Predictors of in-hospital outcomes for diverticular bleeding patients: a retrospective analysis of National Inpatient Sample data (2016-2020).

Background: Diverticular bleeding is the leading cause of lower gastrointestinal bleeding, affecting 3-5% of patients with diverticulosis. Current management protocols include resuscitation, diagnosis via direct visualization, computed tomography imaging, endoscopic interventions, angioembolization, and surgery when needed. However, predictive factors for outcomes and optimal interventions remain ambiguous. Methods: This retrospective cohort study analyzed data from the National Inpatient Sample (NIS) database (2016-2020) to determine predictors of adverse in-hospital outcomes in diverticular bleeding patients without perforation or abscess. Demographic and clinical data were extracted, and multivariate regression models were applied. Analysis was conducted using R statistical software (version 4.1.3), with significance set at P<0.05. Results: A total of 28,269 patients hospitalized for diverticular bleeding were identified. Age >85 years, moderate to severe Charlson Comorbidity Index, hypovolemic shock, blood transfusion requirement, and requirement for colectomy were significantly associated with greater in-hospital mortality. Factors such as late colonoscopy timing and colon resection led to longer hospital stays, while arterial embolization was predicted by older age, Black race, hypovolemic shock, and blood transfusion. Predictors of colon resection included advanced age, presence of colon cancer, and hypovolemic shock. Conclusions: Our retrospective study identified significant predictors of in-hospital outcomes among patients with diverticular bleeding, informing risk stratification and management strategies. Further research is warranted to validate these findings and refine management algorithms for improved patient care. Integrating these insights into clinical practice may enhance outcomes and guide personalized interventions in diverticular bleeding management.

Integration of measurable residual disease by WT1 gene expression and flow cytometry identifies pediatric patients with high risk of relapse in acute myeloid leukemia.

Background: Molecular testing plays a pivotal role in monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML), aiding in the refinement of risk stratification and treatment guidance. Wilms tumor gene 1 (WT1) is frequently upregulated in pediatric AML and serves as a potential molecular marker for MRD. This study aimed to evaluate WT1 predictive value as an MRD marker and its impact on disease prognosis. Methods: Quantification of WT1 expression levels was analyzed using the standardized European Leukemia Network real-time quantitative polymerase chain reaction assay (qRT-PCR) among a cohort of 146 pediatric AML patients. Post-induction I and intensification I, MRD response by WT1 was assessed. Patients achieving a ≥2 log reduction in WT1MRD were categorized as good responders, while those failing to reach this threshold were classified as poor responders. Results: At diagnosis, WT1 overexpression was observed in 112 out of 146 (76.7%) patients. Significantly high levels were found in patients with M4- FAB subtype (p=0.018) and core binding fusion transcript (CBF) (RUNX1::RUNX1T1, p=0.018, CBFB::MYH11, p=0.016). Following induction treatment, good responders exhibited a reduced risk of relapse (2-year cumulative incidence of relapse [CIR] 7.9% vs 33.2%, p=0.008). Conversely, poor responders' post-intensification I showed significantly lower overall survival (OS) (51% vs 93.2%, p<0.001), event-free survival (EFS) (33.3% vs 82.6%, p<0.001), and higher CIR (66.6% vs 10.6%, p<0.001) at 24 months compared to good responders. Even after adjusting for potential confounders, it remained an independent adverse prognostic factor for OS (p=0.04) and EFS (p=0.008). High concordance rates between WT1-based MRD response and molecular MRD were observed in CBF patients. Furthermore, failure to achieve either a 3-log reduction by RT-PCR or a 2-log reduction by WT1 indicated a high risk of relapse. Combining MFC-based and WT1-based MRD results among the intermediate-risk group identified patients with unfavorable prognosis (positive predictive value [PPV] 100%, negative predictive value [NPV] 85%, and accuracy 87.5%). Conclusion: WT1MRD response post-intensification I serves as an independent prognostic factor for survival in pediatric AML. Integration of WT1 and MFC-based MRD results enhances the reliability of MRD-based prognostic stratification, particularly in patients lacking specific leukemic markers, thereby influencing treatment strategies.

