Publications by authors named "Min Zhan"

139 Publications

Risk prediction for delayed clearance of high-dose methotrexate in pediatric hematological malignancies by machine learning.

Int J Hematol 2021 Jun 25. Epub 2021 Jun 25.

Department of Hematology/Oncology, Shenzhen Children's Hospital, Shenzhen, 518036, People's Republic of China.

This study aimed to establish a predictive model to identify children with hematologic malignancy at high risk for delayed clearance of high-dose methotrexate (HD-MTX) based on machine learning. A total of 205 patients were recruited. Five variables (hematocrit, risk classification, dose, SLC19A1 rs2838958, sex) and three variables (SLC19A1 rs2838958, sex, dose) were statistically significant in univariable analysis and, separately, multivariate logistic regression. The data was randomly split into a "training cohort" and a "validation cohort". A nomogram for prediction of delayed HD-MTX clearance was constructed using the three variables in the training dataset and validated in the validation dataset. Five machine learning algorithms (cart classification and regression trees, naïve Bayes, support vector machine, random forest, C5.0 decision tree) combined with different resampling methods were used for model building with five or three variables. When developed machine learning models were evaluated in the validation dataset, the C5.0 decision tree combined with the synthetic minority oversampling technique (SMOTE) using five variables had the highest area under the receiver operating characteristic curve (AUC 0.807 [95% CI 0.724-0.889]), a better performance than the nomogram (AUC 0.69 [95% CI 0.594-0.787]). The results support potential clinical application of machine learning for patient risk classification.
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http://dx.doi.org/10.1007/s12185-021-03184-wDOI Listing
June 2021

Immune role of the complement component 6 gene and its associated novel miRNA, miR-727, in half-smooth tongue sole (Cynoglossus semilaevis).

Dev Comp Immunol 2021 Oct 30;123:104156. Epub 2021 May 30.

Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao, 266071, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China. Electronic address:

The complement component 6 (C6) gene is a component of the membrane attack complex (MAC), which causes rapid lytic destruction of bacteria. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene stability, including that of immune genes. However, current research on the function of C6 and its regulation by miRNAs is lacking. In the present study, we identified and characterized C6 and a novel miRNA, miR-727 (designated CsC6 and Cse-miR-727, respectively), of the half-smooth tongue sole (Cynoglossus semilaevis) that responded to infection with Vibrio anguillarum, a Gram-negative pathogen of marine fish. The full-length cDNA of CsC6 contained a 256 bp 5' untranslated region (5'-UTR), a 2820 bp open reading frame (ORF) encoding 939 amino acids, and a 205 bp 3'-UTR. SMART analysis showed that CsC6 contains typical C6 domains, including three TSP1 domains, one LDLa domain, one MACPF domain, two CCP domains and two FIMAC domains. CsC6 and Cse-miR-727 are widely expressed in the 13 tissues of half-smooth tongue sole, and their expression in immune tissues is significantly changed after V. anguillarum infection, generally showing an inverse trend. We confirmed that CsC6 was the target gene of Cse-miR-727 using the dual luciferase reporter assay and that Cse-miR-727 regulated CsC6 at the protein level using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The hepatic expression levels of not only the MAC components C7, C8α, C8β, C8γ and C9 but also the MAPKs, NF-κβ, AP-1, IL1β, IL6 and TNFα, which are involved in many signaling pathways, changed significantly in half-smooth tongue sole following stimulation with the Cse-miR-727 agomir and inhibitor. This evidence suggested that CsC6 could be mediated by Cse-miR-727 to affect MAC assembly and immune signaling pathways in half-smooth tongue soles. To our best knowledge, this study is the first to investigate the regulatory mechanism and immune response of complement genes mediated by miRNAs in fish.
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http://dx.doi.org/10.1016/j.dci.2021.104156DOI Listing
October 2021

Exploring the Mechanism of Zhibai Dihuang Decoction in the Treatment of Ureaplasma Urealyticum-Induced Orchitis Based on Integrated Pharmacology.

Front Pharmacol 2021 10;12:602543. Epub 2021 May 10.

College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China.

Ureaplasma urealyticum (UU) infection is the most common cause of male infertility. Zhibai Dihuang Decoction (ZBDHD) can improve the rate of forwarding motility sperm, sperm deformity rate, seminal plasma zinc and refined berry sugar levels. The potential targets of ZBDHD are obtained from The Encyclopedia of Traditional Chinese Medicine (ETCM). Orchitis-related targets were collected from the Genecards and OMIM databases. The Cytoscape and the Database for Annotation, Visualization and Integrated Discovery (DAVID) were utilized to construct and analyzed the networks. Finally, a rat model of orchitis caused by UU infection was used to detect related indicators of mitochondrial energy metabolism using TUNEL apoptosis detection technology, loss cytometry, Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) and Western Blot. A total of 795 ZBDHD targets and 242 orchitis-related targets were obtained. The "ZBDHD- orchitis PPI network" was constructed and analyzed. ZBDHD can regulate signaling pathways and biological processes related to mitochondrial energy metabolism. The results of experimental studies have shown that ZBDHD maintains the integrity of sperm mitochondrial respiratory chain function by enhancing mitochondrial Na-K-ATPase and Ca2-Mg-ATPase activities, promotes the synthesis of mitochondrial ATP, and improves sperm energy supply, thereby improving the motility, vitality and survival rate of sperm, and effectively improving the quality of semen in UU-infected rats ( < 0.05). This study discovered the multi-pathway mechanism of ZBDHD intervention in UU-induced orchitis through integrated pharmacological strategies, which provides a reference for further research on the mechanism of ZBDHD intervention in orchitis in the direction of mitochondrial energy metabolism.
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http://dx.doi.org/10.3389/fphar.2021.602543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141734PMC
May 2021

Risk of Potentially Inappropriate Medications in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Am J Kidney Dis 2021 May 23. Epub 2021 May 23.

Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland.

Rationale & Objective: Adults with chronic kidney disease (CKD) may be at increased risk of adverse effects from use of potentially inappropriate medications (PIMs). Our objective was to assess whether PIM exposure has an independent association with CKD progression, hospitalizations, mortality, or falls.

Study Design: Retrospective observational study.

Setting & Participants: Chronic Renal Insufficiency Cohort (CRIC) study; 3,929 adults with CKD enrolled 2003-2008 and followed prospectively until December 2011.

Exposure: PIM exposure was defined as prescriptions for any medications to be avoided in older adults as defined by the 2015 American Geriatrics Society Beers Criteria.

Outcome: Hospitalization count, death, a composite kidney disease end point of CKD progression or initiation of kidney replacement therapy (KRT), KRT, and fall events assessed 1 year after PIM exposure.

