Publications by authors named "Philip Wong"

341 Publications

Alternative treatment of hip pain from advanced hip osteoarthritis utilizing cooled radiofrequency ablation: single institution pilot study.

Skeletal Radiol 2021 Oct 5. Epub 2021 Oct 5.

Emory University School of Medicine, Atlanta, GA, USA.

Objective: To establish the effectiveness of cooled radiofrequency ablation in managing hip pain from osteoarthritis at 6 months after receiving treatment in patients who failed conservative treatments and are not surgical candidates due to comorbidities or unwillingness to undergo arthroplasty surgery by targeting the femoral and obturator branches and assessing the degree of hip pain relief and change of function.

Materials And Methods: This prospective pilot study includes a total of 11 consecutive patients experiencing persistent chronic hip pain in the setting of advanced osteoarthritis. Patients initially underwent anesthetic blocks of the obturator and femoral nerve branches to determine cooled radiofrequency ablation candidacy. After adequate response to the anesthetic blocks (> 50% immediate pain relief), patients were subjected to the procedures 2-3 weeks later. Treatment response was evaluated utilizing clinically validated questionnaires and visual analog score in order to assess impact on pain severity, stiffness, and functional activities of daily living. Follow-up outcome scores were collected up to 6 months after cooled radiofrequency ablation procedure.

Results: A total of 11 hips were treated consecutively between August 2019 and March 2020 (mean patient age 61.4 years; 8 M:3F). The mean total HOOS score improved significantly from baseline at 17.0 ± 6.0 to 52.9 ± 5.4 at a mean of 6.2 months after treatment (p < 0.0001), with significant improvement in mean pain score from 16.1 ± 6.6 to 53.4 ± 7.4 (p < 0.0001) and mean stiffness score from 15.0 ± 8.1 to 53.6 ± 11.0 (p < 0.0001). No major complications were encountered. No patients went on to re-treatment, surgery, or other intervention.

Conclusion: Image-guided obturator and femoral nerve cooled radiofrequency ablation is effective and safe in treating chronic hip pain/stiffness in the setting of advanced osteoarthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00256-021-03927-0DOI Listing
October 2021

Loss of TDP-43 in male germ cells causes meiotic failure and impairs fertility in mice.

J Biol Chem 2021 Sep 29:101231. Epub 2021 Sep 29.

Meiotic arrest is a common cause of human male infertility, but the causes of this arrest are poorly understood. TAR DNA binding protein of 43 kDa (TDP-43) is highly expressed in spermatocytes in the preleptotene and pachytene stages of meiosis. TDP-43 is linked to several human neurodegenerative disorders wherein its nuclear clearance accompanied by cytoplasmic aggregates underlie neurodegeneration. Exploring the functional requirement for TDP-43 for spermatogenesis for the first time, we show here that conditional knockout (cKO) of the Tardbp gene (encoding TDP-43) in male germ cells of mice leads to reduced testis size, depletion of germ cells, vacuole formation within the seminiferous epithelium, and reduced sperm production. Fertility trials also indicated severe subfertility. Spermatocytes of cKO mice showed failure to complete prophase I of meiosis with arrest at the mid-pachytene stage. Staining of SYCP3 and γH2AX, markers of the meiotic synaptonemal complex and DNA damage, respectively, and Super Illumination Microscopy revealed non-homologous pairing and synapsis defects. Quantitative RT-PCR showed reduction in the expression of genes critical for prophase I of meiosis, including Spo11, Rec8, and Rad21L, as well as those involved in the retinoic acid pathway, critical for entry into meiosis. RNA-seq showed 1036 up- and 1638 downregulated genes (FDR <0.05) in the Tardbp cKO testis, impacting meiosis pathways. Our work reveals a crucial role for TDP-43 in male meiosis and suggests that some forms of meiotic arrest seen in infertile men may result from the loss of function of TDP-43.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbc.2021.101231DOI Listing
September 2021

Hypoxic Jumbo Spheroids On-A-Chip (HOnAChip): Insights into Treatment Efficacy.

Cancers (Basel) 2021 Aug 11;13(16). Epub 2021 Aug 11.

Insitute of Biomedical Engineering, Polytechnique Montréal, 2500 Chemin de Polytechnique, Montréal, QC H3T 1J4, Canada.

Hypoxia is a key characteristic of the tumor microenvironment, too rarely considered during drug development due to the lack of a user-friendly method to culture naturally hypoxic 3D tumor models. In this study, we used soft lithography to engineer a microfluidic platform allowing the culture of up to 240 naturally hypoxic tumor spheroids within an 80 mm by 82.5 mm chip. These jumbo spheroids on a chip are the largest to date (>750 µm), and express gold-standard hypoxic protein CAIX at their core only, a feature absent from smaller spheroids of the same cell lines. Using histopathology, we investigated response to combined radiotherapy (RT) and hypoxic prodrug Tirapazamine (TPZ) on our jumbo spheroids produced using two sarcoma cell lines (STS117 and SK-LMS-1). Our results demonstrate that TPZ preferentially targets the hypoxic core (STS117: = 0.0009; SK-LMS-1: = 0.0038), but the spheroids' hypoxic core harbored as much DNA damage 24 h after irradiation as normoxic spheroid cells. These results validate our microfluidic device and jumbo spheroids as potent fundamental and pre-clinical tools for the study of hypoxia and its effects on treatment response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13164046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394550PMC
August 2021

Brain metabolism in tau and amyloid mouse models of Alzheimer's disease: An MRI study.

NMR Biomed 2021 09 29;34(9):e4568. Epub 2021 May 29.

Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Alzheimer's disease (AD) is the leading cause of cognitive impairment and dementia in elderly individuals. According to the current biomarker framework for "unbiased descriptive classification", biomarkers of neurodegeneration, "N", constitute a critical component in the tri-category "A/T/N" system. Current biomarkers of neurodegeneration suffer from potential drawbacks such as requiring invasive lumbar puncture, involving ionizing radiation, or representing a late, irreversible marker. Recent human studies have suggested that reduced brain oxygen metabolism may be a new functional marker of neurodegeneration in AD, but the heterogeneity and the presence of mixed pathology in human patients did not allow a full understanding of the role of oxygen extraction and metabolism in AD. In this report, global brain oxygen metabolism and related physiological parameters were studied in two AD mouse models with relatively pure pathology, using advanced MRI techniques including T -relaxation-under-spin-tagging (TRUST) and phase contrast (PC) MRI. Additionally, regional cerebral blood flow (CBF) was determined with pseudocontinuous arterial spin labeling. Reduced global oxygen extraction fraction (by -18.7%, p = 0.008), unit-mass cerebral metabolic rate of oxygen (CMRO ) (by -17.4%, p = 0.04) and total CMRO (by -30.8%, p < 0.001) were observed in Tau4RΔK mice-referred to as the tau AD model-which manifested pronounced neurodegeneration, as measured by diminished brain volume (by -15.2%, p < 0.001). Global and regional CBF in these mice were not different from those of wild-type mice (p > 0.05), suggesting normal vascular function. By contrast, in B6;SJL-Tg [APPSWE]2576Kha (APP) mice-referred to as the amyloid AD model-no brain volume reduction, as well as relatively intact brain oxygen extraction and metabolism, were found (p > 0.05). Consistent with the imaging data, behavioral measures of walking distance were impaired in Tau4RΔK mice (p = 0.004), but not in APP mice (p = 0.88). Collectively, these findings support the hypothesis that noninvasive MRI measurement of brain oxygen metabolism may be a promising biomarker of neurodegeneration in AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nbm.4568DOI Listing
September 2021

