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1. Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

Author

Knip M., Akerblom H. K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H. -M., Dupre J., Fraser W. D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J. P., Lawson M. L., Ludvigsson J., Madacsy L., Mahon J. L., Ormisson A., Palmer J. P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N. H., Virtanen S. M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S. P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D. W., Brown C., Craig M., Johnston A., Bere L. J., Clarson C. L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J. -P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D. K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H. J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E. A. C., Woo V., Boland A., Clark H. D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J. C., Sauro V., Tawagi G. F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M. J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M. -C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E. A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J. C., Dawson C., Joyce C., Newhook L. A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M. J., Penner M., Sankaran K., Hardy-Brown K., King N., White R. A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M. -A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H. -M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A. -L., Hamalainen A. -M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A. S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S. -L., Selvenius J., Siljander H., Haanpaa P. -L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A. -M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A. R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M. -L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M. -L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G. B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y. M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M. B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J. A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J. R., Chueca M., Cortazar A., Echarte G., Frutos T. G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M. T., Hawkins F. G., Hernandez R., Herranz L., Pallardo L. F., Deibarra L. S., Fernandez B. H., Luis J. L., Ortiz-Quintana L., Recarte P. P., Arnau D. R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A. -M., Konefal M. S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A. -K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A. -B., Lyden G. -B., Nilsson N. -O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T. O., Andersson A. -C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I. -B., Strigard E., Svensson B. -L., Aman J., Breivik G. -E., Detlofsson I. -L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M. E., Gilmour C., Klein M. B., Lain C., Salerno D., Smith M. E., Vats K., Pfaff D. J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., Pediatrics, Knip M., Akerblom H.K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H.-M., Dupre J., Fraser W.D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J.P., Lawson M.L., Ludvigsson J., Madacsy L., Mahon J.L., Ormisson A., Palmer J.P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N.H., Virtanen S.M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S.P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D.W., Brown C., Craig M., Johnston A., Bere L.J., Clarson C.L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J.-P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D.K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H.J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E.A.C., Woo V., Boland A., Clark H.D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J.C., Sauro V., Tawagi G.F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M.J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M.-C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E.A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J.C., Dawson C., Joyce C., Newhook L.A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M.J., Penner M., Sankaran K., Hardy-Brown K., King N., White R.A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M.-A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H.-M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A.-L., Hamalainen A.-M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A.S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S.-L., Selvenius J., Siljander H., Haanpaa P.-L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A.-M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A.R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M.-L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M.-L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G.B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y.M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M.B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J.A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J.R., Chueca M., Cortazar A., Echarte G., Frutos T.G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M.T., Hawkins F.G., Hernandez R., Herranz L., Pallardo L.F., Deibarra L.S., Fernandez B.H., Luis J.L., Ortiz-Quintana L., Recarte P.P., Arnau D.R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A.-M., Konefal M.S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A.-K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A.-B., Lyden G.-B., Nilsson N.-O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T.O., Andersson A.-C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I.-B., Strigard E., Svensson B.-L., Aman J., Breivik G.-E., Detlofsson I.-L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M.E., Gilmour C., Klein M.B., Lain C., Salerno D., Smith M.E., Vats K., Pfaff D.J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., University of Zurich, and Knip, Mikael

Subjects
Male, Risk, medicine.medical_specialty, Casein, Breastfeeding, 030209 endocrinology & metabolism, 610 Medicine & health, 2700 General Medicine, Endocrinology and Diabetes, Disease-Free Survival, law.invention, Follow-Up Studie, Nutrition Policy, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, SDG 3 - Good Health and Well-being, law, Internal medicine, Diabetes mellitus, medicine, Humans, Cumulative incidence, 030212 general & internal medicine, Child, Infant Nutritional Physiological Phenomena, Original Investigation, 2. Zero hunger, Type 1 diabetes, business.industry, Hazard ratio, Absolute risk reduction, Infant, Newborn, Caseins, General Medicine, ta3121, medicine.disease, Infant Formula, 3. Good health, Diabetes Mellitus, Type 1, Infant formula, 10036 Medical Clinic, Endokrinologi och diabetes, Female, business, Human, Follow-Up Studies
Abstract

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [HD040364, HD042444, HD051997]; Canadian Institutes of Health Research; Commission of the European Communities [QLK1-2002-00372]; European Foundation for the Study of Diabates/JDRF/Novo Nordisk; Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]; Dutch Diabetes Research Foundation; Finnish Diabetes Research Foundation; JDRF

Published
2018

2. The energy trilemma

Author

Rinkenen, Jenny, Shove, Elizabeth, Torriti, Jacopo, Rinkinen, J., Shove, E., Rinkenen, Jenny, Shove, Elizabeth, Torriti, Jacopo, Rinkinen, J., and Shove, E.

Published
2019

6. Abstract 86

Author

Rinkinen, J, primary, Enchakalody, B, additional, Holcomb, S, additional, Dombrowski, A, additional, Wang, SC, additional, Buchman, SR, additional, and Levi, B, additional

Published
2012
Full Text
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8. Rebound

Author

Marsden, G, Rinkinen, J, Shove, E, and Toritti, J

Abstract

The concept of rebound effect relates to the direct and indirect effects of efficiency improvements over different time periods. The notion can provide useful insights that should prevent policy makers from being drawn into over simplistic and over optimistic assumptions about the effects of technological improvements on the reduction of energy demand. As well as providing an overview on the rebound literature, the chapter highlights a range of assumptions that need to be made in order to give rebound meaning in contemporary energy policy. The chapter concludes that analyses of rebound fail to capture broader social transformations and provide only a partial view of the changing demand for energy.

Published
2019

9. Therapeutic Options for Migraines in the Microsurgical Patient: A Scoping Review.

Author

Stearns SA, Xun H, Haddad A, Rinkinen J, Bustos VP, and Lee BT

Subjects
Humans, Postoperative Complications prevention & control, Postoperative Complications etiology, Postoperative Complications therapy, Plastic Surgery Procedures methods, Plastic Surgery Procedures adverse effects, Microsurgery methods, Migraine Disorders prevention & control, Migraine Disorders etiology
Abstract

