Memorial Hospital

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
\nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198,
\nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544,
\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
\nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007,
\nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591,
\nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930,
\nThierry Arnould1773, Ivica Arsov2120, Katsuhiko Asanuma675, Valerie Askanas1924, Eric Asselin1867, Ryuichiro Atarashi794,
\nSally S Atherton369, Julie D Atkin713, Laura D Attardi1131, Patrick Auberger1787, Georg Auburger379, Laure Aurelian1727,
\nRiccardo Autelli1992, Laura Avagliano1029,1755, Maria Laura Avantaggiati364, Limor Avrahami1166, Suresh Awale1986,
\nNeelam Azad404, Tiziana Bachetti568, Jonathan M Backer28, Dong-Hun Bae1933, Jae-sung Bae677, Ok-Nam Bae409,
\nSoo Han Bae2117, Eric H Baehrecke1729, Seung-Hoon Baek17, Stephen Baghdiguian1368,
\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
\nG abor B anhegyi1052, Haijun Bao2109, Benoit Barbeau1363, Maria D Barrachina2007, Esther Barreiro467, Bonnie Bartel997,
\nAlberto Bartolom e222, Diane C Bassham550, Maria Teresa Bassi1046, Robert C Bast Jr1273, Alakananda Basu1798,
\nMaria Teresa Batista1578, Henri Batoko1336, Maurizio Battino970, Kyle Bauckman2085, Bradley L Baumgarner1909,
\nK Ulrich Bayer1594, Rupert Beale1553, Jean-Fran¸cois Beaulieu1360, George R. Beck Jr48,294, Christoph Becker336,
\nJ David Beckham1595, Pierre-Andr e B edard749, Patrick J Bednarski301, Thomas J Begley1135, Christian Behl1419,
\nChristian Behrends757, Georg MN Behrens406, Kevin E Behrns1627, Eloy Bejarano26, Amine Belaid490,
\nFrancesca Belleudi1041, Giovanni B enard497, Guy Berchem706, Daniele Bergamaschi983, Matteo Bergami1401,
\nBen Berkhout1441, Laura Berliocchi714, Am elie Bernard1749, Monique Bernard1354, Francesca Bernassola1880,
\nAnne Bertolotti791, Amanda S Bess272, S ebastien Besteiro1351, Saverio Bettuzzi1828, Savita Bhalla913,
\nShalmoli Bhattacharyya973, Sujit K Bhutia838, Caroline Biagosch1159, Michele Wolfe Bianchi520,1378,1381,
\nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112,
\nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812,
\nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287,
\nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308,
\nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901,
\nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141,
\nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374,
\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
\nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217,
\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
\nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318,
\nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462,
\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

An inquiry has been made into conditions which may influence the viability of 1×1 cm areas of biopsied rabbit skin during refrigeration at 0° and 6-8°C. Since the availability of oxygen, as well as the nature of the storage medium, had an, important influence on the preservation of viability at these two temperatures, these relationships may be of interest to those wishing to store or ship tissues for surgical and other purposes. Tissues separated from the circulation rapidly become anoxemic and necrotic at room or body temperatures. This condition may be prevented in uterine or intestinal strips by oxygenation or by chilling., The survival of ligated limbs and of the cells in whole embryos, or organs, is optimal (among the widely spaced temperatures which have been studied) at 0°. At this temperature respiration is minimal, while oxygen solubility in water is twice that at 30°. Though Lambert Carrel, and Hetherington and Craig found 0 to 7° favorable for preserving the small masses of crowded cells in embryonic tissue fragments, there is considerable evidence that the thin perimeter of migrating and dividing cells in established tissue cultures has maximal longevity around 30° and are unable to re-establish growth after refrigeration for a few days., , Upon considering the fact that large tissues are killed more rapidly at higher temperatures and small groups of thinly spread cells at low temperatures, it seemed not unlikely that one of the common denominators might be a question of oxygen supply and demand. Methods. After shaving and scrubbing, the chosen area of rabbit skin was covered for 2 minutes with a wet pack of tincture of iodine diluted 1:2 in water, and again scrubbed with alcohol. The strips of biopsied skin, either full- or half-skin depth were cut into 1×1 cm pieces.

