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1. Estimated GFR and the Effect of Intensive Blood Pressure Lowering After Acute Intracerebral Hemorrhage

Author

Anderson, C.S., Chalmers, J., Arima, H., Davis, S., Heeley, E., Huang, Y., Lavados, P., Neal, B., Parsons, M.W., Lindley, R., Morgenstern, L., Robinson, T., Stapf, C., Tzourio, C., Wang, J.G., Chen, S., Chen, X.Y., Cui, L., Liu, Z., Lu, C., Wang, J., Wu, S., Xu, E., Yang, Q., Zhang, C., Zhang, J., Beer, R., Schmutzhard, E., Redondo, P., Kaste, M., Soinne, L., Tatlisumak, T., Wartenberg, K., Ricci, S., Klijn, K., Azevedo, E., Chamorro, A., Arnold, M., Fischer, U., Kaul, S., Pandian, J., Boyini, H., Singh, S., Rabinstein, A.A., Estol, C., Silva, G., Olavarria, V.V., Robinson, T.G., Simes, R.J., Bousser, M.-G., Hankey, G., Jamrozik, K., Johnston, S.C., Li, S., Bailey, K., Cheung, T., Delcourt, C., Chintapatla, S., Ducasse, E., Erho, T., Hata, J., Holder, B., Knight, E., Leroux, M., Sassé, T., Odgers, E., Walsh, R., Wolfowicz, Z., Chen, G., Fuentes, S., Peng, B., Schneble, H.-M., Wang, M.-X., Billot, L., Heritier, S., Li, Q., Woodward, M., Abimbola, S., Anderson, S., Chan, E., Cheng, G., Chmielnik, P., Leighton, S., Liu, J.-Y., Rasmussen, B., Saxena, A., Tripathy, S., Armenis, M., Baig, M.A., Naidu, B., Starzec, G., Steley, S., Moles, A., Ruiz, A., Zimmermann, M., Marinho, J., Alves, S., Angelim, R., Araujo, J., Kawakami, L., Bustos, C., Gonzalez, F., Munoz Venturelli, P., Chen, X., Jia, R., Li, N., Qu, S., Shu, Y., Song, A., Sun, J., Xiao, J., Zhao, Y., Huang, Q., Vicaut, E., Chamam, A., Viaud, M.-C., Dert, C., Fiedler, U., Jovis, V., Kabla, S., Marchand, S., Pena, A., Rochaud, V., Mallikarjuna, K., Hasan, N., Berge, E., Sandset, E.C., Forårsveen, A.S., Richardson, D., Kumar, T., Lewin, S., Poulter, N., Field, J., Anjum, A., Wilson, A., Perelmuter, H., Agarie, A.M., Barboza, A.G., Recchia, L.A., Miranda, I.F., Rauek, S.G., Duplessis, R.J., Dewey, H., Walker, L., Petrolo, S., Bladin, C., Sturm, J., Crimmins, D., Griffiths, D., Schutz, A., Zenteno, V., Miteff, F., Spratt, N., Kerr, E., Levi, C.R., Phan, T.G., Ma, H., Sanders, L., Moran, C., Wong, K., Read, S., Henderson, R., Wong, A., Hull, R., Skinner, G., Hand, P., Yan, B., Tu, H., Campbell, B., Blacker, D.J., Wijeratne, T., Pathirage, M., Jasinararchchi, M., Matkovic, Z., Celestino, S., Gruber, F., Vosko, M.R., Diabl, E., Rathmaier, S., Pfausler, B., Helbok, R., Fazekas, F., Fischer, R., Poltrum, B., Zechner, B., Trummer, U., Rutgers, M.P., Peeters, A., Dusart, A., Duray, M.-C., Parmentier, C., Ferrao-Santos, S., Brouns, R., De Raedt, S., De Smedt, A., VanHooff, R.-J., De Keyser, J., Martins, S.C.O., de Almeida, A.G., Broudani, R., Titton, N.F., de Freitas, G.R., Cardoso, F.M., Giesel, L.M., Lima, N.A., Jr, Ferraz de Almeida, A.C., Gomes, R.B., Borges dos Santos, T.S., Veloso Soares, E.M., Neto, O.L.A., Silva, G.S., Gomes, D.L., de Carvalho, F.A., Miranda, M., Marques, A., Zétola, V.F., de Matia, G., Lange, M.C., Montes, J., Reccius, A., Soto, A., Rivas, R., Klapp, C., Illanes, S., Aguilera, C., Castro, A., Figueroa, C., Benavides, J., Salamanca, P., Concha, M.C., Pajarito, J., Araya, P., Guerra, F., Li, Y., Liu, G., Wang, B., Chong, Y., He, M., Wang, L., Liu, J., Zhang, X., Lai, C., Jiang, H., Cui, S., Tao, Q., Zhang, Y., Yao, S., Xu, M., Xiao, H., Hu, J., Tang, J., Ji, H., Jiang, M., Yu, F., Yang, X., Guo, X., Wang, Y., Wu, L., Gao, Y., Sun, D., Huang, X., Liu, L., Li, P., Jiang, Y., Li, H., Lu, H., Zhou, J., Yuan, C., Qi, X., Qiu, F., Qian, H., Wang, W., Sun, W., Li, F., Liu, R., Peng, Q., Ren, Z., Fan, C., Wang, H., Wang, T., Shi, F., Duan, C., Chen, Z., Tan, X., Zhao, Z., Chen, J., Han, T., Zhang, L., Hu, Q., Hou, Q., Zhao, X., Zeng, G., Ma, L., Wang, F., Zeng, L., Guo, Z., Fu, Y., Song, Y., Tai, L., Liu, X., Su, X., Yang, Y., Dong, R., Xu, Y., Tian, S., Cheng, S., Su, L., Xie, X., Xu, T., Geng, D., Yan, X., Fan, H., Zhao, N., Wang, S., Yang, J., Yan, M., Li, L., Li, Z., Xu, X., Lian, Y., Sun, H., Liu, D., Wang, N., Tang, Q., Han, Z., Feng, L., Cui, Y., Tian, J., Chang, H., Sun, X., Liu, C., Wen, Z., Lin, Q., Sun, L., Hu, B., Zou, M., Bao, Q., Lin, X., Zhao, L., Tian, X., Wang, X., Li, X., Hao, L., Duan, Y., Wang, R., Wei, Z., Ren, S., Ren, H., Dong, Y., Cheng, Y., Liu, W., Han, J., Zhang, Z., Zhu, J., Qian, J., Sun, Y., Liu, K., Long, F., Peng, X., Zhang, Q., Yuan, Z., Wang, C., Huang, M., He, P., You, Y., Xia, J., Zhou, L., Hou, Y., Qi, Y., Mei, L., Lu, R., Ping, L., Zhou, S., Zhang, S., Zou, R., Guo, J., Li, M., Wei, W., Curtze, S., Saarela, M., Strbian, D., Scheperjans, F., De Broucker, T., Henry, C., Cumurciuc, R., Ibos-Augé, N., Zéghoudi, A.-C., Pico, F., Dereeper, O., Simian, M.-C., Boisselier, C., Mahfoud, A., Timsit, S., Merrien, F.M., Guillon, B., Sevin, M., Herisson, F., Magne, C., Ameri, A., Cret, C., Stefanizzi, S., Klapzcynski, F., Denier, C., Sarov-Riviere, M., Reiner, P., Mawet, J., Hervé, D., Buffon, F., Touzé, E., Domigo, V., Lamy, C., Calvet, D., Pasquini, M., Alamowitch, S., Favrole, P., Muresan, I.-P., Crozier, S., Rosso, C., Pires, C., Leger, A., Deltour, S., Cordonnier, C., Henon, H., Rossi, C., Zuber, M., Bruandet, M., Tamazyan, R., Join-Lambert, C., Juettler, E., Krause, T., Maul, S., Endres, M., Jungehulsing, G.J., Hennerici, M., Griebe, M., Sauer, T., Knoll, K., Huber, R., Knauer, K., Knauer, C., Raubold, S., Schneider, H., Hentschel, H., Lautenschläger, C., Schimmel, E., Dzialowski, I., Foerch, C., Lorenz, M., Singer, O., Meyer dos Santos, I.M.R., Hartmann, A., Hamann, A., Schacht, A., Schrader, B., Teíchmann, A., Wartenberg, K.E., Mueller, T.J., Jander, S., Gliem, M., Boettcher, C., Rosenkranz, M., Beck, C., Otto, D., Thomalla, G., Cheng, B., Wong, K.S., Leung, T.W., Soo, Y.O.Y., Prabhakar, S., Kesavarapu, S.R., Gajjela, P.K., Chenna, R.R., Ummer, K., Basheer, M., Andipet, A., Jagarlapudi, M.K.M., Mohammed, A.U.R., Pawar, V.G., Eranki, S.S.K., Singh, Y., Akhtar, N., Borah, N.C., Ghose, M., Choudhury, N., Ichaporia, N.R., Shendge, J., Khese, S., Pamidimukkala, V., Inbamuthaiah, P., Nuthakki, S.R., Tagallamudi, N.M.R., Gutti, A.K., Khurana, D., Kesavarapu, P., Jogi, V., Garg, A., Samanta, D., Sarma, G.R.K., Nadig, R., Mathew, T., Anandan, M.A., Caterbi, E., Zini, A., Cavazzuti, M., Casoni, F., Pentore, R., Falzone, F., Mazzoli, T., Greco, L.M., Menichetti, C., Coppola, F., Cenciarelli, S., Gallinella, E., Mattioni, A., Condurso, R., Sicilia, I., Zampolini, M., Corea, F., Barbi, M., Proietti, C., Toni, D., Pieroni, A., Anzini, A., Falcou, A., Demichele, M., Klijn, C.J.M., Tveiten, A., Thortveit, E.T., Pettersen, S., Holand, N., Hitland, B., Johnsen, S.H., Eltoft, A., Wasay, M., Kamal, A., Iqrar, A., Ali, L., Begum, D., Gama, G., Fonseca, L., Moreira, G., Veloso, L.M., Pinheiro, D., Paredes, L., Rozeira, C., Gregorio, T., Segura Martin, T., Ayo, O., Garcia-Garcia, J., Feria Vilar, I., Gómez Fernández, I., Amaro, S., Urra, X., Obach, V., Cervera, A., Silva, Y., Serena, J., Castellanos, M., Terceno, M., Van Eendenburg, C., Weck, A., Findling, O., Lüdi, R., Warburton, E.A., Day, D., Butler, N., Bumanlag, E., Caine, S., Steele, A., Osborn, M., Dodd, E., Murphy, P., Esisi, B., Brown, E., Hayman, R., Baliga, V.K.V., Minphone, M., Kennedy, J., Reckless, I., Pope, G., Teal, R., Michael, K., Manawadu, D., Kalra, L., Lewis, R., Mistry, B., Cattermole, E., Hassan, A., Mandizvidza, L., Bamford, J., Brooks, H., Bedford, C., Whiting, R., Baines, P., Hussain, M., Harvey, M., Fotherby, K., McBride, S., Bourke, P., Morgan, D., Jennings-Preece, K., Price, C., Huntley, S., Riddell, V.E., Storey, G., Lakey, R.L., Subramanian, G., Jenkinson, D., Kwan, J., David, O., Tiwari, D., James, M., Keenan, S., Eastwood, H., Shaw, L., Kaye, P., Button, D., Madigan, B., Williamson, D., Dixit, A., Davis, J., Hossain, M.O., Ford, G.A., Parry-Jones, A., O'Loughlin, V., Jarapa, R., Naing, Z., Lovelock, C., O'Reilly, J., Khan, U., Bhalla, A., Rudd, A., Birns, J., Werring, D.J., Law, R., Perry, R., Jones, I., Erande, R., Roffe, C., Natarajan, I., Ahmad, N., Finney, K., Lucas, J., Mistri, A., Eveson, D., Marsh, R., Haunton, V., Fugate, J.E., Lepore, S.W., Zheng, Danni, Sato, Shoichiro, Arima, Hisatomi, Heeley, Emma, Delcourt, Candice, Cao, Yongjun, Chalmers, John, and Anderson, Craig S.

