Publications by authors named "Vimal Patel"

121 Publications

Enhanced Solubility and Bioavailability of Dolutegravir by Solid Dispersion Method: In Vitro and In Vivo Evaluation-a Potential Approach for HIV Therapy.

AAPS PharmSciTech 2021 Apr 9;22(3):127. Epub 2021 Apr 9.

Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad, 382481, India.

Being a candidate of BCS class II, dolutegravir (DTG), a recently approved antiretroviral drug, possesses solubility issues. The current research was aimed to improve the solubility of the DTG and thereby enhance its efficacy using the solid dispersion technique. In due course, the miscibility study of the drug was performed with different polymers, where Poloxamer 407 (P407) was found suitable to move forward. The solid dispersion of DTG and P407 was formulated using solvent evaporation technique with a 1:1 proportion of drug and polymer, where the solid-state characterization was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffraction. No physicochemical interaction was found between the DTG and P407 in the fabricated solid dispersion; however, crystalline state of the drug was changed to amorphous as evident from the X-ray diffractogram. A rapid release of DTG was observed from the solid dispersion (>95%), which is highly significant (p<0.05) as compared to pure drug (11.40%), physical mixture (20.07%) and marketed preparation of DTG (35.30%). The drug release from the formulated solid dispersion followed Weibull model kinetics. Finally, the rapid drug release from the solid dispersion formulation revealed increased C (14.56 μg/mL) when compared to the physical mixture (4.12 μg/mL) and pure drug (3.45 μg/mL). This was further reflected by improved bioavailability of DTG (AUC: 105.99±10.07 μg/h/mL) in the experimental Wistar rats when compared to the AUC of animals administered with physical mixture (54.45±6.58 μg/h/mL) and pure drug (49.27±6.16 μg/h/mL). Therefore, it could be concluded that the dissolution profile and simultaneously the bioavailability of DTG could be enhanced by means of the solid dispersion platform using the hydrophilic polymer, P407, which could be projected towards improved efficacy of the drug in HIV/AIDS.
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http://dx.doi.org/10.1208/s12249-021-01995-yDOI Listing
April 2021

Alcohol and acute traumatic brain injury in the emergency department.

Emerg Med Australas 2021 Jan 26. Epub 2021 Jan 26.

Department of Surgery and Anaesthesia, University of Otago, Wellington, New Zealand.

Objective: There is limited research from Australasian EDs describing the demographic make-up, injury severity and impact of alcohol in patients requiring computed tomography (CT) for suspected traumatic brain injury (TBI). The present study aims to review the frequency and presenting patterns of patients who consume alcohol prior to presenting with suspected TBI.

Methods: Retrospective observational study of patients referred for head CT to exclude TBI from a major referral centre and regional ED in New Zealand, between 1 September 2018 and 31 August 2019. Comparison groups were defined as 'alcohol involved' or 'no alcohol involved'.

Results: 97/425 (22.8% [95% CI 18.3-27.4]) of included TBI presentations involved alcohol. 73/97 (75.3% [95% CI 58.6-93.5]) were male and 41/97 (42.3% [95% CI 29.3-55.2]) were aged 18-30 years. The alcohol group were more likely to report assault as the injury mechanism (19.6% [95% CI 10.8-28.4] vs 5.2% [95% CI 2.7-7.7], P < 0.05) and have Glasgow Coma Scale scores reflecting more moderate (13.5% [95% CI 5.9-21.1] vs 3.5% [95% CI 1.5-5.6]) and severe (5.6% [95% CI 0.7-10.5] vs 3.2% [95% CI 1.2-5.2] TBI. Presentation times post-injury were delayed compared to the no alcohol group (3.4 h [interquartile range 1.9-14.8] vs 2.8 h [interquartile range 1.8-6.6], P < 0.05).

Conclusion: One quarter of patients with suspected TBI had consumed alcohol prior to their injury. Predominantly, those affected were young males who reported higher rates of assault; however, alcohol use was recorded in all age groups and sex. Alcohol-affected patients presented later, potentially delaying time to diagnosis. The present study supports the call for public health interventions that aim to reduce alcohol misuse.
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http://dx.doi.org/10.1111/1742-6723.13726DOI Listing
January 2021

Incorporation of posttransplant cyclophosphamide as part of standard immunoprophylaxis for all allogeneic transplants: a retrospective, single institution study.

Bone Marrow Transplant 2020 Dec 1. Epub 2020 Dec 1.

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.

