tbuckley/cabot-search huggingface dataset:
Association Between Use of Thiopurines or Tumor Necrosis Factor Antagonists Alone or in Combination and Risk of Lymphoma in Patients With Inflammatory Bowel Disease
Authors: Magali Lemaitre, Julien Kirchgesner, Annie Rudnichi, Fabrice Carrat, Mahmoud Zureik, Franck Carbonnel, Rosemary Dray-Spira
Journal: JAMA (2017)

An increased risk of lymphoma has been reported among patients receiving thiopurines for inflammatory bowel disease (IBD). The risk of lymphoma associated with anti-tumor necrosis factor (TNF) agents either alone or in combination with thiopurines is uncertain.To assess the risk of lymphoma associated with thiopurines and anti-TNF agents, used alone or in combination, for the management of IBD.Nationwide cohort study based on French National Health Insurance databases. Patients aged 18 years or older identified with IBD were included from January 1, 2009, through December 31, 2013, and followed up until December 31, 2015.At each time of the follow-up, patients were categorized as being exposed to thiopurine monotherapy, anti-TNF monotherapy, or combination therapy, or being unexposed.The primary outcome was incident lymphoma.Among the 189 289 patients included (54% women; median age, 43 years [interquartile range, 32-56 years]) and followed up for a median of 6.7 years, 123 069 were never exposed during follow-up, 50 405 were exposed to thiopurine monotherapy, 30 294 to anti-TNF monotherapy, and 14 229 to combination therapy. Overall, 336 lymphoma cases occurred: 220 in unexposed patients (incidence rate [IR] per 1000 person-years, 0.26; 95% CI, 0.23-0.29), 70 in patients exposed to thiopurine monotherapy (IR, 0.54; 95% CI, 0.41-0.67), 32 in patients exposed to anti-TNF monotherapy (IR, 0.41; 95% CI, 0.27-0.55), and 14 in patients exposed to combination therapy (IR, 0.95; 95% CI, 0.45-1.45). In a multivariable Cox model, compared with unexposed patients, the risk of lymphoma was higher among those exposed to thiopurine monotherapy (adjusted hazard ratio [aHR], 2.60; 95% CI, 1.96-3.44; P < .001), anti-TNF monotherapy (aHR, 2.41; 95% CI, 1.60-3.64; P < .001), or combination therapy (aHR, 6.11; 95% CI, 3.46-10.8; P < .001). The risk was higher in patients exposed to combination therapy vs those exposed to thiopurine monotherapy (aHR, 2.35; 95% CI, 1.31-4.22; P < .001) or anti-TNF monotherapy (aHR, 2.53; 95% CI, 1.35-4.77; P < .001).Among adults with IBD, the use of thiopurine monotherapy or anti-TNF monotherapy was associated with a small but statistically significant increased risk of lymphoma compared with exposure to neither medication, and this risk was higher with combination therapy than with each of these treatments used alone. These findings may inform decisions regarding the benefits and risks of treatment.
GENE-29. DEEP PANEL SEQUENCING OF A PROSPECTIVELY COLLECTED GLIOMA COHORT
Authors: Siyuan Zheng, Wei Wei, Ken Chen, Kristin Alfaro-Munoz, Agda Karina Eterovic, Kenna Shaw, Gordon Mills, Funda Meric-Bernstam, Roel Verhaak, W K Alfred Yung, Shiao-Pei Weathers, John de Groot
Journal: Neuro-Oncology (2017)

