SARS-CoV-2-mediated liver injury: pathophysiology and mechanisms of disease.

BACKGROUND: SARS-CoV-2-induced severe inflammatory response can be associated with severe medical consequences leading to multi-organ failure, including the liver. The main mechanism behind this assault is the aggressive cytokine storm that induces cytotoxicity in various organs. Of interest, hepatic stellate cells (HSC) respond acutely to liver injury through several molecular mechanisms, hence furthering the perpetuation of the cytokine storm and its resultant tissue damage. In addition, hepatocytes undergo apoptosis or necrosis resulting in the release of pro-inflammatory and pro-fibrogenic mediators that lead to chronic liver inflammation. AIMS: The aim of this review is to summarize available data on SARS-CoV-2-induced liver inflammation in addition to evaluate the potential effect of anti-inflammatory drugs in attenuating SARS-CoV-2-induced liver inflammation. METHODS: Thorough PubMed search was done to gather and summarize published data on SARS-CoV-2-induced liver inflammation. Additionally, various anti-inflammatory potential treatments were also documented. RESULTS: Published data documented SARS-CoV-2 infection of liver tissues and is prominent in most liver cells. Also, histological analysis showed various features of tissues damage, e.g., hepatocellular necrosis, mitosis, cellular infiltration, and fatty degeneration in addition to microvesicular steatosis and inflammation. Finally, the efficacy of the different drugs used to treat SARS-CoV-2-induced liver injury, in particular the anti-inflammatory remedies, are likely to have some beneficial effect to treat liver injury in COVID-19. CONCLUSION: SARS-CoV-2-induced liver inflammation is a serious condition, and drugs with potent anti-inflammatory effect can play a major role in preventing irreversible liver damage in COVID-19.

Epidemiology and Survival of Colorectal Cancer in Lebanon: A Sub-National Retrospective Analysis.

BACKGROUND: Scarce data exist about colorectal cancer (CRC) presentation and outcomes in Lebanon. The aim of this study is to describe the characteristics of Lebanese patients diagnosed with colorectal cancer, particularly the method of detection, age of onset, stage at presentation, treatment modalities, and survival. METHODS: This is a retrospective study of a cohort of patients with CRC, diagnosed between 2005 and 2010, admitted to 6 major university-affiliated medical centers in Lebanon. RESULTS: The total sample consisted of 586 patients (median age: 64 years; M:F ratio: 1.25). The most common presenting symptoms were changes in bowel habits, abdominal pain, and blood per rectum. Only 3% had been diagnosed by screening colonoscopy. Of the patients diagnosed with CRC younger than 50 years of age, 72.5% had a positive family history (P = .07). More than two-thirds of patients had an advanced stage of the disease III and IV at presentation. The Kaplan-Meier-estimated survival rate was 0%, 44.5%, 70.2%, and 78.5% for those with stage IV, III, II, and I, respectively (P = .0001), and did not vary by age nor gender of the patient. There was no differential in survival estimate for patients with stage II and III by number of chemotherapy cycles received. However, there was a significant difference in median survivorship for patients with metastatic stage IV disease; those who received less than or equal to 9 cycles had a median survivorship of 2 years (CI: 1.31-2.68) compared to 4 years (CI: 2.36-5.63) for those who received more than 9 cycles (P = .047). The cox regression showed while controlling for age and gender that patients diagnosed at stage IV had a hazard ratio of 8.81 (3.20-24.22) compared to those who were diagnosed at stage I (P = .047). CONCLUSIONS: Lebanese patients affected by colorectal cancer tend to present with advanced disease stages, leading to poor prognosis and survival.

Assessment of bleeding in chronic liver disease and coagulopathy using the IMPROVE bleeding criteria.

