Syrian Refugees Seeking Hospital Care in Beirut: A Cross-Sectional Study of Reasons for Hospital Admissions.

INTRODUCTION: Lebanon has the highest Syrian refugee density worldwide. The influx of Syrian refugees has had various impacts on Lebanon, with one of the most significant effects observed in the already exhausted healthcare system. This study aimed to determine the reasons for hospitalization among registered Syrian refugees in Beirut who were admitted to Rafik Hariri University Hospital (RHUH) between December 2017 and June 2020. METHODS: Data from 7,480 diagnosed cases were collected from the RHUH archives between December 2017 and June 2020 and were analyzed using SPSS (IBM Corp., Armonk, NY, USA). The collected data included information related to demographics, admission date, primary diagnosis, and other related medical problems. Variations and correlations were then tested. RESULTS: Of the cases, 73.4% were females; the mean age was 28 ± 16.23 years. Fifty-seven percent of the admitted cases were solely due to pregnancy, childbirth, and puerperium reasons, and 91.14% of the deliveries were single deliveries by cesarean section. Common reasons for hospitalization were injuries (5.8%) and diseases of the digestive system (6.8%), circulatory system (4.7%), and respiratory system (4.4%). Non-communicable diseases (NCDs) constituted 61% of all hospital admissions, while only 6.6% belonged to communicable diseases. Reasons for hospitalization and the type of diagnosed diseases were associated with gender and age groups (p-values <0.001). CONCLUSION: The major reasons for hospitalization among Syrian refugees were related to pregnancies and NCDs. The burden of the Syrian refugee influx on the Lebanese healthcare system can be alleviated by improving community health education, public health services, and conditions for refugees.

Kynureninase Upregulation Is a Prominent Feature of NFR2-Activated Cancers and Is Associated with Tumor Immunosuppression and Poor Prognosis.

The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is frequently activated in various cancer types. Aberrant activation of NRF2 in cancer is attributed to gain-of-function mutations in the NRF2-encoding gene NFE2L2 or a loss of function of its suppressor, Kelch-like ECH-associated protein 1 (KEAP1). NRF2 activation exerts pro-tumoral effects in part by altering cancer cell metabolism. Previously, we reported a novel mechanism of NRF2 tumoral immune suppression through the selective upregulation of the tryptophan-metabolizing enzyme kynureninase (KYNU) in lung adenocarcinoma. In the current study, we explored the relevance of NRF2-mediated KYNU upregulation across multiple cancer types. Specifically, using a gene expression dataset for 9801 tumors representing 32 cancer types from The Cancer Genome Atlas (TCGA), we demonstrated that elevated KYNU parallels increased gene-based signatures of NRF2-activation and that elevated tumoral KYNU mRNA expression is strongly associated with an immunosuppressive tumor microenvironment, marked by high expression of gene-based signatures of Tregs as well as the immune checkpoint blockade-related genes CD274 (PDL-1), PDCD1 (PD-1), and CTLA4, regardless of the cancer type. Cox proportional hazard models further revealed that increased tumoral KYNU gene expression was prognostic for poor overall survival in several cancer types, including thymoma, acute myeloid leukemia, low-grade glioma, kidney renal papillary cell carcinoma, stomach adenocarcinoma, and pancreatic ductal adenocarcinoma (PDAC). Using PDAC as a model system, we confirmed that siRNA-mediated knockdown of NRF2 reduced KYNU mRNA expression, whereas activation of NFE2L2 (the coding gene for NRF2) through either small-molecule agonists or siRNA-mediated knockdown of KEAP1 upregulated KYNU in PDAC cells. Metabolomic analyses of the conditioned medium from PDAC cell lines revealed elevated levels of KYNU-derived anthranilate, confirming that KYNU was enzymatically functional. Collectively, our study highlights the activation of the NRF2-KYNU axis as a multi-cancer phenomenon and supports the relevance of tumoral KYNU as a marker of tumor immunosuppression and as a prognostic marker for poor overall survival.

Utility of hematological and inflammatory biomarkers in predicting recovery in critical Covid-19 patients: Our experience in the largest Covid-19 treating center in Lebanon.

