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1. The multidisciplinary management of bone and soft tissue sarcoma: an essential organizational framework

Author

Siegel GW, Biermann JS, Chugh R, Jacobson JA, Lucas D, Feng M, Chang AC, Smith SR, Wong SL, and Hasen J

Subjects
Medicine (General), R5-920
Abstract

Geoffrey W Siegel,1 J Sybil Biermann,1 Rashmi Chugh,2 Jon A Jacobson,3 David Lucas,4 Mary Feng,5 Andrew C Chang,6 Sean R Smith,7 Sandra Wong,6 Jill L Hasen1 1Department of Orthopedics, 2Department of Medical Oncology, 3Department of Radiology, 4Department of Pathology, 5Department of Radiation, 6Department of Surgery, 7Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA Abstract: The rarity of bone and soft tissue sarcoma, the difficulty in interpretation of imaging and histology, the plethora of treatment modalities, and the complexity and intensity of the treatment contribute to the need for systematic multidisciplinary team management of patients with these diseases. An integrated multidisciplinary clinic and team with a structured sarcoma tumor board facilitate team coordination and communication. This paper reviews the rationale for multidisciplinary management of sarcoma and details the operational structure of the Multidisciplinary Sarcoma Clinic and Sarcoma Tumor Board. The structured Multidisciplinary Sarcoma Tumor Board provides opportunity for improvement in logistics, teaching, quality, and enrollment in clinical trials. Keywords: sarcoma, sarcoma care, sarcoma tumor board, collaborative approach

Published
2015

3. Molecular dynamics and functional characterization of I37R-CFTR lasso mutation provide insights into channel gating activity

Author

Wong, SL, Awatade, NT, Astore, MA, Allan, KM, Carnell, MJ, Slapetova, I, Chen, PC, Capraro, A, Fawcett, LK, Whan, RM, Griffith, R, Ooi, CY, Kuyucak, S, Jaffe, A, Waters, SA, Wong, SL, Awatade, NT, Astore, MA, Allan, KM, Carnell, MJ, Slapetova, I, Chen, PC, Capraro, A, Fawcett, LK, Whan, RM, Griffith, R, Ooi, CY, Kuyucak, S, Jaffe, A, and Waters, SA

Abstract

Characterization of I37R, a mutation located in the lasso motif of the CFTR chloride channel, was conducted by theratyping several CFTR modulators from both potentiator and corrector classes. Intestinal current measurements in rectal biopsies, forskolin-induced swelling (FIS) in intestinal organoids, and short circuit current measurements in organoid-derived monolayers from an individual with I37R/F508del CFTR genotype demonstrated that the I37R-CFTR results in a residual function defect amenable to treatment with potentiators and type III, but not type I, correctors. Molecular dynamics of I37R using an extended model of the phosphorylated, ATP-bound human CFTR identified an altered lasso motif conformation which results in an unfavorable strengthening of the interactions between the lasso motif, the regulatory (R) domain, and the transmembrane domain 2 (TMD2). Structural and functional characterization of the I37R-CFTR mutation increases understanding of CFTR channel regulation and provides a potential pathway to expand drug access to CF patients with ultra-rare genotypes.

Published
2022

4. Air-Liquid-Interface Differentiated Human Nose Epithelium: A Robust Primary Tissue Culture Model of SARS-CoV-2 Infection

Author

Tran, BM, Grimley, SL, McAuley, JL, Hachani, A, Earnest, L, Wong, SL, Caly, L, Druce, J, Purcell, DFJ, Jackson, DC, Catton, M, Nowell, CJ, Leonie, L, Deliyannis, G, Waters, SA, Torresi, J, Vincan, E, Tran, BM, Grimley, SL, McAuley, JL, Hachani, A, Earnest, L, Wong, SL, Caly, L, Druce, J, Purcell, DFJ, Jackson, DC, Catton, M, Nowell, CJ, Leonie, L, Deliyannis, G, Waters, SA, Torresi, J, and Vincan, E

Abstract

The global urgency to uncover medical countermeasures to combat the COVID-19 pandemic caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has revealed an unmet need for robust tissue culture models that faithfully recapitulate key features of human tissues and disease. Infection of the nose is considered the dominant initial site for SARS-CoV-2 infection and models that replicate this entry portal offer the greatest potential for examining and demonstrating the effectiveness of countermeasures designed to prevent or manage this highly communicable disease. Here, we test an air-liquid-interface (ALI) differentiated human nasal epithelium (HNE) culture system as a model of authentic SARS-CoV-2 infection. Progenitor cells (basal cells) were isolated from nasal turbinate brushings, expanded under conditionally reprogrammed cell (CRC) culture conditions and differentiated at ALI. Differentiated cells were inoculated with different SARS-CoV-2 clinical isolates. Infectious virus release into apical washes was determined by TCID50, while infected cells were visualized by immunofluorescence and confocal microscopy. We demonstrate robust, reproducible SARS-CoV-2 infection of ALI-HNE established from different donors. Viral entry and release occurred from the apical surface, and infection was primarily observed in ciliated cells. In contrast to the ancestral clinical isolate, the Delta variant caused considerable cell damage. Successful establishment of ALI-HNE is donor dependent. ALI-HNE recapitulate key features of human SARS-CoV-2 infection of the nose and can serve as a pre-clinical model without the need for invasive collection of human respiratory tissue samples.