Use of ultra-low dose computed tomography versus abdominal plain film for assessment of stone-free rates after shock-wave lithotripsy: implications on emergency room visits, surgical procedures, and cost-effectiveness.

Urolithiasis 2021 May 16. Epub 2021 May 16.

Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA.

The aims of this investigation were: (1) to compare residual stone-fragment (RSF) detection rates of ultra-low dose computed tomography (ULD-CT) and abdominal plain film (KUB) in urolithiasis patients undergoing shock-wave lithotripsy (SWL), and (2) to evaluate the downstream sequelae of utilizing these two disparate imaging pathways of differing diagnostic fidelity. A retrospective chart-review of patients undergoing SWL at two high-volume surgical centers was undertaken (2013-2016). RSF diagnostic rates of ULD-CT and KUB were assessed, and the impact of imaging modality used on subsequent emergency room (ER) visits, unplanned procedures, and cost-effectiveness was investigated. Adjusted analyses examined association between imaging modality used and outcomes, and Markov decision-tree analysis was performed to identify a cost advantageous scenario for ULD-CT over KUB. Of 417 patients studied, 57 (13.7%) underwent ULD-CT while the remaining 360 underwent KUB. The RSF rates were 36.8% and 22.8% in the ULD-CT and KUB groups, respectively (p = 0.019). A 5.6% and 18% of the patients deemed stone-free on ULD-CT and KUB, respectively, returned to the ER (p = 0.040). Similarly, 2.8% and 15.1% needed an unplanned surgery (p = 0.027). These findings were confirmed on multivariable analyses, Odds ratios CT-ULD versus KUB: 0.19 and 0.10, respectively, p < 0.05. With regards to cost-effectiveness, at low ULD-CT charges, the ULD-CT follow-up pathway was economically more favorable, but with increasing ULD-CT charges, the KUB follow-up pathway superseded. ULD-CT seems to provide a more 'true' estimate of stone-free status, and in consequence mitigates unwanted emergency and operating room visits by reducing untimely stent removals and false patient reassurances. Further, at low ULD-CT costs, it may also be economically more favorable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00240-021-01273-3DOI Listing
May 2021

Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of Patients With Multiple Metastases: Findings From the NRG-BR001 Phase 1 Trial.

JAMA Oncol 2021 Jun;7(6):845-852

Ohio State University Comprehensive Cancer Center, Columbus.

Importance: Stereotactic body radiotherapy (SBRT) for oligometastases is hypothesized to improve survival and is increasingly used. Little evidence supports its safe use to treat patients with multiple metastases.

Objective: To establish safety of SBRT dose schedules in patients with 3 to 4 metastases or 2 metastases in close proximity to each other.

Design, Setting, And Participants: This phase 1 trial opened on August 4, 2014, and closed to accrual on March 20, 2018. Metastases to 7 anatomic locations were included: bone/osseous (BO), spinal/paraspinal (SP), peripheral lung (PL), central lung (CL), abdominal-pelvic (AP), mediastinal/cervical lymph node (MC), and liver (L). Six patients could be enrolled per anatomic site. The setting was a consortium of North American academic and community practice cancer centers participating in NRG Oncology trials. Patients with breast, prostate, or non-small cell lung cancer with 3 to 4 metastases or 2 metastases in close proximity (≤5 cm) amenable to SBRT were eligible for this phase 1 study. Statistical analyses were performed from December 31, 2017, to September 19, 2019.

Interventions: The starting dose was 50 Gy in 5 fractions (CL, MC), 45 Gy in 3 fractions (PL, AP, L), and 30 Gy in 3 fractions (BO, SP).

Main Outcomes And Measures: The primary end point was dose-limiting toxicity (DLT) defined by the Common Terminology Criteria for Adverse Events, version 4.0, as specific adverse events (AEs) of grades 3 to 5 (definite or probable per the protocol DLT definition) related to SBRT within 180 days of treatment. Dose levels were considered safe if DLTs were observed in no more than 1 of 6 patients per location; otherwise, the dose at that location would be de-escalated.

Results: A total of 42 patients enrolled, 39 were eligible, and 35 (mean [SD] age, 63.1 [14.2] years; 20 men [57.1%]; 30 White patients [85.7%]) were evaluable for DLT. Twelve patients (34.3%) had breast cancer, 10 (28.6%) had non-small cell lung cancer, and 13 (37.1%) had prostate cancer; there was a median of 3 metastases treated per patient. Median survival was not reached. No protocol-defined DLTs were observed. When examining all AEs, 8 instances of grade 3 AEs, most likely related to protocol therapy, occurred approximately 125 to 556 days from SBRT initiation in 7 patients.

Conclusions And Relevance: This phase 1 trial demonstrated the safety of SBRT for patients with 3 to 4 metastases or 2 metastases in close proximity. There were no treatment-related deaths. Late grade 3 AEs demonstrate the need for extended follow-up in long-surviving patients with oligometastatic disease. Treatment with SBRT for multiple metastases has been expanded into multiple ongoing randomized phase 2/3 National Cancer Institute-sponsored trials (NRG-BR002, NRG-LU002).

Trial Registration: ClinicalTrials.gov Identifier: NCT02206334.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2021.0687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063134PMC
June 2021

Early detection of Alzheimer's disease using creatine chemical exchange saturation transfer magnetic resonance imaging.

Neuroimage 2021 08 18;236:118071. Epub 2021 Apr 18.