Background: There exists an increasing array of treatments proposed to prevent, alleviate, and abort symptoms of a migraine; however, for patients who undergo reconstructive microsurgery, caution must be taken to preserve vascular integrity. This study is the first-to-date scoping review of vascular and bleeding risk of current migraine therapies, with the purpose of identifying potential therapeutic agents for postoperative migraine management appropriate for microsurgical patients., Methods: Currently available migraine therapeutics were compiled from the UpToDate software system and the American Academy of Family Physicians. A PubMed literature review was performed for each therapeutic's effect on bleeding or vascular involvement. Data were compiled into tables of abortive, symptom-controlling and prophylactic, and nonpharmacologic treatments. Expert microsurgeons reviewed the data to provide recommendations for optimized patient care., Results: Triptans and other ergot derivatives demonstrated strong evidence of vasoconstriction and were greatly advised against for immediate postmicrosurgical use. Novel pharmaceutical therapies such as lasmiditan and calcitonin gene-related peptide antagonists have no literature indicating potential for vasoconstriction or hematoma and remain an investigational option for abortive medical treatment. For symptom control, acetaminophen appears the safest option, with clinical judgment and further research needed for use of nonsteroidal antiinflammatory drugs. Alternative treatment techniques may include migraine prophylaxis with botulinum toxin injection or nutraceutical treatment by means of magnesium supplementation or coenzyme Q10 administration, minimizing the need for additional medication in the postoperative setting., Conclusions: Patients undergoing reconstructive microsurgery have a unique medical profile limiting the therapeutic options available to treat migraines. This review provides preliminary evidence to be considered as a guide for prescribing therapeutics for migraine in the postoperative setting., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Published
2024
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10. Readability, Suitability, and Complexity of Online Resources for Lower Extremity Reconstruction.

Author

Hughes CD, Tran BNN, Rinkinen J, Lee BT, and Iorio ML

Subjects
Amputation, Surgical methods, Amputation, Surgical statistics & numerical data, Female, Health Education methods, Humans, Lower Extremity injuries, Male, Patient Satisfaction, Plastic Surgery Procedures methods, Web Archives as Topic, Comprehension, Consumer Health Information organization & administration, Decision Making, Internet statistics & numerical data, Lower Extremity surgery, Surgical Flaps
Abstract

Background: Surgical options for lower extremity reconstruction frequently include a decision between autologous free flap reconstruction and amputation. Patients rely on health education materials for information before making treatment decisions. This study evaluates the quality of online health information for lower extremity reconstruction., Methods: We identified the top 10 Web sites for "leg amputation" and "leg free flap reconstruction." Three validated tools were used to evaluate literacy demand of materials, including (1) the Simple Measure of Gobbledygook for readability; (2) the Peter Mosenthal and Irwin Kirsch readability formula for complexity of nonprose materials such as list, graphs, charts; and (3) the Centers for Disease Control and Prevention's Clear Communication Index (Index). Differences in mean between the 2 groups were compared using Student t test., Results: Average Simple Measure of Gobbledygook reading grades approximated 12th-grade level and were similar between the 2 groups. This is above the recommended level of sixth-grade health literature. Complexity scores for nonprose materials of these groups were within recommended range and corresponded to very low complexity at a fourth- to seventh-grade level. The Centers for Disease Control and Prevention index was higher for amputation literature compared with free flap reconstruction (70% vs 54%), but the difference was not statistically significant., Conclusions: Overall, online health resources for lower extremity amputation and free flap reconstruction do not meet the standard for quality and accessible health information. Free flap reconstruction resources are scarce and complex. Patients facing decisions about extremity reconstruction may not have appropriate online health resources available to them to make informed decisions.

Published
2019
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11. Avascular necrosis of the humeral head following bilateral upper extremity vascular composite allotransplantation: a case report.

Author

Rinkinen J, Molway D, Carty M, Dyer GSM, Pomahac B, Chandraker A, and Talbot SG

Abstract

Vascularised composite allotransplantation (VCA) represents an exciting and emerging field in plastic and reconstructive surgery. Despite the generally good functional and psychosocial outcomes, multiple complications can be associated with the procedure. The authors describe a case of avascular necrosis of the humeral head following successful upper extremity VCA.

Published
2017
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13. Topical Vasodilators in Microsurgery: What Is the Evidence?

Author

Rinkinen J and Halvorson EG

Subjects
Administration, Topical, Constriction, Pathologic drug therapy, Constriction, Pathologic prevention & control, Evidence-Based Medicine, Humans, Intraoperative Complications drug therapy, Plastic Surgery Procedures methods, Vasodilator Agents pharmacology, Intraoperative Complications prevention & control, Microsurgery adverse effects, Microsurgery methods, Plastic Surgery Procedures adverse effects, Vasoconstriction drug effects, Vasodilator Agents administration & dosage
Abstract

Background  Topical vasodilators are frequently used during free tissue transfer to prevent and treat vasospasm and microvascular thrombosis. A variety of agents have been studied and are available, yet most microsurgeons select an agent based on anecdotal evidence or personal training. Our aim was to review the literature on topical vasodilators so microsurgeons can make more informed decisions about which agent to use. Methods  A systemic review of the literature was performed on PubMed, EMBASE, and Google Scholar using keywords "topical vasodilator," "antispasmodic," "vasospasm," "free flaps," and "microsurgery." Studies were included if they provided a comparative quantitative assessment of topical vasodilators and were written in English. In vitro, in vivo , and clinical studies were included. Results  A total of 15 studies were identified and included in our analysis. The three most common classes of topical vasodilator include local anesthetics, phosphodiesterase inhibitors, and calcium channel blockers (CCBs). Of the most commonly used topical vasodilators, CCBs (nifedipine and verapamil) were most effective followed by papaverine and lidocaine. Conclusion  The most effective topical vasodilators appear to be CCBs including nifedipine, nicardipine, and verapamil. Evidence suggests that these agents are more effective than papaverine and lidocaine solutions that are commonly used. Future research should directly compare individual CCBs to assess the most effective agent. Studies to date have focused on vessels other than those used by microsurgeons, and therefore further studies specific to these vessels are warranted., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Published
2017
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14. Proximal Interphalangeal Joint Fibromatosis After Pyrocarbon Implant Insertion: A Case Report.

Author

Rinkinen J, Chetta MD, and Chung KC

Subjects
Arthroplasty, Replacement, Finger, Female, Fibroma diagnostic imaging, Humans, Joint Diseases diagnostic imaging, Postoperative Complications diagnostic imaging, Prosthesis Design, Reoperation, Treatment Outcome, Young Adult, Biocompatible Materials adverse effects, Carbon adverse effects, Fibroma etiology, Finger Joint, Joint Diseases etiology, Joint Prosthesis adverse effects, Postoperative Complications etiology
Abstract

Background: Pyrocarbon implants represent an increasingly popular method to treat proximal interphalangeal joint dysfunction. To this point, no association has been shown between pyrocarbon biomaterials and fibromatosis. We present a potentially serious and destructive complication associated with pyrocarbon arthroplasty. Methods: We demonstrate a clinical case involving pyrocarbon arthroplasty and subsequent fibromatosis development in an otherwise healthy 23-year-old female. To present this association, we illustrate the diagnostic workup involved in a rapidly expanding soft tissue mass of the hand and explain the appropriate treatment. Results: Pyrocarbon arthroplasty was associated with development of locally destructive fibromatosis confirmed by histopathological examination. Treatment involved wide resection with preservation of local structures. Conclusion: We describe the first association between fibromatosis and pyrocarbon biomaterial. Due to fibromatosis destructive effects, clinicians should be aware of potential complications associated with these materials and know how to accurately diagnose and treat these lesions., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Published
2016
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15. Early Development of the Mouse Morphome.