BACKGROUND: COVID-19 pandemic has led to a catastrophic shortage of ICU beds. This has resulted in the need to identify patients that can be discharged early before full clinical recovery. We designed this study to determine if in changes routine tests like CBCD and CRP can be a useful complement to clinical status when deciding to discharge patients from ICU. METHODS: This retrospective study was conducted in Rafic Hariri University Hospital. Levels of biomarkers measured at admission (T1) and within 3 days of outcome (T2) were collected and ratios (T2/T1) were calculated. The Odds Ratios of association between the changes in these biomarkers and outcome were estimated. Multivariate analysis and AUC for the performance of these biomarkers were also conducted. RESULTS: We found on multivariate analysis that reduction in counts of lymphocyte and platelets and elevation in counts of neutrophils and level of CRP (T2/T1 ratio > 1) are strongly associated with mortality with respective ORs estimated at 6.74, 3.26, 5.65 and 4.34 [p-values < 0.001]. AUCs were found to lie in a range of 0.68 to 0.81 indicating fair to good performance. Other factors found to impact survival were AKI, AF and ACS [p-values < 0.01]. In contrast to other studies, risk factors didn't show an association with survival when adjusted for effects of complications and changes in biomarker levels. CONCLUSIONS: Our results confirm that inexpensive tests like lymphocyte count and CRP can be reliably used to follow COVID-19 patients in ICU and to support the decision to discharge patients.

From Tumor Cells to Endothelium and Gut Microbiome: A Complex Interaction Favoring the Metastasis Cascade.

Metastasis is a complicated process through which tumor cells disseminate to distant organs and adapt to novel tumor microenvironments. This multi-step cascade relies on the accumulation of genetic and epigenetic alterations within the tumor cells as well as the surrounding non-tumor stromal cells. Endothelial cells constitute a major player in promoting metastasis formation either by inducing the growth of tumor cells or by directing them towards dissemination in the blood or lymph. In fact, the direct and indirect interactions between tumor and endothelial cells were shown to activate several mechanisms allowing cancer cells' invasion and extravasation. On the other side, gastrointestinal cancer development was shown to be associated with the disruption of the gut microbiome. While several proposed mechanisms have been investigated in this regard, gut and tumor-associated microbiota were shown to impact the gut endothelial barrier, increasing the dissemination of bacteria through the systemic circulation. This bacterial dislocation allows the formation of an inflammatory premetastatic niche in the distant organs promoting the metastatic cascade of primary tumors. In this review, we discuss the role of the endothelial cells in the metastatic cascade of tumors. We will focus on the role of the gut vascular barrier in the regulation metastasis. We will also discuss the interaction between this vascular barrier and the gut microbiota enhancing the process of metastasis. In addition, we will try to elucidate the different mechanisms through which this bacterial dislocation prepares the favorable metastatic niche at distant organs allowing the dissemination and successful deposition of tumor cells in the new microenvironments. Finally, and given the promising results of the studies combining immune checkpoint inhibitors with either microbiota alterations or anti-angiogenic therapy in many types of cancer, we will elaborate in this review the complex interaction between these 3 factors and their possible therapeutic combination to optimize response to treatment.

A 12-Year Comparative Analysis of Hodgkin and Non-Hodgkin Lymphomas in Lebanon: Trend Characteristics and 10-Year Projections.

Background  Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are two common malignancies worldwide and in Lebanon. Analysis of their trends plays a crucial role to better understand their origins and risk factors. This study will probe incidences of both types of lymphomas from 2005 to 2016, aiming to compare between the two malignancies according to age and sex and plot projections until 2026. Methods HL and NHL cases from 2005 to 2016 were collected from the National Cancer Registry of Lebanon. Data was stratified according to age and sex. Age-specific and age-standardized incidence rates were analysed using joinpoint regression; 10-year projections were predicted based on logarithmic models. Results Between 2005 and 2016, NHL was significantly more common than HL. NHL was higher in both genders. HL showed a bimodal age distribution while NHL peaked in elderly patients. NHL incidence rates in males increased significantly from 2005 to 2014 while HL incidence rates showed an insignificant rise. Over the next 10 years, NHL and HL cases are expected to increase in Lebanon. Conclusion HL and NHL are on the rise in Lebanon. Extensive research into the main factors contributing to these lymphomas is crucial in the fight against them. More efforts must be done by the government and health organizations to better control the disease.