Published
2016
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2. The Cost Implications in Ontario, Alberta, and British Columbia of Early Versus Delayed External Cephalic Version in the Early External Cephalic Version 2 (EECV2) Trial

Author

Hutton, E.K., Barrett, J., Carson, G.D., Delisle, M.F., Dunn, M., Edwards, S., Fernandez, A., Gafni, A., Hannah, M.E., Hewson, S., Natale, R., Ohlsson, A., Ross, S.J., Willan, A.R., Windrim, R., Pollard, J.K., Schweitzer, Sylvestre, G., Turtle, P., Bracken, M., Crowley, P., Donner, A., Duley, L., Ehrenkranz, R., Curioni, M., Abalos Gorostiaga, R., Becker, C., Elizabeth, P.A., Errandonea, L., Palermo, M., Ramos, C.A., Trabucco, M., Montes Varela, D., Bertin, M.S., Castaldi, J.L., Mohedano de Duhalde, M., Messina, A., Baumgartner, J., Kovacs, G., Malcolm, B., Neil, J.R., Mahomed, K., Green, A., Child, A., DeVries, B., Phipps, H., Welsh, A., Davis, G.K., Roberts, L., Watts, N.P., Cybulski, M., Gibson, D., Tucker, S., McCahon, I., Sheehan, P., Umstad, M., Milligan, J., Morris, J., Rickard, K., Gardener, G., Jenkins-Manning, S., Boniface, C., Edmondson, M., Watson, D., Ayub, A., Soanes, S., Jordan, A., Fanning, C., Parish, B., Watson, M.A., Reid, D., Scheufler, P., Malott, A.M., Reitsma, A., Haslauer, K.A., Lipp, M., Farquharson, D., Gray, K., Demianczuk, N., Penttinen, E., Herer, E., McLean, K., Aghajafari, F., Williams, S., Moravac, C., Yudin, M., Pollard, J., Miller, L., Anderson, R.B., Good, M., Walker, M.C., Kulkarni, R., Scarfone, R., Cameron, C., Peel, T., Carrillo, J., Cruces, A., Gonzalez, Y., Figueroa Poblete, J., Lama Hormazabal, L., Saez, J., Oyarzun, E., Rioseco, A., Illanes, S., Kottmann, C., Parra, M., Quezada, S., Quiroz, L., Hvidman, L., Mogensen, I.M., Mouritzen, A., Ostberg, B., Abdel-Samad, S.N.M., Al-Hussaini, T., El-Nashar, I., Kirss, F., Rull, K., Ustav, E., Vaas, P., Brink-Spalink, V., Weizsaecker, K., Major, T., Poka, R., Daly, S., Kaneti, H., Rosen, D., Schachter, B., Chayen, B., Harel, L., Hiaeb, Z., Malinger, G., Dukler, D., Lunenfeld, E., AlFaris, L., El-Zibdeh, M., Domzalska-Popadiuk, I., Kobiela, P., Pankrac, Z., Preis, J., Preis, K., Swiatkowska-Freund, M., Cravo, J., Theron, A.M., Theron, G.B., Cronje, H.S., du Plessis, J.M., Munoz, M., Khan, G., Khan, S., Goossens, S., Pieters, M., Roumen, F.J.M.E., ten Cate, F., Smits, F., Heres, M., Krabbendam, E., Airey, R., Farrar, D., Tuffnell, D.J., Heyes, V., Melvin, C., Schram, C., Galimberti, A., Stewart, P., Cresswell, J., McCormick, C., Andrews, J., Fleener, D., Coonrod, D., Jimenez, B.F., Brown, S., Gregg, A., Pitchford, C., Seubert, D., Ahmed, Rashid J., Gafni, Amiram, and Hutton, Eileen K.

