Optimized serum ferritin prediction of iron overload in transfusion-dependent thalassemia: likelihood ratio and age-adjustment approach.

BACKGROUND: Early detection of iron overload in transfusion-dependent thalassemia (TDT) patients is critical to prevent complications and improve survival. OBJECTIVES: Evaluate the utility of serum ferritin (SF) in the prediction of hepatic and myocardial iron overload (HIO and MIO) compared to T2*-MRI. DESIGN: Retrospective SETTINGS: Governmental hospitals. PATIENTS AND METHODS: Patients with TDT who had T2*-MRI examinations between January 2016 to October 2019 were included. The predictive value of SF for detection of HIO and MIO was assessed by measuring area under the curve (AUC). A sample size of 123 cases was calculated to detect a correlation of 0.25 with 90% power and a two-sided type I error of 0.05. MAIN OUTCOME MEASURES: The correlation between SF and estimated hepatic iron concentration. SAMPLE SIZE: 137 TDT patients who required regular blood transfusions. RESULTS: The predictive value of SF was excellent for detection of HIO (AUC=0.83-0.87) but fair for detection of MIO (AUC=0.67). The two independent predictors of MIO were age and SF. The log of (age × SF) enhanced the SF predictive value for MIO (AUC=0.78). SF values of 700 and 1250 mg/L effectively excluded mild and moderate HIO with a sensitivity of 97.8% and 94.2%, respectively (LR-=0.1). While SF values of 1640 and 2150 mg/L accurately diagnosed mild and moderate HIO with a specificity of 95.55% and 96.4%, respectively (LR+>10). A log of (age × SF) cut-off value of 4.15 effectively excluded MIO (LR-=0.1), while a value of 4.65 moderately confirmed MIO (LR+=3.2). CONCLUSIONS: SF is an excellent predictor of hepatic IO in TDT. Age adjustment enhanced its myocardial IO predictive accuracy. Likelihood ratio-based SF cut-off values may help clinicians in risk stratification and treatment decision-making. LIMITATIONS: The laboratory data were gathered retrospectively and although the risk of selection bias for T2*-MRI examination is thought to be low, it cannot be ignored. CONFLICT OF INTEREST: None.

Superior Mediastinal Syndrome Misdiagnosed as Foreign Body Aspiration: A Case Report.

Superior mediastinal syndrome is a life-threatening pediatric oncological emergency that requires high level of awareness and clinical suspicion to avoid misdiagnosis and devastating outcomes. Early diagnostic evaluation and management of underlying etiology are of utmost significance for optimal results. In children, it is most commonly caused by non-Hodgkin's lymphoma and T-cell lymphoblastic leukemia. We report a case of a six-year-old boy with superior mediastinal syndrome secondary to T-cell acute lymphoblastic leukemia, initially misdiagnosed as foreign body aspiration and underwent a procedure with a life-threatening outcome.

Natural Products/Bioactive Compounds as a Source of Anticancer Drugs.

Cancer is one of the major deadly diseases globally. The alarming rise in the mortality rate due to this disease attracks attention towards discovering potent anticancer agents to overcome its mortality rate. The discovery of novel and effective anticancer agents from natural sources has been the main point of interest in pharmaceutical research because of attractive natural therapeutic agents with an immense chemical diversity in species of animals, plants, and microorganisms. More than 60% of contemporary anticancer drugs, in one form or another, have originated from natural sources. Plants and microbial species are chosen based on their composition, ecology, phytochemical, and ethnopharmacological properties. Plants and their derivatives have played a significant role in producing effective anticancer agents. Some plant derivatives include vincristine, vinblastine, irinotecan, topotecan, etoposide, podophyllotoxin, and paclitaxel. Based on their particular activity, a number of other plant-derived bioactive compounds are in the clinical development phase against cancer, such as gimatecan, elomotecan, etc. Additionally, the conjugation of natural compounds with anti-cancerous drugs, or some polymeric carriers particularly targeted to epitopes on the site of interest to tumors, can generate effective targeted treatment therapies. Cognizance from such pharmaceutical research studies would yield alternative drug development strategies through natural sources which could be economical, more reliable, and safe to use.

General Nutritional Profile of Bee Products and Their Potential Antiviral Properties against Mammalian Viruses.