Analytical Approach: Logistic regression and Poisson regression to estimate the associations of PIM exposure with each outcome.

Results: The most commonly prescribed PIMs were proton pump inhibitors and α-blockers. In unadjusted models, any PIM exposure (compared to none) was associated with hospitalizations, death, and fall events. After adjustment, exposure to 1, 2, or≥3 PIMs had a graded association with a higher hospitalization rate (rate ratios of 1.09 [95% CI, 1.01-1.17], 1.18 [95% CI, 1.07-1.30], and 1.35 [95% CI, 1.19-1.53], respectively) and higher odds of mortality (odds ratios of 1.19 [95% CI, 0.91-1.54], 1.62 [95% CI, 1.21-2.17], and 1.65 [95% CI, 1.14-2.41], respectively). In a cohort subset reporting falls (n=1,109), prescriptions for≥3 PIMs were associated with an increased risk of falls (adjusted OR, 2.85 [95% CI, 1.54-5.26]). PIMs were not associated with CKD progression or KRT. Age did not modify the association between PIM count and outcomes.

Limitations: Measurement bias; confounding by indication.

Conclusions: Adults of any age with CKD who are prescribed PIMs have an increased risk of hospitalization, mortality, and falls with the greatest risk occurring after more than 1 PIM prescription.
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http://dx.doi.org/10.1053/j.ajkd.2021.03.019DOI Listing
May 2021

An isotope dilution liquid chromatography-tandem mass spectrometry candidate reference measurement procedure for aldosterone measurement in human plasma.

Anal Bioanal Chem 2021 Jul 20;413(17):4471-4481. Epub 2021 May 20.

Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, Guangdong, China.

Accurate quantitation of aldosterone is clinically important in standardized testing for primary aldosteronism. The results are often variable when performed by clinical immunoassays. To standardize and ensure the accuracy of clinical systems, reference measurement procedures (RMPs) with higher metrological order are required. A simple and reliable isotope dilution LC-IDMS/MS-based measurement procedure for human plasma aldosterone has been developed. This method involved plasma spiked with a deuterium-labelled internal standard, equilibrated for 0.5 h, and extracted by liquid-liquid extraction (LLE) without derivatization. Aldosterone and its structural analogues were baseline separated with a C18-packed UHPLC column with gradient elution within 7 min. The signal intensity variability and measurement imprecision were reduced by bracketing calibration during plasma aldosterone value assignment. The limit of detection (LoD) was 19.4 pmol/L with a signal-to-noise ratio (S/N) > 3. The lowest limit of quantification (LLoQ) was 27.7 pmol/L (S/N > 10 and CV < 10.0%). LLE was performed with 1 mL of n-hexane/ethyl acetate (3:2, v/v), and the extraction recovery was determined to be 92.15 ± 3.54%. The imprecisions were ≤ 3.18% for samples at 124.8, 867.0, and 2628.5 pmol/L. The recoveries were 98.11-101.61%. The relative bias between this candidate RMP and the established RMP was 2.76-1.89%. The linearity response ranged from 27.7 to 2774.4 pmol/L with R = 0.999. The method performance met the requirements of RMPs (≤ 5% total CV and ≤ 3% bias). Furthermore, the developed method was applied to evaluate immunoassays through 41 patient sample comparisons. The calibration and measurement capability (CMC) of this method were also evaluated by measuring these samples. The candidate RMP can serve as an accurate reference baseline for routine methods and can be used for value assignment for reference materials. Selected ion chromatograms by LC-MS/MS using a C18 column for aldosterone and its structural analogues.
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http://dx.doi.org/10.1007/s00216-021-03405-5DOI Listing
July 2021

Machine learning to predict high-dose methotrexate-related neutropenia and fever in children with B-cell acute lymphoblastic leukemia.

Leuk Lymphoma 2021 Apr 26:1-12. Epub 2021 Apr 26.

Department of Hematology/Oncology, Shenzhen Children's Hospital, Shenzhen, People's Republic of China.

Methotrexate (MTX), an antimetabolite for the treatment of leukemia, could cause neutropenia and subsequently fever, which might lead to treatment delay and affect prognosis. Here, we aimed to predict neutropenia and fever related to high-dose MTX using artificial intelligence. This study included 139 pediatric patients newly diagnosed with standard- or intermediate risk B-cell acute lymphoblastic leukemia. Fifty-seven SNPs of 16 genes were genotyped. Univariate and multivariate analysis were used to select SNPs and clinical covariates for model developing. Five machine learning algorithms combined with four resampling techniques were used to build optimal predictive model. The combination of random forest with adaptive synthetic appeared to be the best model for neutropenia (sensitivity = 0.935, specificity = 0.920, AUC = 0.927) and performed best for fever (sensitivity = 0.818, specificity = 0.924, AUC = 0.870). By machine learning, we have developed and validated comprehensive models to predict the risk of neutropenia and fever. Such models may be helpful for medical oncologists in quick decision-making.
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http://dx.doi.org/10.1080/10428194.2021.1913140DOI Listing
April 2021

Targeted intestinal deletion of Rho guanine nucleotide exchange factor 7, βPIX, impairs enterocyte proliferation, villus maturation, and mucosal defenses in mice.

Am J Physiol Gastrointest Liver Physiol 2021 04 10;320(4):G627-G643. Epub 2021 Feb 10.

Veterans Affairs Maryland Healthcare System, Baltimore, Maryland.

Rho guanine nucleotide exchange factors (RhoGEFs) regulate Rho GTPase activity and cytoskeletal and cell adhesion dynamics. βPix, a CDC42/RAC family RhoGEF encoded by is reported to modulate human colon cancer cell proliferation and postwounding restitution of rat intestinal epithelial monolayers. We hypothesized that βPix plays a role in maintaining intestinal epithelial homeostasis. To test this hypothesis, we examined βPix distribution in the human and murine intestine and created mice with intestinal epithelial-selective βPix deletion [βPix/Tg(villin-Cre); CKO mice]. Using conditional knockout (CKO) and control mice, we investigated the consequences of βPix deficiency in vivo on intestinal epithelial and enteroid development, dextran sodium sulfate-induced mucosal injury, and gut permeability. In normal human and murine intestines, we observed diffuse cytoplasmic and moderate nuclear βPix immunostaining in enterocytes. CKO mice were viable and fertile, with normal gross intestinal architecture but reduced small intestinal villus height, villus-to-crypt ratio, and goblet cells; small intestinal crypt cells had reduced Ki67 staining, compatible with impaired cell proliferation. Enteroids derived from control mouse small intestine were viable for more than 20 passages, but those from CKO mice did not survive beyond 24 h despite addition of Wnt proteins or conditioned media from normal enteroids. Adding a Rho kinase (ROCK) inhibitor partially rescued CKO enteroid development. Compared with littermate control mice, dextran sodium sulfate-treated βPix-deficient mice lost more weight and had greater impairment of intestinal barrier function, and more severe colonic mucosal injury. These findings reveal βPix expression is important for enterocyte development, intestinal homeostasis, and resistance to toxic injury. To explore the role of βPix, a guanine nucleotide exchange factor encoded by , in intestinal development and physiology, we created mice with intestinal epithelial cell /βPix deficiency. We found βPix essential for normal small intestinal epithelial cell proliferation, villus development, and mucosal resistance to injury. Moreover, Rho kinase signaling mediated developmental arrest observed in enteroids derived from βPix-deficient small intestinal crypts. Our studies provide insights into the role /βPix plays in intestinal epithelial homeostasis.
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http://dx.doi.org/10.1152/ajpgi.00415.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238171PMC
April 2021

Bounded Confidence Evolution of Opinions and Actions in Social Networks.