Published
2022

5. Comparative effectiveness of cladribine tablets versus other oral disease-modifying treatments for multiple sclerosis: Results from MSBase registry

Author

Spelman, T, Ozakbas, S, Alroughani, R, Terzi, M, Hodgkinson, S, Laureys, G, Kalincik, T, Van der Walt, A, Yamout, B, Lechner-Scott, J, Soysal, A, Kuhle, J, Sanchez-Menoyo, JL, Morgado, YB, La Spitaleri, D, van Pesch, V, Horakova, D, Ampapa, R, Patti, F, Macdonell, R, Al-Asmi, A, Gerlach, O, Oh, J, Altintas, A, Tundia, N, Wong, SL, Butzkueven, H, Spelman, T, Ozakbas, S, Alroughani, R, Terzi, M, Hodgkinson, S, Laureys, G, Kalincik, T, Van der Walt, A, Yamout, B, Lechner-Scott, J, Soysal, A, Kuhle, J, Sanchez-Menoyo, JL, Morgado, YB, La Spitaleri, D, van Pesch, V, Horakova, D, Ampapa, R, Patti, F, Macdonell, R, Al-Asmi, A, Gerlach, O, Oh, J, Altintas, A, Tundia, N, Wong, SL, and Butzkueven, H

Abstract

BACKGROUND: Effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience. OBJECTIVES: Use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs. METHODS: Retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR). RESULTS: Cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54-6.32), 7.04 (4.16-11.93), and 6.52 (3.79-11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts. CONCLUSION: Cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators.

Published
2022

6. School-based research agenda on healthcare simulation for nursing education in Hong Kong

Author

Wong, SL, Gill, BK, Chan, JHM, Cheung, APH, Charm, CYC, Fung, CKM, Lam, CY, Tong, MYT, Lo, CKY, Tsang, AYK, Nestel, D, Wong, SL, Gill, BK, Chan, JHM, Cheung, APH, Charm, CYC, Fung, CKM, Lam, CY, Tong, MYT, Lo, CKY, Tsang, AYK, and Nestel, D

Abstract

BACKGROUND: Healthcare simulation has been used as a pedagogical strategy in nursing education. Evidence has shown one of the positive impacts that simulations replace clinical placement. These wide-ranging initiatives are essential, and they can guide a nursing school's simulation training. However, researching each innovation in the nursing field is beyond the scope. METHODS: To focus our research and develop the capacity and capability to incorporate healthcare simulation in nursing education, we used a consensus building process to establish a school's research agenda. A modified Delphi process was adopted to reach a consensus among 10 nursing faculty members in one university with a visiting professor's support. RESULTS: The three themes were identified as (1) embedding simulation into the baccalaureate in nursing curriculum, (2) designing effective simulation-based education and (3) simulating education in the broader world (adolescents). These themes were further categorised into two areas that used simulation in the educational and community settings. Sixty per cent of the faculty members agreed that the question, 'How can simulation be incorporated into clinical placements to enhance students' learning?' should be the highest research priority. CONCLUSION: This study adds understanding to incorporate simulation-based education in the nursing curriculum and community provides insights into future research.

Published
2021

7. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update

Author

Key, N, Khorana, A, Kuderer, N, Bohlke, K, Lee, A, Arcelus, J, Wong, S, Balaban, E, Flowers, C, Francis, C, Gates, L, Kakkar, A, Levine, M, Liebman, H, Tempero, M, Lyman, G, Falanga, A, Key, NS, Khorana, AA, Kuderer, NM, Lee, AYY, Arcelus, JI, Wong, SL, Balaban, EP, Flowers, CR, Francis, CW, Gates, LE, Kakkar, AK, Levine, MN, Liebman, HA, Tempero, MA, Lyman, GH, Key, N, Khorana, A, Kuderer, N, Bohlke, K, Lee, A, Arcelus, J, Wong, S, Balaban, E, Flowers, C, Francis, C, Gates, L, Kakkar, A, Levine, M, Liebman, H, Tempero, M, Lyman, G, Falanga, A, Key, NS, Khorana, AA, Kuderer, NM, Lee, AYY, Arcelus, JI, Wong, SL, Balaban, EP, Flowers, CR, Francis, CW, Gates, LE, Kakkar, AK, Levine, MN, Liebman, HA, Tempero, MA, and Lyman, GH

