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1. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study

Author

Dolling, David I, Dunn, David T, Sutherland, Katherine A, Pillay, Deenan, Mbisa, Jean L, Parry, Chris M, Post, Frank A, Sabin, Caroline A, Cane, Patricia A, Aitken, Celia, Asboe, David, Webster, Daniel, Cane, Patricia, Castro, Hannah, Dunn, David, Dolling, David, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Geretti, Anna Maria, Goldberg, David, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Rice, Philip, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zuckerman, Mark, Greatorex, Jane, Wildfire, Adrian, O'Shea, Siobhan, Mullen, Jane, Mbisa, Tamyo, Cox, Alison, Tandy, Richard, Hale, Tony, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L, Payne, Brendan, Hay, Phillip, Rice, Phillip, Paynter, Mary, Bibby, David, Kirk, Stuart, MacLean, Alasdair, Gunson, Rory, Coughlin, Kate, Fearnhill, Esther, Fradette, Lorraine, Porter, Kholoud, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Nelson, Mark, Palfreeman, Adrian, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Huntington, Susie, Jose, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C, Garrett, N, Lynch, J, Hand, J, de Souza, C, Fisher, M, Perry, N, Tilbury, S, Gazzard, B, and Nelson, M

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Infectious Diseases, Antimicrobial Resistance, Clinical Research, Infection, Adult, Anti-HIV Agents, Atazanavir Sulfate, Cohort Studies, Drug Resistance, Viral, Female, HIV Infections, HIV Protease, HIV-1, Humans, Male, Medication Adherence, Middle Aged, Mutation Rate, Mutation, Missense, Oligopeptides, Pyridines, Treatment Failure, United States, UK HIV Drug Resistance Database, UK Collaborative HIV Cohort Study, HIV, drug resistance mutations, naive patients, protease inhibitors, virological failure, Microbiology, Pharmacology and Pharmaceutical Sciences, Clinical sciences, Pharmacology and pharmaceutical sciences
Abstract

ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.ResultsFour hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P < 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P < 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.ConclusionsViral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.

Published
2013

2. A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance: A retrospective, single-center study and the generation of www.emergencyprotocol.net

Author

Rossi A., Hoogeveen I. J., Lubout C. M. A., de Boer F., Fokkert-Wilts M. J., Rodenburg I. L., van Dam E., Grunert S. C., Martinelli D., Scarpa M., Dekker H., te Boekhorst S. T., van Spronsen F. J., Derks T. G. J., de Baere L., Bellettato C., Bosch A. M., Sallago J. B., Botto L. D., Brunner-Krainz M., Caroe C., Casswall T., Contreras Pulido E. L., Couce M. L., Dessein A. -F., Donati M. A., Eyskens F., Moura De Souza C. F., Fraile P. Q., Fuchs S. A., Gasperini S., Haas D., Hernandez E. M., Hochuli M., Hugon A., Karall D., Koeberl D., Labrune P., Lajic S., van Lingen C., Maiorana A., Mention K., Moenig I., Mohnike K., Montanari C., Nassogne M. -C., Parini R., Rahman S., Reyes M., Schwantje M., Skouma A., Strisciuglio P., Thiel M., Weinstein D., Ziagaki A., Amsterdam Gastroenterology Endocrinology Metabolism, Center for Liver, Digestive and Metabolic Diseases (CLDM), Rossi, A., Hoogeveen, I. J., Lubout, C. M. A., de Boer, F., Fokkert-Wilts, M. J., Rodenburg, I. L., van Dam, E., Grunert, S. C., Martinelli, D., Scarpa, M., Dekker, H., te Boekhorst, S. T., van Spronsen, F. J., Derks, T. G. J., de Baere, L., Bellettato, C., Bosch, A. M., Sallago, J. B., Botto, L. D., Brunner-Krainz, M., Caroe, C., Casswall, T., Contreras Pulido, E. L., Couce, M. L., Dessein, A. -F., Donati, M. A., Eyskens, F., Moura De Souza, C. F., Fraile, P. Q., Fuchs, S. A., Gasperini, S., Haas, D., Hernandez, E. M., Hochuli, M., Hugon, A., Karall, D., Koeberl, D., Labrune, P., Lajic, S., van Lingen, C., Maiorana, A., Mention, K., Moenig, I., Mohnike, K., Montanari, C., Nassogne, M. -C., Parini, R., Rahman, S., Reyes, M., Schwantje, M., Skouma, A., Strisciuglio, P., Thiel, M., Weinstein, D., and Ziagaki, A.

Subjects
Adult, Male, medicine.medical_specialty, Telemedicine, Adolescent, fatty acid oxidation disorders, glycogen storage diseases, eHealth, emergency treatment, hypoglycemia, telemedicine, Lipid Metabolism, Inborn Error, Context (language use), Hypoglycemia, Glycogen Storage Disease Type I, Single Center, Lipid Metabolism, Inborn Errors, Young Adult, glycogen storage disease, Retrospective Studie, Genetics, Medicine, Humans, Adverse effect, Child, Genetics (clinical), Retrospective Studies, Coma, business.industry, Fatty Acids, Infant, Newborn, Infant, Original Articles, Fasting, Middle Aged, medicine.disease, fatty acid oxidation disorder, Child, Preschool, Emergency medicine, Observational study, Original Article, Female, medicine.symptom, business, Oxidation-Reduction, Fatty Acid, Human
Abstract

INTRODUCTION: Patients with inborn errors of metabolism causing fasting intolerance can experience acute metabolic decompensations. Long-term data on outcomes using emergency letters are lacking.METHODS: This is a retrospective, observational, single-center study of the use of emergency letters based on a generic emergency protocol in patients with hepatic glycogen storage diseases (GSD) or fatty acid oxidation disorders (FAOD). Data on hospital admissions, initial laboratory results and serious adverse events were collected. Subsequently, the website www.emergencyprotocol.net was generated in the context of the CONNECT MetabERN eHealth project following multiple meetings, protocol revisions and translations.RESULTS: Representing 470 emergency protocol years, 127 hospital admissions were documented in 54/128(42%) patients who made use of emergency letters generated based on the generic emergency protocol. Hypoglycemia (here defined as glucose concentration 5 years. Convulsions, coma or death were not documented. By providing basic information, emergency letters for individual patients with hepatic GSD or the main FAOD can be generated at www.emergencyprotocol.net, in 9 different languages.DISCUSSION: Generic emergency protocols are safe and easy for home management by the caregivers and the first hour in-hospital management to prevent metabolic emergencies in patients with hepatic GSD and medium-chain Acyl CoA dehydrogenase deficiency. The website www.emergencyprotocol.net is designed to support families and healthcare providers to generate personalized emergency letters for patients with hepatic GSD and the main FAOD. This article is protected by copyright. All rights reserved.

Published
2021

3. ALK-negative anaplastic large cell lymphoma: features and outcomes of 235 patients from the International T-Cell Project

Author

Shustov, A., Cabrera, M. E., Civallero, M., Bellei, M., Y. H., Ko, Manni, M., Skrypets, T., Horwitz, S. M., de Souza, C. A., Radford, J. A., Bobillo, S., Prates, M. V., Ferreri, A. J. M., Chiattone, C., Spina, M., Vose, J. M., Chiappella, A., Laszlo, D., Marino, D., Stelitano, C., Federico, M., Savage, K., Connors, J., Gascoyne, R., Chhanabhai, M., Wilson, W., Jaffe, E. S., Armitage, J. O., Weisenburger, D. D., Anderson, J., Ullrich, F., Bast, M., Hochberg, E., Harris, N., Smogorzews ka, A., Levine, A., Nathwani, B. N., Miller, T., Rimsza, L., Montserrat, E., Lopez-Guillermo, A., Campo, E., Cuadros, M., Ferreira, J. A., Delgado, B. M., Holte, H., Delabie, J., Rudiger, T., Muller-Hermelink, K., Reimer, P., Adam, P., Wilhelm, M., Schmitz, N., Nerl, C., Lister, A., Norton, A., Maclennan, K. A., Zinzani, P. L., Pileri, S. A., Bellai, M., Luminari, S., Coiffier, B., Berger, F., Tanin, I., Wannakrairot, P., W. Y., Au, Liang, R., Loong, F., Rajan, S., Sng, I., Tobinai, K., Matsuno, Y., Morishima, Y., Nakamura, S., Seto, M., Tanimoto, M., Yoshino, T., Suzumiya, J., Ohshima, K., and Kim, W. -S.

Subjects
Male, Oncology, medicine.medical_specialty, Anaplastic Lymphoma, Clinical Trials and Observations, T-Lymphocytes, medicine.medical_treatment, International Prognostic Index, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Anaplastic Lymphoma Kinase, Prospective Studies, Prospective cohort study, Anaplastic large-cell lymphoma, Etoposide, Retrospective Studies, Chemotherapy, Manchester Cancer Research Centre, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Receptor Protein-Tyrosine Kinases, Hematology, medicine.disease, Lymphoma, Transplantation, Lymphoma, Large-Cell, Anaplastic, Female, business, medicine.drug
Abstract

Anaplastic lymphoma kinase–negative anaplastic large cell lymphoma (ALK– ALCL) is an aggressive neoplasm of T-cell/null-cell lineage. The T-Cell Project is a global prospective cohort study that consecutively enrolled patients newly diagnosed with peripheral T-cell lymphoma, registered through a centralized computer database between September 2006 and February 2018. Of 1553 validated cases from 74 sites in 13 countries worldwide, 235 were reported as ALK– ALCL. The median age at diagnosis was 54 years (range, 18-89 years), with a male predominance (62%). Stage III to IV disease was identified in 71% of patients, bulky disease and bone marrow involvement were uncommon, and 66% of patients presented with a low (0-1) International Prognostic Index score. Of all treated patients, 85% received multiagent initial chemotherapy, and 8% were consolidated with autologous hematopoietic cell transplantation. The initial overall and complete response rates were 77% and 63%, respectively. After a median follow-up of 52 months (95% confidence interval [CI], 41-63), the median progression-free survival (PFS) and overall survival (OS) were 41 months (95% CI, 17-62) and 55 months (95% CI, 36-75), respectively. The 3- and 5-year PFS rates were 52% and 43%, and the 3- and 5-year OS rates were 60% and 49%. Treatments containing both anthracycline and etoposide were associated with superior OS (P = .05) but not PFS (P = .18). In this large prospective cohort study, outcomes comparable to those previously reported in the retrospective International Peripheral T-Cell Lymphoma Project were observed. The study underscores the need for introducing novel platforms for ALK– ALCL and establishes a benchmark for future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT01142674.

Published
2021

4. Glycogen storage diseases: Twenty-seven new variants in a cohort of 125 patients

Author

Carlos Eduardo Steiner, Franciele Cabral Pinheiro, Fishinger Moura de Souza C, Bettio Soares M, Tatiéle Nalin, Erlane Marques Ribeiro, Ribeiro Valadares E, Schwartz Ivd, Porta G, and Fernanda Sperb-Ludwig

Subjects
0301 basic medicine, Male, medicine.medical_specialty, G6PC, lcsh:QH426-470, next‐generation sequencing, 030105 genetics & heredity, Gastroenterology, DNA sequencing, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, Internal medicine, molecular diagnosis, Genetics, medicine, Glycogen storage disease, Humans, Allele, Molecular Biology, Gene, Genetics (clinical), Glycogen, business.industry, Liver Diseases, High-Throughput Nucleotide Sequencing, Ion semiconductor sequencing, Original Articles, medicine.disease, Glycogen Storage Disease, Prognosis, lcsh:Genetics, 030104 developmental biology, hepatic GSD, chemistry, Cohort, Mutation, Female, Original Article, business, Biomarkers, Brazil, Follow-Up Studies
Abstract

Background Hepatic glycogen storage diseases (GSDs) are a group of rare genetic disorders in which glycogen cannot be metabolized to glucose in the liver because of enzyme deficiencies along the glycogenolytic pathway. GSDs are well‐recognized diseases that can occur without the full spectrum, and with overlapping in symptoms. Methods We analyzed a cohort of 125 patients with suspected hepatic GSD through a next‐generation sequencing (NGS) gene panel in Ion Torrent platform. New variants were analyzed by pathogenicity prediction tools. Results Twenty‐seven new variants predicted as pathogenic were found between 63 variants identified. The most frequent GSD was type Ia (n = 53), followed by Ib (n = 23). The most frequent variants were p.Arg83Cys (39 alleles) and p.Gln347* (14 alleles) in G6PC gene, and p.Leu348Valfs (21 alleles) in SLC37A4 gene. Conclusions The study presents the largest cohort ever analyzed in Brazilian patients with hepatic glycogenosis. We determined the clinical utility of NGS for diagnosis. The molecular diagnosis of hepatic GSDs enables the characterization of diseases with similar clinical symptoms, avoiding hepatic biopsy and having faster results., The study presents the largest cohort ever analyzed in Brazilian patients with hepatic glycogenosis. Thirty new mutations predicted as pathogenic were found in the 65 variants identified. We determined the clinical utility of next‐generation sequence (NGS) for diagnosis. The molecular diagnosis of hepatic GSDs enables the characterization of diseases with similar clinical symptoms, avoiding hepatic biopsy and having faster results.

Published
2019

5. Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance

Author

Geretti, AM, White, E, Orkin, C, Tostevin, A, Tilston, P, Chadwick, D, Leen, C, Sabin, C, Dunn, DT, Asboe, D, Pozniak, A, Cane, P, Churchill, D, Clark, D, Collins, S, Delpech, V, Douthwaite, S, Dunn, D, Fearnhill, E, Porter, K, Stirrup, O, Fraser, C, Gunson, R, Hale, A, Hue, S, Lazarus, L, Leigh-Brown, A, Mbisa, T, Mackie, N, Nastouli, E, Pillay, D, Phillips, A, Smit, E, Templeton, K, Volz, E, Williams, I, Zhang, H, Dawkins, J, O'Shea, S, Mullen, J, Cox, A, Tandy, R, Fawcett, T, Hopkins, M, Booth, C, Garcia-Diaz, A, Renwick, L, Schmid, ML, Payne, B, Hubb, J, Dustan, S, Kirk, S, Bradley-Stewart, A, Ainsworth, J, Allan, S, Anderson, J, Babiker, A, Gazzard, B, Gilson, R, Gompels, M, Hay, P, Hill, T, Johnson, M, Jose, S, Kegg, S, Martin, F, Mital, D, Nelson, M, Palfreeman, A, Post, F, Pritchard, J, Sabin, CA, Schwenk, A, Tariq, A, Trevelion, R, Ustianowski, A, Walsh, J, Thornton, A, Huntington, S, Glabay, A, Shidfar, S, Lynch, J, Hand, J, De Souza, C, Perry, N, Tilbury, S, Youssef, E, Mabika, T, Mandalia, S, Munshi, S, Adefisan, A, Taylor, C, Gleisner, Z, Ibrahim, F, Campbell, L, Baillie, K, Brima, N, Miller, S, Wood, C, Youle, M, Lampe, F, Smith, C, Tsintas, R, Chaloner, C, Hutchinson, S, Winston, A, Weber, J, Ramzan, F, Carder, M, Wilson, A, Morris, S, Lewszuk, A, Faleye, A, Ogunbiyi, V, Mitchell, S, Kemble, C, Russell-Sharpe, S, Gravely, J, Harte, A, Spencer, H, Jones, R, Cumming, S, Atkinson, C, Edgell, V, Allen, J, Murphy, C, and Gunder, I

Subjects
0301 basic medicine, Oncology, Male, HIV Infections, Drug resistance, Kaplan-Meier Estimate, chemistry.chemical_compound, 0302 clinical medicine, 1108 Medical Microbiology, Abacavir, Antiretroviral Therapy, Highly Active, INFECTION, Pharmacology (medical), Pharmacology & Pharmacy, 030212 general & internal medicine, Original Research, Proteolytic enzymes, Lamivudine, virus diseases, Viral Load, Prognosis, ANTIRETROVIRAL TREATMENT, Infectious Diseases, Treatment Outcome, Cohort, RNA, Viral, Female, 1115 Pharmacology and Pharmaceutical Sciences, UK HIV Drug Resistance Database and UK CHIC Study, Life Sciences & Biomedicine, Viral load, 0605 Microbiology, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Efavirenz, Genotype, TRANSMISSION, Anti-HIV Agents, 030106 microbiology, REGIMENS, Emtricitabine, Microbiology, 03 medical and health sciences, Internal medicine, Drug Resistance, Viral, medicine, Humans, Protease Inhibitors, Alleles, Pharmacology, Science & Technology, TREATMENT-NAIVE PATIENTS, business.industry, HIV, INDIVIDUALS, chemistry, Amino Acid Substitution, Mutation, HIV-1, business
Abstract

Objectives: In subjects with transmitted thymidine analogue mutations (TAMs), boosted PIs (PI/b) are often chosen to overcome possible resistance to the NRTI backbone. However, data to guide treatment selection are limited. Our aim was to obtain firmer guidance for clinical practice using real-world cohort data.Methods: We analysed 1710 subjects who started a PI/b in combination with tenofovir or abacavir plus emtricitabine or lamivudine, and compared their virological outcomes with those of 4889 patients who started an NNRTI (predominantly efavirenz), according to the presence of ≥1 TAM as the sole form of transmitted drug resistance.Results: Participants with ≥1 TAM comprised predominantly MSM (213 of 269, 79.2%), subjects of white ethnicity (206 of 269, 76.6%) and HIV-1 subtype B infections (234 of 269, 87.0%). Most (203 of 269, 75.5%) had singleton TAMs, commonly a revertant of T215Y or T215F (112 of 269, 41.6%). Over a median of 2.5 years of follow-up, 834 of 6599 (12.6%) subjects experienced viraemia (HIV-1 RNA >50 copies/mL). The adjusted HR for viraemia was 2.17 with PI/b versus NNRTI-based therapy (95% CI 1.88-2.51; P Conclusions: In this cohort, patients harbouring ≥1 TAM as the sole form of transmitted drug resistance gained no apparent virological advantage from starting first-line ART with a PI/b.

