, respectively (p < 0.001). CONCLUSIONS: HER2-positive tumors are not homogeneous; stronger ER/PR co-expression may weaken the beneficial effect of anti-HER2 therapy. Such findings may have potential implication on modifying anti-HER2 treatment based on the strength of HR expression.

From bugs to drugs: Combating antimicrobial resistance by discovering novel antibiotics.

INTRODUCTION: Antimicrobial resistance (AMR) is emerging at an alarming rate as mortality due to resistant pathogens could rise to 10 million per year by 2050. Since AMR is against all clinically utilized antibiotics, finding novel antimicrobials with unexploited targets remains the main goal worldwide.  Soil microorganisms produce natural products as a significant number of drugs in clinical use are derived from these metabolites. Actinomycetes and Myxobacteria are soil dwelling microorganisms that produce secondary metabolites to be screened for antibacterial activity. More than 80% of clinically utilized antibiotics are either natural products or natural product-derived molecules such as vancomycin, teicoplanin, daptomycin, and tetracycline. This study aims to isolate and identify novel antimicrobials from Actinomycetes and Myxobacteria. METHODOLOGY: Soil samples were collected from several areas in Lebanon. Samples were serially diluted for Actinomycetes isolation and boiled for Myxobacteria extraction, then plated on suitable media. Colonies obtained were purified and subjected to genomic DNA extraction then 16s rRNA analysis. Novel isolates were tested for their antimicrobial activity against Gram-positive Bacillus subtilis (ATCC 6051), Staphylococcus aureus (ATCC 29213, Newman, N315), Enterococcus faecalis (ATCC 19433), and Enterococcus faecium (DSMZ 17050), and Gram-negative Escherichia coli (ATCC 9637), Klebsiella pneumoniae (DSMZ), Pseudomonas aeruginosa (ATCC 27853, MEXAB), and Acinetobacter baumannii (ATCC 15308). RESULTS: Strain isolation and cultivation yielded a number of novel isolates whose extracts demonstrated strong antibacterial activity against pathogens including MRSA, VRE, and Escherichia coli (ATCC 9637). CONCLUSION: Our efforts now focus on purifying these compounds, elucidate their structures and study their mode of action.