Publications by authors named "Gregory Lee"

156 Publications

Lymphatic Pathways of the Thorax: Predictable Patterns of Spread.

AJR Am J Roentgenol 2021 03 30;216(3):649-658. Epub 2020 Dec 30.

Department of Radiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160.

This article reviews thoracic lymphatic pathways and tributaries, discusses lymphatic anatomic variants and their clinical implications, and emphasizes common patterns of thoracic lymphadenopathy from extrapulmonary malignancies. Recognition of common patterns and pathways of thoracic lymphatic drainage can help identify the site of tumor origin and allow a more focused examination of disease extent, both of which are important for disease prognosis and management.
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http://dx.doi.org/10.2214/AJR.20.23523DOI Listing
March 2021

Accessory and Incomplete Lung Fissures: Clinical and Histopathologic Implications.

J Thorac Imaging 2020 Oct 16. Epub 2020 Oct 16.

Department of Radiology, Mayo Clinic, Jacksonville, FL.

Objective: This article reviews the anatomy, histology, and disease processes of pulmonary fissures, with emphasis on clinical implications of accessory and incomplete fissures.

Conclusion: Accessory and incomplete pulmonary fissures are often overlooked during routine imaging but can have profound clinical importance. Knowledge of fissure anatomy could improve diagnostic accuracy and inform prognosis for oncologists, interventional pulmonologists, and thoracic surgeons.
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http://dx.doi.org/10.1097/RTI.0000000000000558DOI Listing
October 2020

Certification and Credentials of Intravitreal Injection Proceduralists in the United States.

Ophthalmol Retina 2020 Oct 15. Epub 2020 Oct 15.

Retina Center of Minnesota, Minneapolis, Minnesota. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2020.10.006DOI Listing
October 2020

Atypical language representation as a protective factor against verbal memory decline following epilepsy surgery.

Epilepsy Behav 2020 11 18;112:107451. Epub 2020 Sep 18.

Barrow Neurological Institute, United States of America. Electronic address:

Objective: An important role of neuropsychology in the preoperative evaluation of epilepsy surgery candidates is to assess risk for postoperative memory decline. One factor associated with postoperative verbal memory decline is surgery in the language-dominant temporal lobe (TL). The aim of the study was to determine whether atypical language representation has a protective effect against verbal memory decline following left temporal, frontotemporal, or hippocampal excision.

Methods: Data from 61 patients with medically refractory epilepsy, Wada testing, and pre- and postsurgical memory assessment from four comprehensive epilepsy surgery centers were gathered and examined for pre- to postsurgical memory change. Wada testing was used to determine language dominance (left vs. atypical [bilateral + right]). Postoperative memory change was examined at both the individual (using nonparametric analyses) and group (using parametric analyses) levels for the two language dominance groups.

Results: Significant postoperative verbal memory decline was observed in the left hemisphere language-dominant group, while the atypical language group showed verbal memory improvement. Individuals with left hemisphere language dominance were more likely to show postoperative declines in verbal memory, whereas individuals with atypical language dominance were significantly less likely to decline. As expected, there were no significant differences between language groups with regard to postoperative visuospatial memory outcome.

Conclusion: Patients with atypical language dominance had better verbal memory outcomes following left hemisphere resections than those with left hemisphere language dominance suggesting that typical memory substrates likely reorganized along with language. Thus, atypical cerebral organization of language may be considered a protective factor against verbal memory decline following epilepsy surgery involving the left TL.
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http://dx.doi.org/10.1016/j.yebeh.2020.107451DOI Listing
November 2020

Identification of neural and psychophysical predictors of headache reduction after cognitive behavioral therapy in adolescents with migraine.