Malignant gliomas are a group of intracranial cancers associated with disproportionately high mortality and morbidity. Recent studies from The Cancer Genome Atlas (TCGA) and others have provided important insights in the molecular subtypes and genomic alterations of these diseases1,2. Here we report our efforts to translate these insights into the clinic by ultradeep panel sequencing. We prospectively collected a cohort of 234 gliomas consisting of 164 glioblastomas (GBMs) and 64 lower grade gliomas (LGGs). We sequenced 214 tumors for a panel of 202 genes (T200), and 20 tumors for an updated panel of 262 genes (T200.1). For three tumors we sequenced two non-overlapping specimens to evaluate the intratumoral heterogeneity. We detected somatic mutations using a validated in-house protocol3. For the target region of approximately 106 base pairs (T200), we achieved an average depth of 1000x. We identified a total of 2190 somatic mutations (T200). However 12 tumors exhibited much higher mutation densities (≥30 mutations) than the remainder (mean=4, s.t.d=3), likely representing the hypermutator phenotype. TP53 was the most frequently mutated gene, followed by IDH1 and EGFR. We detected at least one EGFR mutations in 24% of LGGs in our cohort, compared with 6% in TCGA (p=3.8 × 10–5). IDH hotspot mutations were found with much higher frequencies in LGG (76%) and secondary GBM (65%) than primary GBM (8%). Univariate and multivariate analyses confirm the prognostic power of IDH mutation which was predicative of better outcome after adjusting for age, histology, grade, and extent of surgical resection. Nine of the 12 hypermuators were lower grade or secondary GBM, and seven were clearly associated with temozolomide as compared to none of the three primary or recurrent glioblastoma hypermutators. Our study suggests targeted sequencing can recapitulate previous findings and can be a useful approach in the clinical setting.
Beneficial Effect of Carotid Endarterectomy in Symptomatic Patients with High-Grade Carotid Stenosis
Authors: H J M Barnett, D W Taylor, R B Haynes, D L Sackett, S J Peerless, G G Ferguson, A J Fox, R N Rankin, V C Hachinski, D O Wiebers, M Eliasziw
Journal: New England Journal of Medicine (1991)

Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis.
SLUG down-regulates the expression of the tight junction proteins Occludin, Claudin-4 and Claudin-5 and confers invasive behavior to gastric carcinoma cells in an in vitro model
Authors: Catarina Alves, Maria Oliveira, Barbara Gomes, Raquel Seruca, Karl-Friedrich Becker, Fatima Carneiro
Journal: Cancer Research (2008)

5365  The transcription factor Slug plays an important role in Epithelial-Mesenchymal Transition (EMT) during embryonic development, by down-regulating the expression of epithelial genes, such as E-cadherin, conferring increased migration capabilities to cells. It has been proposed that EMT-like processes occur during tumor progression and invasion, in which cancer cells detach and migrate to organs away from the primary tumor. We have previously shown that Slug is overexpressed in primary gastric carcinomas (GC) and that its expression together with E-cadherin down-regulation was associated with the presence of distant metastasis and advanced TNM stages.  The aim of the present work was to further evaluate the role of Slug in GC progression in an in vitro GC model. For that, gastric carcinoma-derived NCI-N87 cells were stably transfected with human Slug. Despite the well described relationship between Slug expression and E-cadherin down-regulation, we found that this adhesion molecule was not the main target of Slug in our model, although some levels of down-regulation were observed. Instead, Slug expression resulted in the disassembly of tight junctions, through the down-regulation of Occludin, Claudin-4 and Claudin-5, as well as de novo expression of N-cadherin. Furthermore, it resulted in increased migration capabilities and invasion on Matrigel and in the decrease in cell-cell adhesion ability of these cells.  These findings suggest that Slug overexpression plays a critical role in the context of GC progression and invasion, leading to the loss of expression of important tight junction proteins and promoting invasive and motile behavior of cells.
Come l'Europa sta affrontando la resistenza antibiotica
Authors: M J Struelens
Journal: Eurosurveillance (2004)

In questo numero, Witte e colleghi descrivono l'emergenza, iniziata nel 2002 in Germania, dei casi di infezione da Staphylococcus aureus meticillino-resistente acquisito in comunita (c-MSRA) e produttore di leucocidina Panton-Valentine. Questo rapporto chiarisce la rapida disseminazione geografica in tutta Europa di questa variante emergente, iper-virulenta, di un vecchio patogeno.
Abstract 20397: The Impact of Healthy Lifestyle on Life Expectancy in the U.S. Population
Authors: Yanping Li, An Pan, Dong D Wang, Xiaoran Liu, Klodian Dhana, Oscar H Franco, Stephen Kaptoge, Emanuele D Angelantonio, Meir Stampfer, Willett C Walter, Frank B Hu
Journal: Circulation (2017)