IEEE Trans Cybern 2021 Jan 15;PP. Epub 2021 Jan 15.

Inspired by the continuous opinion and discrete action (CODA) model, bounded confidence and social networks, the bounded confidence evolution of opinions and actions in social networks is investigated and a social network opinions and actions evolutions (SNOAEs) model is proposed. In the SNOAE model, it is assumed that each agent has a CODA for a certain issue. Agents' opinions are private and invisible, that is, an individual agent only knows its own opinion and cannot obtain other agents' opinions unless there is a social network connection edge that allows their communication; agents' actions are public and visible to all agents and impact other agents' actions. Opinions and actions evolve in a directed social network. In the limitation of the bounded confidence, other agents' actions or agents' opinions noticed or obtained by network communication, respectively, are used by agents to update their opinions. Based on the SNOAE model, the evolution of the opinions and actions with bounded confidence is investigated in social networks both theoretically and experimentally with a detailed simulation analysis. Theoretical research results show that discrete actions can attract agents who trust the discrete action, and make agents to express extreme opinions. Simulation experiments results show that social network connection probability, bounded confidence, and the opinion threshold of action choice parameters have strong impacts on the evolution of opinions and actions. However, the number of agents in the social network has no obvious influence on the evolution of opinions and actions.
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http://dx.doi.org/10.1109/TCYB.2020.3043635DOI Listing
January 2021

Comparing Home Upper Extremity Activity with Clinical Evaluations of Arm Function in Chronic Stroke.

Arch Rehabil Res Clin Transl 2020 Jun;2(2)

VA Maryland Health Care System - Baltimore Veterans Affairs Medical Center.

Objective: To determine if clinical evaluations of post-stroke arm function correspond to everyday motor performance indexed by arm accelerometers.

Design: Cross-sectional study analyzing baseline data from a larger trial (NCT02665052).

Setting: Outpatient research center.

Participants: Twenty community-dwelling adults with chronic arm motor deficits (stroke≥6mo).

Intervention: 72-hours of home wrist-worn accelerometry during normal routine.

Main Outcome Measures: Clinical evaluations included the Fugl-Meyer (FM), Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), and two self-assessments: the Motor Activity Log (MAL) and hand motor subscale of the Stroke Impact Scale (SIS). Accelerometer-derived variables included quantifications of movement intensity (magnitude) and duration of arm use.

Results: Participants had moderate arm impairment (FM 36.1 ± 9.4). The accelerometer-derived mean magnitude ratio correlated significantly with the FM ( = 0.60, p < 0.01), WMFT functional score ( = 0.59, p < 0.01), and ARAT ( = 0.50, p < 0.05). The hours of use ratio correlated with the MAL amount of use ( = 0.58, p < 0.01) and quality of movement ( = 0.61, p < 0.01). Total paretic hours did not correlate with the FM, WMFT or ARAT, and intensity variables did not correlate with the MAL or SIS.

Conclusions: Participants with higher baseline function had greater intensity of paretic arm movement at home; similarly, those who perceived they had less disability used their paretic arm more relative to their non-paretic arm. However, some participants with higher clinical scores did not exhibit greater arm use in everyday life, possibly due to neglect and learned non-use. Therefore, individualized home accelerometry profiles could provide valuable insight to better tailor post-stroke rehabilitation.
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http://dx.doi.org/10.1016/j.arrct.2020.100048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739859PMC
June 2020

Predictors of early postoperative pain interference following orthopaedic surgery.

J Orthop 2020 Nov-Dec;22:579-583. Epub 2020 Nov 13.

Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA.

Introduction: Despite the increasing incidence of orthopaedic surgeries, there is a lack of data reporting on patient experience and recovery following surgery. As such, there is a need to better characterize the natural history of pain interference (PI) after orthopaedic surgery to better manage patients' expectations and recovery.

Purpose: To identify factors associated with greater pain interference two weeks following orthopaedic surgery.

Methods: All patients undergoing elective outpatient orthopaedic surgery at a single urban academic institution were evaluated preoperatively from August 2016 to March 2018. Patients completed a baseline assessment consisting of demographic information, PROMIS computer adaptive testing in 6 domains including Pain Interference (PI), Physical Function, Social Satisfaction, Fatigue, Anxiety, and Depression. Two weeks following surgery, patients completed the same questionnaires along with assessments of Improvement and Satisfaction. Bivariate and multivariable regression analyses were performed. Categorical data was compared with ANOVA and continuous data was compared with Spearman's correlation coefficient (r).

Results: 435 patients (age = 41.1 ± 15.7, 47% female) were studied. Mean PI was 60.1 ± 7.0 prior to surgery and 61.7 ± 7.6 at 2 weeks postoperative. Worse 2 week PROMIS PI was associated with lower extremity surgery, prior surgery on the joint, preoperative opioid use, depression, lower income, lower education, and higher ASA score (p < 0.05). Better 2 week PROMIS PI was correlated with better baseline and better 2 week scores on all outcome measures. Multivariable analysis demonstrated that lower extremity surgery, worse preoperative pain scores, and worse preoperative pain interference were independent predictors of worse pain interference after surgery.

Conclusion: Early postoperative pain interference is associated with function, demographic, and psychosocial factors.
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http://dx.doi.org/10.1016/j.jor.2020.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688990PMC
November 2020

Viscosity and Structure of Water and Ethanol within GO Nanochannels: A Molecular Simulation Study.

J Phys Chem B 2020 12 17;124(48):10961-10970. Epub 2020 Nov 17.

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 211816, China.

