Combined hepatic resection and ablation for high burden of colorectal liver metastases demonstrates safety and durable survival.

BACKGROUND: Hepatic resection (HR) and thermal ablation of Colorectal Liver Metastases (CRLM) have each individually demonstrated safety and survival benefit. We sought to provide our experience with the combination of HR + ablation within one operation for patients with multiple CRLM. METHODS: Review of a single institution database of patients who underwent HR + ablation between 2010 and 2019. RESULTS: 161 patients were identified who underwent HR + ablation for isolated CRLM (mean age: 59, male 63.4%). 125 (77.6%) patients had bilobar disease and 92 (57.1%) patients had ≥5 tumors. 28 (17.4%) patients experienced minor (grade 1 or 2) complications while 20 (12.4%) had grade 3-5 complications. Patients who underwent simultaneous colon resection with HR + ablation had a higher complication rate (22 of 47, 46.8%) than those undergoing HR + ablation only (26 of 114, 22.8%, p = 0.002). Median and 5-year OS for all patients undergoing HR + ablation was 38.2 months and 33.2%, respectively. 5-year hepatic recurrence free survival was 23.5%. Patients with 5 or more tumors demonstrated no difference in median survival compared to those with fewer than 5 tumors (37.0 months vs 38.4 months, p = 0.326). CONCLUSIONS: In this population of CRLM patients with a relatively high burden of disease, HR + ablation demonstrated an acceptable safety profile as well as durable long-term survival.

Lower odds of COVID-19-related mortality in hospitalised patients with type II diabetes mellitus: A single-centre study.

BACKGROUND: COVID-19 infection in patients with type 2 diabetes mellitus (T2DM) -a chronic illness in Lebanon-is not well described. METHODS: This was a single-centre retrospective observational study of 491 patients, including 152 patients with T2DM, who were hospitalised for COVID-19 between 20 August 2020 and 21 April 2021. Data on clinical characteristics, laboratory and radiological findings and outcomes were collected from the electronic medical records. Clinical characteristics and in-hospital mortality between patients with and without T2DM infected with COVID-19 using multivariate analysis were compared. RESULTS: Patients with T2DM were significantly older than those without T2DM (mean age, 68.7 vs. 60.3 years). Patients with T2DM were more likely to present with a body temperature of <38.3°C (83.9% vs. 69.9%) and less likely to present with chest pain (3.9% vs. 9.1%) and sore throat (2.0% vs. 6.8%). Patients with T2DM were more likely to be hypertensive (76.35% vs. 41%) and dyslipidaemic (58.6% vs. 25.7%) and had more frequent underlying coronary artery disease (33.6% vs. 12.4%). The rates of patients with creatinine levels of ≥1.17 mg/L and troponin T levels of ≥4 ng/dL were higher in the T2DM group than in the non-T2DM group (30.4% vs. 15% and 93.3% vs. 83.1%, respectively). Patients with T2DM were more likely to be admitted to the intensive care unit (ICU) (34.2% vs. 22.1%), require invasive ventilation (18.4% vs. 10.3%) and receive vasopressors (16.4% vs. 10.0%). Increasing age and the use of invasive ventilation and vasopressors were associated with higher odds of mortality (odds ratio (OR), 1.08, 9.95 and 19.83, respectively), whereas longer ICU stay was associated with lower odds of mortality (OR, 0.38). The odds of mortality were lower in the T2DM group than in the non-T2DM group (OR, 0.27). CONCLUSION: Among patients hospitalised for COVID-19, those with T2DM were older, presented with milder symptoms and had more comorbidities and higher troponin T levels compared with those without T2DM. Despite the worse clinical course, the patients with T2DM had lower odds of mortality than those without T2DM.

Association Between Conduit Type and Outcomes After Open Repair of Popliteal Artery Aneurysms.

