Khaled O. Alsaad

Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection – clinicopathological and ultrastructural study

The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome – coronavirus (MERS‐CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS‐CoV infection and represent a base of MERS‐CoV histopathology.

Magnetic Fluorescent Nanoformulation for Intracellular Drug Delivery to Human Breast Cancer, Primary Tumors, and Tumor Biopsies: Beyond Targeting Expectations

We report the development of a chemotherapeutic nanoformulation made of polyvinylpyrrolidone-stabilized magnetofluorescent nanoparticles (Fl-PMNPs) loaded with anticancer drugs as a promising drug carrier homing to human breast cancer cells, primary tumors, and solid tumors. First, nanoparticle uptake and cell death were evaluated in three types of human breast cells: two metastatic cancerous MCF-7 and MDA-MB-231 cells and nontumorigenic MCF-10A cells. While Fl-PMNPs were not toxic to cells even at the highest concentrations used, Dox-loaded Fl-PMNPs showed significant potency, effectively killing the different breast cancer cells, albeit at different affinities. Interestingly and superior to free Dox, Dox-loaded Fl-PMNPs were found to be more effective in killing the metastatic cells (2- to 3-fold enhanced cytotoxicities for MDA-MB-231 compared to MCF-7), compared to the normal noncancerous MCF-10A cells (up to 8-fold), suggesting huge potentials as selective anticancer agents. Electron and live confocal microscopy imaging mechanistically confirmed that the nanoparticles were successfully endocytosed and packaged into vesicles inside the cytoplasm, where Dox is released and then translocated to the nucleus exerting its cytotoxic action and causing apoptotic cell death. Furthermore, commendable and enhanced penetration in 3D multilayered primary tumor cells derived from primary lesions as well as in patient breast tumor biopsies was observed, killing the tumor cells inside. The designed nanocarriers described here can potentially open new opportunities for breast cancer patients, especially in theranostic imaging and hyperthermia. While many prior studies have focused on targeting ligands to specific receptors to improve efficacies, we discovered that even with passive-targeted tailored delivery system enhanced toxic responses can be attained.

Fatal Subacute Hepatic Failure in a Patient with AA-Type Amyloidosis: Case Report

Although systemic amyloidosis of amyloid-associated protein (AA) type (secondary or reactive amyloidosis) frequently involves the liver, it rarely causes clinically apparent liver disease. Mild elevation of alkaline phosphatase and hepatomegaly are the most common biochemical and clinical findings, respectively. We report a case of systemic amyloidosis of AA type, which clinically presented as subacute hepatic failure and resulted in a fatal clinical course in a 69-year-old man. To the best of our knowledge, this is the fifth case of hepatic amyloidosis of AA type that clinically presented as fatal subacute hepatic failure, an unusual clinical presentation for hepatic involvement by systemic AA-type amyloid.

Ultra-Small fatty acid-stabilized magnetite nanocolloids synthesized by in situ hydrolytic precipitation

Simple, fast, large-scale, and cost-effective preparation of uniform controlled magnetic nanoparticles remains a major hurdle on the way towards magnetically targeted applications at realistic technical conditions. Herein, we present a unique one-pot approach that relies on simple basic hydrolytic in situ coprecipitation of inexpensive metal salts (Fe2+ and Fe3+) compartmentalized by stabilizing fatty acids and aided by the presence of alkylamines. The synthesis was performed at relatively low temperatures (∼80°C) without the use of high-boiling point solvents and elevated temperatures. This method allowed for the production of ultra-small, colloidal, and hydrophobically stabilized magnetite metal oxide nanoparticles readily dispersed in organic solvents. The results reveal that the obtained magnetite nanoparticles exhibit narrow size distributions, good monodispersities, high saturation magnetizations, and excellent colloidal stabilities. When the [fatty acid] : [Fe] ratio was varied, control over nanoparticle diameters within the range of 2-10 nm was achieved. The amount of fatty acid and alkylamine used during the reaction proved critical in governing morphology, dispersity, uniformity, and colloidal stability. Upon exchange with water-soluble polymers, the ultra-small sized particles become biologically relevant, with great promise for theranostic applications as imaging and magnetically targeted delivery vehicles.

Predictors of significant fibrosis in chronic hepatitis B patients with low viremia.