Pain 2021 Feb;162(2):372-381

Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Abstract: Cognitive behavioral therapy (CBT) is a psychological intervention that involves development of coping strategies to reduce the experience of pain. Although CBT is a promising intervention to reduce headache days in patients with migraine, it may not be effective for all patients. Thus, there is a need to identify markers that could predict which patients will respond to CBT. We aimed to determine whether baseline brain function and amygdalar connectivity, assessed by functional magnetic resonance imaging, or pain modulation capacities, assessed by the conditioned pain modulation (CPM) response, can predict a reduction in headache days after CBT in adolescents with migraine. Patients with migraine (n = 20; age range 10-17 years) completed 8 weekly CBT sessions. The CPM response was examined in the trapezius and the leg. Headache days significantly decreased after CBT (P < 0.001). Greater functional connectivity before CBT between the right amygdala and frontal gyrus, anterior cingulate cortex, and precentral gyrus was related to greater headache reduction after CBT. Greater reduction in headache days after CBT was related with less efficient CPM response before CBT at the trapezius (r = -0.492, P = 0.028) but not at the leg. This study found that headache reduction after CBT was related to right amygdala connectivity with frontal and sensorimotor regions at baseline as well as baseline pain modulation capacities. These findings suggest that individual differences in brain function and pain modulation can be associated with clinical improvements and help with determination of CBT responsiveness.
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http://dx.doi.org/10.1097/j.pain.0000000000002029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855380PMC
February 2021

Reply to "Pulmonary Sarcoidlike Granulomatosis".

AJR Am J Roentgenol 2020 08;215(2):W26

University of Kansas Medical Center, Kansas City, MO.

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http://dx.doi.org/10.2214/AJR.20.22940DOI Listing
August 2020

A Case of Atraumatic Acute Compartment Syndrome: Beware of the Existence of This Orthopaedic Emergency: A Case Report.

JBJS Case Connect 2020 Apr-Jun;10(2):e0497

1Emory University School of Medicine, Atlanta, Georgia 2Morehouse School of Medicine, Atlanta, Georgia.

Case: We present a 44-year-old man diagnosed with atraumatic, idiopathic acute compartment syndrome (ACS) of the left lower extremity treated with an emergent single incision fasciotomy with the release of the anterior and lateral compartments. The patient's condition was diagnosed without delay and successfully treated, resulting in a full recovery.

Conclusion: Immediate diagnosis and emergent surgical treatment of atraumatic ACS is critical in preventing surgical complications and preserving function of the limb. Recognition of this condition existing in the absence of the typical history of an inciting event or underlying predisposition is important to avoid missing the need for emergent surgical intervention.
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http://dx.doi.org/10.2106/JBJS.CC.19.00497DOI Listing
February 2021

Cerebral microvascular and microstructural integrity is regionally altered in patients with systemic lupus erythematosus.

Arthritis Res Ther 2020 06 8;22(1):135. Epub 2020 Jun 8.

Division of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA.

Background: To measure regional brain microvascular and microstructural changes in childhood-onset SLE (cSLE) using diffusion-weighted imaging (DWI) at multiple b values and investigate relationships of those measures with neurocognitive function and disease activity.

Methods: In this cross-sectional, case-control study, vascular volume fraction, effective diffusion, parenchymal diffusion, and blood flow parameters were regionally compared in cSLE patients and matched healthy controls. These markers of microvascular and microstructural integrity were derived by diffusion-weighted brain MRI and intravoxel incoherent motion (IVIM) modeling. Formal neurocognitive testing was completed focused on the domains of attention, visuoconstructional ability, working memory, and psychomotor speed. Test scores and measures of disease severity were regressed against regional microvascular integrity parameters among cSLE patients.

Results: Formal cognitive testing confirmed normal cognitive ability among all cSLE patients included in the analysis (n = 11). Nevertheless, reduction in blood volume fraction coincided with increased effective diffusion and flow parameters in cSLE patients vs. controls in posterior brain regions including the cuneus and precuneus. Regional microvascular measures correlated (|r| = 0.54-0.66) with neuropsychiatric scores and disease activity among cSLE patients.

Conclusions: There is imaging evidence, using IVIM, of degraded microvascular integrity in cSLE patients with normal cognitive ability. The observed regional changes correspond with posterior vascular border zones. These outcomes appear consistent with regional gray matter volume loss previously observed in cSLE patients with overt neurocognitive deficits, supporting the notion that adverse vascular changes precede loss of cognitive ability in cSLE. Longitudinal studies are needed to confirm the findings of this initial study.
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http://dx.doi.org/10.1186/s13075-020-02227-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281933PMC
June 2020

Alterations in Brain Function After Cognitive Behavioral Therapy for Migraine in Children and Adolescents.