Bee products have been extensively employed in traditional therapeutic practices to treat several diseases and microbial infections. Numerous bioactive components of bee products have exhibited several antibacterial, antifungal, antiviral, anticancer, antiprotozoal, hepatoprotective, and immunomodulatory properties. Apitherapy is a form of alternative medicine that uses the bioactive properties of bee products to prevent and/or treat different diseases. This review aims to provide an elaborated vision of the antiviral activities of bee products with recent advances in research. Since ancient times, bee products have been well known for their several medicinal properties. The antiviral and immunomodulatory effects of bee products and their bioactive components are emerging as a promising alternative therapy against several viral infections. Numerous studies have been performed, but many clinical trials should be conducted to evaluate the potential of apitherapy against pathogenic viruses. In that direction, here, we review and highlight the potential roles of bee products as apitherapeutics in combating numerous viral infections. Available studies validate the effectiveness of bee products in virus inhibition. With such significant antiviral potential, bee products and their bioactive components/extracts can be effectively employed as an alternative strategy to improve human health from individual to communal levels as well.

Nicotine and cotinine quantification after a 4-week inhalation of electronic cigarette vapors in male and female mice using UPLC-MS/MS.

OBJECTIVES: To detect the cotinine and nicotine serum concentrations of female and male C57BL/6J mice after a 4-week exposure to electronic (e)-cigarette vapors using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). METHODS: This experimental study was carried out at an animal facility and laboratories, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, between January and August 2020. A 4-week exposure to e-cigarettes was carried out using male and female mice and serum samples were obtained for cotinine and nicotine quantification using UPLC-MS/MS. The chromatographic procedures involved the use of a BEH HSS T3 C18 column (100 mm x 2.1 mm, 1.7 µm) with acetonitrile as a mobile phase and 0.1% formic acid (2:98 v/v). RESULTS: The applied methodology has highly efficient properties of detection, estimation, and extraction, where the limit of quantification (LOQ) for nicotine was 0.57 ng/mL and limit of detection (LOD) for nicotine was 0.19 ng/mL, while the LOQ for cotinine was 1.11 ng/mL and LOD for cotinine was 0.38 ng/mL. The correlation coefficient was r2>0.99 for both compounds. The average recovery rate was 101.6±1.33 for nicotine and 100.4±0.54 for cotinine, while the precision and accuracy for cotinine and nicotine were less than 6.1. The serum cotinine level was higher in males (433.7±19.55) than females (362.3±16.27). CONCLUSION: This study showed that the gender factor might play a crucial role in nicotine metabolism.

Lipid-Based Nanoparticle Formulation of Diallyl Trisulfide Chemosensitizes the Growth Inhibitory Activity of Doxorubicin in Colorectal Cancer Model: A Novel In Vitro, In Vivo and In Silico Analysis.

Garlic's main bioactive organosulfur component, diallyl trisulfide (DATS), has been widely investigated in cancer models. However, DATS is not suitable for clinical use due to its low solubility. The current study seeks to improve DATS bioavailability and assess its chemopreventive and chemosensitizing properties in an AOM-induced colorectal cancer model. The polyethylene glycol coated Distearoylphosphatidylcholine/Cholesterol (DSPC/Chol) comprising DATS-loaded DATSL and doxorubicin (DOXO)-encapsulated DOXL liposomes was prepared and characterized. The changes in the sensitivity of DATS and DOXO by DATSL and DOXL were evaluated in RKO and HT-29 colon cancer cells. The synergistic effect of DATSL and DOXL was studied by cell proliferation assay in the combinations of IC10, IC25, and IC35 of DATSL with the IC10 of DOXL. AOM, DATSL, and DOXL were administered to different groups of mice for a period of 21 weeks. The data exhibited ~93% and ~46% entrapment efficiency of DATSL and DOXL, respectively. The size of sham liposomes was 110.5 nm, whereas DATSL and DOXL were 135.5 nm and 169 nm, respectively. DATSL and DOXL exhibited significant sensitivity in the cell proliferation experiment, lowering their IC50 doses by more than 8- and 14-fold, respectively. However, the DATSL IC10, IC25, and IC35 showed escalating chemosensitivity, and treated the cells in combination with DOXL IC10. Analysis of histopathological, cancer marker enzymes, and antioxidant enzymes revealed that the high dose of DATSL pretreatment and DOXL chemotherapy is highly effective in inhibiting AOM-induced colon cancer promotion. The combination of DATSL and DOXL indicated promise as a colorectal cancer treatment in this study. Intermolecular interactions of DATS and DOXO against numerous cancer targets by molecular docking indicated MMP-9 as the most favourable target for DATS exhibiting binding energy of -4.6 kcal/mol. So far, this is the first research to demonstrate the chemopreventive as well as chemosensitizing potential of DATSL in an animal model of colorectal cancer.