Abstract

PURPOSE: To provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs published from August 1, 2014, through December 4, 2018. ASCO convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS: The systematic review included 35 publications on VTE prophylaxis and treatment and 18 publications on VTE risk assessment. Two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in patients with cancer reported that edoxaban and rivaroxaban are effective but are linked with a higher risk of bleeding compared with low-molecular-weight heparin (LMWH) in patients with GI and potentially genitourinary cancers. Two additional RCTs reported on DOACs for thromboprophylaxis in ambulatory patients with cancer at increased risk of VTE. RECOMMENDATIONS: Changes to previous recommendations: Clinicians may offer thromboprophylaxis with apixaban, rivaroxaban, or LMWH to selected high-risk outpatients with cancer; rivaroxaban and edoxaban have been added as options for VTE treatment; patients with brain metastases are now addressed in the VTE treatment section; and the recommendation regarding long-term postoperative LMWH has been expanded. Re-affirmed recommendations: Most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for all outpatients with cancer. Patients undergoing major cancer surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE.Additional information is available at www.asco.org/supportive-care-guidelines.

Published
2020

8. Proteomic Analysis of Extracellular HMGB1 Identifies Binding Partners and Exposes Its Potential Role in Airway Epithelial Cell Homeostasis

Author

Wong, SL, To, J, Santos, J, Allam, VSRR, Dalton, JP, Djordjevic, SP, Donnelly, S, Padula, MP, and Sukkar, MB

Subjects
Proteomics, Biochemistry & Molecular Biology, Humans, Homeostasis, chemical and pharmacologic phenomena, Epithelial Cells, Respiratory Mucosa, HMGB1 Protein, Protein Binding
Abstract

© 2017 American Chemical Society. The release of damage-associated molecular patterns (DAMPs) by airway epithelial cells is believed to play a crucial role in the initiation and development of chronic airway conditions such as asthma and chronic obstructive pulmonary disease (COPD). Intriguingly, the classic DAMP high-mobility group box-1 (HMGB1) is detected in the culture supernatant of airway epithelial cells under basal conditions, indicating a role for HMGB1 in the regulation of epithelial cellular and immune homeostasis. To gain contextual insight into the potential role of HMGB1 in airway epithelial cell homeostasis, we used the orthogonal and complementary methods of high-resolution clear native electrophoresis, immunoprecipitation, and pull-downs coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile HMGB1 and its binding partners in the culture supernatant of unstimulated airway epithelial cells. We found that HMGB1 presents exclusively as a protein complex under basal conditions. Moreover, protein network analysis performed on 185 binding proteins revealed 14 that directly associate with HMGB1: amyloid precursor protein, F-actin-capping protein subunit alpha-1 (CAPZA1), glyceraldehyde-3 phosphate dehydrogenase (GAPDH), ubiquitin, several members of the heat shock protein family (HSPA8, HSP90B1, HSP90AA1), XRCC5 and XRCC6, high mobility group A1 (HMGA1), histone 3 (H3F3B), the FACT (facilitates chromatin transcription) complex constituents SUPT1H and SSRP1, and heterogeneous ribonucleoprotein K (HNRNPK). These studies provide a new understanding of the extracellular functions of HMGB1 in cellular and immune homeostasis at the airway mucosal surface and could have implications for therapeutic targeting.

