abstract of New England Journal of Medicine www.lib.hukm.ukm.my Volume 359, Number 24 & 25- 11 & 18 Dec, 2008 UKM Medical Centre Library © NEJM - 359(24)&(25), 11 & 18 Dec, 2008 1 table of contents ARTICLES Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. Bejon, P., John Lusingu, Ally Olotu, Amanda Leach, Marc Lievens, Johan Vekemans, Salum Mshamu, Trudie Lang, Jayne Gould, Marie-Claude Dubois, Marie-Ange Demoitie, Jean-Francois Stallaert, Preeti Vansadia, Terrell Carter, Patricia Njuguna, Ken O. Awuondo, Anangisye Malabeja, Omar Abdul, Samwel Gesase, Neema Mturi, Chris J. Drakeley, Barbara Savarese, Tonya Villafana, W. Ripley Ballou, Joe Cohen, Eleanor M. Riley, Martha M. Lemnge, Kevin Marsh, and Lorenz von Seidlein. Outbreak of adverse reactions associated with contaminated heparin. Blossom, D.B., Alexander J. Kallen, Priti R. Patel, Alexis Elward, Luke Robinson, Ganpan Gao, Robert Langer, Kiran M. Perkins, Jennifer L. Jaeger, Katie M. Kurkjian, Marilyn Jones, Sarah F. Schillie, Nadine Shehab, Daniel Ketterer, Ganesh Venkataraman, Takashi Kei Kishimoto, Zachary Shriver, Ann W. McMahon, K. Frank Austen, Steven Kozlowski, Arjun Srinivasan, George Turabelidze, Carolyn V. Gould, Matthew J. Arduino, and Ram Sasisekharan. Thrombolysis during resuscitation for out-of-Hospital Cardiac Arrest. Bottiger, B.W., Hans-Richard Arntz, Douglas A. Chamberlain, Erich Bluhmki, Ann Belmans, Thierry Danays, Pierre A. Carli, Jennifer A. Adgey, Christoph Bode, Volker Wenzel. Effect of aspirin or r esistant starch on colorectal neoplasia in the lynch syndrome. Burn, J., D. Timothy Bishop, Jukka-Pekka Mecklin, Finlay Macrae, Gabriela Moslein, Sylviane Olschwang, Marie-Luise Bisgaard, Raj Ramesar, Diana Eccles, Eamonn R. Maher, Lucio Bertario, Heikki J. Jarvinen, Annika Lindblom, D. Gareth Evans, Jan Lubinski, Patrick J. Morrison, Judy W.C. Ho, Hans F.A. Vasen, Lucy Side, Huw J.W. Thomas, Rodney J. Scott, Malcolm Dunlop, Gail Barker, Faye Elliott, Jeremy R. Jass, Ricardo Fodde, Henry T. Lynch, and John C. Mathers. An obesity-associated FTO gene variant and increased energy intake in children. Cecil, J.E., Roger Tavendale, Peter Watt, Marion M. Hetherington, and Colin N.A. Palmer A trial of combination antimalarial therapies in children from Papua New Guinea. Karunajeewa, H.A., Ivo Mueller, Michele Senn, Enmoore Lin, Irwin Law, Servina Gomorrai, Olive Oa, Suzanne Griffin, Kaye Kotab, Penias Suano, Nandao Tarongka, Alice Ura, Dulcie Lautu, Madhu Page-Sharp, Rina Wong, Sam Salman, Peter Siba, Kenneth F. Ilett, and Timothy M.E. Davis. Dicer, drosha, and outcomes in patients with ovarian cancer. Merritt, W.M., Yvonne G. Lin, Liz Y. Han, Aparna A. Kamat, Whitney A. Spannuth, Rosemarie Schmandt, Diana Urbauer, Len A. Pennacchio, Jan-Fang Cheng, Alpa M. Nick, Michael T. Deavers, Alexandra Mourad-Zeidan, Hua Wang, Peter Mueller, Marc E. Lenburg, Joe W. Gray, Samuel Mok, Michael J. Birrer, Gabriel Lopez-Berestein, Robert L. Coleman, Menashe Bar-Eli, and Anil K. Sood. Alfuzosin and symptoms of chronic prostatitis–chronic pelvic pain syndrome. Nickel, J.C., John N. Krieger, Mary McNaughton-Collins, Rodney U. Anderson, Michel Pontari, Daniel A. Shoskes, Mark S. Litwin, Richard B. Alexander, Paige C. White, Richard Berger, Robert Nadler, Michael O’Leary, Men Long Liong, Scott Zeitlin, Shannon Chuai, J. Richard Landis, John W. Kusek, Leroy M. Nyberg, Anthony J. Schaeffer. Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. Salim Abdulla, Rolf Oberholzer, Omar Juma, Sulende Kubhoja, Francisca Machera, Christopher Membi, Said Omari, Alwisa Urassa, Hassan Mshinda, Ajuza Jumanne, Nahya Salim, Mwanjaa Shomari, Thomas Aebi, David M. Schellenberg, Terrell Carter, Tonya Villafana, Marie-Ange Demoitie, Marie-Claude Dubois, Amanda Leach, Marc Lievens, Johan Vekemans, Joe Cohen, W. Ripley Ballou, and Marcel Tanner. CLINICAL PRACTICE Prevention and treatment of seasonal influenza. Glezen, W.P. IMAGES IN CLINICAL MEDICINE Subungual exostosis. A. Campanelli and L. Borradori. Bone destruction and regeneration in a patient with breast cancer. A. Malani and R. M. Abou-Jawde. Periungual Tungiasis. M. Muehlstaedt. Postpartum venous thromboembolism. R. Zalts and T. Hayek. CASE RECORDS OF THE MASSACHUSETTES GENERAL HOSPITAL Case 39-2008: a 51- year-old woman with splenomegaly and anemia. Abramson, J.S., Manjil Chatterji, and Aliyah Rahemtullah. Case 38-2008 — A 58-Year-Old Man with Hemophilia, Hepatocellular Carcinoma, and Intractable Bleeding. Dzik, W.H., Michael Laposata, Martin Hertl, Warren S. Sandberg, Manjil Chatterji, M.D., and Joseph Misdraji. REVIEW ARTICLE Medical progress: emporomandibular disorders. Scrivani, S., David A. Keith, and Leonard B. Kaban. NEJM - 359 (24)&(25), 11 & 18 Dec, 2008 2 ARTICLES Bejon, P., John Lusingu, Ally Olotu, Amanda Leach, Marc Lievens, Johan Vekemans, Salum Mshamu, Trudie Lang, Jayne Gould, MarieClaude Dubois, Marie-Ange Demoitie, JeanFrancois Stallaert, Preeti Vansadia, Terrell Carter, Patricia Njuguna, Ken O. Awuondo, Anangisye Malabeja, Omar Abdul, Samwel Gesase, Neema Mturi, Chris J. Drakeley, Barbara Savarese, Tonya Villafana, W. Ripley Ballou, Joe Cohen, Eleanor M. Riley, Martha M. Lemnge, Kevin Marsh, and Lorenz von Seidlein. (2008). Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. New En gland Journal of Medicine, 359 (24), 24122415. Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure. RTS,S/AS01E shows promise as a candidate malaria vaccine. Blossom, D.B., Alexander J. Kallen, Priti R. Patel, Alexis Elward, Luke Robinson, Ganpan Gao, Robert Langer, Kiran M. Perkins, Jennifer L. Jaeger, Katie M. Kurkjian, Marilyn Jones, Sarah F. Schillie, Nadine Shehab, Daniel Ketterer, Ganesh Venkataraman, Takashi Kei Kishimoto, Zachary Shriver, Ann W. McMahon, K. Frank Austen, Steven Kozlowski, Arjun Srinivasan, George Turabelidze, Carolyn V. Gould, Matthew J. Arduino, and Ram Sasisekharan. (2008). Outbreak of adverse reactions associated with contaminated heparin. New England Journal of Medicine, 359 (25), 2674-7684. In January 2008, the Centers for Disease Control and Prevention began a nationwide investigation of severe adverse reactions that were first detected in a single hemodialysis facility. Preliminary findings suggested that heparin was a possible cause of the reactions. Heparin contaminated with OSCS was epidemiologically linked to adverse reactions in this nationwide outbreak. The reported clinical features of many of the cases further support the conclusion that contamination of heparin with OSCS was the cause of the outbreak. England Journal of Medicine, 359 (25), 2651-2662. Approximately 70% of persons who have an out-ofhospital cardiac arrest have underlying acute myocardial infarction or pulmonary embolism. Therefore, thrombolysis during cardiopulmonary resuscitation may improve survival. When tenecteplase was used without adjunctive antithrombotic therapy during advanced life support for out-of-hospital cardiac arrest, we did not detect an improvement in outcome, in comparison with placebo. Burn, J., D. Timothy Bishop, Jukka-Pekka Mecklin, Finlay Macrae, Gabriela Moslein, Sylviane Olschwang, Marie-Luise Bisgaard, Raj Ramesar, Diana Eccles, Eamonn R. Maher, Lucio Bertario, Heikki J. Jarvinen, Annika Lindblom, D. Gareth Evans, Jan Lubinski, Patrick J. Morrison, Judy W.C. Ho, Hans F.A. Vasen, Lucy Side, Huw J.W. Thomas, Rodney J. Scott, Malcolm Dunlop, Gail Barker, Faye Elliott, Jeremy R. Jass, Ricardo Fodde, Henry T. Lynch, and John C. Mathers. (2008). Effect of aspirin or resistant starch on colorectal neoplasia in the lynch syndrome. New England Journal of Medicine, 359 (24), 2567-2578. Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect on the colon. The use of aspirin, resistant starch, or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. Cecil, J.E., Roger Tavendale, Peter Watt, Marion M. Hetherington, and Colin N.A. Palmer. (2008). An obesity-associated FTO gene variant and increased energy intake in children. New England Journal of Medicine, 359 (24), 2558-2566. Variation in the fat mass and obesity–associated (FTO) gene has provided the most robust associations with common obesity to date. However, the role of FTO variants in modulating specific components of energy balance is unknown. The FTO variant that confers a predisposition to obesity does not appear to be involved in the regulation of energy expenditure but may have a role in the control of food intake and food choice, suggesting a link to a hyperphagic phenotype or a preference for energy-dense foods. Bottiger, B.W., Hans-Richard Arntz, Douglas A. Chamberlain, Erich Bluhmki, Ann Belmans, Thierry Danays, Pierre A. Carli, Jennifer A. Adgey, Christoph Bode, Volker Wenzel. (2008). Thrombolysis during resuscitation for out-of-Hospital Cardiac Arrest. New NEJM - 359(24)&(25), 11 & 18 Dec, 2008 3 Karunajeewa, H.A., Ivo Mueller, Michele Senn, Enmoore Lin, Irwin Law, Servina Gomorrai, Olive Oa, Suzanne Griffin, Kaye Kotab, Penias Suano, Nandao Tarongka, Alice Ura, Dulcie Lautu, Madhu Page-Sharp, Rina Wong, Sam Salman, Peter Siba, Kenneth F. Ilett, and Timothy M.E. Davis. (2008). A trial of combination antimalarial therapies in children from Papua New Guinea. New England Journal of Medicine, 359 (24), 2545-2557. Malaria control is difficult where there is intense yearround transmission of multiple plasmodium species, such as in Papua New Guinea. The most effective regimens were artemether–lumefantrine against P. falciparum and dihydroartemisinin–piperaquine against P. vivax. The relatively high rate of treatment failure with dihydroartemisinin–piperaquine against P. falciparum may reflect cross-resistance between chloroquine and piperaquine. Merritt, W.M., Yvonne G. Lin, Liz Y. Han, Aparna A. Kamat, Whitney A. Spannuth, Rosemarie Schmandt, Diana Urbauer, Len A. Pennacchio, Jan-Fang Cheng, Alpa M. Nick, Michael T. Deavers, Alexandra MouradZeidan, Hua Wang, Peter Mueller, Marc E. Lenburg, Joe W. Gray, Samuel Mok, Michael J. Birrer, Gabriel Lopez-Berestein, Robert L. Coleman, Menashe Bar-Eli, and Anil K. Sood. (2008). Dicer, drosha, and outcomes in patients with ovarian cancer. New England Journal of Medicine, 359 (25), 2641-2650. We studied Dicer and Drosha, components of the RNAinterference machinery, in ovarian cancer. Our findings indicate that levels of Dicer and Drosha mRNA in ovarian-cancer cells have associations with outcomes in patients with ovarian cancer. Nickel, J.C., John N. Krieger, Mary McNaughtonCollins, Rodney U. Anderson, Michel Pontari, Daniel A. Shoskes, Mark S. Litwin, Richard B. Alexander, Paige C. White, Richard Berger, Robert Nadler, Michael O’Leary, Men Long Liong, Scott Zeitlin, Shannon Chuai, J. Richard Landis, John W. Kusek, Leroy M. Nyberg, Anthony J. Schaeffer. (2008). Alfuzosin and symptoms of chronic prostatitis–chronic pelvic pain syndrome. New England Journal of Medicine, 359 (25), 2663-2673. In men with chronic prostatitis–chronic pelvic pain syndrome, treatment with alpha-adrenergic receptor blockers early in the course of the disorder has been reported to be effective in some, but not all, relatively small randomized trials. Our findings do not support the use of alfuzosin to reduce the symptoms of chronic prostatitis–chronic pelvic pain syndrome in men who have not received prior treatment with an alpha- blocker. Salim Abdulla, Rolf Oberholzer, Omar Juma, Sulende Kubhoja, Francisca Machera, Christopher Membi, Said Omari, Alwisa Urassa, Hassan Mshinda, Ajuza Jumanne, Nahya Salim, Mwanjaa Shomari, Thomas Aebi, David M. Schellenberg, Terrell Carter, Tonya Villafana, Marie-Ange Demoitie, Marie-Claude Dubois, Amanda Leach, Marc Lievens, Johan Vekemans, Joe Cohen, W. Ripley Ballou, and Marcel Tanner. (2008). Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. New England Journal of Medicine, 359 (24), 2533-2544. The RTS,S/AS malaria vaccine is being developed for delivery through the World Health Organization’s Expanded Program on Immunization (EPI). We assessed the feasibility of integrating RTS,S/AS02D into a standard EPI schedule for infants. The use of the RTS,S/AS02D vaccine in infants had a promising safety profile, did not interfere with the immunologic responses to coadministered EPI antigens, and reduced the incidence of malaria infection. CLINICAL PRACTICE Glezen, W.P. (2008). Prevention and treatment of seasonal influenza. New England Journal of Medicine, 359 (24), 2579-2585. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations. In February 2007, fever developed in a previously healthy 15-year-old girl, with a peak temperature of 102°F (38.9°C) and mild upper respiratory congestion. The next day she was seen by her primary care physician. A rapid screening test for group A streptococcus was negative, and oseltamivir was prescribed. After two doses, she continued to have fever and also had nausea and emesis, . . . IMAGES IN CLINICAL MEDICINE A. Campanelli and L. Borradori. (2008). Subungual exostosis. New England Journal of Medicine, 359 (25), e31. A 12-year-old girl with an unremarkable history was evaluated for a nodule of the lateral nail fold on the right hallux that had been present for 3 months (Panel A). The lesion, which was initially believed to be a wart, was treated with a topical salicylic acid preparation, with no improvement. The nodule measured 10 mm in diameter, and the distal nail plate showed onycholysis and had been destroyed. A radiograph revealed a calcifying projection on the dorsolateral part of the distal phalanx, continuous with NEJM - 359 (24)&(25), 11 & 18 Dec, 2008 4 the underlying bone (Panel B), the features of which were consistent with a subungual exostosis. . . . CASE RECORDS OF THE MASSACHUSETTES GENERAL HOSPITAL A. Malani and R. M. Abou-Jawde. (2008). Bone destruction and regeneration in a patient with breast cancer. New England Journal of Medicine, 359 (24), 2586. A 58-year-old woman presented with a cavitating left breast lesion and increasing pain in the left arm. For over a year she had noticed an enlarging breast mass but did not seek medical advice. Imaging showed metastatic disease in the chest and brain. Serum calcium and alkaline phosphatase levels were within the normal range. Since she had a marked decrease in function of her left arm, a plain radiograph was obtained. The image disclosed a destructive process involving the proximal humerus, with multiple pathologic fractures, presumably due to bony metastatic disease (Panel A). Palliative left total mastectomy was performed. The . . . Abramson, J.S., Manjil Chatterji, and Aliyah Rahemtullah. (2008). Case 39-2008: a 51year-old woman with splenomegaly and anemia. New England Journal of Medicine, 359 (25), 2707-2718. Dr. Jeffrey A. Barnes (Hematology–Oncology): A 51year-old woman was admitted to this hospital because of anemia and splenomegaly. The patient was in her usual state of health until approximately 2 months