The addition of posttransplant cyclophosphamide (PTCy) to standard graft-versus-host disease (GVHD) prophylaxis following haploidentical blood stem transplants has resulted in relatively low rates of GVHD. As GVHD remains a major cause of morbidity and mortality in patients receiving transplants from matched donors, we began to use PTCy in all blood stem cell transplants in 2016 and compared our recent experience with PTCy after matched sibling and unrelated donor transplants (N = 49) to the earlier 2-year period (N = 41) when PTCy was not used. Endpoints included graft-versus-host, relapse-free-survival (GRFS), overall survival, non-relapse mortality, and percentage of patients disease-free and off immunosuppression (DFOI) at 1 year and at the last follow-up. The difference in GRFS between the standard and the PTCy cohort was not statistically significant. There was a statistically improved relapse-free and overall survival in the PTCY cohort that was due to a significant decrease in non-relapse mortality secondary to GVHD. There was also a borderline statistically improved DFOI at 1 year and at last follow-up in the PTCY group. These results suggest that PTCy after HLA-matched transplants provides at least comparable efficacy to other GVHD strategies and may allow more frequent discontinuation of immunosuppression.
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http://dx.doi.org/10.1038/s41409-020-01144-2DOI Listing
December 2020

The Safety and Feasibility of Transitioning From Transfemoral to Transradial Access Left Ventricular Endomyocardial Biopsy.

J Invasive Cardiol 2020 Dec 10;32(12):E349-E354. Epub 2020 Nov 10.

St. Bartholomew's Hospital, W. Smithfield, London EC1A 7BE, United Kingdom.

Background: Left ventricular endomyocardial biopsy (LVEMB) is commonly performed via the transfemoral route. Radial access may help reduce vascular access complications, but there are few data on the safety and feasibility of transradial LVEMB.

Objective: Describe the safety and feasibility of transitioning from transfemoral to transradial access LVEMB.

Methods: This is a single-center, prospective, observational cohort study. Fifty procedures in 49 patients were included, 25 (50%) via the femoral route and 25 (50%) via the radial route.

Results: The cohort had a mean age of 47 ± 13 years and the most common indication for LVEMB was myocarditis. From June 2015 until September 2016, all procedures (n = 21) were performed via the femoral approach; thenceforth, there was a gradual transition to the radial approach. More tissue samples were obtained when the procedure was performed via the femoral approach (P<.01). The minimum sampling target of 3 specimens was not met in 4 patients (16%) via the radial approach and in 1 patient (4%) via the femoral approach. Complications occurred in 3/25 transradial procedures (12%; 2 cardiac perforations and 1 forearm hematoma) and 3/25 transfemoral procedures (12%; 1 cardiac perforation, 1 femoral artery pseudoaneurysm, and 1 ventricular fibrillation). Cardiac perforations via the transradial approach occurred during the early transition period. There were no deaths.

Conclusions: Transradial LVEMB is feasible, with a similar complication profile to femoral procedures, but associated with a smaller number of specimens. Transitioning from transfemoral to transradial procedures may initially be associated with a higher risk of complications and potentially a lower diagnostic yield.
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December 2020

Nanotherapeutics in Neuropathologies: Obstacles, Challenges and Recent Advancements in CNS Targeted Drug Delivery Systems.

Curr Neuropharmacol 2020 Aug 7. Epub 2020 Aug 7.

Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad. India.

Neurology and associated nanotherapeutics is a complex field in terms of therapeutics and neurological disorder complexity. Brain is an intricate appendage and requires more precise embattled treatment for the particular diseases and hence it's a broad scale for developing more targeted drug deliveries. The brain is one of the most inaccessible tissues of the body due to the existence of the blood-brain barrier (BBB), thus delivery of drugs inside the brain is a striking dare and it is also tricky to treat central nervous system (CNS) complications pharmacologically. The therapeutic aspiration is to accomplish a lowest drug meditation in the brain tissues so as to gain favoured therapeutic results. To devastate this obstacle, nanotechnology is engaged in the field of targeted brain drug delivery and neuropathology targeting. These carriers hold myriad ability as they may augment the drug delivery into the brain by shielding them from degradation and prolonging their transmission in the blood, as well as promoting their transport through the BBB. Nanopharmaceuticals are quickly sprouting as new avenue that is engaged with the drug-loaded nanocarriers to demonstrate unique physicochemical properties and tiny size range for penetrating into the central nervous system. The enchantment behind their therapeutic achievement is the condensed drug dose and inferior toxicity, whereby restricting the therapeutic compound to the specific site. Therefore, in this article we have tried to recapitulate the advances the novel scopes for the brain targeted drug delivery for complex neurological disorders.
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http://dx.doi.org/10.2174/1570159X18666200807143526DOI Listing
August 2020

3D Printing Technologies: Recent Development and Emerging Applications in Various Drug Delivery Systems.

AAPS PharmSciTech 2020 Aug 3;21(6):220. Epub 2020 Aug 3.

Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, 382481, India.