Author

Hampel JA, Rinkinen J, Peterson JR, Agarwal S, Loder S, Eboda O, Enchakalody B, Wang SC, Buchman SR, and Levi B

Subjects
Animals, Body Weights and Measures, Bone and Bones, Disease Models, Animal, Female, Humans, Mice, Mice, Inbred C57BL, Prospective Studies, Retrospective Studies, X-Ray Microtomography, Bone Density, Bone Diseases, Metabolic diagnosis, Image Processing, Computer-Assisted, Phantoms, Imaging, Tomography, X-Ray Computed methods
Abstract

Introduction: Analytical morphomics focuses on extracting objective and quantifiable data from clinical computed tomography (CT) scans to measure patients' frailty. Studies are currently retrospective in nature; therefore, it would be beneficial to develop animal models for well-controlled, prospective studies. The aim of this study is to develop an in vivo microCT protocol for the longitudinal acquisition of whole-body images suitable for morphomic analyses of bone., Methods: The authors performed phantom studies on 2 microCT systems (Inveon and CT120) to study tissue radiodensity and further characterize system performance for collecting animal data. The authors also describe their design of a phantom-immobilization device using phantoms and an ovariectomized (OVX) mouse., Results: The authors discovered increased consistency along the z-axis for scans acquired on the Inveon compared with CT120, and calibration by individual slice reduces variability. Objects in the field of view had more impact on measurement acquired using the CT120 compared with the Inveon. The authors also found that using the middle 80% of slices for data analysis further decreased variability, on both systems. Moreover, bone-mineral-density calibration using the QCT Pro Mini phantom improved bone-mineral-density estimates across energy spectra, which helped confirm our technique. Comparison of weekly body weights and terminal uterine mass between sham and OVX groups validated our model., Discussion: The authors present a refined microCT protocol to collect reliable and objective data. This data will be used to establish a platform for research animal morphomics that can be used to test hypotheses developed from clinical human morphomics.

Published
2016
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16. The Systemic Effect of Burn Injury and Trauma on Muscle and Bone Mass and Composition.

Author

Rinkinen J, Hwang CD, Agarwal S, Oluwatobi E, Peterson J, Loder S, Brownly RC, Cummings T, Cederna PS, and Levi B

Subjects
Achilles Tendon, Animals, Biopsy, Needle, Burns pathology, Burns surgery, Disease Models, Animal, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Multiple Trauma, Muscular Atrophy diagnostic imaging, Muscular Atrophy pathology, Random Allocation, Reference Values, Risk Assessment, Tendon Injuries pathology, Tendon Injuries surgery, Tenotomy adverse effects, Tenotomy methods, X-Ray Microtomography methods, Bone Density physiology, Burns complications, Muscle, Skeletal pathology, Muscular Atrophy etiology, Tendon Injuries complications
Abstract

Background: By understanding the global inflammatory effects on distant myopathies, surgeons can better guide the rehabilitative process for burn patients. The authors tested the systemic effect of burn injury on distant injured muscle and native bone using immunohistochemistry and validated a new morphometric analytic modality to reproducibly quantify muscle atrophy using computed tomographic imaging., Methods: In vivo studies were performed on C57/BL6 mice using an Achilles tenotomy with concurrent burn injury model. Total muscle and bone (tibia and fibula) volume/density were quantified near the site of Achilles tenotomy using micro-computed tomography at 5, 7, and 9 to 12 weeks after surgery. The impact of burn injury on the inflammatory cascade [nuclear factor (NF)-κB, p-NF-κB] and the interconnected protein catabolism signaling pathway (Atrogin-1) was assessed by immunohistochemistry., Results: Muscle volume and density at the site of Achilles tenotomy in burned mice were significantly diminished compared with nonburned mice at 5 weeks and 9 to 12 weeks. Similar decreases in muscle volume and density were observed when comparing tenotomy to no tenotomy. Cortical bone health remained stable in burn/tenotomy mice compared with tenotomy. Muscle atrophy was associated with up-regulation of p-NF-κB, NF-κB, and Atrogin-1 assessed by immunohistochemistry., Conclusions: Burn injury significantly decreases muscle volume and density. Increased muscle atrophy using our computed tomographic morphometric analysis correlated with a significant increase in intramuscular inflammatory markers and proteolysis enzymes. This study demonstrates a unique characterization of how burn injuries may worsen local myopathy. Moreover, it provides a novel approach for quantifying muscle atrophy over an expanded period.

Published
2015
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17. Morphomic analysis as an aid for preoperative risk stratification in patients undergoing major head and neck cancer surgery.

Author

Rinkinen J, Agarwal S, Beauregard J, Aliu O, Benedict M, Buchman SR, Wang SC, and Levi B

Subjects
Adult, Aged, Female, Head and Neck Neoplasms pathology, Humans, Logistic Models, Male, Middle Aged, Postoperative Complications epidemiology, ROC Curve, Retrospective Studies, Risk, Tomography, X-Ray Computed, Head and Neck Neoplasms surgery
Abstract

Background: Patients undergoing major head and neck cancer surgery (MHNCS) may develop significant postoperative complications. To minimize the risk of complications, clinicians often assess multiple measures of preoperative health in terms of medical comorbidities. One emerging method to decrease surgical complications is preoperative assessment of patient frailty measured by specific tissue characteristics. We hypothesize that morphomic characteristics of the temporalis region serve as predictive markers for the development of complications after MHNCS., Methods: We performed a retrospective review of 69 patients with available computed tomography (CT) imaging who underwent MHNCS from 2006-2012. To measure temporalis region characteristics, we used morphomic analysis of available preoperative CT scans to map out the region. All available CT scans had been performed as part of the patient's routine work-up and were not ordered for morphomic analysis. We describe the correlation among temporalis fat pad volume (TFPV), mean zygomatic arch thickness, and incidence of postoperative complications., Results: We noted significant difference in the zygomatic bone thickness and TFPV between patients who had medical complications, surgical complications, or total major complications and those who did not. Furthermore, by use of binary logistic regression, our data suggest decreased TFPV and zygomatic arch thickness are stronger predictors of developing postoperative complications than previously studies preoperative characteristics., Conclusions: We describe morphomic analysis of the temporalis region in patients undergoing MHNCS to identify patients at risk for complications. Regional anatomic morphology may serve as a marker to objectively determine a patient's overall health. Use of the temporalis region is appropriate in patients undergoing MHNCS because of the availability of preoperative scans as part of routine work up for head and/or neck cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Published
2015
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18. Role of anatomical region and hypoxia on angiogenic markers in adipose-derived stromal cells.