Effect of pentoxifylline on endothelial dysfunction, oxidative stress and inflammatory markers in STEMI patients.

Aim: ST-elevation myocardial infarction (STEMI) patients suffer higher mortality and adverse outcomes linked to endothelial dysfunction (ED). Methods: 43 patients were randomized to pentoxifylline (PTX) 400 mg thrice daily (n = 22) or placebo (n = 21). Soluble vascular cell adhesion molecule-1, malondialdehyde, interleukin-1 (IL-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) were assessed at baseline and 2 months. Results: After 2 months, no significant difference was observed in markers' levels between the 2 groups. However, a within-group comparison revealed a statistically significant change in hs-CRP in the PTX group (10.057 (9.779-10.331) versus 9.721 (6.102-10.191)), p = 0.032. Conclusion: PTX for 2 months in STEMI patients was safe and well-tolerated but had no significant detectable effect on ED, oxidative stress or inflammatory markers. Clinical Trial Registration: NCT04367935 (ClinicalTrials.gov).

This study examined the effect and the safety of a drug called pentoxifylline in patients who have recently had a heart attack. Pentoxifylline can possibly reduce inflammation and is used for patients with blood flow issues. The study involved 43 participants, 22 receiving pentoxifylline and 21 receiving a placebo for 2 months. We measured different markers related to inflammation and heart health before and after. Overall, there was no significant difference between the groups, but patients who received pentoxifylline experienced less inflammation according to only one of the markers measured. This study concluded that the prescription of pentoxifylline after a heart attack is safe, well-tolerated and without notable side effects. Still, we recommend larger and longer studies to be sure of its effect.

Hematopoietic effect of echinochrome on phenylhydrazine-induced hemolytic anemia in rats.

Background: Hemolytic anemia (HA) is a serious health condition resulting from reduced erythrocytes' average life span. Echinochrome (Ech) is a dark-red pigment found in shells and spines of sea urchins. Aim: Studying the potential therapeutic effect of Ech on phenylhydrazine (PHZ)-induced HA in rats. Methods: Eighteen rats were divided into three groups (n = 6): the control group, the phenylhydrazine-induced HA group and the Ech group, injected intraperitoneally with PHZ and supplemented with oral Ech daily for 6 days. Results: Ech resulted in a considerable increase in RBCs, WBCs, and platelets counts, hemoglobin, reduced glutathione, catalase, and glutathione-S-transferase levels, and a significant decrease in aspartate & alanine aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, creatinine, urea, urate, malondialdehyde & nitric oxide levels in anemic rats. Histopathological examination of liver and kidney tissue samples showed marked improvement. Conclusion: Ech ameliorated phenylhydrazine-induced HA with a hepatorenal protective effect owing to its anti-inflammatory and antioxidant properties.

New nicotinamide derivatives as potential anticancer agents targeting VEGFR-2: design, synthesis, in vitro, and in silico studies.

Herin, new nicotinamide candidates were designed and synthesized as VEGFR-2 inhibitors. In vitro antiproliferative activities were assessed against MCF-7, HepG-2 and HCT-116 cancer cell lines. The top cytotoxic members 15a, 15b, 16, 18a, and 18b were estimated against their selected target (VEGFR-2). Further mechanistic tests were studied for the most potent cytotoxic candidate 18a, these studies revealed the ability of compound 18a to hinder the progression of HCT-116 cells at S and Pre-G1phases besides boosting early and late apoptosis. Also compound 18a was found to significantly decrease the levels immunomodulatory proteins TNF-α and IL-6 while showing a four-fold rise in an apoptotic marker caspase-3 when compared to control cells. The therapeutic index of the designed derivatives was evaluated by computational ADMET and toxicity calculations as well as their potentiality to occupy the VEGFR-2 active site was signposted by molecular docking assessments. Finally, molecular dynamic simulation studies of compound 18a-VEGFR-2 complex indicated the high steadiness of compound 18a in the VEGFR-2 active site. This study presents compound 18a as a lead candidate that can be optimized to get a strong VEGFR-2 inhibitor.Communicated by Ramaswamy H. Sarma.