F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Detecting Alzheimer's disease (AD) at an early stage brings a lot of benefits including disease management and actions to slow the progression of the disease. Here, we demonstrate that reduced creatine chemical exchange saturation transfer (CrCEST) contrast has the potential to serve as a new biomarker for early detection of AD. The results on wild type (WT) mice and two age-matched AD models, namely tauopathy (Tau) and Aβ amyloidosis (APP), indicated that CrCEST contrasts of the cortex and corpus callosum in the APP and Tau mice were significantly reduced compared to WT counterpart at an early stage (6-7 months) (p < 0.011). Two main causes of the reduced CrCEST contrast, i.e. cerebral pH and creatine concentration, were investigated. From phantom and hypercapnia experiments, CrCEST showed excellent sensitivity to pH variations. From MRS results, the creatine concentration in WT and AD mouse brain was equivalent, which suggests that the reduced CrCEST contrast was dominated by cerebral pH change involved in the progression of AD. Immunohistochemical analysis revealed that the abnormal cerebral pH in AD mice may relate to neuroinflammation, a known factor that can cause pH reduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2021.118071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321389PMC
August 2021

Non-alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta-analysis.

JGH Open 2021 Apr 25;5(4):434-445. Epub 2021 Feb 25.

Department of Medicine McGill University Health Centre Montreal Quebec Canada.

Background And Aim: Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are prevalent conditions sharing common pathogenic factors. We performed a systematic literature review and meta-analysis aiming to investigate the association between NAFLD and PCOS among premenopausal PCOS patients.

Methods: Relevant studies were systematically identified from scientific databases until 2019. We calculated pooled odds ratio (OR) using a random-effect model, and heterogeneity was addressed through . Subgroup analyses and meta-regression for various covariates were performed.

Results: Of the 1833 studies retrieved, 23 studies with 7148 participants qualified for quantitative synthesis. The pooled result showed that women with PCOS had a 2.5-fold increase in the risk of NAFLD compared to controls (pooled OR 2.49, 95% confidence interval [CI] 2.20-2.82). In subgroup analyses comparing PCOS to controls, South American/Middle East PCOS patients had a greater risk of NAFLD (OR 3.55, 95% CI 2.27-5.55) compared to their counterpart from Europe (OR 2.22, 95% CI 1.85-2.67) and Asia (OR 2.63, 95% CI 2.20-3.15). Insulin resistance and metabolic syndrome were more frequent in the PCOS group (OR 1.97, 95% CI 1.44-2.71 and OR 3.39, 95% CI 2.42-4.76, respectively). Study quality and body mass index (BMI) were the only covariates that showed a relationship with the outcome in the meta-regression, with a regression coefficient of -2.219 (95% CI -3.927 to -0.511) and -1.929 (95% CI -3.776 to -0.0826), respectively.

Conclusions: This meta-analysis indicates that premenopausal PCOS patients are associated with 2.5-fold increase in the risk of NAFLD, and BMI seems to be the main cofactor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgh3.12512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035436PMC
April 2021

Effectiveness and Renal Safety of Tenofovir Alafenamide Fumarate among Chronic Hepatitis B Patients: Real-World Study.

J Viral Hepat 2021 06 1;28(6):942-950. Epub 2021 Apr 1.

Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada.

Tenofovir alafenamide fumarate (TAF) has high plasma stability resulting in fewer renal adverse events compared to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. We aimed to study the effectiveness and renal safety of TAF in a real-world setting, in patients with or without compromised kidney function. CHB patients (Nucleos(t)ide Analogue [NA]-naïve or experienced) who received TAF >1 year from 11 academic institutions as part of the Canadian Hepatitis B Network (CanHepB) were included. Kidney function was measured by estimated glomerular filtration rate (eGFR) as per Cockcroft-Gault. Patients were followed for up to 160 weeks. Of 176 patients receiving TAF, 143 switched from NA (88% TDF), and 33(19%) were NA naïve. Majority of NA-naïve patients (75%) achieved undetectable HBV DNA after one year of TAF treatment. Majority of patients with eGFR <60 mL/min who had renal deterioration during TDF (76%) reversed to eGFR increase after one year of TAF (p=0.009). Among patients with stage 2 chronic kidney disease (CKD) (eGFR 60-89), the estimated eGFR decline during TDF was halted after switching to TAF (p=0.09). NA-experienced patients with abnormal ALT before TAF showed a significant decline after switching to TAF: -0.005 [-0.006 - -0.004] log ULN U/L/month, p<0.001). In CHB patients, TAF was safe, well-tolerated and effective in this real-world cohort. Switching to TAF led to improved kidney function, particularly in those with stage 2 CKD, which suggests that the indication for TAF in the guidelines could be extended to patients with an eGFR higher than 60 mL/min.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvh.13500DOI Listing
June 2021

Novel Negative Pressure Protective Box in Upper Digestive Endoscopy: A Prospective Case Series.

Am J Gastroenterol 2021 06;116(6):1339-1341

Division of Gastroenterology and Hepatology, McGill University Health Center, McGill University, Montreal, Quebec, Canada.

In the context of the Severe Acute Respiratory Syndrome Coronavirus 2 pandemic, we have developed a novel negative pressure aerosol protector for upper endoscopy (TRACEY). TRACEY is the first endoscopic enclosure to have passed stringent testing for aerosol protection. The following describes its clinical use in a single-center prospective case series. Overall, 15 patients were included. All endoscopic procedures were successful without premature removal of TRACEY. In addition, its use did not lead to significant patient discomfort, technical hinderance, or adverse events. TRACEY seems to offer a safe and easy to use aerosol protection for upper endoscopy and a potential Severe Acute Respiratory Syndrome Coronavirus 2 mitigation strategy in endoscopy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14309/ajg.0000000000001221DOI Listing
June 2021

Discovery of Selective Pituitary Adenylate Cyclase 1 Receptor (PAC1R) Antagonist Peptides Potent in a Maxadilan/PACAP38-Induced Increase in Blood Flow Pharmacodynamic Model.

J Med Chem 2021 03 15;64(6):3427-3438. Epub 2021 Mar 15.

Therapeutic Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, United States.

Inhibition of the pituitary adenylate cyclase 1 receptor (PAC1R) is a novel mechanism that could be used for abortive treatment of acute migraine. Our research began with comparative analysis of known PAC1R ligand scaffolds, PACAP38 and Maxadilan, which resulted in the selection of des(24-42) Maxadilan, , as a starting point. C-terminal modifications of improved the peptide metabolic stability and . SAR investigations identified synergistic combinations of amino acid replacements that significantly increased the PAC1R inhibitory activity of the analogs to the pM IC range. Our modifications further enabled deletion of up to six residues without impacting potency, thus improving peptide ligand binding efficiency. Analogs and exhibited robust efficacy in the rat Maxadilan-induced increase in blood flow (MIIBF) pharmacodynamic model at 0.3 mg/kg subcutaneous dosing. The first cocrystal structure of a PAC1R antagonist peptide () with PAC1R extracellular domain is reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.0c01396DOI Listing
March 2021

A Houdini act: Transient loss of Jka resulting in anti-Jk3 antibody formation.

