Publications by authors named "Peter Chang"

402 Publications

Outcomes of Artificial Intelligence Volumetric Assessment of Kidneys and Renal Tumors for Preoperative Assessment of Nephron Sparing Interventions.

J Endourol 2021 Apr 13. Epub 2021 Apr 13.

University of California Irvine School of Medicine, 12219, Radiological Sciences, Orange, California, United States.

Background Renal cell carcinoma is the most common kidney cancer and the 13th most common cause of cancer death worldwide. Partial nephrectomy and percutaneous ablation, increasingly utilized to treat small renal masses and preserve renal parenchyma, require precise preoperative imaging interpretation. We sought to develop and evaluate a convolutional neural network (CNN), a type of deep learning artificial intelligence, to act as a surgical planning aid by determining renal tumor and kidney volumes via segmentation on single-phase computed tomography (CT). Materials and Methods After institutional review board approval, the CT images of 319 patients were retrospectively analyzed. Two distinct CNNs were developed for (1) bounding cube localization of the right and left hemi-abdomen and (2) segmentation of the renal parenchyma and tumor within each bounding cube. Training was performed on a randomly selected cohort of 269 patients. CNN performance was evaluated on a separate cohort of 50 patients using Sorensen-Dice coefficients (which measures the spatial overlap between the manually segmented and neural network derived segmentations) and Pearson correlation coefficients. Experiments were run on a GPU-optimized workstation with a single NVIDIA GeForce GTX Titan X (12GB, Maxwell architecture). Results Median Dice coefficients for kidney and tumor segmentation were 0.970 and 0.816, respectively; Pearson correlation coefficients between CNN-generated and human-annotated estimates for kidney and tumor volume were 0.998 and 0.993 (p < 0.001), respectively. End-to-end trained CNNs were able to perform renal parenchyma and tumor segmentation on a new test case in an average of 5.6 seconds. Conclusions Initial experience with automated deep learning artificial intelligence demonstrates that it is capable of rapidly and accurately segmenting kidneys and renal tumors on single-phase contrast-enhanced CT scans and calculating tumor and renal volumes.
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http://dx.doi.org/10.1089/end.2020.1125DOI Listing
April 2021

Integrating Eye Tracking and Speech Recognition Accurately Annotates MR Brain Images for Deep Learning: Proof of Principle.

Radiol Artif Intell 2021 Jan 11;3(1):e200047. Epub 2020 Nov 11.

Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065 (J.N.S., D.G., N.S., R.Y., S.E.W., A.H.); The National Institutes of Health Clinical Center, Bethesda, Md (H.C., B.J.W.); Department of Radiology, Columbia University Medical Center, New York, NY (S.J.); Department of Radiology, University of California-Irvine, Irvine, Calif (P.D.C.); Department of Radiology & Imaging Sciences, Emory University, Atlanta, Ga (E.K.); and Center for Research in Computer Vision, University of Central Florida, Orlando, Fla (U.B.).

Purpose: To generate and assess an algorithm combining eye tracking and speech recognition to extract brain lesion location labels automatically for deep learning (DL).

Materials And Methods: In this retrospective study, 700 two-dimensional brain tumor MRI scans from the Brain Tumor Segmentation database were clinically interpreted. For each image, a single radiologist dictated a standard phrase describing the lesion into a microphone, simulating clinical interpretation. Eye-tracking data were recorded simultaneously. Using speech recognition, gaze points corresponding to each lesion were obtained. Lesion locations were used to train a keypoint detection convolutional neural network to find new lesions. A network was trained to localize lesions for an independent test set of 85 images. The statistical measure to evaluate our method was percent accuracy.

Results: Eye tracking with speech recognition was 92% accurate in labeling lesion locations from the training dataset, thereby demonstrating that fully simulated interpretation can yield reliable tumor location labels. These labels became those that were used to train the DL network. The detection network trained on these labels predicted lesion location of a separate testing set with 85% accuracy.

Conclusion: The DL network was able to locate brain tumors on the basis of training data that were labeled automatically from simulated clinical image interpretation.© RSNA, 2020.
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http://dx.doi.org/10.1148/ryai.2020200047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845782PMC
January 2021

Clinical features, visual outcome, and poor prognostic factors in occlusive retinal vasculitis.

Can J Ophthalmol 2021 Apr 7. Epub 2021 Apr 7.

Massachusetts Eye Research and Surgery Institution, Waltham, Mass.; Ocular Immunology and Uveitis Foundation, Waltham, Mass.; Harvard Medical School, Boston, Mass.. Electronic address:

Objective: To investigate the clinical features, treatment, and visual outcome of occlusive retinal vasculitis (ORV), with a focal analysis on prognostic factors associated with poor visual outcome.

Methods: We conducted a retrospective cohort study in patients diagnosed with ORV with at least 6 months of follow-up. Demographic data, ocular features, best corrected visual acuity (BCVA), fluorescein angiography, therapy regimens, and outcomes were collected from the Massachusetts Eye Research and Surgery Institution database from 2006 to 2017. Multivariate logistic regression was performed to analyze the factors independently predicting poor visual outcome.

Results: Fifth-two patients (69 eyes) were enrolled, 42 with noninfectious cause, 9 with infectious cause, and 1 with masquerade uveitis. Systemic inflammatory diseases, including necrotizing vasculitis, sarcoidosis, multiple sclerosis, systemic lupus erythematosus, and Behçet's disease comprised the causes of ORV. Forty of the 42 patients with noninfectious ORV received immunomodulatory therapy (IMT), and 35 patients (87.5%) were able to achieve steroid-free remission. Compared with the BCVA at the initial visit (0.66 [±0.11] logMAR), there was significant improvement at the most recent visit (0.37 [±0.07] logMAR, p = 0.001). A multivariate analysis demonstrated that optic nerve atrophy, macular ischemia, and poor BCVA at initial presentation were independently correlated with poor visual outcome.

Conclusions: ORV could be caused by a wide spectrum of systemic inflammatory diseases. Aggressive IMT is preferred to achieve a steroid-free durable remission for noninfectious ORV. Optic nerve atrophy, macular ischemia, and poor BCVA at the initial visit predict a poor visual outcome.
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http://dx.doi.org/10.1016/j.jcjo.2021.03.001DOI Listing
April 2021

Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.

Lancet Oncol 2021 04;22(4):450-462

Moores Cancer Center, UC San Diego Health, La Jolla, CA, USA.

Background: Chemoradiotherapy is the standard of care for unresected locally advanced squamous cell carcinoma of the head and neck. We aimed to assess if addition of avelumab (anti-PD-L1) to chemoradiotherapy could improve treatment outcomes for this patient population.

Methods: In this randomised, double-blind, placebo-controlled, phase 3 study, patients were recruited from 196 hospitals and cancer treatment centres in 22 countries. Patients aged 18 years or older, with histologically confirmed, previously untreated, locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity (unselected for PD-L1 status), an Eastern Cooperative Oncology Group performance status score of 0 or 1, and who could receive chemoradiotherapy were eligible. Patients were randomly assigned (1:1) centrally by means of stratified block randomisation with block size four (stratified by human papillomavirus status, tumour stage, and nodal stage, and done by an interactive response technology system) to receive 10 mg/kg avelumab intravenously every 2 weeks plus chemoradiotherapy (100 mg/m cisplatin every 3 weeks plus intensity-modulated radiotherapy with standard fractionation of 70 Gy [35 fractions during 7 weeks]; avelumab group) or placebo plus chemoradiotherapy (placebo group). This was preceded by a single 10 mg/kg avelumab or placebo lead-in dose given 7 days previously and followed by 10 mg/kg avelumab or placebo every 2 weeks maintenance therapy for up to 12 months. The primary endpoint was progression-free survival by investigator assessment per modified Response Evaluation Criteria in Solid Tumors, version 1.1, in all randomly assigned patients. Adverse events were assessed in patients who received at least one dose of avelumab or placebo. This trial is registered with ClinicalTrials.gov, NCT02952586. Enrolment is no longer ongoing, and the trial has been discontinued.