PreOperative Planning for Adult Spinal Deformity Goals: Level Selection and Alignment Goals.

Adult Spinal Deformity (ASD) is a complex pathologic condition with significant impact on quality of life, including pain, loss of function, and fatigue. Achieving realignment goals is crucial for long-term results. Reliable preoperative planning strategies, including nomograms, measurement tools, and level selection, are key to maximizing the likelihood of achieving a good outcome following ASD corrective surgery. This review covers recent literature on such strategies, including review of the different targets for realignment and their association with outcomes (both patients-reported outcomes and complications), selection of upper and lower instrumented vertebrae, and the latest innovation in preoperative planning for deformity surgery.

Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs.

Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC50 values ranging from 2.03 to 13.39 µg/mL, exhibiting higher activities than thalidomide against all tested cancer cell lines. Compound XIIIa was the most potent candidate, with an IC50 of 2.03 ± 0.11, 2.51 ± 0.2, and 0.82 ± 0.02 µg/mL compared to 11.26 ± 0.54, 14.58 ± 0.57, and 16.87 ± 0.7 µg/mL for thalidomide against HepG-2, PC3, and MCF-7 cells, respectively. Furthermore, compound XIVc reduced the expression of NFκB P65 levels in HepG-2 cells from 278.1 pg/mL to 63.1 pg/mL compared to 110.5 pg/mL for thalidomide. Moreover, compound XIVc induced an eightfold increase in caspase-8 levels with a simultaneous decrease in TNF-α and VEGF levels in HepG-2 cells. Additionally, compound XIVc induced apoptosis and cell cycle arrest. Our results reveal that the new candidates are potential anticancer candidates, particularly XIIIa and XIVc. Consequently, they should be considered for further evaluation for the development of new anticancer drugs.

Design, synthesis, in silico studies, and biological evaluation of novel pyrimidine-5-carbonitrile derivatives as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers.

A novel series of pyrimidine-5-carbonitrile derivatives bearing benzylidene and hydrazone moieties with different linkers (spacers) were designed and synthesized as possible inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The newly synthesized compounds were evaluated in vitro for their cytotoxic activities against two human cancer cell lines namely colon cancer (HCT-116) and breast cancer (MCF-7) using sorafenib as a standard anticancer drug. Compounds 9d, 11e, 12b, and 12d showed higher cytotoxic activities than sorafenib with IC50 values ranging from 1.14 to 10.33 µM. In particular, compound 11e exhibited excellent activities against HCT-116 and MCF-7 with IC50 values of 1.14 and 1.54 µM, respectively. Moreover, compound 11e exhibited about 47.32-fold cytotoxic activity against normal human fibroblast (WI-38) cells, lower than the cytotoxicity against the cancer cells. Compounds 11e and 12b were the most potent VEGFR-2 inhibitors with IC50 values of 0.61 and 0.53 µM, respectively, compared to sorafenib. Bedsides, compound 11e arrested the HCT-116 cell growth at S and sub-G1 phases, induced a significant increase in the apoptotic cells, and caused remarkable decrease in the levels of TNF-α, IL-6, and caspase-3. Finally, the binding patterns of the target derivatives were investigated through the docking study against the proposed molecular target (VEGFR-2, PDB ID 1YWN). The results of molecular docking studies showed similar binding modes to sorafenib against VEGFR-2. In addition, molecular dynamic simulations revealed the stability of compound 11e in the active site for 100 ns.

Novel promising benzoxazole/benzothiazole-derived immunomodulatory agents: Design, synthesis, anticancer evaluation, and in silico ADMET analysis.