Published
2016
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3. External validation of prognostic models to predict stillbirth using International Prediction of Pregnancy Complications (IPPIC) Network database: individual participant data meta-analysis

Author

Allotey, J., Whittle, R., Snell, K. I. E., Smuk, M., Townsend, R., von Dadelszen, P., Heazell, A. E. P., Magee, L., Smith, G. C. S., Sandall, J., Thilaganathan, B., Zamora, J., Riley, R. D., Khalil, A., Thangaratinam, S., Coomarasamy, A., Kwong, A., Savitri, A. I., Salvesen, K. A., Bhattacharya, S., Uiterwaal, C. S. P. M., Staff, A. C., Andersen, L. B., Olive, E. L., Redman, C., Sletner, L., Daskalakis, G., Macleod, M., Abdollahain, M., Ramirez, J. A., Masse, J., Audibert, F., Magnus, P. M., Jenum, A. K., Baschat, A., Ohkuchi, A., Mcauliffe, F. M., West, J., Askie, L. M., Mone, F., Farrar, D., Zimmerman, P. A., Smits, L. J. M., Riddell, C., Kingdom, J. C., van de Post, J., Illanes, S. E., Holzman, C., van Kuijk, S. M. J., Carbillon, L., Villa, P. M., Eskild, A., Chappell, L., Prefumo, F., Velauthar, L., Seed, P., van Oostwaard, M., Verlohren, S., Poston, L., Ferrazzi, E., Vinter, C. A., Nagata, C., Brown, M., Vollebregt, K. C., Takeda, S., Langenveld, J., Widmer, M., Saito, S., Haavaldsen, C., Carroli, G., Olsen, J., Wolf, H., Zavaleta, N., Eisensee, I., Vergani, P., Lumbiganon, P., Makrides, M., Facchinetti, F., Sequeira, E., Gibson, R., Ferrazzani, S., Frusca, T., Norman, J. E., Figueiro, E. A., Lapaire, O., Laivuori, H., Lykke, J. A., Conde-Agudelo, A., Galindo, A., Mbah, A., Betran, A. P., Herraiz, I., Trogstad, L., Smith, G. G. S., Steegers, E. A. P., Salim, R., Huang, T., Adank, A., Zhang, J., Meschino, W. S., Browne, J. L., Allen, R. E., Costa, F. D. S., Klipstein-Grobusch Browne, K., Crowther, C. A., Jorgensen, J. S., Forest, J. -C., Rumbold, A. R., Mol, B. W., Giguere, Y., Kenny, L. C., Ganzevoort, W., Odibo, A. O., Myers, J., Yeo, S. A., Goffinet, F., Mccowan, L., Pajkrt, E., Teede, H. J., Haddad, B. G., Dekker, G., Kleinrouweler, E. C., Lecarpentier, E., Roberts, C. T., Groen, H., Skrastad, R. B., Heinonen, S., Eero, K., Anggraini, D., Souka, A., Cecatti, J. G., Monterio, I., Pillalis, A., Souza, R., Hawkins, L. A., Gabbay-Benziv, R., Crovetto, F., Figuera, F., Jorgensen, L., Dodds, J., Patel, M., Aviram, A., Papageorghiou, A., Khan, K., Clinicum, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Allotey, J, Whittle, R, Snell, K, Smuk, M, Townsend, R, von Dadelszen, P, Heazell, A, Magee, L, Smith, G, Sandall, J, Thilaganathan, B, Zamora, J, Riley, R, Khalil, A, Thangaratinam, S, Coomarasamy, A, Kwong, A, Savitri, A, Salvesen, K, Bhattacharya, S, Uiterwaal, C, Staff, A, Andersen, L, Olive, E, Redman, C, Sletner, L, Daskalakis, G, Macleod, M, Abdollahain, M, Ramirez, J, Masse, J, Audibert, F, Magnus, P, Jenum, A, Baschat, A, Ohkuchi, A, Mcauliffe, F, West, J, Askie, L, Mone, F, Farrar, D, Zimmerman, P, Smits, L, Riddell, C, Kingdom, J, van de Post, J, Illanes, S, Holzman, C, van Kuijk, S, Carbillon, L, Villa, P, Eskild, A, Chappell, L, Prefumo, F, Velauthar, L, Seed, P, van Oostwaard, M, Verlohren, S, Poston, L, Ferrazzi, E, Vinter, C, Nagata, C, Brown, M, Vollebregt, K, Takeda, S, Langenveld, J, Widmer, M, Saito, S, Haavaldsen, C, Carroli, G, Olsen, J, Wolf, H, Zavaleta, N, Eisensee, I, Vergani, P, Lumbiganon, P, Makrides, M, Facchinetti, F, Sequeira, E, Gibson, R, Ferrazzani, S, Frusca, T, Norman, J, Figueiro, E, Lapaire, O, Laivuori, H, Lykke, J, Conde-Agudelo, A, Galindo, A, Mbah, A, Betran, A, Herraiz, I, Trogstad, L, Steegers, E, Salim, R, Huang, T, Adank, A, Zhang, J, Meschino, W, Browne, J, Allen, R, Costa, F, Klipstein-Grobusch Browne, K, Crowther, C, Jorgensen, J, Forest, J, Rumbold, A, Mol, B, Giguere, Y, Kenny, L, Ganzevoort, W, Odibo, A, Myers, J, Yeo, S, Goffinet, F, Mccowan, L, Pajkrt, E, Teede, H, Haddad, B, Dekker, G, Kleinrouweler, E, Lecarpentier, E, Roberts, C, Groen, H, Skrastad, R, Heinonen, S, Eero, K, Anggraini, D, Souka, A, Cecatti, J, Monterio, I, Pillalis, A, Souza, R, Hawkins, L, Gabbay-Benziv, R, Crovetto, F, Figuera, F, Jorgensen, L, Dodds, J, Patel, M, Aviram, A, Papageorghiou, A, Khan, K, Tampere University, Obstetrics and Gynaecology, APH - Quality of Care, Amsterdam Reproduction & Development (AR&D), APH - Personalized Medicine, APH - Digital Health, and Obstetrics and gynaecology

