994 results on '"Thomas J Walsh"'
Search Results
2. Therapeutic Bacteriophages for Gram-Negative Bacterial Infections in Animals and Humans
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Panagiotis, Zagaliotis, Jordyn, Michalik-Provasek, Jason J, Gill, and Thomas J, Walsh
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Microbiology (medical) ,Infectious Diseases ,Immunology ,Immunology and Allergy ,Molecular Biology - Abstract
Drug-resistant Gram-negative bacterial pathogens are an increasingly serious health threat causing worldwide nosocomial infections with high morbidity and mortality. Of these, the most prevalent and severe are Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Salmonella typhimurium. The extended use of antibiotics has led to the emergence of multidrug resistance in these bacteria. Drug-inactivating enzymes produced by these bacteria, as well as other resistance mechanisms, render drugs ineffective and make treatment of such infections more difficult and complicated. This makes the development of novel antimicrobial agents an urgent necessity. Bacteriophages, which are bacteria-killing viruses first discovered in 1915, have been used as therapeutic antimicrobials in the past, but their use was abandoned due to the widespread availability of antibiotics in the 20th century. The emergence, however, of drug-resistant pathogens has re-affirmed the need for bacteriophages as therapeutic strategies. This review describes the use of bacteriophages as novel agents to combat this rapidly emerging public health crisis by comprehensively enumerating and discussing the innovative use of bacteriophages in both animal models and in patients infected by Gram-negative bacteria.
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- 2022
3. New Developments in Pediatric Antifungal Pharmacology
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Andreas H, Groll, Emmanuel, Roilides, and Thomas J, Walsh
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Microbiology (medical) ,Echinocandins ,Antifungal Agents ,Infectious Diseases ,Mycoses ,Pediatrics, Perinatology and Child Health ,Humans ,Child - Published
- 2022
4. Pharmacokinetic modelling of caspofungin to develop an extended dosing regimen in paediatric patients
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Silke Gastine, Georg Hempel, Michael N Neely, Thomas J Walsh, and Andreas H Groll
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Pharmacology ,Microbiology (medical) ,Echinocandins ,Antifungal Agents ,Infectious Diseases ,Caspofungin ,Humans ,Pharmacology (medical) ,Child ,Monte Carlo Method ,Invasive Fungal Infections - Abstract
Background Echinocandins are commonly used in treatment and prophylaxis of invasive fungal diseases. Intravenous daily dosing for prophylaxis in the outpatient setting can however become a hurdle for adequate compliance in the paediatric population. Objectives Simulations were performed to assess extended twice-weekly dosing for antifungal prophylaxis using caspofungin. Methods A population pharmacokinetic model was developed based on previously published data from children aged 3 months to 17 years. Using the final model, Monte Carlo simulations were performed to assess the dose needed for adequate exposure in a twice-weekly setting. Mean weekly AUC0–24 h/MIC together with reported AUC0–24 h from previously reported paediatric trials were used to guide adequate exposure. Results and Conclusions A two-compartment model with linear elimination and allometric scaling using fixed exponents was found most adequate to describe the given paediatric populations. Simulations showed that a 200 mg/m2 twice-weekly regimen with maximal 200 mg total dose should result in exposures matching registered daily dosing as well as commonly used pharmacokinetic/pharmacodynamic targets.
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- 2022
5. Impact of a Rapid Molecular Test for Klebsiella pneumoniae Carbapenemase and Ceftazidime-Avibactam Use on Outcomes After Bacteremia Caused by Carbapenem-Resistant Enterobacterales
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Michael J, Satlin, Liang, Chen, Angela, Gomez-Simmonds, Jamie, Marino, Gregory, Weston, Tanaya, Bhowmick, Susan K, Seo, Steven J, Sperber, Angela C, Kim, Brandon, Eilertson, Sierra, Derti, Stephen G, Jenkins, Michael H, Levi, Melvin P, Weinstein, Yi-Wei, Tang, Tao, Hong, Stefan, Juretschko, Katherine L, Hoffman, Thomas J, Walsh, Lars F, Westblade, Anne-Catrin, Uhlemann, and Barry N, Kreiswirth
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Microbiology (medical) ,Infectious Diseases - Abstract
Background Patients with bacteremia due to carbapenem-resistant Enterobacterales (CRE) experience delays until appropriate therapy and high mortality rates. Rapid molecular diagnostics for carbapenemases and new β-lactam/β-lactamase inhibitors may improve outcomes. Methods We conducted an observational study of patients with CRE bacteremia from 2016 to 2018 at 8 New York and New Jersey medical centers and assessed center-specific clinical microbiology practices. We compared time to receipt of active antimicrobial therapy and mortality between patients whose positive blood cultures underwent rapid molecular testing for the Klebsiella pneumoniae carbapenemase (KPC) gene (blaKPC) and patients whose cultures did not undergo this test. CRE isolates underwent antimicrobial susceptibility testing by broth microdilution and carbapenemase profiling by whole-genome sequencing. We also assessed outcomes when ceftazidime-avibactam and polymyxins were used as targeted therapies. Results Of 137 patients with CRE bacteremia, 89 (65%) had a KPC-producing organism. Patients whose blood cultures underwent blaKPC PCR testing (n = 51) had shorter time until receipt of active therapy (median: 24 vs 50 hours; P = .009) compared with other patients (n = 86) and decreased 14-day (16% vs 37%; P = .007) and 30-day (24% vs 47%; P = .007) mortality. blaKPC PCR testing was associated with decreased 30-day mortality (adjusted odds ratio: .37; 95% CI: .16–.84) in an adjusted model. The 30-day mortality rate was 10% with ceftazidime-avibactam monotherapy and 31% with polymyxin monotherapy (P = .08). Conclusions In a KPC-endemic area, blaKPC PCR testing of positive blood cultures was associated with decreased time until appropriate therapy and decreased mortality for CRE bacteremia, and ceftazidime-avibactam is a reasonable first-line therapy for these infections.
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- 2022
6. Food and Drug Administration Public Workshop Summary—Development Considerations of Antifungal Drugs to Address Unmet Medical Need
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Yuliya Yasinskaya, Shukal Bala, Ursula Waack, Cheryl Dixon, Karen Higgins, Jason N Moore, Caroline J Jjingo, Elizabeth O'Shaughnessy, Philip Colangelo, Radu Botgros, Sumathi Nambiar, David Angulo, Aaron Dane, Tom Chiller, Michael R Hodges, Taylor Sandison, William Hope, Thomas J Walsh, Peter Pappas, Aspasia Katragkou, Laura Kovanda, John H Rex, Kieren A Marr, Luis Ostrosky-Zeichner, Shohko Sekine, Monika Deshpande, Sunita J Shukla, and John Farley
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Microbiology (medical) ,Infectious Diseases - Abstract
Pressing challenges in the treatment of invasive fungal infections (IFIs) include emerging and rare pathogens, resistant/refractory infections, and antifungal armamentarium limited by toxicity, drug-drug interactions, and lack of oral formulations. Development of new antifungal drugs is hampered by the limitations of the available diagnostics, clinical trial endpoints, prolonged trial duration, difficulties in patient recruitment, including subpopulations (eg, pediatrics), and heterogeneity of the IFIs. On 4 August 2020, the US Food and Drug Administration convened a workshop that included IFI experts from academia, industry, and other government agencies to discuss the IFI landscape, unmet need, and potential strategies to facilitate the development of antifungal drugs for treatment and prophylaxis. This article summarizes the key topics presented and discussed during the workshop, such as incentives and research support for drug developers, nonclinical development, clinical trial design challenges, lessons learned from industry, and potential collaborations to facilitate antifungal drug development.