Author

Rinkinen J, Lisiecki J, Oluwatobi E, Peterson J, De La Rosa S, Ranganathan K, Wang SC, Cederna PS, and Levi B

Subjects
Adult, Cell Differentiation physiology, Female, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit analysis, Mesenchymal Stem Cells, Middle Aged, NF-kappa B analysis, Neovascularization, Physiologic, Real-Time Polymerase Chain Reaction, Vascular Endothelial Growth Factor A analysis, Vascular Endothelial Growth Factor B analysis, Adipose Tissue cytology
Abstract

Background: Recent research into adipose-derived stem cells (ASCs) suggests that anatomical location has a major impact on the metabolic profile and differentiation capacity of ASCs. By having a better understanding of how various ASCs respond to cellular stressors such as hypoxia, which are induced during routine surgical procedures, we can facilitate future development of cell-based therapies to improve wound healing., Patients and Methods: Human ASCs were isolated from the superficial and deep adipose layers of four patients undergoing elective abdominoplasty. ASCs were cultured in hypoxic (1% O2, 5% CO2, and 94% N2) conditions. After 12 and 48 hours, ASCs were assessed for markers of angiogenesis by mRNA levels of vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor B (VEGF-B), and hypoxia inducible factor 1 α (HIF-1α). Western blot analysis was performed to assess levels of VEGF-A, p-NF-κB, and NF-κB. In addition, in vitro analysis of angiogenesis was performed using Matrigel assay (BD Biosciences, Franklin Lakes, NJ)., Results: We observed significant increases in deep ASC's VEGF-A, VEGF-B, and HIF-1α mRNA expression compared with the superficial layer after 24-hour hypoxia (p < 0.05). Similar results were found when examining protein expression levels, with the deep ASCs expressing significantly larger amounts of VEGF-A and p-NF-κB (p < 0.05) compared with the superficial layer., Conclusion: Our results suggest that significant variations exist in the angiogenic profile of superficial and deep ASCs. We demonstrate that superficial ASCs are less prone to transcribe potent chemokines for angiogenesis, such as VEGF-A, VEGF-B, and HIF-1α and are less likely to translate VEGF-A and NF-κB. This may help with the selection of specific stem cell donor sites in future models for stem cell therapy., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Published
2015
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19. Abdominal wall dynamics after component separation hernia repair.

Author

Lisiecki J, Kozlow JH, Agarwal S, Ranganathan K, Terjimanian MN, Rinkinen J, Brownley RC, Enchakalody B, Wang SC, and Levi B

Subjects
Adult, Anatomic Landmarks, Fascia diagnostic imaging, Hernia, Ventral diagnostic imaging, Humans, Middle Aged, Rectus Abdominis diagnostic imaging, Retrospective Studies, Skin, Spine, Subcutaneous Fat diagnostic imaging, Subcutaneous Fat surgery, Tomography, X-Ray Computed, Wound Healing, Abdominal Wall surgery, Fasciotomy, Hernia, Ventral surgery, Herniorrhaphy methods, Rectus Abdominis surgery
Abstract

Background: The component separation technique (CST) is an important technique now used frequently in complex ventral hernia repair (VHR). Although this technique has demonstrated superior success rates, there is a paucity of research describing how release of the external obliques coupled with rectus myofascial advancement alters the morphology of the abdominal architecture. In this study, we apply the new concept of analytic morphomics to describe the immediate changes in morphology of the abdomen that take place after VHR by CST., Methods: We identified 21 patients who underwent VHR by CST and received both preoperative and postoperative computed tomography scans between 2004 and 2009 in our clinical database. The surgical technique involved incisional release of the external oblique muscle lateral to the linea semilunaris with rectus abdominis myofascial advancement in all patients. Using semiautomated morphomic analysis, we measured the pre- and post-operative dimensions of the abdominal wall including the anterior-posterior distance from the anterior vertebra-to-skin and fascia along with the circumferential area of the skin and fascial compartments. Paired Student t-tests were used to compare pre- and post-operative values., Results: After hernia repair, there was a decrease in the anterior vertebra-to-skin distance (16.6 cm-15.8 cm, P = 0.007). There were also decreases in total body area (968.0 cm(2)-928.6 cm(2), P = 0.017) and total body circumference (113.6 cm-111.4 cm, P = 0.016). The distance from fascia to skin decreased as well, almost to the point of statistical significance (3.3 cm-2.9 cm, P = 0.0505). Interestingly, fascia area and circumference did not decrease significantly after the operation (578.2 cm(2)-572.5 cm(2), P = 0.519, and 89.1 cm-88.6 cm, P = 0.394, respectively)., Conclusions: Morphomic analysis can be used to compare and pre- and post-operative changes in patients undergoing abdominal surgery. Our study demonstrates that component separation affects the dimensions of the entire abdomen, but leaves the fascia area and circumference relatively unchanged. These changes in the abdominal wall may help explain the muscular changes observed as a result of this operation and demonstrate that this is a functional operation that restores fascial area. By better defining the effects of this procedure, we can better understand the reason for its clinical success., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Published
2015
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20. Cross-sectional area of the abdomen predicts complication incidence in patients undergoing sternal reconstruction.

Author

Kozlow JH, Lisiecki J, Terjimanian MN, Rinkinen J, Brownley RC, Agarwal S, Wang SC, and Levi B

Subjects
Adult, Aged, Fascia anatomy & histology, Female, Humans, Incidence, Intra-Abdominal Fat anatomy & histology, Male, Middle Aged, Obesity complications, Obesity epidemiology, Obesity pathology, Postoperative Complications epidemiology, Postoperative Complications pathology, Predictive Value of Tests, Preoperative Period, Risk Factors, Sternum diagnostic imaging, Subcutaneous Fat anatomy & histology, Tomography, X-Ray Computed, Treatment Outcome, Abdomen anatomy & histology, Body Surface Area, Postoperative Complications etiology, Plastic Surgery Procedures adverse effects, Plastic Surgery Procedures methods, Sternum surgery
Abstract