Headache 2020 06 23;60(6):1165-1182. Epub 2020 Apr 23.

Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objectives: This basic mechanistic study examined the changes in brain activation and resting-state connectivity after 8 weeks of CBT in youth with migraine.

Background: Cognitive behavioral therapy (CBT) is a psychological intervention that is effective in reducing pain in migraine patients. However, the neural mechanisms underlying CBT in adolescents with migraine are not yet known.

Methods: Eighteen adolescents with migraine (15 females, age 15.1 ± 2.1 years [mean ± SD]) completed 8 weekly CBT sessions. Before the first and after the final CBT session, participants underwent structural and resting-state blood-oxygen-level-dependent contrast MRI scans. Arterial spin labeling was also used to examine brain activation during the resting state. For connectivity analyses, the right and left amygdala were chosen as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated.

Results: Headache frequency decreased from 15 ± 7.4 headaches per month before CBT to 10 ± 7.4 after CBT (P < .001). After CBT, greater brain activations in frontal regions involved in cognitive regulation of pain were found. In addition, after CBT increased connectivity between the amygdala and frontal regions was observed. Associations between brain activation and amygdalar connectivity with a reduction in headache frequency were also observed.

Conclusions: Alterations in brain function and amygdalar connectivity with areas involved in nociceptive processing, cognitive function, and emotional regulation may underlie the ability of CBT to aid in the prevention of headaches in migraine patients.
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http://dx.doi.org/10.1111/head.13814DOI Listing
June 2020

Return to Duty After Mini-Open Arthroscopic-Assisted Treatment of Femoroacetabular Impingement in an Active Military Population.

Arthrosc Sports Med Rehabil 2019 Nov 30;1(1):e15-e23. Epub 2019 Aug 30.

Mayo Clinic-Arizona, Scottsdale, Arizona, U.S.A.

Purpose: To report the return-to-duty rate and surgical outcomes in a military population after mini-open arthroscopic-assisted surgery for femoroacetabular impingement (FAI) in an effort to affirm its efficacy.

Methods: A retrospective review of consecutive active-duty patients receiving mini-open arthroscopic-assisted surgery for FAI between 2007 and 2011 was performed. Patients younger than 18 years, non-active-duty patients, and patients with prior hip surgery were excluded. Demographic, radiographic, and duty-status data were collected. The primary outcome measure was a return to duty. Outcome scores were obtained in a proportion of the cohort, including the modified Harris Hip Score, Single Assessment Numeric Evaluation score, Western Ontario and McMaster Universities Osteoarthritis Index score, patient satisfaction score, and Veterans RAND 12 (VR-12) score. All patients had achieved a minimum of 1 year of follow-up at the time of assessment. All values for significance were set at .05 or lower.

Results: Of 182 patients (average age, 30.4 years), 156 (86%) were available for follow-up with return-to-duty data at an average of 2.8 years (range, 1-6 years). Of the patients, 78% returned to full duty (53%) or returned to duty with restrictions (25%). Outcome scores were available for 101 of 182 patients (55%) with duty rates similar to the total cohort (81% who returned to duty: 58% with no restrictions and 23% with restrictions). Return to duty correlated with improved outcomes compared with those who were medically discharged with respect to the modified Harris Hip Score (68.2 vs 54.5, < .03), Single Assessment Numeric Evaluation score (48.2 vs 25.3, < .02), and VR-12 physical (39.7 vs 33.2, < .05) and VR-12 mental (54.5 vs 43.4, < .005) scores.

Conclusions: Mini-open arthroscopic-assisted surgery for FAI is successful in returning most service members to duty at short-term follow-up. Return correlates with improved outcome scores, although previously reported minimally clinical important difference and patient acceptable symptomatic state threshold values were not uniformly achieved.

Level Of Evidence: Level IV, retrospective case series.
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http://dx.doi.org/10.1016/j.asmr.2019.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120864PMC
November 2019

ASSESSING THE ABILITY OF PREOPERATIVE QUANTITATIVE SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS TO PREDICT VISUAL OUTCOME IN IDIOPATHIC MACULAR HOLE SURGERY.