Published
2018

6. Development and application of a new measure of engagement in out‐patient HIV care

Author

Howarth, AR, Burns, FM, Apea, V, Jose, S, Hill, T, Delpech, VC, Evans, A, Mercer, CH, Michie, S, Morris, S, Sachikonye, M, Sabin, C, Ainsworth, Jonathan, Allan, Sris, Anderson, Jane, Babiker, Abdel, Chadwick, David, Dunn, David, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hay, Phillip, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Martin, Fabiola, Nelson, Mark, Orkin, Chloe, Palfreeman, Adrian, Phillips, Andrew, Pillay, Deenan, Post, Frank, Pritchard, Jillian, Schwenk, Achim, Tariq, Anjum, Trevelion, Roy, Walsh, John, Thornton, Alicia, Huntington, Susie, Glabay, Adam, Perry, N., Tilbury, S., Youssef, E., Churchill, D., Everett, R., Asboe, D., Mandalia, S., Korat, H., Taylor, C., Gleisner, Z., Ibrahim, F., Campbell, L., Brima, N., Williams, I., Youle, M., Lampe, F., Smith, C., Tsintas, R., Chaloner, C., Hutchinson, S., Mackie, N., Winston, A., Weber, J., Ramzan, F., Carder, M., Lynch, J., Hand, J., Souza, C., Anderson, J., Munshi, S., Miller, S., Wood, C., Leen, C., Wilson, A., Morris, S., Memon, K., Lewszuk, A., Cope, E., Gibson, J., Main, P., Mitchell, S., Hunter, M., Dhillon, M., Russell‐Sharpe, S., Harte, A., Clay, S., Tariq, A., Spencer, H., Jones, R., Cumming, S., and Atkinson, C.

Subjects
Adult, Male, patient engagement, Adolescent, HIV, HIV Infections, out‐patient care, retention measure, Middle Aged, Patient Acceptance of Health Care, United Kingdom, Cohort Studies, Interviews as Topic, Young Adult, cohort study, Ambulatory Care, Humans, Female, Original Research, Aged
Abstract

Objectives Commonly used measures of engagement in HIV care do not take into account that the frequency of attendance is related to changes in treatment and health status. This study developed a new measure of engagement in care (EIC) incorporating clinical factors. Methods We conducted semi‐structured interviews with eight HIV physicians to identify factors associated with the timing of patients' next scheduled appointments. These factors informed the development of an algorithm to classify each month of follow‐up as “in care” (on or before the time of the next expected attendance) or “out of care” (after the time of the next expected attendance). The EIC algorithm was applied to data from the UK Collaborative HIV Cohort (UK CHIC) study, a large clinical cohort study. Results The interviews indicated that time to next appointment varied depending on psychosocial and physical comorbidities, and clinical factors (time since diagnosis, AIDS diagnosis, treatment status, CD4 count and viral load). The resulting EIC algorithm was applied to 44 432 patients; 83.9% of the 3 021 224 person‐months were “in care”. Greater EIC was independently associated with older age, white ethnicity, HIV acquisition through sex between men, current use of antiretroviral therapy (ART), a higher nadir CD4 count, later calendar year and being seen at the clinic for the first time within the last year. Conclusions This algorithm describing engagement in HIV care incorporates a time‐updated measure of patients' treatment and health status. It adds to the options available for measuring this key performance indicator.

Published
2016

7. Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

Author

Jose, S., Quinn, K., Dunn, D., Cox, A., Sabin, C., Fidler, S., Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hay, Phillip, Johnson, Margaret, Kegg, Stephen, Leen, C., Martin, Fabiola, Nelson, Mark, Palfreeman, Adrian, Post, F., Pritchard, Jillian, Sachikonye, Memory, Schwenk, Achim, Tariq, Anjum, Walsh, John, Hill, Teresa, Jose, Sophie, Phillips, Andrew, Sabin, Caroline, Thornton, Alicia, Dunn, David, Glabay, Adam, Fisher, M., Perry, N., Tilbury, S., Youssef, E., Churchill, D., Gazzard, B., Nelson, M., Everett, R., Asboe, D., Mandalia, S., Korat, H., Taylor, C., Gleisner, Z., Ibrahim, F., Campbell, L., Gilson, R., Brima, N., Williams, I., Johnson, M., Youle, M., Lampe, F., Smith, C., Tsintas, R., Chaloner, C., Hutchinson, S., Phillips, A., Hill, T., Thornton, A., Huntington, S., Walsh, J., Mackie, N., Winston, A., Weber, J., Ramzan, F., Carder, M., Orkin, C., Lynch, J., Hand, J., de Souza, C., Anderson, J., Munshi, S., Ainsworth, J., Schwenk, A., Miller, S., Wood, C., Wilson, A., Morris, S., Gompels, M., Allan, S., Palfreeman, A., Memon, K., Lewszuk, A., Chadwick, D., Cope, E., Gibson, J., Kegg, S., Main, P., Mitchell, Hunter, Hay, P., Dhillon, M., Martin, F., Russell-Sharpe, S., Harte, A., Clay, S., Tariq, A., Spencer, H., Jones, R., Pritchard, J., Cumming, S., Atkinson, C., Delpech, Valerie, Sachikony, M., Aitken, Celia, Asboe, David, Pozniak, Anton, Cane, Patricia, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Douthwaite, Samuel, Fearnhill, Esther, Porter, Kholoud, Tostevin, Anna, White, Ellen, Fraser, Christophe, Geretti, Anna Maria, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mbisa, Tamyo, Mackie, Nicola, Moses, Samuel, Orkin, Chloe, Nastouli, Eleni, Pillay, Deenan, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Webster, Daniel, Williams, Ian, Zhang, Hongyi, Greatorex, Jane, O'Shea, Siobhan, Mullen, Jane, Cox, Alison, Tandy, Richard, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L., Payne, Brendan, Pereira, Spiro, Hubb, Jonathan, Kirk, Stuart, Gunson, Rory, Bradley-Stewart, Amanda, and Medical Research Council (MRC)

Subjects
0301 basic medicine, Male, HAART, HIV Infections, Treatment failure, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Antiretroviral Therapy, Highly Active, Pharmacology (medical), 030212 general & internal medicine, Treatment Failure, virological failure, Health Policy, UK CHIC and UK HDRD Steering Committees, Virological failure, 3. Good health, Antiretroviral therapy, Patient benefit, Infectious Diseases, Female, medicine.symptom, Life Sciences & Biomedicine, Viral load, Cart, medicine.medical_specialty, Anti-HIV Agents, Short Communication, antiretroviral therapy, CD4 count, Asymptomatic, 03 medical and health sciences, HIV-INFECTION, Virology, Internal medicine, Drug Resistance, Viral, medicine, Humans, Science & Technology, business.industry, HIV resistance, 1103 Clinical Sciences, 030112 virology, CD4 Lymphocyte Count, Immunology, Mutation, business
Abstract

Objectives No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. Methods In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. Results Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count

Published
2015

8. HDAC Inhibitors as Novel Anti-Cancer Therapeutics

Author

De Souza C and Biswa Prasun Chatterji

Subjects
Cancer Research, Mocetinostat, Antineoplastic Agents, Pharmacology, Biology, Histone Deacetylases, Romidepsin, Patents as Topic, chemistry.chemical_compound, Neoplasms, Panobinostat, Drug Discovery, medicine, Animals, Humans, Pharmacology (medical), Molecular Targeted Therapy, Givinostat, Cell Proliferation, Entinostat, General Medicine, Gene Expression Regulation, Neoplastic, Histone Deacetylase Inhibitors, Trichostatin A, Oncology, chemistry, Drug Design, Histone deacetylase, Belinostat, medicine.drug
Abstract

Malignant growth of cells is a condition characterized by unchecked cellular proliferation, genetic instability and epigenetic dysregulation. Up-regulated HDAC (Histone Deacetylase) enzyme activity is associated with a closed chromatin assembly and subsequent gene repression, forming a characteristic feature of malignantly transformed cells. Novel therapeutics are now targeting the zinc containing HDAC enzymes for treating various types of cancers. Recently, a spate of drugs acting via HDAC inhibition have been undergoing clinical trials and several patents present exciting molecules like PCI-24781 (Abexinostat), ITF- 2357 (Givinostat); MS-275 (Entinostat), MGCD 0103 (Mocetinostat), LBH-589 (Panobinostat), FK228 (Romidepsin), PXD-101 (Belinostat) and Valproic Acid to be used as alternatives or adjuvants to traditional chemotherapeutics. However, only three HDAC inhibitors have acquired FDA approval till date. Recently, PXD-101 obtained FDA approval for the treatment of Refractory or Relapsed Peripheral T cell lymphoma. The current article reviews patents that have introduced novel molecules that are HDAC isoform specific, superior to first generation HDAC inhibitors like SAHA (Suberoylanilide Hydroxamic Acid) and TSA (Trichostatin A) and can be modified structurally to reduce toxic side effects and increase specificity. These molecules can combine the best characteristics of an ideal HDAC inhibiting drug either as monotherapy or in combinatorial therapy for cancer treatment thus, indicating promise to be included in the next generation of target specific HDAC inhibiting drugs.

Published
2015

9. Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure

Author

Jose, Sophie, Hamzah, Lisa, Campbell, Lucy J., Hill, Teresa, Fisher, Martin, Leen, Clifford, Gilson, Richard, Walsh, John, Nelson, Mark, Hay, Phillip, Johnson, Margaret, Chadwick, David, Nitsch, Dorothea, Jones, Rachael, Sabin, Caroline A., Post, Frank A., Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Delpech, Valerie, Dunn, David, Gazzard, Brian, Gompels, Mark, Kegg, Stephen, Orkin, Chloe, Palfreeman, Adrian, Phillips, Andrew, Pillay, Deenan, Post, Frank, Sabin, Caroline, Sachikonye, Memory, Schwenk, Achim, Huntington, Susie, Josie, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C., Garrett, N., Lynch, J., Hand, J., de Souza, C., Fisher, M., Perry, N., Tilbury, S., Churchill, D., Gazzard, B., Nelson, M., Waxman, M., Asboe, D., Mandalia, S., Delpech, V., Anderson, J., Munshi, S., Korat, H., Poulton, M., Taylor, C., Gleisner, Z., Campbell, L., Gilson, R., Brima, N., Williams, I., Schwenk, A., Ainsworth, J., Wood, C., Miller, S., Johnson, M., Youle, M., Lampe, F., Smith, C., Grabowska, H., Chaloner, C., Puradiredja, D., Walsh, J., Weber, J., Ramzan, F., Mackie, N., Winston, A., Leen, C., Wilson, A., Gompels, M., Allan, S., Palfreeman, A., Moore, A., Chadwick, D., Wakeman, K., Main, Paul, Mitchell, Hunter, and Dhillon, Mandip

Subjects
Adult, Male, eGFR slopes, kidney, Anti-HIV Agents, Adenine, renal function, Organophosphonates, HIV Infections, highly active antiretroviral therapy, Middle Aged, Viral Load, tenofovir, Drug Administration Schedule, Cohort Studies, Major Articles and Brief Reports, eGFR, HIV/AIDS, Humans, Female, Kidney Diseases, Glomerular Filtration Rate, Proportional Hazards Models
Abstract

Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Methods. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. Results. We observed declines in the eGFR during TDF exposure (mean slopes, −15.7 mL/minute/1.73 m2/year [95% confidence interval {CI}, −20.5 to −10.9] during the first 3 months and −3.1 mL/minute/1.73 m2/year [95% CI, −4.6 to −1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m2/year [95% CI, 8.9–16.1] during the first 3 months and 0.8 mL/minute/1.73 m2/year [95% CI, .1–1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. Conclusions. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided.

Published
2014

10. Effects of beta-alanine supplementation on performance and muscle fatigue in athletes and non-athletes of different sports: a systematic review

Author

Donner Alves F, Berti Zanella P, and Guerini De Souza C

Subjects
0301 basic medicine, medicine.medical_specialty, Physical Exertion, beta-Alanine, Carnosine, Physical Therapy, Sports Therapy and Rehabilitation, Athletic Performance, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Oxygen Consumption, Medicine, Humans, Orthopedics and Sports Medicine, Exercise physiology, Muscle, Skeletal, Exercise, Randomized Controlled Trials as Topic, Muscle fatigue, biology, business.industry, Athletes, 030229 sport sciences, biology.organism_classification, Clinical trial, 030104 developmental biology, chemistry, Dietary Supplements, Muscle Fatigue, Physical therapy, Red meat, business, Evidence synthesis
Abstract

Introduction Beta-alanine (BA) is a non-essential amino acid that can be synthesized in the liver and obtained from diet, particularly from white and red meat. Increased availability of BA via dietary supplement, may improve performance of athletes. The aim of this study was to conduct a review of the use of BA supplementation as an ergogenic aid to improve performance and fatigue resistance in athletes and non-athletes. Evidence acquisition In this systematic review, a search in PubMed and Bireme databases was performed for the terms "beta-alanine," "beta-alanine and exercise," "carnosine" or "carnosine and exercise" in the titles or abstracts. We included randomized, clinical trials published between 2005 and 2015. Evidence synthesis Twenty-three studies were selected. Most of them included physically active individuals. The mean intervention period was 5.2±1.8 weeks, and mean BA dose was 4.8±1.3 g/day. The main outcome measures were blood lactate, pH, perceived exertion, power and physical working capacity at fatigue threshold. After BA supplementation, no statistically significant difference was observed in total work, exercise performance time, oxygen consumption and time to exhaustion. Conclusions BA supplementation seems to improve perceived exertion and biochemical parameters related to muscle fatigue and less evidence was found for improvement in performance.

Published
2016

11. Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: An observational cohort study

Author

Patterson, M. C, Mengel, E, Vanier, M. T, Schwierin, B, Muller, A, Cornelisse, P, Pineda, M, Amado-Fondo, A, Amraoui, Y, Andria, G, Arellano, M, Audoin, B, Azcona, C, Barr, C, Baruteau, J, Baumgartner, C, Bell, L, Bembi, B, Benneddif, K, Bernard, G, Bobocea, N, Bodzioch, M, Boettcher, T, Bonnan, M, Broue, P, Bruni, A, Caceres, M, Camino, R, Campbell, E, Cances, C, Cannell, P, Cesar, J, Chabrol, B, Chakrapani, A, Colao, R, Collet, A, Corsetti, T, Cousins, A, Covanis, A, Cox, T, Cuisset, J. M, Dardis, A, Das, A, Deegan, P, Dengler, T, Deodato, F, Derralynn, H, Di Donato, I, Di Rocco, M, Dinopoulos, A, Pakiela, D, Eckehard, S, Engelen, M, Eyer, D, Fecarotta, S, Federico, A, Filla, A, Fiumara, A, Fonseca, M. J, Gabrielli, O, Garcia, T, Garrote, J, Gissen, P, Giugliani, L, Greenberg, C, Heron, B, Hertzberg, C, Higgins, F, Hill, A, Hiwot, T, Hlavata, A, Hörbe-Blindt, A, Howley, E, Hussain, N, Illsinger, S, Imrie, J, Jacklin, E, Jones, S, Jovanovic, A, Kaczmarek, V, Kaphan, E, Kibaek, M, Kleinhans, P, Klünemann, Kh, Koch, S. M, Koegl-Wallner, W, Kolnikova, M, Korenke, G. C, Korinthenberg, R, Kumari, S, Lachmann, R, Lee Ann, L, Likopoulou, L, Lilienthal, E, Link, B, Lippold, M, Lopez-Laso, E, Luecke, T, Lundgren, J, Mackrell, M, Madruga, M, Maletta, R, Malinova, V, Manners, J, Marinei, R, Marquardt, T, Martins, E, Martins, A. M, Martins, N, Mcalister, L, Mccabe, A, Mckie, M, Mcmahon, S, Meehan, M, Meldgaard Lund, A, Mendozah, C, Meyer, A, Mielke, S, Milligan, A, Mir, P, Moisa, M, Mombelli, C, Morris, L, Müller Vom Hagen, J, Munoz, B, Murphy, E, Nagarajan, L, Neto, P. B, Nevsimalova, S, Nia, S, Nicolai, J, Niemann, D, Niktari, G, O'Callaghan, M. D. M, Paucar-Arce, M, Peers, K, Peintinger, L, Peralta, M, Pérez, J, Perez-Poyato, M, Petrariu, A, Puschmann, A, Raiman, J, Rask, O, Rataj, J, Raymond-Gaynor, C, Reichelt, G, Ribeiro, E, Riches, V, Roberts, A, Roelants, J, Rohrbach, M, Rokicki, D, Rolfs, A, Russo, C, Rutsch, F, Saleem, R, Santos, M, Schmutz, P, Schwahn, B, Sedel, F, Semotok, J, Sharma, R, Silska, S, Silva, A, Simmons, L, Sivera, R, Skorpen, J, Sole, G, Souza, C, Stadlober-Degwerth, M, Starling, J, Temudo, T, Tomas, M, Tranchant, C, Uziel, G, Valayannopoulous, V, Van Den Hout, H, Van Der Tol, L, Van Spronsen, F, Vellodi, A, Verdu, A, Vilchez, J. J, Vinaixa, A, Visser, G, Voelker, J, Waldek, S, Walter, A, Walterfang, M, Wein, U, Widner, H, Wilcke, C, Wildish, L, Wraith, E, Wright, N, Xaidara, A, Yamamoto, M, Zallocco, F, Zielke, S, Patterson, Mc, Mengel, E, Vanier, Mt, Schwierin, B, Muller, A, Cornelisse, P, Pineda, M, Registry investigators, Npc, Filla, Alessandro, Russo, CINZIA VALERIA, Neurology, Paediatric Neurology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ANS - Amsterdam Neuroscience, and Graduate School

