50 Years Ago in The Journal of Pediatrics

50 Years Ago in The Journal of Pediatrics March 2018 ORIGINAL ARTICLES 23. Krauss BS, Krauss BA, Green SM. Videos in clinical medicine. 28. Austin PW, Gerber L, Karrar AK. Fatigue in chronic liver disease: exploring Managing procedural anxiety in children. N Engl J Med 2016;374: the role of the autonomic nervous system. Liver Int 2015;35:1489-91. e19. 29. Bajaj JS. Diagnosing minimal hepatic encephalopathy: from the ivory tower 24. Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, et al. Evalu- to the real world. Gastroenterology 2015;149:1330-3. ation of the pediatric patient for liver transplantation: 2014 practice guide- 30. Zink AN, Perez-Leighton CE, Kotz CM. The orexin neuropeptide system: line by the American Association for the Study of Liver Diseases, American physical activity and hypothalamic function throughout the aging process. Society of Transplantation and the North American Society for Pediat- Front Syst Neurosci 2014;8:211. ric Gastroenterology, Hepatology and Nutrition. Hepatology 2014;60:362- 31. Berzigotti A, Saran U, Dufour JF. Physical activity and liver diseases. 98. Hepatology 2016;63:1026-40. 25. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly 32. Patterson C, So S, Schneiderman JE, Stephens D, Stephens S. Physical ac- people. Lancet 2013;381:752-62. tivity and its correlates in children and adolescents post-liver trans- 26. Cederholm T. Overlaps between frailty and sarcopenia definitions. Nestle plant. Pediatr Transplant 2016;20:227-34. Nutr Inst Workshop Ser 2015;83:65-9. 33. Ampuero J, Simon M, Montoliu C, Jover R, Serra MA, Cordoba J, et al. 27. van den Berg-Emons R, van Ginneken B, Wijffels M, Tilanus H, Metselaar Minimal hepatic encephalopathy and critical flicker frequency are asso- H, Stam H, et al. Fatigue is a major problem after liver transplantation. ciated with survival of patients with cirrhosis. Gastroenterology Liver Transpl 2006;12:928-33. 2015;149:1483-9. A Study of “Total Therapy” of Acute Lymphocytic Leukemia in Children George P, Hernendez K, Hustu O, Borella L, Holton C, Pinkel D. J Pediatr 1968;72:399-408 hildhood acute lymphoblastic leukemia, once universally fatal, now has cure rates that approach (and for some C clinical subgroups, exceed) 90%. Farber et al first demonstrated transient clinical responses to folate antagonists in the 1940s. However, it was not until the 1960s that combining multidrug therapy with continuation of mainte- nance chemotherapy well beyond the point of morphologic remission led to durable responses. Building on these early experiences, George et al reported in 1968 on the first “Total Therapy” protocol conducted at St Jude Research Hos- pital. The overall strategy remains the standard for the treatment of acute lymphocytic leukemia today: alternating combinations of drugs, consolidating remission with intensive postinduction chemotherapy followed by prolonged main- tenance, and incorporating therapy specifically designed to prevent primary central nervous system relapse. Their pa- tients experienced a median survival of 135 weeks and a median of 78 weeks in complete remission, and at the time of their report almost one-half of the patients were still alive, several remaining in remission more than 3 years after diagnosis—results that would have been considered impossible just a few years before. During the intervening 50 years, improved outcomes largely have come about not through any major break- throughs in treatment—indeed, the armamentarium of chemotherapy agents used for childhood acute lymphocytic leukemia is only modestly larger than in the 1960s—but rather through progressive incremental improvements in care. Just as St Jude is currently enrolling into “Total XVII,” the pediatric cooperative groups and consortia in North America and Europe have conducted many large multi-institutional trials that successively have built on each other’s successes—a testimony to the progress that can result from carefully designed and executed clinical research combined with an in- ternational commitment to collaboration. Such research is likely to become even more important as we enter the era of precision medicine and the development of therapies that more specifically target the abnormal molecules and path- ways that drive the malignant phenotype of most cancers. William S. Ferguson,MD Division of Pediatric Hematology-Oncology Saint Louis University of Medicine St Louis, Missouri Reference 1. Farber S, Diamond LK, Mercer RD, Sylvester RF, Wolff JA. Temporary remission in acute leukemia in children produced by folic acid antago- nist, 4-amintopteroul-glutamic acid (aminopterin). N Engl J Med 1948;223:787-93. Frailty in Children with Liver Disease: A Prospective Multicenter Study http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Pediatrics Elsevier