Background: Sternal reconstruction with vascularized flaps is central to the management of sternal wound infections and mediastinitis but carries a high risk of complications. There is a need to identify reliable predictors of complication risk to help inform patients and clinicians in preparation for surgery. Unfortunately, body mass index and serum albumin may not be reliable predictors of complication rates. Analytic morphomics provides a robust quantitative method to measure patients' obesity as it pertains to their risk of complications in undergoing sternal reconstruction., Methods: We identified 34 patients with preoperative computed tomography scans of the abdomen from a cohort of sternal reconstructions performed between 1997 and 2010. Using semiautomated analytic morphomics, we identified the patients' skin and fascia layers between the ninth and 12th thoracic spine levels; from these landmarks, we calculated morphomic measurements of the patients' abdomens, including their total body cross sectional area and the cross sectional area of their subcutaneous fat. We obtained the incidence of complications from chart review and correlated the incidence of complications (including seroma, hematoma, recurrent wounds, mediastinitis, tracheostomy, and death) with patients' morphomic measurements., Results: Sixty-two percent of patients (n = 21) suffered complications after their operation. Those who suffered from complications, relative to those who did not have complications, had increased visceral fat area (12,547.2 mm(2)versus 6569.9 mm(2), P = 0.0080), subcutaneous fat area (16,520.2 mm(2)versus 8020.1 mm(2), P = 0.0036), total body area (91,028.6 mm(2)versus 67,506.5 mm(2), P = 0.0022), fascia area (69,238.4 mm(2)versus 56,730.9 mm(2), P = 0.0118), total body circumference (1101.8 mm versus 950.2 mm, P = 0.0017), and fascia circumference (967.5 mm versus 868.1 mm, P = 0.0077). We also demonstrated a significant positive correlation between the previously mentioned morphomic measurements and the incidence of complications in multivariate logistic regression models, with odds ratios ranging from 1.19-3.10 (P values ranging from 0.010-0.022)., Conclusions: Increases in abdominal morphomic measurements correlate strongly with the incidence of complications in patients undergoing sternal reconstruction. This finding may influence preoperative risk stratification and surgical decision making in this patient population., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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21. Morphomic analysis for preoperative donor site risk assessment in patients undergoing abdominal perforator flap breast reconstruction: a proof of concept study.

Author

Levi B, Rinkinen J, Kidwell KM, Benedict M, Stein IC, Lisiecki J, Enchakalody B, Wang SC, Kozlow JH, and Momoh AO

Subjects
Adult, Female, Humans, Imaging, Three-Dimensional, Mammaplasty methods, Middle Aged, Preoperative Period, ROC Curve, Retrospective Studies, Risk Assessment, Surgical Wound Dehiscence epidemiology, Tomography, X-Ray Computed methods, Transplant Donor Site, Perforator Flap
Abstract

Background: Morphomics are three-dimensional measurements of aspects of the human anatomy generated by computed tomographic (CT) imaging. The purpose of this study was to generate preliminary data on the efficacy of morphomics, as a potential risk stratification tool, in predicting abdominal donor site wound-healing complications in patients undergoing abdominal perforator flap breast reconstruction. Patients and, Methods: In total, 58 consecutive patients undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction were evaluated. Using preoperative CT scan data, we quantified patients' body area, visceral and subcutaneous fat, fascia area, and body depth between T12 and L4. Associations between morphomic measures and complication rates were examined using t-tests and logistic regression., Results: Of the 58 patients, 11 (19%) patients developed a wound dehiscence and 47 (81%) patients healed their abdominal incision without complications. Patients with a dehiscence had a significantly higher body mass index (BMI) (34.32 vs. 29.26 kg/m(2), p = 0.014) than patients without a dehiscence. Multiple morphometric measures including higher visceral fat area (p = 0.003) were significant predictors of abdominal donor site wound dehiscence. BMI (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.03-1.32; p = 0.017) and visceral fat area (OR, 1.24; 95% CI, 1.08-1.42; p = 0.002) were independently significant predictors for wound dehiscence in the entire sample. Only visceral fat area retained its predictive ability in patients with a BMI > 30 kg/m(2)., Conclusions: Morphomic measurements correlate with the likelihood of developing postoperative donor site dehiscence after DIEP flap breast reconstruction. As a proof of concept study, this demonstrates that objective data obtained from CT scans may help in preoperatively assessing the risk for donor site wound healing complications in patients undergoing DIEP flap breast reconstruction., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Published
2014
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22. Skin allograft and vascularized composite allograft: potential for long-term efficacy in the context of lymphatic modulation.

Author

Rinkinen J, Selley R, Agarwal S, Loder S, and Levi B

Subjects
Adaptive Immunity immunology, Antigen Presentation immunology, Burns immunology, Chimerism, Composite Tissue Allografts blood supply, Composite Tissue Allografts immunology, Graft Rejection immunology, Graft Survival immunology, Humans, Lymph Node Excision, Allografts blood supply, Allografts immunology, Burns surgery, Lymph Nodes immunology, Skin Transplantation methods
Abstract

Tissue transplantation restores form and function in burn patients. The treatment of burn injuries is influenced by severity, location, and the percentage of total body surface area. There have been a number of different techniques developed to temporize and repair the destroyed tissue. However, in patients with large wound burden, sufficient donor site tissue may not be available for autograft harvesting. Such extensive burns necessitate other temporary and permanent options for wound coverage such as skin or vascularized composite allografts (VCA). Rejection of these tissues presents an ongoing problem which is currently managed using a host of systemic immunosuppressive medications. This article discusses the mechanism behind the innate and adaptive immune systems rejection of the allografts. By understanding these pathways, various techniques using immunomodulatory protocols have led to increased allograft survival. However, our primary interest lies in the initial recognition of the graft. We tailor this article to have a specific emphasis on lymphatic modulation as a potential adjunctive therapy. Reviews of the studies evaluating the effect of lymph node modulation on graft survival are described with future implications to allograft transplant research.

Published
2014
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23. Targeted radiosensitization with PARP1 inhibition: optimization of therapy and identification of biomarkers of response in breast cancer.

Author

Feng FY, Speers C, Liu M, Jackson WC, Moon D, Rinkinen J, Wilder-Romans K, Jagsi R, and Pierce LJ

Subjects
Benzimidazoles pharmacology, Blotting, Western, Breast drug effects, Breast metabolism, Breast Neoplasms pathology, Breast Neoplasms radiotherapy, Cell Proliferation drug effects, Cell Survival drug effects, Cells, Cultured, DNA Repair drug effects, DNA Repair radiation effects, Female, Flow Cytometry, Fluorescent Antibody Technique, Humans, Biomarkers, Tumor analysis, Breast Neoplasms drug therapy, Poly(ADP-ribose) Polymerase Inhibitors, Radiation Tolerance drug effects, Radiation-Sensitizing Agents pharmacology
Abstract