Importance: Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. Objective: To determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer. Design, Setting, and Participants: Patients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015. Interventions: Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient. Main Outcomes and Measures: The primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response. Results: Among 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0-110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77-1.01; P = .08). The median progression-free survival was 10.5 months in the cetuximab-chemotherapy group and 10.6 months in the bevacizumab-chemotherapy group with a stratified HR of 0.95 (95% CI, 0.84-1.08; P = .45). Response rates were not significantly different, 59.6% vs 55.2% for cetuximab and bevacizumab, respectively (difference, 4.4%, 95% CI, 1.0%-9.0%, P = .13). Conclusions and Relevance: Among patients with KRAS wt untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment. Trial Registration: clinicaltrials.gov identifier: NCT00265850.

Department of Anaesthesia; Orillia Soldiers' Memorial Hospital; Orillia, Ontario, Canada L3V 1Y2; E-mail: oyston@oyston.comJames C. Eisenach, M.D., EditorURL: http://www3.ncbi.nlm.nih.gov/Omim/Sponsor: Johns Hopkins University, Baltimore, MarylandAuthor: Dr. Victor A. McKusick and colleaguesWeb Version: National Center for Biotechnology InformationReaders of this column may be interested in Online Mendelian Inheritance in Man (OMIM) for two reasons: Firstly, some patients have genetic conditions that must be considered when planning anesthesia. Secondly, it is an excellent demonstration of the use of the Internet to make a vast amount of medical information widely available in a format that is more convenient to use and more up-to-date than would be possible in any other way.OMIM is a database with 9,145 entries, each reviewing a specific genetic disease, which is continually being updated at the rate of 60 new entries and 500 revisions per month by Dr. Victor A. McKusick and his colleagues at Johns Hopkins University and elsewhere. It has been made freely available on the Web by the National Center for Biotechnology Information. The site begins with a warning: "OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. Non-medical users are strongly urged to seek the assistance of an expert in the interpretation of OMIM text and images."The site consists of plain text with small link buttons. Animations, Java, frames, plug-ins, and multimedia are not used. Unfortunately, a link to the Cedars-Sinai Medical Center Genetics Image Archive was not available at the time of this review.For anesthesiologists, the most important feature is the search engine. Type in almost any variation of any name for an inherited disease, and, if spelling is correct, a link will be provided to the appropriate entry for that disease. Because many genetic syndromes have various names, this is more convenient than most textbook indices. A facility that offers alternative spelling when a search produces no results would be a useful addition.Each disease entry is presented as a Web page. A Table ofcontents provides shortcuts to sections that typically include "Clinical Features," "Diagnosis," "Clinical Management," and "References," and several sections that would only interest a geneticist, such as "Population Genetics." A clinical synopsis is sometimes available as a separate Web page.Each entry is referenced heavily, with links from the text to the relevant PubMed abstract. The full text can be ordered online through "Loansome Doc." There are extensive links to MEDLINE and to other genetics resources. Each page has a link to a form that can be used to add comments or new information.I compared OMIM to two standard anesthetic textbooks, Anesthesia and Co-Existing Disease, 3rd edition, 1993, by Stoelting and Dierdorf, and Anesthesia and Uncommon Diseases, 4th edition, 1998, by Benumof. I searched each resource for information about five genetic conditions of interest to anesthetists, which I saw recently in the preadmission clinic.The anesthetic textbooks both had extensive and detailed accounts of this condition, indexed under both words. OMIM has 11 pages about "hyperthermia of anesthesia." This contains a good history of the disease from the first case report in 1962 to recent developments, but no practical information for anesthesiologists. There was no link to clinical resources such as the Malignant Hyperthermia Association of the United States Emergency Hotline.The anesthetic texts mentioned pseudocholinesterase only in the context of liver disease. OMIM had no relevant information. Perhaps an inherited enzyme deficiency is not really a disease, but it was surprising that none of the resources mentioned this condition.Both anesthetic textbooks had more than a page of information, although Anesthesia and Uncommon Diseases indexed acute intermittent porphyria under "H" for "hepatic porphyrias." Both textbooks listed safe and unsafe anesthetic drugs. OMIM has 23 pages of text with 82 references. Although the section about clinical features mentions that attacks can be precipitated by barbiturates or sulfonamides, there was not enough information to plan a safe anesthetic.Both anesthetic texts had brief entries that mentioned difficult tracheal intubation and the risk of malignant hyperthermia. OMIM produced five pages of information, including 26 references (compared with five between the two textbooks), but none of the references were to anesthesia journals, and there was no mention of difficult tracheal intubation or malignant hyperthermia.Anesthesia and Co-Existing Disease had 134 words, half of which was about anesthetic implications, indexed under both names, whereas Anesthesia and Uncommon Diseases provided 118 words, indexed only under "Osler-Weber-Rendu." Each had one reference. OMIM had 16 pages and 82 references. An extensive history section included fascinating nuggets, including the correct pronunciation ("OHz-ler, ren-DYU, and VAY-ber"), with a note that Weber "pronounced his name in the Germanic manner even though he was born in England."OMIM is an invaluable resource for physicians dealing with patients with genetic diseases. It uses the Web to make medical information accessible in a way that should inspire other specialties to develop similar resources. Although it does not contain enough anesthesia-related information to act as a sole source of information about genetic conditions for anesthesiologists, it would be of great benefit to any anesthesiologist writing a consult note, preparing rounds, or publishing a case report about a patient with an inheritable condition.John Oyston, M.B., B.S., F.F.A.R.C.S.Department of Anaesthesia; Orillia Soldiers' Memorial Hospital; Orillia, Ontario, Canada L3V 1Y2; E-mail: oyston@oyston.com

Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and persistent (>21 d) activation of JNK, in particular JNK1, in GFAP-expressing astrocytes in the spinal cord. In contrast, p38 mitogen-activated protein kinase activation was found in spinal microglia after SNL, which had fallen to near basal level by 21 d. Intrathecal infusion of a JNK peptide inhibitor, D-JNKI-1, did not affect normal pain responses but potently prevented and reversed SNL-induced mechanical allodynia, a major symptom of neuropathic pain. Intrathecal D-JNKI-1 also suppressed SNL-induced phosphorylation of the JNK substrate, c-Jun, in spinal astrocytes. However, SNL-induced upregulation of GFAP was not attenuated by spinal D-JNKI-1 infusion. Furthermore, SNL induced a rapid (<12 h) but transient activation of JNK in the L5 (injured) but not L4 (intact) DRG. JNK activation in the DRG was mainly found in small-sized C-fiber neurons. Infusion of D-JNKI-1 into the L5 DRG prevented but did not reverse SNL-induced mechanical allodynia. Finally, intrathecal administration of an astroglial toxin, l-alpha-aminoadipate, reversed mechanical allodynia. Our data suggest that JNK activation in the DRG and spinal cord play distinct roles in regulating the development and maintenance of neuropathic pain, respectively, and that spinal astrocytes contribute importantly to the persistence of mechanical allodynia. Targeting the JNK pathway in spinal astroglia may present a new and efficient way to treat neuropathic pain symptoms.