The Effect of Liposomal Diallyl Disulfide and Oxaliplatin on Proliferation of Colorectal Cancer Cells: In Vitro and In Silico Analysis.

Diallyl disulfide (DADS) is one of the main bioactive organosulfur compounds of garlic, and its potential against various cancer models has been demonstrated. The poor solubility of DADS in aqueous solutions limits its uses in clinical application. The present study aimed to develop a novel formulation of DADS to increase its bioavailability and therapeutic potential and evaluate its role in combination with oxaliplatin (OXA) in the colorectal cancer system. We prepared and characterized PEGylated, DADS (DCPDD), and OXA (DCPDO) liposomes. The anticancer potential of these formulations was then evaluated in HCT116 and RKO colon cancer cells by different cellular assays. Further, a molecular docking-based computational analysis was conducted to determine the probable binding interactions of DADS and OXA. The results revealed the size of the DCPDD and DCPDO to be 114.46 nm (95% EE) and 149.45 nm (54% EE), respectively. They increased the sensitivity of the cells and reduced the IC50 several folds, while the combinations of them showed a synergistic effect and induced apoptosis by 55% in the cells. The molecular docking data projected several possible targets of DADS and OXA that could be evaluated more precisely by these novel formulations in detail. This study will direct the usage of DCPDD to augment the therapeutic potential of DCPDO against colon cancer in clinical settings.

Anti-neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis Secondary to Hydralazine: A Case Report.

Hydralazine is a vasodilator used in the treatment of resistant hypertension. It is a safe and widely used antihypertensive medicine. Its common adverse effects include headache, rebound tachycardia, fluid retention, and angina. It is a rare cause of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with pulmonary and renal involvement. We report a case of a 74-year-old woman, with over eight years of use of hydralazine, who presented to the hospital with shortness of breath and cough. Blood work revealed deranged renal function with high creatinine levels. Serology workup was positive for anti-histone antibodies (AHA), anti-nuclear antibodies (ANA), myeloperoxidase (MPO) ANCA and proteinase-3 (PR-3) ANCA. Renal biopsy showed diffusely flattened tubular epithelium, focal micro vesicular degeneration, and focal loss of the brush border of the proximal tubular epithelium. Hydralazine was stopped and the patient was treated with corticosteroids, resulting in the resolution of her kidney injury.

The value of [68Ga]Ga-DOTA-TATE PET/CT in diagnosis and management of suspected pituitary tumors.

BACKGROUND: Gallium 68-tetraazacyclododecane-tetraacetic acid-octreotate ([68Ga]Ga-DOTA-TATE) is a selective somatostatin analogue ligand, which shows increased affinity for somatostatin receptor subtype (SSTR) 2 and has been used routinely for imaging neuroendocrine tumors with PET/CT. We investigated the utility of [68Ga]Ga-DOTA-TATE positron emission tomography/computed tomography (PET/CT) in patients with suspected pituitary pathology. We reviewed imaging for twenty consecutive patients (8 men, 12 women, mean age of 48.2, range 14-78) with suspected pituitary pathology who were referred for [68Ga]Ga-DOTA-TATE PET/CT. RESULTS: Nine patients presented with recurrent Cushing's syndrome following surgical resection of pituitary adenomas due to recurrent Cushing's disease (seven patients) and ectopic ACTH secreting tumor (2 patients). All seven patients with recurrent Cushing's disease showed positive pituitary [68Ga]Ga-DOTA-TATE uptake while both cases of ectopic hormonal secretion had absented pituitary uptake. In 1 of these 2 patients, [68Ga]Ga-DOTA-TATE was able to localize the source of ectopic ACTH tumor. Six patients presented de novo with Cushing's due to ectopic ACTH secretion; [68Ga]Ga-DOTA-TATE PET/CT was able to localize ectopic tumors in six of eight patients (3 lungs, 2 pancreases, 1 mid-gut) There was high uptake [68Ga]Ga-DOTA-TATE in 3 cases of recurrent central hyperthyroidism (SUVmax 6.6-14.3) and 2 cases of prolactinoma (SUVmax 5.5 and 11.3). CONCLUSION: Absent [68Ga]Ga-DOTA-TATE activity in the pituitary fossa is useful in excluding pituitary disease in recurrent Cushing's. Recurrent pituitary thyrotropinomas and prolactinomas showed moderate to high pituitary activity. In addition, in Cushing's syndrome, [68Ga]Ga-DOTA-TATE is useful for detection of ectopic sources of ACTH production, especially where anatomic imaging is negative.

