The clinical and financial impact of remote clinical oncology pharmacist engagement in community-based practices within The US Oncology Network.

INTRODUCTION: The integration of clinical oncology pharmacists into multidisciplinary healthcare teams is not well-described in the community practice setting. This study aims to analyze the clinical and financial impact of a remote-based clinical oncology pharmacist in four community oncology practices within The US Oncology Network. METHODS: Oncology-trained clinical pharmacists electronically reviewed chemotherapy orders for clinical optimization and financial stewardship within four community oncology practices. Each pharmacist was appointed at 0.5 full-time equivalents per practice. Financial, clinical, and workload metrics were tracked to monitor the impact of pharmacist engagement. RESULTS: Over 12 months, 5716 order reviews were completed with an intervention rate of 57%. The most common interventions identified by the pharmacists were interventions with clinical impact on the patient (36%), followed by dose rounding (35%) and therapeutic interchange (30%). Overall, interventions improved the cumulative practice margins by $1,455,033 and reduced total medication costs by $5,962,551. The average program return on investment was 415% (range 100-915%). CONCLUSION: Community oncology practices seek to provide high-value care in a lean, resource-constrained model. An oncology clinical pharmacist is a cost-effective and clinically invaluable care team member in community oncology practice. Pharmacists in this setting identified opportunities to improve medication safety and regimen optimization and demonstrated a significant tremendous financial impact on small-scale budgets in community oncology.

Efficacy of supplemental MCT oil on seizure reduction of adult drug-resistant epilepsy - a single-center open-label pilot study.

OBJECTIVE: We set out to determine whether adding medium chain triglyceride (MCT) oil as a dietary supplement to standard diet in adult subjects with intractable epilepsy in a U.S. neurology clinical practice was associated with a reduction in number of seizures. We secondarily aimed to determine whether subjects experienced any side effects and whether there was a presence of urinary ketones while using MCT oil as a dietary supplement. METHODS: Adult patients with intractable epilepsy were recruited at standard of care clinical visits with their epileptologist. Once enrolled, subjects were instructed to supplement their diet with MCT oil as tolerated twice daily for three months (including a 1-2 week titration period, followed by a 1-2 week tapering off window) while keeping a seizure diary to record total number of seizures, presence of urinary ketones, and any side effects. RESULTS: Our data although limited by small sample size, shows that there is an estimated 42% reduction (p < 0.0001) in the rate of seizures. The MCT oil supplementation was well tolerated by most subjects except for minor GI side effects like nausea and loose stools. Most subjects developed ketones in their urine at some point during the trial. CONCLUSIONS: MCT oil supplementation reduced seizure frequency in study participants. The reported side effects included mild nausea, stomachache, loose stools. A placebo-controlled study will be more informative.

Reliability of ultrasound ovarian-adnexal reporting and data system amongst less experienced readers before and after training.