BACKGROUND: In this study, the authors utilized the IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) bleeding definition to explore the safety profile of pharmacologic venous thromboembolism (VTE) prophylaxis in patients with chronic liver disease (CLD) and concurrent coagulopathy (INR ≥1.5). METHODS: A retrospective study was conducted on 193 adult patient admissions with a diagnosis of CLD and INR ≥1.5 not due to therapeutic anticoagulation. Patients were stratified based on their receipt of pharmacological thromboprophylaxis or not during hospitalization. The rates of overall bleeding, defined as the composite of major bleeding and clinically relevant non-major bleeding; major bleeding; and clinically relevant non-major bleeding, within 14 days of admission were evaluated. Secondary endpoints included the rates of thrombosis and mortality. RESULTS: The composite of overall bleeding occurred in 17.6% of the admissions. More patients in the group not receiving pharmacological thromboprophylaxis had overall bleeding (18.5% vs 10%), major bleeding (13.3% vs 10%), and clinically relevant non-major bleeding (14.5% vs 5%), with overlapping 95% CI. When stratified per pharmacological thromboprophylaxis status, IMPROVE bleeding risk score (BRS) ≥ 7 was associated with higher rates of overall bleeding, major bleeding, and clinically relevant non-major bleeding as compared to IMPROVE BRS <7, whether patients received or did not receive pharmacological thromboprophylaxis. The overall incidence of in-hospital mortality among our study population was 15.5%. Receiving pharmacological thromboprophylaxis was markedly associated with higher in-hospital mortality (OR = 16.58, 95% CI = 4.47-61.45). CONCLUSION: This study shows that the IMPROVE BRS calculated on admission may serve as a guide for omission of thromboprophylaxis in advanced CLD.

Irritable bowel syndrome: prevalence, risk factors in an adult Lebanese population.

BACKGROUND: Very few studies report on the prevalence of irritable bowel syndrome (IBS) and its correlates in the Middle East. This study investigated Irritable Bowel Syndrome (IBS) prevalence in a sample of Lebanese adult individuals and associated demographic and behavioral lifestyle factors. METHODS: This is an observational population-based study. The target population is working Lebanese adults, eighteen-to-sixty five years old. The sample was selected from a convenience population of bank employees in different geographical areas in Lebanon. The study participants completed an anonymous self-administered questionnaire, to collect data on their socio-demographic, behavioral and life style characteristics, and diagnostic questions following Rome III criteria to assess IBS occurrence. The difference in IBS prevalence by socio-demographic characteristics, smoking, alcohol consumption, and physical activity was assessed by using the Chi-square test. Logistic regression adjusted odds ratios were used to investigate the association between risk factors and IBS. RESULTS: Data was collected from 553 individuals and consisted of 52.8% females (mean age 35.9 years, SD = 11.9) and 47.2% males (mean age = 36.1 years, SD = 10.3). The prevalence of IBS in the study population according to Rome III criteria was 20.1%. The bivariate analysis indicated that being younger than 30 years old, a female, an ever water pipe smoker, an ever alcohol consumer are significantly associated with a higher prevalence of IBS. Educational level, cigarettes smoking and physical exercise were not significantly associated with IBS occurrence. The logistic regression adjusted odds ratio showed that females were 1.67 times more likely to have IBS than males (P˂ 0.05). The participants aged less than 30 years old were at a higher risk of having IBS (P˂ 0.01). Those who ever smoked waterpipe were 1.63 times more likely to have IBS than those who never smoked waterpipe (P˂ 0.05). Those who were ever alcohol drinkers were twice as likely to have IBS than never-drinkers (P˂ 0.01). CONCLUSION: New data on the high prevalence of IBS in an adult population in Lebanon has been reported. This is also the first study to investigate and show an association of waterpipe smoking and IBS. Further longitudinal studies are warranted to determine whether this association is causal.

An optimized xylene-free protein extraction method adapted to formalin-fixed paraffin embedded tissue sections for western blot analysis.