Findings: Between Dec 12, 2016, and Jan 29, 2019, from 907 patients screened, 697 patients were randomly assigned to the avelumab group (n=350) or the placebo group (n=347). Median follow-up for progression-free survival was 14·6 months (IQR 8·5-19·6) in the avelumab group and 14·8 months (11·6-18·8) in the placebo group. Median progression-free survival was not reached (95% CI 16·9 months-not estimable) in the avelumab group and not reached (23·0 months-not estimable) in the placebo group (stratified hazard ratio 1·21 [95% CI 0·93-1·57] favouring the placebo group; one-sided p=0·92). The most common grade 3 or worse treatment-related adverse events were neutropenia (57 [16%] of 348 patients in the avelumab group vs 52 [15%] of 344 patients in the placebo group), mucosal inflammation (50 [14%] vs 45 [13%]), dysphagia (49 [14%] vs 47 [14%]), and anaemia (41 [12%] vs 44 [13%]). Serious treatment-related adverse events occurred in 124 (36%) patients in the avelumab group and in 109 (32%) patients in the placebo group. Treatment-related deaths occurred in two (1%) patients in the avelumab group (due to general disorders and site conditions, and vascular rupture) and one (<1%) in the placebo group (due to acute respiratory failure).

Interpretation: The primary objective of prolonging progression-free survival with avelumab plus chemoradiotherapy followed by avelumab maintenance in patients with locally advanced squamous cell carcinoma of the head and neck was not met. These findings may help inform the design of future trials investigating the combination of immune checkpoint inhibitors plus CRT.

Funding: Pfizer and Merck KGaA, Darmstadt, Germany.
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http://dx.doi.org/10.1016/S1470-2045(20)30737-3DOI Listing
April 2021

Midterm Outcomes of Posterior Medial Meniscus Root Tear Repair: A Systematic Review.

Am J Sports Med 2021 Mar 29:363546521998297. Epub 2021 Mar 29.

Department of Orthopaedic Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.

Background: Whereas there has been growing interest in surgical repair of posterior medial meniscus root tears (PMMRTs), our understanding of the medium- and long-term results of this procedure is still evolving.

Purpose: To report midterm clinical outcomes from PMMRT repairs.

Study Design: Systematic review.

Methods: A literature review for this systematic analysis was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We identified studies that reported the results of arthroscopic repair of PMMRTs. Functional and imaging outcomes were reviewed and summarized.

Results: In total, 28 studies with a total of 994 patients (83% female) with an overall mean age of 57.1 were included in this review. Clinical outcomes (Lysholm, International Knee Documentation Committee, Hospital for Special Surgery, and Tegner scores) were improved at final follow-up in all studies. Of patients, 49% had radiographic progression of at least 1 grade in the Kellgren-Lawrence scale at a mean follow-up of 4.0 years in 11 studies. Cartilage degeneration had progressed at least 1 grade on magnetic resonance imaging scans in 23% of patients at a mean follow-up of 31.6 months in 4 studies.

Conclusion: PMMRT repairs provide a functional benefit with consistent improvements in clinical outcome scores. There is some evidence that PMMRT repair slows the progression of osteoarthritis but does not prevent it at midterm follow-up.
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http://dx.doi.org/10.1177/0363546521998297DOI Listing
March 2021

Results of a Randomized Phase II Trial of Intense Androgen Deprivation Therapy prior to Radical Prostatectomy in Men with High-Risk Localized Prostate Cancer.

J Urol 2021 Mar 8:101097JU0000000000001702. Epub 2021 Mar 8.

Dana-Farber Cancer Institute, Boston, Massachusetts.

Purpose: This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368).

Materials And Methods: Eligible patients had a Gleason score ≥4+3=7, PSA >20 ng/mL or T3 disease and lymph nodes <20 mm. In Part 1, patients were randomized 1:1 to apalutamide, abiraterone acetate, prednisone and leuprolide (AAPL) or abiraterone, prednisone, leuprolide (APL) for 6 cycles (1 cycle=28 days) followed by radical prostatectomy. Surgical specimens underwent central review. The primary end point was the rate of pathologic complete response or minimum residual disease (minimum residual disease, tumor ≤5 mm). Secondary end points included prostate specific antigen response, positive margin rate and safety. Magnetic resonance imaging and tissue biomarkers of pathologic outcomes were explored.

Results: The study enrolled 118 patients at 4 sites. Median age was 61 years and 94% of patients had high risk disease. The combined pathologic complete response or minimum residual disease rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%; 1-sided 95% CI -11%, 14%; 1-sided p=0.4). No new safety signals were observed. There was low concordance and correlation between posttherapy magnetic resonance imaging assessed and pathologically assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor.

Conclusions: Intense neoadjuvant hormone therapy in high-risk prostate cancer resulted in favorable pathologic responses (tumor 5 mm) in 21% of patients. Pathologic responses were similar between treatment arms. Part 2 of this study will investigate the impact of adjuvant hormone therapy on biochemical recurrence.
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http://dx.doi.org/10.1097/JU.0000000000001702DOI Listing
March 2021

Contemporary Incidence and Predictors of Occult Inguinal Lymph Node Metastases in Men With Clinically Node-negative (cN0) Penile Cancer.

Urology 2021 Feb 24. Epub 2021 Feb 24.

Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA. Electronic address:

Objective: To (1) examine the contemporary incidence of occult inguinal LN metastases and (2) identify predictors of occult inguinal LN metastases to improve selection of cN0 patients for inguinal lymphadenectomy (ILND).

Methods: We identified 590 men with cTany cN0 cM0 penile cancer who underwent partial/radical penectomy and ILND from 2006-2016 in the NCDB. Rates of pN+ disease were examined, and a multivariable regression model was constructed to identify features associated with pN+ disease.

Results: Tumors were ≤pT1 in 21%, pT2 in 43%, and pT3/pT4 in 24% of patients. A median of 15 (IQR 8-22) LNs were removed at ILND. The overall pN+ rate was 24% and did not vary over the study period. The pN+ rate, stratified by pT stage, varied from 18-33%. On multivariable analysis, only higher tumor grade (OR 2.16; P = 0.02 for grade 2; OR 2.81; P = 0.005 for grade 3-4, versus grade 1) and lymphovascular invasion (OR 3.12; P <0.001) were independently associated with pN+ disease, whereas pT stage was not.

Conclusion: The contemporary rate of occult LN metastases in men with cN0 penile cancer remains high at approximately 24%. Our results suggest that high tumor grade and/or lymphovascular invasion are better determinants of lymph node involvement than primary tumor stage.
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http://dx.doi.org/10.1016/j.urology.2021.02.019DOI Listing
February 2021

Reply by Authors.

J Urol 2021 Feb 26:101097JU000000000000157503. Epub 2021 Feb 26.