Introduction: There is a lack of comprehensive evaluations regarding the impact of lifestyle factors on premature mortality and life expectancy in the U.S. population. Hypothesis: Life expectancy c...
NCMP-10. SURVIVAL BENEFIT OF ANTIEPILEPTIC DRUGS IN PATIENTS WITH GLIOBLASTOMA
Authors: Hirotomo Tanaka, Takashi Sasayama, Masamitsu Nishihara, Masashi Morikawa, Mitsuru Ikeda, Kazuhiro Tanaka, Eiji Kohmura
Journal: Neuro-Oncology (2017)
Vigilancia de la legionelosis en un hospital del norte de Italia, entre mayo de 1998 y septiembre de 1999
Authors: P Borella, A Bargelini, S Pergolizzi, R Mazzuconi, G Gesu, R Vaiani, G Stancanelli, P Nizzero, C Curti, G Aggazzotti
Journal: Eurosurveillance (1999)

En 1997, la incidencia global de la legionelosis en Europa fue de 3,9 casos por millon de personas, siendo Malta (0) y Noruega (0,2) los paises con tasas mas bajas y Dinamarca (24) el pais con la tasa mas alta (1). Italia declaro noventa casos (1,5 casos/millon), un 20% de los cuales fueron de origen nosocomial (2), aunque las deficiencias observadas tanto en el diagnostico como en las declaraciones enviadas podrian ser la razon principal de esta baja incidencia.
P1.01-065 Treatment Beyond Progression with Nivolumab in Patients with Advanced Non-Squamous NSCLC: Results from the Italian Expanded Access Program
Authors: E. Cortesi, F. Grossi, R. Chiari, G. Azzarello, R. Berardi, D. Tassinari, G. Palmiotti, C. Verusio, A. Ardizzoia, L. Fioretto, L. Livi, S. Giusti, A. Bearz, G. Ceresoli, F. Piantedosi, A. Frassoldati, E. Ricevuto, G. Fasola, P. Marchetti, G. Puppo
Journal: Journal of Thoracic Oncology (2017)
MA 20.01 Fiducial Marker Placement Using Electromagnetic Navigation Bronchoscopy in the Prospective, Multicenter NAVIGATE Study
Authors: M. Bowling, E. Folch, S. Khandhar, J. Kazakov, W. Krimsky, G. Lemense, P. Linden, B. Murillo, M. Nead, C. Teba, C. Towe, C. Anciano
Journal: Journal of Thoracic Oncology (2017)
OA 04.01 Randomized Trial of Systematic Lymph Node Dissection versus Bilateral Mediastinal Lymphadenectomy in Patients with Non-Small Cell Carcinoma
Authors: J. Kuzdzal, Ł. Hauer, J. Hauer, J. Warmus, P. Kocon, Ł. Trybalski, Z. Grochowski, J. Włodarczyk, T. Gil, T. Smęder
Journal: Journal of Thoracic Oncology (2017)
Estimations de la fréquence des dons de sang infectés par le VHB, VHC et VIH dans la réserve de sang au Royaume-Uni, 1996 à 2003
Authors: K Soldan, K Davison, B Dow
Journal: Eurosurveillance (2005)

Recemment, plusieurs nouveaux tests ont ete introduit dans les services de transfusion sanguine britanniques afin d’ameliorer la securite des produits sanguins. La frequence (ou le risque) d’introduction, dans la reserve de sang, de dons de sang infectes par le virus de l’hepatite B (VHB), le virus de l’hepatite C (VHC) ou le VIH , a ete estimee sur la periode 1996-2003 au cours de laquelle ont ete mis en place le depistage genomique viral (DGV) pour le VHC, le test combine VIH antigene-anticorps et le DGV pour le HIV. 
La frequence d’introduction d’un don infecte dans la reserve du sang liee i) a la fenetre silencieuse, ii) a l’echec du test , et iii) aux erreurs humaines et techniques lors du depistage, a ete evaluee. Le risque du a la fenetre silencieuse a ete estime en se basant sur l’incidence de l’infection chez les donneurs et la duree de la fenetre silencieuse pour les tests utilises, avec un ajustement permettant de tenir compte des intervalles intra-dons atypiques chez les donneurs avec une seroconversion.
La frequence estimee des dons infectieux presents dans le reserve du sang entre 1996-2003 etait respectivement de 1,66, 0,80 et 0,14 par million pour le VHB, le VHC et le VIH. Les resultats pour le DGV VHC ont montre une reduction de 95% du risque VHC. Quant au risque estime pour le VIH, il a ete reduit de 10% a la suite de l’introduction du test combine VIH antigene-anticorps et du DGV. 
Au Royaume-Uni, le risque de transmission du VHB, VHC et HIV par transfusion a diminue depuis 1996 grâce aux progres du depistage sur les dons de sang; bien que la reduction en terme de risque absolu soit faible. L’amelioration de la securite des produits sanguins par rapport au VHB, VHC et VIH passe par une reduction de la fenetre silencieuse des tests, et peut-etre plus encore, par une vigilance accrue quant aux erreurs techniques et a la selection des donneurs.
Première épidémie d’Escherichia coli O157 producteur de vérotoxine au Danemark
Authors: C Jensen, S Ethelberg, A Gervelmeyer, E M Nielsen, K Ep Olsen, K Mølbak
Journal: Eurosurveillance (2006)