BACKGROUND: The 2018 ovarian-adnexal reporting and data system (O-RADS) guidelines are aimed at providing a system for consistent reports and risk stratification for ovarian lesions found on ultrasound. It provides key characteristics and findings for lesions, a lexicon of descriptors to communicate findings, and risk characterization and associated follow-up recommendation guidelines. However, the O-RADS guidelines have not been validated in North American institutions or amongst less experienced readers. AIM: To evaluate the diagnostic accuracy and inter-reader reliability of ultrasound O-RADS risk stratification amongst less experienced readers in a North American institution with and without pre-test training. METHODS: A single-center retrospective study was performed using 100 ovarian/adnexal lesions of varying O-RADS scores. Of these cases, 50 were allotted to a training cohort and 50 to a testing cohort via a non-randomized group selection process in order to approximately equal distribution of O-RADS categories both within and between groups. Reference standard O-RADS scores were established through consensus of three fellowship-trained body imaging radiologists. Three PGY-4 residents were independently evaluated for diagnostic accuracy and inter-reader reliability with and without pre-test O-RADS training. Sensitivity, specificity, positive predictive value, negative predictive value (NPV), and area under the curve (AUC) were used to measure accuracy. Fleiss kappa and weighted quadratic (pairwise) kappa values were used to measure inter-reader reliability. Statistical significance was P < 0.05. RESULTS: Mean patient age was 40 ± 16 years with lesions ranging from 1.2 to 22.5 cm. Readers demonstrated excellent specificities (85%-100% pre-training and 91%-100% post-training) and NPVs (89%-100% pre-training and 91-100% post-training) across the O-RADS categories. Sensitivities were variable (55%-100% pre-training and 64%-100% post-training) with malignant O-RADS 4 and 5 Lesions pre-training and post-training AUC values of 0.87-0.95 and 0.94-098, respectively (P < 0.001). Nineteen of 22 (86%) misclassified cases in pre-training were related to mischaracterization of dermoid features or wall/septation morphology. Fifteen of 17 (88%) of post-training misclassified cases were related to one of these two errors. Fleiss kappa inter-reader reliability was 'good' and pairwise inter-reader reliability was 'very good' with pre-training and post-training assessment (k = 0.76 and 0.77; and k = 0.77-0.87 and 0.85-0.89, respectively). CONCLUSION: Less experienced readers in North America achieved excellent specificities and AUC values with very good pairwise inter-reader reliability. They may be subject to misclassification of potentially malignant lesions, and specific training around dermoid features and smooth vs irregular inner wall/septation morphology may improve sensitivity.

Universal posttransplant cyclophosphamide after allogeneic transplant, a retrospective single institution study.

BACKGROUND: The excellent results of posttransplant cyclophosphamide in decreasing graft-versus-host disease (GVHD) after haploidentical (HI) allogeneic transplant have challenged current donor selection algorithms. PATIENTS AND METHODS: We compared outcomes after matched sibling (MSD) versus alternative donor transplant using identical graft-versus-host disease (GVHD) prophylaxis including posttransplant cyclophosphamide (PTCy. Endpoints included engraftment, time outside of the hospital in the first 100 days after transplant, overall survival (OS), non-relapse mortality (NRM) and percentage of patients disease-free and off immunosuppression (DFOI) at one year and at the last follow-up. RESULTS: There were significant differences at baseline between matched donor versus HI donor transplants with higher disease-risk index (DRI), more female-to-male donor recipient pairs and a higher percentage of Black patients in the HI group. Engraftment and time out of the hospital favored MSD and matched unrelated donor transplants. Multivariate analysis showed that high DRI and Black race were associated with decreased survival and Black race was associated with a higher NRM. CONCLUSIONS: With the use of PTCy, our results support current donor selection algorithms. The finding of decreased survival and increased NRM in Black patients requires confirmation in a larger number of patients as well as the development of mitigation strategies.

Design and In-silico study of bioimaging fluorescence Graphene quantum dot-Bovine serum albumin complex synthesized by diimide-activated amidation.

Graphene quantum dot possesses advantageous characteristics like tunable fluorescence, nanometer size, low cytotoxicity, high biocompatibility enabling them as an ideal material for fluorescence bio-imaging. It exhibits a unique characteristic of DNA cleavage activity enhancer, gene/drug carrier, and anticancer targeting applications. In this article, we discussed the preparation of graphene quantum dot through the bottom-up method. Carbodiimide-activated amidation reactions were used for the functionalization of graphene quantum dot with Bovine Serum Albumin. Fluorescence spectroscopy data showed that the graphene quantum dot has size-dependent fluorescence emission. TEM and AFM studies showed that the size of graphene quantum dot was around 20 nm with narrow size distribution. Carbodiimide-activated amidation conjugation was successful in binding the protein onto graphene quantum dot and these conjugates were characterized by DLS, FTIR, fluorescence spectroscopy, and agarose gel electrophoresis. We also studied the structural-based in-silico molecular dynamic simulation by AutoDock, PyRx, and Discovery Studio Visualizer. Based on the virtual screening analysis and higher negative energy incorporation, it is observed that graphene quantum dot conjugated with bovine serum albumin quickly and formed is highly stable complex, which makes them a potential candidate for future applications in the field of bio-imaging, bio-sensing, gene/drug delivery, and tumor theragnostic.