BACKGROUND: The purposes of this retrospective study were to review the results of isolated subtalar arthrodesis in adults and to identify factors influencing the union rate. The hypotheses were that (1) the overall outcome is acceptable but is not as favorable as previously reported, (2) complication rates, especially the nonunion rate, are higher than previously reported, and (3) factors contributing to a less favorable union rate can be identified. METHODS: Between January 1988 and July 1995, 184 consecutive isolated subtalar arthrodeses were performed in 174 adults (115 men and fifty-nine women) whose average age was forty-three years (range, eighteen to seventy-nine years). Eighty patients (46 percent) were smokers. The indications for the procedure included posttraumatic arthritis after a fracture of the calcaneus (109 feet), a fracture of the talus (thirteen feet), or a subtalar dislocation (thirteen feet); primary subtalar arthritis (thirteen feet); failure of a previous subtalar arthrodesis (twenty-eight feet); and residual congenital deformity (eight feet). Rigid internal fixation with one or two screws was used for all feet. Bone graft was used in 145 feet; the types of graft material included cancellous autograft (ninety-four feet), structural autograft (twenty-nine feet), cancellous allograft (seventeen feet), and structural allograft (five feet). Bone graft was not used in the remaining thirty-nine feet. RESULTS: Clinical and radiographic follow-up examinations were performed for 148 (80 percent) of the 184 feet at an average of fifty-one months (range, twenty-four to 130 months) postoperatively. The average ankle-hindfoot score according to the modified scale of the American Orthopaedic Foot and Ankle Society (maximum possible score, 94 points) improved from 24 points preoperatively to 70 points at follow-up. Thirty feet had clinical evidence of nonunion. The union rate was 84 percent (154 of 184) overall, 86 percent (134 of 156) after primary arthrodesis, and 71 percent (twenty of twenty-eight) after revision arthrodesis. The union rate was 92 percent (ninety-three of 101 feet) for nonsmokers and 73 percent (sixty-one of eighty-three feet) for smokers (p < 0.05). Intraoperative inspection revealed that 42 percent (seventy-eight) of the 184 feet had evidence of more than two millimeters of avascular bone at the subtalar joint; all thirty nonunions occurred in this group (p < 0.05). A nonunion occurred in three of the five feet that had been treated with structural allograft and in two of the six feet in which the subtalar arthrodesis had been performed adjacent to the site of a previous ankle arthrodesis. After elimination of the subgroups of feet in patients who smoked, those that had had a failure of a previous subtalar arthrodesis, those that had been treated with a structural graft, and those that had had the subtalar arthrodesis adjacent to the site of a previous ankle arthrodesis, the union rate improved to 96 percent (seventy-three of seventy-six). Complications other than nonunion included prominent hardware requiring screw removal (thirty-six of 184 feet; 20 percent), lateral impingement (fifteen of 148 feet; 10 percent), symptomatic valgus malalignment (five of 148 feet; 3 percent), symptomatic varus malalignment (four of 148 feet; 3 percent), and infection (five of 184 feet; 3 percent). CONCLUSIONS: To the best of our knowledge, the present study includes the largest reported series of isolated subtalar arthrodeses in adults. Our results suggest that the outcome following isolated subtalar arthrodesis is not as favorable as has been reported in previous studies. The rate of union was significantly diminished by smoking, the presence of more than two millimeters of avascular bone at the arthrodesis site, and the failure of a previous subtalar arthrodesis (p < 0.05 for all). Other factors that probably affect the union rate include the use of structural allograft and performance of the arthrodesis adjac

The incretin system has become an important target in the treatment of type 2 diabetes in recent years, and glucagon-like peptide 1 (GLP-1) is of particular interest for its glucose-lowering effects. The physiological response to oral ingestion of nutrients, involving the incretin system, is reduced in some patients with type 2 diabetes but may be augmented by administration of GLP-1 receptor agonists. The GLP-1 receptor agonists currently approved in the United States for the treatment of type 2 diabetes include exenatide (administered twice daily), liraglutide and lixisenatide (administered once daily), and the once-weekly agents exenatide extended-release, albiglutide, and dulaglutide. These agents have been shown to reduce A1C (by ∼0.8-1.6%), body weight (by ∼1-3 kg), blood pressure, and lipids. GLP-1 receptor agonists are associated with a low risk of hypoglycemia, and the most common adverse effects are gastrointestinal. Proper patient selection and education can assist in achieving positive treatment outcomes.

Summary and conclusionsDifferentiation between life and death in unicellular beings should be based upon criteria which are more convenient and fundamental than measurements of capacity for growth. The principle of ion (eosin) exclusion has been substantiated as a simple, rapid tool for this purpose. The conditions for valid observations in cell and tissue cultures have been delineated in respect to: eosin, serum and electrolyte concentrations. These simplified methods have replaced cultivation procedures in studies on: the effects of exposure to pancreatin and to drying, and the exposure of sensitive cells to tuberculin; storage of stock suspensions of cells without renewal of medium; and use of such methods for investigating nutritional or metabolic requirements.