Subjects
Calibration (statistics), Perinatal Death, Overfitting, Cohort Studies, Fetal Development, 0302 clinical medicine, Discriminative model, 3123 Gynaecology and paediatrics, Models, Pregnancy, GROWTH RESTRICTION, Statistics, Medicine, Prenatal, 030212 general & internal medicine, Ultrasonography, RISK, 030219 obstetrics & reproductive medicine, PRETERM, Radiological and Ultrasound Technology, LOW-DOSE ASPIRIN, DIAGNOSIS TRIPOD, Obstetrics and Gynecology, General Medicine, Statistical, Stillbirth, Prognosis, Pregnancy Complication, external validation, individual participant data, intrauterine death, prediction model, stillbirth, Female, Humans, Infant, Newborn, Models, Statistical, Pregnancy Complications, Regression Analysis, Risk Assessment, Ultrasonography, Prenatal, 3. Good health, PREECLAMPSIA, Meta-analysis, Human, Cohort study, Prognosi, MEDLINE, Regression Analysi, WEEKS GESTATION, 03 medical and health sciences, VELOCIMETRY, Radiology, Nuclear Medicine and imaging, RECURRENCE, business.industry, Infant, Newborn, R1, HYPERTENSIVE DISORDERS, Reproductive Medicine, Sample size determination, Cohort Studie, RG, business, RA, Predictive modelling
Abstract

Objective Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. Conclusions The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. (c) 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Published
2022
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18. Etiopathogenesis, prediction, and prevention of preeclampsia.

Author

Correa, P. J., Palmeiro, Y., Soto, M. J., Ugarte, C., and Illanes, S. E.

Subjects
PREECLAMPSIA prevention, HYPERTENSIVE crisis, ETIOLOGY of diseases, PREVENTIVE medicine, SENSITIVITY analysis
Abstract

Hypertensive disorders are a major cause of maternal death. Preeclampsia (PE) affects about 5% of pregnancies and is associated to high cardiovascular death risk. Understanding of its origin and cause is difficult and many etiologies have been proposed. So far, little can be done for real prevention and the only treatment is pregnancy interruption, increasing the child’s risk for prematurity complications. Early markers of disease are a promising path for understanding the pathogenesis and developing new strategies for prediction and eventually disease prevention. [ABSTRACT FROM PUBLISHER]

Published
2016
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23. First-trimester uterine artery Doppler and adverse pregnancy outcome: a meta-analysis involving 55,974 women.

Author

Velauthar, L, Plana, M N, Kalidindi, M, Zamora, J, Thilaganathan, B, Illanes, S E, Khan, K S, Aquilina, J, and Thangaratinam, S

Abstract

Objectives: To determine the accuracy with which uterine artery Doppler in the first trimester of pregnancy predicts pre-eclampsia and fetal growth restriction, particularly early-onset disease. Methods: We searched MEDLINE (1951-2012), EMBASE (1980-2012) and the Cochrane Library (2012) for relevant citations without language restrictions. Two reviewers independently selected studies that evaluated the accuracy of first-trimester uterine artery Doppler to predict adverse pregnancy outcome and performed data extraction to construct 2 × 2 tables. We synthesized sensitivity and specificity for various Doppler indices using a bivariate random-effects model. Results: From 1866 citations, we identified 18 studies (55,974 women). The sensitivity and specificity of abnormal uterine artery flow velocity waveform (FVW) in the prediction of early-onset pre-eclampsia were 47.8% (95% CI: 39.0-56.8) and 92.1% (95% CI: 88.6-94.6), and in the prediction of early-onset fetal growth restriction were 39.2% (95% CI: 26.3-53.8) and 93.1% (95% CI: 90.6-95.0), respectively. The sensitivities for predicting any pre-eclampsia and fetal growth restriction were 26.4% (95% CI: 22.5-30.8) and 15.4% (95% CI: 12.4-18.9), respectively, and the specificities were 93.4% (95% CI: 90.4-95.5%) and 93.3% (95% CI: 90.9-95.1), respectively. The number needed to treat (NNT) with aspirin to prevent one case of early-onset pre-eclampsia fell from 1000 to 173 and from 2500 to 421 for background risks varying between 1% and 0.4%, respectively. Conclusions: First-trimester uterine artery Doppler is a useful tool for predicting early-onset pre-eclampsia, as well as other adverse pregnancy outcomes. Based on the NNT, abnormal uterine artery Doppler in low-risk women achieves a sufficiently high performance to justify aspirin prophylaxis in those who test positive. [ABSTRACT FROM AUTHOR]

Published
2014
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25. Prevention of Early-onset Neonatal Group B Streptococcal Disease.

Author

Soto Marió, M. J., Valenzuela, I., Vásquez, A. E., and Illanes, S. E.

Subjects
STREPTOCOCCUS agalactiae, OPPORTUNISTIC infections, GASTROINTESTINAL system, SEPTICEMIA in children, NEONATAL diseases, ANTIBIOTICS
Abstract

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is an opportunistic pathogen that colonizes the gastrointestinal and genitourinary tracts of up to 50% of healthy adults and newborns; it is responsible for significant morbidity and mortality. Early detection can be used to establish the use of antibiotic prophylaxis to significantly reduce neonatal sepsis. This article reviews methods of detection and prevention of GBS infection in the neonate. [ABSTRACT FROM AUTHOR]

Published
2013
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27. Early detection of cell-free fetal DNA in maternal plasma

Author

Illanes, S., Denbow, M., Kailasam, C., Finning, K., and Soothill, P.W.

Subjects
*DNA, *BLOOD plasma, *KARYOTYPES, *GESTATIONAL age
Abstract

Abstract: Objectives: We aimed to establish the earliest gestational age at which fetal DNA in maternal plasma could be detected and whether this was reliable at 12–13 weeks'' gestation. Study design: A prospective observational cohort study of 32 pregnancies either after IVF or before prenatal diagnosis by CVS. Maternal blood was taken and RT-PCR was carried out to detect the multi-copy Y chromosome associated DSY14 gene. The end point was gender as assessed at delivery or on karyotype. Results: Y signal was obtained as early as 14 days post conception (4 weeks'' gestation) and has a good prediction rate by 12 weeks'' gestation. Conclusion: Free fetal DNA allows very early prediction of fetal sex in some cases and could be useful for clinical use for X-linked conditions by the end of the first trimester. [Copyright &y& Elsevier]

Published
2007
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28. P12.08: Complete resolution of acute anemia and heart failure sith single IUT in parvovirus B19 hydropic fetus.

Author

Rojas, C., Díaz, P., Arriagada, F., Jaques, D., Guiloff, N., Yamamoto, M., and Illanes, S.

Subjects
PARVOVIRUS B19, HEART failure, HYDROPS fetalis, ANEMIA, FETUS, ERYTHROCYTES
Abstract

Parvovirus B19 is a well know cause of fetal hydrops. In a routine ultrasound assessment hydrops fetalis 21 weeks: severe skin edema, ascites, pericardial effusion, cardiomegaly and bivalvular regurgitation. All Parvovirus B19 hydrops may be offered in utero therapy. [Extracted from the article]

Published
2018
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29. EP12.02: Longitudinal twins' growth pattern in Clínica Davila, Chile.

Author

Aleuanlli, I., De la Rivera, M., Marfull, C., Scheppeler, M., Illanes, S., Figueroa, H., Nien, J., and Yamamoto, M.