The behavior of liquids in two-dimensional (2-D) graphene oxide (GO) nanopores is important for developing GO-based nanoscience and nanofluidics. Herein, molecular dynamics simulation was carried out to study the equilibrium structures and shear viscosity for water and ethanol confined within 2-D GO nanochannels. It was observed that both species obviously exhibit structured features near GO surfaces. The confined viscosities are anisotropic with axial shear viscosity larger than vertical viscosity. The axial shear viscosities of water and ethanol are greatly enhanced for the 2-D GO nanochannels, wherein the viscosity features a decreased pattern with the pore width. Compared with water molecules, the confinement of GO channels has more effect on the viscosity of ethanol molecules. The confined shear viscosity can be described by combining contributions of the interfacial layer viscosity and the bulk-like viscosity. The influences of oxidation degrees and pore widths on the structure and transport properties have been systematically investigated, in which the interlayer viscosity is the critical determining factor. The confined structures and surface interaction were applied to interpret the transport properties of confined liquids. The enhanced interfacial layer viscosity can be attributed to the surface hydrogen-bonding interaction arising from the oxygen-containing functional groups.
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http://dx.doi.org/10.1021/acs.jpcb.0c07147DOI Listing
December 2020

The endothelial protein C receptor plays an essential role in the maintenance of pregnancy.

Sci Adv 2020 Nov 6;6(45). Epub 2020 Nov 6.

Division of Pediatric Pathology, Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.

Placenta-mediated pregnancy complications are a major challenge in the management of maternal-fetal health. Maternal thrombophilia is a suspected risk factor, but the role of thrombotic processes in these complications has remained unclear. Endothelial protein C receptor (EPCR) is an anticoagulant protein highly expressed in the placenta. EPCR autoantibodies and gene variants are associated with poor pregnancy outcomes. In mice, fetal EPCR deficiency results in placental failure and in utero death. We show that inhibition of molecules involved in thrombin generation or in the activation of maternal platelets allows placental development and embryonic survival. Nonetheless, placentae exhibit venous thrombosis in uteroplacental circulation associated with neonatal death. In contrast, maternal EPCR deficiency results in clinical and histological features of placental abruption and is ameliorated with concomitant Par4 deficiency. Our findings unveil a causal link between maternal thrombophilia, uterine hemorrhage, and placental abruption and identify Par4 as a potential target of therapeutic intervention.
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http://dx.doi.org/10.1126/sciadv.abb6196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673707PMC
November 2020

PROMIS physical function two weeks following orthopaedic surgery.

J Clin Orthop Trauma 2020 Oct 11;11(Suppl 5):S837-S843. Epub 2020 Jun 11.

Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA.

Many patients opt for elective orthopaedic procedures to regain physical function. However, little data exist about patient-reported early postoperative function.

Purpose: To characterize physical function two weeks postoperative from upper and lower extremity orthopaedic surgery and to determine pre-operative factors that are associated with physical function two weeks following surgery.

Methods: Patients 17 years and older undergoing elective orthopaedic surgery at one institution were enrolled prospectively and completed questionnaires prior to surgery and again two weeks postoperatively. The questionnaires included: six of the PROMIS computer adaptive questionnaires: Physical Function (PF), Pain Interference, Fatigue, Social Satisfaction, Anxiety, and Depression; a joint-specific function questionnaire, a joint numeric pain scale, and a body numeric pain scale. Physical activity levels were measured using Tegner, IPAQ, and Marx. Responses were analyzed using Spearman's correlation coefficient, ANOVA, and multivariate linear stepwise regression with two-week PF as the dependent variable.

Results: 435 patients (47% female) with mean age 41.1 ± 15.7 were included in our final analysis. Mean baseline PF score was 42.1 and mean two-week PF score was 35.5 (p < .0001). Patients undergoing upper extremity surgery had higher PF at two weeks than those undergoing lower extremity surgery (39.1 vs 32.2, p < .0001). Younger age, Hispanic ethnicity, preoperative narcotic use, injury prior to surgery, and procedure all had a significant relationship with lower 2-week postoperative PF score (p < 0.05). Numerous baseline and 2-week measures were correlated with postoperative PF score, with 2-week Social Satisfaction demonstrating the strongest correlation (r = 0.604, p < .0001). Multivariable regression confirmed that the better preoperative PF score and upper extremity surgery were independent preoperative predictors of better 2-week PF scores.

Conclusions: Patients have a significant decline in physical function following orthopaedic surgery, with those undergoing lower extremity surgery having a significantly greater decline. Many factors are associated with activity levels, including mental health, pain, and satisfaction. This information can be used to help manage patients' short-term expectations.
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http://dx.doi.org/10.1016/j.jcot.2020.06.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503061PMC
October 2020

Preoperative expectations and early postoperative met expectations of extremity orthopaedic surgery.

J Clin Orthop Trauma 2020 Oct 16;11(Suppl 5):S829-S836. Epub 2020 Jun 16.

Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Preoperative patient expectations and met expectations are likely associated with the outcome of treatment. However, there is a lack of data regarding the preoperative expectations and early postoperative met expectations of patients undergoing extremity orthopaedic surgery. The purpose of this study was to identify the predictors of early postoperative met expectations in a cohort of patients undergoing extremity orthopaedic surgery and to assess the relationship between patient expectations and patient-reported outcome (PRO) measures. We hypothesized that patients with higher preoperative expectation scores and higher postoperative met expectation scores would have better early postoperative outcomes.

Methods: Four hundred thirty-five patients age seventeen and older who underwent extremity orthopaedic surgery at one institution were prospectively enrolled in this study. Each patient completed a preoperative questionnaire that included an assessment of demographics, pain, function, general health, treatment expectations, activity level, and Patient-Reported Outcome Measurement Information System (PROMIS) computer adaptive testing. Expectations were evaluated using the Expectations Domain of the Musculoskeletal Outcomes Data Evaluation and Management System (MODEMS) questionnaire. Patients completed a follow-up questionnaire two weeks after surgery that also assessed MODEMS met expectations and satisfaction (Surgical Satisfaction Questionnaire (SSQ-8)).

Results: The mean preoperative expectation score was 86.95 ± 16.59, and the mean postoperative met expectation score was 55.02 ± 27.63 (0-100 scale with 100 representing the highest level of expectations). Greater met expectations were significantly associated with white race (p = 0.025), college degree (p = 0.011), and higher income (p = 0.002). Greater met expectations were also significantly associated with greater postoperative physical function, social satisfaction, activity level, and subjective improvement, as well as lower pain interference, joint pain, body pain, fatigue, anxiety, and depression (p < 0.01 for each). Multivariable analysis results found that less postoperative joint pain and greater postoperative social satisfaction, improvement, and physical function were all significant independent predictors of greater met expectations at two weeks postoperative (p < 0.01 for each).