Retina 2021 Jan;41(1):29-36

Department of Ophthalmology, NYU Langone Health, New York, New York; and.

Purpose: To determine which spectral domain optical coherence tomography biomarkers of idiopathic macular hole (MH) correlate with the postoperative best-corrected visual acuity (BCVA) in anatomically closed MH.

Methods: Retrospective analysis of spectral domain optical coherence tomography scans of 44 patients presenting with MH followed for a mean of 17 months. Widths of MH aperture, base, and ellipsoid zone disruption were calculated from presenting foveal spectral domain optical coherence tomography B-scans. Macular hole base area and ellipsoid zone disruption area were calculated through the custom in-house software.

Results: Poorer postoperative BCVA correlated with increased preoperative choroidal hypertransmission (r = 0.503, P = 0.0005), minimum diameter (r = 0.491, P = 0.0007), and base diameter (r = 0.319, P = 0.0348), but not with preoperative ellipsoid zone width (r = 0.199, P = 0.2001). Applying en-face analysis, the BCVA correlated weakly with preoperative ellipsoid zone loss area (r = 0.380, P = 0.013), but not with preoperative MH base area (r = 0.253, P = 0.1058).

Conclusion: Increased MH minimum diameter, base diameter, base area, and choroidal hypertransmission are correlated with a poorer postoperative BCVA. Ellipsoid zone loss measurements were not consistently correlated with a BCVA. Choroidal hypertransmission width may be an easy-to-visualize predictive imaging biomarker in MH surgery.
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http://dx.doi.org/10.1097/IAE.0000000000002797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529763PMC
January 2021

Sarcoidosis: A Diagnosis of Exclusion.

AJR Am J Roentgenol 2020 01 31;214(1):50-58. Epub 2019 Oct 31.

Department of Radiology, University of Kansas Medical Center, Kansas City, KS.

This article will review the typical and atypical imaging features of sarcoidosis, identify entities that may be mistaken for sarcoidosis, and discuss patterns and clinical scenarios that suggest an alternative diagnosis. Radiologists must be familiar with the characteristic findings in sarcoidosis and be attentive to situations that suggest alternative diagnoses. The radiologist plays a major role in prompt diagnosis and one that may help reduce patient morbidity and mortality.
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http://dx.doi.org/10.2214/AJR.19.21436DOI Listing
January 2020

EVALUATION OF SEGMENTAL RETINAL ARTERITIS WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Retin Cases Brief Rep 2019 Jul 15. Epub 2019 Jul 15.

Department of Ophthalmology, New York University School of Medicine, New York, New York.

Purpose: To describe the vascular anatomy and intraluminal flow characteristics of segmental retinal arteritis (SRA) using structural and angiographic optical coherence tomography (OCT).

Methods: Retrospective case series of consecutive patients presenting with SRA. All patients were evaluated at presentation with fundus photography, spectral domain OCT, and OCT angiography. One patient was imaged with dense B-scan OCT angiography.

Results: Three eyes of three male patients were evaluated. All examinations were consistent with reactivation of ocular toxoplasmosis with an area of active retinochoroiditis adjacent to a focal chorioretinal scar. Spectral domain OCT through areas of SRA noted on clinical examination demonstrated areas of hyperreflectivity circumscribing the affected vessel with a normoreflective lumen. Optical coherence tomography angiography and dense B-scan OCT angiography demonstrated narrowing of the intraluminal flow signal that correlated with areas of segmental hyperreflectivity on spectral domain OCT. Vascular sections proximal and distal to areas of SRA showed normal flow signal.

Conclusion: Vessels with SRA demonstrated hyperreflectivity highlighting the vessel wall on spectral domain OCT. Optical coherence tomography angiography showed narrowing of the flow signal within these segments suggesting reduced lumen diameter. Coupling these finding with previous indocyanine green imaging findings in SRA, the collective data suggest the plaques are localized within the vessel wall to either the endothelium or the muscular tunica media without occlusion of the vessel lumen.
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http://dx.doi.org/10.1097/ICB.0000000000000900DOI Listing
July 2019

Long-Term Multimodal Imaging of Solar Retinopathy.