Sustained locoregional control of breast cancer is a significant issue for certain patients. Inhibition of PARP1 is a promising strategy for radiosensitization (RS). We sought to optimize therapy with PARP1 inhibition and radiation (RT) by establishing the most effective treatment schedule, degree of PARP1-mediated RS, and identify early biomarkers predictive of efficacy in breast cancer models. Using clonogenic survival assays, we assessed intrinsic radiosensitivity and RS induced by PARP1 inhibition in breast cancer cell lines. Potential biomarkers of response were evaluated using western blotting, flow cytometry, and immunofluorescence with validation in vivo using tumor xenograft experiments. Across a panel of BC and normal breast epithelial cell lines, the PARP1 inhibitor ABT-888 preferentially radiosensitizes breast cancer (vs. normal) cells with enhancement ratios (EnhR) up to 2.3 independent of intrinsic BC subtype or BRCA mutational status. Concurrent and adjuvant therapy resulted in the highest EnhR of all schedules tested. The degree of RS did not correlate with pretreatment markers of PARP1 activity, DNA damage/repair, or cell cycle distribution. Increases in PARP1 activity 24 h after RT were associated with sensitivity after combination treatment. Findings were confirmed in breast cancer xenograft models. Our study demonstrates that PARP1 inhibition improves the therapeutic index of RT independent of BC subtype or BRCA1 mutational status and that PARP1 activity may serve as a clinically relevant biomarker of response. These studies have led to a clinical trial (TBCRC024) incorporating intratreatment biomarker analyses of PARP1 inhibitors and RT in breast cancer patients.

Published
2014
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24. Use of temporal morphomic indices as a clinically important variable in the diagnosis of nonsyndromic craniosynostosis.

Author

Rinkinen J, Wang L, Zhang P, Lisiecki J, Enchakalody B, Holcombe S, Dombrowski A, Wang SC, Buchman SR, and Levi B

Subjects
Adipose Tissue pathology, Female, Humans, Imaging, Three-Dimensional, Infant, Male, Retrospective Studies, Craniosynostoses diagnostic imaging, Craniosynostoses pathology, Radiographic Image Interpretation, Computer-Assisted, Temporal Muscle diagnostic imaging, Temporal Muscle pathology, Tomography, X-Ray Computed
Abstract

Introduction: Preoperative computed tomography (CT) evaluation of patients with nonsyndromic craniosynostosis (NSC) has focused on the bony cranial vault while ignoring the surrounding soft tissues. In this study, we posit that novel CT-derived temporal muscle and temporal fat pad morphomics (tissue thickness, area, and volume) can be used to calculate temporal morphomic indices (TMIs), which are unique to each NSC subtype (metopic, coronal, and sagittal) and divergent from normal individuals., Methods: High-throughput image analysis was used to reconstruct the 3-dimensional anatomy and quantify a TMI. These steps were completed in a semiautomated method using algorithms programmed in MATLAB v13.0. Differences in TMI across various craniosynostosis subtypes were assessed using Wilcoxon nonparametric tests for both patients with NSC and a control cohort of patients with trauma., Results: Using preoperative CT images, we evaluated 117 children with NSC from the University of Michigan Health System and 50 age-matched control patients between 1999 and 2011. Results indicate significant differences in TMI among the normal and NSC groups, with normal patients having significantly higher TMI values than patients with metopic, sagittal, and coronal synostosis. In addition, significant differences were found to exist between each craniosynostosis category., Conclusions: Patients with craniosynostosis demonstrate diminished temporalis muscle and overlying fat pad volume and thickness compared with control patients. The unique changes in temporal morphomics presented in this article demonstrate not only that the bony calvaria is affected by craniosynostosis but also that there exist quantifiable aberrations in the temporalis muscle and temporal fat pad. The methodologies described offer a novel methodology to use pre-existing CT scans to glean additional preoperative information on the soft tissue characteristics of patients with craniosynostosis.

Published
2014
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25. Use of morphometric assessment of body composition to quantify risk of surgical-site infection in patients undergoing component separation ventral hernia repair.

Author

Levi B, Zhang P, Lisiecki J, Terjimanian MN, Rinkinen J, Agarwal S, Holcombe SA, Kozlow JH, Wang SC, and Kuzon WM

Subjects
Comorbidity, Female, Humans, Logistic Models, Male, Middle Aged, Preoperative Period, Risk Assessment, Surgical Mesh, Tomography, X-Ray Computed, Abdominal Fat diagnostic imaging, Body Composition, Hernia, Ventral epidemiology, Hernia, Ventral surgery, Obesity epidemiology, Surgical Wound Infection epidemiology
Abstract

Background: Body mass index does not allow accurate risk stratification for individuals undergoing component separation repair of ventral hernias. The authors hypothesized that tissue morphology measurements (morphomics) of preoperative computed tomography scans stratify the risk of surgical site infection in patients undergoing ventral hernia repair with a component separation technique., Methods: The authors identified 93 patients who underwent component release ventral hernia repair (2004 to 2012). The surgical technique involved release of the external oblique muscle lateral to the linea semilunaris. Using analytic morphomic techniques, the authors measured patients' morphology using routine preoperative computed tomography scans. Two-sample t test was used to evaluate the effect of morphomic and demographic factors on surgical-site infection. Separate logistic regression analyses were performed on these morphomic factors to evaluate their predictive value in assessing the risk of surgical site infection, controlling for demographic covariates., Results: Surgical site infections were observed in 31 percent (n = 29) of the population. Subcutaneous fat area, total body area, and total body circumference had increased odds ratios for surgical site infection (p = 0.004, 0.014, and 0.012, respectively), indicating that these measures are better associated with surgical site infection than body mass index. These calculations control for demographic covariates, confirming that these morphomic parameters are predictive of surgical site infection., Conclusion: Specific morphomic values serve as superior predictors of surgical site infection in patients undergoing component separation technique hernia repair than currently used values such as body mass index., Clinical Question/level of Evidence: Risk, III.

Published
2014
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27. Adipose-derived mesenchymal stem cells from ventral hernia repair patients demonstrate decreased vasculogenesis.

Author

Lisiecki J, Rinkinen J, Eboda O, Peterson J, De La Rosa S, Agarwal S, Dimick J, Varban OA, Cederna PS, Wang SC, and Levi B

Subjects
Adult, Cells, Cultured, Female, Humans, Male, Mesenchymal Stem Cells pathology, Middle Aged, Hernia, Ventral metabolism, Hernia, Ventral pathology, Hernia, Ventral surgery, Mesenchymal Stem Cells metabolism, Neovascularization, Physiologic, RNA biosynthesis, Vascular Endothelial Growth Factor A biosynthesis
Abstract

Introduction: In adipose tissue healing, angiogenesis is stimulated by adipose-derived stromal stem cells (ASCs). Ventral hernia repair (VHR) patients are at high risk for wound infections. We hypothesize that ASCs from VHR patients are less vasculogenic than ASCs from healthy controls., Methods: ASCs were harvested from the subcutaneous fat of patients undergoing VHR by the component separation technique and from matched abdominoplasty patients. RNA and protein were harvested on culture days 0 and 3. Both groups of ASCs were subjected to hypoxic conditions for 12 and 24 hours. RNA was analyzed using qRT-PCR, and protein was used for western blotting. ASCs were also grown in Matrigel under hypoxic conditions and assayed for tubule formation after 24 hours., Results: Hernia patient ASCs demonstrated decreased levels of VEGF-A protein and vasculogenic RNA at 3 days of growth in differentiation media. There were also decreases in VEGF-A protein and vasculogenic RNA after growth in hypoxic conditions compared to control ASCs. After 24 hours in hypoxia, VHR ASCs formed fewer tubules in Matrigel than in control patient ASCs., Conclusion: ASCs derived from VHR patients appear to express fewer vasculogenic markers and form fewer tubules in Matrigel than ASCs from abdominoplasty patients, suggesting decreased vasculogenic activity.