Eleven novel benzoxazole/benzothiazole-based thalidomide analogs were designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against HepG-2, HCT-116, PC3, and MCF-7 cells. Generally, the open analogs with semicarbazide and thiosemicarbazide moieties (10, 13a-c, 14, and 17a,b) exhibited higher cytotoxic activities than derivatives with closed glutarimide moiety (8a-d). In particular, compound 13a (IC50 = 6.14, 5.79, 10.26, and 4.71 µM against HepG-2, HCT-116, PC3, and MCF-7, respectively) and 14 (IC50 = 7.93, 8.23, 12.37, and 5.43 µM, respectively) exhibited the highest anticancer activities against the four tested cell lines. The most active compounds 13a and 14 were further evaluated for their in vitro immunomodulatory activities on tumor necrosis factor-alpha (TNF-α), caspase-8 (CASP8), vascular endothelial growth factor (VEGF), and nuclear factor kappa-B p65 (NF-κB p65) in HCT-116 cells. Compounds 13a and 14 showed a remarkable and significant reduction in TNF-α. Furthermore, they showed significant elevation in CASP8 levels. Also, they significantly inhibited VEGF. In addition, compound 13a showed significant decreases in the level of NF-κB p65 while compound 14 demonstrated an insignificant decrease with respect to thalidomide. Moreover, our derivatives exhibited good in silico absorption, distribution, metabolism, elimination, toxicity (ADMET) profiles.

High-resolution melting assay for rapid, simultaneous detection of JAK2, MPL and CALR variants.

AIMS: Identification of recurrent genetic alterations in JAK2, MPL and CALR remains crucial in the diagnosis of Philadelphia-negative myeloproliferative neoplasms (MPNs). Current laboratory testing algorithms may entail batching and/or sequential testing, involving multiple testing modalities and sometimes send-out testing that increase the technical and economic demands on laboratories while delaying patient diagnoses. To address this gap, an assay based on PCR and high-resolution melting (HRM) analysis was developed for simultaneous evaluation of JAK2 exons 12-14, MPL exon 10 and CALR exon 9, embodied in the HemeScreen® (hereafter 'HemeScreen') MPN assay. METHODS: The HemeScreen MPN assay was validated with blood and bone marrow samples from 982 patients with clinical suspicion for MPN. The HRM assay and Sanger sequencing were performed in independent Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories with Sanger sequencing (supported by droplet digital PCR) serving as the gold standard. RESULTS: HRM and Sanger sequencing had an overall concordance of 99.4% with HRM detecting 133/139 (96%) variants confirmed by sequencing (9/10 MPL, 25/25 CALR, 99/104 JAK2), including 114 single nucleotide variants and 25 indels (3-52 bp). Variants consisted of disease-associated (DA) variants (89%), variants of unclear significance (2%) and non-DA variants (9%) with a positive predictive value of 92.3% and negative predictive value of 99.5%. CONCLUSIONS: These studies demonstrate the exquisite accuracy, sensitivity and specificity of the HRM-based HemeScreen MPN assay, which serves as a powerful, clinically applicable platform for rapid, simultaneous detection of clinically relevant, somatic disease variants.

Mild Pancreatitis Induced by Linagliptin Revealed by a Medication Review.

As dipeptidyl peptidase-4 inhibitors are becoming more utilized in the treatment of diabetes, it is important to recognize their side effects and become more familiar with them. As these side effects arise, physicians are more prepared to recognize and discontinue these medications. This case report describes a 34-year-old male who initially presented with a hemoglobin A1c greater than 16%. After titration of his diabetic medications, he presented with pancreatitis diagnosed by symptoms and imaging. Common causes of pancreatitis were ruled out, including biliary pathology, alcohol use, tobacco use, elevated calcium levels, and hypertriglyceridemia. The patient followed up in the clinic with persistent symptoms. A review of his medication list revealed pancreatitis as a side effect of linagliptin. After holding this medication, his symptoms improved over the course of a month.

A Rare Case of Rapidly Progressive Extragonadal Mature Cystic Teratoma Presenting With Chest Pain.

Mature cystic teratomas represent the most prevalent subtype of germ cell tumors affecting the ovaries. Typically, these neoplasms are benign and characterized by a slow growth pattern. Nevertheless, malignant transformation of these tumors is a rare event that may occur. Despite their typically indolent behavior, some cases may exhibit rapid growth rates and give rise to a variety of complications, including rupture and consequent manifestation of a wide range of clinical signs and symptoms. This report details the case of a 49-year-old woman who presented to the hospital with a chief complaint of chest pain. The onset of her symptoms occurred several days prior to admission and was associated with fatigue without shortness of breath. Imaging studies, including computed tomography angiography and magnetic resonance imaging of the chest, revealed a mediastinal mass measuring 5.9 x 7.4 cm in a cross-sectional area that displayed features consistent with a mature cystic teratoma, including the presence of soft tissue, fat, fluid, and areas of calcification. Notably, a prior computed tomography scan of the chest, performed 20 months before her presentation, did not reveal any evidence of masses. The patient subsequently underwent successful robot-assisted resection of the mediastinal mass, with complete resolution of her symptoms. Histopathologic examination of the excised mass confirmed the absence of malignancy.