Transfus Med 2021 Aug 12;31(4):303-304. Epub 2021 Mar 12.

Australian Red Cross Lifeblood, Brisbane, Queensland, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tme.12770DOI Listing
August 2021

Inhibiting cardiac myeloperoxidase alleviates the relaxation defect in hypertrophic cardiomyocytes.

Cardiovasc Res 2021 03 10. Epub 2021 Mar 10.

National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.

Aims: Hypertrophic cardiomyopathy (HCM) is characterised by cardiomyocyte hypertrophy and disarray, and myocardial stiffness due to interstitial fibrosis, which result in impaired left ventricular filling and diastolic dysfunction. The latter manifests as exercise intolerance, angina, and dyspnoea. There is currently no specific treatment for improving diastolic function in HCM. Here, we investigated whether myeloperoxidase (MPO) is expressed in cardiomyocytes and provides a novel therapeutic target for alleviating diastolic dysfunction in HCM.

Methods And Results: Human cardiomyocytes derived from control induced pluripotent stem cells (iPSC-CMs) were shown to express MPO, with MPO levels being increased in iPSC-CMs generated from two HCM patients harbouring sarcomeric mutations in the MYBPC3 and MYH7 genes. The presence of cardiomyocyte MPO was associated with higher chlorination and peroxidation activity, increased levels of 3-chlorotyrosine-modified cardiac myosin binding protein-C (MYBPC3), attenuated phosphorylation of MYBPC3 at Ser-282, perturbed calcium signalling, and impaired cardiomyocyte relaxation. Interestingly, treatment with the MPO inhibitor, AZD5904, reduced 3-chlorotyrosine-modified MYBPC3 levels, restored MYBPC3 phosphorylation, and alleviated the calcium signalling and relaxation defects. Finally, we found that MPO protein was expressed in healthy adult murine and human cardiomyocytes, and MPO levels were increased in diseased hearts with left ventricular hypertrophy.

Conclusion: This study demonstrates that MPO inhibition alleviates the relaxation defect in hypertrophic iPSC-CMs through MYBPC3 phosphorylation. These findings highlight cardiomyocyte MPO as a novel therapeutic target for improving myocardial relaxation associated with HCM, a treatment strategy which can be readily investigated in the clinical setting, given that MPO inhibitors are already available for clinical testing.

Translational Perspective: There are currently no specific therapies for improving diastolic function in patients with HCM. We show for the first time that myeloperoxidase (MPO) is present in and is up-regulated in cardiomyocytes derived from human iPSCs obtained from HCM patients, where it impairs cardiomyocyte relaxation by reducing phosphorylation of cardiac MYBPC3. Treatment with the MPO inhibitor, AZD5904, restored MYBPC3 phosphorylation and alleviated the relaxation defect, demonstrating cardiomyocyte MPO to be a novel therapeutic target for improving diastolic function in HCM, a treatment strategy which can be evaluated in HCM patients given that MPO inhibitors are already available for clinical testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvab077DOI Listing
March 2021

Multiparametric exercise stress cardiovascular magnetic resonance in the diagnosis of coronary artery disease: the EMPIRE trial.

J Cardiovasc Magn Reson 2021 03 4;23(1):17. Epub 2021 Mar 4.

National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore.

Background: Stress cardiovascular magnetic resonance (CMR) offers assessment of ventricular function, myocardial perfusion and viability in a single examination to detect coronary artery disease (CAD). We developed an in-scanner exercise stress CMR (ExCMR) protocol using supine cycle ergometer and aimed to examine the diagnostic value of a multiparametric approach in patients with suspected CAD, compared with invasive fractional flow reserve (FFR) as the reference gold standard.

Methods: In this single-centre prospective study, patients who had symptoms of angina and at least one cardiovascular disease risk factor underwent both ExCMR and invasive angiography with FFR. Rest-based left ventricular function (ejection fraction, regional wall motion abnormalities), tissue characteristics and exercise stress-derived (perfusion defects, inducible regional wall motion abnormalities and peak exercise cardiac index percentile-rank) CMR parameters were evaluated in the study.

Results: In the 60 recruited patients with intermediate CAD risk, 50% had haemodynamically significant CAD based on FFR. Of all the CMR parameters assessed, the late gadolinium enhancement, stress-inducible regional wall motion abnormalities, perfusion defects and peak exercise cardiac index percentile-rank were independently associated with FFR-positive CAD. Indeed, this multiparametric approach offered the highest incremental diagnostic value compared to a clinical risk model (χ for the diagnosis of FFR-positive increased from 7.6 to 55.9; P < 0.001) and excellent performance [c-statistic area under the curve 0.97 (95% CI: 0.94-1.00)] in discriminating between FFR-normal and FFR-positive patients.

Conclusion: The study demonstrates the clinical potential of using in-scanner multiparametric ExCMR to accurately diagnose CAD.

Trial Registration: ClinicalTrials.gov, NCT03217227, Registered 11 July 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03217227?id=NCT03217227&draw=2&rank=1&load=cart.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12968-021-00705-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931509PMC
March 2021

Clinicoradiographic predictors of percutaneous bone biopsy results among patients with suspected thoracolumbar spine infection.

Skeletal Radiol 2021 Sep 12;50(9):1801-1808. Epub 2021 Feb 12.

Department of Radiology and Imaging Sciences Section of Musculoskeletal Imaging, Emory University Hospital, 59 Executive Park South, 4th Floor Suite, 4009, 30329, Atlanta, GA, USA.

Background: Image-guided percutaneous thoracolumbar spine biopsy is frequently performed in the setting of suspected septic facet arthritis or discitis osteomyelitis (DOM). There are limited data regarding factors associated with a positive biopsy result among these patients.

Materials And Methods: Patients with suspected DOM who underwent spine biopsy were identified. Samples yielding a positive culture and/or histopathology suggestive of acute osteomyelitis were considered positive. The associations between selected medical comorbidities, laboratory values, pre-biopsy antibiotic administration, imaging findings and biopsy results were investigated.

Results: 121 patients underwent percutaneous biopsy with 35.5% yielding positive results. Biopsy results showed no correlation with comorbidities. The only laboratory value that correlated with a positive biopsy yield was blood culture positivity (p = 0.03). The imaging findings that correlated with a positive biopsy yield were the presence of a paraspinal fluid collection or epidural abscess (p = 0.003 and 0.018, respectively). Sampling paraspinal fluid collections, when present, resulted in a higher rate of a positive biopsy yield compared to sampling of bone or disc (p = 0.006). Patients who received antibiotics had a higher rate of a positive biopsy yield (p = 0.014). In those with positive blood cultures, biopsy yielded the same antimicrobial susceptibility profile in 13/14 cases.