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- 2023
7. Mechanistic Insights to Combating NDM- and CTX-M-Coproducing Klebsiella pneumoniae by Targeting Cell Wall Synthesis and Outer Membrane Integrity
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Nicholas M. Smith, Katie Rose Boissonneault, Liang Chen, Vidmantas Petraitis, Ruta Petraitiene, Xun Tao, Jieqiang Zhou, Yinzhi Lang, Povilas Kavaliauskas, Zackery P. Bulman, Patricia N. Holden, Raymond Cha, Jürgen B. Bulitta, Barry N. Kreiswirth, Thomas J. Walsh, and Brian T. Tsuji
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Pharmacology ,Microbial Sensitivity Tests ,Clinical Therapeutics ,Ceftazidime ,beta-Lactamases ,Anti-Bacterial Agents ,Aztreonam ,Drug Combinations ,Klebsiella pneumoniae ,Infectious Diseases ,Cell Wall ,Klebsiella ,Animals ,Pharmacology (medical) ,Rabbits ,Azabicyclo Compounds ,Polymyxin B - Abstract
Metallo-β-lactamase (MBL)-producing Gram-negative bacteria cause infections associated with high rates of morbidity and mortality. Currently, a leading regimen to treat infections caused by MBL-producing bacteria is aztreonam combined with ceftazidime-avibactam. The purpose of the present study was to evaluate and rationally optimize the combination of aztreonam and ceftazidime-avibactam with and without polymyxin B against a clinical Klebsiella pneumoniae isolate producing NDM-1 and CTX-M by use of the hollow fiber infection model (HFIM). A novel de-escalation approach to polymyxin B dosing was also explored, whereby a standard 0-h loading dose was followed by maintenance doses that were 50% of the typical clinical regimen. In the HFIM, the addition of polymyxin B to aztreonam plus ceftazidime-avibactam significantly improved bacterial killing, leading to eradication, including for the novel de-escalation dosing strategy. Serial samples from the growth control and monotherapies were explored in a Galleria mellonella virulence model to assess virulence changes. Weibull regression showed that low-level ceftazidime resistance and treatment with monotherapy resulted in increased G. mellonella mortality (P
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- 2023
8. One size does not fit all: variations by ethnicity in demographic characteristics of men seeking fertility treatment across North America
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Peter N. Kolettis, Kirk C. Lo, Robert E. Brannigan, Scott I. Zeitlin, Tung Chin M. Hsieh, Jared M. Bieniek, James M. Dupree, Edmund Y. Ko, Susan Lau, Victor Chow, James M. Hotaling, Ajay K. Nangia, Jason C. Hedges, Armand Zini, Mary K. Samplaski, Aaron Spitz, Keith Jarvi, Eugene F. Fuchs, David Shin, Andrew B. Chen, James F. Smith, Jay I. Sandlow, Thomas J. Walsh, Marc A. Fisher, Katherine Lajkosz, Marc Goldstein, Trustin Domes, Ethan D. Grober, and J. C. Trussell
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Retrospective review ,business.industry ,media_common.quotation_subject ,Ethnic group ,Outcome measures ,Obstetrics and Gynecology ,Fertility ,Race (biology) ,Reproductive Medicine ,Male fertility ,Biologic Factors ,Medicine ,Racial differences ,business ,Demography ,media_common - Abstract
Objective To compare racial differences in male fertility history and treatment. Design Retrospective review of prospectively collected data. Setting North American reproductive urology centers. Patient(s) Males undergoing urologist fertility evaluation. Intervention(s) None. Main Outcome Measure(s) Demographic and reproductive Andrology Research Consortium data. Result(s) The racial breakdown of 6,462 men was: 51% White, 20% Asian/Indo-Canadian/Indo-American, 6% Black, 1% Indian/Native, Conclusion(s) Racial differences exist for males undergoing fertility evaluation by a reproductive urologist. Better understanding of these differences in history in conjunction with societal and biologic factors can guide personalized care, as well as help to better understand and address disparities in access to fertility evaluation and treatment.
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- 2021
9. Candida auris Pan-Drug-Resistant to Four Classes of Antifungal Agents
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Samantha E. Jacobs, Jonathan L. Jacobs, Emily K. Dennis, Sarah Taimur, Meenakshi Rana, Dhruv Patel, Melissa Gitman, Gopi Patel, Sarah Schaefer, Kishore Iyer, Jang Moon, Victoria Adams, Polina Lerner, Thomas J. Walsh, YanChun Zhu, Mohammed Rokebul Anower, Mayuri M. Vaidya, Sudha Chaturvedi, and Vishnu Chaturvedi
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Pharmacology ,Infectious Diseases ,Antifungal Agents ,Drug Resistance, Fungal ,Mechanisms of Resistance ,Humans ,Pharmacology (medical) ,Microbial Sensitivity Tests ,Candida auris ,Phylogeny - Abstract
Candida auris is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of C. auris clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area. We performed genome, and drug-resistance analysis of C. auris isolates from a patient who underwent multi-visceral transplantation. Whole-genome comparisons of 19 isolates, collected over 72 days, revealed closed similarity (Average Nucleotide Identity > 0.9996; Aligned Percentage > 0.9764) and a distinct subcluster of NY C. auris South Asia Clade I. All isolates had azole-linked resistance in ERG11(K143R) and CDR1(V704L). Echinocandin resistance first appeared with FKS1(S639Y) mutation and then a unique FKS1(F635C) mutation. Flucytosine-resistant isolates had mutations in FCY1, FUR1, and ADE17. Two pan-drug-resistant C. auris isolates had uracil phosphoribosyltransferase deletion (FUR1[1Δ33]) and the elimination of FUR1 expression, confirmed by a qPCR test developed in this study. Besides ERG11 mutations, four amphotericin B-resistant isolates showed no distinct nonsynonymous variants suggesting unknown genetic elements driving the resistance. Pan-drug-resistant C. auris isolates were not susceptible to two-drug antifungal combinations tested by checkerboard, Etest, and time-kill methods. The fungal population pattern, discerned from SNP phylogenetic analysis, was consistent with in-hospital or inpatient evolution of C. auris isolates circulating locally and not indicative of a recent introduction from elsewhere. The emergence of pan-drug-resistance to four major classes of antifungals in C. auris is alarming. Patients at high risk for drug-resistant C. auris might require novel therapeutic strategies and targeted pre-and/or posttransplant surveillance.
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- 2022
10. Osteoarticular Mycoses
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Maria N. Gamaletsou, Blandine Rammaert, Barry Brause, Marimelle A. Bueno, Sanjeet S. Dadwal, Michael W. Henry, Aspasia Katragkou, Dimitrios P. Kontoyiannis, Matthew W. McCarthy, Andy O. Miller, Brad Moriyama, Zoi Dorothea Pana, Ruta Petraitiene, Vidmantas Petraitis, Emmanuel Roilides, Jean-Pierre Sarkis, Maria Simitsopoulou, Nikolaos V. Sipsas, Saad J. Taj-Aldeen, Valérie Zeller, Olivier Lortholary, Thomas J. Walsh, Laiko General Hospital, University of Athens School of Medicine, Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Hospital for Special Surgery, Far Eastern Federal University (FEFU), City of Hope National Medical Center, Nationwide Children's Hospital, The Ohio State University School of Medicine, The University of Texas M.D. Anderson Cancer Center [Houston], Weill Medical College of Cornell University [New York], New York Presbyterian Hospital, NIH Clinical Center, Bethesda, Maryland, Hippokration General Hospital, Aristotle University of Thessaloniki, Hamad Medical Corporation [Doha, Qatar], Groupe Hospitalier Diaconesses Croix Saint-Simon, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique évolutive, modélisation et santé (GEMS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Center for Innovative Therapeutics and Diagnostics, Richmond, Virginia
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Microbiology (medical) ,cryptococcosis ,phaeohyphomycosis ,General Immunology and Microbiology ,histoplasmosis ,Epidemiology ,coccidioidomycosis ,Public Health, Environmental and Occupational Health ,osteomyelitis ,candidiasis ,mucormycosis ,antifungal therapy ,Infectious Diseases ,aspergillosis ,mycoses ,[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology - Abstract
Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.
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- 2022
11. Meeting the Challenges of Sepsis in Severe Coronavirus Disease 2019: A Call to Arms
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Thomas J Walsh, Rick A Bright, Aparna Ahuja, Matthew W McCarthy, Richard A Marfuggi, and Steven Q Simpson
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Infectious Diseases ,Oncology - Abstract
Sepsis is a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis may be caused by bacterial, fungal, or viral pathogens. The clinical manifestations exhibited by patients with severe coronavirus disease 2019 (COVID-19)-related sepsis overlap with those exhibited by patients with sepsis from secondary bacterial or fungal infections and can include an altered mental status, dyspnea, reduced urine output, tachycardia, and hypotension. Critically ill patients hospitalized with severe acute respiratory syndrome coronavirus 2 infections have increased risk for secondary bacterial and fungal infections. The same risk factors that may predispose to sepsis and poor outcome from bloodstream infections (BSIs) converge in patients with severe COVID-19. Current diagnostic standards for distinguishing between (1) patients who are critically ill, septic, and have COVID-19 and (2) patients with sepsis from other causes leave healthcare providers with 2 suboptimal choices. The first choice is to empirically administer broad-spectrum, antimicrobial therapy for what may or may not be sepsis. Such treatment may not only be ineffective and inappropriate, but it also has the potential to cause harm. The development of better methods to identify and characterize antimicrobial susceptibility will guide more accurate therapeutic interventions and reduce the evolution of new antibiotic-resistant strains. The ideal diagnostic test should (1) be rapid and reliable, (2) have a lower limit of detection than blood culture, and (3) be able to detect a specific organism and drug sensitivity directly from a clinical specimen. Rapid direct detection of antimicrobial-resistant pathogens would allow targeted therapy and result in improved outcomes in patients with severe COVID-19 and sepsis.