Design, synthesis, anticancer evaluation, and in silico ADMET analysis of novel thalidomide analogs as promising immunomodulatory agents.

Immunomodulatory medications like thalidomide and its analogs prevent the production of some proinflammatory cytokines linked to cancer. A new series of thalidomide analogs were designed and synthesized in order to develop potential antitumor immunomodulatory agents. The antiproliferative activities of the new candidates against a panel of three human cancer cell lines (HepG-2, PC3 and MCF-7) were assessed in comparison to thalidomide as a positive control. The obtained results showed the relative significant potency of 18f (IC50 = 11.91 ± 0.9, 9.27 ± 0.7, and 18.62 ± 1.5 µM) and 21b (IC50 = 10.48 ± 0.8, 22.56 ± 1.6, and 16.39 ± 1.4 µM) against the mentioned cell lines, respectively. These results were comparable to thalidomide (IC50 = 11.26 ± 0.54, 14.58 ± 0.57, and 16.87 ± 0.7 µM, respectively). To see to what extent the biological properties of the new candidates are relative to those of thalidomide, the effects of 18f and 21b on the expression levels of TNF-α, CASP8, VEGF, and NF-κB P65 were evaluated. Significant reductions in the proinflammatory TNF-α, VEGF, and NF-κB P65 levels in HepG-2 cells were observed after exposure to compounds 18f and 21b. Furthermore, a sharp increase in CASP8 levels was detected. The obtained results revealed that 21b is of greater significance than thalidomide in TNF-α and NF-κB P65 inhibition. The in silico ADMET and toxicity studies showed that most of tested candidates have a good profile of drug-likeness and low toxicity potential.

The Impact of Granulocyte Colony-Stimulating Factor Administration in a Neutropenic Cancer Patient With COVID-19-Related Acute Respiratory Distress Syndrome.

Chemotherapy-induced neutropenia is a serious adverse effect found in cancer patients treated with chemotherapy. As these patients are at risk of infections, granulocyte colony-stimulating factors (G-CSF) are commonly used in these patients to increase neutrophil counts. This report describes a case of a 73-year-old female with metastatic breast cancer treated with letrozole and palbociclib who presented to the hospital with flu-like symptoms and a positive SARS-CoV-2 test. She was saturating well on room air without the need for supplemental oxygen initially, however, she was febrile and lab work revealed neutropenia. Subsequently, she was given two doses of Tbo-filgrastim. Her respiratory status deteriorated shortly afterward and she required supplemental oxygen. The chest X-ray obtained at that time revealed increased atelectasis or infiltration in the middle and lower lung fields, and computed tomography angiography of the chest revealed bilateral patchy airspace and ground glass opacities. The timeline from symptom onset along with her imaging findings suggested COVID-19-related acute respiratory distress syndrome (ARDS) as a possible explanation for her respiratory status decline. Interestingly, her neutrophil-to-lymphocyte ratio (NLR) had consistently increased, along with her respiratory status deterioration, after the completion of the two doses of G-CSF. The patient was treated with dexamethasone. Her respiratory status eventually improved prior to discharge.

Design, synthesis, anticancer evaluation, in silico docking and ADMET analysis of novel indole-based thalidomide analogs as promising immunomodulatory agents.