Deparaffinization of formalin-fixed paraffin embedded (FFPE) tissues with xylene currently remains a major challenge to the biomedical community. We developed an efficient xylene-free protocol to isolate proteins from archived FFPE human tissue sections. A total of 79 different types of FFPE tissue sections of 8 µm thickness were obtained from various archived FFPE specimens. Deparaffinization was conducted by gently washing each section with around 1 ml of hot distilled water (≈80°C). The deparaffinized tissues were homogenized in lysis buffer, and the isolated proteins were quantified and efficiently resolved using western blot analysis for the presence of Protein kinase B (PKB/AKT) and ß-actin. Moreover, a significant amount of proteins was successfully isolated with an average of 2.31 µg/µl. The migration pattern of AKT and ß-actin obtained from the specimens was similar to the positive control obtained from protein lysates prepared from in vitro cultured MDA231 cancer cell lines. AKT was successfully identified in all specimens, and ß-actin protein was resolved with an efficiency higher than 80%. The entire extraction procedure requires only 20 minutes. This newly developed technique is an efficient, safe, cost-effective, and rapid method to isolate proteins from FFPE tissue sections adequate for molecular analysis.

A novel xylene-free deparaffinization method for the extraction of proteins from human derived formalin-fixed paraffin embedded (FFPE) archival tissue blocks.

Protein detection methods in formalin-fixed paraffin embedded (FFPE) tissue blocks are widely used in research and clinical setting in order to diagnose or to confirm a diagnosis of various types of diseases. Therefore, multiple protein extraction methods from FFPE tissue sections have been developed in this regard. However, the yield and the quality of proteins extracted from FFPE tissues are significantly reduced in blocks stored for longer periods of time. Regardless the protein extraction method used, tissue sections must be first deparaffinized with xylene, and then washed in serial dilutions of ethanol in order to remove the toxic organic solvent "xylene" and rehydrate the tissue. The objective of this study was first to develop a method to deparaffinize FFPE blocks that excludes the use of toxic solvent "xylene". Second minimize the time required to perform the extraction. Here we describe a method where:•The entire paraffin embedded blocks are deparaffinized and rehydrated using only hot distilled water as a substitute for both xylene and ethanol•The entire procedure takes about 15 min•Deparaffinized blocks are immediately homogenized in lysis buffer, and the obtained lysate analyzed by Western blot. With this new modified technique, we were able to successfully detect actin and AKT proteins in lysates from blocks embedded in paraffin for up to 9 years.

The pattern of self-poisoning among Lebanese children and adolescents in two tertiary care centres in Lebanon.

AIM: Self-poisoning in childhood and adolescence is a major problem for health authorities all over the world. The objective of this study was to determine the pattern of self-poisoning in Lebanese children and adolescents. MATERIALS AND METHODS: This prospective study included all cases of poisoning in individuals aged 0-18 years who presented to the emergency department of two major hospitals in Beirut, Lebanon over a period of 1 year. Participants were divided into two age groups (0-12 years and 12-18 years). These cases were followed to record the applied treatment and whether the patient was admitted or discharged. RESULTS: There were 110 self-poisoning incidents, of which 74 (67%) were in female patients. The predominant type of poisoning was with pharmaceutical products (68.2%). Accidental self-poisoning was significantly more common in the younger age group among both genders compared with the older age group (p < 0.0001). There were significantly more poisoned male children (72%) than male adolescents (28%) (p = 0.003); whereas among females, poisoned adolescents were significantly more common (64%) than poisoned children (36%) (p = 0.009). Moreover, poisoning with pharmaceuticals was significantly higher in the young male group compared to the older age group and older female group compared to the younger age group (p = 0.0007 and p = 0.01, respectively). In total, 78% of patients were discharged home following basic observation, charcoal or gastric lavage. CONCLUSION: Female adolescents are more at risk of deliberate self-intoxication after the age of 12 years compared to males, whereas males younger than 12 years are more likely to suffer from accidental poisoning. Preventative strategies include screening adolescents at high risk of self-harm in order to offer adequate counselling, while providing anticipatory guidance for parents of children in the younger age group.