The 3D printing is considered as an emerging digitized technology that could act as a key driving factor for the future advancement and precise manufacturing of personalized dosage forms, regenerative medicine, prosthesis and implantable medical devices. Tailoring the size, shape and drug release profile from various drug delivery systems can be beneficial for special populations such as paediatrics, pregnant women and geriatrics with unique or changing medical needs. This review summarizes various types of 3D printing technologies with advantages and limitations particularly in the area of pharmaceutical research. The applications of 3D printing in tablets, films, liquids, gastroretentive, colon, transdermal and intrauterine drug delivery systems as well as medical devices have been briefed. Due to the novelty and distinct features, 3D printing has the inherent capacity to solve many formulation and drug delivery challenges, which are frequently associated with poorly aqueous soluble drugs. Recent approval of Spritam® and publication of USFDA technical guidance on additive manufacturing related to medical devices has led to an extensive research in various field of drug delivery systems and bioengineering. The 3D printing technology could be successfully implemented from pre-clinical phase to first-in-human trials as well as on-site production of customized formulation at the point of care having excellent dose flexibility. Advent of innovative 3D printing machineries with built-in flexibility and quality with the introduction of new regulatory guidelines would rapidly integrate and revolutionize conventional pharmaceutical manufacturing sector.
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http://dx.doi.org/10.1208/s12249-020-01771-4DOI Listing
August 2020

COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options.

Cardiovasc Res 2020 08;116(10):1666-1687

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.
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http://dx.doi.org/10.1093/cvr/cvaa106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197627PMC
August 2020

Therapeutics and Research Related to Glioblastoma: Advancements and Future Targets.

Curr Drug Metab 2020 ;21(3):186-198

Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 712-749, Korea.

Glioblastoma, the most common primary brain tumor, has been recognized as one of the most lethal and fatal human tumors. It has a dismal prognosis, and survival after diagnosis is less than 15 months. Surgery and radiotherapy are the only available treatment options at present. However, numerous approaches have been made to upgrade in vivo and in vitro models with the primary goal of assessing abnormal molecular pathways that would be suitable targets for novel therapeutic approaches. Novel drugs, delivery systems, and immunotherapy strategies to establish new multimodal therapies that target the molecular pathways involved in tumor initiation and progression in glioblastoma are being studied. The goal of this review was to describe the pathophysiology, neurodegeneration mechanisms, signaling pathways, and future therapeutic targets associated with glioblastomas. The key features have been detailed to provide an up-to-date summary of the advancement required in current diagnosis and therapeutics for glioblastoma. The role of nanoparticulate system graphene quantum dots as suitable therapy for glioblastoma has also been discussed.
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http://dx.doi.org/10.2174/1389200221666200408083950DOI Listing
January 2020

Hepatic hemangiomas: the various imaging avatars and its mimickers.

Radiol Med 2020 Sep 5;125(9):801-815. Epub 2020 Apr 5.

Department of Radiology and Diagnostic Imaging, Faculty of Medicine and Dentistry, University of Alberta, 8440 112 St NW, Edmonton, AB, T6G 2B7, Canada.

Hemangiomas are the most common benign tumors of the liver. These lesions are typically asymptomatic, solitary and almost always discovered incidentally, and in recent years with advances in imaging technology these lesions are being detected more frequently. Although, in majority of the cases, the imaging diagnosis of a liver hemangioma is clearly and confidently established, not all hemangiomas present with their characteristic or typical appearance on imaging. Occasionally, these lesions do present with an atypical pattern, and can be confused with other malignant lesions such as hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular-cholangiocarcinoma and angiosarcoma. In this article, we review with illustrations the diverse imaging appearances of hemangiomas on the commonly used imaging modalities, as well as provide a gamut of common and uncommonly encountered hemangioma mimickers. Knowledge of the various atypical avatars of this benign lesion is important and can help one circumvent diagnostic errors, thereby potentially avoiding unnecessary surgeries.
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http://dx.doi.org/10.1007/s11547-020-01185-zDOI Listing
September 2020

Abdominal and pelvic radiographs of medical devices and materials- part 2: neurologic and genitourinary devices and materials.

Diagn Interv Radiol 2020 May;26(3):160-167

Department of Radiology and Diagnostic Imaging, University of Alberta School of Medicine and Dentistry, Edmonton, Canada.

Radiographs of the abdomen and pelvis are routinely obtained as a standard part of clinical care for the abdomen and pelvis. Brisk advances in technology over the last few decades have resulted in a multitude of medical devices and materials. Recognizing and evaluating these devices on abdominal and pelvic radiographs are critical, yet increasingly a difficult endeavor. In addition, multiple devices serving different purposes may have a similar radiographic appearance and position causing confusion for the interpreting radiologist. The role of the radiologist is to not only identify accurately these medical objects, but also to confirm for their accurate placement and to recognize any complications that could affect patient care, management or even be potentially life threatening. An extensive online search of literature showed our review article to be the most comprehensive work on medical devices and materials of the abdomen and pelvis, and in this second part of our two-part series, we discuss in depth about the neurologic and genitourinary devices seen on abdominal and pelvic radiographs.
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http://dx.doi.org/10.5152/dir.2019.19391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239358PMC
May 2020

Improvement of oral bioavailability of carvedilol by liquisolid compact: optimization and pharmacokinetic study.