Possible Tracheal Relaxant and Antimicrobial Effects of the Essential Oil of Ethiopian Thyme Species (Thymus serrulatus Hochst. ex Benth.): A Multiple Mechanistic Approach.

The genus Thymus is traditionally used for the treatment of hyperactive airways complaints. The purpose of the current study is to investigate the potential tracheal relaxant effect and possible mechanism(s) of the essential oil of Thymus serrulatus (TS Oil) in isolated guinea pig tracheal tissues. The essential oil was obtained from the fresh erial parts of Thymus serrulatus, and its phyto-components were identified by GC-MS analysis. Guinea pig tracheal preparations were used for testing the tracheal relaxant effect of TS Oil with the determination of the mechanism(s) involved in this relaxation. GC-MS findings reveal that terpenes, fragrance constituents, saponins, and higher fatty acids are present in TS Oil. In isolated guinea pig trachea, TS Oil inhibited carbachol (CCh, 1 µM) and K+ (80 mM)-induced contractions in a pattern similar to that of dicyclomine. TS Oil, at 0.3 mg/ml, shifted parallel CCh-curves towards the right, followed by a non-parallel shift at higher concentration (1 mg/ml), thus suppressing maximum response in the same manner as produced by dicyclomine. Pretreatment of tissues with TS Oil (1 and 3 mg/ml) also produced a rightward shift of Ca++ concentration-response curves (CRCs) in the same manner as caused by verapamil. Further, TS Oil at low concentrations (0.3 and 1 mg/ml) shifted isoprenaline-induced inhibitory CRCs towards the left and increased cAMP levels in isolated tracheal homogenates similar to papaverine, a phosphodiesterase (PDE) inhibitor. In the antimicrobial assay performed by the agar well diffusion method, TS Oil was found most active against Candida albicans and Staphylococcus aureus where the zone of inhibition measured was 28 mm. Additionally, there was little difference between standard strains of gram-positive and gram-negative bacteria. However, methicillin-resistant S. aureus (MRSA) showed a small zone of inhibition as compared to standard strains (22 mm). From these results, it can be concluded that the essential oil of T. serrulatus has the potential to produce antimicrobial effects while causing tracheal relaxation mediated possibly by anticholinergic effects, Ca++ channel blockade, and PDE inhibition whereas additional mechanism(s) cannot be ruled out.

Decline in radioiodine use but not total thyroidectomy in thyroid cancer patients treated in the United Arab Emirates - A retrospective study.

OBJECTIVES: To assess the trend of clinicopathological features and treatment modalities in patients with thyroid cancer (TC) in the largest oncology center in the United Arab Emirates (UAE). METHODS: A retrospective analysis of patients with TC presenting to a tertiary care hospital in Al Ain, UAE between September 2008 and December 2018 identified using ICD 9 & 10 codes was performed. Data on demographics, histopathology, surgical extent, and use of Radioiodine (RAI) were extracted. Exact logistic and ordinal logistic regressions were performed to analyze the annual trend in features and management of TC, and logistic regression analysis was performed to identify predictors of total thyroidectomy and RAI use. RESULTS: A total of 762 patients were included in the analysis (mean age: 39.6 ± 12.6 years, 45 (60%) women). The majority (92.2%) were diagnosed with papillary thyroid cancer (PTC) and 83.9% had tumor size of <4 cm. All patients underwent surgery (93.8% total thyroidectomy, 6.2% lobectomy) and 77.4% received RAI therapy overall with a significant (p < 0.001) decline from 100% in 2008 to 60% in 2018. In multivariate analysis, nationality, and lymph node (LN) involvement were significant predictors of total thyroidectomy, while nationality, LNs, year of diagnosis, and tumor size significantly predicted RAI use. CONCLUSION: Most patients in our cohort were diagnosed with localized PTC with no significant change in the extent of surgical approach but a substantial decline in RAI therapy administration over time. Nationality and LN involvement were significant predictors of surgical extent and RAI use.