Published
2018

22. The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma

Author

BUSSE WW, PEDERSEN S, PAUWELS RA, TAN WC, CHEN YZ, LAMM CJ, Eckmayr J, Riedler J, Wurzinger G, Ott G, Zarkovic J, Schulheim A, Götz M, Schinko H, Thomüller I, de Backer W, van Bever H, Verleden G, de Boeck C, Aumann J, Vincken W, Dab I, de Vuyst P, de Jonghe M, Casimir G, Joos G, de Baets F, Bogaerts Y, Halloy JL, Bartsch P, Thiriaux J, Pohunek P, Rybníćek O, Skopková O, Pavelková L, Broź P, Ohnutková E, Novotná B, Baly J, Krćmová I, Kuralová Z, Koćí T, Honomichlová H, Kaśák V, Panzner P, Vondra V, Némećková J, Seberová E, Sykora T, Vít P, Turzíková J, Sörensen T, Neldam S, Peter J, Kludt J, Hansen UB, Knudsen T, Schultz PJ, Rost D, Jensen F, Kinnula V, Saarelainen P, Eho Remes M, Valovirta E, Venho KK, Kokko E, Järvinen M, Toljamo T, Taivainen A, Kava T, Herrala J, Kuusela AL, Nordgren P, Syvänen P, Godard P, Rufin P, Anton M, Aubert JP, Grosclaude M, Brambilla C, Archaud P, Racineux JL, Muir JF, Albertini M, Le Roux P, Simmons A, Bartuschka B, von Berg A, Bergmann V, Berns J, Bisping Arnold A, Blum HC, Garanin G, Brückner OJ, Burbach P, Sudhoff H, Feldmann M, Schmoller T, Wozny HW, Galaske R, Huptas M, Kaecke J, Köcher V, Laule Peschel M, Lohr E, Goldberg J, Drescher T, Reeh W, Rabe U, Rehn L, Scheffler NK, Steinmetz KO, Stutz PM, Weber HH, Uhde C, Ullner R, Vehar H, Krohn EU, Orosz M, Devai A, Uhereczky G, Rajkay K, Gönczi F, Györi E, Dobra G, Puha K, Sztancsik Z, Gömöri K, Dolinay T, Bittera I, Palinkasi S, Cseke Z, Bisits M, Bjämer D, Holme JI, Langhammer A, Hunstad K, Holmboe JH, Grangård E, Solberg DA, Grönneröd TA, Salkowitsch MB, Oymar K, Iversen K, Szczeklik A, Chyrek Borowska S, Mincewicz G, Malaczynska T, Latos T, Obtulowicz K, Emeryk A, Gorski P, Nowak D, Szmidt M, Alkiewicz J, Ziolo G, Spychalski L, Chmielewska Szewczyk D, Nowacka K, Pirozynski M, Prokurat H, Boznanski A, Malolepszy J, Rogala E, Kozielski J, Eriksson UL, Wahlestedt H, Selberg M, Larsson R, Rignér K, Alm B, Aronsson M, Winnergård I, Lagerwall M, Martinsons U, Berlin L, Rydberg B, Weston D, Johnson ME, Barrett C, Siafakas N, Mantzourani E, Orphanidou D, Trakopoulos G, Tzannes S, Kotsovoulou V, Dimadi M, Amfilochiou A, Priftis K, Papageorgiou Saxoni F, Christaki P, Tsanakas I, Paraskevi M, Bousmoukilia S, Spiropoulos K, Anthrakopoulos M, Roussos C, Bentur Alkouby L, Heimer D, Tal A, Horowitz I, Soferman R, Katz Y, Stav D, Weiler Z, Bibi H, Rottem M, Mandelberg A, Geller C, Roizin H, Weiler Ravell D, Kramer MR, Schwartz Y, Rossi A, Foresi A, Giuntini C, Bisetti A, Scoditti S, Tranfa C, Zacchello F, Giovannini M, Boner A, Fabbri LM, Girbino G, Barberio G, Cacciari E, Montefort S, Parascandalo R, Pato R, de Lourdes Chieira M, Moreira C, Chieira DS, Brito U, Borges FD, Marques AC, Figueiredo MM, Dias F, de Almeida AB, Cesar Ramos J, Valente MJ, Pereira JD, Nunes C, Riberio MF, Marques A, Carvalho MQ, de Azevedo MV, de Almeida AR, Pinto JA, Matos Mde F, Afonso A, Dos Santos JM, Fernandez CV, Agustin IC, Bejarano JM, Santos AA, Font ET, Huet EH, Lorente TL, Pujol MM, Munoz AP, Aineto PS, Forns SB, Areu JB, Casan P, Garcia JM, Rodriguez AV, Segura PA, Gil RS, Ciscar CP, Garcia JF, Jimenez TV, Gonzalez JI, Andres FQ, Bueno TA, Baticon CO, Miguel CR, Garcia FD, Hernando HV, Vina AL, Matia RA, Cumplido AS, Andueza MC, Cabra MS, Navarro PL, Rodriguez FA, Li JH, Landry D, O'Keefe D, Muram BF, Conter HS, Tweel D, Peters SD, Adelglass J, Baker JW, Berger WE, Bernstein DI, Blake KV, Amelong P, Casale TB, Charous BL, Chervinsky P, Condemi JJ, Cook D, Creticos PS, de Graff AC Jr, Smith T, Ellis MH, Grossman J, Halverson PC, Galant S, Hollingsworth H, Jackson C, Jacobs RL, Welch M, Kraemer MJ, Leflein J, Lemanske RF, Liebhaber MI, Lockey R, Kelly B, Mendelson L, Nayak A, Pearlman DS, Ruff M, Schwartz B, Scott MB, Shapiro GG, Silk HJ, Skoner DP, Stoloff S, Swamy