Ophthalmic Surg Lasers Imaging Retina 2019 06;50(6):388-392

This is a rare, multimodal imaging report spanning a decade of monitoring in a patient with chronic solar retinopathy showing the natural course of the disease. Spectral-domain optical coherence tomography (SD-OCT) showed mild widening of subfoveal loss of ellipsoid and interdigitation zones bilaterally, progressive retinal pigment epithelial thinning in the right eye, and hyperplasia in the left eye. Structural en face OCT showed subfoveal tissue loss bilaterally. There was no leakage on fluorescein angiography and OCT angiography (OCTA), and dense B-scan OCTA images were unremarkable. Microperimetry revealed bilateral decreased central sensitivity and eccentric fixation in the left eye. Vision remained stable throughout. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:388-392.].
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http://dx.doi.org/10.3928/23258160-20190605-08DOI Listing
June 2019

Retinal Pigment Deposition Secondary to Iatrogenic Pigment Dispersion.

Ophthalmol Retina 2019 06 27;3(6):536-538. Epub 2018 Dec 27.

Department of Ophthalmology, New York University School of Medicine, New York, NY. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2018.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327716PMC
June 2019

Zika Virus-Associated Guillain-Barré Syndrome in a Returning US Traveler.

Infect Dis Clin Pract (Baltim Md) 2018 Nov;26(6):e80-e84

Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University, School of Medicine.

Zika virus (ZIKV) infection has been associated with Guillain-Barré Syndrome (GBS). Roughly 60% of people in countries such as the U.S. live in areas at risk for seasonal spread of ZIKV. ZIKV belongs to a class of diseases that is not typically seen in hospital settings across the U.S. and Europe. We describe the case presentation, management, and treatment of ZIKV infection complicated by GBS. A 64-year-old woman with recent travel to the Dominican Republic presented with rash followed by an acute, ascending polyneuropathy consistent with GBS. She was confirmed to have an acute ZIKV infection by detection of ZIKV nucleic acid by reverse transcription-polymerase chain reaction. She met Brighton Collaboration criteria level 1 evidence for GBS. She received two courses of intravenous immunoglobulin and slowly improved, though still had weakness at discharge. More research is needed to identify the pathophysiology behind ZIKV-associated GBS and its optimal treatment. Prevention is fundamental to limiting infection and spread of ZIKV.
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http://dx.doi.org/10.1097/IPC.0000000000000654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433380PMC
November 2018

Modulating protein-protein interaction networks in protein homeostasis.

Curr Opin Chem Biol 2019 06 23;50:55-65. Epub 2019 Mar 23.

Department of Pharmaceutical Chemistry and the Small Molecule Discovery Center, University of California, San Francisco, CA, USA. Electronic address:

Protein-protein interactions (PPIs) occur in complex networks. These networks are highly dependent on cellular context and can be extensively altered in disease states such as cancer and viral infection. In recent years, there has been significant progress in developing inhibitors that target individual PPIs either orthosterically (at the interface) or allosterically. These molecules can now be used as tools to dissect PPI networks. Here, we review recent examples that highlight the use of small molecules and engineered proteins to probe PPIs within the complex networks that regulate protein homeostasis. Researchers have discovered multiple mechanisms to modulate PPIs involved in host/viral interactions, deubiquitinases, the ATPase p97/VCP, and HSP70 chaperones. However, few studies have evaluated the effect of such modulators on the target's network or have compared the biological implications of different modulation strategies. Such studies will have an important impact on next generation therapeutics.
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http://dx.doi.org/10.1016/j.cbpa.2019.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609442PMC
June 2019

Effects of a Comprehensive Performance Improvement Strategy on Postoperative Adverse Events in Head and Neck Surgery.

Otolaryngol Head Neck Surg 2019 05 28;160(5):799-809. Epub 2018 Aug 28.

1 Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California-San Diego, San Diego, CA, USA.

Objectives: We aimed to demonstrate the efficacy of a multifaceted performance improvement regimen to reduce the incidence of adverse events following a spectrum of head and neck surgical procedures.