L’article suivant decrit la premiere epidemie d’Escherichia coli producteur de verotoxine (VTEC) survenant dans la communaute au Danemark. Vint-cinq patients (18 enfants et 7 adultes) presentant une infection a VTEC O157:H- confirmee par culture et parta
Vigilancia de las salmonellas: logros y direcciones futuras
Authors: W van Pelt
Journal: Eurosurveillance (1999)

Esta edicion especial de Eurosurveillance trata del progreso que ha experimentado la red Enter-net en la vigilancia y control de brotes de salmonelosis humana en Europa. Esta red ha establecido una base de datos internacional, que se actualiza regularmente, y una colaboracion entre expertos que han permitido el exito de varias acciones de salud publica en Europa. El articulo sobre Salmonella typhimurium multiresistente de la Republica Checa ilustra la importancia que reviste la reciente ampliacion del programa, que ha permitido la inclusion de la vigilancia de resistencia antimicrobiana de salmonelosis y extender la red para dar cabida a otros paises Europeos.
GENE-56. DEPLETION OF 5-HYDROXYMETHYLCYTOSINE IN AGGRESSIVE G-CIMP SUBTYPE
Authors: Thais Sarraf Sabedot, Laila Poisson, Ana C deCarvalho, Houtan Noushmehr
Journal: Neuro-Oncology (2017)

5-hydroxymethylcytosine (5hmC) is an oxidation product of 5-methylcytosine, a reaction potentially mediated by the Tet family of enzymes. Levels of 5hmC were reported to be lower in glioblastoma and because gliomas carrying an IDH1/2 mutation (high or low grade) manifest a CpG island methylator phenotype (G-CIMP), we decided to investigate 5hmC levels in G-CIMP subtypes, G-CIMP-high and G-CIMP-low, due to their distinct clinical outcome, independent of histological grade. We generated genome-wide maps of 5hmC for G-CIMP-low (n=4) and G-CIMP-high (n=6) samples by hMeDIP-seq (~ 46M reads per sample). We also have additional whole-genome bisulfite sequencing (WGBS) data for G-CIMP-low (n=1), G-CIMP-high (n=2) and non-tumor brain (n=2) samples. When we compared hMeDIP-seq with WGBS, we found a positive correlation between DNA hypomethylation and depletion of 5hmC in G-CIMP-low. As reported in previous studies, the highest concentration of 5hmC is within gene bodies (75% vs. 25% in intergenic regions). However, we observed an unbalanced level of 5hmC in G-CIMP subtypes (68,397 5hmC peaks lost in G-CIMP-low vs. 2,554 gained, FDR < 0.05). G-CIMP-high has an abundant number of 5hmC peaks, whereas G-CIMP-low seems to have poor 5hmC density in the same regions. We observed G-CIMP-low may arise from G-CIMP-high during tumor recurrence, and we suggest that loss of 5hmC within G-CIMP tumors lead to a more aggressive phenotype. Interestly, 85% of peaks associated with loss of 5hmC overlap regions with loss of intergenic enhancer activity in G-CIMP-low, as defined by H3K27ac peaks. Furthermore, 22% of genes with intronic loss of 5hmC in G-CIMP-low samples are downregulated (FDR < 0.05). We did not find any distinct genomic alterations associated with G-CIMP-low nor did we observe differential expression of genes from the Tet family, we suggest that a yet to be determined alternative mechanism may be driving an aberrant loss of 5hmC in G-CIMP-low.
Alopecia/hair loss in all patients treated with trastuzumab and paclitaxel: myth or reality?
Authors: D. Loparco, M. Caloro, L. Orlando, E.S. Lutrino, P. Schiavone, C. Caliolo, A. Quaranta, P. Fedele, E. Mazzoni, N. Calvani, M. Cinefra, P. Ferrara, L.L. Falcone, A. Lanzilotti, V. Capone, D. Cristina, G. Lotti, A. Ricco, A. Morleo, S. Cinieri
Journal: Annals of Oncology (2017)
P2.01-047 A Phase 1 Trial of Dose Escalated BGB324 in Combination with Docetaxel for Previously Treated Advanced NSCLC
Authors: D. Gerber, P. Levin, F. Fattah, R. Brekken, P. Currykosky, J. Padro, M. Yule, K. Wnuk-Lipinska, E. Nævdal, A. Boniecka, G. Gausdal, J. Lorens
Journal: Journal of Thoracic Oncology (2017)
P2.17-001 Pulmonary Inflammatory Myofibroblastic Tumor with TPM4-ALK Translocation
Authors: K. Okuda, T. Watanabe, R. Oda, T. Sakane, O. Kawano, H. Haneda, S. Moriyama, R. Nakanishi
Journal: Journal of Thoracic Oncology (2017)
HOUT-14. TIME TO PROGRESSION AND VOLUME AT PROGRESSION DEPEND ON DEFINITION OF PROGRESSION IN GLIOBLASTOMA
Authors: Roelant S Eijgelaar, Anna M E Bruynzeel, Frank J Lagerwaard, Domenique M J Müller, Freek Teunissen, Frederik Barkhof, Marcel van Herk, Philip C de Witt Hamer, Marnix G Witte
Journal: Neuro-Oncology (2017)