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- 2022
12. Focused multivector ultraviolet (FMUV) technology rapidly eradicates SARS-CoV-2 in-vitro: Implications for hospital disinfection of COVID-19 environments
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Steven Park, David S. Perlin, Sean Fitzgerald, Vidmantas Petraitis, and Thomas J. Walsh
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Disinfection ,Technology ,Infectious Diseases ,SARS-CoV-2 ,Ultraviolet Rays ,Epidemiology ,Health Policy ,Public Health, Environmental and Occupational Health ,COVID-19 ,Humans ,Hospitals - Abstract
Focused Multivector Ultraviolet technology rapidly killed the SARS-CoV-2 coronavirus in-vitro. Plates were inoculated with a mean of greater than 10
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- 2022
13. Adenovirus viremia after in vivo T-cell depleted allo-transplant in adults: low lymphocyte counts are associated with uncontrolled viremia and fatal outcomes
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Markus Plate, Thomas J. Walsh, Koen van Besien, Sebastian Mayer, Alexandra Gomez-Arteaga, Alex Drelick, Hanna Rennert, Michael J. Satlin, Tsiporah B. Shore, Ok-Kyong Chaekal, Catherine B. Small, Rosemary Soave, Zhengming Chen, Rosy Priya L. Kodiyanplakkal, Jingmei Hsu, Nina Orfali, and Adrienne A. Phillips
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Cancer Research ,business.industry ,Incidence (epidemiology) ,T cell ,Lymphocyte ,virus diseases ,Viremia ,Hematology ,medicine.disease ,Cell therapy ,medicine.anatomical_structure ,Oncology ,In vivo ,Cord blood ,Immunology ,Medicine ,Cumulative incidence ,business - Abstract
The incidence of adenovirus viremia and the role of screening in preventing adenovirus disease in adult transplant recipients are not well defined. Between January 2017 and May 2020, 262 allogeneic transplants were performed using in vivo T-cell depletion. Adenovirus viremia was found in 59 patients for a cumulative incidence of 10% by one hundred days and 23% (95% CI 20-26%) by one year. There was a higher incidence of viremia associated with cord blood transplant (p = .04). No other patient, donor or transplant characteristics were identified that predicted for viremia. In 47 patients (80%), viremia remained well below 200,000 copies/mL and resolved. Twelve patients developed high level viremia. Treatment with antivirals and in some cases adoptive cell therapy, was often ineffective and only two survived. Low lymphocyte count at initial detection of adenovirus viremia was the best predictor of uncontrolled disease.
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- 2021
14. Efficacy of Cefiderocol in Experimental Stenotrophomonas maltophilia Pneumonia in Persistently Neutropenic Rabbits
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Vidmantas Petraitis, Ruta Petraitiene, Povilas Kavaliauskas, Ethan Naing, Andrew Garcia, Benjamin N. Georgiades, Roger Echols, Robert A. Bonomo, Yoshinori Yamano, Michael J. Satlin, and Thomas J. Walsh
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Pharmacology ,Adult ,Stenotrophomonas maltophilia ,Siderophores ,Pneumonia ,Microbial Sensitivity Tests ,Anti-Bacterial Agents ,Cephalosporins ,Infectious Diseases ,Trimethoprim, Sulfamethoxazole Drug Combination ,Humans ,Animals ,Pharmacology (medical) ,Rabbits ,Gram-Negative Bacterial Infections - Abstract
Stenotrophomonas maltophilia is an important cause of pneumonia in immunocompromised patients. Cefiderocol is a parenteral siderophore cephalosporin with potent in vitro activity against S. maltophilia .
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- 2022
15. Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?
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Alessia Catalano, Domenico Iacopetta, Jessica Ceramella, Azzurra Chiara De Maio, Giovanna Basile, Federica Giuzio, Maria Grazia Bonomo, Stefano Aquaro, Thomas J. Walsh, Maria Stefania Sinicropi, Carmela Saturnino, Athina Geronikaki, and Giovanni Salzano
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Health (social science) ,Plant Science ,Health Professions (miscellaneous) ,Microbiology ,Food Science - Abstract
The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID-19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID-19 led to increasing importance of a new disease called post-COVID syndrome. The term post-COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID-19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID-19 disease and post-COVID syndrome.
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- 2022
16. Multicenter Collaborative Study of the Interaction of Antifungal Combinations against
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Joseph, Meletiadis, David R, Andes, Shawn R, Lockhart, Mahmoud A, Ghannoum, Cindy C, Knapp, Luis, Ostrosky-Zeichner, Michael A, Pfaller, Vishnu, Chaturvedi, and Thomas J, Walsh
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Combination antifungal therapy is widely used but not well understood. We analyzed the spectrophotometric readings from a multicenter study conducted by the New York State Department of Health to further characterize the in vitro interactions of the major classes of antifungal agents against
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- 2022
17. Diagnostic yield of chromosomal microarray and trio whole exome sequencing in cryptogenic cerebral palsy
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Alla Kuzminsky, Liora Sagi, Adi Aran, Luba Blumkin, Tehila Klopstock, Dorit Lev, Dafna Guttman, Lilach Shemer Meiri, Reeval Segel, Suleyman Gulsuner, Michal Yechieli, Mary Claire King, Varda Gross-Tsur, Aviva Fattal, Paul Renbaum, Hilla Ben-Pazi, Ephrat Lahad Levy, Sharon Zeligson, Nira Schneebaum Sender, Dorit Shmueli, Thomas J. Walsh, and Amnon Lahad
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0301 basic medicine ,medicine.medical_specialty ,Candidate gene ,Movement disorders ,DNA Copy Number Variations ,Microarray ,medicine.disease_cause ,Cerebral palsy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Exome Sequencing ,Genetics ,medicine ,Humans ,Genetics (clinical) ,Exome sequencing ,Genetic testing ,Mutation ,medicine.diagnostic_test ,business.industry ,Cerebral Palsy ,Point mutation ,Microarray Analysis ,medicine.disease ,030104 developmental biology ,Child, Preschool ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveTo determine the yield of genetic diagnoses using chromosomal microarray (CMA) and trio whole exome sequencing (WES), separately and combined, among patients with cryptogenic cerebral palsy (CP).MethodsTrio WES of patients with prior CMA analysis for cryptogenic CP, defined as disabling, non-progressive motor symptoms beginning before the age of 3 years without known cause.ResultsGiven both CMA analysis and trio WES, clinically significant genetic findings were identified for 58% of patients (26 of 45). Diagnoses were eight large CNVs detected by CMA and 18 point mutations detected by trio WES. None had more than one severe mutation. Approximately half of events (14 of 26) were de novo. Yield was significantly higher in patients with CP with comorbidities (69%, 22 of 32) than in those with pure motor CP (31%, 4 of 13; p=0.02). Among patients with genetic diagnoses, CNVs were more frequent than point mutations among patients with congenital anomalies (OR 7.8, 95% CI 1.2 to 52.4) or major dysmorphic features (OR 10.5, 95% CI 1.4 to 73.7). Clinically significant mutations were identified in 18 different genes: 14 with known involvement in CP-related disorders and 4 responsible for other neurodevelopmental conditions. Three possible new candidate genes for CP were ARGEF10, RTF1 and TAOK3.ConclusionsCryptogenic CP is genetically highly heterogeneous. Genomic analysis has a high yield and is warranted in all these patients. Trio WES has higher yield than CMA, except in patients with congenital anomalies or major dysmorphic features, but these methods are complementary. Patients with negative results with one approach should also be tested by the other.