Methods: We conducted a chart review of patients who underwent a head and neck procedure between January 1, 2013, and October 30, 2015, at our institution, including 392 patients (450 procedures) before the quality improvement regimen was implemented (October 1, 2013) and 942 patients (1136 procedures) after implementation. Multivariate statistical models were used to investigate the association of clinical parameters and the intervention with postoperative adverse event rate.

Results: The incidence of adverse events decreased from 12.9% to 7.2% (95% CI, 2.46%-9.38%) after the intervention. Male sex (adjusted odds ratio [ORadj] = 1.57; 95% CI, 1.06-2.31) and the intervention (ORadj = 0.51; 95% CI, 0.35-0.74) were predictive of overall adverse event incidence by univariate and multivariate analyses. Although patient comorbid status, quantified with the Charlson Comorbidity Index, was not found to affect overall adverse event risk, each 1-point increase in index score was associated with a 17% relative increase (ORadj = 1.17; 95% CI, 1.03-1.33) in the odds of a high-grade adverse event.

Discussion: Comprehensive performance improvement programs can improve perioperative adverse event risk in head and neck surgery. Patient comorbid status and sex are considerations during assessment of the likelihood of high-grade and overall adverse event risk, respectively.

Implications For Practice: Given the cost of surgical complications, a comprehensive approach to perioperative risk mitigation is warranted.
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http://dx.doi.org/10.1177/0194599818793887DOI Listing
May 2019

Inadvertent self-induced macular laser injury in an 8-year-old girl.

J AAPOS 2018 Oct 19;22(5):397-398. Epub 2018 Jun 19.

Department of Ophthalmology, New York University School of Medicine, New York, New York. Electronic address:

An 8-year-old girl with a history of type 1 diabetes was referred for an evaluation of pigment changes in the right macula. Curvilinear hypopigmented streaks were noted in the fovea, with corresponding disruption of the photoreceptor layer on spectral domain optical coherence tomography. On further questioning, a history of laser pointer play 2 years prior was elicited, with acknowledgement of direct laser pointing in the child's eye. The family was advised to remove any commercial laser devices from the home, and observation of the pathology was recommended.
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http://dx.doi.org/10.1016/j.jaapos.2018.03.005DOI Listing
October 2018

Establishing a Multidisciplinary Head and Neck Clinical Pathway: An Implementation Evaluation and Audit of Dysphagia-Related Services and Outcomes.

Dysphagia 2019 02 19;34(1):89-104. Epub 2018 Jun 19.

Greater Baltimore Medical Center, The Milton J Dance, Jr. Head and Neck Center, Johns Hopkins Head & Neck Surgery, Johns Hopkins Voice Center, Baltimore, MD, USA.

Head and neck cancer (HNC) guidelines recommend regular multidisciplinary team (MDT) monitoring and early intervention to optimize dysphagia outcomes; however, many factors affect the ability to achieve these goals. The aims of this study were to explore the barriers/facilitators to establishing and sustaining a MDT HNC care pathway and to examine the dysphagia-related speech-language pathology (SLP) and dietetic components of the pathway. Using the Consolidated Framework for Implementation Research (CFIR), a mixed methods study design was used to evaluate an established MDT HNC pathway. Ten MDT members provided perceptions of facilitators/barriers to implementing and sustaining the pathway. Patients attending the SLP and dietetic components of the pathway who commenced treatment between 2013 and 2014 (n = 63) were audited for attendance, outcome data collected per visit, and swallowing outcomes to 24-month post-treatment. Dysphagia outcomes were compared to a published cohort who had received intensive prophylactic dysphagia management. Multiple CFIR constructs were identified as critical to implementing and sustaining the pathway. Complexity was a barrier. Patient attendance was excellent during treatment, with low rates of non-compliance (< 15%) to 24 months. Collection of clinician/patient outcome tools was good during treatment, but lower post-treatment. Dysphagia outcomes were good and comparable to prior published data. The pathway provided patients with access to regular supportive care and provided staff opportunities to provide early and ongoing dysphagia monitoring and management. However, implementing and sustaining a HNC pathway is complex, requiring significant staff resources, financial investment, and perseverance. Regular audits are necessary to monitor the quality of the pathway.
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http://dx.doi.org/10.1007/s00455-018-9917-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349813PMC
February 2019

Lung squamous cell carcinoma cells express non-canonically glycosylated IgG that activates integrin-FAK signaling.