Subjects
TWINS, FETAL development
Abstract

Birthweight of twins are lower than singletons. Triplets, monoamniotic twins, severe malformations, fetus with aneuploidies, TRAP and TTTS were excluded. Twins had lower weight than singletons and there was a significant reduction after 34 weeks of gestational age (z score -0.64, 95%CI -0.79 to -0.48, p<0.001. [Extracted from the article]

Published
2018
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33. P19.05: Longitudinal estimation of fetal growth by ultrasound: a new proposal for the assessment of intrauterine growth restriction.

Author

Nien, J., Illanes, S., Cabrera, C., Schepeler, M., Figueroa, H., Martinez, J., and Osorio, E.

Subjects
*FETAL development, *ULTRASONIC imaging, ABSTRACTS
Abstract

An abstract of the conference paper "Longitudinal estimation of fetal growth by ultrasound: a new proposal for the assessment of intrauterine growth restriction," by J. Nien and colleagues is presented.

Published
2009
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34. Simulated lunar microgravity transiently arrests growth and induces osteocyte-chondrocyte lineage differentiation in human Wharton's jelly stem cells.

Author

Subramanian A, Ip CHL, Qin W, Liu X, W D Carter S, Oguz G, Ramasamy A, E Illanes S, Biswas A, G Perron G, L Fee E, W L Li S, K Y Seah M, A Choolani M, and W Kemp M

Abstract

Human Wharton's jelly stem cells (hWJSCs) are multipotent stem cells that are extensively employed in biotechnology applications. However, the impact of simulated lunar microgravity (sμG) on the growth, differentiation, and viability of this cell population is incompletely characterized. We aimed to determine whether acute (72 h) exposure to sμG elicited changes in growth and lineage differentiation in hWJSCs and if putative changes were maintained once exposure to terrestrial gravity (1.0 G) was restored. hWJSCs were cultured under standard 1.0 G conditions prior to being passaged and cultured under sμG (0.16 G) using a random positioning machine. Relative to control, hWJSCs cultured under sμG exhibited marked reductions in growth but not viability. Cell population expression of characteristic stemness markers (CD 73, 90, 105) was significantly reduced under sμG conditions. hWJSCs had 308 significantly upregulated and 328 significantly downregulated genes when compared to 1.0 G culture conditions. Key markers of cell replication, including MKI67, were inhibited. Significant upregulation of osteocyte-chondrocyte lineage markers, including SERPINI1, MSX2, TFPI2, BMP6, COMP, TMEM119, LUM, HGF, CHI3L1 and SPP1, and downregulation of cell fate regulators, including DNMT1 and EZH2, were detected in sμG-exposed hWJSCs. When returned to 1.0 G for 3 days, sμG-exposed hWJSCs had accelerated growth, and expression of stemness markers increased, approaching normal (i.e. 95%) levels. Our data support earlier findings that acute sμG significantly reduces the cell division potential of hWJSCs and suggest that acute sμG-exposure induces reversible changes in cell growth accompanied by osteocyte-chondrocyte changes in lineage differentiation., (© 2024. The Author(s).)

Published
2024
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35. A Quinoa Protein Hydrolysate Fractionated by Electrodialysis with Ultrafiltration Membranes Improves Maternal and Fetal Outcomes in a Mouse Model of Gestational Diabetes Mellitus.

Author

Busso D, González A, Santander N, Saavedra F, Quiroz A, Rivera K, González J, Olmos P, Marette A, Bazinet L, Illanes S, and Enrione J

Subjects
Humans, Mice, Female, Animals, Pregnancy, Protein Hydrolysates chemistry, Ultrafiltration, Hypoglycemic Agents, Peptides chemistry, Diabetes, Gestational therapy, Glucose Intolerance, Chenopodium quinoa
Abstract

Scope: Quinoa intake exerts hypoglycemic and hypolipidemic effects in animals and humans. Although peptides from quinoa inhibit key enzymes involved in glucose homeostasis in vitro, their in vivo antidiabetic properties have not been investigated., Methods and Results: This study evaluated the effect of oral administration of a quinoa protein hydrolysate (QH) produced through enzymatic hydrolysis and fractionation by electrodialysis with ultrafiltration membrane (EDUF) (FQH) on the metabolic and pregnancy outcomes of Lepdb/+ pregnant mice, a preclinical model of gestational diabetes mellitus. The 4-week pregestational consumption of 2.5 mg mL -1 of QH in water prevented glucose intolerance and improves hepatic insulin signaling in dams, also reducing fetal weights. Sequencing and bioinformatic analyses of the defatted FQH (FQHD) identified 11 peptides 6-10 amino acids long that aligned with the quinoa proteome and exhibited putative anti-dipeptidyl peptidase-4 (DPP-IV) activity, confirmed in vitro in QH, FQH, and FDQH fractions. Peptides homologous to mouse and human proteins enriched for biological processes related to glucose metabolism are also identified., Conclusion: Processing of quinoa protein may be used to develop a safe and effective nutritional intervention to control glucose intolerance during pregnancy. Further studies are required to confirm if this nutritional intervention is applicable to pregnant women., (© 2023 Wiley-VCH GmbH.)

Published
2023
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36. Small extracellular vesicles from pregnant women with maternal supraphysiological hypercholesterolemia impair endothelial cell function in vitro.

Author

Contreras-Duarte S, Escalona-Rivano R, Cantin C, Valdivia P, Zapata D, Carvajal L, Brito R, Cerda Á, Illanes S, Gutiérrez J, and Leiva A

Subjects
Infant, Newborn, Female, Humans, Pregnancy, Endothelial Cells metabolism, Pregnant Women, Placenta metabolism, Nitric Oxide metabolism, Cholesterol metabolism, Hypercholesterolemia metabolism, Extracellular Vesicles metabolism
Abstract

Maternal physiological hypercholesterolemia MPH, maternal total cholesterol (TC) levels at term of pregnancy ≤280 mg/dL) occurs to assure fetal development. Maternal supraphysiological hypercholesterolemia (MSPH, TC levels >280 mg/dL) is a pathological condition associated with maternal, placental, and fetal endothelial dysfunction and early neonatal atherosclerosis development. Small extracellular vesicles (sEVs) are delivered to the extracellular space by different cells, where they modulate cell functions by transporting active signaling molecules, including proteins and miRNA., Aim: To determine whether sEVs from MSPH women could alter the function of endothelial cells (angiogenesis, endothelial activation and nitric oxide synthesis capacity)., Methods: This study included 24 Chilean women (12 MPH and 12 MSPH). sEVs were isolated from maternal plasma and characterized by sEV markers (CD9, Alix and HSP70), nanoparticle tracking analysis, transmission electron microscopy, and protein and cholesterol content. The endothelial cell line HMEC-1 was used to determine the uptake of labeled sEVs and the effects of sEVs on cell viability, endothelial tube formation, endothelial cell activation, and endothelial nitric oxide expression and function., Results: In MSPH women, the plasma concentration of sEVs was increased compared to that in MPH women. MSPH-sEVs were highly taken up by HMEC-1 cells and reduced angiogenic capacity and the expression and activity of eNOS without changing cell viability or endothelial activation compared to MPH-sEVs., Conclusion: sEVs from MSPH women impair angiogenesis and nitric oxide synthesis in endothelial cells, which could contribute to MSPH-associated endothelial dysfunction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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37. Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury.