Subjects
Male, Pediatrics, Neurology, Cohort Studies, 0302 clinical medicine, Miglustat, Medicine, Enzyme Inhibitor, Genetics(clinical), Pharmacology (medical), Prospective Studies, Young adult, Enzyme Inhibitors, Prospective cohort study, Child, Genetics (clinical), Medicine(all), 0303 health sciences, Medicine (all), Niemann-Pick disease type C, Niemann-Pick Disease, Type C, General Medicine, 3. Good health, Treatment Outcome, Child, Preschool, Cohort, Disease Progression, Female, medicine.drug, Cohort study, Human, Adult, medicine.medical_specialty, Registry, 1-Deoxynojirimycin, Adolescent, 03 medical and health sciences, Young Adult, Disease registry, Swallowing, Humans, 030304 developmental biology, business.industry, Research, Prospective Studie, Cohort Studie, business, 030217 neurology & neurosurgery
Abstract

BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat. METHODS: The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if

Published
2015

12. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib:A multicenter international myeloma working group study

Author

Kumar S. K., Lee J. H., Lahuerta J. J., Morgan G., Richardson P. G., Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X., Hulin C., Klein S. K., Sonneveld P., Siegel D., Bladé J., Goldschmidt H., Jagannath S., Miguel J. S., Orlowski R., Palumbo A., Sezer O., Rajkumar S. V., Durie B. G. International Myeloma Working Group Abildgaard N, Abonour R, Alexanian R, Alsina M, Anderson KC, Attal M, Avet Loiseau H, Badros A, Baris D, Barlogie B, Bataille R, Beksaç M, Belch A, Ben Yehuda D, Bensinger B, Bergsagel PL, Bird J, Bladé J, Boccadoro M, Chanan Khan A, Chen WM, Child T, Chim J, Chng WJ, Comenzo R, Crowley J, Dalton W, Davies F, de Souza C, Delforge M, Dimopoulos M, Dispenzieri A, Drach J, Drake M, Durie BG, Einsele H, Facon T, Fantl D, Fermand JP, Fonseca R, Gahrton G, García Sanz R, Gasparetto C, Gertz M, Gibson J, Giralt S, Goldschmidt H, Greipp P, Hajek R, Hardan I, Hari P, Harousseau JL, Hata H, Hattori Y, Heffner T, Ho J, Hungria V, Ida S, Jacobs P, Jagannath S, Johnsen HE, Jian H, Joshua D, Jurczyszyn A, Kawano M, Kröger N, Kumar S, Kyle RA, Lacy M, Lahuerta JJ, Landgren O, Laubach J, Lee JH, LeLeu X, Lentzsch S, Lokhorst H, Lonial S, Ludwig H, Maiolino A, Mateos M, Mehta J, Mellqvist UH, Merlini G, Mikhael J, Morales AR, Moreau P, Morgan G, Nahi H, Munshi N, Niesvizky R, Nouel A, Novis Y, Orlowski R, Palumbo A, Pavlovsky S, Pilarski L, Powles R, Raje N, Rajkumar SV, Reece D, Reiman T, Richardson PG, Roodman D, Rosiñol L, San Miguel J, Sezer O, Shah JJ, Shaughnessy J, Shimizu K, Shustik C, Siegel D, Singhal S, Sonneveld P, Spencer A, Stadtmauer E, Stewart K, Terpos E, Tosi P, Tricot G, Turesson I, Van Camp B, Van Ness B, Van Riet I, Vande Broek I, Vanderkerken K, Vescio R, Vesole D, Waage A, Wang M, Weber D, Westin J, Wheatley K, Zonder J., CAVO, MICHELE, Kumar S.K., Lee J.H., Lahuerta J.J., Morgan G., Richardson P.G., Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X., Hulin C., Klein S.K., Sonneveld P., Siegel D., Bladé J., Goldschmidt H., Jagannath S., Miguel J.S., Orlowski R., Palumbo A., Sezer O., Rajkumar S.V., Durie B.G. International Myeloma Working Group Abildgaard N, Abonour R, Alexanian R, Alsina M, Anderson KC, Attal M, Avet-Loiseau H, Badros A, Baris D, Barlogie B, Bataille R, Beksaç M, Belch A, Ben-Yehuda D, Bensinger B, Bergsagel PL, Bird J, Bladé J, Boccadoro M, Cavo M, Chanan-Khan A, Chen WM, Child T, Chim J, Chng WJ, Comenzo R, Crowley J, Dalton W, Davies F, de Souza C, Delforge M, Dimopoulos M, Dispenzieri A, Drach J, Drake M, Durie BG, Einsele H, Facon T, Fantl D, Fermand JP, Fonseca R, Gahrton G, García-Sanz R, Gasparetto C, Gertz M, Gibson J, Giralt S, Goldschmidt H, Greipp P, Hajek R, Hardan I, Hari P, Harousseau JL, Hata H, Hattori Y, Heffner T, Ho J, Hungria V, Ida S, Jacobs P, Jagannath S, Johnsen HE, Jian H, Joshua D, Jurczyszyn A, Kawano M, Kröger N, Kumar S, Kyle RA, Lacy M, Lahuerta JJ, Landgren O, Laubach J, Lee JH, LeLeu X, Lentzsch S, Lokhorst H, Lonial S, Ludwig H, Maiolino A, Mateos M, Mehta J, Mellqvist UH, Merlini G, Mikhael J, Morales AR, Moreau P, Morgan G, Nahi H, Munshi N, Niesvizky R, Nouel A, Novis Y, Orlowski R, Palumbo A, Pavlovsky S, Pilarski L, Powles R, Raje N, Rajkumar SV, Reece D, Reiman T, Richardson PG, Roodman D, Rosiñol L, San Miguel J, Sezer O, Shah JJ, Shaughnessy J, Shimizu K, Shustik C, Siegel D, Singhal S, Sonneveld P, Spencer A, Stadtmauer E, Stewart K, Terpos E, Tosi P, Tricot G, Turesson I, Van Camp B, Van Ness B, Van Riet I, Vande Broek I, Vanderkerken K, Vescio R, Vesole D, Waage A, Wang M, Weber D, Westin J, Wheatley K, Zonder J., and Hematology

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, NATURAL HISTORY, Antineoplastic Agents, Context (language use), RELAPSE, Article, Recurrence, Internal medicine, medicine, Humans, Immunologic Factors, Elotuzumab, Survival analysis, Multiple myeloma, Aged, Aged, 80 and over, Isatuximab, Bortezomib, business.industry, Hematology, Middle Aged, Pomalidomide, medicine.disease, Survival Analysis, Surgery, Regimen, SURVIVAL, Disease Progression, Female, Multiple Myeloma, business, medicine.drug
Abstract

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T-0). The median age at diagnosis was 58 years, and time from diagnosis to T-0 was 3.3 years. Following T-0, 213 (74%) patients had a treatment recorded with one or more regimens (median = 1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including >= partial response in 69 (32%). The median overall survival and event-free survival from T-0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs. Leukemia (2012) 26, 149-157; doi:10.1038/leu.2011.196; published online 29 July 2011