Cancer Lett 2018 08 17;430:148-159. Epub 2018 May 17.

Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Peking University Center for Human Disease Genomics, Beijing, 100191, China. Electronic address:

It is increasingly recognized that many human carcinomas express immunoglobulin (Ig) molecules that are distinct from B-cell-derived Ig and play important roles in cancer initiation, progression, and metastasis. However, the molecular mechanisms underlying the functions of cancer-derived Ig remain elusive. Here, we report that lung squamous cell carcinoma (LSCC) cells frequently express high levels of cancer IgG (CIgG) that is specifically recognized by a monoclonal antibody RP215. RP215 recognizes CIgG via a novel epitope that involves an N-glycan modification at a non-consensus site within the C1 domain. We demonstrate that RP215 recognized CIgG (RP215-CIgG) promotes survival, migration and in vivo growth of LSCC cells, and these oncogenic activities are strongly inhibited by RP215. Mechanistically, RP215-CIgG executes its oncogenic function through interacting with the integrin α6β4 complex and activating the FAK and Src pathways. Notably, the CIgG-integrin-FAK signaling depends on the N-glycan epitope, which is inhibited by RP215. Together, our studies identified a novel CIgG molecule that activates the oncogenic integrin-FAK signaling in LSCC cells. In addition, the activity of CIgG is inhibited by RP215, providing an attractive target for antibody-based therapy of LSCC.
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http://dx.doi.org/10.1016/j.canlet.2018.05.024DOI Listing
August 2018

Brain gray matter volume differences in obese youth with type 2 diabetes: a pilot study.

J Pediatr Endocrinol Metab 2018 Mar;31(3):261-268

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Background: Adults with type 2 diabetes (T2D) have significantly lower gray matter volume (GMV) compared to healthy peers. Whether GMV differences exist in youth with T2D remains unclear. Thus, we compared global and regional GMV between obese youth with T2D with age, race and sex similar healthy controls.

Methods: In a cross-sectional study, 20 obese youth with T2D underwent T1-weighted brain magnetic resonance imaging (MRI). Comparisons were made to 20 age, race and sex similar controls. Differences in global and regional GMV between groups were identified using voxel-based morphometry (VBM).

Results: Youth with T2D had a significantly lower global GMV-to-intracranial volume ratio (0.51±0.02 in T2D vs. 0.53±0.02 in controls, p=0.02, Cohen's d=0.85). There were 14 regions where GMV was significantly lower in the T2D group, and nine of these were found in either the temporal or occipital lobes. There were six regions with increased GMV in T2D. All regional differences were significant at p<0.05 after adjusting for multiple comparisons.

Conclusions: Results from this pilot study show obese youth with T2D have significantly lower global GMV and regional GMV differences, when compared to their age, race and sex similar peers. Future work is needed to determine whether these brain findings are a direct result of adolescent-onset T2D.
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http://dx.doi.org/10.1515/jpem-2017-0349DOI Listing
March 2018

Improving the Quality of Clinical Neuropsychological Research: Mandatory Use of Reporting Guidelines.

Arch Clin Neuropsychol 2017 Sep;32(6):631-651

University of South Florida, Tampa, FL, USA.

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http://dx.doi.org/10.1093/arclin/acx054DOI Listing
September 2017

Single-shot turbo spin echo acquisition for in vivo cardiac diffusion MRI.