KN, Atkins FM, Szefler SJ, Vandewalker M, Wald J, Weinstein SF, Wong DA, Wu F, Goldstein S, Murthy KC, Dolmann A, Gene R, Casas JC, Piovano C, Segal E, Balanzat AM, Taborda J, Truganti A, Teper A, Garrood J, Patel MJ, Hogan C, Russel G, Zhu YJ, Cao L, Liu SY, Miao JZ, Ding DJ, Yao WZ, Liu YN, Chen P, Kong SQ, Pang L, Sun B, Li ZM, Li GS, Chen PL, Zhu Q, Zhang TX, Wang XH, Wei S, Deng WW, Zhou X, Ji YY, Luo WT, Li Q, Zhu HR, Sheng JY, Ma JY, Zhang DP, Ji CZ, Xia XR, Zhang ZY, Yin KS, Yiang J, Li Y, Tang PW, Liu FG, Wang HP, Zhong NS, Rong ZS, Tang YC, Lin CY, Liu JS, Liu HZ, Cai DM, Yang JC, Ma QF, Mangunnegoro H, Wijono CA, Tobing NH, Rahajoe NN, Sugito, Surjanto E, Hisyam B, Alsagaff H, Santosa G, Kim YY, Park CS, Kim MK, Cho YJ, Choi DC, Jee YK, Mohan J, Yogeswery S, Wong SL, Kuan GL, Koh CT, Quah BS, de Bruyne J, Liam CK, Avila MM, Cuevas F, Chavaje N, Topete LA, Badillo I, Ponce M, Merida JC, Espinosa AG, Ledezma JM, García JA, Morales GG, Gomez JM, Martinez FJ, Ramos JE, Dorantes JR, Gonzalez CC, Vera JG, Bayardo RG, Melendez AP, Loyola CB, Suárez MA, de Guia T, Balgos A, Bautista N, Realiza T, Diaz D, Yu C, Mendoza Wi JA, Juaneza R, Bigornia R, Mansukhani P, Cacanindin DN, Wah LB, Hon YK, Yau OY, Moh CO, Tang WY, Dippenaar YD, Kirsten DL, Maraschin EF, Ossip MS, Visser SS, Mouton WL, Mercer M, Cassim KM, Macleod AH, Bateman ED, Leaver R, Morison A, Nel H, von Delft KH, Vermeulen JH, Weinberg EG, Lund RJ, Weber HC, Kuo SH, Kuo HP, Wang JL, Hsiue TR, Wang JH, Ching CD, Vangveeravong M, Pothiratana C, Trakultivakorn M, Kongpanichkul A, Thamanavat B, Fuangtong R, Suntornlohanakul S, Youngchaiyud P, Teeratakulpisarn J, Boonsawat W, Viriyachaiyo V, Direkwattanachai C, Visitsunthorn N., MIRAGLIA DEL GIUDICE, Michele, Busse, Ww, Pedersen, S, Pauwels, Ra, Tan, Wc, Chen, Yz, Lamm, Cj, Eckmayr, J, Riedler, J, Wurzinger, G, Ott, G, Zarkovic, J, Schulheim, A, Götz, M, Schinko, H, Thomüller, I, de Backer, W, van Bever, H, Verleden, G, de Boeck, C, Aumann, J, Vincken, W, Dab, I, de Vuyst, P, de Jonghe, M, Casimir, G, Joos, G, de Baets, F, Bogaerts, Y, Halloy, Jl, Bartsch, P, Thiriaux, J, Pohunek, P, Rybníćek, O, Skopková, O, Pavelková, L, Broź, P, Ohnutková, E, Novotná, B, Baly, J, Krćmová, I, Kuralová, Z, Koćí, T, Honomichlová, H, Kaśák, V, Panzner, P, Vondra, V, Némećková, J, Seberová, E, Sykora, T, Vít, P, Turzíková, J, Sörensen, T, Neldam, S, Peter, J, Kludt, J, Hansen, Ub, Knudsen, T, Schultz, Pj, Rost, D, Jensen, F, Kinnula, V, Saarelainen, P, Eho Remes, M, Valovirta, E, Venho, Kk, Kokko, E, Järvinen, M, Toljamo, T, Taivainen, A, Kava, T, Herrala, J, Kuusela, Al, Nordgren, P, Syvänen, P, Godard, P, Rufin, P, Anton, M, Aubert, Jp, Grosclaude, M, Brambilla, C, Archaud, P, Racineux, Jl, Muir, Jf, Albertini, M, Le Roux, P, Simmons, A, Bartuschka, B, von Berg, A, Bergmann, V, Berns, J, Bisping Arnold, A, Blum, Hc, Garanin, G, Brückner, Oj, Burbach, P, Sudhoff, H, Feldmann, M, Schmoller, T, Wozny, Hw, Galaske, R, Huptas, M, Kaecke, J, Köcher, V, Laule Peschel, M, Lohr, E, Goldberg, J, Drescher, T, Reeh, W, Rabe, U, Rehn, L, Scheffler, Nk, Steinmetz, Ko, Stutz, Pm, Weber, Hh, Uhde, C, Ullner, R, Vehar, H, Krohn, Eu, Orosz, M, Devai, A, Uhereczky, G, Rajkay, K, Gönczi, F, Györi, E, Dobra, G, Puha, K, Sztancsik, Z, Gömöri, K, Dolinay, T, Bittera, I, Palinkasi, S, Cseke, Z, Bisits, M, Bjämer, D, Holme, Ji, Langhammer, A, Hunstad, K, Holmboe, Jh, Grangård, E, Solberg, Da, Grönneröd, Ta, Salkowitsch, Mb, Oymar, K, Iversen, K, Szczeklik, A, Chyrek Borowska, S, Mincewicz, G, Malaczynska, T, Latos, T, Obtulowicz, K, Emeryk, A, Gorski, P, Nowak, D, Szmidt, M, Alkiewicz, J, Ziolo, G, Spychalski, L, Chmielewska Szewczyk, D, Nowacka, K, Pirozynski, M, Prokurat, H, Boznanski, A, Malolepszy, J, Rogala, E, Kozielski, J, Eriksson, Ul, Wahlestedt, H, Selberg, M, Larsson, R, Rignér, K, Alm, B, Aronsson, M, Winnergård, I, Lagerwall, M, Martinsons, U, Berlin, L, Rydberg, B, Weston, D, Johnson, Me, Barrett, C, Siafakas, N, Mantzourani, E, Orphanidou, D, Trakopoulos, G, Tzannes, S, Kotsovoulou, V, Dimadi, M, Amfilochiou, A, Priftis, K, Papageorgiou