Liposomal drug delivery of Corchorus olitorius leaf extract containing phytol using design of experiment (DoE): In-vitro anticancer and in-vivo anti-inflammatory studies.

Phytol, a pharmacologically active compound present in Corchorus olitorius leaf exhibit a range of activity including anti-inflammatory, antioxidant, anticancer, hepatoprotective etc. However, phytol is poorly soluble and absorbed through the intestine wall, therefore the aim of this study is to develop liposomal drug delivery of Corchorus olitorius leaf extract with an average particle size below 150 nm and drug loading efficiency of ≥ 85 %. The impact of different process parameters and material attributes were studied on the average particle size and polydispersity of liposomal batches using design of experiment (DoE). Corchorus olitorius leaf extraction was performed using maceration method and characterised using GC-MS. Liposomal batches of Corchorus olitorius leaf extract were characterized using Malvern zetasizer, transmission electron microscopy (TEM) and UV spectroscopy. The in-vivo anti-inflammatory study of the liposomal preparation of phytol was evaluated using a rat model and in-vitro cancer cell line study was performed on AML and Leukamia cell lines. GC-MS study data showed that phytol is present in C. olitorius leaf extract. Process parameters and material attributes perspective processing temperature, buffer pH and drug: lipid ratio is found as major parameters affecting the average particle size and PDI value of liposomes. Liposomes were prepared in the range of 80-250 nm and optimized batches of liposomes showed drug entrapment efficiency of 60-88 %. In-vivo anti-inflammatory study showed significant activity for C. olitorius leaf extract against carrageenan induced paw edema, which is significantly increased while delivered through liposomes. In-vitro cancer cell line study data suggests that liposomal delivery of phytol was more active at lower concentration compared to pure phytol, for specific cell lines.

Phytochemical constituents and anticancer activities of Tarchonanthus camphoratus essential oils grown in Saudi Arabia.

Tarchonanthus Camphoratus L. is traditionally known for its various medicinal purposes. In this study, the T. camphoratus essential oil (TCEO) was isolated via steam distillation, and its chemical constituents were determined using GC-MS. The in vitro antiproliferative effects of TCEO on A549, HepG2, MCF-7 cancer cells, and HUVEC non-tumor cells was investigated using an MTT assay. Flow cytometry analysis was conducted to evaluate cell cycle distribution using propidium iodide staining, and cell death mode using Annexin V-FITC/PI assays. The expression of some apoptosis related genes was investigated using qRT-PCR. Major constituents of TCEO included fenchol, borneol, 3-cyclohexene-1-methanol and 3-ethyl-3-methyl. Cell viability test showed that TCEO is highly effective against MCF-7 cells with IC50 12.5 µg/mL. Cell cycle arrest at the G1/S phase, and apoptosis mediation were evident in the presence of TCEO. Gene expression analysis of several pro-apoptotic and anti-apoptotic genes revealed the initiation of apoptosis in TCEO-MCF-7 cells. In conclusion, our study confirms the antiproliferative activity of the T. camphoratus essential oil.

Combination Treatment with Sodium Nitrite and Isoquercetin on Endothelial Dysfunction among Patients with CKD: A Randomized Phase 2 Pilot Trial.