Background and Aim: The data on the prevalence and predictors of significant fibrosis (≥F2, METAVIR) in chronic hepatitis B virus (HBV) patients with low viremia are limited. We aimed to assess both the prevalence predictors of ≥F2 fibrosis in hepatitis B envelope antigen-negative patients with HBV DNA <20,000 IU/mL. Methods: Hepatitis B envelope antigen-negative patients (n=213) with mean HBV DNA <2000 IU/mL (n=97) and HBV DNA 2000 to 20,000 IU/mL (n=116) were included and all had liver biopsy. Variables significantly associated with ≥F2 fibrosis on an univariate analysis were included in a multivariate logistic regression model. Results: Overall, 40 (18.8%) patients had ≥F2 fibrosis, with no difference between those with mean HBV DNA <2000 IU/mL (19.6%) compared with patients with HBV DNA of 2000 to 20,000 IU/mL (18.1%; P=0.782). Fibrosis ≥F2 was similar in patients with HBV DNA <2000 versus 2000 to 20,000 IU/mL in relation to varying alanine aminotransferase thresholds (P>0.05), and was less frequent in persistently normal alanine aminotransferase patients (13.6%) when compared with those with elevated or fluctuating levels (25.3%, P=0.030). Fewer patients under 40 years of age had ≥F2 fibrosis (12.5%) as compared with older ones (28.2%; P=0.004). Logistic regression analysis identified higher aspartate aminotransferase [odds ratio (OR), 6.21; 95% confidence interval (CI), 2.48-15.54; P<0.0001], lower albumin (OR, 0.86; 95% CI, 0.78-0.95; P=0.002), platelet count (OR, 0.99; 95% CI, 0.98-0.99; P=0.013), and age (OR, 1.05; 95% CI, 1.01-1.09; P=0.024) as independent predictors of significant fibrosis. Conclusions: A small but significant minority of HBV patients with low viremia harbor significant fibrosis, although its rate is not different in those with viremia above or below 2000 IU/mL. Our findings may guide in decisions regarding liver biopsy and treatment in this category of patients.

Urinary bladder radiotherapy-related chondroblastic osteosarcoma: Rare case report and review of literature

Radiation-related osteosarcomas are well described malignant mesenchymal neoplasms, yet their pathogenesis is not fully understood. They are generally classified into either skeletal osteosarcomas, or their and rare soft tissue counterpart. The occurrence of osteosarcoma in the urinary bladder (UB) following radiotherapy is exceedingly rare. To the best of our knowledge, only two cases of radiation-related urinary bladder osteosarcoma have been published; we herein describe another case of an 85-year-old man who developed post radiotherapy chondroblastic osteosarcoma of the urinary bladder four years following initial surgical resection and radiotherapy for bladder urothelial carcinoma. We believe that this is the first case of radiation-related chondroblastic osteosarcoma arising in the urinary bladder. In addition, we review the literature and explore the possible histogenesis of this rare neoplasm.

Clinical Presentation, Treatment Outcome and Predictors of Severity in Autoimmune Hepatitis: A Retrospective, Multicenter Experience: Aljumah AA et al . Predictors of severity in AIH

AIM: Autoimmune Hepatitis (AIH) is a chronic hepatitis of unknown etiology. It affects adults and children and can progress to cirrhosis. We aim to investigate the mode of presentation, predictors of severity and treatment outcome of AIH in Saudi patients. METHODS: This is a multicenter retrospective study that involved patients diagnosed with AIH from 3 tertiary hospitals. Clinical, biochemical, radiological and histopathological data were collected and treatment outcomes were reported. RESULTS: A total of 212 patients were included. Female: male ratio was 3:2 and the mean age was 36.2 ± 16.8 years while 50 patients (23.6%) were above age of 50. Abnormal liver function tests (LFTs) were found in (45%). Presentation was chronic in 37.7%, acute in 30.7%, with evidence of liver cirrhosis in 28.8% and with a fulminant disease in 2.8%. Antinuclear antibody (ANA) and Anti-smooth muscle antibody (ASMA) were negative in 65 (30.6%) and 74 (35%) patients respectively. Pre-treatment liver biopsies in 166 patients showed advanced fibrosis (stage 3 and 4) in 63.3%. On multivariate analysis, platelets, alanine transaminase (ALT) level and immunoglobulin G (IgG) level were predictors of fibrosis. Complete response was achieved in 74.5% while 9% had partial response and 16.5% had no response to treatment. CONCLUSION: The majority of AIH patients had advanced fibrosis at the time of diagnosis and liver cirrhosis was found in nearly one-third of cases. IgG, ALT, and platelet were predictors of advanced fibrosis. Complete response to treatment was achieved in two-third of patients. Relying on autoimmune markers for diagnosis can be misleading.