In the present work, novel 16 indole-based thalidomide analogs were designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against HepG-2, HCT-116, PC3 and MCF-7 cell lines. Generally, the opened analogs of glutarimide ring exhibited higher activities than the closed ones. Compounds 21a-b and 11d,g showed strong potencies against all tested cell lines with IC50 values ranging from 8.27 to 25.20 µM comparable to that of thalidomide (IC50 values ranging from 32.12 to 76.91 µM). The most active compounds were further evaluated for their in vitro immunomodulatory activities via estimation of human tumor necrosis factor alpha (TNF-α), human caspase-8 (CASP8), human vascular endothelial growth factor (VEGF), and nuclear factor kappa-B P65 (NF-κB P65) in HCT-116 cells. Thalidomide was used as a positive control. Compounds 11g, 21a and 21b showed remarkable significant reduction in TNF-α. Furthermore, compounds 11g, 21a and 21b showed significant elevation in CASP8 levels. Compounds 11g and 21a significantly inhibited VEGF. In addition, derivatives 11d, 11g and 21a showed significant decrease in level of NF-κB p65. Moreover, our derivatives exhibited good in silico docking and ADMET profile.Communicated by Ramaswamy H. Sarma.

A Case of Left Ventricular Thrombus and Herpetic Esophagitis in an Immunocompetent Patient With COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with thrombosis, both venous and arterial, but the mechanism behind this coagulation is not fully understood. Several cases involving coronavirus disease 2019 (COVID-19)-positive patients with left ventricular thrombus (LVT), particularly in those with low ejection fraction, have been reported. This report describes a case of a 57-year-old male patient who presented to the hospital with altered mental status and a positive SARS-CoV-2 polymerase chain reaction (PCR) test. CT of the chest revealed the presence of an LVT, and transthoracic echocardiography showed a reduced ejection fraction and confirmed the presence of the thrombus. The patient also reported epigastric chest pain and several bloody bowel movements. A colonoscopy revealed internal hemorrhoids. An esophagogastroduodenoscopy revealed the presence of multiple esophageal ulcers, and biopsy results confirmed herpes simplex virus (HSV) infection. The patient had no history of organ or bone marrow transplant, long-term immunosuppressive therapy, or HIV infection. He was eventually discharged on apixaban for his LVT and acyclovir for his HSV esophagitis.

The influence of intra-aortic balloon counter pulsation on central venous blood oxygen saturation.

OBJECTIVES: We aim at identifying the changes in venous blood saturation values that associates intra-aortic balloon pump (IABP) in cardiac surgery patients with reduced left ventricular function (LVF). METHODS: A retrospective observational study was conducted in a cardiothoracic intensive care unit (CTICU) in a tertiary cardiac center over 5 years in Qatar. A total of 114 patients with at least moderate impairment of LVF with ejection fraction (EF) less than 40% were enrolled. According to the association of IABP, patients were segregated into two groups with and without IABP (groups 1, 40 patients and group 2, 74 patients). Sequential arterial and venous blood gases were analyzed. The primary outcome was to analyze the changes in the central venous saturation (ScvO2) in both groups and the secondary outcome was to analyze whether these changes affect the overall outcome in terms of intensive care unit (ICU) length of stay. RESULTS: There was no significant difference between both groups with regard to age, preoperative EF, hemoglobin, and arterial oxygen saturation (SaO2) in blood gases. Patients with IABP have a higher cScvO2 when compared to the other group (71.5 ± 12.5 vs 63.5 ± 9.3, 68.3 ± 12.6 vs 60.1 ± 9.5, 62.7 ± 10.8 vs 55.63 ± 8.1, and 60.6 ± 7.6 vs 54.9 ± 8.1; p = 0.04, 0.05, 0.03, and 0.5, respectively). However, generalized estimating equations (GEE) analysis showed that compared with the participants showing that there is a decreasing trend in mean levels within the groups during follow-ups, overall difference between both groups' mean levels was not statistically significant. CONCLUSIONS: In this study, we observed that after cardiac surgeries, patients with IABP had non-significant higher ScvO2 when compared with a corresponding group with moderate impairment of LVF. Further prospective studies are required to validate these findings.

Clinical features and outcomes of infective endocarditis: a single-centre experience.