Published
2012

13. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

Author

Lodi, Sara, Del Amo, Julia, Moreno, Santiago, Bucher, H. C., Furrer, Hansjakob, Logan, Roger, Sterne, Jonathan, Pérez-Hoyos, Santiago, Jarrín, Inma, Phillips, Andrew, Olson, Ashley, Van Sighem, Ard, Reiss, Peter, Sabin, C., Jose, Sophie, Justice, Amy, Goulet, Joseph, Miró, José M., Ferrer, Elena, Meyer, Laurence, Seng, Rémonie, Vourli, Georgia, Antoniadou, Anastasia, Dabis, Francois, Vandenhede, Mari Anne, Costagliola, Dominique, Abgrall, S., Hernán, Miguel A., Hernan, Miguel, Bansi, L., Hill, T., Dunn, D., Porter, K., Glabay, A., Orkin, C., Thomas, R., Jones, K., Fisher, M., Perry, N., Pullin, A., Churchill, D., Gazzard, B., Nelson, M., Asboe, D., Bulbeck, S., Mandalia, S., Clarke, J., Delpech, V., Anderson, J., Munshi, S., Post, F., Easterbrook, P., Khan, Y., Patel, P., Karim, F., Duffell, S., Gilson, R., Man, S. L., Williams, I., Gompels, M., Dooley, D., Schwenk, A., Ainsworth, J., Johnson, M., Youle, M., Lampe, F., Smith, C., Grabowska, H., Chaloner, C., Ismajani Puradiredja, D., Phillips, A., Walsh, J., Weber, J., Kemble, C., Mackie, N., Winston, A., Leen, C., Wilson, A., Bezemer, D. O., Gras, L. A.J., Kesselring, A. M., Van Sighem, A. I., Zaheri, S., Van Twillert, G., Kortmann, W., Branger, J., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., Van Der Meer, J. T.M., Wit, F. W.M.N., Godfried, M. H., Reiss, P., Van Der Poll, T., Nellen, F. J.B., Lange, J. M.A., Geerlings, S. E., Van Vugt, M., Pajkrt, D., Bos, J. C., Van Der Valk, M., Grijsen, M. L., Wiersinga, W. J., Brinkman, K., Blok, W. L., Frissen, P. H.J., Schouten, W. E.M., Van Den Berk, G. E.L., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M.E., Lauw, F. N., Van Eeden, A., Verhagen, D. W.M., Van Agtmael, M. A., Perenboom, R. M., Claessen, F. A.P., Bomers, M., Peters, E. J.G., Richter, C., Van Der Berg, J. P., Gisolf, E. H., Schippers, E. F., Van Nieuwkoop, C., Van Elzakker, E. P., Leyten, E. M.S., Gelinck, L. B.S., Pronk, M. J.H., Bravenboer, B., Kootstra, G. J., Delsing, C. E., Sprenger, H. G., Doedens, R., Scholvinck, E. H., Van Assen, S., Bierman, W. F.W., Soetekouw, R., Ten Kate, R. W., Van Vonderen, M. G.A., Van Houte, D. P.F., Kroon, F. P., Van Dissel, J. T., Arend, S. M., De Boer, M. G.J., Jolink, H., Ter Vollaard, H. J.M., Bauer, M. P., Weijer, S., El Moussaoui, R., Lowe, S., Schreij, G., Oude Lashof, A., Posthouwer, D., Koopmans, P. P., Keuter, M., Van Der Ven, A. J.A.M., Ter Hofstede, H. J.M., Dofferhoff, A. S.M., Warris, A., Van Crevel, R., Van Der Ende, M. E., De Vries-Sluijs, T. E.M.S., Schurink, C. A.M., Nouwen, J. L., Nispen Tot Pannerden, M. H., Verbon, A., Rijnders, B. J.A., Van Gorp, E. C.M., Hassing, R. J., Smeulders, A. W.M., Hartwig, N. G., Driessen, G. J.A., Den Hollander, J. G., Pogany, K., Juttmann, J. R., Van Kasteren, M. E.E., Hoepelman, A. I.M., Mudrikova, T., Schneider, M. M.E., Jaspers, C. A.J.J., Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W.M., Barth, R. E., Geelen, S. P.M., Wolfs, T. F.W., Bont, L. J., Van Den Berge, M., Stegeman, A., Groeneveld, P. H.P., Alleman, M. A., Bouwhuis, J. W., Barin, F., Burty, C., Duvivier, C., Enel, P., Fredouille-Heripret, L., Gasnault, J., Khuong, M. A., Mahamat, A., Pilorgé, F., Tattevin, P., Salomon, Valérie, Jacquemet, N., Costagliola, D., Grabar, S., Guiguet, M., Lanoy, E., Lièvre, L., Mary-Krause, M., Selinger-Leneman, H., Lacombe, J. M., Potard, V., Bricaire, F., Herson, S., Katlama, C., Simon, A., Desplanque, N., Girard, P. M., Meynard, J. L., Meyohas, M. C., Picard, O., Cadranel, J., Mayaud, C., Pialoux, G., Clauvel, J. P., Decazes, J. M., Gérard, L., Molina, J. M., Diemer, M., Sellier, P., Bentata, M., Honoré, P., Jeantils, V., Tassi, S., Mechali, D., Taverne, B., Bouvet, E., Crickx, B., Ecobichon, J. L., Matheron, S., Picard-Dahan, C., Yeni, P., Berthé, H., Dupont, C., Chandemerle, C., Mortier, E., De Truchis, P., Tisne-Dessus, D., Weiss, L., Salmon, D., Auperin, I., Gilquin, J., Roudière, L., Viard, J. P., Boue, F., Fior, R., Delfraissy, J. F., Goujard, C., Jung, C., Lesprit, Ph, Vittecoq, D., Fraisse, P., Lang, J. M., Rey, D., Beck-Wirth, G., Stahl, J. P., Lecercq, P., Gourdon, F., Laurichesse, H., Fresard, A., Lucht, F., Bazin, C., Verdon, R., Chavanet, P., Arvieux, C., Michelet, C., Choutet, P., Goudeau, A., Maître, M. F., Hoen, B., Eglinger, P., Faller, J. P., Borsa-Lebas, F., Caron, F., Reynes, J., Daures, J. P., May, T., Rabaud, C., Berger, J. L., Rémy, G., Arlet-Suau, E., Cuzin, L., Massip, P., Thiercelin Legrand, M. F., Pontonnier, G., Viget, N., Yasdanpanah, Y., Dellamonica, P., Pradier, C., Pugliese, P., Aleksandrowicz, K., Quinsat, D., Ravaux, I., Tissot-Dupont, H., Delmont, J. P., Moreau, J., Gastaut, J. A., Poizot Martin, I., Retornaz, F., Soubeyrand, J., Galinier, A., Ruiz, J. M., Allegre, T., Blanc, P. A., Bonnet-Montchardon, D., Lepeu, G., Granet-Brunello, P., Esterni, J. P., Pelissier, L., Cohen-Valensi, R., Nezri, M., Chadapaud, S., Laffeuillade, A., Billaud, E., Raffi, F., Boibieux, A., Peyramond, D., Livrozet, J. M., Touraine, J. L., Cotte, L., Trepo, C., Strobel, M., Bissuel, F., Pradinaud, R., Sobesky, M., Cabié, A., Gaud, C., Contant, M., Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Haerry, D., Fux, C. A., Gorgievski, M., Günthard, H., Hasse, B., Hirsch, H. H., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez De Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Casabona, J., Gallois, A., Esteve, A., Podzamczer, D., Murillas, J., Gatell, J. M., Manzardo, C., Tural, C., Clotet, B., Ferrer, E., Riera, M., Segura, F., Navarro, G., Force, L., Vilaró, J., Masabeu, A., García, I., Guadarrama, M., Cifuentes, C., Dalmau, D., Jaen, Agustí, C., Montoliu, A., Pérez, I., Gargoulas, Freyra, Blanco, J. L., Garcia-Alcaide, F., Martínez, E., Mallolas, J., López-Dieguez, M., García-Goez, J. F., Sirera, G., Romeu, J., Jou, A., Negredo, E., Miranda, C., Capitan, M. C., Saumoy, M., Imaz, A., Tiraboschi, J. M., Murillo, O., Bolao, F., Peña, C., Cabellos, C., Masó, M., Vila, A., Sala, M., Cervantes, M., Jose Amengual, Ma, Navarro, M., Penelo, E., Barrufet, P., Bejarano, G., Molina, J., Alvaro, M., Mercadal, J., Fernandez, Juanse, Ospina, Jesus E., Muñoz, M. A., Caro-Murillo, A. M., Sobrino, P., Jarrín, I., Gomez Sirvent, J. L., Rodríguez, P., Aleman, M. R., Alonso, M. M., Lopez, A. M., Hernandez, M. I., Soriano, V., Labarga, P., Barreiro, P., Medrano, J., Rivas, P., Herrero, D., Blanco, F., Vispo, M. E., Martín, L., Ramírez, G., De Diego, M., Rubio, R., Pulido, F., Moreno, V., Cepeda, C., Hervás, Rl, Iribarren, J. A., Arrizabalaga, J., Aramburu, M. J., Camino, X., Rodrí-guez-Arrondo, F., Von Wichmann, M. A., Pascual, L., Goenaga, M. A., Gutierrez, F., Masia, M., Ramos, J. M., Padilla, S., Sanchez-Hellín, V., Bernal, E., Escolano, C., Montolio, F., Peral, Y., Berenguer, J., Lopez, J. C., Miralles, P., Cosín, J., Sanchez, M., Gutierrez, I., Ramírez, M., Padilla, B., Vidal, F., Sanjuan, M., Peraire, J., Veloso, S., Vilades, C., Lopez-Dupla, M., Olona, M., Vargas, M., Aldeguer, J. L., Blanes, M., Lacruz, J., Salavert, M., Montero, M., Cuéllar, S., De Los Santos, I., Sanz, J., Oteo, J. A., Blanco, J. R., Ibarra, V., Metola, L., Sanz, M., Pérez-Martínez, L., Sola, J., Uriz, J., Castiello, J., Reparaz, J., Arriaza, M. J., Irigoyen, C., Moreno, S., Antela, A., Casado, J. L., Dronda, F., Moreno, A., Pérez, M. J., López, D., Gutiérrez, C., Hernández, B., Pumares, M., Martí, P., García, L., Page, C., García, F., Hernández, J., Peña, A., Muñoz, L., Parra, J., Viciana, P., Leal, M., López-Cortés, L. F., Trastoy, M., Mata, R., Justice, A. C., Fiellin, D. A., Rimland, D., Jones-Taylor, C., Oursler, K. A., Titanji, R., Brown, S., Garrison, S., Rodriguez-Barradas, M., Masozera, N., Goetz, M., Leaf, D., Simberkoff, M., Blumenthal, D., Leung, J., Butt, A., Hoffman, E., Gibert, C., Peck, R., Mattocks, K., Braithwaite, S., Brandt, C., Bryant, K., Cook, R., Conigliaro, J., Crothers, K., Chang, J., Crystal, S., Day, N., Erdos, J., Freiberg, M., Kozal, M., Gandhi, N., Gaziano, M., Gerschenson, M., Good, B., Gordon, A., Goulet, J. L., Hernán, M. A., Kraemer, K., Lim, J., Maisto, S., Miller, P., Mole, L., O'Connor, P., Papas, R., Robins, J. M., Rinaldo, C., Roberts, M., Samet, J., Tierney, B., Whittle, J., Babiker, A., Brettle, R., Darbyshire, J., Goldberg, D., Hawkins, D., Jaffe, H., Johnson, A., McLean, K., Pillay, D., Cursley, Adam, Ewings, Fiona, Fairbrother, Keith, Louisa Gnatiuc, S. L., Murphy, Brendan, Douglas, G., Kennedy, N., Pritchard, J., Andrady, U., Rajda, N., Maw, R., McKernan, S., Drake, S., Gilleran, G., White, D., Ross, J., Toomer, S., Hewart, R., Wilding, H., Woodward, R., Dean, G., Heald, L., Horner, P., Glover, S., Bansaal, D., Eduards, S., Carne, C., Browing, M., Das, R., Stanley, B., Estreich, S., Magdy, A., O'Mahony, C., Fraser, P., Hayman, B., Jebakumar, S. P.R., Joshi, U., Ralph, S., Wade, A., Mette, R., Lalik, J., Summerfield, H., El-Dalil, A., France, J. A., White, C., Robertson, R., Gordon, S., McMillan, S., Morris, S., Lean, C., Vithayathil, K., McLean, L., Winter, A., Gale, D., Jacobs, S., Tayal, S., Short, L., Green, S., Williams, G., Sivakumar, K., Bhattacharyya, N. D., Monteiro, E., Minton, J., Dhar, J., Nye, F., De Souza, C. B., Isaksen, A., McDonald, L., Franca, A., William, L., Jendrulek, I., Peters, B., Shaunak, S., El-Gadi, S., Easterbrook, P. J., Mazhude, C., Johnstone, R., Fakoya, A., McHale, J., Waters, A., Kegg, S., Mitchell, S., Byrne, P., Rice, P., Fidler, S., Mullaney, S. A., McCormack, S., David, D., Melville, R., Phillip, K., Balachandran, T., Mabey-Puttock, S., Sukthankar, A., Murphy, C., Wilkins, E., Ahmad, S., Haynes, J., Evans, E., Ong, E., Grey, R., Meaden, J., Bignell, C., Loay, D., Peacock, K., Girgis, M. R., Morgan, B., Palfreeman, A., Wilcox, J., Tobin, J., Tucker, L., Saeed, A. M., Chen, F., Deheragada, A., Williams, O., Lacey, H., Herman, S., Kinghorn, D., Devendra, V. S., Wither, J., Dawson, S., Rowen, D., Harvey, J., Bridgwood, A., Singh, G., Chauhan, M., Kellock, D., Young, S., Dannino, S., Kathir, Y., Rooney, G., Currie, J., FitzGerald, M., Devendra, S., Keane, F., Booth, G., Green, T., Arumainayyagam, J., Chandramani, S., Rajamanoharan, S., Robinson, T., Curless, E., Gokhale, R., Tariq, A., Luzzi, G., Fairley, I., Wallis, F., Smit, E., Ward, F., Loze, B., Morlat, P., Bonarek, M., Bonnet, F., Nouts, C., Louis, I., Reliquet, V., Sauser, F., Biron, C., Mounoury, O., Hue, H., Brosseau, D., Ghosn, J., Rannou, M. T., Bergmann, J. F., Badsi, E., Rami, A., Parrinello, M., Samanon-Bollens, D., Campa, P., Tourneur, M., Desplanques, N., Jeanblanc, F., Chiarello, P., Makhloufi, D., Blanc, A. P., Allègre, T., Baillat, V., Lemoing, V., Merle De Boever, C., Tramoni, C., Sobesky, G., Abel, S., Beaujolais, V., Slama, L., Chakvetadze, C., Berrebi, V., Fournier, I., Gerbe, J., Koffi, K., Augustin-Normand, C., Miailhes, P., Thoirain, V., Brochier, C., Souala, F., Ratajczak, M., Beytoux, J., Jacomet, C., Rouveix, E., Morelon, S., Olivier, C., Lortholary, O., Dupont, B., Maignan, A., Ragnaud, J. M., Raymond, I., Leport, C., Jadand, C., Jestin, C., Longuet, P., Boucherit, S., Sereni, D., Lascoux, C., Prevoteau, F., Sobel, A., Levy, Y., Lelievre, J. D., Lascaux, A. S., Dominguez, S., Dumont, C., Aumâitre, H., Delmas, B., Saada, M., Medus, M., Guillevin, L., Tahi, T., Yazdanpanah, Y., Pavel, S., Marien, M. C., Drenou, B., Beck, C., Benomar, M., Tubiana, R., Ait Mohand, H., Chermak, A., Ben Abdallah, S., Touam, F., Drobacheff, C., Folzer, A., Obadia, M., Prudhomme, L., Bonnet, E., Balzarin, F., Pichard, E., Chennebault, J. M., Fialaire, P., Loison, J., Galanaud, P., Boué, F., Bornarel, D., Six, M., Ferret, P., Batisse, D., Gonzales-Canali, G., Devidas, A., Chevojon, P., Turpault, I., Lafeuillade, A., Cheret, A., Philip, G., Morel, P., Timsit, J., Amirat, N., Brancion, C., Cabane, J., Tredup, J., Stein, A., Ravault, I., Chavanet, C., Buisson, M., Treuvetot, S., Nau, P., Bastides, F., Boyer, L., Wassoumbou, S., Oksenhendeler, E., Bernard, L., Domart, Y., Merrien, D., Greder Belan, A., Gayraud, M., Bodard, L., Meudec, A., Beuscart, C., Daniel, C., Pape, E., Vinceneux, P., Simonpoli, A. M., Zeng, A., Fournier, L., Fuzibet, J. G., Sohn, C., Rosenthal, E., Quaranta, M., Chaillou, S., Sabah, M., Audhuy, B., Schieber, A., Moreau, P., Niault, M., Vaillant, O., Huchon, G., Compagnucci, A., De Lacroix Szmania, I., Richier, L., Lamaury, I., Saint-Dizier, F., Garipuy, D., Drogoul, M. P., Fabre, G., Lambert De Cursay, G., Abraham, B., Perino, C., Lagarde, P., David, F., Roche-Sicot, J., Saraux, J. L., Leprêtre, A., Fampin, B., Uludag, A., Morin, A. S., Bletry, O., Zucman, D., Regnier, A., Girard, J. J., Quinsat, D. T., Heripret, L., Grihon, F., Houlbert, D., Ruel, M., Chemlal, K., Debab, Y., Tremollieres, F., Perronne, V., Slama, B., Perré, P., Miodovski, C., Guermonprez, G., Dulioust, A., Boudon, P., Malbec, D., Patey, O., Semaille, C., Deville, J., Remy, G., Béguinot, I., Chambrin, V., Pignon, C., Estocq, G. A., Levy, A., Duracinsky, M., Le Bras, P., Ngussan, M. S., Peretti, D., Medintzeff, N., Lambert, T., Segeral, O., Lezeau, P., Laurian, Y., Piketty, C., Karmochkine, M., Eliaszewitch, M., Jayle, D., Kazatchkine, M., Colasante, U., Duval, X., Nouaouia, W., Vilde, J. L., Bollens, D., Binet, D., Diallo, B., Fonquernie, L., Lagneau, J. L., Launay, O., Pietrie, M. P., Sicard, D., Stieltjes, N., Michot, J., Bourdillon, F., Obenga, G., Escaut, L., Bolliot, C., Schneider, L., Iguertsira, M., Tomei, C., Dhiver, C., Tissot Dupont, H., Vallon, A., Gallais, J., Gallais, H., Durant, J., Mondain, V., Perbost, I., Cassuto, J. P., Karsenti, J. M., Venti, H., Ceppi, C., Krivitsky, J. A., Bouchaud, O., Honore, P., Delgado, J., Rouzioux, C., Burgard, M., Boufassa, L., Peynet, J., Pérez-Hoyos, S., Del Amo, J., Alvarez, D., Monge, S., Muga, R., Sanvisens, A., Tor, J., Rivas, I., Vallecillo, G., Del Romero, J., Raposo, P., Rodríguez, C., Vera, M., Hurtado, I., Belda, J., Fernandez, E., Alastrue, I., Santos, C., Tasa, T., Juan, A., Trullen, J., Garcia De Olalla, P., Cayla, J., Masdeu, E., Knobel, H., Mirò, J. M., Sambeat, M. A., Guerrero, R., Rivera, E., Marco, A., Quintana, M., Gonzalez, C., Castilla, J., Guevara, M., De Mendoza, C., Zahonero, N., Ortíz, M., Paraskevis, D., Touloumi, G., Pantazis, N., Bakoyannis, G., Gioukari, V., Antoniadou, A., Papadopoulos, A., Petrikkos, G., Daikos, G., Psichogiou, M., Gargalianos-Kakolyris, P., Xylomenos, G., Katsarou, O., Kouramba, A., Ioannidou, P., Kordossis, T., Kontos, A., Lazanas, M., Chini, M., Tsogas, N., Panos, G., Paparizos, V., Leuow, K., Kourkounti, S., Sambatakou, H., Mariolis, I., Skoutelis, A., Papastamopoulos, V., Baraboutis, I., Internal medicine, APH - Aging & Later Life, Pediatric surgery, CCA - Innovative therapy, ICaR - Circulation and metabolism, ICaR - Ischemia and repair, Graduate School, Paediatric Infectious Diseases / Rheumatology / Immunology, Landsteiner Laboratory, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, Global Health, Center of Experimental and Molecular Medicine, APH - Amsterdam Public Health, AII - Inflammatory diseases, and ARD - Amsterdam Reproduction and Development

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Opportunistic infection, AIDS-Related Opportunistic Infections, Immunology, Population, Retinitis, HIV Infections, Article, 17 Psychology And Cognitive Sciences, Young Adult, Immune reconstitution inflammatory syndrome, Antiretroviral Therapy, Highly Active, Neoplasms, Virology, Internal medicine, medicine, Humans, Immunology and Allergy, education, Inverse probability weighting, Aged, education.field_of_study, business.industry, Developed Countries, Incidence, Progressive multifocal leukoencephalopathy, Hazard ratio, HIV, virus diseases, 11 Medical And Health Sciences, Middle Aged, 06 Biological Sciences, medicine.disease, United States, Europe, Infectious Diseases, Anti-Retroviral Agents, Unmasking, Female, Cytomegalovirus retinitis, business
Abstract

Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis.Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting.Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis.Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries.

Published
2014

14. Video-assisted cardiac surgery: 6 years of experience

Author

Jeronimo Antonio, Fortunato Júnior, Marcelo Luiz, Pereira, André Luiz M, Martins, Daniele de Souza C, Pereira, Maria Evangelista, Paz, Luciana, Paludo, Alcides, Branco Filho, and Branka, Milosewich

Subjects
Male, Postoperative Complications, Treatment Outcome, Heart Diseases, Humans, Female, Video-Assisted Surgery, Cardiac Surgical Procedures, Length of Stay, Middle Aged
Abstract

Minimally invasive and video-assisted cardiac surgery (VACS) has increased in popularity over the past 15 years. The small incisions have been associated with a good aesthetic effect and less surgical trauma, therefore less postoperative pain and rapid recovery.To present our series with VACS, after 6 years of use of the method.136 patients underwent VACS, after written consent, between September 2005 and October 2011, 50% for men and age of 47.8 ± 15, 4 anos, divided into two groups: with cardiopulmonary (CEC) (GcCEC=105 patients): mitral valve disease (47/105), aortic disease (39/105), congenital heart disease (19/105) and without extracorporeal circulation (CEC) (GsCEC=31 patients): cardiac resynchronization (18/ 31), cardiac tumor (4/31) and minimally invasive coronary artery bypass grafting (6/31). GcCEC was held in right minithoracotomy (3 to 5 cm) and femoral access to perform cannulation.In GcCEC, mean length of ICU stay and hospital stay were respectively 2.4 ± 4.5 days and 5.0 ± 6.8 days. Twelve patients presented complications in post-operative and five (4.8%) death. Ninety-three (88.6%) patients evolved uneventful, were extubated in operating room, and remained a mean of 1.8 ± 0.9 days in ICU and 3.6 ± 1.3 days in the hospital. In GsCEC, were mean 1.3 ± 0.7 days in ICU and 2.9 ± 1.4 days in hospital and without complications or deaths.The results found in this series are comparable to those of world literature and confirm the method as an option the conventional technique.

Published
2011

15. Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study

Author

Prosperi, Mc1, Mackie, N, Di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, Fm, Van Laethem, K, Bansi, L, van de Vijver DA, Geretti, Am, De Luca, A, Giacometti A, SEHERE c. o. n. s. o. r. t. i. u. m., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Carla Re, M, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, d'Arminio Monforte, A, Cicconi, P, Rusconi, S, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Bello, Fd, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Fadda, G, Vullo, Vincenzo, Turriziani, O, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, Pd, Rossi, C, Grossi, P, Seminari, E, Poletti, F, Mondino, V, Malena, M, Lattuada, E, Lengauer, T, Däumer, M, Hoffmann, D, Schülter, E, Müller, C, Oette, M, Reuter, S, Esser, S, Fätkenheuer, G, Rockstroh, J, Incardona, F, Rosen Zvi, M, Clotet, B, Thalme, A, Svedhem, V, Bratt, G, Gargiulo, F, Lapadula, G, Manca, N, Paraninfo, G, Quiros Roldan, E, Carosi, G, Castelnuovo, F, Vandamme, Am, Van Wijngaerden, E, Ainsworth, J, Anderson, J, Babiker, A, Dunn, D, Easterbrook, P, Fisher, M, Gazzard, B, Garrett, N, Gilson, R, Gompels, M, Hill, T, Johnson, M, Leen, C, Orkin, C, Phillips, A, Pillay, D, Porter, K, Post, F, Sabin, C, Sadiq, T, Schwenk, A, Walsh, J, Delpech, V, Palfreeman, A, Glabay, A, Lynch, J, Hand, J, de Souza, C, Perry, N, Tilbury, S, Churchill, D, Nelson, M, Waxman, M, Mandalia, S, Kall, M, Korat, H, Taylor, C, Ibrahim, F, Campbell, L, James, L, Brima, N, Williams, I, Youle, M, Lampe, F, Smith, C, Grabowska, H, Chaloner, C, Puradiredja, Di, Weber, J, Ramzan, F, Carder, M, Wilson, A, Dooley, D, Asboe, D, Pozniak, A, Cameron, S, Cane, P, Chadwick, D, Clark, D, Collins, S, Lazarus, L, Dolling, D, Fearnhill, E, Castro, H, Coughlin, K, Zuckerman, M, Booth, C, Goldberg, D, Hale, A, Kaye, S, Kellam, P, Leigh Brown, A, Smit, E, Templeton, K, Tilston, P, Tong, W, Zhang, H, Ushiro Lumb, I, Oliver, T, Bibby, D, Mitchell, S, Mbisa, T, Wildfire, A, Tandy, R, Shepherd, J, Maclean, A, Bennett, D, Hopkins, M, Garcia Diaz, A, Kirk, S, Sloot, P. M., Virology, Prosperi, M, Mackie, N, di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, F, van laethem, K, Bansi, L, van de Vijver, D, Geretti, A, de luca, A, and Mancuso, S

Subjects
Male, Drug Resistance, HIV Infections, Drug resistance, Cohort Studies, 0302 clinical medicine, Genotype, HIV Infection, Pharmacology (medical), 030212 general & internal medicine, Viral, 0303 health sciences, Proteolytic enzymes, Genotypic testing, HIV, Viral load, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Europe, Female, HIV-1, Humans, RNA, Viral, Viral Proteins, Drug Resistance, Viral, Mutation, Missense, Viral Load, Pharmacology, Infectious Diseases, 3. Good health, Cohort, Cohort study, Human, Microbiology (medical), Biology, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Viral Protein, 030306 microbiology, Anti-HIV Agent, Virology, Reverse transcriptase, Regimen, genotypic testing, viral load, Immunology, Mutation, RNA, Missense, Cohort Studie
Abstract

Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load

Published
2011

16. Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada

Author

May, MT, Gill, MJ, Wittkop, L, Klein, M, Sabin, C, Harrigan, PR, Dunn, D, Vehreschild, JJ, Rubio, R, Mocroft, A, Cavassini, M, Reiss, P, Monforte, AD, Zangerle, R, Ingle, SM, Hill, T, Jose, S, Sterne, JAC, Boulle, A, Stephan, C, Miro, JM, Chene, G-V, Costagliola, D, Dabis, F, Del Amo, J, Van Sighem, A, Vehreschild, J, Gill, J, Guest, J, Haerry, DH-U, Hogg, R, Justice, A, Obel, N, Crane, H, Smith, C, Saag, M, Sterling, T, Teira, R, Williams, M, Sterne, J, May, M, Ingle, S, Trickey, A, Ainsworth, J, Anderson, J, Babiker, A, Chadwick, D, Delpech, V, Fisher, M, Gazzard, B, Gilson, R, Hay, P, Gompels, M, Johnson, M, Kegg, S, Leen, C, Mackie, N, Nelson, M, Orkin, C, Palfreeman, A, Phillips, A, Pillay, D, Post, F, Sachikonye, M, Schwenk, A, Walsh, J, Thornton, A, Huntington, S, Glabay, A, Garrett, N, Lynch, J, Hand, J, De Souza, C, Perry, N, Tilbury, S, Youssef, E, Churchill, D, Waxman, M, Asboe, D, Mandalia, S, Munshi, S, Awosika, D, Korat, H, Taylor, C, Gleisner, Z, Ibrahim, F, Campbell, L, Baillie, K, Cope, E, Gibney, M, Gibson, J, Brima, N, Williams, I, Miller, S, Wood, C, Youle, M, Lampe, F, Chaloner, C, Winston, A, Weber, J, Ramzan, F, Carder, M, Wilson, A, Morris, S, Allan, S, Moore, A, Fox, L, Bojanowski, J, Lewszuk, A, Main, P, Mitchell, D, Hunter, D, Dhillon, M, Martin, F, Douglas, S, Russell-Sharp, S, Amsterdam institute for Infection and Immunity, Amsterdam Public Health, and Global Health

Subjects
Male, 0301 basic medicine, IMPACT, DIVERSITY, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Immunology and Allergy, Medicine, 030212 general & internal medicine, Cooperative Behavior, Viral failure, Hazard ratio, viral failure, 11 Medical And Health Sciences, Middle Aged, Prognosis, Antiretroviral therapy, 3. Good health, Europe, Infectious Diseases, Anti-Retroviral Agents, INFECTIONS, Cohort, Female, Life Sciences & Biomedicine, NAIVE PATIENTS, Cohort study, Adult, Canada, medicine.medical_specialty, Genotype, Epidemiology and Social, antiretroviral therapy, Immunology, 17 Psychology And Cognitive Sciences, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Virology, Internal medicine, Humans, TYPE-1 SUBTYPES, Mortality, COMBINATION ANTIRETROVIRAL THERAPY, HIV-1 subtype, Science & Technology, business.industry, DISEASE PROGRESSION, 06 Biological Sciences, medicine.disease, Survival Analysis, mortality, IMMUNOLOGICAL RESPONSE, 030112 virology, Confidence interval, Regimen, HIV-1, prognosis, T-CELL DECLINE, business, RESISTANCE
Abstract

Objectives: To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure.Design: Collaborative analysis of data from eight European and three Canadian cohorts. Methods: Adults (N>20 000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4+ cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression.Results: The most prevalent subtypes were B (15 419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104 649 person-years of observation, 1172/20 784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4+ cell count below, or more than, 100 cells/ml, respectively. There was no difference in mortality between subtypes A, B and C after viral failure.Conclusion: Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors.

Published
2015

17. Leptospirosis with atrial flutter (a case report)

Author

D«SQ»Souza C, Dwivedi S, and Balasubramanian R

Subjects
Male, complications, diagnosis, etiology, lcsh:R, lcsh:Medicine, India, Case Report, Electrocardiography, Atrial Flutter, Leptospira interrogans serovar canicola, Humans, epidemiology, Leptospirosis, physiopathology, Human, Aged
Published
1990

18. The association of socioeconomic status and use of crack/cocaine with unprotected anal sex in a cohort of men who have sex with men in Rio de Janeiro, Brazil

Author

Vieira Souza, C. T., Diaz, T., Sutmoller, F., and Francisco Bastos

Subjects
Adult, Male, Adolescent, Sexual Behavior, Middle Aged, Health Surveys, Cohort Studies, Infectious Diseases, Risk-Taking, Socioeconomic Factors, HIV Seronegativity, Surveys and Questionnaires, Multivariate Analysis, Crack Cocaine, Humans, Pharmacology (medical), Homosexuality, Male, Substance Abuse, Intravenous, Brazil
Abstract

To evaluate the relation between illicit drug use, sexual practices, and socioeconomic status, we analyzed data from the baseline interview of a cohort of 675 men who have sex with men conducted from 1994 to 1999 in Rio de Janeiro, Brazil. Bivariate analyses of factors associated with crack/cocaine use with sex revealed that men who reported crack/cocaine use were significantly ( p.05) more likely than men who did not report drug use to be unemployed (42.7% vs. 29.1%), to have an income of$250 per month (70.7% vs. 60.9%), to have8 years of education (69.5% vs. 50.9%), to report bisexual activity (81.7% vs. 41.7%), and to engage in commercial sex (72.0% vs. 37.9%). Multivariate analysis of factors associated with unprotected anal sex with casual male partners in the last 6 months demonstrated that the following variables were associated with this outcome: an income$250 per month (adjusted odds ratio [AOR] = 1.73, 95% confidence interval [CI]: 1.04-2.87), less than 8 years of education (AOR = 2.21, CI: 1.38-3.53), a greater sense of vulnerability (AOR = 2.58, CI: 1.54-4.33), a willingness to participate in vaccine trials (AOR = 1.91, CI: 1.20-3.05), and use of crack/cocaine (AOR = 1.91, CI: 1.05-3.46). Our findings suggest that HIV prevention programs for these men need to address drug use and how drug use may influence sexual behaviors.

19. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study

Author

Dolling, David I., Dunn, David T., Sutherland, Katherine A., Pillay, Deenan, Mbisa, Jean L., Parry, Chris M., Post, Frank A., Sabin, Caroline A., Cane, Patricia A., Aitken, Celia, Asboe, David, Webster, Daniel, Cane, Patricia, Castro, Hannah, Dunn, David, Dolling, David, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Geretti, Anna Maria, Goldberg, David, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Rice, Philip, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zuckerman, Mark, Greatorex, Jane, Wildfire, Adrian, O'Shea, Siobhan, Mullen, Jane, Mbisa, Tamyo, Cox, Alison, Tandy, Richard, Hale, Tony, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L., Payne, Brendan, Hay, Phillip, Rice, Phillip, Paynter, Mary, Bibby, David, Kirk, Stuart, MacLean, Alasdair, Gunson, Rory, Coughlin, Kate, Fearnhill, Esther, Fradette, Lorraine, Porter, Kholoud, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Nelson, Mark, Palfreeman, Adrian, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Huntington, Susie, Jose, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C., Garrett, N., Lynch, J., Hand, J., de Souza, C., Fisher, M., Perry, N., Tilbury, S., Gazzard, B., Nelson, M., Waxman, M., Asboe, D., Mandalia, S., Delpech, V., Anderson, J., Munshi, S., Korat, H., Welch, J., Poulton, M., MacDonald, C., Gleisner, Z., Campbell, L., Gilson, R., Brima, N., Williams, I., Schwenk, A., Ainsworth, J., Wood, C., Miller, S., Johnson, M., Youle, M., Lampe, F., Smith, C., Grabowska, H., Chaloner, C., Puradiredja, D., Walsh, J., Weber, J., Ramzan, F., Mackie, N., Winston, A., Leen, C., Wilson, A., Allan, S., Palfreeman, A., Moore, A., and Wakeman, K.

Subjects
Male, Mutation rate, Pyridines, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, THERAPY, Cohort Studies, 0302 clinical medicine, HIV Protease, Mutation Rate, 1108 Medical Microbiology, Genotype, Pharmacology (medical), 030212 general & internal medicine, Pharmacology & Pharmacy, Treatment Failure, drug resistance mutations, Original Research, 0303 health sciences, virological failure, UK Collaborative HIV Cohort Study (UK CHIC), Proteolytic enzymes, virus diseases, Middle Aged, 3. Good health, Infectious Diseases, Female, 1115 Pharmacology and Pharmaceutical Sciences, Life Sciences & Biomedicine, Oligopeptides, medicine.drug, Cohort study, 0605 Microbiology, Microbiology (medical), Adult, medicine.medical_specialty, Anti-HIV Agents, Atazanavir Sulfate, protease inhibitors, Mutation, Missense, RITONAVIR, Biology, Microbiology, Medication Adherence, 03 medical and health sciences, Internal medicine, SCORE, Drug Resistance, Viral, medicine, Humans, 030304 developmental biology, Pharmacology, Science & Technology, HIV, Virology, naive patients, United States, Atazanavir, Regimen, HIV-1, Ritonavir, UK HIV Drug Resistance Database (UKHDRD)
Abstract

Author(s): Dolling, David I; Dunn, David T; Sutherland, Katherine A; Pillay, Deenan; Mbisa, Jean L; Parry, Chris M; Post, Frank A; Sabin, Caroline A; Cane, Patricia A; UK HIV Drug Resistance Database (UKHDRD); UK Collaborative HIV Cohort Study (UK CHIC) | Abstract: ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.ResultsFour hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P l 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P l 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.ConclusionsViral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.

20. [Evolution of antibiotic-resistance Staphylococcus aureus in Saint Camille Medical Centre in Ouagadougou]

Author

Sd, Karou, Mc, Nadembega, Zeba B, Dp, Ilboudo, Djeneba Ouermi, Pignatelli S, Pietra V, Gbeassor M, De Souza C, and Simpore J

Subjects
Adult, Male, Academic Medical Centers, Staphylococcus aureus, Suppuration, Sputum, Microbial Sensitivity Tests, Staphylococcal Infections, Urine, beta-Lactams, Anti-Bacterial Agents, Erythromycin, Drug Resistance, Multiple, Bacterial, Burkina Faso, Humans, Ampicillin, Female, Gentamicins, Pristinamycin, Oleandomycin, Retrospective Studies
Abstract

Monitoring the antibiotic resistance of microorganisms in a specific geographic area can be useful in developing new approaches to first-intention antibiotherapy.The purpose of this study was to describe the evolution of resistance of Staphylococcus aureus to antibiotics routinely used at Saint Camille Medical Centre in Ouagadougou, Burkina Faso from 1996 to 2006.Strains of S. aureus, isolated from various pathologic sources were tested to determine their susceptibility to antibiotics. Sensitivity tests were performed in accordance with the guidelines of the Antibiogram Committee of the French Society for Microbiology (version 2007).During the study period, 1160 staphylococci strains were isolated including 73.45% identified as S. aureus. Susceptibility tests demonstrated a significant increase in resistance to beta-lactam antibiotics. The proportion of strains showing resistance to ampicillin reached 58.29% in 2000. Resistance to these antibiotics regressed significantly from 2000 to 2006. Resistance to pristinamycin and erythromycin showed a tendency to increase while resistance to gentamicin and oleandomycin showed no statistically significant change.This study demonstrated that S. aureus was the most common Staphylococcus genus present at the center and that it was resistant to several antibiotics. Reducing use of beta-lactam probably accounted for the significant decline in resistance to this type of antibiotic. Care should also be given to the use of other antibiotics such as pristinamycin and erythromycin since resistance appears to be increasing.

21. Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyrosine kinase inhibitor optimization and selectivity study

Author

Richard N. Yu, Tillmann Krahnke, Timothy P. Hughes, Ricardo Pasquini, François Guilhot, Michele Baccarani, Stuart L. Goldberg, Jacob M. Rowe, Matt Kalaycio, Hagop M. Kantarjian, Fabrizio Pane, Beatriz Moiraghi, Jorge E. Cortes, Carmino Antonio De Souza, Dong-Wook Kim, Marc Rudoltz, Elena Tothova, Brian J. Druker, Susan Branford, Jerald P. Radich, Cortes, Je, Baccarani, M, Guilhot, F, Druker, Bj, Branford, S, Kim, Dw, Pane, Fabrizio, Pasquini, R, Goldberg, Sl, Kalaycio, M, Moiraghi, B, Rowe, Jm, Tothova, E, De Souza, C, Rudoltz, M, Yu, R, Krahnke, T, Kantarjian, Hm, Radich, Jp, Hughes, T. P., Hughes, Tp, Cortes JE, Baccarani M, Guilhot F, Druker BJ, Branford S, Kim DW, Pane F, Pasquini R, Goldberg SL, Kalaycio M, Moiraghi B, Rowe JM, Tothova E, De Souza C, Rudoltz M, Yu R, Krahnke T, and Kantarjian HM

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Myeloid, Adolescent, medicine.drug_class, Antineoplastic Agents, Gastroenterology, Tyrosine-kinase inhibitor, Piperazines, Young Adult, Internal medicine, medicine, Humans, Adverse effect, Protein Kinase Inhibitors, Aged, Dose-Response Relationship, Drug, business.industry, Myeloid leukemia, Imatinib, ORIGINAL REPORTS, Middle Aged, Protein-Tyrosine Kinases, medicine.disease, Surgery, Leukemia, medicine.anatomical_structure, Imatinib mesylate, Pyrimidines, Treatment Outcome, Oncology, Benzamides, Leukemia, Myeloid, Chronic-Phase, Imatinib Mesylate, Female, business, Chronic myelogenous leukemia, medicine.drug
Abstract

Purpose To evaluate the safety and efficacy of initial treatment with imatinib mesylate 800 mg/d (400 mg twice daily) versus 400 mg/d in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Patients and Methods A total of 476 patients were randomly assigned 2:1 to imatinib 800 mg (n = 319) or 400 mg (n = 157) daily. The primary end point was the major molecular response (MMR) rate at 12 months. Results At 12 months, differences in MMR and complete cytogenetic response (CCyR) rates were not statistically significant (MMR, 46% v 40%; P = .2035; CCyR, 70% v 66%; P = .3470). However, MMR occurred faster among patients randomly assigned to imatinib 800 mg/d, who had higher rates of MMR at 3 and 6 months compared with those in the imatinib 400-mg/d arm (P = .0035 by log-rank test). CCyR also occurred faster in the 800-mg/d arm (CCyR at 6 months, 57% v 45%; P = .0146). The most common adverse events were edema, gastrointestinal problems, and rash, and all were more common in patients in the 800-mg/d arm. Grades 3 to 4 hematologic toxicity also occurred more frequently in patients receiving imatinib 800 mg/d. Conclusion MMR rates at 1 year were similar with imatinib 800 mg/d and 400 mg/d, but MMR and CCyR occurred earlier in patients treated with 800 mg/d. Continued follow-up is needed to determine the clinical significance of earlier responses on high-dose imatinib.