Time to progression (TTP) is an established response measure, and at progression patients can be included in trials. Standards for imaging interpretation of progression are lacking. We determined the differences in time to progression and in tumor volumes at progression between three methods to assess progression. From a consecutive cohort of 97 patients with glioblastoma in 2012 or 2013, 63 had MRI follow-up after initial treatment to evaluate progression. TTPclinical was determined by multidisciplinary evaluation in clinical practice; TTPRANO by the RANO criteria for trial inclusion; and TTPconsensus by multidisciplinary consensus review (neuroradiologist, neurosurgeon, 2 radiation oncologists) looking back on all MRI information (on average 3.9 follow-up MRIs per patient, range 1-11) with knowledge of further progression and death, postulated as gold standard. MRIs were co-registered to facilitate the consensus review and the maximum perpendicular tumor diameters and volumes were based on enhancing tumor segmentations. No patient was without progression with consensus review, one with clinical practice evaluation and 22 with RANO criteria. The median TTPconsensus was 36 weeks, TTPclinical 40 weeks and TTPRANO 57 weeks. The median overall survival was 64 weeks. The median progression volume was 8.8 mL with consensus review, 17 mL with clinical practice evaluation, and 38 mL with RANO. TTP and volume at progression vary considerably depending on definition of progression. Different purposes may require different progression criteria. Early detection with small volumes may be useful to evaluate progression locations in relation to initial treatment, but can only be determined after the course of disease. RANO criteria may be useful for reproducible clinical trial inclusion, but at the price of later detection with larger volumes. Progression according to RANO criteria is considerably later than clinical practice evaluation in this cohort, potentially introducing lead time bias in trials.
P3.01-041 The Robustness of Allele-Specific qPCR Assays for Detection of EGFR Mutations in Plasma Cell-Free DNA from NSCLC Patients
Authors: A. Szpechcinski, K. Duk, P. Wojcik, W. Kupis, P. Rudzinski, M. Bryl, G. Czyzewicz, T. Orlowski, J. Chorostowska-Wynimko
Journal: Journal of Thoracic Oncology (2017)
ACTR-75. A MULTICENTER, 3-ARM, OPEN-LABEL, PHASE IIA CLINICAL TRIAL TO EVALUATE SAFETY AND EFFICACY OF TANIBIRUMAB (VEGFR2 MAB), IN PATIENTS WITH RECURRENT GBM ASSESSED WITH K-TRANS AND INITIAL AREA UNDER THE GADOLINIUM CONCENTRATION-TIME CURVE (IAUGC)
Authors: Lawrence Cher, Anna Nowak, George Iatropoulos, Weon Sup Lee, Seon Young Lee, Sang Ryeol Shim, Jin San Yoo
Journal: Neuro-Oncology (2017)