INTRODUCTION: Prior studies have demonstrated acceptable midterm outcomes with prosthetic conduits for above-knee bypass for occlusive disease in patients with inadequate segment great saphenous vein (GSV). In this study we aimed to investigate whether this holds true for open repair of popliteal artery aneurysms (PAA). METHODS: We queried the Vascular Quality Initiative data for patients who underwent open PAA repair (OPAR). We divided the cohort into three groups based on the conduit used: GSV, other autologous veins, or prosthetic graft. Study outcomes included primary patency, freedom from major amputation, amputation-free survival, and overall survival at 1 y. Kaplan-Meier survival estimates, log-rank tests and multivariable Cox regression were used to compare outcomes between study groups. RESULTS: A total of 4016 patients underwent bypass for PAA from January 2010 to October 2021. The three cohorts were significantly different in many demographic and clinical characteristics. The adjusted odds of postoperative amputation among symptomatic patients were 3-fold higher for prosthetic conduits compared to the GSV (odds ratio, 3.20; 95% CI, 1.72-5.92; P < 0.001). For the 1-y outcomes, the adjusted risk of major amputation was almost 3-fold higher for patients with symptomatic disease undergoing bypass with prosthetic conduits (hazard ratio [HR], 2.97; 95% CI, 1.35-6.52; P = 0.007). When compared with GSV, prosthetic conduits were associated with 96% increased risk of death when used for repair in symptomatic patients (adjusted hazard ratio (aHR), 1.96; 95% CI, 1.29-2.97; P = 0.002) but no significant association with mortality in asymptomatic patients (aHR, 0.83; 95% CI, 0.37-1.87; P = 0.652). When compared with GSV, prosthetic conduits were associated with a 2-fold increased risk of 1-y major amputation or death when used for repair in symptomatic patients (aHR, 2.03; 95% CI, 1.40-2.94; P < 0.001) but no significant association with mortality in asymptomatic patients (aHR, 0.91; 95% CI, 0.42-1.98; P = 0.816). Comparing bypass with other veins to the GSV among patients with symptomatic disease, there was no statistically significant difference in major amputation risk (HR; 2.44; 95% CI, 0.55-10.82; P = 0.242) and no difference in the adjusted risk of all-cause mortality (aHR, 0.77; 95% CI, 0.26-2.44; P = 0.653). There were no differences in the adjusted risk of loss of primary patency comparing other veins to GSV (HR, 1.53; 95% CI, 0.85-2.76; P = 0.154) and prosthetic conduits to GSV (HR, 0.85; 95% CI, 0.57-1.26; P = 0.422). CONCLUSIONS: This large study shows that among patients undergoing OPAR, 1-y primary patency does not differ between conduit types. However, prosthetic conduits are associated with significantly higher risk of amputation and death compared to GSV among symptomatic patients. Though non-GSV autologous veins are less often used for OPAR, they have comparably acceptable outcomes as GSV.

Evolution of COVID-19 infection characteristics in a Lebanese cohort of inpatients during different pandemic periods.

This study aims to describe COVID-19 patients characteristics, laboratory and imaging results, and the different outcomes of patients admitted to the Lebanese American University Medical Center-Rizk Hospital over a period of 9 months. In this observational retrospective study, data were obtained from electronic medical records of 491 male and female patients from the ages of 17 to 97. Analysis of the patients was performed in 3 periods: August 2020 to October 20 November 202020 to January 2021 and February 2021 to April 2021 corresponding with 3 waves of newly diagnosed cases during this period. The sample showed a male predominance with an average age of 63. The average hospitalization length was 10.1 days. The majority of patients were discharged to quarantine. The distribution of hospitalized cases was significantly correlated to the monthly distribution of newly COVID-19 cases in Lebanon. There was no significant difference in patient's characteristics between the 3 periods of the study (gender, age, body mass index, smoking, and medical conditions). Clinical presentations of the patients varied between the 3 periods. Similarly, the course and outcome of infection varied. Patients received less oxygen during period 1, while more patients were cured during period 3. This study presents the first Lebanese cohort of COVID-19 patients with their medical background, clinical presentation, laboratory results, radiological findings and course of infection with its outcome. It also shows how the relations between the medical manifestation of the COVID-19 pandemic and the socio-political measures of infection control are deeply intertwined.

Effect of combination of prophylactic or therapeutic anticoagulation with aspirin on the outcomes of hospitalized COVID-19 patients: An observational retrospective study.