Published
2010

22. A global metagenomic map of urban microbiomes and antimicrobial resistance

Author

Nadine Farhat, Tomoki Takeda, Astred Castro, Ken McGrath, Khaliun Sanchir, Iman Hajirasouliha, Eunice So, Laraib Zafar, Diana N. Nunes, Harun Mustafa, Amy Zhang, Priscilla Lisboa, Christian Schori, Marisano James, Jasna Chalangal, Sebastien Halary, Shahryar Rana, Yunmi Lee, Oli Schacher, Liliana Godoy, David A. Coil, Phanthira Pugdeethosal, Michelle D. Williams, German Marchandon, Angela Cantillo, Naoya Takahashi, Christopher Mozsary, Juana Gonzalez, Patrick K. H. Lee, Gerardo de Lamotte, Alessandro Robertiello, Steven Du, Fabienne Velter, Stefan G. Stark, Miguel Carbajo, Vincent Matthys, David A. Westfall, Julia Boeri, Irène Mauricette Mendy, Jonathan Cedillo, Francesco Oteri, Robert W. Crawford, Takayuki Ito, Tina Wunderlin, Maureen Muscat, David Paez-Espino, Carmen Urgiles, Aida Nesimi, Steffen Schaaf, Adan Ramirez-Rojas, Kunihiko Miyake, Christopher E. Mason, Anais Cardenas, Sharah Islam, Diego Benítez, Melissa Pool Pizzi, Kianna Ciaramella, Ciro Borrelli, Riham Islam, Dorottya Nagy-Szakal, Abd-Manaaf Bakere, Ait-hamlat Adel, Olha Lakhneko, Badamnyambuu Iderzorig, Ana Valeria Castro, Adam Phillips, Robert A. Petit, Flavia Corsi, Romain Conte, Krista Ryon, Soojin Jang, Joseph Benson, Fernanda de Souza Gomes Kehdy, Cindy Wang, Nicole Mathews, Jenn-Wei Chen, Rachel Paras, Paulina Pastuszek, Abigail Lyons, Paul Roldán, Muntaha Munia, Pierre Nicolas, Cassie L. Ettinger, Kyrylo Pyrshev, Katterinne N. Mendez, Eduardo Castro-Nallar, Valeriia Dotsenko, Michelle Tuz, Krizzy Mallari, Eileen Png, Yuya Sonohara, Tanja Miketic, Stéphane Delmas, Shu Zhang, Masaki Sato, Yuanting Zheng, Jifeng Zhu, Roland Häusler, Lucie Bittner, Savlatjon Rahmatulloev, Jonathan Foox, Bruno D'Alessandro, Alketa Plaku, Faisal Alquaddoomi, Yang Zhang, Kern Rei Chng, Juliana Lago, Allaeddine Chettouh, Tamera Henry, Houtan Noushmehr, Tranette Gregory, Sara Abdul Majid, Frank J. Kelly, Benjamin Pulatov, Laurie Casalot, Takema Kajita, Lennard Epping, Thais Fernanda Bartelli, Eftar Moniruzzaman, Renee Vivancos-Koopman, Thirumalaisamy P. Velavan, Tracy W. Liu, Yelyzaveta Tymoshenko, Alma Plaku, Nika Gurianova, Ambar Mendez, Anna Tomaselli, Sonia Dorado, Donato Giovannelli, Hira Choudhry, Synti Ng, Sheelta S. Kumar, Jennifer Q. Lu, Weijun Liang, Ellen Koag, Dennis Gankin, Maria João Amorim, Gwenola Simon, Kiyoshi Suganuma, Mikhail Karasikov, Christos A. Ouzounis, Madelyn May, Eran Elhaik, Stephan Ossowski, Kevin Bolzli, Matthew Arthur, Yuya Oto, Jananan Pathmanathan, Salah Mahmoud, Kou Takahashi, Brunna Marques, Kelly French, Felipe Sepúlveda, Shusei Yoshikawa, Paulo Thiago de Souza Santos, Andrew N. Gray, Juliana S Bernardes, Felipe Segato, Björn Brindefalk, George C. Yeh, Jhovana L. Velasco Flores, Jill Sullivan, Silva Baburyan, Denisse Flores, Russell Y. Neches, Sabrina Persaud, Rasheena Wright, Takumi Togashi, Verónica Antelo, Nao Kato, Skye Felice, Tatjana Mustac, Daisy Donnellan, Katerine Carrillo, Anna Litskevitch, Catalina García, Sota Ito, Naya Eady, Andrew Wan, Irene Meng, Sophie Guasco, Danilo Ercolini, Francesca De Filippis, Vincent Lemaire, Luice Fan, Lothar H. Wieler, Mariia Rybak, Jorge Sanchez, Jonathan S. Gootenberg, Itsuki Tomita, Maritza S Mosella, Laura Garcia, Natalka Makogon, Daisy Cheung, Hitler Francois Vasquez Arevalo, Freddy Asenjo, Gabriela P. Branco, Erika Cifuentes, Chloé Dequeker, Aspassia D. Chatziefthimiou, Alexis Terrero, Roy Meoded, Isabelle de Oliveira Moraes, Shaleni K. Singh, Orgil-Erdene Molomjamts, Karishma Miah, Laurent David, Wolfgang Haehr, Dao Phuong Giang, Romain Lannes, Prashanthi Ratnanandan, Ryota Yamanaka, Riccardo Vicedomini, Sadaf Ayaz, Oluwatosin M. Osuolale, Laura E. Vann, Gregory Chem, Andrea Gonzalez, Aszia Burrell, Ariel Chernomoretz, Sakura Ishizuka, Michelle Rivera, Avigdor Nosrati, Michelle B. Chen, Juliette Auvinet, Nils Ordioni, Tomoro Warashina, Guillaume Blanc, Tomislav Ivankovic, Christina Black, Lauren E. Hittle, David Hess-Homeier, Michael Kozhar, Hamood Suliman, Karobi Moitra, Saher Rahiel, Spyridon Gkotzis, Jenny Arevalo, Shaikh B. Iqbal, Beth Mutai, Mohammed Mohsin, Scott Tighe, Sylvie Collin, Yoshitaka Saito, Wayne Menary, Youping Deng, Lucy Lee, Esmeralda Jiminez, Ayuki Watanabe, Nikos C. Kyrpides, Natasha Mohan, Angelika Pupiec, Dedan Githae, Simone Cawthorne, Jonathan A. Eisen, Tomoki Iwashiro, Chiaki Homma, Thomas Saw Aung, Laura Molina, Marcus H. Y. Leung, Ophélie Da Silva, Yan Ling Wong, Hosna Noorzi, Mario Moreno, Alina Butova, Leming Shi, Brian W. Wong, Sarah S. Jackson, Moses Lin, Annabelle Meagher, Pujita Das, Catherine Burke, Mitsuki Ota, Maria Domenica Moccia, Nicolas Sprinsky, Catherine E. Pugh, David C. Green, Fazlina Fauzi, Erdenetsetseg Batdelger, Annie Geiger, Valeria Ventorino, Tolulope Oluwadare, Delisia Cuebas, Catalina Truong, Leonardo Posada, Michael Angelov, Tathiane M. Malta, Amanda Ng, Francesca Nadalin, Arya Hawkins-Zafarnia, Yuh Shiwa, Athena Mitsios, Milton Ozório Moraes, Manolo Laiola, Kalyn Ali, Jaden J.A. Hastings, Ikuto Saito, Maheen Shakil, Chisato Suzuki, Elena M. Vayndorf, Hubert Rehrauer, Ajay Menon, Kaitlan Russell, Aliyah Shari, Rebecca Smith, Gregorio Iraola, Max Priestman, Alan Briones, Silver A. Wolf, Camila Gonzalez-Poblete, Eleonora De Lazzari, Shirley Chiu, Michelle Ki, Irene Hoxie, Marianne Jaubert, Ayantu Jinfessa, Ryan J. King, Nghiem Xuan Hoan, Jalia Bynoe, Jacob Friedman, Aneisa Ramcharan, Pablo Fresia, Cristina Muñoz, Muhammad Afaq, Anyi Tang, Médine Benchouaia, Isabella Kuniko T. Takenaka, Anastasia Chasapi, Areeg Naeem, Hannah Benisty, Cecilia N. Cossio, Nathalie Hüsser, Mahfuza Sabina, Thais S. Sabedot, JoAnn Jacobs, Camila P. E. de Souza, Manuela Oliveira, Jean-Pierre Bouly, Mariko Usui, Wilson Miranda, Natalia Marciniak, Hiram Caballero, Samuel Weekes, Alexandra B. Graf, Emily Leong, Tatyana Nikolayeva, Dominique Thomas, Charlotte Greselle, Cecilia Salazar, Sreya Ray Chaudhuri, Kevin Becher, Sandra Roth, Ryusei Miura, Kari Oline Bøifot, Dimitri Manoir, Oliver Toth, Chandrima Bhattacharya, Manuel Perez, Isha Lamba, Takafumi Tsurumaki, Timothy D. Read, Anna-Lena M. Schinke, Ryan Sankar, Le Huu Song, Narasimha Rao Nedunuri, Emmanuel Dias-Neto, Ana Flávia Costa, Adiell Melamed, Christelle Desnues, Natalie R. Davidson, Aaron E. Darling, Hyung Jun Kim, Josephine Galipon, Jacqueline Orrego, Dimitar Vassilev, Michael Huber, Nur Hazlin Hazrin-Chong, Gaston H. Gonnet, Kaymisha Knights, Osman U. Sezerman, Dmitry Meleshko, Eunice Thambiraja, Jingcheng Yang, Aubin Fleiss, Gloria Nguyen, Katelyn Jackson, Nuria Aventin, Stephanie L. Hyland, Andrea Hässig, Catharine Aquino, Simona Lysakova, Israel O. Osuolale, Kasia Sluzek, Rania Siam, Alina Frolova, Samuel Hernandez, Yui Him Lo, Bazartseren Boldgiv, Ben Young, Maryna Korshevniuk, Majelia Ampadu, Yuk Man Tang, Amanda L. Muehlbauer, Sade Thomas, Gabriel Figueroa, Alexis Rivera, Lisbeth Pineda, Alexandra Dutan, Jennifer M. Tran, Chris K. Deng, Vedbar S. Khadka, Paola Florez de Sessions, Elizabeth Humphries, Hugues Richard, Hiba Naveed, Nora C. Toussaint, Mahshid Khavari, Maria del Mar Vivanco Ruiz, Antonin Thiébaut, Nicolás Rascovan, Marius Dybwad, Orhan Özcan, Lawrence Kwong, David Danko, Shaira Khan, Andrea Tassinari, Silvia Beurmann, Tsoi Ying Lai, Nanami Kubota, Tieliu Shi, Diana Chicas, Evan E. Afshin, Hirokazu Yano, Jonas Krebs, Mayuko Nakagawa, Hyun Jung Lee, Irene González Navarrete, Rachid Ounit, Lucia E. Alvarado-Arnez, Masaki Nasu, Allison Chan, Harilanto Andrianjakarivony, Jennifer Amachee, Mahdi Taye, Wan Chiew Ng, Kathryn O’Brien, Shino Ishikawa, Tristan Bitard-Feildel, Sora Takagi, Felix Hartkopf, Niamh B. O’Hara, Marcos A. S. Fonseca, Subhamitra Pakrashi, Amrit Kaur, Eva Hell, Patricia Vera-Wolf, Naimah Munim, Luiza Ferreira de Araújo, Mizuki Igarashi, Brianna Pompa-Hogan, Alessandra Carbone, Anne-Sophie Benoiston, Eric Helfrich, Michael A. Suarez-Villamil, Omar O. Abudayyeh, Natasha Abdullah, Jaime J. Fuentes, Juan Carlos Forero, Tetiana Yeskova, Denis Bertrand, Sambhawa Priya, Denisse Maldonado, Agier Nicolas, Ana Valeria B Castro, Starr Chatziefthimiou, André Kahles, Aaishah Francis, Fernanda Arredondo, Emilio Tarcitano, Irvind Buttar, Alex Alexiev, Jennifer Molinet, Sarah Shalaby, Itunu A. Oluwadare, Jason Sperry, Katrin Bakhl, Ana M. Cañas, Sofia Ahsanuddin, Miar Elaskandrany, Elodie Laine, Sven Bönigk, Johannes Werner, Stephen Eduard Boja Ruiz, Gargi Dayama, Paulina Buczansla, Brandon Valentine, Bharath Prithiviraj, Toni Bode, Stas Zubenko, Jake Cohen, Guilllaume Jospin, Zulena Saravi, Per O. Ljungdahl, Inderjit Kaur, Mauricio Moldes, Giuseppe KoLoMonaco, Denise Syndercombe Court, Sonia Bouchard, Sonia Losim, Sookwon Moon, Heba Shaaban, Suraj Patel, Sibo Zhu, Sarh Aly, Arif Asyraf Md Supie, LaShonda Dorsey, Juan Guerra, François Baudon, Rantimi A. Olawoyin, Alexia Bordigoni, Iqra Faiz, Mathilde Garcia, Gabriella Mason-Buck, María Gabriela Portilla, Niranjan Nagarajan, Fumie Takahara, Nancy Merino, Watson Andrew, Gina Kim, Yuma Sato, Hyenah Shim, Marie-Laure Jerier, Affifah Saadah Ahmad Kassim, Katerina Kuchin, Daniel Butler, Paweł P. Łabaj, Nadezhda Kobko-Litskevitch, Emmanuel F. Mongodin, Yuto Togashi, Paula Rodríguez, Pilar Lopez Hernandez, Xiaoqing Chen, Maria A. Sierra, Olga Nikolayeva, Manon Loubens, Colleen Conger, Hikaru Shirahata, Chenhao Li, Timothy Donahoe, Youngja Park, Lucia Elena Alvarado Arnez, Salama Chaker, Francisco Chavez, Alessandra Breschi, Jorge L. Sanchez, Kaung Myat San, Nayra Aguilar Rojas, Marcos Abraao, Kai Sasaki, Bryan Nazario, Olena Yemets, Klas I. Udekwu, Lynn M. Schriml, Anisia Peters, Aliaksei Holik, Mark Hernandez, Emile Faure, Malay Bhattacharyya, Josef W. Moser, Núria Andreu Somavilla, María Mercedes Zambrano, Kannan Rajendran, Gabriela E. Albuquerque, Tao Qing, Kazutoshi Tsuda, Ymke De Jong, Princess Osma, Mayra Arauco Livia, Javier Quilez Oliete, Carl Chrispin, Hyun Woo Joo, Ingrid Lafontaine, Nala An, Seisuke Sato, Felipe Segato Dezem, Andrew Maltez Thomas, Alexandre Desert, Xiao Wen Cai, O. Osuolale, Jun Wu, Coral Pardo-Esté, Courtney Robinson, Yuri Matsuzaki, Marina Nieto-Caballero, Cem Meydan, Ralph Schlapbach, Mark Menor, Sofia Castro, Rachel Kwong, Brittany Blyther, Olexandr Lykhenko, Jason R. Schriml, Christian Brion, Jenessa Orpilla, Juan A. Ugalde, Elsy Mankah Ngwa, Álvaro Aranguren, Lauren Mak, Matías Giménez, Ashanti Narce, Torsten Semmler, Stefan I. Tsonev, Abdollahi Nika, Katherine E. Dahlhausen, Monika Devi, Gunnar Rätsch, Oasima Muner, Carla Bello, Muhammad Al-Fath Amran, Anyelic Rosario, Melissa Ortega, Andrea Patrignani, Ante Peros, Elias McComb, Ryo Sato, Ireen Alam, Clara N. Dias, Soma Tanaka, Dayana Calderon, Ran Blekhman, Mathilde Mignotte, Alicia Boyd, Jochen Hecht, Thomas Neff, Xinzhao Tong, Josue Alicea, Kiara Olmeda, Sonia Marinovic, Carme Arnan, Kohei Ito, Samantha L. Goldman, Marianna S. Serpa, Renee Richer, Kaisei Sato, Jordana M. Silva, Akash Keluth Chavan, Sangwan Kim, Laís Pereira Ferreira, Sophie Vacant, Nowshin Sayara, Haruo Suzuki, Madeline Leahy, Juan C. Severyn, Sierra Vincent, Masaru Tomita, Maliha Mamun, Lucinda B. Davenport, Gabriella Oken, Dagmara Lewandowska, Gustavo Adolfo Malca Salas, Andrii Kuklin, Tyler Wong, Charlie Feigin, Eric Minwei Liu, Sonia L. Ghose, Daniela Bezdan, Antonietta La Storia, Juan P. Escalera-Antezana, Nuno Rufino de Sousa, Samuel M. Gerner, Weill Cornell Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Genome Institute of Singapore (GIS), Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), AUTRES, Massachusetts Institute of Technology (MIT), Indian Statistical Institute [Kolkata], University of Minnesota System, Universidad Andrés Bello [Santiago] (UNAB), California State University [Sacramento], University of Naples Federico II, University of Hawaii, Institut méditerranéen d'océanologie (MIO), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN), Medical Genomics Group, University College of London [London] (UCL)-UCL Cancer Institute, Norwegian Defence Research Establishment (FFI), Lund University [Lund], Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, University of Vienna [Vienna], King‘s College London, University of Colorado [Boulder], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur Korea - Institut Pasteur de Corée, Fudan University [Shanghai], City University of Hong Kong [Hong Kong] (CUHK), Stockholm University, University of Maryland School of Medicine, University of Maryland System, Fundação Oswaldo Cruz (FIOCRUZ), University of São Paulo (USP), Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Barcelona Institute of Science and Technology (BIST), Elizade University, Acibadem Mehmet Ali Aydınlar University, Paléogénomique microbienne - Microbial paleogenomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Robert Koch Institute [Berlin] (RKI), East China Normal University [Shangaï] (ECNU), Cairo University, Vietnamese-German Center for Medical Research, Keio University, Université du Vermont, Universidad del Desarrollo, University of Sofia, University of Alaska [Fairbanks] (UAF), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Corporación Corpogen-Research Center, Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Weill Cornell Medicine [Cornell University], Cornell University [New York], University of Naples Federico II = Università degli studi di Napoli Federico II, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Universidade de São Paulo = University of São Paulo (USP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Софийски университет = Sofia University, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad Andrés Bello - UNAB (CHILE), Acibadem University Dspace, Danko, D., Bezdan, D., Afshin, E. E., Ahsanuddin, S., Bhattacharya, C., Butler, D. J., Chng, K. R., Donnellan, D., Hecht, J., Jackson, K., Kuchin, K., Karasikov, M., Lyons, A., Mak, L., Meleshko, D., Mustafa, H., Mutai, B., Neches, R. Y., Ng, A., Nikolayeva, O., Nikolayeva, T., Png, E., Ryon, K. A., Sanchez, J. L., Shaaban, H., Sierra, M. A., Thomas, D., Young, B., Abudayyeh, O. O., Alicea, J., Bhattacharyya, M., Blekhman, R., Castro-Nallar, E., Canas, A. M., Chatziefthimiou, A. D., Crawford, R. W., De Filippis, F., Deng, Y., Desnues, C., Dias-Neto, E., Dybwad, M., Elhaik, E., Ercolini, D., Frolova, A., Gankin, D., Gootenberg, J. S., Graf, A. B., Green, D. C., Hajirasouliha, I., Hastings, J. J. A., Hernandez, M., Iraola, G., Jang, S., Kahles, A., Kelly, F. J., Knights, K., Kyrpides, N. C., Labaj, P. P., Lee, P. K. H., Leung, M. H. Y., Ljungdahl, P. O., Mason-Buck, G., Mcgrath, K., Meydan, C., Mongodin, E. F., Moraes, M. O., Nagarajan, N., Nieto-Caballero, M., Noushmehr, H., Oliveira, M., Ossowski, S., Osuolale, O. O., Ozcan, O., Paez-Espino, D., Rascovan, N., Richard, H., Ratsch, G., Schriml, L. M., Semmler, T., Sezerman, O. U., Shi, L., Shi, T., Siam, R., Song, L. H., Suzuki, H., Court, D. S., Tighe, S. W., Tong, X., Udekwu, K. I., Ugalde, J. A., Valentine, B., Vassilev, D. I., Vayndorf, E. M., Velavan, T. P., Wu, J., Zambrano, M. M., Zhu, J., Zhu, S., Mason, C. E., Abdullah, N., Abraao, M., Adel, A. -H., Afaq, M., Al-Quaddoomi, F. S., Alam, I., Albuquerque, G. E., Alexiev, A., Ali, K., Alvarado-Arnez, L. E., Aly, S., Amachee, J., Amorim, M. G., Ampadu, M., Amran, M. A. -F., An, N., Andrew, W., Andrianjakarivony, H., Angelov, M., Antelo, V., Aquino, C., Aranguren, A., Araujo, L. F., Vasquez Arevalo, H. F., Arevalo, J., Arnan, C., Alvarado Arnez, L. E., Arredondo, F., Arthur, M., Asenjo, F., Aung, T. S., Auvinet, J., Aventin, N., Ayaz, S., Baburyan, S., Bakere, A. -M., Bakhl, K., Bartelli, T. F., Batdelger, E., Baudon, F., Becher, K., Bello, C., Benchouaia, M., Benisty, H., Benoiston, A. -S., Benson, J., Benitez, D., Bernardes, J., Bertrand, D., Beurmann, S., Bitard-Feildel, T., Bittner, L., Black, C., Blanc, G., Blyther, B., Bode, T., Boeri, J., Boldgiv, B., Bolzli, K., Bordigoni, A., Borrelli, C., Bouchard, S., Bouly, J. -P., Boyd, A., Branco, G. P., Breschi, A., Brindefalk, B., Brion, C., Briones, A., Buczansla, P., Burke, C. M., Burrell, A., Butova, A., Buttar, I., Bynoe, J., Bonigk, S., Boifot, K. O., Caballero, H., Cai, X. W., Calderon, D., Cantillo, A., Carbajo, M., Carbone, A., Cardenas, A., Carrillo, K., Casalot, L., Castro, S., Castro, A. V., Castro, A., Castro, A. V. B., Cawthorne, S., Cedillo, J., Chaker, S., Chalangal, J., Chan, A., Chasapi, A. I., Chatziefthimiou, S., Chaudhuri, S. R., Chavan, A. K., Chavez, F., Chem, G., Chen, X., Chen, M., Chen, J. -W., Chernomoretz, A., Chettouh, A., Cheung, D., Chicas, D., Chiu, S., Choudhry, H., Chrispin, C., Ciaramella, K., Cifuentes, E., Cohen, J., Coil, D. A., Collin, S., Conger, C., Conte, R., Corsi, F., Cossio, C. N., Costa, A. F., Cuebas, D., D'Alessandro, B., Dahlhausen, K. E., Darling, A. E., Das, P., Davenport, L. B., David, L., Davidson, N. R., Dayama, G., Delmas, S., Deng, C. K., Dequeker, C., Desert, A., Devi, M., Dezem, F. S., Dias, C. N., Donahoe, T. R., Dorado, S., Dorsey, L., Dotsenko, V., Du, S., Dutan, A., Eady, N., Eisen, J. A., Elaskandrany, M., Epping, L., Escalera-Antezana, J. P., Ettinger, C. L., Faiz, I., Fan, L., Farhat, N., Faure, E., Fauzi, F., Feigin, C., Felice, S., Ferreira, L. P., Figueroa, G., Fleiss, A., Flores, D., Velasco Flores, J. L., Fonseca, M. A. S., Foox, J., Forero, J. C., Francis, A., French, K., Fresia, P., Friedman, J., Fuentes, J. J., Galipon, J., Garcia, M., Garcia, L., Garcia, C., Geiger, A., Gerner, S. M., Ghose, S. L., Giang, D. P., Gimenez, M., Giovannelli, D., Githae, D., Gkotzis, S., Godoy, L., Goldman, S., Gonnet, G. H., Gonzalez, J., Gonzalez, A., Gonzalez-Poblete, C., Gray, A., Gregory, T., Greselle, C., Guasco, S., Guerra, J., Gurianova, N., Haehr, W., Halary, S., Hartkopf, F., Hawkins-Zafarnia, A., Hazrin-Chong, N. H., Helfrich, E., Hell, E., Henry, T., Hernandez, S., Hernandez, P. L., Hess-Homeier, D., Hittle, L. E., Hoan, N. X., Holik, A., Homma, C., Hoxie, I., Huber, M., Humphries, E., Hyland, S., Hassig, A., Hausler, R., Husser, N., Petit, R. A., Iderzorig, B., Igarashi, M., Iqbal, S. B., Ishikawa, S., Ishizuka, S., Islam, S., Islam, R., Ito, K., Ito, S., Ito, T., Ivankovic, T., Iwashiro, T., Jackson, S., Jacobs, J., James, M., Jaubert, M., Jerier, M. -L., Jiminez, E., Jinfessa, A., De Jong, Y., Joo, H. W., Jospin, G., Kajita, T., Ahmad Kassim, A. S., Kato, N., Kaur, A., Kaur, I., de Souza Gomes Kehdy, F., Khadka, V. S., Khan, S., Khavari, M., Ki, M., Kim, G., Kim, H. J., Kim, S., King, R. J., Kolomonaco, G., Koag, E., Kobko-Litskevitch, N., Korshevniuk, M., Kozhar, M., Krebs, J., Kubota, N., Kuklin, A., Kumar, S. S., Kwong, R., Kwong, L., Lafontaine, I., Lago, J., Lai, T. Y., Laine, E., Laiola, M., Lakhneko, O., Lamba, I., de Lamotte, G., Lannes, R., De Lazzari, E., Leahy, M., Lee, H., Lee, Y., Lee, L., Lemaire, V., Leong, E., Lewandowska, D., Li, C., Liang, W., Lin, M., Lisboa, P., Litskevitch, A., Liu, E. M., Liu, T., Livia, M. A., Lo, Y. H., Losim, S., Loubens, M., Lu, J., Lykhenko, O., Lysakova, S., Mahmoud, S., Majid, S. A., Makogon, N., Maldonado, D., Mallari, K., Malta, T. M., Mamun, M., Manoir, D., Marchandon, G., Marciniak, N., Marinovic, S., Marques, B., Mathews, N., Matsuzaki, Y., Matthys, V., May, M., Mccomb, E., Meagher, A., Melamed, A., Menary, W., Mendez, K. N., Mendez, A., Mendy, I. M., Meng, I., Menon, A., Menor, M., Meoded, R., Merino, N., Miah, K., Mignotte, M., Miketic, T., Miranda, W., Mitsios, A., Miura, R., Miyake, K., Moccia, M. D., Mohan, N., Mohsin, M., Moitra, K., Moldes, M., Molina, L., Molinet, J., Molomjamts, O. -E., Moniruzzaman, E., Moon, S., de Oliveira Moraes, I., Moreno, M., Mosella, M. S., Moser, J. W., Mozsary, C., Muehlbauer, A. L., Muner, O., Munia, M., Munim, N., Muscat, M., Mustac, T., Munoz, C., Nadalin, F., Naeem, A., Nagy-Szakal, D., Nakagawa, M., Narce, A., Nasu, M., Navarrete, I. G., Naveed, H., Nazario, B., Nedunuri, N. R., Neff, T., Nesimi, A., Ng, W. C., Ng, S., Nguyen, G., Ngwa, E., Nicolas, A., Nicolas, P., Nika, A., Noorzi, H., Nosrati, A., Nunes, D. N., O'Brien, K., O'Hara, N. B., Oken, G., Olawoyin, R. A., Oliete, J. Q., Olmeda, K., Oluwadare, T., Oluwadare, I. A., Ordioni, N., Orpilla, J., Orrego, J., Ortega, M., Osma, P., Osuolale, I. O., Osuolale, O. M., Ota, M., Oteri, F., Oto, Y., Ounit, R., Ouzounis, C. A., Pakrashi, S., Paras, R., Pardo-Este, C., Park, Y. -J., Pastuszek, P., Patel, S., Pathmanathan, J., Patrignani, A., Perez, M., Peros, A., Persaud, S., Peters, A., Phillips, A., Pineda, L., Pizzi, M. P., Plaku, A., Pompa-Hogan, B., Portilla, M. G., Posada, L., Priestman, M., Prithiviraj, B., Priya, S., Pugdeethosal, P., Pugh, C. E., Pulatov, B., Pupiec, A., Pyrshev, K., Qing, T., Rahiel, S., Rahmatulloev, S., Rajendran, K., Ramcharan, A., Ramirez-Rojas, A., Rana, S., Ratnanandan, P., Read, T. D., Rehrauer, H., Richer, R., Rivera, A., Rivera, M., Robertiello, A., Robinson, C., Rodriguez, P., Rojas, N. A., Roldan, P., Rosario, A., Roth, S., Ruiz, M., Boja Ruiz, S. E., Russell, K., Rybak, M., Sabedot, T. S., Sabina, M., Saito, I., Saito, Y., Malca Salas, G. A., Salazar, C., San, K. M., Sanchez, J., Sanchir, K., Sankar, R., de Souza Santos, P. T., Saravi, Z., Sasaki, K., Sato, Y., Sato, M., Sato, S., Sato, R., Sato, K., Sayara, N., Schaaf, S., Schacher, O., Schinke, A. -L. M., Schlapbach, R., Schori, C., Schriml, J. R., Segato, F., Sepulveda, F., Serpa, M. S., De Sessions, P. F., Severyn, J. C., Shakil, M., Shalaby, S., Shari, A., Shim, H., Shirahata, H., Shiwa, Y., Da Silva, O., Silva, J. M., Simon, G., Singh, S. K., Sluzek, K., Smith, R., So, E., Andreu Somavilla, N., Sonohara, Y., Rufino de Sousa, N., Souza, C., Sperry, J., Sprinsky, N., Stark, S. G., La Storia, A., Suganuma, K., Suliman, H., Sullivan, J., Supie, A. A. M., Suzuki, C., Takagi, S., Takahara, F., Takahashi, N., Takahashi, K., Takeda, T., Takenaka, I. K., Tanaka, S., Tang, A., Man Tang, Y., Tarcitano, E., Tassinari, A., Taye, M., Terrero, A., Thambiraja, E., Thiebaut, A., Thomas, S., Thomas, A. M., Togashi, Y., Togashi, T., Tomaselli, A., Tomita, M., Tomita, I., Toth, O., Toussaint, N. C., Tran, J. M., Truong, C., Tsonev, S. I., Tsuda, K., Tsurumaki, T., Tuz, M., Tymoshenko, Y., Urgiles, C., Usui, M., Vacant, S., Vann, L. E., Velter, F., Ventorino, V., Vera-Wolf, P., Vicedomini, R., Suarez-Villamil, M. A., Vincent, S., Vivancos-Koopman, R., Wan, A., Wang, C., Warashina, T., Watanabe, A., Weekes, S., Werner, J., Westfall, D., Wieler, L. H., Williams, M., Wolf, S. A., Wong, B., Wong, Y. L., Wong, T., Wright, R., Wunderlin, T., Yamanaka, R., Yang, J., Yano, H., Yeh, G. C., Yemets, O., Yeskova, T., Yoshikawa, S., Zafar, L., Zhang, Y., Zhang, S., Zhang, A., Zheng, Y., and Zubenko, S.