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- 2021
18. Efficacy of Non-Testosterone–Based Treatment in Hypogonadal Men: A Review
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David Chernobylsky, Tan V. Le, Suresh C. Sikka, Kole Prasad Akula, Tony Chen, Jacob W. Greenberg, Omer A. Raheem, and Thomas J. Walsh
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Adult ,Male ,Selective Estrogen Receptor Modulators ,Oncology ,Infertility ,medicine.medical_specialty ,Hormone Replacement Therapy ,medicine.drug_class ,Urology ,Endocrinology, Diabetes and Metabolism ,030232 urology & nephrology ,Male infertility ,Human chorionic gonadotropin ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Androgen deficiency ,medicine ,Humans ,Testosterone ,Fertility preservation ,030219 obstetrics & reproductive medicine ,Aromatase inhibitor ,Aromatase Inhibitors ,business.industry ,Hypogonadism ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Reproductive Medicine ,Selective estrogen receptor modulator ,business - Abstract
Although testosterone replacement therapy is an effective treatment for hypogonadism, there are safety concerns regarding potential cardiovascular risks and fertility preservation.To assess the effect of selective estrogen receptor modulator (SERM), aromatase inhibitor, and human chorionic gonadotropin (hCG) on total testosterone (TT) levels and hypogonadism.We performed a systematic literature review from 1987 to 2019 via PubMed, Cochrane review, and Web of Science. Terms used were infertility, hypogonadism, alternative to testosterone therapy, selective estrogen receptor modulator, aromatase inhibitor, and human chorionic gonadotropin. Studies that reported an effect of TT and hypogonadism after treatment of each medication were selected. Hypogonadal symptoms were assessed by the Androgen Deficiency of The Aging Male (ADAM) questionnaire. Aggregated data were analyzed via Chi-squared analysis.From literature, 25 studies were selected; of which, 12 evaluated efficacy of aromatase inhibitor, 8 evaluated SERMs, and 5 evaluated hCG effects. For SERMs, 512 patients with mean age 42.3 ± 1.94 years showed mean TT before treatment vs after treatment (167.9 ± 202.8 [ng/dl] vs 366.2 ± 32.3 [ng/dl], P .0001 [180.5-216.1 95% confidence interval {CI}]). For aromatase inhibitor, 375 patients with mean age 54.1 ± 0.67 years showed mean TT before treatment vs after treatment (167.9 ± 202.8 [ng/dl] vs 366.2 ± 32.3 [ng/dl], P .0001 [180.5-216.1 95% CI]). SERMs also showed ADAM before treatment vs after treatment (4.95 ± 0.28 vs 5.50 ± 0.19, P .0001 [0.523-0.581 95% CI]). For hCG, 196 patients with mean age 41.7 ± 1.5 years showed mean TT before treatment vs after treatment (284.5 ± 13.6 [ng/dl] vs 565.6 ± 39.7 [ng/dl], P .0001 [275.2-287.0 95% CI]). In addition, hCG also showed ADAM before treatment vs after treatment (28.1 ± 2.0 vs 30.9 ± 2.3, P .0001 [2.313 95% CI]).Non-testosterone therapies are efficacious in hypogonadal men. Our results show statistically significant improvement in TT and ADAM scores in all 3 medications after treatment. Future studies are warranted to elucidate the relationship between improved hypogonadism and erectile function in the setting of non-testosterone-based treatment. Raheem OA, Chen TT, Le TV, et al. Efficacy of Non-Testosterone-Based Treatment in Hypogonadal Men: A Review. Sex Med Rev 2021;9:381-392.
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- 2021
19. 'The Back-up Vasectomy Reversal.' Simultaneous Sperm Retrieval and Vasectomy Reversal in the Couple With Advanced Maternal Age: A Cost-Effectiveness Analysis
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Thomas J. Walsh, James R. Craig, Philip J. Cheng, Alexander W. Pastuszak, Joseph P. Alukal, James M. Hotaling, and Jaewhan Kim
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Infertility ,medicine.medical_specialty ,In vitro fertilisation ,business.industry ,Cost effectiveness ,Obstetrics ,Urology ,media_common.quotation_subject ,medicine.medical_treatment ,030232 urology & nephrology ,Vasectomy ,Vasectomy reversal ,Fertility ,medicine.disease ,Testicular sperm extraction ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,Advanced maternal age ,business ,media_common - Abstract
Objective To determine the cost-effectiveness of different fertility options in men who have undergone vasectomy in couples with a female of advanced maternal age (AMA). The options include vasectomy reversal (VR), sperm retrieval (SR) with in vitro fertilization (IVF), and the combination of VR and SR with IVF, which is a treatment pathway that has been understudied. Materials and Methods Using TreeAge software, a model-based cost-utility analysis was performed estimating the cost per quality-adjusted life years (QALY) in couples with infertility due to vasectomy and advanced female age over a period of one year. The model stratified for female age (35-37, 38-40, >40) and evaluated four strategies: VR followed by natural conception (NC), SR with IVF, VR and SR followed by failed NC and then IVF, and VR and SR followed by failed IVF and then NC. QALY estimates and outcome probabilities were obtained from the literature and average patient charges were calculated from high-volume centers. Results The most cost-effective fertility strategy was to undergo VR and try for NC (cost-per-QALY: $7,150 (35-37 y), $7,203 (38-40 y), and $7,367 (>40 y)). The second most cost-effective strategy was the “back-up vasectomy reversal”: undergo VR and SR, attempt IVF and switch to NC if IVF fails. Conclusion In couples with a history of vasectomy and female of AMA, it is most cost-effective to undergo a VR. If the couple opts for SR for IVF, it is more cost-effective to undergo a concomitant VR than SR alone.
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- 2021
20. Genetic Heterogeneity and Core Clinical Features of NOG-Related-Symphalangism Spectrum Disorder
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Kathleen A. Leppig, Thomas J. Walsh, Dawson Wells, Dror Gilony, Karen B. Avraham, Mary Claire King, Ryan J. Carlson, Jay T. Rubinstein, Suleyman Gulsuner, Zippora Brownstein, and Alicia M. Quesnel
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Foot Deformities, Congenital ,business.industry ,Genetic heterogeneity ,Point mutation ,Tarsal Bones ,medicine.disease ,Bioinformatics ,Article ,Stapes ,Sensory Systems ,Conductive hearing loss ,Genetic Heterogeneity ,Synostosis ,Otorhinolaryngology ,Temporal bone ,medicine ,Humans ,Otosclerosis ,Missense mutation ,Neurology (clinical) ,business ,Hand Deformities, Congenital ,Carpal Bones ,Chromosomal Deletion - Abstract
Objectives To better distinguish NOG-related-symphalangism spectrum disorder (NOG-SSD) from chromosomal 17q22 microdeletion syndromes and to inform surgical considerations in stapes surgery for patients with NOG-SSD. Background Mutations in NOG cause a variety of skeletal syndromes that often include conductive hearing loss. Several microdeletions of chromosome 17q22 lead to severe syndromes with clinical characteristics that overlap NOG-SSD. Isolated deletion of NOG has not been described, and therefore the contribution of NOG deletion in these syndromes is unknown. Methods Two families with autosomal dominant NOG-SSD exhibited stapes ankylosis, facial dysmorphisms, and skeletal and joint anomalies. In each family, NOG was evaluated by genomic sequencing and candidate mutations confirmed as damaging by in vitro assays. Temporal bone histology of a patient with NOG-SSD was compared with temporal bones of 40 patients diagnosed with otosclerosis. Results Family 1 harbors a 555 kb chromosomal deletion encompassing only NOG and ANKFN1. Family 2 harbors a missense mutation in NOG leading to absence of noggin protein. The incus-footplate distance of the temporal bone was significantly longer in a patient with NOG-SSD than in patients with otosclerosis. Conclusion The chromosomal microdeletion of family 1 led to a phenotype comparable to that due to a NOG point mutation and much milder than the phenotypes due to other chromosome 17q22 microdeletions. Severe clinical findings in other microdeletion cases are likely due to deletion of genes other than NOG. Based on temporal bone findings, we recommend that surgeons obtain longer stapes prostheses before stapes surgery in individuals with NOG-SSD stapes ankylosis.