BACKGROUND AND OBJECTIVES: Endothelial dysfunction is common among patients with CKD. We tested the efficacy and safety of combination treatment with sodium nitrite and isoquercetin on biomarkers of endothelial dysfunction in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, double-blind, placebo-controlled phase 2 pilot trial enrolled 70 patients with predialysis CKD. Thirty-five were randomly assigned to combination treatment with sodium nitrite (40 mg twice daily) and isoquercetin (225 mg once daily) for 12 weeks, and 35 were randomly assigned to placebo. The primary outcome was mean change in flow-mediated vasodilation over the 12-week intervention. Secondary and safety outcomes included biomarkers of endothelial dysfunction, inflammation, and oxidative stress as well as kidney function, methemoglobin, and adverse events. Intention-to-treat analysis was conducted. RESULTS: Baseline characteristics, including age, sex, race, cigarette smoking, history of hypertension and diabetes, use of renin-angiotensin system blockers, BP, fasting glucose, lipid profile, kidney function, urine albumin-creatinine ratio, and endothelial biomarkers, were comparable between groups. Over the 12-week intervention, flow-mediated vasodilation increased 1.1% (95% confidence interval, -0.1 to 2.3) in the treatment group and 0.3% (95% confidence interval, -0.9 to 1.5) in the placebo group, and net change was 0.8% (95% confidence interval, -0.9 to 2.5). In addition, changes in biomarkers of endothelial dysfunction (vascular adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, vWf, endostatin, and asymmetric dimethylarginine), inflammation (TNF-α, IL-6, C-reactive protein, IL-1 receptor antagonist, and monocyte chemoattractant protein-1), and oxidative stress (oxidized LDL and nitrotyrosines) were not significantly different between the two groups. Furthermore, changes in eGFR, urine albumin-creatinine ratio, methemoglobin, and adverse events were not significantly different between groups. CONCLUSIONS: This randomized phase 2 pilot trial suggests that combination treatment with sodium nitrite and isoquercetin did not significantly improve flow-mediated vasodilation or other endothelial function biomarkers but also did not increase adverse events compared with placebo among patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Nitrite, Isoquercetin, and Endothelial Dysfunction (NICE), NCT02552888.

Membranous Glomerulonephritis as an Uncommon Presentation of Secondary Syphilis: A Reminder on Therapeutic Decision-Making in Clinical Practice.

Membranous glomerulonephritis is one of the common causes of nephrotic syndrome in the adult population. It is idiopathic in the majority of patients, but the secondary forms can be seen in the setting of autoimmune disease, cancer, infection, and following exposure to certain medications. However, subclinical syphilis-related membranous nephropathy remains a particularly rare clinicopathologic entity in modern times. In this article, we chronicle an interesting case of latent syphilis masquerading as membranous glomerulonephritis, which resolved with benzathine penicillin without requiring immunosuppressive treatment. We further supplement this paper with a concise review of the relevant literature that delineates the utility of appropriate antibiotic therapy in the management of luetic membranous nephropathy. Clinicians should remain cognizant of secondary syphilis while evaluating patients for possible glomerulonephritis or those presenting with proteinuria. Additionally, patients with hepatitis B, hepatitis C, and human immunodeficiency virus infections are not infrequently coinfected with Treponema pallidum. Therefore, a high index of suspicion for systemic manifestations of syphilis such as nephrotic syndrome is warranted in the setting of a coinfection. Prompt diagnosis and treatment of syphilis may result in resolution of proteinuria, without the need for standard immunosuppressive therapy commonly used in clinical practice.

Primary renal lymphoma: a comprehensive review of the pathophysiology, clinical presentation, imaging features, management and prognosis.

Primary renal lymphoma (PRL) is defined as a non-Hodgkin's lymphoma restricted to kidneys with the absence of extensive nodal disease. It is an exceedingly rare clinicopathological entity, accounting for 0.7% of extranodal lymphomas. Published medical literature regarding the natural history and clinical outcomes of PRL remains limited. We describe a case of a young patient who presented with left shoulder pain, continuous fever, and unexplained weight loss as atypical initial manifestations of bilateral PRL, confirmed with the standard set of investigations. Furthermore, this article reviews the literature and discusses various aspects of PRL, including pathophysiology, presentation patterns, imaging and pathological characteristics, management, and prognosis. This paper serves to provide an update and aims to enhance the understanding of PRL. Timely diagnosis and treatment are imperative to achieve improved outcomes. Clinicians should maintain a high index of suspicion in order to prevent morbidity and mortality associated with this serious disease.

The protective effect of losartan against sorafenib induced cardiotoxicity: Ex-vivo isolated heart and metabolites profiling studies in rat.