Subjects
Urban Population, Drug Resistance, Sequence assembly, Microbiologia, microbiome, global health, computer.software_genre, Medical and Health Sciences, shotgun sequencing, BGC, 0302 clinical medicine, Databases, Genetic, 11. Sustainability, Global health, AMR, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, built environment, metagenome, antimicrobial resistance, NGS, de novo assembly, biology, Shotgun sequencing, Microbiota, built Environment, Bacterial, Biodiversity, Biological Sciences, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infection, Biotechnology, Geospatial analysis, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Article, General Biochemistry, Genetics and Molecular Biology, Databases, 03 medical and health sciences, Antibiotic resistance, Genetic, Drug Resistance, Bacterial, International MetaSUB Consortium, Genetics, Humans, Microbiome, 030304 developmental biology, Human Genome, 06 Biological Sciences, 15. Life on land, biology.organism_classification, Resistènica als medicaments antiinfecciosos, SAÚDE PÚBLICA, Genòmica, 13. Climate action, Evolutionary biology, Metagenomics, Antimicrobial Resistance, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, computer, 030217 neurology & neurosurgery, Archaea, Developmental Biology
Abstract

Summary We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities., Graphical abstract, Highlights • Cities possess a consistent “core” set of non-human microbes • Urban microbiomes echo important features of cities and city-life • Antimicrobial resistance genes are widespread in cities • Cities contain many novel bacterial and viral species, This systematic, worldwide catalog of urban microbiomes represents a metagenomic atlas important for understanding the ecology, virulence, and antibiotic resistance of city-specific microbial communities.

Published
2021

23. Glycogen storage disease type Ia: Current management options, burden and unmet needs

Author

A. Rossi, Heather Saavedra, Philippe Labrune, Vassili Valayannopoulos, Ayesha Ahmad, Nerea López Maldonado, Terry G J Derks, Sarah C. Grünert, David Rodriguez-Buritica, Carolina Fischinger Moura de Souza, Rebecca Riba-Wolman, John J. Mitchell, Rupal Naik Gupta, Foekje de Boer, María L. Couce, Derks, T. G. J., Rodriguez-Buritica, D. F., Ahmad, A., de Boer, F., Couce, M. L., Grunert, S. C., Labrune, P., Lopez Maldonado, N., Fischinger Moura de Souza, C., Riba-Wolman, R., Rossi, A., Saavedra, H., Gupta, R. N., Valayannopoulos, V., and Mitchell, J.

Subjects
Liver/metabolism, Quality of life, medicine.medical_specialty, Review, Disease, Glycemic Control, Carbohydrate metabolism, Glycogen Storage Disease Type I, Kidney, chemistry.chemical_compound, Cost of Illness, Glycogen storage disease type Ia, Long-term complication, Medicine, Glucose homeostasis, Humans, TX341-641, Intensive care medicine, Uncooked cornstarch, Health Services Needs and Demand, Nutrition and Dietetics, Glycogen, business.industry, Nutrition. Foods and food supply, Burden of disease, Disease Management, Starch, long-term complications, Hypoglycemia/etiology, Hypoglycemia, Dietary treatment, Cost of Illne, Kidney/metabolism, chemistry, Liver, Metabolic control analysis, Anxiety, Glycemic Control/methods, Glycogen Storage Disease Type I/complications, medicine.symptom, business, Psychosocial, Starch/administration & dosage, Food Science, Unmet need, Human
Abstract

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists if a single dose of UCCS is delayed/missed or in cases of gastrointestinal intolerance. UCCS therapy is imprecise, does not treat the cause of disease, may trigger secondary metabolic manifestations and may not prevent long-term complications. We review the importance of and challenges associated with achieving good glycaemic/metabolic control in individuals with GSDIa and how this should be balanced with age-specific psychosocial development towards independence, management of anxiety and preservation of quality of life (QoL). The unmet need for treatment strategies that address the cause of disease, restore glucose homeostasis, reduce the risk of hypoglycaemia/secondary metabolic perturbations and improve QoL is also discussed.

Published
2021

24. Sexual dysfunctions in female university students and the correlation with body image: a cross-sectional study

Author

Paula Rodrigues Eberhardt, Rosalia Ragusa, Patrícia Viana da Rosa, Taís Marques Cerentini, Pasquale De Franciscis, Cislaine Machado de Souza, Luis Henrique Telles da Rosa, Valentina Lucia La Rosa, Gaetano Riemma, Salvatore Caruso, Rodrigues Eberhardt, P., La Rosa, V. L., Marques Cerentini, T., Caruso, S., Ragusa, R., De Franciscis, P., Riemma, G., Machado de Souza, C., Telles da Rosa, L. H., and Viana da Rosa, P.

Subjects
Universities, Cross-sectional study, body image, education, Sexual dysfunction, Human sexuality, Computer-assisted web interviewing, Correlation, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), university, Surveys and Questionnaires, medicine, Humans, 030212 general & internal medicine, Sexual Dysfunctions, Psychological, Students, 030219 obstetrics & reproductive medicine, Obstetrics and Gynecology, sexuality, Psychiatry and Mental health, Clinical Psychology, Sexual Dysfunction, Physiological, Cross-Sectional Studies, Reproductive Medicine, quality of life, Female, medicine.symptom, Psychology, Clinical psychology
Abstract

Purpose: This study aims to correlate female sexual dysfunctions and dissatisfaction with female university students' body image. Methods: 276 female university students completed an online questionnaire, including sociodemographic data, the Female Sexual Function Index, and the Body Shape Questionnaire. Results: 31.1% reported some degree of dissatisfaction with body image, and 39.5% had a risk of female sexual dysfunction. The majority of women with a risk of female sexual dysfunctions (69.4%) had no concerns with shape, and the majority of women without sexual problems (67.7%) had no concerns with shape. Pearson’s coefficient underlined no correlation between Body Shape Questionnaire and Female Sexual Function Index domains. Conclusion: The body image perception did not seem to affect the sexual function of female university students in our sample. However, it is important to further investigate these variables to improve women’s quality of life.

Published
2020

25. The epileptology of GNB5 encephalopathy

Author

Giuseppe Merla, Alison M. Muir, Boris Keren, Natascia Malerba, Chontelle King, Ingrid E. Scheffer, Peter Kannu, Brian H.Y. Chung, Gemma Poke, Mahendranath Moharir, Michele Germano, Carolina Fischinger Moura de Souza, Jasmine L.F. Fung, Guillem de Valles-Ibáñez, Heather C Mefford, Thorsten Stanley, Lynette G. Sadleir, Zhuo Shao, Anne Isabelle Vermersch, Cyril Mignot, Adina Ilea, Cheuk Wing Fung, Suzanne Davis, Poke, G., King, C., Muir, A., de Valles Ibáñez, G., Germano, M., de Souza, C., Fung, J., Chung, B., Fung, Cw, Mignot, C., Ilea, A., Keren, B., Davis, S., Stanley, T., Moharir, M., Kannu, P., Shao, Z., Malerba, N., Merla, G, Mefford, Hc, Scheffer, Ie, and Sadleir, Lg.