Author

Toro L, Barrientos V, León P, Rojas M, Gonzalez M, González-Ibáñez A, Illanes S, Sugikawa K, Abarzúa N, Bascuñán C, Arcos K, Fuentealba C, Tong AM, Elorza AA, Pinto ME, Alzamora R, Romero C, and Michea L

Subjects
Acute Kidney Injury etiology, Animals, Bone Marrow Cells drug effects, Disease Models, Animal, Erythroid Precursor Cells drug effects, Erythropoietin pharmacology, Fibroblast Growth Factor-23, Humans, Male, Mice, Inbred C57BL, Prospective Studies, Rats, Sprague-Dawley, Receptors, Erythropoietin agonists, Receptors, Erythropoietin metabolism, Recombinant Proteins pharmacology, Sepsis blood, Sepsis complications, Shock, Hemorrhagic blood, Shock, Hemorrhagic complications, Time Factors, Up-Regulation, Acute Kidney Injury blood, Bone Marrow Cells metabolism, Erythroid Precursor Cells metabolism, Erythropoietin blood, Fibroblast Growth Factors blood
Abstract

It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI. We found that erythroid progenitor cells of bone marrow express FGF23. Erythropoietin increased FGF23 expression in vivo and in bone marrow cell cultures via the homodimeric erythropoietin receptor. In experimental AKI secondary to hemorrhagic shock or sepsis in rodents, there was a rapid increase of plasma erythropoietin, and an induction of bone marrow FGF23 expression together with a rapid increase of circulating FGF23. Blockade of the erythropoietin receptor fully prevented the induction of bone marrow FGF23 and partially suppressed the increase of circulating FGF23. Finally, there was an early increase of both circulating FGF23 and erythropoietin in a cohort of patients with severe sepsis who developed AKI within 48 hours of admission. Thus, increases in plasma erythropoietin and erythropoietin receptor activation are mechanisms implicated in the increase of plasma FGF23 in AKI., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Published
2018
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38. Reliability of Hand-Held Transcranial Doppler with M-mode Ultrasound in Middle Cerebral Artery Measurement.

Author

Venturelli PM, Brunser AM, Gaete J, Illanes S, López J, Olavarría VV, Reccius A, Brinck P, González F, Cavada G, and Lavados PM

Abstract

Purpose: To determine the intra- and interrater agreement of mean flow velocity (MFV) and pulsatility index (PI) measurement in middle cerebral arteries, assessed by transcranial Doppler (TCD) with M-mode., Methods: Masked experienced neurosonologists performed TCD with M-mode using handheld probe in healthy adult volunteers. The Bland-Altman method for concordance and intraclass correlation coefficient were used., Results: Seventy-seven healthy volunteers and seven raters participated (3 on regular TCD shift and 4 off-shift). The intrarater absolute mean difference between measurements was 5.5 cm/s [95% confidence interval (CI), 4.7-6.3] for MVF and 0.073 (95% CI, 0.063-0.083) for PI. The difference between MFV measurements was significantly higher in off-shift raters ( p = 0.015). The interrater absolute mean difference between measurements was 6.5 cm/s (95% CI, 5.5-7.5) for MVF and 0.065 (95% CI, 0.059-0.071) for PI. No influence was found for the middle cerebral artery side, volunteer's sex, or age, and there was no significant difference between raters. The intraclass correlation coefficient was 82.2% (95% CI 77.8-85.6) and 72.9% (95% CI 67.4-77.6) for MFV and PI, respectively., Conclusions: There exists good intra- and interrater agreement in MFV and PI measurements using M-mode TCD. These results support the use of this noninvasive tool and are important for clinical and investigational purposes., Competing Interests: Conflicts of interest: PMV, AMB, JG, SI, JL, AR, and PML performed TCD in their regular clinical practice, and it is included in their salary. VVO, PB, FG, and GC declare no conflicts of interest.

Published
2017
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39. IFPA meeting 2015 workshop report II: mechanistic role of the placenta in fetal programming; biomarkers of placental function and complications of pregnancy.

Author

Andraweera PH, Bobek G, Bowen C, Burton GJ, Correa Frigerio P, Chaparro A, Dickinson H, Duncombe G, Hyett J, Illanes SE, Johnstone E, Kumar S, Morgan TK, Myers J, Orefice R, Roberts CT, Salafia CM, Thornburg KL, Whitehead CL, and Bainbridge SA

Subjects
Biomarkers, Female, Humans, Pregnancy, Fetal Development physiology, Placenta physiology, Placentation physiology, Pregnancy Complications physiopathology
Abstract

Workshops are an integral component of the annual International Federation of Placenta Association (IFPA) meeting, allowing for networking and focused discussion related to specialized topics on the placenta. At the 2015 IFPA meeting (Brisbane, Australia) twelve themed workshops were held, three of which are summarized in this report. These workshops focused on various aspects of placental function, particularly in cases of placenta-mediated disease. Collectively, these inter-connected workshops highlighted the role of the placenta in fetal programming, the use of various biomarkers to monitor placental function across pregnancy, and the clinical impact of novel diagnostic and surveillance modalities in instances of late onset fetal growth restriction (FGR)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2016
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40. Intraventricular Bleeding and Hematoma Size as Predictors of Infection Development in Intracerebral Hemorrhage: A Prospective Cohort Study.

Author

Vial F, Brunser A, Lavados P, and Illanes S

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Bacterial Infections diagnosis, Bacterial Infections immunology, Cerebral Angiography methods, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage immunology, Chi-Square Distribution, Computed Tomography Angiography, Cross Infection diagnosis, Cross Infection immunology, Disability Evaluation, Female, Hematoma diagnostic imaging, Hematoma immunology, Humans, Immunocompromised Host, Logistic Models, Magnetic Resonance Angiography, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, Young Adult, Bacterial Infections microbiology, Cerebral Hemorrhage complications, Cross Infection microbiology, Hematoma etiology
Abstract

Background: Acute intracerebral hemorrhage (ICH) is associated with increased susceptibility to bacterial infection. The physiopathology of this phenomenon is not very clear. We conducted a prospective observational study investigating the correlation and independent predictors of infections in patients with ICH., Patients and Methods: Patients admitted between April 1997 and June 2013 with ICH diagnosis were evaluated for inclusion and exclusion criteria., Results: Two hundred twenty-two patients were included in this study. Ninety four patients (42.6%) presented with an infection during hospitalization being more common than pneumonia (30%) and urinary tract infections (14%). Intraventricular hemorrhage (IVH) (95% confidence interval [CI], 62.7% versus 39.3%; P < .001) and higher ICH score (95% CI, 2.31% versus 1.67%; P = .0014) were more common in patients who had infections. We found the following risk factors for having an infection in patients with ICH: IVH (odds ratio [OR] 2.3; 95% IC, 1.3-4.1), each point of ICH score (OR 1.3; 95% CI, 1.1-1.6), and having a hematoma volume larger than 30 cc (OR 2.0; 95% CI, 1.1-3.5). The localization of the hematoma was not found to be relevant., Conclusions: ICH score, size of the hematoma, and presence of IVH are independent risk factors for having an infection after ICH., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Published
2016
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41. Correlation between Maternal Characteristics during Early Pregnancy, Fetal Growth Rate and Newborn Weight in Healthy Pregnancies.