Regimens for managing thromboembolic complications of COVID-19 are still not very well established. The present study compares the clinical characteristics and outcomes of patients hospitalized with COVID-19 receiving different anticoagulation regimens with and without aspirin. This is a retrospective observational study of 491 patients hospitalized for COVID-19 from August 2020 to April 2021. Data regarding clinical characteristics, laboratory findings, and outcomes of patients receiving different anticoagulation with and without aspirin regimens was collected, according to which 5 patient groups were defined: received no anticoagulation (NAA), prophylactic anticoagulation with (PA) or without aspirin (PAA) and therapeutic anticoagulation with (TA) or without aspirin (TAA). The average age was highest in the TAA group. Desaturation was highest in the TA and TAA groups. Diabetes, hypertension, dyslipidemia and coronary artery disease were the most prevalent in aspirin groups (PAA and TAA) as was heart failure in the TA and TAA groups and cancer in the TA and PAA groups. Elevated troponin was observed in the PAA and TAA groups. TA and TAA patients received oxygen therapy, needed ICU admission overall, and required invasive ventilation and vasopressors the most. Prophylactic anticoagulation groups (PA and PAA) had the highest patient survival rates. Patients with severe COVID-19 infections were more likely to receive higher, therapeutic, anticoagulation doses. Aspirin was given to patients with preexisting comorbidities, but it had no statistically significant impact on the outcomes of the different groups. Groups receiving prophylactic anticoagulation had the best survival outcomes.

The Antioxidant and Proapoptotic Effects of Sternbergia clusiana Bulb Ethanolic Extract on Triple-Negative and Estrogen-Dependent Breast Cancer Cells In Vitro.

BACKGROUND: Sternbergia clusiana belongs to the Amaryllidaceae family and is recognized for the valuable biological activity of its major bioactive compounds. The aim of the current is to evaluate the anticancer effects of the ethanolic bulb extract of Sternbergia clusiana (ScBEE) on breast cancer cells in vitro and to further reveal the underlying cellular mechanism. METHODS: An MTS cell viability assay was performed on MDA-MB-231 and MCF-7 cells, along with cell cycle analysis, cell death ELISA, Western blot analysis and an ROS production assay to decipher the mechanism of death. LC-MS/MS was also performed to identify the chemical composition of this ethanolic extract. RESULTS: The results show a selective antiproliferative effect on both cell lines with no effect on normal mesenchymal stem cells. Further analysis suggested the activation of the apoptotic pathway as reflected by the increase in cellular and DNA fragmentation and alterations in apoptotic proteins such as Bax, Bcl-2 and c-PARP. ScBEE was also found to exhibit antioxidant effect, as shown by a decrease in ROS production. The underlying mechanism of action was explained by the presence of several bioactive compounds identified by LC-MS/MS, including alkaloids, terpenoids and phenols, which are elaborated in the manuscript. CONCLUSION: This study highlights the antioxidant and anticancerous properties of S.clusiana for breast cancer treatment.

Intravenous high dose vitamin C and selected antiviral drugs in hospitalized COVID-19 patients: a descriptive cohort study.

INTRODUCTION: There is lack of universal agreement on the management of COVID-19. Intravenous high dose vitamin C (HDVC), remdesivir (RDV), and favipiravir (FPV) have been suggested as part of the treatment regimens and only RDV is approved by the Food and Drug Administration (FDA) so far. There is no study in Lebanon that addresses the descriptive cohort of HDVC and antiviral therapy amongst COVID-19 inpatients. Our goal was to highlight such a cohort. METHODOLOGY: A retrospective electronic chart review of COVID-19 inpatients was done over a period of 10 months (August 2020 to April 2021). Comparative data analysis was performed between HDVC and non-HDVC (NHDVC) groups, and RDV and FPV groups. RESULTS: Among HDVC patients, 70.1% (p = 0.035) and 67.2% (p = 0.008) had dyspnea and desaturation respectively. Patients on HDVC were less likely to remain in hospital for more than 20 days (p = 0.003). HDVC patients were more likely to be on oxygen therapy with 74.7% (p = 0.002). RDV patients were more likely to be on other COVID-19-related medications during hospitalization including the use of tofacitinib, baricitinib, tocilizumab, and anticoagulation as recommended in the guidelines. Statistical significance was noted for the status on discharge as 90.1% of the patients that received RDV were discharged after clinical improvement, compared to the 74.2% of the FPV patients. CONCLUSIONS: Further research is needed to establish local guidelines for the treatment of COVID-19. A significant role of HDVC and FPV might resurface if randomized control trials are conducted.