Subjects
0301 basic medicine, Male, Pediatrics, medicine.medical_specialty, Adolescent, Encephalopathy, 03 medical and health sciences, Epilepsy, Young Adult, 0302 clinical medicine, medicine, Humans, Child, Cerebral atrophy, Brain Diseases, business.industry, GTP-Binding Protein beta Subunits, medicine.disease, Hypotonia, Hypsarrhythmia, Pedigree, Epileptic spasms, Burst suppression, 030104 developmental biology, Neurology, Child, Preschool, Cerebellar atrophy, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Pathogenic variants in GNB5 cause an autosomal recessive neurodevelopmental disorder with neonatal sinus bradycardia. Seizures or epilepsy occurred in 10 of 22 previously reported cases, including 6 children from one family. We delineate the epileptology of GNB5 encephalopathy. Our nine patients, including five new patients, were from seven families. Epileptic spasms were the most frequent seizure type, occurring in eight of nine patients, and began at a median age of 3 months (2 months to 3 years). Focal seizures preceded spasms in three children, with onset at 7 days, 11 days, and 4 months. One child presented with convulsive status epilepticus at 6 months. Three children had burst suppression on electroencephalography (EEG), three had hypsarrhythmia, and one evolved from burst suppression to hypsarrhythmia. Background slowing was present in all after age 3 years. Magnetic resonance imaging (MRI) showed cerebral atrophy in one child and cerebellar atrophy in another. All nine had abnormal development prior to seizure onset and ultimately had profound impairment without regression. Hypotonia was present in all, with contractures developing in two older patients. All individuals had biallelic pathogenic variants in GNB5, predicted by in silico tools to result in protein truncation and loss-of-function. GNB5 developmental and epileptic encephalopathy is characterized by epileptic spasms, focal seizures, and profound impairment. Wiley Periodicals, Inc. © 2019 International League Against Epilepsy

Published
2019

26. Validation of a reaction volume reduction protocol for analysis of Y chromosome haplotypes targeting DNA databases

Author

S M Souza, A F Caldas Junior, Reginaldo Inojosa Carneiro Campello, R. A. Queiroz, T C Oliveira, A A Antunes, E P Soriano, G G Porto, Marcus Vitor Diniz de Carvalho, K C N Rabêlo, C A Souza, Sergio Crovella, Sandra Maria dos Santos, Souza, C A, Oliveira, T C, Crovella, S, Santos, S M, Rabêlo, K C N, Soriano, E P, Carvalho, M V D, Junior, A F Calda, Porto, G G, Campello, R I C, Antunes, A A, Queiroz, R A, and Souza, S M

Subjects
Male, Validation study, Sample (material), Forensic genetics, Biology, computer.software_genre, Y chromosome, Polymerase Chain Reaction, chemistry.chemical_compound, Genetics, Humans, Volume reduction, Y haplotype, Molecular Biology, Uniparental markers, Uniparental marker, Chromosomes, Human, Y, Database, Genetic profiles, General Medicine, Forensic genetic, Haplotypes, chemistry, Volume (thermodynamics), Reagent, Databases, Nucleic Acid, computer, DNA, Microsatellite Repeats
Abstract

The use of Y chromosome haplotypes, important for the detection of sexual crimes in forensics, has gained prominence with the use of databases that incorporate these genetic profiles in their system. Here, we optimized and validated an amplification protocol for Y chromosome profile retrieval in reference samples using lesser materials than those in commercial kits. FTA(®) cards (Flinders Technology Associates) were used to support the oral cells of male individuals, which were amplified directly using the SwabSolution reagent (Promega). First, we optimized and validated the process to define the volume and cycling conditions. Three reference samples and nineteen 1.2 mm-diameter perforated discs were used per sample. Amplification of one or two discs (samples) with the PowerPlex(®) Y23 kit (Promega) was performed using 25, 26, and 27 thermal cycles. Twenty percent, 32%, and 100% reagent volumes, one disc, and 26 cycles were used for the control per sample. Thereafter, all samples (N = 270) were amplified using 27 cycles, one disc, and 32% reagents (optimized conditions). Data was analyzed using a study of equilibrium values between fluorophore colors. In the samples analyzed with 20% volume, an imbalance was observed in peak heights, both inside and in-between each dye. In samples amplified with 32% reagents, the values obtained for the intra-color and inter-color standard balance calculations for verification of the quality of the analyzed peaks were similar to those of samples amplified with 100% of the recommended volume. The quality of the profiles obtained with 32% reagents was suitable for insertion into databases.

Published
2017

27. Human autosomal DNA and X chromosome STR profiles obtained from Chrysomya albiceps (Diptera: Calliphoridae) larvae used as a biological trace

Author

Sergio Crovella, A B R Santos, T C Oliveira, K C N Rabêlo, S M Santos, C A Souza, Oliveira, T C, Santos, A B R, Rabelo, K C N, Souza, C A, Santos, S M, and Crovella, S

Subjects
030231 tropical medicine, Dipterians, Forensic genetics, Biology, Real-Time Polymerase Chain Reaction, Chromosomes, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Haplotype, Genetics, Animals, Humans, Short tandem repeat, 030216 legal & forensic medicine, Chrysomya albiceps, Forensic entomology, Calliphoridae, Molecular Biology, Uniparental marker, Uniparental markers, Chromosomes, Human, X, Animal, Short tandem repeats, DNA, Digestive System, Diptera, Genetic Loci, Haplotypes, Larva, Microsatellite Repeats, Forensic genetic, General Medicine, biology.organism_classification, DNA extraction, genomic DNA, chemistry, Microsatellite Repeat, Microsatellite, Dipterian, Human
Abstract

The use of insects to answer questions in criminal investigations, as well as a combination of forensic genetic techniques to obtain human DNA from the organisms, especially necrophagous dipterians, have gained ground in recent decades among researchers and professionals in this area. The objective of our study was to evaluate and compare two methods of human DNA extraction, commonly used for forensic samples, to obtain human autosomal DNA and X chromosome short tandem repeat profiles from the digestive tract of Chrysomya albiceps (Diptera: Calliphoridae) larvae. Immature specimens were collected from corpses at the Institute of Forensic Medicine of Pernambuco and raised in bovine ground meat to allow stabilization of the colony. Groups of larvae in the third instar were provided with bovine ground meat plus human blood for 48 h, dissected, and then subjected to DNA extraction. DNA was extracted using two methods: a DNA IQ™ kit and a phenol-chloroform method. Genomic DNA was amplified using AmpFℓSTR(®) Identifiler(®) Plus PCR and Argus-X-12(®) kits, and samples were sequenced to determine if the two extraction techniques generated reliable profiles that were compatible with a reference sample. The existence of comparable profiles from both techniques demonstrates the usefulness of dipteran larvae for obtaining human DNA from corpses, which can be further used to correlate genetic profiles in a crime scene when other traces are not available. However, several variables still require revision; thus, the technique should be further investigated for its validity, security, and, in particular, its reproducibility.

Published
2016

28. Outcome of patients with chronic myeloid leukemia and a low-risk score: allogeneic hematopoietic stem cell transplantation in the era of targeted therapy. A report from the EBMT Chronic Malignancies Working Party

Author

Koenecke, C., Heim, D., Biezen, A. van, Heuser, M., Aljurf, M., Kyrcz-Krzemien, S., Volin, L., Souza, C.A. de, Gedde-Dahl, T., Sengeloev, H., Schanz, U., Komarnicki, M., Arroyo, C.H., Tholouli, E., Gluckman, E., Esquirol, A., Yakoub-Agha, I., Gurman, G., Olavarria, E., Kroger, N., Rovira, M., Kahls, P., Alegre, A., Nemet, D., Stamatovic, D., Vitek, A., Hamladji, R., Hellmann, A., Chybicka, A., Wiktor-Jedrzejczak, W., Maiolino, A., Borne, P.V.D., Chevallier, P., Littlewood, T., Crawley, C., Mistrik, M., Schafer-Eckart, K., Orchard, K., Maertens, J., Lint, M. van, Ethell, M., Vettenranta, K., Broom, A., Deconinck, E., Schaap, N., Petersen, E., Espiga, C.R., Bartolomeo, P. di, Brown, P., Beelen, D., Leblond, V., Leleu, X., Carlson, K., Milpied, N., Collin, M., Johansson, J., Cairoli, R., Serwe, H., Schleuning, M., Ozturk, M., Lisukov, I.A., Robinson, S., Uckan-Cetinkaya, D., Rohrlich, P., Visani, G., Merli, F., Sanz, M., Michallet, M., Halaburda, K., O'Brien, T., Jindra, P., Feldman, L., Theobald, M., Favre, C., Rodeghiero, F., Finke, J., Koenecke, C, Heim, D, Van Biezen, A, Heuser, M, Aljurf, M, Kyrcz-Krzemien, S, Volin, L, De Souza, C, Gedde-Dahl, T, Sengeloev, H, Schanz, U, Komarnicki, M, Arroyo, C, Tholouli, E, Gluckman, E, Esquirol, A, Yakoub-Agha, I, Gurman, G, Olavarria, E, Kroger, N, Cairoli, R, and University of Zurich

Subjects
0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Adolescent, 2747 Transplantation, medicine.medical_treatment, 2720 Hematology, Decision Making, Medizin, 610 Medicine & health, Hematopoietic stem cell transplantation, Risk Assessment, Targeted therapy, 03 medical and health sciences, Young Adult, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Transplantation, Homologous, Molecular Targeted Therapy, Progenitor cell, Child, Transplantation, Homologou, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, medicine.disease, Algorithm, 030104 developmental biology, Graft-versus-host disease, Treatment Outcome, 10032 Clinic for Oncology and Hematology, Immunology, Female, Stem cell, business, Algorithms, Human, 030215 immunology, Chronic myelogenous leukemia
Abstract

Outcome of patients with chronic myeloid leukemia and a low-risk score: allogeneic hematopoietic stem cell transplantation in the era of targeted therapy. A report from the EBMT Chronic Malignancies Working Party

Published
2016

29. Detecting multiple DNA human profile from a mosquito blood meal

Author

V. B Tavares, Sergio Crovella, K C N Rabêlo, C A Souza, Cleide Maria Ribeiro de Albuquerque, Lucas André Cavalcanti Brandão, Ronald Moura, T C Oliveira, S M Santos, Rabêlo, K C N, Albuquerque, C M R, Tavares, V B, Santos, S M, Souza, C A, Oliveira, T C, Moura, R R, Brandão, L A C, and Crovella, S

Subjects
Forensic Genetics, Male, 0301 basic medicine, Forensic Genetic, Bites and Sting, chemistry.chemical_compound, Aedes aegypti, Aedes, Crime scene, Bites and Stings, DNA mixture, Genetics, biology, medicine.diagnostic_test, DNA mixtures, General Medicine, Healthy Volunteer, Healthy Volunteers, DNA profiling, Microsatellite Repeat, Female, Crime, Forensic DNA, Mosquito blood meal, Animals, Blood Cells, DNA, DNA Fingerprinting, Genetic Testing, Humans, Microsatellite Repeats, Molecular Biology, Aede, Human, 03 medical and health sciences, Blood Cell, medicine, Genetic testing, Animal, business.industry, fungi, biology.organism_classification, Blood meal, Biotechnology, 030104 developmental biology, chemistry, Suspect, business
Abstract

Criminal traces commonly found at crime scenes may present mixtures from two or more individuals. The scene of the crime is important for the collection of various types of traces in order to find the perpetrator of the crime. Thus, we propose that hematophagous mosquitoes found at crime scenes can be used to perform genetic testing of human blood and aid in suspect investigation. The aim of the study was to obtain a single Aedes aegypti mosquito profile from a human DNA mixture containing genetic materials of four individuals. We also determined the effect of blood acquisition time by setting time intervals of 24, 48, and 72 h after the blood meal. STR loci and amelogenin were analyzed, and the results showed that human DNA profiles could be obtained from hematophagous mosquitos at 24 h following the blood meal. It is possible that hematophagous mosquitoes can be used as biological remains at the scene of the crime, and can be used to detect human DNA profiles of up to four individuals.

Published
2016

30. Distribution of forensic marker allelic frequencies in Pernambuco, Northestern Brazil

Author

C A Souza, T C Oliveira, S M Santos, K C N Rabêlo, Sergio Crovella, Ronald Moura, Paulo Roberto Eleutério de Souza, Santos, S. M., Souza, C. A., Rabelo, K. C. N., Souza, P., Moura, R. R., Oliveira, T. C., and Crovella, Sergio

Subjects
Forensic Genetics, Genetic Markers, Heterozygote, Population data, Population, Autosomal STR, Locus (genetics), Paternity, Biology, Polymerase Chain Reaction, Loss of heterozygosity, Genetic, Gene Frequency, Autosomal STRs, Human identification, Genetics, Molecular Biology, Humans, Allele, education, Allele frequency, education.field_of_study, General Medicine, DNA Fingerprinting, Forensic science, Forensic identification, Genetics, Population, Microsatellite, Brazil, Microsatellite Repeats
Abstract

Pernambuco is one of the 27 federal units of Brazil, ranking seventh in the number of inhabitants. We examined the allele frequencies of 13 short tandem repeat loci (CFS1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, vWA, and TPOX), the minimum recommended by the Federal Bureau of Investigation and commonly used in forensic genetics laboratories in Brazil, in a sample of 609 unrelated individuals from all geographic regions of Pernambuco. The allele frequencies ranged from 5 to 47.2%. No significant differences for any loci analyzed were observed compared with other publications in other various regions of Brazil. Most of the markers observed were in Hardy-Weinberg equilibrium. The occurrence of the allele 47.2 (locus FGA) and alleles 35.1 and 39 (locus D21S11), also described in a single study of the Brazilian population, was observed. The other forensic parameters analyzed (matching probability, power of discrimination, polymorphic information content, paternity exclusion, complement factor I, observed heterozygosity, expected heterozygosity) indicated that the studied markers are very informative for human forensic identification purposes in the Pernambuco population.

Published
2015

31. Trace samples of human blood in mosquitoes as a forensic investigation tool

Author

Cleide Maria Ribeiro de Albuquerque, T C Oliveira, N.C.L. Oliveira, S M Santos, V. B Tavares, C A Souza, K C N Rabêlo, Sergio Crovella, Rabêlo, K. C. N, Albuquerque, C. M. R, Tavares, V. B, Santos, S. M, Souza, C. A, Oliveira, T. C, Oliveira, N. C. L, and Crovella, Sergio

Subjects
Forensic Genetics, Aedes albopictus, Zoology, Aedes aegypti, Mosquitoes blood meal, Gene Frequency, Genetics, medicine, Animals, Humans, Crime scene, Genetic Testing, Forensic entomology, Molecular Biology, Genetic testing, biology, medicine.diagnostic_test, fungi, DNA, General Medicine, biology.organism_classification, DNA Fingerprinting, Culex quinquefasciatus, Culicidae, DNA profiling, Microsatellite, Female, Crime, Forensic DNA, Microsatellite Repeats
Abstract

Investigations of any type of crime invariably starts at the crime scene by collecting evidence. Thus, the purpose of this research was to collect and analyze an entomological trace from an environment that is similar to those of indoor crime scenes. Hematophagous mosquitoes were collected from two residential units; saliva of volunteers that were residents in the units was also collected for genetic analysis as reference samples. We examined the allele frequencies of 15 short tandem repeat loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA) and amelogenin. A total of 26 female hematophagous mosquitoes were identified as Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus; we were able to obtain 11 forensically valid genetic profiles, with a minimum of 0.028203 ng/μL of human DNA. Thus, the results of this study showed that it was possible to correlate human genetic information from mosquitoes with the volunteer reference samples, which validates the use of this information as forensic evidence. Furthermore, we observed mixed genetic profiles from one mosquito. Therefore, it is clearly important to collect these insects indoors where crimes were committed, because it may be possible to find intact genetic profiles of suspects in the blood found in the digestive tract of hematophagous mosquitoes for later comparison to identify an offender and/or exclude suspects.

Published
2015

32. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia : results from the 24-month follow-up of the BELA trial

Author

Karin Gogat, Tim H. Brümmendorf, Ladan Duvillie, Carmino Antonio De Souza, François Guilhot, Dmitri Pavlov, Athena Countouriotis, Jorge E. Cortes, Carlo Gambacorti-Passerini, Brümmendorf, T, Cortes, J, de Souza, C, Guilhot, F, Duvillié, L, Pavlov, D, Gogat, K, Countouriotis, A, and GAMBACORTI PASSERINI, C

Subjects
Male, Oncology, Quinoline, Fusion Proteins, bcr-abl, Piperazines, Tyrosine-kinase inhibitor, Antineoplastic Agent, tyrosine kinase inhibitor, hemic and lymphatic diseases, Odds Ratio, CML, Aged, 80 and over, Aniline Compounds, Hematology, medicine.diagnostic_test, Haematological Malignancy, Aniline Compound, Middle Aged, Treatment Outcome, Tolerability, Benzamides, Leukemia, Myeloid, Chronic-Phase, Imatinib Mesylate, Quinolines, Female, Nitrile, Bosutinib, Human, medicine.drug, medicine.medical_specialty, chronic myeloid leukaemia, medicine.drug_class, Protein Kinase Inhibitor, Antineoplastic Agents, bosutinib, Neutropenia, Follow-Up Studie, Benzamide, Internal medicine, Nitriles, medicine, Humans, ddc:610, Adverse effect, Piperazine, Protein Kinase Inhibitors, Aged, business.industry, Imatinib, medicine.disease, BCR-ABL1, Pyrimidines, Pyrimidine, Mutation, Immunology, business, Liver function tests, Follow-Up Studies
Abstract

British journal of haematology 168(1), 69-81 (2015). doi:10.1111/bjh.13108, Published by Wiley-Blackwell, Oxford [u.a.]

Published
2015
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