Conclusion: The presence of a paraspinal fluid collection or epidural abscess is correlated with positive biopsy yield, and paraspinal fluid collections should be targeted for biopsy. Other imaging findings did not correlate with biopsy yield. Biopsy may not offer additional information for patients with positive blood cultures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00256-021-03735-6DOI Listing
September 2021

X-ray on chip: Quantifying therapeutic synergies between radiotherapy and anticancer drugs using soft tissue sarcoma tumor spheroids.

Radiother Oncol 2021 04 29;157:175-181. Epub 2021 Jan 29.

Institut du Cancer de Montréal, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Canada; Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal (CHUM), Canada; Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. Electronic address:

Purpose: Radioresistance, tumor microenvironment, and normal tissue toxicity from radiation limit the efficacy of radiotherapy in treating cancers. These challenges can be tackled by the discovery of new radiosensitizing and radioprotecting agents aimed at increasing the therapeutic efficacy of radiotherapy. The goal of this work was to develop a miniaturized microfluidic platform for the discovery of drugs that could be used in combination with radiotherapy. The microfluidic system will allow the toxicity testing of cancer spheroids to different combinations of radiotherapy and molecular agents.

Materials And Methods: An orthovoltage-based technique was used to expose the devices to multiple X-ray radiation doses simultaneously. Radiation dose-dependent DNA double-strand breaks in soft tissue sarcoma (STS) spheroids were quantified using comet assays. Analysis of proliferative death using clonogenic assays was also performed, and synergy between treatments with Talazoparib, Pazopanib, AZD7762, and radiotherapy was quantified using dedicated statistical tests.

Results: The developed microfluidic system with simple magnetic valves was capable of growing 336 homogeneous STS spheroids. The irradiation of the microfluidic system with an orthovoltage-based technique enabled the screening of sixteen drug-radiotherapy combinations with minimal reagent consumption. Using this framework, we predicted a therapeutic synergy between a novel anticancer drug Talazoparib and radiotherapy for STS. No synergy was found between RT and either Pazopanib or AZD7762, as the combinations were found to be additive.

Conclusion: This methodology lays the basis for the systemic search for molecular agent/radiotherapy synergies among preexisting pharmaceutical compounds libraries, in the hope to identify failed drug candidates in monotherapy that, in the presence of radiotherapy, would make it through clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2021.01.018DOI Listing
April 2021

Senolytic Targeting of Bcl-2 Anti-Apoptotic Family Increases Cell Death in Irradiated Sarcoma Cells.

Cancers (Basel) 2021 Jan 21;13(3). Epub 2021 Jan 21.

Institut du Cancer de Montréal (ICM), Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900 St. Denis Street, Montreal, QC H2X 0A9, Canada.

Radiotherapy (RT) is a key component of cancer treatment. Most of the time, radiation is given after surgery but for soft-tissue sarcomas (STS), pre-surgical radiation is commonly utilized. However, despite improvements in RT accuracy, the rate of local recurrence remains high and is the major cause of death for patients with STS. A better understanding of cell fates in response to RT could provide new therapeutic options to enhance tumour cell killing by RT and facilitate surgical resection. Here, we showed that irradiated STS cell cultures do not die but instead undergo therapy-induced senescence (TIS), which is characterized by proliferation arrest, senescence-associated β-galactosidase activity, secretion of inflammatory cytokines and persistent DNA damage. STS-TIS was also associated with increased levels of the anti-apoptotic Bcl-2 family of proteins which rendered cells targetable using senolytic Bcl-2 inhibitors. As oppose to radiation alone, the addition of senolytic agents Venetoclax (ABT-199) or Navitoclax (ABT-263) after irradiation induced a rapid apoptotic cell death in STS monolayer cultures and in a more complex three-dimensional culture model. Together, these data suggest a new promising therapeutic approach for sarcoma patients who receive neoadjuvant RT. The addition of senolytic agents to radiation treatments may significantly reduce tumour volume prior to surgery and thereby improve the clinical outcome of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13030386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866159PMC
January 2021

Intravascular large B-cell lymphoma presenting with extensive pulmonary embolism.

Br J Haematol 2021 02 18;192(4):677. Epub 2020 Dec 18.

Department of Haematology and Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Herston, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17182DOI Listing
February 2021

Prevalence and predictors of nonalcoholic fatty liver disease in South Asian women with polycystic ovary syndrome.

World J Gastroenterol 2020 Nov;26(44):7046-7060

Department of Medicine, McGill University Health Centre, Montreal H4A3J1, Canada.

Background: Polycystic ovary disease (PCOS) may be a risk factor for nonalcoholic fatty liver disease (NAFLD) due to common pathogenetic pathways, including insulin resistance and obesity. Both PCOS and NAFLD are more severe in South Asian women. Data on NAFLD in South Asian women with PCOS are lacking.

Aim: To investigate prevalence and predictors of NAFLD and liver fibrosis in PCOS patients from South Asia.

Methods: We conducted an observational routine screening program by means of transient elastography (TE) with associated controlled attenuation parameter (CAP). NAFLD was defined as CAP ≥ 288 decibels per meter. Significant liver fibrosis (stage 2 and higher out of 4) was defined as TE measurement ≥ 8.0 kilopascals. Elevated alanine aminotransferase (ALT) was defined as ALT > 24 IU/L, as per upper limit of normal reported in South Asian women. Biochemical hyperandrogenism was defined as free androgen index > 5. Predictors of NAFLD were determined by logistic regression analysis.

Results: 101 PCOS patients (mean age 36.3 years) with no significant alcohol intake or viral hepatitis were included. Prevalence of NAFLD and significant liver fibrosis was 39.6% and 6.9%, respectively. Elevated ALT was observed in 40% and 11.5% of patients with and without NAFLD, respectively. After adjusting for duration of PCOS and insulin resistance measured by homeostasis model for assessment of insulin resistance, independent predictors of NAFLD were higher body mass index [adjusted odds ratio (aOR) 1.30, 95% confidence interval (CI): 1.13-1.52], hyperandrogenism (aOR: 5.32, 95%CI: 1.56-18.17) and elevated ALT (aOR: 3.54, 95%CI: 1.10-11.47). Lifetime cardiovascular risk was higher in patients with NAFLD compared to those without NAFLD (0.31 ± 0.11 0.26 ± 0.13).