Conclusion: Greater preoperative expectations are associated with better activity and less pain two weeks after surgery. Met expectations of extremity orthopaedic surgery were associated with postoperative physical function, social satisfaction, activity, pain, anxiety, depression, and subjective improvement. These results may have implications for preoperative counseling and risk factor modification.
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http://dx.doi.org/10.1016/j.jcot.2020.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503149PMC
October 2020

Early patient satisfaction following orthopaedic surgery.

J Clin Orthop Trauma 2020 Oct 27;11(Suppl 5):S823-S828. Epub 2020 Jun 27.

Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: The healthcare industry is shifting its focus from traditional clinical outcome measures to patient satisfaction metrics. This change has caused orthopaedic surgeons to become increasingly interested in factors influencing patient satisfaction, which would allow them to potentially modify these factors in an effort to increase postoperative satisfaction. The objective of this study was to identify factors associated with patient satisfaction two weeks following extremity orthopaedic surgery.

Methods: Patients completed questionnaires preoperatively to assess demographics, activity, pain, expectations, and Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing for Physical Function, Pain Interference, Social Satisfaction, Depression, Anxiety, and Fatigue. Two weeks after their operation, patients completed the same questionnaires in addition to an Improvement Survey and Met Expectations. Satisfaction was assessed with the Surgical Satisfaction Questionnaire.

Results: Greater surgical satisfaction two weeks following orthopaedic surgery was associated with higher education, alcohol use, better scores on all PROMIS domains at baseline and two weeks, greater activity levels at baseline and two weeks, less bodily pain at baseline and two weeks, less pain in the surgical site at two weeks, greater met expectations, and greater improvement (p < 0.05).

Conclusion: This study provides important information about patient satisfaction two weeks after orthopaedic surgery.
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http://dx.doi.org/10.1016/j.jcot.2020.06.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503134PMC
October 2020

Conditional reflex to urine culture: Evaluation of a diagnostic stewardship intervention within the Veterans' Affairs and Centers for Disease Control and Prevention Practice-Based Research Network.

Infect Control Hosp Epidemiol 2021 Feb 25;42(2):176-181. Epub 2020 Aug 25.

Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, Maryland.

Objective: In the absence of pyuria, positive urine cultures are unlikely to represent infection. Conditional urine reflex culture policies have the potential to limit unnecessary urine culturing. We evaluated the impact of this diagnostic stewardship intervention.

Design: We conducted a retrospective, quasi-experimental (nonrandomized) study, with interrupted time series, from August 2013 to January 2018 to examine rates of urine cultures before versus after the policy intervention. We compared 3 intervention sites to 3 control sites in an aggregated series using segmented negative binomial regression.

Setting: The study included 6 acute-care hospitals within the Veterans' Health Administration across the United States.

Participants: Adult patients with at least 1 urinalysis ordered during acute-care admission, excluding pregnant patients or those undergoing urological procedures, were included.

Methods: At the intervention sites, urine cultures were performed if a preceding urinalysis met prespecified criteria. No such restrictions occurred at the control sites. The primary outcome was the rate of urine cultures performed per 1,000 patient days. The safety outcome was the rate of gram-negative bloodstream infection per 1,000 patient days.

Results: The study included 224,573 urine cultures from 50,901 admissions in 24,759 unique patients. Among the intervention sites, the overall average number of urine cultures performed did not significantly decrease relative to the preintervention period (5.9% decrease; P = 0.8) but did decrease by 21% relative to control sites (P < .01). We detected no significant difference in the rates of gram-negative bloodstream infection among intervention or control sites (P = .49).

Conclusions: Conditional urine reflex culture policies were associated with a decrease in urine culturing without a change in the incidence of gram-negative bloodstream infection.
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http://dx.doi.org/10.1017/ice.2020.400DOI Listing
February 2021

In Reply to 'No Obvious Impact of NSAIDs on Risk of Kidney Failure: Causal or Another Selection Bias'.

Am J Kidney Dis 2020 11 31;76(5):742-743. Epub 2020 Jul 31.

University of Maryland School of Medicine, Baltimore, MD.

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http://dx.doi.org/10.1053/j.ajkd.2020.06.010DOI Listing
November 2020

Effect of urine reflex culturing on rates of cultures and infections in acute and long-term care.

Antimicrob Resist Infect Control 2020 06 29;9(1):96. Epub 2020 Jun 29.

Department of Infection Control, VA Maryland Health Care System, Baltimore, MD, USA.

Background: Urine cultures are often positive in the absence of a urinary tract infection (UTI). Pyuria is generally considered necessary to diagnose a UTI.

Problem: Urine cultures are often positive in the absence of UTI leading to unnecessary antibiotics.

Methods: Quasi-experimental pre-post study of all patient urine cultures ordered in a VA acute care hospital, emergency department (ED), and two long-term care (LTC) facilities from August 2016 to August 2018. Urine cultures performed per 100 days were compared pre- (August 2016 to July 2017) versus post-intervention (August 2017 to August 2018) using interrupted time series negative binomial regression.

Intervention: We examined whether reflexing to urine culture only if a urinalysis (UA) found greater than 10 WBC/hpf decreased urine culturing.

Results: In acute-care, reflex culturing resulted in a 39% time series regression analysis adjusted decrease in the rate of cultures performed (pre-intervention, 3.6 cultures/100 days vs. Post-intervention, 1.8 cultures/100 days, p < 0.001). Pre-intervention, 29% (4/14) of Catheter-associated UTI (CAUTI) would not have been reported if reflex culturing was employed. In the ED, reflex culturing was associated with a 38% (p = 0.0015) regression analysis adjusted decrease in cultures, from 5.4/100 visits to 3.3/100 visits. In LTC, there was a small absolute, but regression analysis adjusted increase of 89% (p = 0.0018) in rates from (0.4/100 days to 0.5/100 days).

Conclusion: In acute care and ED, urine reflex culturing decreased the number of urine cultures performed. A small absolute increase was seen between pre-post time periods in LTC. Reflex testing generally decreases cultures and may lead to more accurate diagnoses of CAUTI.
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http://dx.doi.org/10.1186/s13756-020-00762-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325138PMC
June 2020

Brain-Selective Estrogen Therapy Prevents Androgen Deprivation-Associated Hot Flushes in a Rat Model.

Pharmaceuticals (Basel) 2020 Jun 10;13(6). Epub 2020 Jun 10.

Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.