Sorafenib, a tyrosine kinase inhibitor that is used in the treatment of hepatocellular and renal cell carcinoma, was reported to induce cardiotoxicity. This study aimed to investigate the potential cardioprotective effect of losartan against sorafenib-induced cardiotoxicity in rat. Sorafenib significantly reduced the left ventricular pressure, heart rate dp/dt max & dp/dt min (indexes of myocardial contractility and relaxation; respectively), and prolonged both the systolic and diastolic periods. Coadminstration of losartan significantly reversed the effects of sorafenib on heart rate, dp/dt max and dp/dt min. In addition, there was a tendency for losartan to reverse sorafenib reduction in left ventricular pressure and perfusion pressure but it did not reach statistical significance. A GC-MS non-targeted based metabolites profiling of rat plasma revealed elevated metaboites, including urea and fatty acids levels, associated with sorafenib induced cardiotoxicity. However, only glycine and lactic acid were statistically significant. Interestingly, losartan co-administration with sorafenib restored these changes, and resulted in a significantly reduced glycine, urea and some fatty acids levels namely; Cis-vaccenic acid, oleic acid, stearic acid and undecanoic acid. In addition, based on histology results, losartan coadminitration almost obviated sorafenib-induced changes in cardiac tissues. The study suggests that losartan has the potential to exert a protective effect against sorafenib-induced cardiotoxicity.

The value of 18F-FDG PET-CT and 131I-norcholesterol scintigraphy in the characterization of high-risk adrenal masses.

PURPOSE: To assess the value of F-FDG PET-computed tomography (CT) and I-norcholesterol scintigraphy in noninvasive characterization of high-risk adrenal lesions using surgical pathology as the gold standard. METHODS: We retrospectively reviewed clinical cases referred to the adrenal multidisciplinary team in a tertiary centre over the last 6 years. Inclusion criteria were the presence of indeterminate adrenal lesions and performance of combined imaging with 2-deoxy-2-[fluorine-18] fluoro- D-glucose Positron emission tomography/ computed tomography and I-norcholesterol scans. The accuracy of CT, PET-CT and I-norcholesterol findings was assessed by comparison with the postoperative histopathological outcome. RESULTS: Sixteen patients fulfilled the inclusion criteria. Ten underwent unilateral adrenalectomy, and six had clinical follow-up. The number of cases categorized as concerning on the basis of unenhanced CT, F-FDG PET-CT and I-norcholesterol was 11, 9 and 2, respectively. The mean diameter of adrenal lesions was 4.5 ± 1.9 cm. Average SUVmax of the FDG-avid adrenal lesions was 5.0 ± 2.0 (range 3.5-9.7). Fourteen adrenal masses showed I-norcholesterol uptake. All adrenal masses turned out to be benign lesions. CONCLUSION: Conventional CT and FDG PET parameters are not adequately specific for determination of a benign lesion in this selected cohort of high-risk patients. Use of I-norcholesterol in this patient cohort may provide additional value.

Treatment of cardiac nocardiosis in a post-renal transplant patient of systemic nocardiosis.

In general, nocardia infects immunosuppressed patients, however, sometimes it can also infect immunocompetent individuals. Nocardia infection can disseminate to any organ system of the body but the pulmonary system is the most commonly involved system. In some rare cases, the heart can also be involved and the resulting cardiac mycetoma can be treated successfully with antimicrobials without the need of surgery, unlike fungal cardiac mycetomas wherein surgery may be required in addition to antimicrobial therapy. We present an interesting case of post-renal transplant cardiac nocardiosis, which was treated successfully with a course of antibiotics.

Stenotrophomonas skull base osteomyelitis presenting as necrotizing otitis externa: Unmasking by CT and MRI-case report and review.

Necrotizing or malignant otitis externa in patients presenting with mild clinical findings can pose as a tip of the iceberg; computed tomography (CT) and/or magnetic resonance imaging (MRI) unveils the clinical-imaging discrepancy and unmasks the presence of skull-base osteomyelitis (SBO). Pseudomonas aeruginosa is the most common causative pathogen of SBO, followed by fungal and other rare bacterial organisms. This report presents a rare case in an elderly diabetic patient, where the pathogen Stenotrophomonas maltophilia was isolated. There have been no previous reported cases in the literature of SBO caused by this pathogen. The hallmark of SBO on computed tomography or magnetic resonance imaging is soft tissue inflammatory changes under the central skull base with associated bone erosion. This may result in the peculiar appearance of the "Ovoid Gap" sign. SBO can be due to nonotogenic sources, namely: sinogenic, rhinogenic, pharnygogenic, or odontogenic infections. Low threshold for imaging is advised in immunosuppressed and elderly diabetic patients.