Conclusion: Despite their young age, NAFLD diagnosed by TE with CAP is a frequent comorbidity in South Asian women with PCOS and is strongly associated with higher body mass index and hyperandrogenism. Non-invasive screening strategies could help early diagnosis and initiation of interventions, including counselling on weight loss, cardiovascular risk stratification and linkage to hepatology care where appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v26.i44.7046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701948PMC
November 2020

Distinct Hepatitis B and HIV co-infected populations in Canada.

J Viral Hepat 2021 03 2;28(3):517-527. Epub 2021 Jan 2.

University of Calgary, Calgary, Alberta, Canada.

Due to shared modes of exposure, HIV-HBV co-infection is common worldwide. Increased knowledge of the demographic and clinical characteristics of the co-infected population will allow us to optimize our approach to management of both infections in clinical practice. The Canadian Hepatitis B Network Cohort was utilized to conduct a cross-sectional evaluation of the demographic, biochemical, fibrotic and treatment characteristics of HIV-HBV patients and a comparator HBV group. From a total of 5996 HBV-infected patients, 335 HIV-HBV patients were identified. HIV-HBV patients were characterized by older median age, higher male and lower Asian proportion, more advanced fibrosis and higher anti-HBV therapy use (91% vs. 30%) than the HBV-positive / HIV seronegative comparator group. A history of reported high-risk exposure activities (drug use, high-risk sexual contact) was more common in HIV-HBV patients. HIV-HBV patients with reported high-risk exposure activities had higher male proportion, more Caucasian ethnicity and higher prevalence of cirrhosis than HIV-HBV patients born in an endemic country. In the main cohort, age ≥60 years, male sex, elevated ALT, the presence of comorbidity and HCV seropositivity were independent predictors of significant fibrosis. HIV seropositivity was not an independent predictor of advanced fibrosis (adj OR 0.75 [95%CI: 0.34-1.67]). In conclusion, Canadian co-infected patients differed considerably from those with mono-infection. Furthermore, HIV-HBV-infected patients who report high-risk behaviours and those born in endemic countries represent two distinct subpopulations, which should be considered when engaging these patients in care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvh.13453DOI Listing
March 2021

Quality of Life: A Prospective Randomized Trial of Palliative Volumetric Arc Therapy Versus 3-Dimensional Conventional Radiation Therapy.

Int J Radiat Oncol Biol Phys 2021 04 28;109(5):1431-1439. Epub 2020 Nov 28.

Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal, Montréal, Canada.

Purpose: Volumetric arc therapy (VMAT) is a radiation therapy (RT) technique that spares normal tissues from high and intermediate RT doses but increases the volume of tissues receiving low doses of RT compared with 3-dimensional conformal RT (3DCRT). We hypothesized that palliative VMAT would reduce the detriment to patient quality of life (QOL) compared with palliative 3DCRT.

Methods And Materials: This phase 2 trial randomized patients to palliative RT using VMAT or 3DCRT to 1 painful site of metastatic disease in the trunk. Treating physicians could choose 8 Gy in 1 fraction or 20 Gy in 5 fractions to stratify randomization. The primary endpoint was the change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30) global health status QOL subscale at 1 week after RT. Repeated measures analysis of variance was used to assess the relationship of patient QOL over time with other factors.

Results: From July 2014 to November 2017, 37 patients who underwent 3DCRT and 32 patients who underwent VMAT were randomized into the study. Median overall survival was 9 months. Overall pain responses to RT were equivalent (P = .53) between the techniques. Patient compliance in returning QOL questionnaires was 94%, 81%, and 69% at baseline, 1 week after RT, and 1 month after RT, respectively. At 1 week after RT, change in global QOL was not significantly (P = .31) different between VMAT versus 3DCRT. At 4 weeks after RT, VMAT induced significantly (P = .049) less global QOL deterioration than 3DCRT did. Patients who underwent VMAT maintained better physical (P = .012), role (P = .041), and social (P = .025) functioning, but they reported more diarrhea symptoms (P = .017) than in the 3DCRT group.

Conclusions: Palliative VMAT and 3DCRT did not differ in their ability to control pain; however, palliative VMAT induced fewer QOL detriments than 3DCRT did at 4 weeks after RT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2020.11.061DOI Listing
April 2021

The Impact of Pathological Narcissism on Affect Following Social Rejection.

J Pers Disord 2021 Oct 27;35(5):691-707. Epub 2020 Oct 27.

Long Island University - Brooklyn, New York.

Previous research has shown that narcissism is associated with interpersonal difficulties and maladaptive affective responses to social rejection. In the current studies, the authors examined two phenotypes of pathological narcissism, narcissistic grandiosity and narcissistic vulnerability, and their impact on individuals' affective responses in two distinctive social rejection paradigms. Participants from Study 1 (N = 239), recruited from a multicultural university and Amazon's Mechanical Turk, completed Cyberball, a computerized social rejection paradigm. Participants from Study 2 (N = 238) were recruited from a multicultural university and participated in an in vivo group rejection paradigm in a laboratory. Results indicated that following the rejection in both studies, narcissistic vulnerability positively predicted explicit negative affect and state anger. In addition, the positive relationship between narcissistic vulnerability and explicit negative affect was moderated by greater implicit negative affect in Study 2. The implications and limitations of these findings are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1521/pedi_2020_34_492DOI Listing
October 2021

Hemizygous deletion of Tbk1 worsens neuromuscular junction pathology in TDP-43 transgenic mice.

Exp Neurol 2021 01 8;335:113496. Epub 2020 Oct 8.

Department of Neurology, University of Ulm, Ulm, Germany; Division of Neurodegenerative Disorders, Department of Neurology, Mannheim Center for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Germany. Electronic address:

Mutations in the genes TARDBP (encoding the TDP-43 protein) and TBK1 can cause familial ALS. Neuronal cytoplasmatic accumulations of the misfolded, hyperphosphorylated RNA-binding protein TDP-43 are the pathological hallmark of most ALS cases and have been suggested to be a key aspect of ALS pathogenesis. Pharmacological induction of autophagy has been shown to reduce mutant TDP-43 aggregates and alleviate motor deficits in mice. TBK1 is exemplary for several other ALS genes that regulate autophagy. Consequently, we employed double mutant mice with both a heterozygous Tbk1 deletion and transgenic expression of human TDP-43 to test the hypothesis that impaired autophagy reduces intracellular clearance of an aggregation-prone protein and enhances toxicity of mutant TDP-43. The heterozygous deletion of Tbk1 did not change expression or cellular distribution of TDP-43 protein, motor neuron loss or reactive gliosis in the spinal cord of double-mutant mice at the age of 19 months. However, it aggravated muscle denervation and, albeit to a small and variable degree, motor dysfunction in TDP-43 transgenic mice, as similarly observed in the SOD1 transgenic mouse model for ALS before. Conclusively, our findings suggest that TBK1 mutations can affect the neuromuscular synapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.expneurol.2020.113496DOI Listing
January 2021

T and Small Protrusion (TAP) vs Double-Kissing Crush Technique: Insights From In Vitro Models.