The VEGF signal transduction pathway is upregulated in GBM. We evaluated Tanibirumab, a mAb to VEGFR2, in an open-label, dose-escalation, 3-arm, Phase 2a clinical trial. Primary and secondary endpoints were safety and efficacy (6-month PFS, ORR, DCR and OS). Eligibility criteria included 1st or 2nd recurrence of GBM, measurable disease, and no prior bevacizumab. Patients were enrolled in 3 arms: Arm 1 (8mg/kg d1,8,15/q28 days); Arm 2 (12mg/kg d1,8,15/q28 days) and Arm 3 (12mg/kg weekly). Response evaluation with MRI (RANO criteria) including DCE, was performed 8 weekly. 12 patients were enrolled: 3 patients each in first 2 arms 6 in Arm 3. Half had second recurrence. All patients have progressed. No dose limiting toxicities (DLT) were observed. Cutaneous hemangiomas (CH) were frequent (83% of patients) and all G2 or less. No drug-related G3 or 4 AEs were observed. All SAEs were unrelated to the study drug apart from G2 bleeding haemangioma and G2 cerebral haemorrhage. Typical AEs with bevacizumab (hypertension; impaired wound healing) were not observed. No objective radiological responses occurred. 3 patients demonstrated stable disease (SD); 2 patients had SD till weeks 60 (Arm 1) & 40 (3). This was correlated with the highest expression of VEGFR2 using immunohistochemistry on archival tumour and blood vessels. Only 2 patients needed to initiate or increase corticosteroids while on treatment suggesting reduced oedema. K-trans and IAUGC showed no difference between baseline and first post-treatment scans. Tanibirumab can be safely administered to patients with recurrent GBM, with CH being common. SD was seen in 2 patients up to 15 months, with some indication that tissue VEGFR2 expression may be a response biomarker. There was no correlation of response with vascular imaging. Clinical trial information: NCT03033524
Circulating angiogenesis-related markers as predictors of benefit from regorafenib in metastatic colorectal cancer (mCRC) patients (pts)
Authors: C. Antoniotti, F. Marmorino, M. Pennati, N. Zaffaroni, D. Rossini, B. Borelli, G. Zucchelli, R. Moretto, F. Pietrantonio, G. Masi, F. Vannini, C. Colombo, A. Saettini, S. Gini, L. Delliponti, E. Pfanner, I. Brunetti, A. Falcone, C. Cremolini
Journal: Annals of Oncology (2017)
Comparison of Molecular Testing Modalities for Detection of ROS1 Rearrangements in a Cohort of Positive Patient Samples
Authors: Kurtis D. Davies, Anh T. Le, Jamie Sheren, Hala Nijmeh, Katherine Gowan, Kenneth L. Jones, Marileila Varella-Garcia, Dara L. Aisner, Robert C. Doebele
Journal: Journal of Thoracic Oncology (2018)
Waterborne Disease Outbreaks Associated With Environmental and Undetermined Exposures to Water — United States, 2013–2014
Authors: R. Paul McClung, David M. Roth, Marissa Vigar, Virginia A. Roberts, Amy M. Kahler, Laura A. Cooley, Elizabeth D. Hilborn, Timothy J. Wade, Kathleen E. Fullerton, Jonathan S. Yoder, Vincent R. Hill
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Waterborne disease outbreaks in the United States are associated with a wide variety of water exposures and are reported annually to CDC on a voluntary basis by state and territorial health departments through the National Outbreak Reporting System (NORS). A majority of outbreaks arise from exposure to drinking water (1) or recreational water (2), whereas others are caused by an environmental exposure to water or an undetermined exposure to water. During 2013-2014, 15 outbreaks associated with an environmental exposure to water and 12 outbreaks with an undetermined exposure to water were reported, resulting in at least 289 cases of illness, 108 hospitalizations, and 17 deaths. Legionella was responsible for 63% of the outbreaks, 94% of hospitalizations, and all deaths. Outbreaks were also caused by Cryptosporidium, Pseudomonas, and Giardia, including six outbreaks of giardiasis caused by ingestion of water from a river, stream, or spring. Water management programs can effectively prevent outbreaks caused by environmental exposure to water from human-made water systems, while proper point-of-use treatment of water can prevent outbreaks caused by ingestion of water from natural water systems.