Published
2014
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28. Temporalis muscle morphomics: the psoas of the craniofacial skeleton.

Author

Ranganathan K, Terjimanian M, Lisiecki J, Rinkinen J, Mukkamala A, Brownley C, Buchman SR, Wang SC, and Levi B

Subjects
Adult, Age Factors, Aged, Body Mass Index, Female, Humans, Male, Middle Aged, Tomography, X-Ray Computed, Psoas Muscles anatomy & histology, Temporal Muscle anatomy & histology
Abstract

Background: The psoas muscle has been shown to predict patient outcomes based on the quantification of muscle area using computed tomography (CT) scans. The accuracy of morphomic analysis on other muscles has not been clearly delineated. In this study, we determine the correlation between temporalis muscle mass, psoas muscle area, age, body mass index (BMI), and gender., Methods: Temporalis and psoas muscle dimensions were determined on all trauma patients who had both abdominal and maxillofacial CT scans at the University of Michigan between 2004 and 2011. Age, BMI, and gender were obtained through chart review. Univariate and multivariate analyses were performed to determine the relative relationship between morphomic data of the temporalis and psoas muscles and the ability of such information to correspond with clinical variables, such as BMI, age, and gender., Results: A total of 646 patients were included in the present study. Among the 249 (38.5%) women and 397 (61.5%) men, the average age was 49.2 y. Average BMI was 27.9 kg/m². Total psoas muscle area directly correlated with mean temporalis muscle thickness (r = 0.57, P < 0.001). There was an indirect correlation between age and psoas muscle area (r = -0.52, P < 0.001) and temporalis muscle thickness (r = -0.36, P < 0.001). Neither psoas nor temporalis measurements correlated strongly with BMI (r = 0.18, P < 0.001; r = 0.14, P = 0.002), although stronger correlations were found in a more "frail," subgroup as defined by a BMI of <20 (r = 0.59, P = 0.002)., Conclusions: We demonstrate that dimensions of the temporalis muscle can be quantified and may serve as a proxy for age. Going forward, we aim to assess the utility of temporalis and psoas morphomics in predicting complication rates among trauma patients admitted to the hospital to predict outcomes in the future., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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29. Morphomic measurement of the temporalis muscle and zygomatic bone as novel predictors of hospital-based clinical outcomes in patients with mandible fracture.

Author

Lisiecki J, Zhang P, Wang L, Rinkinen J, De La Rosa S, Enchakalody B, Brownley RC, Wang SC, Buchman SR, and Levi B

Subjects
Adult, Aged, Comorbidity, Female, Glasgow Coma Scale, Humans, Male, Mandible diagnostic imaging, Mandible surgery, Middle Aged, Patient Care Planning, Prognosis, Plastic Surgery Procedures, Temporal Muscle pathology, Treatment Outcome, Zygoma pathology, Bone Density physiology, Cephalometry methods, Fracture Healing physiology, Health Status Indicators, Image Interpretation, Computer-Assisted, Mandibular Fractures diagnostic imaging, Mandibular Fractures surgery, Temporal Muscle diagnostic imaging, Temporal Muscle surgery, Tomography, X-Ray Computed, Zygoma diagnostic imaging, Zygoma surgery
Abstract

Introduction: Patients with mandibular fracture often have comorbidities and concomitant injuries making the decision for when and how to operate a challenge. Physicians describe "temporalis wasting" as a finding that indicates frailty; however, this is a subjective finding without quantitative values. In this study, we demonstrate that decreased morphomic values of the temporalis muscle and zygomatic bone are an objective measure of frailty associated with increased injury-induced morbidity as well as negative impact on overall hospital-based clinical outcomes in patients with mandible fracture., Methods: Computed tomographic (CT) scans from all patients with a diagnosis of a mandible fracture in the University of Michigan trauma registry and with a hospital admission were collected from the years 2004 to 2011. Automated, high-throughput CT analysis was used to reconstruct the anatomy and quantify morphomic values (temporalis volume, area and thickness, and zygomatic thickness) in these patients using MATLAB v13.0 (MathWorks Inc, Natick, MA, USA). Subsequently, a subset of 16 individuals with a Glasgow Coma Scale of 14 or 15 was analyzed to control for brain injury. Clinical data were obtained, and the association between morphomic measurements and clinical outcomes was evaluated using Pearson correlation for unadjusted analysis and multiple regression for adjusted analysis., Results: The mean age of patients in the study was 47.1 years. Unadjusted analysis using Pearson correlation revealed that decreases in zygomatic bone thickness correlated strongly with increases in hospital, intensive care unit, and ventilator days (P < 0.0001, P = 0.0003, and P = 0.0017, respectively). Furthermore, we found that decreases in temporalis mean thickness correlated with increases in hospital and ventilator days (P = 0.0264 and P = 0.0306, respectively). Similarly, decreases in temporalis local mean thickness are significantly correlated with increases in hospital and ventilator days (P = 0.0232 and P = 0.0472, respectively)., Conclusions: Decreased thicknesses of the zygomatic bone and temporalis muscle are significantly correlated with higher hospital, ventilator, and intensive care unit days in patients with mandibular fracture receiving reconstructive operations. This morphomic methodology provides an accurate, quantitative means to evaluate craniofacial trauma patient frailty, injury, and outcomes using routinely obtained CT scans. In the future, we plan to apply this approach to determine preoperative risk stratification and assist in surgical planning.

Published
2013
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30. Temporal morphomics as a model for determining preoperative risk of blood transfusion in nonsyndromic craniosynostosis patients.