The pro-apoptotic properties of a phytonutrient rich infusion of A. cherimola leaf extract on AML cells.

Annonaceae family has broad uses in herbal medicine for treatment of several diseases, whether through seeds' or leaves' extracts. The present study investigates the antiproliferative and antitumor activity of Annona cherimola aqueous leaf (AAL) extract/infusion in acute myeloid leukemia (AML) cell lines in vitro. High-resolution LC-MS was first used to analyze the composition of the aqueous extract. Cell proliferation assay, Annexin V staining, cell cycle analysis, dual Annexin V/PI staining, cell death quantification by ELISA, ROS level detection and Western Blotting were then performed to elucidate the therapeutic effects of AAL extract. The results obtained revealed a potent antioxidant activity of AAL extract. Moreover, the extract exhibited dose- and time-dependent antiproliferative effects on AML cell lines by decreasing cell viability with an IC50 of 5.03% (v/v) at 24 h of treatment of KG-1 cells. This decrease in viability was accompanied with a significant increase in apoptotic cell death with cell cycle arrest and flipping of the phosphatidylserine from the inner to the outer leaflet of the cell membrane. The respective overexpression and downregulation of proapoptotic proteins like cleaved caspase-8, cleaved PARP-1 and Bax and antiapoptotic proteins like Bcl-2 further validated the apoptotic pathway induced by AAL on AML cells. Finally, LC-MS revealed the presence of several compounds like fatty acids, terpenes, phenolics, cinnamic acids and flavonoids that could contribute to the antioxidant and anti-cancer effects of this herbal infusion. In addition to the generally known nutritional effects of the Annona cherimola fruit and leaves, the presented data validates the antioxidant and anti-cancerous effects of the leaf infusion on AML cell lines, proposing its potential therapeutic use against acute myeloid leukemia with future in vivo and clinical trials.

E-cigarette aerosol induced cytotoxicity, DNA damages and late apoptosis in dynamically exposed A549 cells.

In this study, the acute toxicological impacts associated with electronic cigarettes consumption were determined using a novel dynamic exposure methodology. The methodology was deployed to test various e-cigarette generated aerosols in A549 cell cultures. The e-liquid chemical profiling was achieved using GC-MS analysis while toxicity of diluted e-liquids aerosols was reported using numerous cytotoxicity assays. The presented findings pointed to acute aerosol exposure (thirty puffs at 40 W of power and higher) inducing significant cytotoxic, genotoxic, and apoptotic induction in exposed cells. These findings highlighted the significant risks posed by e-cigarette usage. The proposed methodology proved to be a useful tool for future screening of e-liquids generated aerosols toxicity. Future research is needed to establish the chronic toxicity resulting from long-term e-cigarette consumption.

The selective anti-proliferative and pro-apoptotic effect of A. cherimola on MDA-MB-231 breast cancer cell line.

BACKGROUND: Herbal medicines have been a major target for numerous studies through the past years as an alternative treatment for cancer, mainly due to their minimal effects on normal healthy cells. Annona cherimola, popularly known as Cherimoya, is an edible natural fruit rich in phytochemical components and known to possess various biological activities. Previous studies have reported the anti-cancerous effect of A. cherimola ethanolic leaf extract (AELE) on leukemia. This study aims at studying the potential anti-cancer activity of this extract in vitro in two different breast cancer cell lines, namely MDA-MB-231 and MCF-7, in addition to investigating its toxicity on normal mesenchymal stem cells. METHODS: The anti-proliferative effect of AELE was evaluated via cell viability assay. Propidium iodide staining, Cell Death Detection ELISA and flow cytometry analysis of Annexin V binding were used to assess cell cycle progression, DNA fragmentation and apoptosis induction, respectively. Protein expression was determined via Western Blot analysis to decipher the underlying apoptotic molecular mechanism induced upon AELE treatment. RESULTS: The anti-proliferative effect of the extract was found to be selective on the triple-negative breast cancer cell line (MDA-MB-231) in a time- and dose-dependent manner with an IC50 of 390.2 µg/mL at 48 h, with no cytotoxic effects on normal murine mesenchymal stem cells. The pro-apoptotic effect was confirmed by the increase in cellular and DNA fragmentation, flipping of the phosphatidylserine moiety to the outer leaflet, and the increase in Annexin V binding. The underlying molecular mechanism revealed the involvement of the mitochondrial pathway, as shown by alterations in mitochondrial permeability and the upregulation of cytochrome c expression. CONCLUSION: All the data presented in our study suggest that AELE exhibits a selective anti-proliferative and pro-apoptotic effect on the chemo-resistant MDA-MB-231 breast cancer cells, providing evidence for the anti-tumor effects of A. cherimola.