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- 2021
21. Does Type 1 Diabetes Affect Male Infertility: Type 1 Diabetes Exchange Registry-Based Analysis
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Judy N. Fustok, Thomas J. Walsh, Irl B. Hirsch, Marc J. Rogers, Marah Hehemann, and Omer A. Raheem
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Infertility ,Type 1 diabetes ,education.field_of_study ,030219 obstetrics & reproductive medicine ,Multivariate analysis ,endocrine system diseases ,business.industry ,media_common.quotation_subject ,Population ,030209 endocrinology & metabolism ,Fertility ,Diabetic retinopathy ,medicine.disease ,Male infertility ,03 medical and health sciences ,0302 clinical medicine ,medicine ,General Earth and Planetary Sciences ,Household income ,business ,education ,General Environmental Science ,Demography ,media_common - Abstract
Introduction: The prevalence of type 1 diabetes (T1D) has been increasing over the last few decades and is commonly believed to negatively impact male fertility. We aimed to estimate the prevalence of infertility among men with T1D and to characterize potential clinical predictors for male infertility among men with T1D. Methods: We used data collected from the T1D Exchange Registry from 2012 to 2017. Men with T1D completed an infertility questionnaire indicating whether they had ever had problems conceiving a child or had ever received abnormal results from infertility testing. Collected data included age at questionnaire, age at diagnosis of T1D, duration of T1D, race/ethnicity, insurance status, education level, annual household income, hemoglobin A1c (HbA1c), low density lipoprotein (LDL), diabetic retinopathy, micro/macroalbuminuria, and renal failure. Results: The survey was completed by 2171 registry members, 33 (1.5%) of whom reported male infertility. Mean age at questionnaire was 38 and 56 years in the fertile and infertile groups, respectively (P < 0.001). There was no statistically significant difference in the mean age at T1D diagnosis (16 and 27 years), mean duration of T1D at questionnaire (22 and 30 years), white non-Hispanic ethnicity (1906/2138, 89% versus 30/33, 91%), private insurance (1509/2138, 79% versus 30/33, 91%), and annual household income in US dollars ≥ $100,000 (757/2138, 45% versus 16/33, 55%) in the fertile and infertile men, respectively. On multivariate analysis, for each year of advancing age, men were 5% more likely to experience infertility. Age at questionnaire was the only significant predictor of infertility (OR 1.05; 95%CI 1.03 to 1.08). Age at T1D diagnosis (OR 1.01; 95%CI 0.99 to 1.04), duration of T1D (OR 0.99; 95%CI 0.96 to 1.01), mean HbA1C (OR 1.03; 95%CI 0.77 to 1.37), diabetic retinopathy (OR 1.04; 95%CI 0.50 to 2.15), and mean LDL (OR 1.01; 95%CI 0.99 to 1.02) failed to independently predict infertility; however, presence of renal failure (OR 3.38; 95%CI 0.94 to 12.13) and micro/macroalbuminuria (OR 1.27; 95%CI 0.42 to 3.82) trended toward increased odds of infertility. Conclusions: This study highlights the prevalence of male infertility among men with T1D. Beyond age, there were no independent clinical predictors for male infertility among men with T1D; however, men with clinical evidence of diabetes-associated renal compromise trended toward greater odds of infertility. Further studies of fertility in this growing, at-risk population are warranted.
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- 2021
22. Priapism
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Akash A. Kapadia, Kevin Ostrowski, and Thomas J. Walsh
- Published
- 2021
23. Colonization With Fluoroquinolone-Resistant Enterobacterales Decreases the Effectiveness of Fluoroquinolone Prophylaxis in Hematopoietic Cell Transplant Recipients
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Rianna Malherbe, Michael Hovan, Stephen G. Jenkins, Koen van Besien, Lars F. Westblade, Jingmei Hsu, Alexandra Gomez-Arteaga, Thomas J. Walsh, Claire Douglass, Catherine B. Small, Michael J. Satlin, Sebastian Mayer, Rosemary Soave, Adrienne A. Phillips, Marisa La Spina, Emily Davidson, Liang Chen, and Barry N. Kreiswirth
- Subjects
0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,medicine.medical_treatment ,030106 microbiology ,Bacteremia ,Levofloxacin ,Hematopoietic stem cell transplantation ,Neutropenia ,03 medical and health sciences ,0302 clinical medicine ,Ciprofloxacin ,Neoplasms ,Internal medicine ,Enterobacterales ,medicine ,Humans ,Colonization ,030212 general & internal medicine ,Retrospective Studies ,Hematopoietic cell ,business.industry ,Broth microdilution ,Hematopoietic Stem Cell Transplantation ,Antibiotic Prophylaxis ,medicine.disease ,Transplant Recipients ,Anti-Bacterial Agents ,Transplantation ,Major Articles and Commentaries ,Infectious Diseases ,business ,Fluoroquinolones ,medicine.drug - Abstract
Background Levofloxacin prophylaxis is recommended to prevent gram-negative bloodstream infections (BSIs) in patients with prolonged chemotherapy-induced neutropenia. However, increasing fluoroquinolone resistance may decrease the effectiveness of this approach. Methods We assessed the prevalence of colonization with fluoroquinolone-resistant Enterobacterales (FQRE) among patients admitted for hematopoietic cell transplantation (HCT) from November 2016 to August 2019 and compared the risk of gram-negative BSI between FQRE-colonized and noncolonized patients. All patients received levofloxacin prophylaxis during neutropenia. Stool samples were collected upon admission for HCT and weekly thereafter until recovery from neutropenia, and underwent selective culture for FQRE. All isolates were identified and underwent antimicrobial susceptibility testing by broth microdilution. FQRE isolates also underwent whole-genome sequencing. Results Fifty-four of 234 (23%) patients were colonized with FQRE prior to HCT, including 30 of 119 (25%) allogeneic and 24 of 115 (21%) autologous HCT recipients. Recent antibacterial use was associated with FQRE colonization (P = .048). Ninety-one percent of colonizing FQRE isolates were Escherichia coli and 29% produced extended-spectrum β-lactamases. Seventeen (31%) FQRE-colonized patients developed gram-negative BSI despite levofloxacin prophylaxis, compared to only 2 of 180 (1.1%) patients who were not colonized with FQRE on admission (P Conclusions Nearly one-third of HCT recipients with pretransplant FQRE colonization developed gram-negative BSI while receiving levofloxacin prophylaxis, and infections were typically caused by their colonizing strains. In contrast, levofloxacin prophylaxis was highly effective in patients not initially colonized with FQRE.
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- 2021
24. Comparison between Perianal Swab and Stool Specimens for Detecting Colonization with Extended-Spectrum Beta-Lactamase-Producing and Fluoroquinolone-Resistant Enterobacterales
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Jeffrey M. Kubiak, Michael Hovan, Emily Davidson, Claire Douglass, Kevin Burgos, Thomas J. Walsh, Lars F. Westblade, and Michael J. Satlin
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Gastrointestinal Tract ,Microbiology (medical) ,Enterobacteriaceae ,Hematopoietic Stem Cell Transplantation ,Humans ,Bacteriology ,beta-Lactamases ,Anti-Bacterial Agents ,Fluoroquinolones - Abstract
Stool specimens are frequently used to detect gastrointestinal tract colonization with antimicrobial-resistant enteric bacteria, but they cannot be rapidly collected. Perianal swab specimens can be collected more quickly and efficiently, but data evaluating their suitability as a specimen type for this purpose are sparse. We performed selective culture for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and fluoroquinolone-resistant Enterobacterales (FQRE) using paired perianal swab and stool specimens that were collected within 1 day of each other from hematopoietic cell transplant recipients and patients with acute leukemia. Nineteen (7.6%) of 251 stool specimens yielded ESBL-E and 64 (26%) of 246 stool specimens yielded FQRE. The positive percent agreement of perianal swab specimens compared to stool specimens was 95% (18/19; 95% confidence interval [CI], 74% to 100%) for detecting ESBL-E and 95% (61/64; 95% CI, 87% to 99%) for detecting FQRE. The concordance between specimen types was 98% (95% CI, 97% to 100%). Perianal swabs are a reliable specimen type for surveillance of the gastrointestinal tract for ESBL-E and FQRE.
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- 2022
25. Ultraviolet Rate Constants of Pathogenic Bacteria: A Database of Genomic Modeling Predictions
- Author
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Wladyslaw Kowalski, William P. Bahnfleth, Normand Brais, and Thomas J. Walsh
- Abstract
A database of bacterial ultraviolet (UV) susceptibilities is developed from an empirical model that correlates genomic parameters with UV rate constants. Software is used to count and evaluate potential ultraviolet photodimers and identifying hot spots in bacterial genomes. The method counts dimers that potentially form between adjacent bases that occur at specific genomic motifs such as TT, TC, CT, & CC. Hot spots are identified where clusters of three or more consecutive pyrimidines can enhance absorption of UV photons. The model incorporates nine genomic parameters into a single variable for each species that represents its relative dimerization potential. The bacteria model is based on a curve fit of the dimerization potential to the ultraviolet rate constant data for 92 bacteria species represented by 216 data sets from published studies. There were 4 outliers excluded from the model resulting in a 98% Confidence Interval. The curve fit resulted in a Pearson correlation coefficient of 80%. All identifiable bacteria important to human health, including zoonotic bacteria, were included in the database and predictions of ultraviolet rate constants were made based on their specific genomes. This database is provided to assist healthcare personnel and researchers in the event of outbreaks of bacteria for which the ultraviolet susceptibility is untested and where it may be hazardous to assess due to virulence. Rapid sequencing of the complete genome of any emerging pathogen will now allow its ultraviolet susceptibility to be estimated with equal rapidity. Researchers are invited to challenge these predictions.ImportanceThis research demonstrates the feasibility of using the complete genomes of bacteria to determine their susceptibility to ultraviolet light. Ultraviolet rate constants can now be estimated in advance of any laboratory test. The genomic methods developed herein allow for the assembly of a complete database of ultraviolet susceptibilities of pathogenic bacteria without resorting to laboratory tests. This UV rate constant information can be used to size effective ultraviolet disinfection systems for any specific bacterial pathogen when it becomes a problem.