Saxoni, F, Christaki, P, Tsanakas, I, Paraskevi, M, Bousmoukilia, S, Spiropoulos, K, Anthrakopoulos, M, Roussos, C, Bentur Alkouby, L, Heimer, D, Tal, A, Horowitz, I, Soferman, R, Katz, Y, Stav, D, Weiler, Z, Bibi, H, Rottem, M, Mandelberg, A, Geller, C, Roizin, H, Weiler Ravell, D, Kramer, Mr, Schwartz, Y, Rossi, A, Foresi, A, Giuntini, C, Bisetti, A, Scoditti, S, Tranfa, C, Zacchello, F, Giovannini, M, Boner, A, MIRAGLIA DEL GIUDICE, Michele, Fabbri, Lm, Girbino, G, Barberio, G, Cacciari, E, Montefort, S, Parascandalo, R, Pato, R, de Lourdes Chieira, M, Moreira, C, Chieira, D, Brito, U, Borges, Fd, Marques, Ac, Figueiredo, Mm, Dias, F, de Almeida, Ab, Cesar Ramos, J, Valente, Mj, Pereira, Jd, Nunes, C, Riberio, Mf, Marques, A, Carvalho, Mq, de Azevedo, Mv, de Almeida, Ar, Pinto, Ja, Matos Mde, F, Afonso, A, Dos Santos, Jm, Fernandez, Cv, Agustin, Ic, Bejarano, Jm, Santos, Aa, Font, Et, Huet, Eh, Lorente, Tl, Pujol, Mm, Munoz, Ap, Aineto, P, Forns, Sb, Areu, Jb, Casan, P, Garcia, Jm, Rodriguez, Av, Segura, Pa, Gil, R, Ciscar, Cp, Garcia, Jf, Jimenez, Tv, Gonzalez, Ji, Andres, Fq, Bueno, Ta, Baticon, Co, Miguel, Cr, Garcia, Fd, Hernando, Hv, Vina, Al, Matia, Ra, Cumplido, A, Andueza, Mc, Cabra, M, Navarro, Pl, Rodriguez, Fa, Li, Jh, Landry, D, O'Keefe, D, Muram, Bf, Conter, H, Tweel, D, Peters, Sd, Adelglass, J, Baker, Jw, Berger, We, Bernstein, Di, Blake, Kv, Amelong, P, Casale, Tb, Charous, Bl, Chervinsky, P, Condemi, Jj, Cook, D, Creticos, P, de Graff AC, Jr, Smith, T, Ellis, Mh, Grossman, J, Halverson, Pc, Galant, S, Hollingsworth, H, Jackson, C, Jacobs, Rl, Welch, M, Kraemer, Mj, Leflein, J, Lemanske, Rf, Liebhaber, Mi, Lockey, R, Kelly, B, Mendelson, L, Nayak, A, Pearlman, D, Ruff, M, Schwartz, B, Scott, Mb, Shapiro, Gg, Silk, Hj, Skoner, Dp, Stoloff, S, Swamy, Kn, Atkins, Fm, Szefler, Sj, Vandewalker, M, Wald, J, Weinstein, Sf, Wong, Da, Wu, F, Goldstein, S, Murthy, Kc, Dolmann, A, Gene, R, Casas, Jc, Piovano, C, Segal, E, Balanzat, Am, Taborda, J, Truganti, A, Teper, A, Garrood, J, Patel, Mj, Hogan, C, Russel, G, Zhu, Yj, Cao, L, Liu, Sy, Miao, Jz, Ding, Dj, Yao, Wz, Liu, Yn, Chen, P, Kong, Sq, Pang, L, Sun, B, Li, Zm, Li, G, Chen, Pl, Zhu, Q, Zhang, Tx, Wang, Xh, Wei, S, Deng, Ww, Zhou, X, Ji, Yy, Luo, Wt, Li, Q, Zhu, Hr, Sheng, Jy, Ma, Jy, Zhang, Dp, Ji, Cz, Xia, Xr, Zhang, Zy, Yin, K, Yiang, J, Li, Y, Tang, Pw, Liu, Fg, Wang, Hp, Zhong, N, Rong, Z, Tang, Yc, Lin, Cy, Liu, J, Liu, Hz, Cai, Dm, Yang, Jc, Ma, Qf, Mangunnegoro, H, Wijono, Ca, Tobing, Nh, Rahajoe, Nn, Sugito, Surjanto, E, Hisyam, B, Alsagaff, H, Santosa, G, Kim, Yy, Park, C, Kim, Mk, Cho, Yj, Choi, Dc, Jee, Yk, Mohan, J, Yogeswery, S, Wong, Sl, Kuan, Gl, Koh, Ct, Quah, B, de Bruyne, J, Liam, Ck, Avila, Mm, Cuevas, F, Chavaje, N, Topete, La, Badillo, I, Ponce, M, Merida, Jc, Espinosa, Ag, Ledezma, Jm, García, Ja, Morales, Gg, Gomez, Jm, Martinez, Fj, Ramos, Je, Dorantes, Jr, Gonzalez, Cc, Vera, Jg, Bayardo, Rg, Melendez, Ap, Loyola, Cb, Suárez, Ma, de Guia, T, Balgos, A, Bautista, N, Realiza, T, Diaz, D, Yu, C, Mendoza Wi, Ja, Juaneza, R, Bigornia, R, Mansukhani, P, Cacanindin, Dn, Wah, Lb, Hon, Yk, Yau, Oy, Moh, Co, Tang, Wy, Dippenaar, Yd, Kirsten, Dl, Maraschin, Ef, Ossip, M, Visser, S, Mouton, Wl, Mercer, M, Cassim, Km, Macleod, Ah, Bateman, Ed, Leaver, R, Morison, A, Nel, H, von Delft, Kh, Vermeulen, Jh, Weinberg, Eg, Lund, Rj, Weber, Hc, Kuo, Sh, Kuo, Hp, Wang, Jl, Hsiue, Tr, Wang, Jh, Ching, Cd, Vangveeravong, M, Pothiratana, C, Trakultivakorn, M, Kongpanichkul, A, Thamanavat, B, Fuangtong, R, Suntornlohanakul, S, Youngchaiyud, P, Teeratakulpisarn, J, Boonsawat, W, Viriyachaiyo, V, Direkwattanachai, C, and Visitsunthorn, N.