The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1097/JU.0000000000001575.03DOI Listing
February 2021

Single-Laboratory Validation Study of a Rapid TD-NMR method for Quantitation of Total Fat in Sunflower Oil Powder.

J AOAC Int 2021 Feb 19. Epub 2021 Feb 19.

Herbalife International of America, 990 West 190th Street, Torrance, CA 90502.

Background: A rapid total fat quantitation method for sunflower oil powder was developed using time domain nuclear magnetic resonance (TD-NMR). Currently, industry has three major methods for the total fat quantitation: gravimetric analysis after ether extraction (AOAC 933.05 and 989.05), gas chromatography with flame ionization detector (GC-FID AOAC 996.06), and high resolution NMR. The gravimetric analysis method takes a day using highly flammable solvents, and the GC-FID method takes two days requiring harsh chemicals for hydrolyzation, extraction, and methylation. High resolution NMR spectroscopy method requires simpler sample preparation and shorter analysis time compared to the other two methods. Often, only required sample preparation step is to dissolve a sample in a solvent. The acquisition time depends on types of analyzing nuclei and sample. The vegetable oil analysis by 13C NMR takes about four hours per sample. 1H NMR usually takes less time to analyze. In contrast, TD-NMR relaxometry method takes only an hour to prepare and analyze samples if the test is for total fat only. The acquisition time is 40 s per sample, and samples are analyzed "as is". A rapid analysis method in a quality control laboratory is very crucial for laboratory efficiency in releasing products. In this paper, a single-laboratory validation study is described for a rapid TD-NMR method to quantitate total fat in sunflower oil powder.

Objectives: This validation work is to provide documented evidence for the method validity as well as the method performance.

Methods: The method used Bruker minispec mq-20 NMR analyzer® with minispec plus® software. Hahn-echo pulse program was used in the method to collect spin echo signal to determine total fat content.

Results: The linearity/range result from ten standards (0, 21, 42, 63, 83, 92, 100, 108, 117, and 125%) has the coefficients of determination (R2) of 1.0000. The 100% level is 1.2 g of fat in 2.5 g sample, which is targeted fat content in a sunflower oil powder raw material. The method is specific for the quantitation of total fat in sunflower oil powder with no background interference from the matrix. The precision result of the six replicate samples at 100% level is 0.3% RSD. The accuracies measured from triplicate analysis of 80, 100, and 120% sample matrices are 100, 100, and 100% average recoveries, respectively. The ruggedness of the test method is 0.4% RSD of 12 analysis from two analysts (6 results from each analyst) on the different days.

Conclusions: The test method is proven to be specific, linear, precise, accurate, rugged, and suitable for intended use of quantitative analysis for total fat in sunflower oil powder.

Highlights: Traditional methods of gravimetric or GC-FID for total fat analysis of raw materials require lengthy sample preparation and experiment time. Laboratory needs to spend a day to perform gravimetric analysis following ether extraction method and 2 days for GC-FID method. In addition, these test methods use highly flammable and harsh chemicals that generate hazardous chemical wastes. These hazardous wastes are harmful to analysts and environments. In contrast, TD-NMR method is safe, environmentally friendly, and fast. Therefore, TD-NMR is a preferred method for quality control laboratories.
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http://dx.doi.org/10.1093/jaoacint/qsab022DOI Listing
February 2021

Genomic diversity and genome-wide association analysis related to yield and fatty acid composition of wild American oil palm.

Plant Sci 2021 Mar 24;304:110731. Epub 2020 Oct 24.

Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, 43000, Malaysia. Electronic address:

Existing Elaeis guineensis cultivars lack sufficient genetic diversity due to extensive breeding. Harnessing variation in wild crop relatives is necessary to expand the breadth of agronomically valuable traits. Using RAD sequencing, we examine the natural diversity of wild American oil palm populations (Elaeis oleifera), a sister species of the cultivated Elaeis guineensis oil palm. We genotyped 192 wild E. oleifera palms collected from seven Latin American countries along with four cultivated E. guineensis palms. Honduras, Costa Rica, Panama and Colombia palms are panmictic and genetically similar. Genomic patterns of diversity suggest that these populations likely originated from the Amazon Basin. Despite evidence of a genetic bottleneck and high inbreeding observed in these populations, there is considerable genetic and phenotypic variation for agronomically valuable traits. Genome-wide association revealed several candidate genes associated with fatty acid composition along with vegetative and yield-related traits. These observations provide valuable insight into the geographic distribution of diversity, phenotypic variation and its genetic architecture that will guide choices of wild genotypes for crop improvement.
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http://dx.doi.org/10.1016/j.plantsci.2020.110731DOI Listing
March 2021

The allergic myocardial infarction dilemma: is it the anaphylaxis or the epinephrine?

J Thromb Thrombolysis 2021 Feb 5. Epub 2021 Feb 5.

Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore.

We highlight two distinct cases of myocardial infarction occurring concurrently with anaphylaxis at our centre in Singapore. The first case had cardiac symptoms and electrocardiogram changes concomitant with his anaphylaxis presentation, suggestive of Kounis syndrome, while the second case presented with anaphylaxis and only developed cardiac symptoms and electrocardiogram changes after treatment with intramuscular epinephrine, suggestive of epinephrine-induced myocardial infarction. Both these conditions are uncommon and under-recognised, and we review the current literature to compare the similarities and differences in their clinical manifestations, pathophysiology, and management. Kounis syndrome occurs secondary to mast cell degranulation ultimately resulting in coronary vasospasm, platelet activation and inflammatory response, whereas epinephrine causes platelet aggregation. Therefore, treatment priorities of Kounis syndrome are treatment of allergy, treatment of vasospasm, and treatment with anti-platelet therapy and revascularization if coronary plaques are present. For epinephrine-induced myocardial infarction, after epinephrine treatment is discontinued, considerations in management are re-vascularisation or pharmacotherapy. Further research will help with better understanding of both conditions and formulation of clinical management guidelines.
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http://dx.doi.org/10.1007/s11239-021-02389-4DOI Listing
February 2021

ALDH2 deficiency induces atrial fibrillation through dysregulated cardiac sodium channel and mitochondrial bioenergetics: A multi-omics analysis.

Biochim Biophys Acta Mol Basis Dis 2021 May 27;1867(5):166088. Epub 2021 Jan 27.

Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.

Point mutation in alcohol dehydrogenase 2 (ALDH2), ALDH2*2 results in decreased catalytic enzyme activity and has been found to be associated with different human pathologies. Whether ALDH2*2 would induce cardiac remodeling and increase the attack of atrial fibrillation (AF) remains poorly understood. The present study evaluated the effect of ALDH2*2 mutation on AF susceptibility and unravelled the underlying mechanisms using a multi-omics approach including whole-genome gene expression and proteomics analysis. The in-vivo electrophysiological study showed an increase in the incidence and reduction in the threshold of AF for the mutant mice heterozygous for ALDH2*2 as compared to the wild type littermates. The microarray analysis revealed a reduction in the retinoic acid signals which was accompanied by a downstream reduction in the expression of voltage-gated Na channels (SCN5A). The treatment of an antagonist for retinoic acid receptor resulted in a decrease in SCN5A transcript levels. The integrated analysis of the transcriptome and proteome data showed a dysregulation of fatty acid β-oxidation, adenosine triphosphate synthesis via electron transport chain, and activated oxidative responses in the mitochondria. Oral administration of Coenzyme Q10, an essential co-factor known to meliorate mitochondrial oxidative stress and preserve bioenergetics, conferred a protection against AF attack in the mutant ALDH2*2 mice. The multi-omics approach showed the unique pathophysiology mechanisms of concurrent dysregulated SCN5A channel and mitochondrial bioenergetics in AF. This inspired the development of a personalized therapeutic agent, Coenzyme Q10, to protect against AF attack in humans characterized by ALDH2*2 genotype.
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http://dx.doi.org/10.1016/j.bbadis.2021.166088DOI Listing
May 2021

Outcomes of Post-Neoadjuvant Intense Hormone Therapy and Surgery for High Risk Localized Prostate Cancer: Results of a Pooled Analysis of Contemporary Clinical Trials.