The current and future aspects of glioblastoma: Immunotherapy a new hope?

Glioblastoma (GBM) is the most perilous and highly malignant in all the types of brain tumor. Regardless of the treatment, the diagnosis of the patients in GBM is very poor. The average survival rate is only 21 months after multimodal combinational therapies, which include chemotherapy, radiation, and surgery. Due to the intrusive and infiltrative nature of GBM, it requires elective therapy for specific targeting of tumor cells. Tumor vaccine in a form of immunotherapy has potential to address this need. Nanomedicine-based immunotherapies have clutch the trigger of systemic and specific immune response against tumor cells, which might be the approach to eliminating the unrelieved cancer. In this mechanism, combination of immunomodulators with specific target and appropriate strategic vaccines can stifle tumor anti-immune defense system and/or increase the capabilities of the body to move up immunity against the tumor. Here, we explore the different types of immunotherapies and vaccines for brain tumor treatment and their clinical trials, which bring the feasibility of the future of personalized vaccine of nanomedicine-based immunotherapies for the brain tumor. We believe that immunotherapy could result in a significantly more stable reaction in GBM patients.

Diagnostic accuracy and inter-observer reliability of the O-RADS scoring system among staff radiologists in a North American academic clinical setting.

PURPOSE: The objective of this study is to evaluate the diagnostic accuracy, interobserver variability, and common lexicon pitfalls of the ACR O-RADS scoring system among staff radiologists without prior experience to O-RADS. MATERIALS AND METHODS: After independent review of the ACR O-RADS publications and 30 training cases, three fellowship-trained, board-certified staff radiologists scored 50 pelvic ultrasound exams using the O-RADS system. The diagnostic accuracy and area under receiver operating characteristic were analyzed for each reader. Overall agreement and pair-wise agreement between readers were also analyzed. RESULTS: Excellent specificities (92 to 100%), NPVs (92 to 100%), and variable sensitivities (72 to 100%), PPVs (66 to 100%) were observed. Considering O-RADS 4 and O-RADS 5 as predictors of malignancy, individual reader AUC values range from 0.94 to 0.98 (p < 0.001). Overall inter-reader agreement for all 3 readers was "very good," k = 0.82 (0.73 to 0.90, 95% CI, p < 0.001). Pair-wise agreement between readers were also "very good," k = 0.86-0.92. 14 out of 150 lesions were misclassified, with the most common error being down-scoring of a solid lesion with irregular outer contours. CONCLUSION: Even without specific training, experienced ultrasound readers can achieve excellent diagnostic performance and high inter-reader reliability with self-directed review of guidelines and cases. The study highlights the effectiveness of ACR O-RADS as a stratification tool for radiologists and supports its continued use in practice.

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

Neurology and associated nanotherapeutics are a complex field in terms of therapeutics and neurological disorder complexity. The brain is an intricate appendage and requires more precise embattled treatment for the particular diseases and hence it is 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 the 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 abilities 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 a new avenue that is engaged with the drug-loaded nanocarriers to demonstrate unique physicochemical properties and tiny size range for penetrating 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 of the novel scopes for the brain targeted drug delivery for complex neurological disorders.

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

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.

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

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.

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

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.

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

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.

Hepatic hemangiomas: the various imaging avatars and its mimickers.

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.

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

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.

Case 275: Multiple Hepatic Hydatid Cysts.

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.

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

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.

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

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.

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

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 (p < 0.05). Higher uptake of gemcitabine predominantly by HCC (64% of administered dose; p < 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.

Case 275.

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].