Drug Deliv Transl Res 2020 08;10(4):975-985

Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, 382481, India.

Low aqueous solubility is one of the major reasons for the poor clinical efficacy of carvedilol in oral therapy. The aim of the present investigation was to evaluate the potential of liquisolid compact technique to enhance the dissolution rates of carvedilol and thereby the bioavailability. Liquisolid compacts were prepared using polyethylene glycol 400, Neusilin US2 and Aerosil 200. Experimental design and optimization was carried out by applying a 3 factorial design (batches D1-D9) to examine the effects of independent variables (amount of load factor and the excipient ratio) on dependent variables (angle of repose and % drug release). Differential scanning calorimetry and X-ray diffraction studies suggested transformation of carvedilol to amorphous in D6, a key factor responsible for dissolution rate improvement. This effect was evidenced in the dissolution data of D6 (>95% drug dissolved in 30 min) where the drug release kinetics followed Weibull model. It was observed that the amount of load factor influenced angle of repose and excipient ratio affected drug dissolution of liquisolid compacts. Pharmacokinetic profile of D6 was prominent, demonstrating greater carvedilol absorption than the control in rats. The observed increase in systemic bioavailability of carvedilol AUC (p < 0.005) by liquisolid compact is likely due to the improvement in drug solubility. The data observed in the current study demonstrated that the liquisolid compact technique could be a promising strategy to enhance the bioavailability of carvedilol and could be used in oral therapy. Graphical abstract.
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http://dx.doi.org/10.1007/s13346-020-00734-3DOI Listing
August 2020

Abdominal and pelvic radiographs of medical devices and materials-Part 1: gastrointestinal and vascular devices and materials.

Diagn Interv Radiol 2020 Mar;26(2):101-110

Department of Radiology and Diagnostic Imaging, University of Alberta School of Medicine and Dentistry, Edmonton, Canada.

When compared with chest radiographs, medical devices of the abdomen and pelvis are less frequently seen. However, with recent advances in technology the interpreting radiologists are seeing more medical objects on these radiographs. The identification of these devices and materials are crucial for not only enabling the radiologist to understand the underlying background pathology but also for evaluating any related complications. An online survey of literature showed our review article to be the most detailed. In this first part of our two-part series, we discuss about the various gastrointestinal and vascular devices and materials seen on abdominal and pelvic radiographs.
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http://dx.doi.org/10.5152/dir.2019.19390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051258PMC
March 2020

Case 275: Multiple Hepatic Hydatid Cysts.

Radiology 2020 Mar;294(3):716-719

From the Department of Radiology and Diagnostic Imaging, University of Alberta, 8440-112 St, 2A2.41 WMC, Edmonton, AB, Canada T6G 2B7.

HistoryA 61-year-old woman presented to the cardiology service with sinus tachycardia. As part of her work-up, she underwent routine echocardiography that showed a normal heart but incidentally revealed multiple lesions in the liver. An outpatient CT scan was performed to characterize the liver lesions. The patient had emigrated to Canada from the Middle East several years earlier and had no medical history of note; in particular, there was no history of cancer or predisposing factors for chronic liver disease. The patient's clinical examination findings; laboratory test results, including complete blood count; and liver function test results were normal.
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http://dx.doi.org/10.1148/radiol.2019180104DOI Listing
March 2020

Clozapine reduces infiltration into the CNS by targeting migration in experimental autoimmune encephalomyelitis.

J Neuroinflammation 2020 Feb 12;17(1):53. Epub 2020 Feb 12.

School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.

Background: Atypical antipsychotic agents, such as clozapine, are used to treat schizophrenia and other psychiatric disorders by a mechanism that is believed to involve modulating the immune system. Multiple sclerosis is an immune-mediated neurological disease, and recently, clozapine was shown to reduce disease severity in an animal model of MS, experimental autoimmune encephalomyelitis (EAE). However, the mode of action by which clozapine reduces disease in this model is poorly understood.

Methods: Because the mode of action by which clozapine reduces neuroinflammation is poorly understood, we used the EAE model to elucidate the in vivo and in vitro effects of clozapine.