Cardiovasc Revasc Med 2021 03 10;24:11-17. Epub 2020 Sep 10.

National Heart Research Institute of Singapore, National Heart Centre Singapore, Singapore; Department of Biomedical Engineering, National University of Singapore, Singapore. Electronic address:

Background: Percutaneous coronary interventions on complex bifurcation lesions may require implantation of two stents to appropriately treat diffuse side-branch (SB) disease. Comparisons among different bifurcation stenting techniques are continuously attempted by various study designs (bench tests, computer simulations, clinical studies). Among different techniques, double kissing crush (DKC) represents the last evolution for "crushing" while T and small Protrusion (TAP) represents the evolution of "T stenting". Both techniques are actually gaining popularity, but head-to-head comparisons are lacking.

Methods And Results: Two last generation drug-eluting stents (Synergy™, Boston Scientific, MA, USA and Ultimaster™,Terumo Corp., Japan) were implanted in left main bifurcation bench models using TAP (n = 6 sets) and DKC (n = 6 sets) techniques. A peristaltic pump with fresh porcine blood was used to perfuse the blood through the silicone model at a flow rate of 200 ml/min for 4 min. Optical coherence tomography (OCT) was used to assess stent struts geometry and thrombus formation. SB cross sectional area as well as SB obstruction did not significantly differ between the two techniques. Numerical (but not statistically significant) differences were found in terms of malapposed struts (fewer with TAP) and floating struts (fewer with DKC). Thrombus formation after blood perfusion was similar between TAP and DKC technique (1.53 ± 1.12 vs. 1.20 ± 1.01 mm, p = 0.6).

Conclusion: The result of the present in-vitro study shows the absence of significant difference between TAP and DKC in terms of stent struts apposition and acute thrombus formation potential. Despite the completely different technical steps required, both techniques have similar performance according to such articulated pre-clinical evaluation. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?: Due to its limited complexity, T and Protrusion (TAP) technique is considered the to-go technique for bifurcation lesions with good long-term results. Recently, double kissing crush (DKC) technique has been gaining popularity and demonstrated promising results in randomized clinical trials. WHAT DOES THIS STUDY ADD?: This in-vitro bench test study provides a unique detailed OCT comparison and local hemodynamic environment analysis of the two techniques. HOW MIGHT THIS IMPACT ON CLINICAL PRACTICE?: New insights of acute thrombogenicity and computational flow model simulation may guide percutaneous therapeutic strategies of bifurcation lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carrev.2020.09.013DOI Listing
March 2021

Safety and efficacy comparison of three- vs four-needle technique in the management of moderate to severe osteoarthritis of the knee using cooled radiofrequency ablation.

Skeletal Radiol 2021 Apr 24;50(4):739-750. Epub 2020 Sep 24.

Emory University School of Medicine, Atlanta, GA, USA.

Purpose: To analyze the safety and efficacy of image-guided genicular nerve cooled radiofrequency ablation (C-RFA) for the treatment of pain in non-surgical candidates with moderate to severe knee osteoarthritis (OA) and to compare three- vs four-needle technique.

Method: This retrospective study included 50 consecutive patients with pain from moderate to severe knee OA refractory to anti-inflammatory analgesia that failed multiple intra-articular lidocaine-steroid injections and who were non-surgical total knee arthroplasty candidates because of comorbidities. Patients initially underwent anesthetic blocks of the superior medial/lateral femoral and inferior medial tibial genicular nerve branches and in some cases the suprapatellar genicular nerve branch. Radiofrequency ablations of the same nerve branches were performed 1-2 weeks after the nerve blocks. Follow-up outcome was collected at approximately 2 weeks, 1, 3, and 6 months after the C-RFA procedure utilizing VAS and clinically validated questionnaires.

Results: A total of 77 knees were treated. The mean total KOOS score improved significantly from baseline at 24.7 ± 14.1 to 59.4 ± 26.5 at 6 months after treatment (p < 0.0001), with significant improvement in mean pain score from 25.5 ± 15.2 to 64.5 ± 25.2 (p < 0.0001) and mean stiffness score from 35.1 ± 21.9 to 65.8 ± 24.9 (p < 0.0001). At 6 months, 65% of all patients demonstrated decreased opiate medication usage, 79% of patients in the four-needle, and 45% of patients in the three-needle arms (p = 0.03). No complications were reported.

Conclusions: The four-needle treatment approach offers an advantage in the overall efficacy in treating stiffness and pain in patients with moderate-to-severe OA refractory to conservative treatments leading to decreased opiate usage without complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00256-020-03619-1DOI Listing
April 2021

Improved detection of adenomas and sessile serrated polyps is maintained with continuous audit of colonoscopy.

BMJ Open Gastroenterol 2020 07;7(1)

MercyAscot, Auckland, New Zealand.

Background: The audit process may help improve performance indicators for colonoscopy quality but it is unclear whether this is sustained over several years.

Methods: 44138 procedures for 28 endoscopists from 2004 to 2019 were analysed for polyp detection rate and withdrawal time. From 2012, 14 endoscopists were analysed with additional data on polyp histology and number of polyps removed.

Results: Polyp detection increased from 40.7% in 2004 to 62.2% in 2019; removal of polyps>1 cm remained constant (11%). Adenoma detection rate was 25.8% in 2012 and 28.3% in 2019. Sessile serrated polyp (SSP) detection rate increased from 4.5% to 14.7%; most of the increase was in the first 2 years of the histology part of the audit. There was a significant correlation of adenoma detection rate with mean number of adenomas (r=0.72, p=0.004) and a significant correlation of SSP detection with mean number of SSPs (r=0.85, p=0.0001).

Conclusion: The audit process appears to encourage a higher rate of polyp detection. This was due to increased detection of smaller polyps and increased detection of SSPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjgast-2020-000425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368474PMC
July 2020

D-Glucose uptake and clearance in the tauopathy Alzheimer's disease mouse brain detected by on-resonance variable delay multiple pulse MRI.

J Cereb Blood Flow Metab 2021 05 16;41(5):1013-1025. Epub 2020 Jul 16.

F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA.