Annu Int Conf IEEE Eng Med Biol Soc 2016 Aug;2016:5529-5532

Diffusion MRI offers the ability to noninvasively characterize the microstructure of myocardium tissue and detect disease related pathology in cardiovascular examination. This study investigates the feasibility of in vivo cardiac diffusion MRI under free-breathing condition. A high-speed imaging technique, correlation imaging, is used to enable single-shot turbo spin echo for free-breathing cardiac data acquisition. The obtained in vivo cardiac diffusion-weighted images illustrate robust image quality and minor geometry distortions. The resultant diffusion scalar maps show reliable quantitative values consistent with those previously published in the literature. It is demonstrated that this technique has the potential for in vivo free-breathing cardiac diffusion MRI.
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http://dx.doi.org/10.1109/EMBC.2016.7591979DOI Listing
August 2016

Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach.

Arthritis Care Res (Hoboken) 2017 Feb;69(2):299-305

Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.

Objective: To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE).

Methods: In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients.

Results: Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all).

Conclusion: There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study.
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http://dx.doi.org/10.1002/acr.22923DOI Listing
February 2017

Obese adolescents with type 2 diabetes perform worse than controls on cognitive and behavioral assessments.

Pediatr Diabetes 2017 06 29;18(4):297-303. Epub 2016 Mar 29.

Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Background: Children with type 1 diabetes demonstrate worse cognitive performance compared with their peers. Little is known regarding the cognitive and behavioral performance in obese adolescents with type 2 diabetes.

Methods: Cross sectional evaluation of 20 obese adolescents with type 2 diabetes and 20 healthy adolescents was performed in Cincinnati, Ohio. Cognitive tests that included measures of processing speed, working memory, verbal and semantic fluency and parent reports of executive function and problem behavior were compared. Academic achievement and the relationship between cognitive/behavioral scores and diabetes duration and diabetes control (hemoglobin A1c) were assessed in the type 2 diabetes group only.

Results: The type 2 diabetes group had mean duration of diabetes of 2.8 ± 2.2 yr and hemoglobin A1c of 7.9 ± 2.2%. Adolescents with type 2 diabetes scored lower than controls on tests of working and verbal memory and processing speed (all p < 0.05) and worse for Internalizing, Externalizing, and Total Problems behaviors on the Child Behavior Checklist (all p < 0.05). Adolescents with type 2 diabetes scored below the population mean in academic achievement, most notably calculation. Working memory and processing speed were negatively correlated with duration of diabetes (r = -0.50 and -0.47, respectively, p < 0.05).

Conclusions: Obese youth with type 2 diabetes score poorly compared with controls on multiple assessments of cognitive function and adaptive behavior. Further work is needed to determine if these effects are driven by obesity, diabetes or other demographic and socioeconomic risk factors.
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http://dx.doi.org/10.1111/pedi.12383DOI Listing
June 2017

New Editor-in-Chief Introductory Comments.

Authors:
Gregory P Lee

Arch Clin Neuropsychol 2016 May 18;31(3):195-6. Epub 2016 Mar 18.

Augusta, GA, USA

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http://dx.doi.org/10.1093/arclin/acw008DOI Listing
May 2016

Fragment-Based Protein-Protein Interaction Antagonists of a Viral Dimeric Protease.

ChemMedChem 2016 Apr 28;11(8):862-9. Epub 2016 Jan 28.

Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, 94158-2280, USA.

Fragment-based drug discovery has shown promise as an approach for challenging targets such as protein-protein interfaces. We developed and applied an activity-based fragment screen against dimeric Kaposi's sarcoma-associated herpesvirus protease (KSHV Pr) using an optimized fluorogenic substrate. Dose-response determination was performed as a confirmation screen, and NMR spectroscopy was used to map fragment inhibitor binding to KSHV Pr. Kinetic assays demonstrated that several initial hits also inhibit human cytomegalovirus protease (HCMV Pr). Binding of these hits to HCMV Pr was also confirmed by NMR spectroscopy. Despite the use of a target-agnostic fragment library, more than 80 % of confirmed hits disrupted dimerization and bound to a previously reported pocket at the dimer interface of KSHV Pr, not to the active site. One class of fragments, an aminothiazole scaffold, was further explored using commercially available analogues. These compounds demonstrated greater than 100-fold improvement of inhibition. This study illustrates the power of fragment-based screening for these challenging enzymatic targets and provides an example of the potential druggability of pockets at protein-protein interfaces.
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http://dx.doi.org/10.1002/cmdc.201500526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838516PMC
April 2016