50 Years Ago in The Journal of Pediatrics

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Abstract

March 2018 ORIGINAL ARTICLES 23. Krauss BS, Krauss BA, Green SM. Videos in clinical medicine. 28. Austin PW, Gerber L, Karrar AK. Fatigue in chronic liver disease: exploring Managing procedural anxiety in children. N Engl J Med 2016;374: the role of the autonomic nervous system. Liver Int 2015;35:1489-91. e19. 29. Bajaj JS. Diagnosing minimal hepatic encephalopathy: from the ivory tower 24. Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, et al. Evalu- to the real world. Gastroenterology 2015;149:1330-3. ation of the pediatric patient for liver transplantation: 2014 practice guide- 30. Zink AN, Perez-Leighton CE, Kotz CM. The orexin neuropeptide system: line by the American Association for the Study of Liver Diseases, American physical activity and hypothalamic function throughout the aging process. Society of Transplantation and the North American Society for Pediat- Front Syst Neurosci 2014;8:211. ric Gastroenterology, Hepatology and Nutrition. Hepatology 2014;60:362- 31. Berzigotti A, Saran U, Dufour JF. Physical activity and liver diseases. 98. Hepatology 2016;63:1026-40. 25. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly 32. Patterson C, So S, Schneiderman JE, Stephens D, Stephens S. Physical ac- people. Lancet 2013;381:752-62. tivity and its correlates in children and adolescents post-liver trans- 26. Cederholm T. Overlaps between frailty and sarcopenia definitions. Nestle plant. Pediatr Transplant 2016;20:227-34. Nutr Inst Workshop Ser 2015;83:65-9. 33. Ampuero J, Simon M, Montoliu C, Jover R, Serra MA, Cordoba J, et al. 27. van den Berg-Emons R, van Ginneken B, Wijffels M, Tilanus H, Metselaar Minimal hepatic encephalopathy and critical flicker frequency are asso- H, Stam H, et al. Fatigue is a major problem after liver transplantation. ciated with survival of patients with cirrhosis. Gastroenterology Liver Transpl 2006;12:928-33. 2015;149:1483-9. A Study of “Total Therapy” of Acute Lymphocytic Leukemia in Children George P, Hernendez K, Hustu O, Borella L, Holton C, Pinkel D. J Pediatr 1968;72:399-408 hildhood acute lymphoblastic leukemia, once universally fatal, now has cure rates that approach (and for some C clinical subgroups, exceed) 90%. Farber et al first demonstrated transient clinical responses to folate antagonists in the 1940s. However, it was not until the 1960s that combining multidrug therapy with continuation of mainte- nance chemotherapy well beyond the point of morphologic remission led to durable responses. Building on these early experiences, George et al reported in 1968 on the first “Total Therapy” protocol conducted at St Jude Research Hos- pital. The overall strategy remains the standard for the treatment of acute lymphocytic leukemia today: alternating combinations of drugs, consolidating remission with intensive postinduction chemotherapy followed by prolonged main- tenance, and incorporating therapy specifically designed to prevent primary central nervous system relapse. Their pa- tients experienced a median survival of 135 weeks and a median of 78 weeks in complete remission, and at the time of their report almost one-half of the patients were still alive, several remaining in remission more than 3 years after diagnosis—results that would have been considered impossible just a few years before. During the intervening 50 years, improved outcomes largely have come about not through any major break- throughs in treatment—indeed, the armamentarium of chemotherapy agents used for childhood acute lymphocytic leukemia is only modestly larger than in the 1960s—but rather through progressive incremental improvements in care. Just as St Jude is currently enrolling into “Total XVII,” the pediatric cooperative groups and consortia in North America and Europe have conducted many large multi-institutional trials that successively have built on each other’s successes—a testimony to the progress that can result from carefully designed and executed clinical research combined with an in- ternational commitment to collaboration. Such research is likely to become even more important as we enter the era of precision medicine and the development of therapies that more specifically target the abnormal molecules and path- ways that drive the malignant phenotype of most cancers. William S. Ferguson,MD Division of Pediatric Hematology-Oncology Saint Louis University of Medicine St Louis, Missouri Reference 1. Farber S, Diamond LK, Mercer RD, Sylvester RF, Wolff JA. Temporary remission in acute leukemia in children produced by folic acid antago- nist, 4-amintopteroul-glutamic acid (aminopterin). N Engl J Med 1948;223:787-93. Frailty in Children with Liver Disease: A Prospective Multicenter Study

Journal

The Journal of PediatricsElsevier

Published: Mar 1, 2018

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