Hot flushes are best-known for affecting menopausal women, but men who undergo life-saving castration due to androgen-sensitive prostate cancer also suffer from these vasomotor symptoms. Estrogen deficiency in these patients is a direct consequence of androgen deprivation, because estrogens (notably 17β-estradiol, E) are produced from testosterone. Although estrogens alleviate hot flushes in these patients, they also cause adverse systemic side effects. Because only estrogens can provide mitigation of hot flushes on the basis of current clinical practices, there is an unmet need for an effective and safe pharmacotherapeutic intervention that would also greatly enhance patient adherence. To this end, we evaluated treatment of orchidectomized (ORDX) rats with 10β, 17β-dihydroxyestra-1,4-dien-3-one (DHED), a brain-selective bioprecursor prodrug of E. A pilot pharmacokinetic study using oral administration of DHED to these animals revealed the formation of E in the brain without the appearance of the hormone in the circulation. Therefore, DHED treatment alleviated androgen deprivation-associated hot flushes without peripheral impact in the ORDX rat model. Concomitantly, we showed that DHED-derived E induced progesterone receptor gene expression in the hypothalamus without stimulating galanin expression in the anterior pituitary, further indicating the lack of systemic estrogen exposure upon oral treatment with DHED.
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http://dx.doi.org/10.3390/ph13060119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344942PMC
June 2020

Association of glucose variability at the last day of hospitalization with 30-day readmission in adults with diabetes.

BMJ Open Diabetes Res Care 2020 05;8(1)

Division of Endocrinology, Metabolism, and Lipids, Emory University School of Medicine, Atlanta, Georgia, USA.

Objective: To evaluate whether increased glucose variability (GV) during the last day of inpatient stay is associated with increased risk of 30-day readmission in patients with diabetes.

Research Design And Methods: A comprehensive list of clinical, pharmacy and utilization files were obtained from the Veterans Affairs (VA) Central Data Warehouse to create a nationwide cohort including 1 042 150 admissions of patients with diabetes over a 14-year study observation period. Point-of-care glucose values during the last 24 hours of hospitalization were extracted to calculate GV (measured as SD and coefficient of variation (CV)). Admissions were divided into 10 categories defined by progressively increasing SD and CV. The primary outcome was 30-day readmission rate, adjusted for multiple covariates including demographics, comorbidities and hypoglycemia.

Results: As GV increased, there was an overall increase in the 30-day readmission rate ratio. In the fully adjusted model, admissions with CV in the 5th-10th CV categories and admissions with SD in the 4th-10th categories had a statistically significant progressive increase in 30-day readmission rates, compared with admissions in the 1st (lowest) CV and SD categories. Admissions with the greatest CV and SD values (10th category) had the highest risk for readmission (rate ratio (RR): 1.08 (95% CI 1.05 to 1.10), p<0.0001 and RR: 1.11 (95% CI 1.09 to 1.14), p<0.0001 for CV and SD, respectively).

Conclusions: Patients with diabetes who exhibited higher degrees of GV on the final day of hospitalization had higher rates of 30-day readmission.

Trial Registration Number: NCT03508934, NCT03877068.
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http://dx.doi.org/10.1136/bmjdrc-2019-000990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222883PMC
May 2020

Association of Opioids and Nonsteroidal Anti-inflammatory Drugs With Outcomes in CKD: Findings From the CRIC (Chronic Renal Insufficiency Cohort) Study.

Am J Kidney Dis 2020 08 18;76(2):184-193. Epub 2020 Apr 18.

Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD. Electronic address:

Rationale & Objective: Safe analgesic choices are limited in chronic kidney disease (CKD). We conducted a comparative analysis of harm from opioids versus nonsteroidal anti-inflammatory drugs (NSAIDs) in CKD.

Study Design: Prospective cohort study.

Setting & Participants: 3,939 patients with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study.

Exposures: 30-day analgesic use reported at annual visits.

Outcomes: A composite outcome of 50% glomerular filtration rate reduction and kidney failure requiring kidney replacement therapy (KRT), as well as the outcomes of kidney failure requiring KRT, hospitalization, and pre-kidney failure death.

Analytical Approach: Marginal structural models with time-updated exposures.

Results: Participants were followed up for a median of 6.84 years, with 391 (9.9%) and 612 (15.5%) reporting baseline opioid and NSAID use, respectively. Time-updated opioid use was associated with the kidney disease composite outcome, kidney failure with KRT, death (HRs of 1.4 [95% CI, 1.2-1.7], 1.4 [95% CI, 1.1-1.7], and 1.5 [95% CI, 1.2-2.0], respectively), and hospitalization (rate ratio [RR], 1.7; 95% CI, 1.6-1.9) versus opioid nonusers. Similar results were found in an analysis restricted to a subcohort of participants reporting ever using other (nonopioid and non-NSAID) analgesics or tramadol. Time-updated NSAID use was associated with increased risk for the kidney disease composite (HR, 1.2; 95% CI, 1.0-1.5) and hospitalization (RR, 1.1; 95% CI, 1.0-1.3); however, these associations were not significant in the subcohort. The association of NSAID use with the kidney disease composite outcome varied by race, with a significant risk in blacks (HR, 1.3; 95% CI, 1.0-1.7). NSAID use was associated with lower risk for kidney failure with KRT in women and individuals with glomerular filtration rate<45mL/min/1.73m (HRs of 0.63 [95% CI, 0.45-0.88] and 0.77 [95% CI, 0.59-0.99], respectively).

Limitations: Limited periods of recall of analgesic use and potential confounding by indication.

Conclusions: Opioid use had a stronger association with adverse events than NSAIDs, with the latter's association with kidney disease outcomes limited to specific subgroups, notably those of black race.
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http://dx.doi.org/10.1053/j.ajkd.2019.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387229PMC
August 2020

Methods for an Investigation of Neurophysiological and Kinematic Predictors of Response to Upper Extremity Repetitive Task Practice in Chronic Stroke.

Arch Rehabil Res Clin Transl 2019 Dec 10;1(3-4). Epub 2019 Sep 10.

VA Maryland Health Care System, Baltimore VA Medical Center, Baltimore, Maryland.

Objective: To demonstrate the feasibility of algorithmic prediction using a model of baseline arm movement, genetic factors, demographic characteristics, and multimodal assessment of the structure and function of motor pathways. To identify prognostic factors and the biological substrate for reductions in arm impairment in response to repetitive task practice.

Design: This prospective single-group interventional study seeks to predict response to a repetitive task practice program using an intent-to-treat paradigm. Response is measured as a change of ≥5 points on the Upper Extremity Fugl-Meyer from baseline to final evaluation (at the end of training).

Setting: General community.

Participants: Anticipated enrollment of community-dwelling adults with chronic stroke (N = 96; onset≥6mo) and moderate to severe residual hemiparesis of the upper limb as defined by a score of 10-45 points on the Upper Extremity Fugl-Meyer.

Intervention: The intervention is a form of repetitive task practice using a combination of robot-assisted therapy coupled with functional arm use in real-world tasks administered over 12 weeks.