J Urol 2021 Jan 27:101097JU0000000000001632. Epub 2021 Jan 27.

Dana-Farber Cancer Institute, Boston, Massachusetts.

Purpose: We report on the post-radical prostatectomy outcomes of patients enrolled in 3 randomized, multicenter, clinical trials of intense neoadjuvant androgen deprivation therapy prior radical prostatectomy.

Materials And Methods: All patients included were enrolled in trials evaluating intense androgen deprivation therapy followed by radical prostatectomy. The primary end point was time to biochemical recurrence, defined as the time from radical prostatectomy to prostate specific antigen >0.1 ng/ml or start of first post-radical prostatectomy therapy, stratified by pathological response at radical prostatectomy (presence or absence of exceptional pathological response defined as residual tumor at radical prostatectomy measuring 0-5 mm). Secondary end points included metastasis-free survival, overall survival, and time to testosterone recovery.

Results: Overall, 117 patients were included in the analysis, of whom 78.6% (92) had high risk disease. Following neoadjuvant therapy, 21.4% (25) had 0-5 mm of residual tumor, including 9.4% (11) with a pathological complete response. Overall, 49 patients (41.9%) experienced biochemical recurrence and the 3-year biochemical recurrence-free rate was 59.1% (95% CI 49.0-67.9). Of the 25 patients with an exceptional pathological response, 2 patients (8.0%) developed biochemical recurrence while 51.1% of nonresponders (47/92) developed biochemical recurrence. Testosterone recovery was observed in 93.8% of patients (106/113). PTEN loss and intraductal carcinoma were associated with shorter time to biochemical recurrence.

Conclusions: In this pooled analysis of prospective trials, we demonstrate that exceptional pathological response following neoadjuvant therapy is associated with a favorable impact on biochemical recurrence. PTEN loss and intraductal carcinoma were associated with biochemical recurrence. Additional followup is warranted to evaluate the impact on long-term outcomes.
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http://dx.doi.org/10.1097/JU.0000000000001632DOI Listing
January 2021

Combination of pembrolizumab and lenvatinib is a potential treatment option for heavily pretreated recurrent and metastatic head and neck cancer.

J Chin Med Assoc 2021 Apr;84(4):361-367

Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital; Taipei, Taiwan, ROC.

Background: Immunotherapy has become the current standard of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). One potential approach to improve immunotherapy efficacy is to combine pembrolizumab, an anti-PD-1 agent, with lenvatinib, a potent multikinase inhibitor. In this study, we presented our up-to-date experience with pembrolizumab/lenvatinib combination therapy in heavily pretreated R/M HNSCC.

Methods: Patients who had R/M HNSCC, were ineligible for curative treatment, progressed after at least two lines of systemic treatment and had received pembrolizumab/lenvatinib combination therapy were enrolled in this study. The primary endpoint was the objective response rate. The secondary endpoints included the disease control rate, overall survival, progression-free survival, and the duration of response.

Results: A total of 14 patients were enrolled in this study. All the patients had received at least two lines of systemic treatment and radiation therapy, and 71% of patients had failed previous anti-PD-1 treatment. The objective response rate of pembrolizumab/lenvatinib combination therapy was 28.6% (95% confidence interval [CI], 5.0%-52.2%). The disease control rate was 42.9% (95% CI, 17.0%-68.8%). The overall survival and progression-free survival were 6.2 months (95% CI, 2.9-9.6) and 4.6 months (95% CI, 0.05-0.9.2), respectively. Of those who had failed previous anti-PD-1 therapy, partial responses were observed in two patients. All the patients with partial responses were in the tumor proportion score <50 and combined positive score 1 to 19 groups.

Conclusion: Our study provided up-to-date evidence that pembrolizumab/lenvatinib combination therapy achieved objective responses in both heavily pretreated and anti-PD-1 refractory R/M HNSCC patients. This study supported the use of pembrolizumab/lenvatinib combination therapy in R/M HNSCC patients without standard of care.
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http://dx.doi.org/10.1097/JCMA.0000000000000497DOI Listing
April 2021

Increased lead concentrations in the hairs of radiographers in general hospitals.

Sci Rep 2021 Jan 8;11(1):236. Epub 2021 Jan 8.

Tufts University, School of Medicine, Boston, USA.

This study investigated lead concentrations in the hairs of radiographers working in the radiological departments of general hospitals that used lead shielding for radiation protection. We collected scalp hair samples from 32 radiographers working in four radiology departments with lead shielding and 18 administration personnel in the same hospitals without lead shielding. Samples were analyzed for lead concentrations by inductively coupled plasma mass spectrometry. As a result, lead concentrations in the hairs of the radiological technologists were significantly higher than those in the administration staffs (0.72 ± 0.51 vs. 0.19 ± 0.27 μg/g, P < 0.001). The hair lead concentrations were positively and significantly associated with environmental lead concentrations (r = 0.6, P = 0.001), but not associated with age, working duration, and gender distribution.
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http://dx.doi.org/10.1038/s41598-020-80721-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794336PMC
January 2021

Outcomes of Active Surveillance for Young Patients with Small Renal Masses: Prospective Data from the DISSRM Registry.

J Urol 2020 Dec 24:101097JU0000000000001575. Epub 2020 Dec 24.

The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Purpose: A paradigm shift in the management of small renal masses has increased utilization of active surveillance. However, questions remain regarding safety and durability in younger patients.

Materials And Methods: Patients aged 60 or younger at diagnosis were identified from the Delayed Intervention and Surveillance for Small Renal Masses registry. The active surveillance, primary intervention, and delayed intervention groups were evaluated using ANOVA with Bonferroni correction, χ and Fisher's exact tests, and Kruskal-Wallis and Wilcoxon signed-rank tests. Survival outcomes were calculated using the Kaplan-Meier method and compared with the log-rank test.

Results: Of 224 patients with median followup of 4.9 years 30.4% chose surveillance. There were 20 (29.4%) surveillance progression events, including 4 elective crossovers, and 13 (19.1%) patients underwent delayed intervention. Among patients with initial tumor size ≤2 cm, 15.1% crossed over, compared to 33.3% with initial tumor size 2-4 cm. Overall survival was similar in primary intervention and surveillance at 7 years (94.0% vs 90.8%, log-rank p=0.2). Cancer-specific survival remained at 100% for both groups. There were no significant differences between primary and delayed intervention with respect to minimally invasive or nephron-sparing interventions. Recurrence-free survival at 5 years was 96.0% and 100% for primary and delayed intervention, respectively (log-rank p=0.6).