Author

Caradeux J, Serra R, Palmeiro Y, Correa PJ, Valenzuela I, Olguin J, Montenegro L, Nien JK, Osorio E, and Illanes S

Subjects
Adult, Body Mass Index, Body Weight, Cohort Studies, Female, Fetal Weight, Humans, Infant, Newborn, Pregnancy, Pregnancy Trimester, First, Prospective Studies, Pulsatile Flow physiology, Uterine Artery physiology, Birth Weight, Fetal Development, Gestational Age, Maternal Health
Abstract

Background: The objective of this study was to evaluate the association between maternal characteristics in early pregnancy and fetal growth (FG) and birth weight (BW)., Methods: A prospective cohort study was performed in unselected pregnant women who attended an ultrasound evaluation at 11-14 weeks of pregnancy. Medical history, biochemical blood tests, biophysical variables and fetal weight at 20-25 and 30-36 weeks as well as the BW were assessed. Bivariate and multivariate linear models were constructed., Results: In all, 543 patients with normal pregnancy and labor were selected. The multiple regression analysis showed a statistically significant association between maternal body mass index (BMI) in early pregnancy and the uterine artery pulsatility index (UtAPI) in the first trimester with BW (p < 0.0008) and with the ratio of fetal growth between the second and third trimesters (p < 0.0001). No correlation was found between these variables and first trimester levels of hemoglobin or glycemia., Conclusion: Maternal first trimester BMI and UtAPI correlate with the rate of intrauterine FG and with the BW. This evidence highlights the influence of maternal first trimester variables on fetuses with normal growth and the potential role of these variables in fetal programming., (© 2016 S. Karger AG, Basel.)

Published
2016
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42. Multiple myxomatous aneurysms with bypass and clipping in a 37-year-old man.

Author

Saffie P, Riquelme F, Mura J, Urra A, Passig C, Castro Á, and Illanes S

Subjects
Adult, Biopsy, Cerebral Angiography, Heart Neoplasms complications, Heart Neoplasms diagnosis, Humans, Intracranial Aneurysm diagnosis, Intracranial Aneurysm etiology, Magnetic Resonance Imaging, Male, Myxoma complications, Myxoma pathology, Treatment Outcome, Cardiac Surgical Procedures, Heart Neoplasms surgery, Intracranial Aneurysm surgery, Myxoma surgery, Neoplastic Cells, Circulating pathology
Abstract

Background: Cardiac myxoma is the most common cardiac tumor. Neurologic complications are seen in 20%-35%, most frequently embolic ischemic stroke, and rarely secondary to intracranial aneurysms. The mechanism of aneurysm formation in these patients is speculative., Methods: We report, herein, a 37-year-old male with a cardiac myxoma who experienced repeated ischemic stroke and intracerebral hematoma despite resection of heart tumor, secondary to multiple cerebral aneurysm., Results: We offered him surgery with a bypass and clipping, because growing of aneurysm was not suitable for endovascular treatment., Conclusion: Bypass and clipping are possible options in this type of disease. Aneurysm biopsy supports mycotic theory of aneurysm formation., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Published
2015
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43. Exclusion criteria for intravenous thrombolysis in stroke mimics: an observational study.

Author

Brunser AM, Illanes S, Lavados PM, Muñoz P, Cárcamo D, Hoppe A, Olavarria VV, Delgado I, and Díaz V

Subjects
Adult, Aged, Aged, 80 and over, Brain Ischemia diagnosis, Contraindications, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Prospective Studies, Stroke diagnosis, Time Factors, Treatment Outcome, Brain Ischemia drug therapy, Fibrinolytic Agents administration & dosage, Fibrinolytic Agents therapeutic use, Stroke drug therapy, Thrombolytic Therapy, Tissue Plasminogen Activator administration & dosage, Tissue Plasminogen Activator therapeutic use
Abstract

Background: Stroke mimics (SMs) are frequent in emergency departments (EDs), but are treated infrequently with intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis. We aimed at identifying the factors that lead to the exclusion of SMs from thrombolytic therapy., Methods: Consecutive patients presenting to the ED between December 2004 and March 2011 with symptoms that suggested acute ischemic stroke were included., Results: Eight hundred forty-two patients were included in this study; 113 (13.4%) were considered SMs; these patients were younger (P = .01), more frequently diabetic (P = .001), arrived later to the ED (P = .03), had lower National Institutes of Health Stroke Scale scores (P < .001), and higher frequencies of negative diffusion-weighted imaging studies (P = .002). The most common causes of cases of SM were toxic metabolic disorders (n = 34 [30.1%]) and seizures (n = 22 [19.5%]). The most frequent cause of consultation was aphasia (n = 43 [37.6%]). SM patients had a total of 152 contraindications for rt-PA, with 34 (30%) patients having >1 contraindication. The most frequent of these were being beyond the therapeutic window for thrombolysis (n = 96) and having deficits not measurable by the National Institutes of Health Stroke Scale or very mild symptoms before the start of rt-PA (n = 37). Twenty-four (21.2%) patients had both contraindications simultaneously. Two patients (1.76%) in the SM group were candidates for rt-PA but did not receive this treatment because they or their family rejected it. Of 729 stroke patients, 87 (11.9%) did receive rt-PA., Conclusions: SM patients frequently had exclusion criteria for systemic thrombolysis, the most frequent being presenting beyond the established thrombolytic window., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Published
2013
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44. Accuracy of diffusion-weighted imaging in the diagnosis of stroke in patients with suspected cerebral infarct.

Author

Brunser AM, Hoppe A, Illanes S, Díaz V, Muñoz P, Cárcamo D, Olavarria V, Valenzuela M, and Lavados P

Subjects
Aged, Arteries pathology, Brain Ischemia diagnosis, Cerebral Infarction diagnosis, Female, Humans, Male, Middle Aged, Models, Statistical, Observer Variation, Reperfusion, Reperfusion Injury, Reproducibility of Results, Treatment Outcome, Angiography methods, Diffusion Magnetic Resonance Imaging methods, Stroke diagnosis, Stroke pathology, Thrombolytic Therapy methods
Abstract

Background and Purpose: The accuracy of diffusion-weighted imaging (DWI) for the diagnosis of acute cerebral ischemia among patients with suspected ischemic stroke arriving to an emergency room has not been studied in depth., Methods: DWI was performed in 712 patients with acute or subacute focal symptoms that suggested an acute ischemic stroke (AIS), 609 of them with AIS., Results: DWI demonstrated a sensitivity of 90% and specificity of 97%, a positive likelihood ratio of 31 and a negative likelihood ratio of 0.1 for detecting AIS. The overall accuracy was 95%. Of those patients who demonstrated abnormal DWI studies, 99.5% were AIS patients, and of those patients with normal DWI studies 63% were stroke mimics., Conclusions: DWI is accurate in detecting AIS in unselected patients with suspected AIS; a negative study should alert for nonischemic conditions.

Published
2013
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45. Prevention of Early-onset Neonatal Group B Streptococcal Disease.

Author

Marió MJ, Valenzuela I, Vásquez AE, and Illanes SE

Abstract

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is an opportunistic pathogen that colonizes the gastrointestinal and genitourinary tracts of up to 50% of healthy adults and newborns; it is responsible for significant morbidity and mortality. Early detection can be used to establish the use of antibiotic prophylaxis to significantly reduce neonatal sepsis. This article reviews methods of detection and prevention of GBS infection in the neonate.