The laser sheath uses optical fibers, delivering pulsed ultraviolet excimer laser light, to vaporize fibrotic tissue binding intravenous cardiac leads to the vein or heart wall during lead extraction from the implant vein. The total investigational experience with laser sheaths is reported. During the period from October 1995 to December 1999, 2,561 pacing and defibrillator leads were treated in 1,684 patients at 89 sites in the United States with three sizes of laser sheath. Endpoints were complete removal of the lead, partial removal (leaving the tip behind), or failure (abandoning the lead, onset of complications, change to transfemoral or transatrial approach). Minimal follow-up at 30 days was recorded. Of the leads, 90% were completely removed, 3% were partially removed, and the balance were failures. Major perioperative complications (tamponade, hemothorax, pulmonary embolism, lead migration, and death) were observed in 1.9% of patients with in hospital death in 13 (0.8%). Minor complications were seen in an additional 1.4% of patients. Multivariate analysis showed that implant duration was the only preoperative independent predictor of failure; female sex was the only multivariate predictor of complications. Success and complications were not dependent on laser sheath size. At follow-up, various extraction related complications were observed in 2% of patients. The learning curve showed a trend toward fewer complications with experience. Lead extraction with the laser sheath can be safely practiced with high success rates. Success is independent of laser sheath size. Major complications can be expected in < 2% of patients, and occur more often during an investigator's early experience.

From December 1988 to April 1994, the extraction of 2,195 intravascular pacing leads from 1,299 patients was attempted at 193 centers. Indications were: infection (54%, including 10% septicemia), pacemaker reoperation with removal of nonfunctional or incompatible leads (40%), and other causes (6%). Extraction was attempted via the implant vein using locking stylets and dilator sheaths, via the femoral vein using snares, retrieval baskets, and sheaths, or via both approaches. Leads had been implanted for 0.2 months to 24 years (mean 56 months). At the conclusion of the intravascular procedure, 86.8% of the leads were completely removed, 7.5% were partially removed, and 5.7% were not removed. For physicians performing their first case, 12% of leads were not removed; for physicians who had performed more than 10 cases, only 2% of leads were not removed. Of the 189 leads where extraction attempts had previously failed, 75.1% were completely removed, 14.8% were partially removed, and 10.1% were not removed. Scar tissue increased in severity with implant duration, was a complicating factor, and was the main cause of failure to remove leads. Use of the femoral approach increased with implant duration (5% of leads implanted 12 months or less, 11% of leads 13 months to 3 years, 20% of leads 4-7 years, and 31% of leads 8-24 years), primarily because of increasingly abundant scarring and prior lead damage. Fatal and near fatal complications occurred in 2.5%, including 8 (0.6%) deaths (3 hemopericardium/tamponade, 1 hemothorax, 3 pulmonary embolus, 1 stroke).(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied. METHODS: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients. RESULTS: We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval [CI], 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group. CONCLUSIONS: In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.).

While investigating the systemic effects of hista- mine in man, Weiss and his co-workers (1, 2) ob-

INFECTION with Toxoplasma gondii exists in chronic asymptomatic form in approximately 50 per cent of the population in the United States. T. gondii is clinically important in the adult for three major reasons: it may cause lymphadenopathy; as an opportunist, it may cause a lethal infection in the immunologically compromised host; and it is responsible for at least 3000 congenitally infected infants in the United States yearly, thus making correct interpretation of serologic tests in the woman who is pregnant (or thinking of becoming so) an urgent matter.1 , 2 Life CycleThe protozoan T. gondii is found throughout the world in . . .

Cell size and number of three adipose depots, epididymal, retroperitoneal, and subcutaneous, were determined during growth of the obese Zucker rat ("fatty") and nonobese Zucker control. Cellularity of these depots in the adult "fatty" was compared with that in nonobese controls and in nonobese Zucker rats made obese by ventromedial hypothalamic lesions. Epididymal and retroperitoneal depots in the nonobese rat grew by cell enlargement and increase in cell number until the 14th wk, when number became fixed; further increase in depot size occurred by cell enlargement. The subcutaneous depot added cells until the 26th wk. In the Zucker "fatty," cell number increased until the 26th wk in all depots, accompanied by extreme cell enlargement. The enlarged adipose depots of the adult Zucker "fatty," when compared with the nonobese control, are the result of both hypertrophy and hyperplasia. Depot enlargement in the lesioned animal is the result of hypertrophy. "Fatties" have more cells in adipose depots than do lesioned rats. Genetic obesity in the Zucker rat is clearly different from the obesity produced by hypothalamic lesioning.