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- 2022
26. A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer
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Zohar Levi, Sari Lieberman, G Reznick Levi, M Goldenberg, Lior H. Katz, Elizabeth E. Half, Yael Goldberg, L Walsh, D Rothstein, Thomas J. Walsh, T Yablonski Peretz, Ayala Hubert, Ido Laish, Inbal Kedar, Colin C. Pritchard, Lina Basel-Salmon, S Naftaly Nathan, Mary Claire King, R Tomashov-Matar, A Abu Shtaya, Ola Aleme, I Lagovsky, and Sergi Castellví-Bel
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Colorectal cancer ,Genetic counseling ,030105 genetics & heredity ,medicine.disease ,digestive system diseases ,Lynch syndrome ,Human genetics ,03 medical and health sciences ,0302 clinical medicine ,MSH2 ,030220 oncology & carcinogenesis ,Internal medicine ,Epidemiology ,Anticipation (genetics) ,Genetics ,Medicine ,DNA mismatch repair ,business ,Genetics (clinical) - Abstract
Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9–10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.
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- 2021
27. Non-Aspergillus Hyaline Molds: A Host-Based Perspective of Emerging Pathogenic Fungi Causing Sinopulmonary Diseases
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Samantha E. Jacobs and Thomas J. Walsh
- Subjects
Microbiology (medical) ,Plant Science ,Ecology, Evolution, Behavior and Systematics - Abstract
The incidence of invasive sino-pulmonary diseases due to non-Aspergillus hyaline molds is increasing due to an enlarging and evolving population of immunosuppressed hosts as well as improvements in the capabilities of molecular-based diagnostics. Herein, we review the following opportunistic pathogens known to cause sinopulmonary disease, the most common manifestation of hyalohyphomycosis: Fusarium spp., Scedosporium spp., Lomentospora prolificans, Scopulariopsis spp., Trichoderma spp., Acremonium spp., Paecilomyces variotii, Purpureocillium lilacinum, Rasamsonia argillacea species complex, Arthrographis kalrae, and Penicillium species. To facilitate an understanding of the epidemiology and clinical features of sino-pulmonary hyalohyphomycoses in the context of host immune impairment, we utilized a host-based approach encompassing the following underlying conditions: neutropenia, hematologic malignancy, hematopoietic and solid organ transplantation, chronic granulomatous disease, acquired immunodeficiency syndrome, cystic fibrosis, and healthy individuals who sustain burns, trauma, or iatrogenic exposures. We further summarize the pre-clinical and clinical data informing antifungal management for each pathogen and consider the role of adjunctive surgery and/or immunomodulatory treatments to optimize patient outcome.
- Published
- 2023
28. Antifungal efficacy of isavuconazole and liposomal amphotericin B in a rabbit model of Exserohilum rostratum meningoencephalitis: A preclinical paradigm for management of CNS phaeohyphomycosis
- Author
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Patriss W. Moradi, Aspasia Katragkou, Vidmantas Petraitis, Laura L. Kovanda, Ethan Naing, Bo Bo Win Maung, Malcolm Finkelman, Gittel E Sussman-Straus, Thomas J. Walsh, and Ruta Petraitiene
- Subjects
rabbits ,Antifungal Agents ,Pyridines ,Triazole ,Microbial Sensitivity Tests ,Pharmacology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Ascomycota ,Central Nervous System Diseases ,In vivo ,Amphotericin B ,Amphotericin B deoxycholate ,Nitriles ,medicine ,Animals ,Humans ,liposomal amphotericin B ,030212 general & internal medicine ,experimental CNS phaeohyphomycosis ,0303 health sciences ,030306 microbiology ,business.industry ,isavuconazole ,Exserohilum rostratum ,Micafungin ,Disease Management ,Meningoencephalitis ,General Medicine ,Triazoles ,medicine.disease ,In vitro ,Disease Models, Animal ,Phaeohyphomycosis ,Infectious Diseases ,chemistry ,AcademicSubjects/SCI00960 ,Original Article ,Drug Therapy, Combination ,Female ,AcademicSubjects/MED00010 ,business ,medicine.drug - Abstract
Treatment options for Exserohilum rostratum meningoencephalitis and other causes of phaeohyphomycosis of the central nervous system (CNS) are limited, while mortality and morbidity remain high. We therefore evaluated isavuconazole, a new antifungal triazole in comparison to liposomal amphotericin B (LAMB), in vitro and in the rabbit model of Exserohilum rostratum meningoencephalitis. We hypothesized that isavuconazole alone or in combination with LAMB or micafungin may be alternative options for treatment of CNS phaeohyphomycosis. We therefore investigated the in vitro antifungal activity of isavuconazole alone or in combination with amphotericin B deoxycholate (DAMB) or micafungin and efficacy of treatment with isavuconazole and LAMB in a rabbit model of experimental E. rostratum meningoencephalitis. Combination checkerboard plates were used to determine the minimum inhibitory concentrations, minimal lethal concentrations, fractional inhibitory concentration indices, and Bliss surface analysis of isavuconazole and amphotericin B deoxycholate (DAMB), either alone or in combination. As there were no in vitro synergistic or antagonistic interactions for either combination of antifungal agents against the E. rostratum isolates, in vivo studies were conducted with isavuconazole and LAMB as monotherapies. Rabbits were divided in following groups: treated with isavuconazole at 60 mg/kg/d (ISAV60), LAMB at 5.0 (LAMB5), 7.5 (LAMB7.5), and 10 mg/kg/d (LAMB10), and untreated controls (UC). In ISAV60-, LAMB5-, LAMB7.5-, and LAMB10-treated rabbits, significant reductions of fungal burden of E. rostratum in cerebral, cerebellar, and spinal cord tissues (P
- Published
- 2020
29. Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?
- Author
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Andrea J Zimmer, Erica Stohs, Jane Meza, Christopher Arnold, John W Baddley, Pranatharthi Chandrasekar, Zeinab El Boghdadly, Carlos A Gomez, Eileen K Maziarz, Jose G Montoya, Steven Pergam, Kenneth V Rolston, Michael J Satlin, Gowri Satyanarayana, Shmuel Shoham, Lynne Strasfeld, Randy Taplitz, Thomas J Walsh, Jo-Anne H Young, Yuning Zhang, and Alison G Freifeld
- Subjects
Infectious Diseases ,Oncology - Abstract
Background Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.
- Published
- 2022
30. Outcome Disparities Among Men and Women With COVID-19: An Analysis of the New York City Population Cohort
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Joseph P. Alukal, Thomas J. Walsh, Joseph M. Caputo, Nahid Punjani, Mary Ann Chiasson, Lisa Wiechmann, James M. Hotaling, Philip S. Li, Albert S. Ha, and Vinson Wang
- Subjects
Adult ,Male ,Databases, Factual ,Coronavirus disease 2019 (COVID-19) ,Pneumonia, Viral ,Disease ,Risk Assessment ,Cohort Studies ,COVID-19 Testing ,Sex Factors ,Cause of Death ,Outcome Assessment, Health Care ,Case fatality rate ,Humans ,Medicine ,Hospital Mortality ,Healthcare Disparities ,Pandemics ,Aged ,Retrospective Studies ,Cause of death ,Clinical Laboratory Techniques ,business.industry ,COVID-19 ,Retrospective cohort study ,Health Status Disparities ,General Medicine ,Middle Aged ,Hospitalization ,Relative risk ,Female ,New York City ,Coronavirus Infections ,business ,Risk assessment ,Demography ,Cohort study - Abstract
Background Growing evidence suggests a possible sex disparity in COVID-19 disease related outcomes. Objective To explore the sex disparity in COVID-19 cases and outcomes using New York City (NYC) population level data. Setting NYC surveillance data from February 29 to June 12, 2020. Participants Individuals tested for COVID-19 in metropolitan NYC.Outcome Measurements and Statistical Analysis: Outcomes of interest included rates of COVID-19 case positivity, hospitalization and death. Relative risks and case fatality rates were computed for all outcomes based on sex and were stratified by age groups. Results and limitations 911,310 individuals were included, of whom 434,273 (47.65%) were male and 477,037 (52.35%) were female. Men represented the majority of positive cases (n=106,275, 51.36%), a majority of hospitalizations (n=29,847, 56.44%), and a majority of deaths (n=13,054, 59.23%). Following population level adjustments for age and sex, testing rates of men and women were equivalent. The majority of positive cases and hospitalizations occurred in men for all age groups except age g75 years, and death was more likely in men of all age groups. Men were at a statistically significant greater relative risk of case positivity, hospitalization, and death across all age groups except those l18 years of age. The most significant difference for case positivity was observed in the 65n74 age group (RR 1.22, 95%CI 1.19n1.24), for hospitalization in the 45n65 age group (RR 1.85, 95% 1.80n1.90), and for death in the 18n44 age group (RR 3.30, 95% CI 2.82n3.87). Case fatality rates were greater for men in all age-matched comparisons to women. Limitations include the use of an evolving surveillance data set and absence of further demographic characteristics such as ethnographic data. Conclusion Men have higher rates of COVID-19 positivity, hospitalization, and death despite greater testing of women; this trend remains after stratification by age. J Drugs Dermatol. 2020;19(10):960-967. doi:10.36849/JDD.2020.5590.