Published
2008

23. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014

Author

Lyman, G, Bohlke, K, Khorana, A, Kuderer, N, Lee, A, Arcelus, J, Balaban, E, Clarke, J, Flowers, C, Francis, C, Gates, L, Kakkar, A, Key, N, Levine, M, Liebman, H, Tempero, M, Wong, S, Somerfield, M, Falanga, A, Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Somerfield MR, Falanga A, Lyman, G, Bohlke, K, Khorana, A, Kuderer, N, Lee, A, Arcelus, J, Balaban, E, Clarke, J, Flowers, C, Francis, C, Gates, L, Kakkar, A, Key, N, Levine, M, Liebman, H, Tempero, M, Wong, S, Somerfield, M, Falanga, A, Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Somerfield MR, and Falanga A

Abstract

Purpose: To provide current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. Methods: PubMed and the Cochrane Library were searched for randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guidelines from November 2012 through July 2014. An update committee reviewed the identified abstracts. Results: Of the 53 publications identified and reviewed, none prompted a change in the 2013 recommendations. Recommendations: Most hospitalized patients with active cancer require thromboprophylaxis throughout hospitalization. Routine thromboprophylaxis is not recommended for patients with cancer in the outpatient setting. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low-molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those undergoing major abdominal or pelvic surgery with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term secondary prophylaxis (at least 6 months). Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE because of limited data in patients with cancer. Anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should educate patients about the signs and symptoms of VTE.

Published
2015

25. Predictors of indoor BTEX concentrations in Canadian residences

Author

Amanda Wheeler, Wong, Sl, Khoury, C., and Zhu, J.