Most knowledge about absorptive colonic func- tion in man is derived from the study of patients with ileostomies (1, 2) and the comparison of results with the composition of stools of normal subjects. To obtain more direct and quantitative information concerning water and salt absorption from the intact and healthy human colon, the fol- lowing studies were performed.

THROUGH the work of Bernard,1 , 2 Gaskell,3 , 4 Langley,5 6 7 8 Cannon,9 10 11 12 13 14 White,15 , 16 Smithwick,17 18 19 Kuntz20 and others, the diversified activities carried out by the autonomic nervous system have been greatly clarified. However, many aspects of these problems still challenge solution.If a portion of the autonomic nervous system is removed to modify a specific disease process, unrelated physiologic mechanisms will also be affected. The degree to which these other mechanisms may be affected often governs the selection of operative procedures. The results produced by interfering with mechanisms other than those for which the operation is performed might be designated as side-effects or secondary effects. . . .

Importance: Studies showing that patients with cancer from rural areas have worse outcomes than their urban counterparts have relied on cancer population data and did not account for differences in access to care. Clinical trial patients receive protocol-directed care by design, so large clinical trial databases are ideal for examining the impact of rural vs urban residency on outcomes. Objective: To compare the geographic distribution and survival outcomes for rural vs urban patients with cancer treated in clinical trials. Design, Setting, and Participants: In this comparative effectiveness retrospective cohort analysis, 36 995 patients from all 50 states enrolled in 44 phase 3 and phase 2/3 SWOG (formerly the Southwest Oncology Group) treatment trials from January 1, 1986, to December 31, 2012, were examined. Seventeen different cancer-specific analysis cohorts were constructed. Data through January 30, 2018, were analyzed. Main Outcomes and Measures: Rural vs urban residency was defined using the Rural-Urban Continuum Codes developed by the US Department of Agriculture. Multivariate Cox regression was used to estimate the association of residency with overall survival, progression-free survival, and cancer-specific survival, controlling for major disease-specific prognostic factors and demographic variables and stratifying by study. Different definitions of rurality were examined. The distribution of rural vs urban patients by geographic region was described. Results: Overall, 27.7% of patients were 65 years or older (range across 17 cohort analyses, 7.8%-74.5%), 40.3% were female in the non-sex-specific analyses (range across 17 cohort analyses, 28.1%-45.9%), and 10.8% were black (range across 17 cohort analyses, 1.9%-22.4%). Overall, 19.4% of patients (7184 of 36 995) were from rural locations. Rural patients were more likely to be aged 65 years or older (rural, 30.7% aged ≥65 years vs urban, 27.0% aged ≥65 years; difference, 3.7%; 95% CI, 2.5%-4.9%; P < .001), were less likely to be black (rural, 5.4% vs urban, 12.1%; difference, 6.7%; 95% CI, 6.1%-7.3%; P < .001), were similar with respect to sex (rural, 40.4% female vs urban, 39.7% female; difference, 0.6%; 95% CI, -1.4% to 2.6%; P = .53), and were well represented within major US geographic regions (West, Midwest, South, and Northeast). Clinical prognostic factors were similar. In multivariable regression, rural patients with adjuvant-stage estrogen receptor-negative and progesterone receptor-negative breast cancer had worse overall survival (hazard ratio, 1.27; 95% CI, 1.06-1.51; P = .008) and cancer-specific survival (hazard ratio, 1.26; 95% CI, 1.04-1.52; P = .02). No other statistically significant differences for overall, progression-free, or cancer-specific survival were found. Results were consistent regardless of the definition of rurality. Conclusions and Relevance: Rural and urban patients with uniform access to cancer care through participation in a SWOG clinical trial had similar outcomes. This finding suggests that improving access to uniform treatment strategies for patients with cancer may help resolve the disparity in cancer outcomes between rural and urban patients.