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- 2020
31. Efficacy of Amphotericin B in Corneal Preservation Media After Extended Frozen Storage
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Christopher S. Sáles, Megan M W Straiko, Matthew W. McCarthy, Khoa D. Tran, Thomas J. Walsh, Angela S Loo, and Doowon Huh
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Antifungal ,Antifungal Agents ,medicine.drug_class ,Organ Preservation Solutions ,Microbial Sensitivity Tests ,Complex Mixtures ,Culture Media, Serum-Free ,Microbiology ,Cornea ,Amphotericin B ,Amphotericin B deoxycholate ,Candida albicans ,medicine ,Humans ,Log10 reduction ,Cryopreservation ,biology ,Chemistry ,Chondroitin Sulfates ,Dextrans ,Organ Preservation ,biology.organism_classification ,Corpus albicans ,Drug Combinations ,Ophthalmology ,Treatment Outcome ,Frozen storage ,Gentamicins ,Deoxycholic Acid ,medicine.drug - Abstract
Purpose To investigate the antimycotic activity of amphotericin B deoxycholate that has been previously frozen for 28 days before supplementation of Optisol-GS. Methods Triplicate Optisol-GS samples were inoculated with 10 colony-forming units (CFU) of Candida albicans. Each set of triplicate cultures was supplemented with 2.5 μg/mL of amphotericin B that was either freshly resuspended and never frozen, frozen overnight at -20°C and thawed, or frozen at -20°C for 4 weeks and thawed. The cultures were stored at 4°C, with aliquots taken at 0, 6, 24, and 72 hours for quantification. The efficacy of each preparation of amphotericin B in reducing C. albicans growth was assessed at these time points. Results Six hours after antifungal supplementation, there was a 1.33 log10 CFU reduction with freshly resuspended amphotericin B, compared with a 1.31 log10 reduction with amphotericin B that was frozen overnight (P = 0.20) and a 1.18 log10 reduction with amphotericin B that was frozen for 4 weeks (P = 0.05). After 72 hours, there was a 2.72 log10 CFU reduction with freshly resuspended amphotericin B, a 2.64 log10 CFU reduction with amphotericin B that was frozen overnight (P = 0.45), and a 2.18 log10 CFU reduction with amphotericin B that was frozen for 4 weeks (P = 0.05). Conclusions Previously frozen amphotericin B remains highly effective against C. albicans. Optisol-GS supplemented with 2.5 μg/mL amphotericin B that was frozen for 4 weeks at -20°C resulted in >90% CFU reduction by 6 hours and >99% reduction by 72 hours.
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- 2020
32. Testicular Mapping
- Author
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Thomas J. Walsh and Akash A. Kapadia
- Subjects
Azoospermia ,medicine.medical_specialty ,business.industry ,Urology ,General surgery ,FNA Mapping ,030232 urology & nephrology ,Integrated approach ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Reproductive endocrinologist ,Sperm Retrieval ,medicine ,Testis biopsy ,Nonobstructive azoospermia ,business ,Fertility care - Abstract
Guiding a couple with nonobstructive azoospermia requires an integrated approach to care by the urologist and the reproductive endocrinologist. After informing the couple of the implications of the diagnosis, care must be taken to outline the options of parenthood. Most experts agree that sperm retrieval in men can be challenging. This article describes various options of sperm retrieval, historic and contemporary, and highlights the advantages and disadvantages of each. The authors find that using a testicular map can invariably help guide sperm retrieval and overall fertility care. The right approach is one that involves a shared decision with the couple.
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- 2020
33. Management of osteoarticular fungal infections in the setting of immunodeficiency
- Author
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Savvas Papachristou, Nikolaos V. Sipsas, Thomas J. Walsh, Elias Iosifidis, Maria N. Gamaletsou, and Emmanuel Roilides
- Subjects
0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Antifungal Agents ,medicine.medical_treatment ,030106 microbiology ,Antifungal drug ,Arthritis ,Microbiology ,Immunocompromised Host ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Virology ,Osteoarthritis ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,Immunodeficiency ,Arthritis, Infectious ,Surgical approach ,business.industry ,Osteomyelitis ,Immunotherapy ,medicine.disease ,Infectious Diseases ,Mycoses ,business ,Immunosuppressive Agents ,Dimorphic fungus - Abstract
Introduction: Osteoarticular fungal infections (OAFIs) complicate the clinical course of high-risk patients, including immunosuppressed individuals. Their management, however, despite being intricate, is governed by evidence arising from sub-optimal quality research, such as case series. Guidelines are scarce and when present result in recommendations based on low quality evidence. Furthermore, the differences between the management of immunocompromised and immunocompetent patients are not distinct. This is a narrative review after a literature search in PubMed, up to November 2019.Areas covered: The major fungal groups causing osteomyelitis and/or arthritis are Candida spp., Aspergillus spp., non-Aspergillus filamentous fungi, non-Candida yeasts and endemic dimorphic fungi. Their epidemiology is briefly analyzed with emphasis on immunodeficiency and other risk factors. Management of OAFIs includes appropriate antifungal drug therapy (liposomal amphotericin B, triazoles or echinocandins), local surgery and immunotherapy for primary immunodeficiencies. Cessation of immunosuppressive drugs is also mandated.Expert opinion: Management of OAFIs includes affordable and available options and approaches. However, research on therapeutic practices is urgently required to be further improved, due to the rarity of affected patients. Evolution is expected to translate into novel antifungal drugs, less invasive and precise surgical approaches and targeted enhancement of immunoregulatory pathways in defense of challenging fungal pathogens.
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- 2020
34. Comparative evaluation of operating room terminal cleaning by two methods: Focused multivector ultraviolet (FMUV) versus manual-chemical disinfection
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Kristine Goldstein, Donna Armellino, Thomas J. Walsh, Vidmantas Petraitis, and Linti Thomas
- Subjects
Operating Rooms ,Ultraviolet Rays ,Epidemiology ,Hospital quality ,Microbial contamination ,Patient care ,Chemical disinfection ,Comparative evaluation ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,030212 general & internal medicine ,Terminal cleaning ,Process engineering ,Protocol (science) ,Infection Control ,0303 health sciences ,030306 microbiology ,business.industry ,Health Policy ,Public Health, Environmental and Occupational Health ,Parallel process ,Disinfection ,Infectious Diseases ,business ,Disinfectants - Abstract
This non-randomized comparative observational study evaluated the performance of a standard manual-chemical disinfection process with an automated process employing focused multivector ultraviolet (FMUV) light technology during operating room (OR) terminal cleaning.An Association of periOperative Registered Nurses terminal cleaning protocol was modified to incorporate the use of automated FMUV technology that allows workers to occupy the room during operation. This modified protocol was compared with a standard manual-chemical cleaning and disinfection protocol. Equipment surfaces were pre-sampled before and after terminal cleaning. A total of 165 objects were sampled in each process using a 5-point multisided sampling method.The parallel process employing FMUV reduced the active microbial burden by 96.5% from baseline (P.0001), which was over 2.5 times better than the standard process. The standard terminal manual-chemical disinfection process reduced the active microbial burden on sampled objects by 38.4% from baseline (P.0001).The data demonstrates that the performance of standard manual-chemical disinfection alone is variable in a live clinical setting even under the most ideal conditions. By comparison, automated FMUV treatment incorporated in a parallel process consistently produced thorough and significant reductions of microbial contamination levels on all visibly clean patient care equipment.