BACKGROUND: Infective endocarditis (IE) may present with a broad spectrum of symptoms and signs and several tools can be used for diagnosis. Many protocols can be used for in-hospital and out-patient management. The aim of this study was to assess the clinical features, tools used and outcomes of patients diagnosed with IE in one of the tertiary-care university hospitals. METHODS: This study included 90 consecutive patients admitted to the Cardiology Department in a tertiary-care university hospital in Egypt with a diagnosis of IE. RESULTS: The mean age of the studied population was 36.72 years and 76.67% were males. The most common underlying condition was valvular heart disease (48.89%), followed by intravenous drug use (26.67%) and the most common risk factor was smoking (48.89%). The most common clinical presentation was fever (69.67%), followed by dyspnoea (55.56%), and the mean duration from symptom onset until admission was 13.28 ± 9.29 days. Positive cultures were encountered in 45.56% of patients. Surgery was indicated in 91.11% of the patients but it was performed in only 28.89%. Almost a third of patients (34.44%) died in the hospital. After one year of follow up, a further 8.47% of the patients had died, 11.86% had heart failure and 6.78% had undergone a re-do surgery. CONCLUSIONS: Nowadays IE tends to affect a younger group of patients and valvular heart disease is the main underlying condition. The mortality rate due to IE is high in developing countries and IE does not have only immediate and short-term complications, its effects extend to a longer period of time.

Design, synthesis, and biological evaluation of novel bioactive thalidomide analogs as anticancer immunomodulatory agents.

Cancer is still a dangerous disease with a high mortality rate all over the world. In our attempt to develop potential anticancer candidates, new quinazoline and phthalazine based compounds were designed and synthesized. The new derivatives were built in line with the pharmacophoric features of thalidomide. The new derivatives as well as thalidomide were examined against three cancer cell lines, namely: hepatocellular carcinoma (HepG-2), breast cancer (MCF-7) and prostate cancer (PC3). Then the effects on the expression levels of caspase-8, VEGF, NF-κB P65, and TNF-α in HepG-2 cells were evaluated. The biological data revealed the high importance of phthalazine based compounds (24a-c), which were far better than thalidomide with regard to the antiproliferative activity. 24b showed IC50 of 2.51, 5.80 and 4.11 µg mL-1 compared to 11.26, 14.58, and 16.87 µg mL-1 for thalidomide against the three cell lines respectively. 24b raised caspase-8 level by about 7 folds, compared to 8 folds reported for thalidomide. Also, VEGF level in HepG-2 cells treated with 24b was 185.3 pg mL-1, compared to 432.5 pg mL-1 in control cells. Furthermore, the immunomodulatory properties were proven to 24b, which reduced TNF-α level by approximately half. At the same time, NF-κB P65 level in HepG-2 cells treated with 24b was 76.5 pg mL-1 compared to 278.1 and 110.5 pg mL-1 measured for control cells and thalidomide treated HepG-2 cells respectively. Moreover, an in vitro viability study against Vero non-cancerous cell line was investigated and the results reflected a high safety profile of all tested compounds. This work suggests 24b as a promising lead compound for development of new immunomodulatory anticancer agents.

Discovery of New VEGFR-2 Inhibitors: Design, Synthesis, Anti-Proliferative Evaluation, Docking, and MD Simulation Studies.

Four new nicotinamide-based derivatives were designed as antiangiogenic VEGFR-2 inhibitors. The congeners were synthesized possessing the pharmacophoric essential features to bind correctly with the VEGFR-2 active pocket. All members were evaluated for their cytotoxic and VEGFR-2 inhibitory potentialities. Compound 6 was the most potent showingIC50 values of 9.3 ± 0.02 and 7.8 ± 0.025 µM against HCT-116 and HepG-2 cells, respectively, and IC50 of 60.83 nM regarding VEGFR-2 enzyme inhibition. Compound 6 arrested the growth of HCT-116 cells at the pre-G1 and G2-M phases. Further, it induced both early and late apoptosis. Additionally, compound 6 caused a significant decrease in TNF-α and IL6 by 66.42% and 57.34%, respectively. The considered compounds had similar docking performances to that of sorafenib against the VEGFR-2 (PDB ID: 2OH4). The correct binding of compound 6 with VEGFR-2 was validated using MD simulations, and MM-GPSA calculations.