Acute Erythroid Leukemia: From Molecular Biology to Clinical Outcomes.

Acute Erythroid Leukemia (AEL) is a rare and aggressive subtype of Acute Myeloid Leukemia (AML). In 2022, the World Health Organization (WHO) defined AEL as a biopsy with ≥30% proerythroblasts and erythroid precursors that account for ≥80% of cellularity. The International Consensus Classification refers to this neoplasm as "AML with mutated TP53". Classification entails ≥20% blasts in blood or bone marrow biopsy and a somatic TP53 mutation (VAF > 10%). This type of leukemia is typically associated with biallelic TP53 mutations and a complex karyotype, specifically 5q and 7q deletions. Transgenic mouse models have implicated several molecules in the pathogenesis of AEL, including transcriptional master regulator GATA1 (involved in erythroid differentiation), master oncogenes, and CDX4. Recent studies have also characterized AEL by epigenetic regulator mutations and transcriptome subgroups. AEL patients have overall poor clinical outcomes, mostly related to their poor response to the standard therapies, which include hypomethylating agents and intensive chemotherapy. Allogeneic bone marrow transplantation (AlloBMT) is the only potentially curative approach but requires deep remission, which is very challenging for these patients. Age, AlloBMT, and a history of antecedent myeloid neoplasms further affect the outcomes of these patients. In this review, we will summarize the diagnostic criteria of AEL, review the current insights into the biology of AEL, and describe the treatment options and outcomes of patients with this disease.

Targeting CCRL2 enhances therapeutic outcomes in a tuberculosis mouse model.

Tuberculosis (TB) remains among the leading infectious causes of death. Due to the limited number of antimicrobials in the TB drug discovery pipeline, interest has developed in host-directed approaches to improve TB treatment outcomes. C-C motif chemokine-like receptor 2 (CCRL2) is a unique seven-transmembrane domain receptor that is upregulated by inflammatory signals and mediates leucocyte migration. However, little is known about its role in the setting of TB infection. Here, we show that Mycobacterium tuberculosis (Mtb) infection increases CCRL2 protein expression in macrophages and in mouse lungs. To target selectively CCRL2-expressing cells in vivo, we developed a novel mouse anti-CCRL2 antibody-drug conjugate (ADC) linked with the cytotoxic drug SG3249. We tested its adjunctive therapeutic efficacy against TB when combined with the first-line regimen for drug-susceptible TB (isoniazid, rifampin, pyrazinamide, ethambutol; RHZE). The anti-CCRL2 ADC treatment potentiated RHZE efficacy in Mtb-infected mice and decreased gross lung inflammation. CCRL2 expression in lung dendritic cells and alveolar macrophages was lower in mice receiving anti-CCRL2 ADC treatment + RHZE compared to those receiving RHZE alone or the control group, although the total innate cell populations did not differ across treatment groups. Interestingly, neutrophils were completely absent in the anti-CCRL2 ADC treatment + RHZE group, unlike in the other treatment groups. IFN-γ+ and IL17-Α+ T-cell responses, which are associated with optimal TB control, were also elevated in the anti-CCRL2 ADC treatment + RHZE group. Collectively, our findings suggest that CCRL2-targeting approaches may improve TB treatment outcomes, possibly through selective killing of Mtb-infected innate immune cells.

Smoking cessation counselling patterns in cancer patients - survey of Lebanese physicians.

Introduction: Tobacco smoking is a known risk factor for cancer development and smoking cessation can lower this risk and improve outcomes in some cancer patients. Despite that, many cancer patients do not quit smoking after a cancer diagnosis, and smoking cessation counselling is still not routinely provided in cancer care. The aim of this study is to examine patterns in smoking cessation counselling to cancer patients by their treating physicians. Methods: A self-administered, web-based (mobile-friendly), anonymous questionnaire was developed on LimeSurvey and sent by e-mail to Lebanese physicians of different specialties between June 2020 and January 2022. Data were analysed using SPSS and associations between the different items were determined using the χ2 test. Results: A total of 146 physicians filled out the questionnaire. Almost all physicians ask cancer patients about their smoking status, but only 45.9% provide smoking cessation counselling, and only 24% refer patients to smoking cessation counselling programs. Only 27.4% of all respondents have received formal smoking cessation training, and only 27.4% feel capable of providing smoking cessation counselling in their clinic. Specifically, family medicine physicians were more likely to provide smoking cessation counselling in the clinic (69%), more likely to refer patients to a smoking cessation counselling program (44%), and more likely to have received formal smoking cessation counselling training (67%) and more likely to feel capable of providing smoking cessation counselling (93%). Lack of training, lack of knowledge of available programs and the lack of availability of enough programs are leading obstacles contributing to low rates of smoking cessation counselling in cancer patients as reported by the physicians. Conclusion: Our data reveals a deficiency in smoking cessation counselling and referral of cancer patients to smoking cessation counselling programs in our region. This highlights the need for dedicated smoking cessation counselling training for practicing physicians and physicians in training.