The anti-cancer effect of flaxseed lignan derivatives on different acute myeloid leukemia cancer cells.

Flaxseeds have been known for their anti-cancerous effects due to the high abundance of lignans released upon ingestion. The most abundant lignan, secoisolariciresinol diglucoside (SDG), is ingested during the dietary intake of flax, and is then metabolized in the gut into two mammalian lignan derivatives, Enterodiol (END) and Enterolactone (ENL). These lignans were previously reported to possess anti-tumor effects against breast, colon, and lung cancer. This study aims to investigate the potential anti-cancerous effect of the flaxseed lignans SDG, END and ENL on acute myeloid leukemia cells (AML) in vitro and to decipher the underlying molecular mechanism. AML cell lines, (KG-1 and Monomac-1) and a normal lymphoblastic cell line were cultured and treated with the purified lignans. ENL was found to be the most promising lignan, as it exhibits a significant selective dose- and time-dependent cytotoxic effect in both AML cell lines, contrary to normal cells. The cytotoxic effects observed were attributed to apoptosis induction, as revealed by an increase in Annexin V staining of AML cells with increasing ENL concentrations. The increase in the percentage of cells in the pre-G phase, in addition to cell death ELISA analysis, validated cellular and DNA fragmentation respectively. Analysis of protein expression using western blots confirmed the activation of the intrinsic apoptotic pathway upon ENL treatment. This was also accompanied by an increase in ROS production intracellularly. In conclusion, this study demonstrates that ENL has promising anti-cancer effects in AML cell lines in vitro, by promoting DNA fragmentation and the intrinsic apoptotic pathway, highlighting the protective health benefits of flax seeds in leukemia.

Malva pseudolavatera Leaf Extract Promotes ROS Induction Leading to Apoptosis in Acute Myeloid Leukemia Cells In Vitro.

Malva pseudolavatera Webb & Berthel. is a plant from the Malvaceae family that has long been included in the human diet due to its various curative effects. Many plant leaf extracts from the various species of Malva genus have been reported to possess anti-cancer properties, however, studies on M. pseudolavatera Webb & Berthel. leaves have documented anti-inflammatory and anti-oxidant effects with no emphasis on their possible anti-cancer potential. The present study explores the anti-cancer properties of Malva pseudolavatera Webb & Berthel. leaf extract on acute myeloid leukemia (AML) cell lines in vitro and deciphers the underlying molecular mechanism. Treatment of AML cell lines with M. pseudolavatera methanolic leaf extract showed a dose- and time-dependent inhibition of proliferation and a dose-dependent increase in apoptotic hallmarks such as an increase in phosphatidylserine on the outer membrane leaflet and membrane leakage in addition to DNA fragmentation. The pro-apoptotic effect was induced by reactive oxygen species (ROS) as well as an upregulation of cleaved poly(ADP-ribose) polymerase (PARP), increase in Bax/Bcl-2 ratio, andrelease of cytochrome-c from the mitochondria. Major compounds of the extract included methyl linolenate, phytol, γ-sitosterol, and stigmasterol as revealed by gas chromatography coupled with mass spectrometry, and amino acids, amino acid derivatives, tiliroside, 13-hydroxyperoxyoctadecadienoic, and quercitrin as detected by liquid chromatography coupled to mass spectrometry.

The pro-apoptotic effect of a Terpene-rich Annona cherimola leaf extract on leukemic cell lines.