Results: In this study, we report that clozapine treatment reduced the infiltration of peripheral immune cells into the central nervous system (CNS) and that this correlated with reduced expression of the chemokines CCL2 and CCL5 transcripts in the brain and spinal cord. We assessed to what extent immune cell populations were affected by clozapine treatment and we found that clozapine targets the expression of chemokines by macrophages and primary microglia. Furthermore, in addition to decreasing CNS infiltration by reducing chemokine expression, we found that clozapine directly inhibits chemokine-induced migration of immune cells. This direct target on the immune cells was not mediated by a change in receptor expression on the immune cell surface but by decreasing downstream signaling via these receptors leading to a reduced migration.

Conclusions: Taken together, our study indicates that clozapine protects against EAE by two different mechanisms; first, by reducing the chemoattractant proteins in the CNS; and second, by direct targeting the migration potential of peripheral immune cells.
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http://dx.doi.org/10.1186/s12974-020-01733-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014621PMC
February 2020

Malignant transformation of hepatic adenoma complicated by rupture and hemorrhage: An extremely rare clinical entity.

Intractable Rare Dis Res 2019 Nov;8(4):266-270

Department of Radiology & Diagnostic Imaging, University of Alberta Hospital, Edmonton, Canada.

Hepatic adenomas (HAs) are rare benign tumors of the liver and comprise 2% of all liver tumors with an annual incidence of 3-4/100,000 per year in Europe and North America. These tumors may be clinically silent or present with abdominal pain. Although rare, the most important complications associated with this tumor is haemorrhage and malignant transformation to hepatocellular carcinoma. The reported risk of malignant transformation is believed to be 4.2%. We present an extremely rare case report of a young woman on the oral contraceptive pill (OCP) with malignant transformation of a hepatic adenoma complicated additionally by tumor rupture and intraperitoneal bleed. This article therefore highlights the need to carefully evaluate any liver lesion in a young female on the OCP to be a possible adenoma and if confirmed to be so, to consider the potential risks associated with it as well as the need for follow-up imaging in order to avoid life threatening complications.
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http://dx.doi.org/10.5582/irdr.2019.01089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929599PMC
November 2019

Erratum: Chest radiographs - Lines, tubes, non-cardiac medical devices and materials.

SA J Radiol 2019;23(1):1808. Epub 2019 Dec 5.

Department of Radiology and Diagnostic Imaging, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

[This corrects the article DOI: 10.4102/sajr.v23i1.1729.].
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http://dx.doi.org/10.4102/sajr.v23i1.1808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909413PMC
December 2019

Development of Asialoglycoprotein Receptor-Targeted Nanoparticles for Selective Delivery of Gemcitabine to Hepatocellular Carcinoma.

Molecules 2019 Dec 13;24(24). Epub 2019 Dec 13.

Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.

Selective targeting of anticancer drugs to the tumor site is beneficial in the pharmacotherapy of hepatocellular carcinoma (HCC). This study evaluated the prospective of galactosylated chitosan nanoparticles as a liver-specific carrier to improve the therapeutic efficacy of gemcitabine in HCC by targeting asialoglycoprotein receptors expressed on hepatocytes. Nanoparticles were formulated (G1-G5) by an ionic gelation method and evaluated for various physicochemical characteristics. Targeting efficacy of formulation G4 was evaluated in rats. Physicochemical characteristics exhibited by nanoparticles were optimal for administering and targeting gemcitabine effectively to the liver. The biphasic release behavior observed with G4 can provide higher drug concentration and extend the pharmacotherapy in the liver target site. Rapid plasma clearance of gemcitabine (70% in 30 min) from G4 was noticed in rats with HCC as compared to pure drug ( < 0.05). Higher uptake of gemcitabine predominantly by HCC (64% of administered dose; < 0.0001) demonstrated excellent liver targeting by G4, while mitigating systemic toxicity. Morphological, biochemical, and histopathological examination as well as blood levels of the tumor marker, alpha-fetoprotein, in rats confirmed the curative effect of G4. In conclusion, this study demonstrated site-specific delivery and enhanced in vivo anti-HCC efficacy of gemcitabine by G4, which could function as promising carrier in hepatoma.
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http://dx.doi.org/10.3390/molecules24244566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943439PMC
December 2019

Case 273: Pancreatic Duct-to-Portal Vein Fistula with Secondary Portal Vein Pyophlebitis-A Rare Complication of Chronic Pancreatitis.

Radiology 2020 01;294(1):234-237

From the Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, 2A2.41 WMC, 8440-112 St, Edmonton, AB, Canada T6G 2B7.