Conclusions: Active surveillance is a safe initial strategy in younger patients and can avoid unnecessary intervention in a subset for whom it is durable. Crucially, no patient developed metastatic disease on surveillance or recurrence after delayed intervention. This study confirms active surveillance principles can effectively be applied to younger patients.
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http://dx.doi.org/10.1097/JU.0000000000001575DOI Listing
December 2020

Decision regret, adverse outcomes, and treatment choice in men with localized prostate cancer: Results from a multi-site randomized trial.

Urol Oncol 2020 Dec 19. Epub 2020 Dec 19.

Department of Urology, University of Massachusetts Medical Center, Worchester, MA.

Introduction: Men diagnosed with localized prostate cancer must navigate a highly preference-sensitive decision between treatment options with varying adverse outcome profiles. We evaluated whether use of a decision support tool previously shown to decrease decisional conflict also impacted the secondary outcome of post-treatment decision regret.

Methods: Participants were randomized to receive personalized decision support via the Personal Patient Profile-Prostate or usual care prior to a final treatment decision. Symptoms were measured just before randomization and 6 months later; decision regret was measured at 6 months along with records review to ascertain treatment choices. Regression modeling explored associations between baseline variables including race and D`Amico risk, study group, and 6-month variables regret, choice, and symptoms.

Results: At 6 months, 287 of 392 (73%) men returned questionnaires of which 257 (89%) had made a treatment choice. Of that group, 201 of 257 (78%) completely answered the regret scale. Regret was not significantly different between participants randomized to the P3P intervention compared to the control group (P = 0.360). In univariate analyses, we found that Black men, men with hormonal symptoms, and men with bowel symptoms reported significantly higher decision regret (all P < 0.01). Significant interactions were detected between race and study group (intervention vs. usual care) in the multivariable model; use of the Personal Patient Profile-Prostate was associated with significantly decreased decisional regret among Black men (P = 0.037). Interactions between regret, symptoms and treatment revealed that (1) men choosing definitive treatment and reporting no hormonal symptoms reported lower regret compared to all others; and (2) men choosing active surveillance and reporting bowel symptoms had higher regret compared to all others.

Conclusion: The Personal Patient Profile-Prostate decision support tool may be most beneficial in minimizing decisional regret for Black men considering treatment options for newly-diagnosed prostate cancer.

Trial Registration: NCT01844999.
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http://dx.doi.org/10.1016/j.urolonc.2020.11.038DOI Listing
December 2020

Predictive Values of Location and Volumetric MRI Injury Patterns for Neurodevelopmental Outcomes in Hypoxic-Ischemic Encephalopathy Neonates.

Brain Sci 2020 Dec 16;10(12). Epub 2020 Dec 16.

Department of Radiological Sciences, Center for Artificial Intelligence in Diagnostic Medicine (CADIM), University of California, Irvine, CA 92697, USA.

Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication with up to 40-60% long-term morbidity. This study evaluates the distribution and burden of MRI changes as a prognostic indicator of neurodevelopmental (ND) outcomes at 18-24 months in HIE infants who were treated with therapeutic hypothermia (TH). Term or late preterm infants who were treated with TH for HIE were analyzed between June 2012 and March 2016. Brain MRI scans were obtained from 107 TH treated infants. For each infant, diffusion weighted brain image (DWI) sequences from a 3T Siemens scanner were obtained for analysis. Of the 107 infants, 36 of the 107 infants (33.6%) had normal brain MR images, and 71 of the 107 infants (66.4%) had abnormal MRI findings. The number of clinical seizures was significantly higher in the abnormal MRI group ( < 0.001) than in the normal MRI group. At 18-24 months, 76 of the 107 infants (70.0%) showed normal ND stages, and 31 of the 107 infants (29.0%) exhibited abnormal ND stages. A lesion size count >500 was significantly associated with abnormal ND. Similarly, the total lesion count was larger in the abnormal ND group (14.16 vs. 5.29). More lesions in the basal ganglia (BG) and thalamus areas and a trend towards more abnormal MRI scans were significantly associated with abnormal ND at 18-24 months. In addition to clinical seizure, a larger total lesion count and lesion size as well as lesion involvement of the basal ganglia and thalamus were significantly associated with abnormal neurodevelopment at 18-24 months.
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http://dx.doi.org/10.3390/brainsci10120991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765589PMC
December 2020

Automatic Detection and Segmentation of Breast Cancer on MRI Using Mask R-CNN Trained on Non-Fat-Sat Images and Tested on Fat-Sat Images.

Acad Radiol 2020 Dec 11. Epub 2020 Dec 11.

Department of Radiological Sciences, University of California, 164 Irvine Hall, Irvine, CA 92697-5020. Electronic address:

Rationale And Objectives: Computer-aided methods have been widely applied to diagnose lesions on breast magnetic resonance imaging (MRI). The first step was to identify abnormal areas. A deep learning Mask Regional Convolutional Neural Network (R-CNN) was implemented to search the entire set of images and detect suspicious lesions.

Materials And Methods: Two DCE-MRI datasets were used, 241 patients acquired using non-fat-sat sequence for training, and 98 patients acquired using fat-sat sequence for testing. All patients have confirmed unilateral mass cancers. The tumor was segmented using fuzzy c-means clustering algorithm to serve as the ground truth. Mask R-CNN was implemented with ResNet-101 as the backbone. The neural network output the bounding boxes and the segmented tumor for evaluation using the Dice Similarity Coefficient (DSC). The detection performance, and the trade-off between sensitivity and specificity, was analyzed using free response receiver operating characteristic.

Results: When the precontrast and subtraction image of both breasts were used as input, the false positive from the heart and normal parenchymal enhancements could be minimized. The training set had 1469 positive slices (containing lesion) and 9135 negative slices. In 10-fold cross-validation, the mean accuracy = 0.86 and DSC = 0.82. The testing dataset had 1568 positive and 7264 negative slices, with accuracy = 0.75 and DSC = 0.79. When the obtained per-slice results were combined, 240 of 241 (99.5%) lesions in the training and 98 of 98 (100%) lesions in the testing datasets were identified.

Conclusion: Deep learning using Mask R-CNN provided a feasible method to search breast MRI, localize, and segment lesions. This may be integrated with other artificial intelligence algorithms to develop a fully automatic breast MRI diagnostic system.
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http://dx.doi.org/10.1016/j.acra.2020.12.001DOI Listing
December 2020

Safety of semi-depot house dust mite allergen extract in children and adolescents with allergic rhinitis and asthma.

Immunotherapy 2021 Feb 15;13(3):227-239. Epub 2020 Dec 15.

Global Biostatistics, Epidemiology, Medical Writing (GBEM), Merck Serono Co., Ltd, Beijing 100016, China.

Multicenter study to investigate the safety of mite extract product Novo-Helisen Depot, Strengths 1 to 3 (NHD3), as subcutaneous immunotherapy (SCIT), in Chinese children and adolescents with allergic rhinitis (AR) and allergic asthma (AA). We evaluated SCIT-related adverse events (AEs) during NHD3 14-week initial therapy in children (5-11 years) and adolescents (12-17 years) with perennial symptomatic AR and AA. Among 3600 injections in 250 patients, 361/3600 (10.0%) injections caused SCIT-related AEs in 96/250 (38.4%) patients, 321/3600 injections (8.9%) caused local reactions in 89/250 (35.6%) and 40/3600 injections (1.1%) caused systemic reactions in 23/250 (9.2%). Initial SCIT treatment using NHD3 was safe and well tolerated in Chinese children and adolescents with AR and AA.
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http://dx.doi.org/10.2217/imt-2020-0232DOI Listing
February 2021

Clinical Perspective of FDA Approved Drugs With P-Glycoprotein Inhibition Activities for Potential Cancer Therapeutics.