Main Outcome Measures: Upper Extremity Fugl-Meyer Assessment (primary outcome), Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, magnetic resonance imaging, transcranial magnetic stimulation, arm kinematics, accelerometry, and a saliva sample for genetic testing.

Results: Methods for this trial are outlined, and an illustration of interindividual variability is provided by example of 2 participants who present similarly at baseline but achieve markedly different outcomes.

Conclusion: This article presents the design, methodology, and rationale of an ongoing study to develop a predictive model of response to a standardized therapy for stroke survivors with chronic hemiparesis. Applying concepts from precision medicine to neurorehabilitation is practicable and needed to establish realistic rehabilitation goals and to effectively allocate resources.
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http://dx.doi.org/10.1016/j.arrct.2019.100024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155389PMC
December 2019

MicroRNA-based biomarkers for diagnosis of non-small cell lung cancer (NSCLC).

Thorac Cancer 2020 03 28;11(3):762-768. Epub 2020 Jan 28.

Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Background: The development of biomarkers for the early detection of non-small cell lung cancer (NSCLC) is clinically important. We have developed miRNA biomarkers in sputum and plasma, respectively, for NSCLC. Herein, we evaluate whether integrated analysis of the miRNAs across the different types of specimens could improve the early detection of NSCLC.

Methods: Using reverse transcription PCR, we determined expressions of two miRNAs (miRs-31-5p and 210-3p) in sputum and three miRNAs (miRs-21-5p, 210-3p, and 486-5p) in plasma of a training cohort of 76 NSCLC patients and 72 cancer-free smokers. The results were validated in a testing cohort of 56 NSCLC patients and 55 cancer-free smokers.

Results: The panels of two sputum miRNAs and three plasma miRNAs had 65.8-75.0% sensitivities and 83.3-87.5% specificities for diagnosis of NSCLC in the training cohort. The individual sputum or plasma miRNA panel had a higher sensitivity for squamous cell carcinoma or adenocarcinoma of the lung, respectively. From the miRNAs, we optimized an integrated panel of biomarkers consisting of two sputum miRNAs (miRs-31-5p and 210-3p) and one plasma miRNA (miR-21-5p) that had higher sensitivity (85.5%) and specificity (91.7%) for diagnosis of NSCLC compared with the individual panels alone. Furthermore, the performance of the integrated panel of biomarkers was independent of histology and stage of NSCLC, and patients' age, sex, and ethnicity. The performance of the integrated panel of biomarkers was confirmed in the testing cohort.

Conclusions: Integrating biomarkers across different body fluids would synergistically improve the early detection of NSCLC.

Key Points: Lung cancer is a heterogeneous disease and develops from complex aberrations. Integrating sputum and plasma miRNAs has higher accuracy than when they are used alone.
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http://dx.doi.org/10.1111/1759-7714.13337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049510PMC
March 2020

Factors associated with early postoperative survey completion in orthopaedic surgery patients.

J Clin Orthop Trauma 2020 Feb 19;11(Suppl 1):S158-S163. Epub 2019 Jul 19.

Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA.

Purpose: To determine factors associated with survey compliance 2-weeks postoperatively.

Methods: 1269 patients age 17-years and older participating in the Maryland Orthopaedic Registry from August 2015-March 2018 were administered a baseline questionnaire preoperatively and emailed a follow-up questionnaire 10-days postoperatively. Demographics were self-reported and medical records reviewed for relevant medical history.

Results: 609 patients (48.0%) completed both the baseline and 2-week surveys. A decreased likelihood of 2-week survey completion was seen in patients who identified as black, smokers, patients without a college education, patients who were unmarried, unemployed, had a lower income, or covered by government-sponsored insurance (p < 0.05). Other preoperative variables significantly associated with decreased likelihood of completion included surgery on the right side, upper extremity surgery, preoperative opioid use, no specific injury leading to surgery, lower preoperative expectations, depression and fatigue symptoms, and worse pain, function, and activity scores (p < 0.05). Multivariable analysis confirmed race, operative extremity, education, insurance status, smoking, activity level, and pain scores were independent predictors of survey completion.

Conclusion: Several demographic and preoperative variables are associated with survey completion 2-weeks post-orthopaedic surgery. The results provide insight into patient populations that may be targeted in order to assure higher survey compliance and improve analysis of patient-reported outcomes.
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http://dx.doi.org/10.1016/j.jcot.2019.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978185PMC
February 2020

Alcohol consumption and serum metabolite concentrations in young women.

Cancer Causes Control 2020 Feb 11;31(2):113-126. Epub 2019 Dec 11.

Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.

Purpose: Alcohol consumption is an established breast cancer risk factor, though further research is needed to advance our understanding of the mechanism underlying the association. We used global metabolomics profiling to identify serum metabolites and metabolic pathways that could potentially mediate the alcohol-breast cancer association.

Methods: A cross-sectional analysis of reported alcohol consumption and serum metabolite concentrations was conducted among 211 healthy women 25-29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-Up Study (DISC06). Alcohol-metabolite associations were evaluated using multivariable linear mixed-effects regression.

Results: Alcohol was significantly (FDR p < 0.05) associated with several serum metabolites after adjustment for diet composition and other potential confounders. The amino acid sarcosine, the omega-3 fatty acid eicosapentaenoate, and the steroid 4-androsten-3beta,17beta-diol monosulfate were positively associated with alcohol intake, while the gamma-tocopherol metabolite gamma-carboxyethyl hydroxychroman (CEHC) was inversely associated. Positive associations of alcohol with 2-methylcitrate and 4-androsten-3beta,17beta-diol disulfate were borderline significant (FDR p < 0.10). Metabolite set enrichment analysis identified steroids and the glycine pathway as having more members associated with alcohol consumption than expected by chance.

Conclusions: Most of the metabolites associated with alcohol in the current analysis participate in pathways hypothesized to mediate the alcohol-breast cancer association including hormonal, one-carbon metabolism, and oxidative stress pathways, but they could also affect risk via alternative pathways. Independent replication of alcohol-metabolite associations and prospective evaluation of confirmed associations with breast cancer risk are needed.
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http://dx.doi.org/10.1007/s10552-019-01256-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008965PMC
February 2020

Diabetes, metformin and cancer risk in myotonic dystrophy type I.