HistoryA 55-year-old man with a history of chronic pancreatitis secondary to chronic alcohol abuse presented to the hospital with acute abdominal pain, generalized weakness, weight loss, and pyrexia. A clinical examination revealed he was tender to touch in the upper abdomen. Laboratory tests revealed a serum alkaline phosphatase level of 370 U/L (6.1 µkat/L) (normal range, 30-130 U/L [0.5-2.2 µkat/L]), a lipase level of 172 U/L (2.9 µkat/L) (normal range, 0-60 U/L [0-1.0 µkat/L]), a C-reactive protein level of 159 mg/L (1514 nmol/L) (normal value, <8.0 mg/L [76.2 nmol/L]), and a white cell count of 7 × 10/L (normal range, [4-11] × 10/L). During the present admission, the patient underwent urgent CT for his acute symptoms. His relevant medical history included a hospital admission 2 months earlier for abdominal discomfort. Given his history of chronic pancreatitis, baseline abdominal MRI was performed to determine the cause of his symptoms and to assess the pancreas.
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http://dx.doi.org/10.1148/radiol.2019171373DOI Listing
January 2020

Chest radiographs of cardiac devices (Part 2): Ventricular assist devices.

SA J Radiol 2019 31;23(1):1732. Epub 2019 Jul 31.

Department of Radiology and Diagnostic Imaging, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

Heart failure is considered a worldwide pandemic affecting 26 million people globally. Patients who are unfit or waiting for cardiac transplantation may benefit from alternate mechanical support therapies using ventricular assist devices. It is not uncommon for radiologists, especially those working in institutions with a high volume of cardiac transplantations, to be presented with radiographs containing these devices. The role of the radiologist is not only to accurately identify these devices, but also to evaluate for any complications.
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http://dx.doi.org/10.4102/sajr.v23i1.1732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837777PMC
July 2019

Chest radiographs of cardiac devices (Part 1): Cardiovascular implantable electronic devices, cardiac valve prostheses and Amplatzer occluder devices.

SA J Radiol 2019 31;23(1):1730. Epub 2019 Jul 31.

Department of Radiology and Diagnostic Imaging, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

Several new innovative cardiac devices have been created over the last few decades. Chest radiographs (CXRs) are the most common imaging investigations undertaken because of their value in evaluating the cardiorespiratory system. It is important for the interpreting radiologist to not only identify these iatrogenic objects but also to assess for their accurate placement, as well as for any complications related to their placement, which may be seen either on the immediate post-procedural CXR or on a follow-up CXR.
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http://dx.doi.org/10.4102/sajr.v23i1.1730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837806PMC
July 2019

Chest radiographs of cardiac devices (Part 1): Lines, tubes, non-cardiac medical devices and materials.

SA J Radiol 2019 29;23(1):1729. Epub 2019 Jul 29.

Department of Radiology and Diagnostic Imaging, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

Chest radiographs (CXRs) are the most common imaging investigations undertaken because of their value in evaluating the cardiorespiratory system. They play a vital role in intensive care units for evaluating the critically ill. It is therefore very common for the radiologist to encounter tubes, lines, medical devices and materials on a daily basis. It is important for the interpreting radiologist not only to identify these iatrogenic objects, but also to look for their accurate placement as well as for any complications related to their placement, which may be seen either on the immediate post-procedural CXR or on a follow-up CXR. In this article, we discussed and illustrated the routinely encountered tubes and lines that one may see on a CXR as well as some of their complications. In addition, we also provide a brief overview of other important non-cardiac medical devices and materials that may be seen on CXRs.
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http://dx.doi.org/10.4102/sajr.v23i1.1729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837827PMC
July 2019

Caution in using 3D-EAUS as the first-line diagnostic tool in the preoperative work up for perianal fistulas.

Radiol Med 2020 02 2;125(2):155-156. Epub 2019 Nov 2.

Department of Radiology and Diagnostic Imaging, Faculty of Medicine and Dentistry, University of Alberta, 8440 112 St NW, Edmonton, AB, T6G 2B7, Canada.

MRI is considered the de facto imaging modality for evaluating perianal fistulas, primarily due to its excellent soft tissue contrast, operator independence, multiplanar capabilities and excellent field of view. Tridimensional endoanal ultrasound (3D-EAUS) is inferior to MRI in identifying and/or evaluating ischiorectal/supralevator tracks/extensions and therefore could end up providing incomplete and even inaccurate information (e.g. misclassification of tracks) to the surgeon, with a missed track potentially leading to recurrence of the disease.
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http://dx.doi.org/10.1007/s11547-019-01101-0DOI Listing
February 2020

Case 275.

Radiology 2019 11;293(2):471-472

From the Department of Radiology and Diagnostic Imaging, University of Alberta, 8440-112 St, 2A2.41 WMC, Edmonton, AB, Canada T6G 2B7.

HistoryA 61-year-old woman presented to the cardiology service with sinus tachycardia. As part of her work-up, she underwent routine echocardiography that showed a normal heart but incidentally revealed multiple lesions in the liver (Fig 1). An outpatient CT scan was performed to characterize the liver lesions (Figs 2-5). The patient had emigrated to Canada from the Middle East several years earlier and had no medical history of note; in particular, there was no history of cancer or predisposing factors for chronic liver disease. The patient's clinical examination findings; laboratory test results, including complete blood count; and liver function test results were normal.[Figure: see text][Figure: see text][Figure: see text][Figure: see text][Figure: see text].
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http://dx.doi.org/10.1148/radiol.2019180133DOI Listing
November 2019

Accuracy of findings in the diagnosis of uterine adenomyosis on ultrasound.