Front Oncol 2020 16;10:561936. Epub 2020 Nov 16.

Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.

P-glycoprotein (also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 () plays a crucial role in determining response against medications, including cancer therapeutics. It is now well established that p-glycoprotein acts as an ATP dependent pump that pumps out small molecules from cells. Ample evidence exist that show p-glycoprotein expression levels correlate with drug efficacy, which suggests the rationale for developing p-glycoprotein inhibitors for treatment against cancer. Preclinical and clinical studies have investigated this possibility, but mostly were limited by substantial toxicities. Repurposing FDA-approved drugs that have p-glycoprotein inhibition activities is therefore a potential alternative approach. In this review, we searched the Drugbank Database (https://www.drugbank.ca/drugs) and identified 98 FDA-approved small molecules that possess p-glycoprotein inhibition properties. Focusing on the small molecules approved with indications against non-cancer diseases, we query the scientific literature for studies that specifically investigate these therapeutics as cancer treatment. In light of this analysis, potential development opportunities will then be thoroughly investigated for future efforts in repositioning of non-cancer p-glycoprotein inhibitors in single use or in combination therapy for clinical oncology treatment.
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http://dx.doi.org/10.3389/fonc.2020.561936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704056PMC
November 2020

Development and external validation of a prognostic tool for COVID-19 critical disease.

PLoS One 2020 9;15(12):e0242953. Epub 2020 Dec 9.

Department of Radiological Sciences, University of California, Irvine, California, United States of America.

Background: The rapid spread of coronavirus disease 2019 (COVID-19) revealed significant constraints in critical care capacity. In anticipation of subsequent waves, reliable prediction of disease severity is essential for critical care capacity management and may enable earlier targeted interventions to improve patient outcomes. The purpose of this study is to develop and externally validate a prognostic model/clinical tool for predicting COVID-19 critical disease at presentation to medical care.

Methods: This is a retrospective study of a prognostic model for the prediction of COVID-19 critical disease where critical disease was defined as ICU admission, ventilation, and/or death. The derivation cohort was used to develop a multivariable logistic regression model. Covariates included patient comorbidities, presenting vital signs, and laboratory values. Model performance was assessed on the validation cohort by concordance statistics. The model was developed with consecutive patients with COVID-19 who presented to University of California Irvine Medical Center in Orange County, California. External validation was performed with a random sample of patients with COVID-19 at Emory Healthcare in Atlanta, Georgia.

Results: Of a total 3208 patients tested in the derivation cohort, 9% (299/3028) were positive for COVID-19. Clinical data including past medical history and presenting laboratory values were available for 29% (87/299) of patients (median age, 48 years [range, 21-88 years]; 64% [36/55] male). The most common comorbidities included obesity (37%, 31/87), hypertension (37%, 32/87), and diabetes (24%, 24/87). Critical disease was present in 24% (21/87). After backward stepwise selection, the following factors were associated with greatest increased risk of critical disease: number of comorbidities, body mass index, respiratory rate, white blood cell count, % lymphocytes, serum creatinine, lactate dehydrogenase, high sensitivity troponin I, ferritin, procalcitonin, and C-reactive protein. Of a total of 40 patients in the validation cohort (median age, 60 years [range, 27-88 years]; 55% [22/40] male), critical disease was present in 65% (26/40). Model discrimination in the validation cohort was high (concordance statistic: 0.94, 95% confidence interval 0.87-1.01). A web-based tool was developed to enable clinicians to input patient data and view likelihood of critical disease.

Conclusions And Relevance: We present a model which accurately predicted COVID-19 critical disease risk using comorbidities and presenting vital signs and laboratory values, on derivation and validation cohorts from two different institutions. If further validated on additional cohorts of patients, this model/clinical tool may provide useful prognostication of critical care needs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242953PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725393PMC
December 2020

Dynamic Changes of Convolutional Neural Network-based Mammographic Breast Cancer Risk Score Among Women Undergoing Chemoprevention Treatment.

Clin Breast Cancer 2020 Nov 17. Epub 2020 Nov 17.

Department of Radiology and Breast Imaging Section, New York-Presbyterian/Columbia University Medical Center, New York, NY. Electronic address:

Introduction: We investigated whether our convolutional neural network (CNN)-based breast cancer risk model is modifiable by testing it on women who had undergone risk-reducing chemoprevention treatment.

Materials And Methods: We conducted a retrospective cohort study of patients diagnosed with atypical hyperplasia, lobular carcinoma in situ, or ductal carcinoma in situ at our institution from 2007 to 2015. The clinical characteristics, chemoprevention use, and mammography images were extracted from the electronic health records. We classified two groups according to chemoprevention use. Mammograms were performed at baseline and subsequent follow-up evaluations for input to our CNN risk model. The 2 chemoprevention groups were compared for the risk score change from baseline to follow-up. The change categories included stayed high risk, stayed low risk, increased from low to high risk, and decreased from high to low risk. Unordered polytomous regression models were used for statistical analysis, with P < .05 considered statistically significant.

Results: Of 541 patients, 184 (34%) had undergone chemoprevention treatment (group 1) and 357 (66%) had not (group 2). Using our CNN breast cancer risk score, significantly more women in group 1 had shown a decrease in breast cancer risk compared with group 2 (33.7% vs. 22.9%; P < .01). Significantly fewer women in group 1 had an increase in breast cancer risk compared with group 2 (11.4% vs. 20.2%; P < .01). On multivariate analysis, an increase in breast cancer risk predicted by our model correlated negatively with the use of chemoprevention treatment (P = .02).

Conclusions: Our CNN-based breast cancer risk score is modifiable with potential utility in assessing the efficacy of known chemoprevention agents and testing new chemoprevention strategies.
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http://dx.doi.org/10.1016/j.clbc.2020.11.007DOI Listing
November 2020

Widefield Fundus Fluorescein Angiography Features of Uveitis Associated with Juvenile Idiopathic Arthritis.

Ocul Immunol Inflamm 2020 Dec 2:1-10. Epub 2020 Dec 2.

Massachusetts Eye Research and Surgery Institution, Waltham, Massachusetts, USA.

Purpose: To evaluate the wide-field fundus fluorescein angiography (WFA) characteristics of uveitis associated with juvenile idiopathic arthritis (JIA-uveitis).

Methods: Retrospective review of records. WFA with Spectralis (Heidelberg) of JIA-uveitis patients were analyzed using the scoring system by Angiography Scoring for Uveitis Nomenclature.

Results: Thirty-seven eyes of 20 patients were studied. A total score of at least 1 was noted in 27 eyes (72.97%). WFA features included optic disc hyperfluorescence (51.35%), macular leakage (27.03%), retinal vascular staining/leakage at posterior pole (27.03%) and peripheral retina (64.86%), capillary leakage at the posterior pole (37.84%), and peripheral retina (59.46%). A decision to change the management plan was made in 8 of 9 patients with bilateral quiet anterior chambers after WFA results.