before admission, when fatigue developed, followed by night sweats, left-upper-quadrant fullness, early satiety, edema of the legs, and dyspnea on exertion. Furosemide was prescribed, but symptoms persisted. One month before admission, she was admitted to another hospital. On examination, the spleen extended to the pelvic brim and the legs were edematous. A direct Coombs’ test was negative for IgG and complement. Other laboratory-test results are shown in Table 1. . . M. Muehlstaedt. (2008). Periungual Tungiasis. New England Journal of Medicine, 359 (24),e30. A healthy 35-year-old man presented with small eggs and a brownish lesion on the medial edge of his right big toe (Panel A). Two weeks before presentation, he had returned from a holiday trip to Brazil, where he had been barefoot. The patient was afebrile and without malaise. The brownish part (the decomposing adult sand flea) was excised, and multiple eggs appeared after the application of lateral pressure (Panel B). After disinfection, a sterile dressing was applied. The patient had a complete recovery with no additional symptoms. Tungiasis is an ectoparasitosis in which the fertilized female sand flea . . . R. Zalts and T. Hayek. (2008). Postpartum venous thromboembolism. New England Journal of Medicine, 359 (25), 2706. A previously healthy 34-year-old woman, gravida 7, para 5, presented on postpartum day 14 with severe low back pain, chest pain, dyspnea, and substantial swelling of both legs after an uneventful cesarean section, performed with combined spinal–epidural anesthesia. During that period she was bedridden. Examination of the pelvis and legs with Doppler ultrasonography revealed bilateral deep venous thrombosis extending to the iliac veins. A computed tomographic (CT) scan of the abdomen and pelvis showed the thrombus extending through the inferior vena cava and both ovarian veins (Panel A, arrowheads). A CT scan of the chest showed pulmonary embolism in the . . . Dzik, W.H., Michael Laposata, Martin Hertl, Warren S. Sandberg, Manjil Chatterji, M.D., and Joseph Misdraji. (2008). Case 38-2008 — A 58-Year-Old Man with Hemophilia, Hepatocellular Carcinoma, and Intractable Bleeding. New England Journal of Medicine, 359 (24), 2587-2597. Dr. Abner Louissaint (Pathology): A 58-year-old man with hemophilia was admitted to this hospital because of hepatitis C infection, hepatocellular carcinoma, and recurrent bleeding. A diagnosis of hemophilia A (factor VIII deficiency) had been made in infancy. The hemophilia was manifested by multiple hemarthroses, was treated with multiple transfusions of blood products and clotting factors, and was complicated by hepatitis C infection (genotype 1a). Two years before admission, a liver biopsy revealed chronic hepatitis with a score of 3 for portal activity and a score of 2 for lobular activity, with bridging . . . REVIEW ARTICLE Scrivani, S., David A. Keith, and Leonard B. Kaban. (2008). Medical progress: emporomandibular disorders. New England Journal of Medicine, 359 (25), 2693-2705. The temporomandibular joint (TMJ) may be affected by inflammatory, traumatic, infectious, congenital, developmental, and neoplastic diseases, as seen in other joints. However, the most common affliction of the TMJ and masticatory apparatus is a group of functional disorders with associated pain that occurs predominantly in women and was previously known as the TMJ pain dysfunction syndrome. Since 1978, there have been substantial changes in the study of etiologic factors, pathophysiology, diagnosis, and management of what are now called temporomandibular disorders. NEJM - 359(24)&(25), 11 & 18 Dec, 2008 5 NEJM - 359 (24)&(25), 11 & 18 Dec, 2008 6 NEJM - 359(24)&(25), 11 & 18 Dec, 2008 7