Abdom Radiol (NY) 2020 03;45(3):842-850

Department of Radiology & Diagnostic Imaging, University of Alberta Hospital, 2A2.41 WMC 8440-112 Street, Edmonton, AB, T6G 2B7, Canada.

Purpose: MRI is the current imaging gold standard to diagnose adenomyosis, but access is often limited by high costs and availability. Transvaginal ultrasound provides a cost-effective, accurate and readily available alternative. The objective of our study was to determine the diagnostic accuracy of commonly described sonographic findings in predicting uterine adenomyosis.

Methods: This retrospective study evaluated 649 MRI studies performed to investigate adenomyosis with a preceding transvaginal ultrasound within 12 months between 2013 and 2018. Two blinded reviewers assessed the presence or absence of six sonographic features: bulky uterus, heterogeneous myometrium, streaky myometrium, myometrial cysts, endometrial-myometrial interface ill-definition, and echogenic linear striations. The sensitivity, specificity, positive and negative predictive values of these features were calculated individually and in combination when compared to MRI as the standard of reference.

Results: Adenomyosis was found in 315 (48.5%) cases on MRI. Ultrasound had a high specificity of 91.8% (95% CI 88.4 to 94.6%) but was less sensitive (36.8% (95% CI 31.5 to 42.4%)) for detecting adenomyosis. Comorbid fibroids or focal adenomyosis did not affect diagnostic accuracy. All six variables were significantly more common in patients with adenomyosis compared to those without. Individually, 'bulky uterus' and 'heterogenous myometrium' each demonstrated a mean sensitivity and specificity > 50%. The best dual combined variables were 'bulky uterus' + 'ill definition of the endometrial-myometrial interface' (sensitivity 39%, specificity 91%). The best triple combined variables were 'bulky uterus', 'heterogeneous myometrium' + 'ill definition of the endometrial-myometrial interface' (sensitivity 38%, specificity 93%).

Conclusion: Transvaginal ultrasound is highly specific for diagnosing uterine adenomyosis, providing a cost-effective and readily available alternative to MRI.
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http://dx.doi.org/10.1007/s00261-019-02231-9DOI Listing
March 2020

Case 273.

Radiology 2019 09;292(3):773-775

From the Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, 2A2.41 WMC, 8440-112 St, Edmonton, AB, Canada T6G 2B7.

HistoryA 55-year-old man with a history of chronic pancreatitis secondary to chronic alcohol abuse presented to the hospital with acute abdominal pain, generalized weakness, weight loss, and pyrexia. A clinical examination revealed he was tender to touch in the upper abdomen. Laboratory tests revealed a serum alkaline phosphatase level of 370 U/L (6.1 µkat/L) (normal range, 30-130 U/L [0.5-2.2 µkat/L]), a lipase level of 172 U/L (2.9 µkat/L) (normal range, 0-60 U/L [0-1.0 µkat/L]), a C-reactive protein level of 159 mg/L (1514 nmol/L) (normal value, <8.0 mg/L [76.2 nmol/L]), and a white cell count of 7 × 10/L (normal range, [4-11] × 10/L). During the present admission, the patient underwent urgent CT for his acute symptoms. His relevant medical history included a hospital admission 2 months earlier for abdominal discomfort. Given his history of chronic pancreatitis, baseline abdominal MRI was performed to determine the cause of his symptoms and to assess the pancreas (Figs 1-3).Figure 1a: Images from axial fat-suppressed T2-weighted MRI (repetition time msec/echo time msec, 1000/87; section thickness, 6 mm) of the upper abdomen obtained 2 months prior to admission. Images from axial fat-suppressed T1-weighted MRI (3.69/1.62; section thickness, 4 mm) of the upper abdomen acquired 60 seconds after intravenous administration of gadopentetate dimeglumine (0.1 mL per kilogram of body weight; Magnevist; Bayer Healthcare, East Mississauga, Ontario) during the current admission.Figure 1b: Images from axial fat-suppressed T2-weighted MRI (repetition time msec/echo time msec, 1000/87; section thickness, 6 mm) of the upper abdomen obtained 2 months prior to admission. Images from axial fat-suppressed T1-weighted MRI (3.69/1.62; section thickness, 4 mm) of the upper abdomen acquired 60 seconds after intravenous administration of gadopentetate dimeglumine (0.1 mL per kilogram of body weight; Magnevist; Bayer Healthcare, East Mississauga, Ontario) during the current admission.Figure 1c: Images from axial fat-suppressed T2-weighted MRI (repetition time msec/echo time msec, 1000/87; section thickness, 6 mm) of the upper abdomen obtained 2 months prior to admission. Images from axial fat-suppressed T1-weighted MRI (3.69/1.62; section thickness, 4 mm) of the upper abdomen acquired 60 seconds after intravenous administration of gadopentetate dimeglumine (0.1 mL per kilogram of body weight; Magnevist; Bayer Healthcare, East Mississauga, Ontario) during the current admission.Figure 1d: Images from axial fat-suppressed T2-weighted MRI (repetition time msec/echo time msec, 1000/87; section thickness, 6 mm) of the upper abdomen obtained 2 months prior to admission. Images from axial fat-suppressed T1-weighted MRI (3.69/1.62; section thickness, 4 mm) of the upper abdomen acquired 60 seconds after intravenous administration of gadopentetate dimeglumine (0.1 mL per kilogram of body weight; Magnevist; Bayer Healthcare, East Mississauga, Ontario) during the current admission.Figure 2:Coronal T2-weighted MRI (repetition time msec/echo time msec, 1000/89; section thickness, 4 mm) of the upper abdomen obtained 2 months prior to admission.Figure 3:Coronal CT image of the abdomen acquired 60 seconds after administration of intravenous contrast material (100 mL of iohexol, Omnipaque 350; GE Healthcare, Princeton, NJ). This CT examination was performed during the current admission.
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http://dx.doi.org/10.1148/radiol.2017171374DOI Listing
September 2019