Int J Cancer 2020 08 19;147(3):785-792. Epub 2019 Dec 19.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

Myotonic dystrophy type I (DM1) is an autosomal dominant multisystem disorder characterized by myotonia and muscle weakness. Type 2 diabetes (T2D) and cancer have been shown to be part of the DM1 phenotype. Metformin, a well-established agent for the management of T2D, is thought to have cancer-preventive effects in the general population. In our study, we aimed to assess the association between T2D, metformin use and the risk of cancer in DM1 patients. We identified a cohort of 913 DM1 patients and an age-, sex- and clinic-matched cohort of 12,318 DM1-free controls from the UK Clinical Practice Research Datalink, a large primary care records database. We used Cox regression models to assess cancer risk in T2D patients who were metformin users or nonusers compared to patients without T2D. Separate analyses were conducted for DM1 patients and controls. T2D was more prevalent in DM1 than in controls (8% vs. 3%, p < 0.0001). DM1 patients with T2D, compared to those without T2D, were more likely to develop cancer (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 1.18-10.97; p = 0.02), but not if they were treated with metformin (HR = 0.43, 95% CI = 0.06-3.35; p = 0.42). Among controls, we observed no significant associations between T2D and cancer risk in either users or nonusers of Metformin (HR = 1.28, 95% CI = 0.91-1.79; p = 0.16 and HR = 1.13, 95% CI = 0.72-1.79; p = 0.59, respectively). These results show an association between T2D and cancer risk in DM1 patients and may provide new insights into the possible benefits of Metformin use in DM1.
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http://dx.doi.org/10.1002/ijc.32801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336337PMC
August 2020

The Effectiveness of Contact Precautions on Methicillin-Resistant Staphylococcus aureus in Long-term Care Across the United States.

Clin Infect Dis 2020 10;71(7):1676-1683

Veterans Affairs Maryland Health Care System, Baltimore, Maryland, USA.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of health care-associated infections in long-term care facilities (LTCFs). The Centers for Disease Control and Prevention recommends contact precautions for the prevention of MRSA within acute care facilities, which are being used within the United States Department of Veterans Affairs (VA) for LTCFs in a modified fashion. The impact of contact precautions in long-term care is unknown.

Methods: To evaluate whether contact precautions decreased MRSA acquisition in LTCFs, compared to standard precautions, we performed a retrospective effectiveness study (pre-post, with concurrent controls) using data from the VA health-care system from 1 January 2011 until 31 December 2015, 2 years before and after a 2013 policy recommending a more aggressive form of contact precautions.

Results: Across 75 414 patient admissions from 74 long-term care facilities in the United States, the overall unadjusted rate of MRSA acquisition was 2.6/1000 patient days. Patients were no more likely to acquire MRSA if they were cared for using standard precautions versus contact precautions in a multivariable, discrete time survival analysis, controlling for patient demographics, risk factors, and year of admission (odds ratio, 0.97; 95% confidence interval, .85-1.12; P = .71).

Conclusions: MRSA acquisition and infections were not impacted by the use of active surveillance and contact precautions in LTCFs in the VA.
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http://dx.doi.org/10.1093/cid/ciz1045DOI Listing
October 2020

Sputum long non-coding RNA biomarkers for diagnosis of lung cancer.

Cancer Biomark 2019 ;26(2):219-227

Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Analysis of molecular changes in sputum may help diagnose lung cancer. Long non-coding RNAs (lncRNAs) play vital roles in various biological processes, and their dysregulations contribute to the development and progression of lung tumorigenesis. Herein, we determine whether aberrant lncRNAs could be used as potential sputum biomarkers for lung cancer.

Methods: Using reverse transcription PCR, we measure expressions of lung cancer-associated lncRNAs in sputum of a discovery cohort of 67 lung cancer patients and 65 cancer-free smokers with benign diseases and a validation cohort of 59 lung cancer patients and 60 cancer-free smokers with benign diseases.

Results: In the discovery cohort, four of the lncRNAs displayed a significantly different level in sputum of lung cancer patients vs.cancer-free smokers with benign diseases (all P< 0.001). From the four lncRNAs, three lncRNAs (SNHG1, H19, and HOTAIR) are identified as a biomarker panel, producing 82.09% sensitivity and 89.23% specificity for diagnosis of lung cancer. Furthermore, the biomarker panel has a higher sensitivity (82.09% vs. 52.24%, P= 0.02) and a similar specificity compared with sputum cytology (89.23% vs. 90.77%, P= 0.45). In addition, the lncRNA biomarker panel had a higher sensitivity (87.50% vs. 70.07%, p= 0.03) for diagnosis of squamous cell carcinoma compared with adenocarcinoma of the lung, while maintaining the same specificity (89.23%). The potential of the sputum lncRNA biomarkers for lung cancer detection is confirmed in the validation cohort.

Conclusion: We have for the first time shown that the analysis of lncRNAs in sputum might be a noninvasive approach for diagnosis of lung cancer.
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http://dx.doi.org/10.3233/CBM-190161DOI Listing
March 2020

Benign tumors in myotonic dystrophy type I target disease-related cancer sites.

Ann Clin Transl Neurol 2019 08 26;6(8):1510-1518. Epub 2019 Jul 26.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Objectives: Recent evidence showed that myotonic dystrophy type I (DM1) patients are at increased risk of certain cancers, but the risk of benign tumors is unknown. We compared the risk of benign tumors in DM1 patients with matched DM1-free individuals and assessed the association between benign tumors and subsequent cancers.

Methods: We identified 927 DM1 patients and 13,085 DM1-free individuals matched on gender, birth-year, clinic, and clinic-registration year from the UK Clinical Practice Research Datalink, a primary care records database. We used Cox regression models for statistical analyses.

Results: DM1 patients had elevated risks of thyroid nodules (Hazard Ratio [HR] = 10.4; 95% Confidence Interval [CI] = 3.91-27.52; P < 0.001), benign tumors of the brain or nervous system (HR = 8.4; 95% CI = 2.48-28.47; P < 0.001), colorectal polyps (HR = 4.3; 95% CI = 1.76-10.41; P = 0.001), and possibly uterine fibroids (HR = 2.7; 95% CI = 1.22-5.88; P = 0.01). Pilomatricomas and salivary gland adenomas occurred almost exclusively in DM1 patients (Fisher's exact P < 0.001). The HR for colorectal polyps was elevated in DM1 males but not in females (HR = 8.2 vs. 1.3, respectively; P-heterogeneity < 0.001), whereas endocrine and brain tumors occurred exclusively in females. The data suggested an association between benign tumors and subsequent cancer in classic DM1 patients (HR = 2.7; 95% CI = 0.93-7.59; P = 0.07).

Interpretation: Our study showed a similar site-specific benign tumor profile to that previously reported for DM1-associated cancers. The possible association between benign tumors and subsequent cancer in classic DM1 patients warrants further investigation as it may guide identifying patients at elevated risk of cancer. Our findings underscore the importance of following population-based screening recommendations in DM1 patients, for example, for colorectal cancer.
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http://dx.doi.org/10.1002/acn3.50856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689687PMC
August 2019
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