Conclusion: More than 70% of JIA-uveitis eyes showed some WFA-evidence of posterior segment inflammation, which changed the course of therapy for a major proportion of patients with no clinically active anterior chamber inflammation.
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http://dx.doi.org/10.1080/09273948.2020.1834586DOI Listing
December 2020

Development and Validation of a UPLC-DAD Method for Quantitative Analysis of Coumarin, trans-Cinnamic Acid, trans-Cinnamaldehyde, and Eugenol in Encapsulated Cinnamon Flavoring Powder.

J AOAC Int 2020 Sep;103(5):1394-1399

Herbalife Nutrition, 990 West 190th Street, Torrance, CA 90502, USA.

Background: Cinnamon is a popular spice used in food products. Its flavor varies by its chemical profile. Cinnamon flavoring powder is a unique form of material with essential oil encapsulated in wall material, which improves the stability and homogeneity but also increases the difficulties for analysis. A specific and rapid method is needed to analyze the main components for its quality and safety.

Objective: An analytical method for the quantification of cinnamon flavoring powder was developed and validated. The characteristic components for analysis were selected as coumarin, trans-cinnamic acid, trans-cinnamaldehyde, and eugenol.

Methods: This quantitation method with ultra-performance liquid chromatography coupled with diode array detector analysis was achieved by material extraction followed by chromatographic separation on C18 columns eluted with a gradient acetonitrile-water mobile phase. The detected wavelength was determined as 280 nm.

Results: Linear regression of calibration curves for each component was validated (R2 > 0.9995). The specificity, LOD and LOQ, precision, accuracy, and ruggedness of the developed method were also evaluated.

Conclusions: Such an approach is applicable for the simultaneous determination of these four characteristic constituents in cinnamon flavoring powder used in manufacturing and quality control of nutritional products.

Highlights: This study describes the selection of four components for analysis, the efficient extraction of them from cinnamon flavoring powder, and the rapid quantitation of these four characteristic components in these materials.
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http://dx.doi.org/10.1093/jaoacint/qsaa031DOI Listing
September 2020

Single-Laboratory Validation Study of a Proton NMR Method for the Determination of L-Arginine, L-Citrulline, and Taurine Contents in Dietary Supplements.

J AOAC Int 2020 Jul;103(4):1140-1147

Herbalife International of America, 990 West 190th Street, Torrance, CA 90502, USA.

Background: A quantitative NMR (qNMR) method can provide rapid analysis compared to chromatographic methods. Sample preparation steps are relatively simpler and run time is shorter. Rapid analysis methods for release tests in quality control laboratories are very important for laboratory efficiency. Here, we describe a single-laboratory validation study for a rapid qNMR analysis of L-arginine, L-citrulline, and taurine in powdered and tablet dietary supplement products.

Objectives: This validation work is to provide documented evidence for the qNMR method validity as well as method performance.

Methods: The method used Bruker 400 MHz high-resolution proton NMR spectroscopy for simultaneous determination of L-arginine, L-citrulline, and taurine contents in dietary supplement product 1 (powder) and dietary supplement product 2 (tablet). The absolute NMR quantitation is based on a principle of universal proton response intensity correlation with the number of protons in each target analyte (amino acids) vs. that of a reference standard (maleic acid).

Results: The test method performance was validated with dietary supplement-1 (powder) and dietary supplement-2 (tablet). The linearity of the method was studied from about 360 mg/g to about 675 mg/g of L-arginine; from about 15 mg/g to about 30 mg/g of L-citrulline; and from about 20 mg/g to about 40 mg/g of taurine in dietary supplement-1, and from about 15 mg/g to about 30 mg/g of taurine in dietary supplement-2. The coefficients of determination (R2) are 1.0000 for L-arginine, 0.9967 for L-citrulline, and 0.9995 for taurine in dietary supplement-1 and 0.9903 for taurine in dietary supplement-2. The accuracies measured from the sample matrices are 102%, 101%, and 100% average recoveries for 80%, 100%, and 120% concentration levels of L-arginine, 105%, 105%, and 103% average recoveries for 80%, 100%, and 120% concentration level of L-citrulline, and 101%, 102%, and 100% average recoveries of taurine for 80%, 100%, 120% concentration levels in dietary supplement-1; and 95, 98%, and 93% average recoveries of taurine for 80%, 100%, 120% concentration levels in dietary supplement-2, respectively. The precisions (RSD) are 1% for L-arginine, 5% for L-citrulline, and 2% for taurine in dietary supplement -1, respectively; and 4% for taurine in dietary supplement-2. The ruggedness of the test method is within 2%, 4%, and 2% for L-arginine, L-citrulline, and taurine for dietary supplement -1, respectively, and within 4% for dietary supplement-2. The method is specific for the quantitation of each nutrient with no background interference from the matrix for the proton peaks of L-arginine, L-citrulline, taurine, and maleic acid (standard).

Conclusions: The test method is proven to be specific, precise, accurate, rugged, and suitable for intended quantitative analysis of L-arginine, L-citrulline, and taurine in powdered and tablet finished products.

Highlights: The simultaneous determination of all three nutrients of L-arginine, L-citrulline, and taurine using proton NMR provides rapid analysis for quality control release tests that is more efficient versus that of two HPLC methods. Previously, our laboratory was using one HPLC method to analyze L-arginine and L-citrulline while using a second HPLC method to analyze taurine. That approach required two HPLC instruments and two analysts for parallel analysis that takes 2 days using volatile and flammable solvents for extraction and chemical derivatization. This rapid NMR method can analyze the sample "as is" with results obtained in less than 4 h, and is efficient, safe, and environmentally friendly. The initial higher NMR instrument investment versus two HPLC instruments is rewarded with high returns for continued quality control tests.
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http://dx.doi.org/10.1093/jaoacint/qsaa002DOI Listing
July 2020

Differentiation of Milk and Whey Protein Concentrates by Microbiome Profiling Using 16S Metagenomics.

J AOAC Int 2020 Nov 17. Epub 2020 Nov 17.

Herbalife Nutrition, 990 West 190th Street, Torrance, CA.

Background: Protein Powder Identification presents a challenge in Quality Control. There is current deliberation of the specificity of methods for the identification of milk proteins, and the consensus identification method of whey protein from the USP-FCC relies on a combined analysis of the testing of Ash, Fat, Lactose, Loss on Drying, and Protein. These methods are non-specific.Milk and whey proteins both contain background DNA content. Both groups of proteins retain source DNA (cow), but also have bacterial DNA from natural flora, the dairy plant, and in whey protein, the cheesemaking process. The DNA in these materials is retained post-processing, even after the pasteurization process.

Objective: By utilizing 16S Metagenomics, the bacterial DNA in protein powders can be sequenced and cross-referenced to a curated library to ultimately create a microbiome profile of these raw materials. This microbiome can be measured for alpha and beta diversity, specifically how many and which species of bacteria are present.

Methods: Using 16S Metagenomics, we measure alpha and beta diversity of the microbiome profile of each protein powder and use principle coordinate analysis to produce differential groupings, providing a novel identification method for raw materials.

Results: In this study, we demonstrate that the microbiome of cow proteins can be used for raw material identification, as the microbiome of milk and whey proteins differ significantly. We also demonstrate that the microbiome of whey protein concentrate can differ from supplier to supplier.

Conclusion: Microbiome profiling by 16S metagenomics can be an important forensic tool for quality control.
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http://dx.doi.org/10.1093/jaoacint/qsaa158DOI Listing
November 2020

Defining Features of Hand Anomalies in Severe Thumb Hypoplasia: A Classification Modification.