BACKGROUND: Smokeless tobacco is consumed in most countries in the world. In view of its widespread use and increasing awareness of the associated risks, there is a need for a detailed assessment of its impact on health. We present the first global estimates of the burden of disease due to consumption of smokeless tobacco by adults. METHODS: The burden attributable to smokeless tobacco use in adults was estimated as a proportion of the disability-adjusted life-years (DALYs) lost and deaths reported in the 2010 Global Burden of Disease study. We used the comparative risk assessment method, which evaluates changes in population health that result from modifying a population's exposure to a risk factor. Population exposure was extrapolated from country-specific prevalence of smokeless tobacco consumption, and changes in population health were estimated using disease-specific risk estimates (relative risks/odds ratios) associated with it. Country-specific prevalence estimates were obtained through systematically searching for all relevant studies. Disease-specific risks were estimated by conducting systematic reviews and meta-analyses based on epidemiological studies. RESULTS: We found adult smokeless tobacco consumption figures for 115 countries and estimated burden of disease figures for 113 of these countries. Our estimates indicate that in 2010, smokeless tobacco use led to 1.7 million DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus and, based on data from the benchmark 52 country INTERHEART study, 4.7 million DALYs lost and 204,309 deaths from ischaemic heart disease. Over 85 % of this burden was in South-East Asia. CONCLUSIONS: Smokeless tobacco results in considerable, potentially preventable, global morbidity and mortality from cancer; estimates in relation to ischaemic heart disease need to be interpreted with more caution, but nonetheless suggest that the likely burden of disease is also substantial. The World Health Organization needs to consider incorporating regulation of smokeless tobacco into its Framework Convention for Tobacco Control.

PURPOSE: This Provisional Clinical Opinion update presents a clinically pragmatic approach to hepatitis B virus (HBV) screening and management. PROVISIONAL CLINICAL OPINION: All patients anticipating systemic anticancer therapy should be tested for HBV by 3 tests-hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and antibody to hepatitis B surface antigen-but anticancer therapy should not be delayed. Findings of chronic HBV (HBsAg-positive) or past HBV (HBsAg-negative and anti-HBc-positive) infection require HBV reactivation risk assessment.Patients with chronic HBV receiving any systemic anticancer therapy should receive antiviral prophylactic therapy through and for minimum 12 months following anticancer therapy. Hormonal therapy alone should not pose a substantial risk of HBV reactivation in patients with chronic HBV receiving hormonal therapy alone; these patients may follow noncancer HBV monitoring and treatment guidance. Coordination of care with a clinician experienced in HBV management is recommended for patients with chronic HBV to determine HBV monitoring and long-term antiviral therapy after completion of anticancer therapy.Patients with past HBV infection undergoing anticancer therapies associated with a high risk of HBV reactivation, such as anti-CD20 monoclonal antibodies or stem-cell transplantation, should receive antiviral prophylaxis during and for minimum 12 months after anticancer therapy completion, with individualized management thereafter. Careful monitoring may be an alternative if patients and providers can adhere to frequent, consistent follow-up so antiviral therapy may begin at the earliest sign of reactivation. Patients with past HBV undergoing other systemic anticancer therapies not clearly associated with a high risk of HBV reactivation should be monitored with HBsAg and alanine aminotransferase during cancer treatment; antiviral therapy should commence if HBV reactivation occurs.Additional information is available at www.asco.org/supportive-care-guidelines.

In the United States alone, there are currently approximately 14.5 million cancer survivors, and this number is expected to increase to 20 million by 2020. Cancer therapies can cause significant injury to the vasculature, resulting in angina, acute coronary syndromes (ACS), stroke, critical limb ischemia, arrhythmias, and heart failure, independently from the direct myocardial or pericardial damage from the malignancy itself. Consequently, the need for invasive evaluation and management in the cardiac catheterization laboratory (CCL) for such patients has been increasing. In recognition of the need for a document on special considerations for cancer patients in the CCL, the Society for Cardiovascular Angiography and Interventions (SCAI) commissioned a consensus group to provide recommendations based on the published medical literature and on the expertise of operators with accumulated experience in the cardiac catheterization of cancer patients. © 2016 Wiley Periodicals, Inc.