Follow-Up of Incidental Renal Lesions on Lumbar Spine MRI.

AJR Am J Roentgenol 2019 09;213(3):W147

University of Alberta, Edmonton, AB, Canada.

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http://dx.doi.org/10.2214/AJR.19.21318DOI Listing
September 2019

Identification of a Multiplex Biomarker Panel for Hypertrophic Cardiomyopathy Using Quantitative Proteomics and Machine Learning.

Mol Cell Proteomics 2020 01 26;19(1):114-127. Epub 2019 Jun 26.

Translational Mass Spectrometry Research Group, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, UK; Institute of Child Health, University College London, London, WC1N 1EH, UK. Electronic address:

Hypertrophic cardiomyopathy (HCM) is defined by pathological left ventricular hypertrophy (LVH). It is the commonest inherited cardiac condition and a significant number of high risk cases still go undetected until a sudden cardiac death (SCD) event. Plasma biomarkers do not currently feature in the assessment of HCM disease progression, which is tracked by serial imaging, or in SCD risk stratification, which is based on imaging parameters and patient/family history. There is a need for new HCM plasma biomarkers to refine disease monitoring and improve patient risk stratification. To identify new plasma biomarkers for patients with HCM, we performed exploratory myocardial and plasma proteomics screens and subsequently developed a multiplexed targeted liquid chromatography-tandem/mass spectrometry-based assay to validate the 26 peptide biomarkers that were identified. The association of discovered biomarkers with clinical phenotypes was prospectively tested in plasma from 110 HCM patients with LVH (LVH+ HCM), 97 controls, and 16 HCM sarcomere gene mutation carriers before the development of LVH (subclinical HCM). Six peptides (aldolase fructose-bisphosphate A, complement C3, glutathione S-transferase omega 1, Ras suppressor protein 1, talin 1, and thrombospondin 1) were increased significantly in the plasma of LVH+ HCM compared with controls and correlated with imaging markers of phenotype severity: LV wall thickness, mass, and percentage myocardial scar on cardiovascular magnetic resonance imaging. Using supervised machine learning (ML), this six-biomarker panel differentiated between LVH+ HCM and controls, with an area under the curve of ≥ 0.87. Five of these peptides were also significantly increased in subclinical HCM compared with controls. In LVH+ HCM, the six-marker panel correlated with the presence of nonsustained ventricular tachycardia and the estimated five-year risk of sudden cardiac death. Using quantitative proteomic approaches, we have discovered six potentially useful circulating plasma biomarkers related to myocardial substrate changes in HCM, which correlate with the estimated sudden cardiac death risk.
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http://dx.doi.org/10.1074/mcp.RA119.001586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944230PMC
January 2020

Blue Nose Sign: Critical Care Presentation of Toxic Ingestion.

Am J Respir Crit Care Med 2019 08;200(4):510

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee.

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http://dx.doi.org/10.1164/rccm.201807-1337IMDOI Listing
August 2019

Limitations in US Diagnosis of Adenomysosis.

Radiographics 2019 Jan-Feb;39(1):303-304

Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, 8440-112 St, 2A2.41 WMC, Edmonton, AB, Canada T6G 2B7.

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http://dx.doi.org/10.1148/rg.2019180204DOI Listing
October 2019