In this study, we applied on-resonance variable delay multiple pulse (onVDMP) MRI to study D-glucose uptake in a mouse model of Alzheimer's disease (AD) tauopathy and demonstrated its feasibility in discriminating AD mice from wild-type mice. The D-glucose uptake in the cortex of AD mice (1.70 ± 1.33%) was significantly reduced compared to that of wild-type mice (5.42 ± 0.70%,  = 0.0051). Also, a slower D-glucose uptake rate was found in the cerebrospinal fluid (CSF) of AD mice (0.08 ± 0.01 min) compared to their wild-type counterpart (0.56 ± 0.1 min,  < 0.001), which suggests the presence of an impaired glucose transporter on both blood-brain and blood-CSF barriers of these AD mice. Clearance of D-glucose was observed in the CSF of wild-type mice but not AD mice, which suggests dysfunction of the glymphatic system in the AD mice. The results in this study indicate that onVDMP MRI could be a cost-effective and widely available method for simultaneously evaluating glucose transporter and glymphatic function of AD. This study also suggests that tau protein affects the D-glucose uptake and glymphatic impairment in AD at a time point preceding neurofibrillary tangle pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0271678X20941264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054725PMC
May 2021

Lipid-weighted intraoperative photoacoustic tomography of breast tumors: Volumetric comparison to preoperative MRI.

Photoacoustics 2020 Jun 24;18:100165. Epub 2020 Apr 24.

Imaging Program, Lawson Health Research Institute, London, Ontario, Canada.

With a lifetime risk of 1 in 8, breast cancer continues to be a major concern for women and their physicians. The optimal treatment of the disease depends on the stage of the cancer at diagnosis, which is typically assessed using medical imaging. However, currently employed imaging systems for breast tumor measurement rarely agree perfectly. Our group developed an Intraoperative Photoacoustic Screening (iPAS) soft tissue scanner featuring high bulk tissue sensitivity, a clinically compatible scan-time of 6 min, imaging depths greater than 2 cm and the capability to visualize whole breast tumors based on their lipid, rather than hemoglobin, profile. Here, we report on the first clinical experience with breast cancer patients by comparing tumor-measurement using iPAS, preoperative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and gold-standard pathology. Tumor size was measured volumetrically for iPAS and DCE-MRI, and separately using maximum diameters for pathology, DCE-MRI and iPAS. Comparisons were performed using Pearson's correlation coefficients, and the non-parametric Wilcoxon signed-rank test. Twelve consecutive patients were included in the study, contingent on pathologically documented invasive carcinoma. iPAS volumetric tumor size was positively correlated to DCE-MRI (Pearson's r = 0.78, p = 0.003) and not significantly different (Wilcoxon, p = 0.97). In comparison to pathology, tumor diameters given by iPAS were positively correlated (Pearson's r = 0.87, p = 0.0002) and significantly different (Wilcoxon, p = 0.0015). The results indicated that volumetric-measurement of invasive breast tumors with iPAS is similar to that of DCE-MRI. On the other hand, tumor diameter measurements were less reliable. Beyond enhancing surgical specimen examination, an extension of this technology to diagnostic imaging promises a new perspective on tumor assessment, potentially improving our current understanding and treatment of breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pacs.2020.100165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226881PMC
June 2020

Bioresorbable Polymeric Scaffold in Cardiovascular Applications.

Int J Mol Sci 2020 May 13;21(10). Epub 2020 May 13.

School of Materials Science and Engineering, Nanyang Technological University, Nanyang Avenue, Singapore 639798, Singapore.

Advances in material science and innovative medical technologies have allowed the development of less invasive interventional procedures for deploying implant devices, including scaffolds for cardiac tissue engineering. Biodegradable materials (e.g., resorbable polymers) are employed in devices that are only needed for a transient period. In the case of coronary stents, the device is only required for 6-8 months before positive remodelling takes place. Hence, biodegradable polymeric stents have been considered to promote this positive remodelling and eliminate the issue of permanent caging of the vessel. In tissue engineering, the role of the scaffold is to support favourable cell-scaffold interaction to stimulate formation of functional tissue. The ideal outcome is for the cells to produce their own extracellular matrix over time and eventually replace the implanted scaffold or tissue engineered construct. Synthetic biodegradable polymers are the favoured candidates as scaffolds, because their degradation rates can be manipulated over a broad time scale, and they may be functionalised easily. This review presents an overview of coronary heart disease, the limitations of current interventions and how biomaterials can be used to potentially circumvent these shortcomings in bioresorbable stents, vascular grafts and cardiac patches. The material specifications, type of polymers used, current progress and future challenges for each application will be discussed in this manuscript.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21103444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279389PMC
May 2020

Alternate treatment approach to subchondral insufficiency fracture of the knee utilizing genicular nerve cooled radiofrequency ablation and adjunctive bisphosphonate supplementation: A case report.

Radiol Case Rep 2020 Jun 5;15(6):691-696. Epub 2020 Apr 5.

Department of Radiology, Emory University School of Medicine, Atlanta, GA, USA.

Subchondral insufficiency fractures of the knee are commonly misdiagnosed fractures that are both very painful and difficult to treat. A conservative treatment modality to control symptoms during rehabilitation has not previously been described. This case report presents the alternate use of cooled radiofrequency ablation technique of the genicular nerves for pain relief and bisphosphonate infusion to address the underlying poor bone mineralization/density with imaging follow-up before and after instituted treatments. A middle-aged female patient presenting with atraumatic pain in the medial aspect of the left knee diagnosed on an original magnetic resonance imaging as an insufficiency fracture and debilitating pain. Multiple-surgeon opinions of total knee arthroplasty were not a consideration the patient wanted or could consider given her lifestyle. Cooled radiofrequency ablation of the genicular nerve branches was performed with significant-complete pain relief achieved that lasted at least 6 months. Bisphosphonate infusions were instituted to address the underlying osteoporosis detected by a dual energy X-ray absorptiometry (DEXA) scan. Clinical performance after the radiofrequency ablations was followed with clinically validated surveys (The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)/Knee Injury and Osteoarthritis Outcome Score (KOOS)) at 2 weeks, 1, 3, and 6 months. Patient was also asked to follow a restricted-modified weight-bearing plan for 3 months followed by physical therapy. Eight weeks apart of bisphosphonate infusions were delivered after proper administration of vitamin D. There was resolution of the insufficiency fracture at the medial femoral condyle between the magnetic resonance imaging exams within 4.5 months apart treated with restricted weight-bearing regimen. Pain resolution, significant improved function, and range of motion were the end results of our instituted treatment plan. This case reports presents an alternate pathway for the treatment of this condition especially when there is lack of consensus among physicians in how to best address this condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radcr.2020.02.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138926PMC
June 2020
-->