Author

Rinkinen J, Terjimanian M, Benedict M, Hiltzik D, Seyi A, Lisiecki J, Wang SC, Buchman SR, and Levi B

Subjects
Blood Loss, Surgical statistics & numerical data, Craniosynostoses diagnostic imaging, Female, Humans, Imaging, Three-Dimensional, Infant, Linear Models, Logistic Models, Male, Multivariate Analysis, Retrospective Studies, Risk Assessment, Subcutaneous Fat anatomy & histology, Temporal Muscle anatomy & histology, Craniosynostoses surgery, Decision Support Techniques, Erythrocyte Transfusion statistics & numerical data, Preoperative Care methods, Subcutaneous Fat diagnostic imaging, Temporal Muscle diagnostic imaging, Tomography, X-Ray Computed
Abstract

Background: Estimates of blood loss during craniosynostosis surgeries have ranged from 42 to 126 percent of infant's total blood volume. Currently, no risk model has been developed to determine the likelihood of needing a blood transfusion. The authors propose an objective model, based on patients' three-dimensional anatomical characteristics, to stratify the likelihood of needing perioperative packed red blood cells., Methods: High-throughput image analysis from already ordered preoperative computed tomographic scans was used to reconstruct the three-dimensional anatomy of the temporalis muscle and overlying temporal fat pad. Using these morphomic measurements, the authors created a risk assessment model of the amount of packed red blood cells infused based on morphomic variations in temporal soft tissue., Results: The authors evaluated 139 infants with nonsyndromic craniosynostosis from the University of Michigan Health System. Results show the need for blood transfusion ranged from 94.1 percent among patients in the smallest quartile for temporal fat pad volume compared with 65.7 percent among the group with the largest quartile for temporal fat pad volume (p = 0.0057). Using multivariable linear regression, temporal fat pad volume (p = 0.012) and fat pad thickness (p = 0.036) were independent predictors for amount of packed red blood cells required., Conclusions: The authors demonstrate that patients with diminished temporal fat pad volume are significantly more likely to need increased packed red blood cell transfusions. In addition, by use of multivariable linear regression, their data suggest that temporal fat pad volume and thickness were independent predictors for the amount of required transfusion of packed red blood cells.

Published
2013
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31. Ascorbic acid and a cytostatic inhibitor of glycolysis synergistically induce apoptosis in non-small cell lung cancer cells.

Author

Vuyyuri SB, Rinkinen J, Worden E, Shim H, Lee S, and Davis KR

Subjects
Cell Line, Tumor, Cell Survival drug effects, Drug Synergism, Humans, Lung Neoplasms metabolism, Antineoplastic Agents pharmacology, Apoptosis drug effects, Ascorbic Acid pharmacology, Carcinoma, Non-Small-Cell Lung metabolism, Glycolysis drug effects
Abstract

Ascorbic acid (AA) exhibits significant anticancer activity at pharmacologic doses achievable by parenteral administration that have minimal effects on normal cells. Thus, AA has potential uses as a chemotherapeutic agent alone or in combination with other therapeutics that specifically target cancer-cell metabolism. We compared the effects of AA and combinations of AA with the glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3-PO) on the viability of three non-small cell lung cancer (NSCLC) cell lines to the effects on an immortalized lung epithelial cell line. AA concentrations of 0.5 to 5 mM caused a complete loss of viability in all NSCLC lines compared to a <10% loss of viability in the lung epithelial cell line. Combinations of AA and 3-PO synergistically enhanced cell death in all NSCLC cell lines at concentrations well below the IC50 concentrations for each compound alone. A synergistic interaction was not observed in combination treatments of lung epithelial cells and combination treatments that caused a complete loss of viability in NSCLC cells had modest effects on normal lung cell viability and reactive oxygen species (ROS) levels. Combination treatments induced dramatically higher ROS levels compared to treatment with AA and 3-PO alone in NSCLC cells and combination-induced cell death was inhibited by addition of catalase to the medium. Analyses of DNA fragmentation, poly (ADP-ribose) polymerase cleavage, annexin V-binding, and caspase activity demonstrated that AA-induced cell death is caused via the activation of apoptosis and that the combination treatments caused a synergistic induction of apoptosis. These results demonstrate the effectiveness of AA against NSCLC cells and that combinations of AA with 3-PO synergistically induce apoptosis via a ROS-dependent mechanism. These results support further evaluation of pharmacologic concentrations of AA as an adjuvant treatment for NSCLC and that combination of AA with glycolysis inhibitors may be a promising therapy for the treatment of NSCLC.

Published
2013
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32. Novel temporalis muscle and fat pad morphomic analyses aids preoperative risk evaluation and outcome assessment in nonsyndromic craniosynostosis.

Author

Rinkinen J, Zhang P, Wang L, Enchakalody B, Terjimanian M, Holcomb S, Wang SC, Buchman SR, and Levi B

Subjects
Blood Transfusion statistics & numerical data, Craniosynostoses surgery, Female, Humans, Infant, Length of Stay statistics & numerical data, Male, Outcome Assessment, Health Care, Predictive Value of Tests, Preoperative Period, Retrospective Studies, Risk Assessment, Adipose Tissue diagnostic imaging, Craniosynostoses diagnostic imaging, Imaging, Three-Dimensional, Radiographic Image Interpretation, Computer-Assisted methods, Temporal Muscle diagnostic imaging, Tomography, X-Ray Computed
Abstract

Introduction: Analytical morphomics is the term we created to describe an innovative, highly automated, anatomically indexed processing of 3D medical imaging data captured during the course of a patients' preoperative CT scan. Our specific aim is to determine the efficacy of craniofacial morphomic indices (CMI) such as temporalis muscle and temporal fat pad morphometric values to predict blood transfusion requirement and hospital stay in a cohort of children with nonsyndromic craniosynostosis (NSC)., Methods: High-throughput, semi-automated image analysis was used to reconstruct the 3-dimensional anatomy of the temporalis muscle and temporal fat pad and to quantify CMIs. The prognostic effect of CMI on clinical outcomes were evaluated among all NSC patients and compared across various craniosynostosis subtypes using Wilcoxon nonparametric tests and Kendall's τ to determine significance., Results: Using preoperative CT images, we evaluated 117 children with NSC from the University of Michigan Health System. Results demonstrate that increased temporal fat pad volume and local temporalis muscle volume are associated with better clinical outcomes in craniosynostosis patients. More specifically, temporal fat pad volume was shown to be a significant predictor of perioperative blood transfusion requirements (P = 0.0033) and increased temporal muscle volume correlated with decreased hospital stay (P = 0.016) when controlling for other covariates including age, sex, weight, and preoperative hematocrit. In addition, the same significant predictors were found when examining individual subtypes of craniosynostosis., Conclusion: Our findings demonstrate that maxillofacial CT scans provide a useful quantitative index reflecting general patient health, risk stratification, and probabilities of intervention in addition to their previously established ability to determine the specific pathology of the patient. We demonstrate that temporal morphomics predict the incidence of blood transfusion, hospital stay, and serve as a proxy for fitness in patients undergoing craniosynostosis surgery.

Published
2013
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