BACKGROUND: The edible fruit Annona cherimola has previously shown many nutritional and medicinal properties. The current study evaluates the anti-cancer and anti-proliferative properties of Annona cherimola ethanolic leaf extract (AELE) on Acute Myeloid Leukemia (AML) cell lines cultured in vitro (Monomac-1 and KG-1). METHODS: The anti-proliferative effect of A. cherimola ethanolic leaf extract was evaluated via cell viability assay. Its pro-apoptotic effect was assessed through Cell Death ELISA and dual Annexin V/PI staining. To further investigate the molecular mechanism by which the extract promoted apoptosis and inhibited the proliferation of the AML cells used, apoptotic protein expression was determined through western blots. Extract composition was elucidated by Gas Chromatography-Mass Spectrometry (GC-MS). RESULTS: Our results showed that the treatment with A. cherimola ethanolic leaf extract exhibited an inhibitory effect on the proliferation of both cancer cell lines used in a dose- and time-dependent manner, with no toxic effects on normal mononuclear cells (MNCs) isolated from human bone marrow. This effect was mediated by DNA fragmentation and apoptosis, as revealed by Cell Death ELISA and dual Annexin V/PI staining. Western blot analysis revealed a Bax/Bcl2 dependent mechanism of apoptosis, as well as PARP cleavage, confirming the apoptotic results observed previously. These effects may be attributed to the presence of terpenes which constitute a large component of the leafy extract, as revealed via GC-MS. CONCLUSION: All the data presented in our study show that the terpene-rich A. cherimola ethanolic leaf extract exhibits an anti-proliferative and pro-apoptotic effect on the AML cell lines used.

The Vitamin E Derivative Gamma Tocotrienol Promotes Anti-Tumor Effects in Acute Myeloid Leukemia Cell Lines.

Acute myeloid leukemia (AML) is a blood cancer characterized by the formation of faulty defective myelogenous cells with morphological heterogeneity and cytogenic aberrations leading to a loss of their function. In an attempt to find an effective and safe AML treatment, vitamin E derivatives, including tocopherols were considered as potential anti-tumor compounds. Recently, other isoforms of vitamin E, namely tocotrienols have been proposed as potential potent anti-cancerous agents, displaying promising therapeutic effects in different cancer types. In this study we evaluated the anti-cancerous effects of γ-tocotrienol, on AML cell lines in vitro. For this purpose, AML cell lines incubated with γ-tocotrienol were examined for their viability, cell cycle status, apoptotic cell death, DNA fragmentation, production of reactive oxygen species and expression of proapoptotic proteins. Our results showed that γ-tocotrienol exhibits time and dose-dependent anti-proliferative, pro-apoptotic and antioxidant effects on U937 and KG-1 cell lines, through the upregulation of proteins involved in the intrinsic apoptotic pathway.

Annona cherimola Seed Extract Activates Extrinsic and Intrinsic Apoptotic Pathways in Leukemic Cells.

Annona cherimola Mill is a large green fruit with black seeds widely known to possess toxic properties due to the presence of Annonaceous acetogenins. The present study investigates the anti-cancer properties of an Annona cherimola Mill ethanolic seed extract on Acute Myeloid Leukemia (AML) cell lines in vitro and elucidates the underlying cellular mechanism. The anti-proliferative effects of the extract on various AML cell lines and normal mesenchymal cells (MSCs) were assessed using WST-1 viability reagent. The pro-apoptotic effect of the extract was evaluated using Annexin V/PI staining and Cell Death ELISA. The underlying mechanism was deciphered by analyzing the expression of various proteins using western blots. Treatment with an A. cherimola seed ethanolic extract promotes a dose- and time-dependent inhibition of the proliferation of various AML cell lines, but not MSCs. Positive Annexin V staining, as well as DNA fragmentation, confirm an increase in apoptotic cell death by upregulating the expression of pro-apoptotic proteins which control both intrinsic and extrinsic pathways of apoptosis. GC/MS analysis revealed the presence of phytosterols, in addition to other bioactive compounds. In conclusion, Annona cherimola Mill seed extract, previously known to possess a potent toxic activity, induces apoptosis in AML cell lines by the activation of both the extrinsic and the intrinsic pathways.