J Hand Surg Am 2020 Nov 12. Epub 2020 Nov 12.

Department of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, MO. Electronic address:

Purpose: To investigate morphologic hand anomalies in children with severe but unclassifiable forms of thumb hypoplasia and radial-sided hand deficiency.

Methods: We identified 15 extremities in 13 patients with severe thumb hypoplasia and associated absent radial-sided digits through the Congenital Upper Limb Differences registry. All patients had forearm involvement. Medical records, clinical photographs, and radiographs were evaluated. Radial longitudinal deficiency (RLD) and thumb hypoplasia were classified according to the Bayne and Klug classification and modified Blauth classification, respectively. Unusual or defining associated hand characteristics were identified and categorized.

Results: The most common type of forearm abnormality was absence of the radius (Bayne and Klug type IV), which was present in 10 extremities in the cohort. All 15 extremities had absent thumbs with loss of additional digits. In 6 patients, RLD was part of a syndrome (46%).

Conclusions: Severe forms of thumb hypoplasia in RLD are uncommon. We propose a further modification of the Blauth classification of thumb hypoplasia, type VI, for improved communication regarding this severe type of radial deficiency involving the hand.

Type Of Study/level Of Evidence: Diagnostic IV.
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http://dx.doi.org/10.1016/j.jhsa.2020.10.005DOI Listing
November 2020

Does the Presence of Chondral Lesions Negatively Affect Patient-Determined Outcomes After Arthroscopic Rotator Cuff Repair?

Orthop J Sports Med 2020 Oct 21;8(10):2325967120957993. Epub 2020 Oct 21.

University of South Dakota, Vermillion, South Dakota, USA.

Background: There are limited data available to guide patients to their prognosis when glenohumeral chondral lesions are found during arthroscopic rotator cuff repair.

Hypothesis: The primary hypothesis was that patients with glenohumeral chondral lesions will have inferior outcomes after arthroscopic rotator cuff repair compared with patients without chondral lesions. The secondary hypothesis was that patients with concomitant chondral lesions will have more severe preoperative symptoms compared with those without chondral lesions.

Study Design: Cohort study; Level of evidence, 3.

Methods: A retrospective analysis was performed of patients who underwent arthroscopic rotator cuff repair between 2008 and 2012. We examined the effects of chondral lesions on patient-determined outcomes, which included the Western Ontario Rotator Cuff Index (WORC), American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test (SST), Single Assessment Numeric Evaluation (SANE), and the Shoulder Activity Level (SAL). Shoulders without chondral lesions were compared with shoulders with chondral lesions to determine whether differences in severity of preoperative symptoms as well as postoperative improvements were statistically significant.

Results: A total of 281 shoulders were included from 273 patients, with a mean follow-up of 3.7 years. In total, 90 shoulders (32%) had concomitant chondral lesions in the glenohumeral joint. The presence and degree of chondral damage were not associated with the severity of preoperative symptoms or the amount of improvement after arthroscopic rotator cuff repair, as determined by patient outcome scores. Shoulders with bipolar chondral lesions had less postoperative improvement in their outcome scores compared with shoulders with unipolar lesions, with significant differences found in the SST ( = .0005), the SANE ( = .005), and the SAL ( = .04). Regardless of this, the majority of shoulders with bipolar chondral lesions (80%-92%) had postoperative improvements that superseded the minimal clinically important difference of the ASES, WORC, and SANE.

Conclusion: At a mean 3.7-year follow-up, the presence of chondral damage did not appear to negatively affect the improvement in patient-determined outcomes after arthroscopic rotator cuff repair. However, improvement in outcomes was negatively affected by the presence of bipolar chondral lesions.
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http://dx.doi.org/10.1177/2325967120957993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588774PMC
October 2020

Health Literacy, eHealth Literacy, Adherence to Infection Prevention and Control Procedures, Lifestyle Changes, and Suspected COVID-19 Symptoms Among Health Care Workers During Lockdown: Online Survey.

J Med Internet Res 2020 11 12;22(11):e22894. Epub 2020 Nov 12.

School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.

Background: The COVID-19 pandemic has imposed a heavy burden on health care systems and governments. Health literacy (HL) and eHealth literacy (as measured by the eHealth Literacy Scale [eHEALS]) are recognized as strategic public health elements but they have been underestimated during the pandemic. HL, eHEALS score, practices, lifestyles, and the health status of health care workers (HCWs) play crucial roles in containing the COVID-19 pandemic.

Objective: The aim of this study is to evaluate the psychometric properties of the eHEALS and examine associations of HL and eHEALS scores with adherence to infection prevention and control (IPC) procedures, lifestyle changes, and suspected COVID-19 symptoms among HCWs during lockdown.

Methods: We conducted an online survey of 5209 HCWs from 15 hospitals and health centers across Vietnam from April 6 to April 19, 2020. Participants answered questions related to sociodemographics, HL, eHEALS, adherence to IPC procedures, behavior changes in eating, smoking, drinking, and physical activity, and suspected COVID-19 symptoms. Principal component analysis, correlation analysis, and bivariate and multivariate linear and logistic regression models were used to validate the eHEALS and examine associations.

Results: The eHEALS had a satisfactory construct validity with 8 items highly loaded on one component, with factor loadings ranked from 0.78 to 0.92 explaining 76.34% of variance; satisfactory criterion validity as correlated with HL (ρ=0.42); satisfactory convergent validity with high item-scale correlations (ρ=0.80-0.84); and high internal consistency (Cronbach α=.95). HL and eHEALS scores were significantly higher in men (unstandardized coefficient [B]=1.01, 95% CI 0.57-1.45, P<.001; B=0.72, 95% CI 0.43-1.00, P<.001), those with a better ability to pay for medication (B=1.65, 95% CI 1.25-2.05, P<.001; B=0.60, 95% CI 0.34-0.86, P<.001), doctors (B=1.29, 95% CI 0.73-1.84, P<.001; B 0.56, 95% CI 0.20-0.93, P=.003), and those with epidemic containment experience (B=1.96, 95% CI 1.56-2.37, P<.001; B=0.64, 95% CI 0.38-0.91, P<.001), as compared to their counterparts, respectively. HCWs with higher HL or eHEALS scores had better adherence to IPC procedures (B=0.13, 95% CI 0.10-0.15, P<.001; B=0.22, 95% CI 0.19-0.26, P<.001), had a higher likelihood of healthy eating (odds ratio [OR] 1.04, 95% CI 1.01-1.06, P=.001; OR 1.04, 95% CI 1.02-1.07, P=.002), were more physically active (OR 1.03, 95% CI 1.02-1.03, P<.001; OR 1.04, 95% CI 1.03-1.05, P<.001), and had a lower likelihood of suspected COVID-19 symptoms (OR 0.97, 95% CI 0.96-0.98, P<.001; OR 0.96, 95% CI 0.95-0.98, P<.001), respectively.

Conclusions: The eHEALS is a valid and reliable survey tool. Gender, ability to pay for medication, profession, and epidemic containment experience were independent predictors of HL and eHEALS scores. HCWs with higher HL or eHEALS scores had better adherence to IPC procedures, healthier lifestyles, and a lower likelihood of suspected COVID-19 symptoms. Efforts to improve HCWs' HL and eHEALS scores can help to contain the COVID-19 pandemic and minimize its consequences.
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http://dx.doi.org/10.2196/22894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674138PMC
November 2020