Published
2013

47. Fetal and neonatal alloimmune thrombocytopenia.

Author

Espinoza JP, Caradeux J, Norwitz ER, and Illanes SE

Abstract

Fetomaternal alloimmune thrombocytopenia (FMAIT) is a relatively uncommon disease, but is the leading cause of severe thrombocytopenia in the newborn. It can cause severe complications and long-term disabilities. The main objective of screening is to reduce both the morbidity and mortality associated with FMAIT, primarily by preventing intracranial hemorrhage. However, controversy surrounds both pre- and antenatal management. This article discusses pathogenesis, screening, diagnosis, and both pre- and neonatal management of FMAIT.

Published
2013

48. Prognosis of cryptogenic ischemic stroke: a prospective single-center study in Chile.

Author

Vallejos J, Jaramillo A, Reyes A, Illanes S, Orellana P, Manterola J, and Díaz V

Subjects
Adult, Aged, Aged, 80 and over, Brain Ischemia diagnosis, Brain Ischemia mortality, Chi-Square Distribution, Chile epidemiology, Diagnostic Imaging methods, Disability Evaluation, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Prognosis, Proportional Hazards Models, Prospective Studies, Recurrence, Risk Factors, Stroke diagnosis, Stroke mortality, Time Factors, Young Adult, Brain Ischemia epidemiology, Stroke epidemiology
Abstract

Approximately 25%-40% of ischemic strokes are considered of unknown cause (ie, cryptogenic). The available information on associated risk factors, functional outcome, and recurrence of this subtype of stroke is limited, especially for the Chilean population. We conducted a prospective cohort study of 380 patients aged ≥ 18 years admitted consecutively to a stroke unit with demonstrated ischemic stroke. The stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The modified Rankin Scale score and Barthel Index were used to assess functional outcome. The Kaplan-Meier product-limit method and Cox proportional hazards regression analysis were used to identify predictors of recurrent stroke during the follow-up period (mean, 2.1 years). Cryptogenic stroke (CS) was diagnosed in 76 patients (20%), 55.2% of them male, with a mean age of 62 ± 17 years. CS was the third most common stroke subtype after the large-artery disease (29%) and cardioembolic (24.4%) subtypes. After adjustment for age and sex, no vascular risk factors or laboratory parameters assessed at the time of admission were found to be predictive of CS. The CS subtype had the lowest rate of stroke recurrence at the end of the follow-up period (n = 4; 2.5% per year; odds ratio, 0.32; 95% confidence interval, 0.11-0.91; P = .022), a favorable functional outcome (mean modified Rankin Scale score, 2; mean Barthel Index, 77), and no increase in mortality risk (odds ratio, 0.73; 95% confidence interval, 0.29-1.77; P = .48). Our findings demonstrate that patients with no definite etiology identified after an extensive workup are at lower risk of recurrence and more likely to have a favorable outcome. No risk factors distinguish CS from other stroke subtypes in our study population., (Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Published
2012
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49. NFAT5 is activated by hypoxia: role in ischemia and reperfusion in the rat kidney.

Author

Villanueva S, Suazo C, Santapau D, Pérez F, Quiroz M, Carreño JE, Illanes S, Lavandero S, Michea L, and Irarrazabal CE

Subjects
Active Transport, Cell Nucleus genetics, Animals, Cell Hypoxia genetics, Cell Nucleus genetics, Cell Nucleus pathology, Gene Knockdown Techniques, HEK293 Cells, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Kidney Cortex blood supply, Kidney Cortex pathology, Kidney Medulla blood supply, Kidney Medulla pathology, Male, Oxygen metabolism, Rats, Reperfusion Injury genetics, Reperfusion Injury pathology, Transcription Factors genetics, Cell Nucleus metabolism, Gene Expression Regulation, Hypoxia-Inducible Factor 1, alpha Subunit biosynthesis, Kidney Cortex metabolism, Kidney Medulla metabolism, Reperfusion Injury metabolism, Transcription Factors biosynthesis
Abstract

The current hypothesis postulates that NFAT5 activation in the kidney's inner medulla is due to hypertonicity, resulting in cell protection. Additionally, the renal medulla is hypoxic (10-18 mmHg); however there is no information about the effect of hypoxia on NFAT5. Using in vivo and in vitro models, we evaluated the effect of reducing the partial pressure of oxygen (PO(2)) on NFAT5 activity. We found that 1) Anoxia increased NFAT5 expression and nuclear translocation in primary cultures of IMCD cells from rat kidney. 2) Anoxia increased transcriptional activity and nuclear translocation of NFAT5 in HEK293 cells. 3) The dose-response curve demonstrated that HIF-1α peaked at 2.5% and NFAT5 at 1% of O(2). 4) At 2.5% of O(2), the time-course curve of hypoxia demonstrated earlier induction of HIF-1α gene expression than NFAT5. 5) siRNA knockdown of NFAT5 increased the hypoxia-induced cell death. 6) siRNA knockdown of HIF-1α did not affect the NFAT5 induction by hypoxia. Additionally, HIF-1α was still induced by hypoxia even when NFAT5 was knocked down. 7) NFAT5 and HIF-1α expression were increased in kidney (cortex and medulla) from rats subjected to an experimental model of ischemia and reperfusion (I/R). 7) Experimental I/R increased the NFAT5-target gene aldose reductase (AR). 8) NFAT5 activators (ATM and PI3K) were induced in vitro (HEK293 cells) and in vivo (I/R kidneys) with the same timing of NFAT5. 8) Wortmannin, which inhibits ATM and PI3K, reduces hypoxia-induced NFAT5 transcriptional activation in HEK293 cells. These results demonstrate for the first time that NFAT5 is induced by hypoxia and could be a protective factor against ischemic damage.

Published
2012
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50. Comparison of humoral neuroinflammation and adhesion molecule expression in two models of experimental intracerebral hemorrhage.

Author

Liesz A, Middelhoff M, Zhou W, Karcher S, Illanes S, and Veltkamp R

Abstract

Background: Inflammatory cascades contribute to secondary injury after intracerebral hemorrhage (ICH) via humoral factors and cell-mediated cytotoxicity. Several experimental models were previously developed to analyze post-hemorrhagic neuroinflammation. However, neuroinflammatory markers have not been compared face-to-face between these models so far, and therefore, pathophysiological conclusions drawn from only one individual model may not be valid., Methods: We compared neuroinflammatory pathways in the two most common murine models: striatal injection of autologous blood or collagenase. Expression of pro- and anti-inflammatory cytokines (IL-1, TNF-α, IFN-γ, IL-6, TGF-β and IL-10) as well adhesion molecule expression (VCAM-1, ICAM-1) was analyzed by RT-PCR at several time points after ICH induction. Outcome and physiological parameters were compared between the models., Results: Both models induced a profound and dynamic increase in the expression of pro-inflammatory cytokines and adhesion molecules. However, blood injection resulted in significantly more pronounced alteration of these markers than collagenase injection. This difference was associated with worse outcome after blood injection compared to the collagenase model despite equal ICH volumes., Conclusions: This is the first study performing a face-to-face comparison of neuroinflammatory pathways in the two most widely used murine ICH models, revealing substantial differences between the models. This discrepancies need to be taken into account in designing future studies employing experimental ICH models, especially when analyzing neuroinflammatory pathways and therapies.

Published
2011
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