Value of chemotherapy post immunotherapy in stage IV non-small cell lung cancer (NSCLC).

BACKGROUND: Lung cancer is the number one cause of mortality among all types of cancer worldwide. Its treatment landscape has shifted from the classic chemotherapy alone to newer regimens based on the discovery of new immunotherapy and targeted therapy drugs. However, chemotherapy is still an option for treatment of advanced non-small cell lung cancer (NSCLC) after progression on immunotherapy alone or in combination with first-line chemotherapy. METHODS: This is a retrospective study based on chart review of patients diagnosed with advanced NSCLC cases who received Docetaxel as second or third line after being treated by immunotherapy and/or chemotherapy in previous lines. The data was collected from the medical records of physicians' clinics in three different hospital centers in Lebanon over the period of 5 years from July 2015 until December 2020. February 2021 was data analysis cut off time. The main aim was to assess the role of Docetaxel post-chemoimmunotherapy for patients with diagnosed NSCLC. RESULTS: A total of 21 patients were included in this study. The majority of our patients were males (81%). As for histologic type, most patients had non-squamous lung cancer (67%) as compared to 33% who had squamous lung cancer. Overall, our study reported a 24% response rate to Docetaxel including stable disease and partial response and a median progression free survival (PFS) of 3 months. The mean time interval elapsed from diagnosis to the initiation of Docetaxel was 11.5 months. CONCLUSION: New therapeutic options should be validated for the treatment of NSCLC in the second and subsequent lines of therapy considering the poor prognosis of this disease. The chemotherapy in second and third line may keep an important role in the treatment after progression on newer agents, but it needs more evidence in prospective studies including a larger number of patients.

The Urogenital System's Role in Diseases: A Synopsis.

The human microbiota contains ten times more microbial cells than human cells contained by the human body, constituting a larger genetic material than the human genome itself. Emerging studies have shown that these microorganisms represent a critical determinant in human health and disease, and the use of probiotic products as potential therapeutic interventions to modulate homeostasis and treat disease is being explored. The gut is a niche for the largest proportion of the human microbiota with myriad studies suggesting a strong link between the gut microbiota composition and disease development throughout the body. More specifically, there is mounting evidence on the relevance of gut microbiota dysbiosis in the development of urinary tract disease including urinary tract infections (UTIs), chronic kidney disease, and kidney stones. Fewer emerging reports, however, are suggesting that the urinary tract, which has long been considered 'sterile', also houses its unique microbiota that might have an important role in urologic health and disease. The implications of this new paradigm could potentially change the therapeutic perspective in urological disease.

COVID-19 and C. auris: A Case-Control Study from a Tertiary Care Center in Lebanon.

Many healthcare centers around the world have reported the surge of Candida auris (C. auris) outbreaks during the COVID-19 pandemic, especially among intensive care unit (ICU) patients. This is a retrospective study conducted at the American University of Beirut Medical Center (AUBMC) between 1 October 2020 and 15 June 2021, to identify risk factors for acquiring C. auris in patients with severe COVID-19 infection and to evaluate the impact of C. auris on mortality in patients admitted to the ICU during that period. Twenty-four non-COVID-19 (COV−) patients were admitted to ICUs at AUBMC during that period and acquired C. auris (C. auris+/COV−). Thirty-two patients admitted with severe COVID-19 (COV+) acquired C. auris (C. auris+/COV+), and 130 patients had severe COVID-19 without C. auris (C. auris−/COV+). Bivariable analysis between the groups of (C. auris+/COV+) and (C. auris−/COV+) showed that higher quick sequential organ failure assessment (qSOFA) score (p < 0.001), prolonged length of stay (LOS) (p = 0.02), and the presence of a urinary catheter (p = 0.015) or of a central venous catheter (CVC) (p = 0.01) were associated with positive culture for C. auris in patients with severe COVID-19. The multivariable analysis showed that prolonged LOS (p = 0.008) and a high qSOFA score (p < 0.001) were the only risk factors independently associated with positive culture for C. auris. Increased LOS (p = 0.02), high "Candida score" (p = 0.01), and septic shock (p < 0.001) were associated with increased mortality within 30 days of positive culture for C. auris. Antifungal therapy for at least 7 days (p = 0.03) appeared to decrease mortality within 30 days of positive culture for C. auris. Only septic shock was associated with increased mortality in patients with C. auris (p = 0.006) in the multivariable analysis. C. auris is an emerging pathogen that constitutes a threat to the healthcare sector.