Subjects
xylenes, benzene, volatile organic compounds, toluene, indoor air quality
Abstract

Background Benzene, toluene, ethylbenzene and m-, p-xylenesand o-xylene (BTEX) are a group of volatile organic compounds that originate from similar sources. Given the potentially negative health implications of BTEX exposure and their prevalence in residential indoor air, it is important to understand typical residential concentrations and identify predictors. Data and methods The 2009 to 2011 Canadian Health Measures Survey included an indoor air component. Questionnaires were administered, and respondents were asked to deploy an air sampler in their home for 7 consecutive days. This analysis is based on BTEX data from 5,191 respondents. Mean BTEX concentrations were examined overall, and by dwelling type and garage configuration. Stepwise regression models were used to examine potential sources of BTEX components. Results Means were 1.95 µg/m3 (benzene), 19.17 µg/m3 (toluene), 4.09 µg/m3 (ethylbenzene), 14.42 µg/m3 (m-, p-xylenes), and 4.16 µg/m3 (o-xylene). Significant predictors of the presence of BTEX included a garage on the property, regular smoking in the home, renovations in the past month, number of occupants, use of paint remover, and use of fragrance. Interpretation Results of this nationally representative study found that BTEX concentrations are relatively low among Canadian residences, and identified several different indoor sources.

Published
2013

35. Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update

Author

Lyman, G, Khorana, A, Kuderer, N, Lee, A, Arcelus, J, Balaban, E, Clarke, J, Flowers, C, Francis, C, Gates, L, Kakkar, A, Key, N, Levine, M, Liebman, H, Tempero, M, Wong, S, Prestrud, A, Falanga, A, Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Prestrud AA, Falanga A, Lyman, G, Khorana, A, Kuderer, N, Lee, A, Arcelus, J, Balaban, E, Clarke, J, Flowers, C, Francis, C, Gates, L, Kakkar, A, Key, N, Levine, M, Liebman, H, Tempero, M, Wong, S, Prestrud, A, Falanga, A, Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Prestrud AA, and Falanga A

Abstract

Purpose: To provide recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. Prophylaxis in the outpatient, inpatient, and perioperative settings was considered, as were treatment and use of anticoagulation as a cancer-directed therapy. Methods: A systematic review of the literature published from December 2007 to December 2012 was completed in MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed evidence to determine which recommendations required revision. Results: Forty-two publications met eligibility criteria, including 16 systematic reviews and 24 randomized controlled trials. Recommendations: Most hospitalized patients with cancer require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for outpatients with cancer. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low-molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major cancer surgery should receive prophylaxis, starting before surgery and continuing for at least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term (6 months) secondary prophylaxis. Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE. Anticoagulation should not be used for cancer treatment in the absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should provide patient education about the signs and symptoms of VTE

Published
2013

36. Chiari-1 Malformation and the Neck-Tongue Syndrome: Cause or Coincidence?

Author

Clifford-Jones Re, Paviour Dc, and Wong Sl

Subjects
Hypoglossal Nerve, Adolescent, Joint Dislocations, Lingual Nerve, Coincidence, Tongue, Humans, Medicine, Paresthesia, Glossopharyngeal Nerve, Neck Pain, business.industry, Nerve Compression Syndromes, Syndrome, General Medicine, Anatomy, Magnetic Resonance Imaging, Arnold-Chiari Malformation, medicine.anatomical_structure, Atlanto-Axial Joint, Head Movements, Female, Neurology (clinical), Spinal Nerve Roots, business
Published
2008

38. Application of Human Liver Microsomes in Metabolism-Based Drug-Drug Interactions: In Vitro-in Vivo Correlations and the Abbott Laboratories Experience

Author

Wong Sl and Rodrigues Ad

Subjects
Drug, biology, Drug development, Pharmacokinetics, In vivo, media_common.quotation_subject, biology.protein, Microsome, Cytochrome P450, Pharmacology, Monooxygenase, In vitro, media_common
Abstract

Publisher Summary It is now known that most of the drug-metabolizing enzyme (DME) systems present in the human liver, for example, cytochrome P450, CYP; UDP-glucuronosyltransferase, UDPGT; Nacetyltransferase, NAT; and NADPH-dependent flavin-containing monooxygenase, FMO are composed of two or more enzymes or “isforms” that can differentially interact with any number of drugs. A well-managed drug-drug interaction, as in the case of ketoconazole and cyclosporin, can potentially be of economic benefit to the patient. Likewise, a potent interaction with an enzyme such as CYP can lead to autoinhibition of metabolism and superior pharmacokinetics. In vitro drug-drug interaction screening is fast becoming a standardized part of the drug development process and, depending on the particular pharmaceutical company and/or NDE, can be performed prospectively, concurrently, or respectively. In most cases, in vitro studies focus on the human liver microsomal CYP “superfamily” of proteins, as our present understanding of this system exceeds that of other DME systems. As the procedures for phenotyping and/or genotyping of clinical subjects become more readily available, in vivo confirmation of the polymorphic oxidations will be greatly facilitated. There is no all-encompassing in vitro and/or in vivo animal model for predicting drug-drug interactions in humans. Because the liver is considered to be the major site of metabolism, most investigators now find themselves routinely performing in vitro human metabolism studies with various combinations of primary cultured hepatocytes, precision-cut liver slices, banks of liver microsomes, and/or cDNA-expressed enzymes.

Published
1997

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