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- 2020
35. Dalbavancin Reduces Hospital Stay and Improves Productivity for Patients with Acute Bacterial Skin and Skin Structure Infections: The ENHANCE Trial
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Justin J Choi, Thomas J. Walsh, Nicholas Pickell, Patrick Gillard, Ronald Copp, Katelyn R. Keyloun, and Matthew W. McCarthy
- Subjects
0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Activities of daily living ,Acute bacterial skin and skin structure infection ,Cost ,medicine.drug_class ,030106 microbiology ,Antibiotics ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Intensive care ,Long-acting antibiotic ,Medicine ,lcsh:RC109-216 ,In patient ,030212 general & internal medicine ,Original Research ,business.industry ,Dalbavancin ,Pragmatic trial ,Infectious Diseases ,Skin structure ,business ,Hospital stay - Abstract
Introduction Admissions for acute bacterial skin and skin structure infections (ABSSSI) are often prolonged because of intravenous (IV) antibiotics. Use of a long-acting IV antibiotic may reduce length of stay (LOS) on a hospitalist service. The ENHANCE ABSSSI trial sought to determine the impact on LOS and work productivity in patients treated with a long-acting IV antibiotic, dalbavancin, vs. usual care at an urban tertiary-care center. Methods A single-center, pre- vs. post-period pragmatic trial at Weill-Cornell Medical Center assessed usual care for consecutively enrolled admitted ABSSSI patients during an observational period (pre-period). Identification and treatment of eligible admitted ABSSSI patients with dalbavancin were implemented in the post-period. Those with life-threatening infections, requiring multiple antibiotics/intensive care, or with unstable comorbidities were excluded. Outcomes were assessed over a 44-day follow-up period. Results Of 48 and 43 patients enrolled, respectively, in the pre- and post-periods, mean infection-related LOS was reduced in the post-period (3.2 days vs. 4.8 days; P = 0.003). Similar results were found in an adjusted LOS analysis. Work productivity and activity impairment outcomes significantly improved in the post-period (P ≤ 0.01). Complete response rates were similar: 50% (pre-period) and 57% (post-period). Among AEs identified, 17% (n = 7) were found to have possible causal relation to dalbavancin in the post-period. Few AEs were serious (n = 3; 7% post-period versus n = 1; 2% pre-period). Conclusion After implementing the ENHANCE ABSSSI pathway, LOS was significantly reduced by almost 2 days, with potential improvements in work productivity and ability to complete daily activities. Trial Registration ClinicalTrials.gov identifier, NCT03233438. Funding Allergan plc. Electronic supplementary material The online version of this article (10.1007/s40121-019-00275-4) contains supplementary material, which is available to authorized users.
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- 2019
36. Orchiectomy as Bridge or Alternative to Vaginoplasty
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Thomas J. Walsh and Marah C. Hehemann
- Subjects
Male ,Gender dysphoria ,medicine.medical_specialty ,Urology ,Gender affirmation ,030232 urology & nephrology ,Healthy tissue ,Limited access ,03 medical and health sciences ,Gynecologic Surgical Procedures ,0302 clinical medicine ,Transgender ,Sex Reassignment Surgery ,Humans ,Medicine ,Orchiectomy ,Gender Dysphoria ,business.industry ,Sex reassignment surgery (female-to-male) ,medicine.disease ,Surgery ,030220 oncology & carcinogenesis ,Vagina ,Vaginoplasty ,Female ,business ,Transsexualism - Abstract
Simple orchiectomy for gender affirmation is a low-risk, minimally invasive, generalizable procedure that eliminates circulating endogenous testosterone, allowing reduced hormonal supplementation. This article describes a technique that serves as a step in definitive phenotypic transition while maximally preserving healthy tissue for future sex reassignment surgery. Orchiectomy should be offered routinely as a bridge or alternative to vaginoplasty, particularly in the setting of limited access to specialized centers for transgender surgery.
- Published
- 2019
37. Pharmacokinetics, Tissue Distribution, and Efficacy of VIO-001 (Meropenem/Piperacillin/Tazobactam) for Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia in Immunocompetent Rabbits with Chronic Indwelling Vascular Catheters
- Author
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Nicholas K. Goldner, Thomas J. Walsh, Ethan Naing, Christina A. Sutherland, Aki Yoneda Kau, Vidmantas Petraitis, Andrew Garcia, Ruta Petraitiene, David P. Nicolau, Christopher Bulow, and Povilas Kavaliauskas
- Subjects
Methicillin-Resistant Staphylococcus aureus ,medicine.medical_specialty ,Bacteremia ,Microbial Sensitivity Tests ,medicine.disease_cause ,Meropenem ,Gastroenterology ,Tazobactam ,Internal medicine ,medicine ,Animals ,Tissue Distribution ,Experimental Therapeutics ,Pharmacology (medical) ,Pharmacology ,business.industry ,Staphylococcal Infections ,medicine.disease ,Methicillin-resistant Staphylococcus aureus ,Anti-Bacterial Agents ,Piperacillin, Tazobactam Drug Combination ,Infectious Diseases ,Pharmacodynamics ,Piperacillin/tazobactam ,Vancomycin ,Rabbits ,business ,Vascular Access Devices ,Piperacillin ,medicine.drug - Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) infections of surgically implanted subcutaneous vascular catheters (SISVCs) cause serious morbidity in patients with chronic illnesses. Previous in vitro and murine models demonstrated the synergistic interaction of equimolar concentrations of meropenem/piperacillin/tazobactam (MPT) (VIO-001) against MRSA infection. We investigated the pharmacokinetics (PK) and efficacy of VIO-001 for the treatment of MRSA bacteremia in immunocompetent rabbits with SISVCs. In PK studies, we determined that optimal dosing to achieve a time above 4× MIC (T(>4×MIC)) of a duration of 3 to 3.30 h required a 1-h infusion with every-4-h (Q4h) dosing. Study groups in efficacy experiments consisted of MPT combinations of 100/150/100 mg/kg of body weight (MPT100), 200/300/200 mg/kg (MPT200), and 400/600/400 mg/kg (MPT400); vancomycin (VAN) at 15 mg/kg; and untreated controls (UC). The inoculum of MRSA isolate USA300-TCH1516 (1 × 10(3) organisms) was administered via the SISCV on day 1 and locked for 24 h. The 8-day therapy started at 24 h postinoculation. There was a significant reduction of MRSA in blood cultures from the SISVCs in all treatment groups, with full clearance on day 4, versus UCs (P
- Published
- 2021
38. Adenovirus viremia after
- Author
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Ok-Kyong, Chaekal, Rosemary, Soave, Zhengming, Chen, Tsiporah, Shore, Sebastian, Mayer, Adrienne, Phillips, Jing, Mei Hsu, Alexandra, Gomez-Arteaga, Hanna, Rennert, Alex, Drelick, Nina, Orfali, Thomas J, Walsh, Catherine B, Small, Rosy Priya L, Kodiyanplakkal, Markus, Plate, Michael J, Satlin, and Koen, van Besien
- Subjects
Adult ,T-Lymphocytes ,Hematopoietic Stem Cell Transplantation ,Humans ,Lymphocyte Count ,Viremia ,Adenoviridae - Abstract
The incidence of adenovirus viremia and the role of screening in preventing adenovirus disease in adult transplant recipients are not well defined. Between January 2017 and May 2020, 262 allogeneic transplants were performed using
- Published
- 2021
39. Outracing champion Gran Turismo drivers with deep reinforcement learning
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Peter R. Wurman, Samuel Barrett, Kenta Kawamoto, James MacGlashan, Kaushik Subramanian, Thomas J. Walsh, Roberto Capobianco, Alisa Devlic, Franziska Eckert, Florian Fuchs, Leilani Gilpin, Piyush Khandelwal, Varun Kompella, HaoChih Lin, Patrick MacAlpine, Declan Oller, Takuma Seno, Craig Sherstan, Michael D. Thomure, Houmehr Aghabozorgi, Leon Barrett, Rory Douglas, Dion Whitehead, Peter Dürr, Peter Stone, Michael Spranger, and Hiroaki Kitano
- Subjects
Automobile Driving ,Competitive Behavior ,Multidisciplinary ,Deep Learning ,Reward ,Video Games ,Autonomous racing ,Reinforcement Learning ,Humans ,Reinforcement, Psychology ,Sports - Abstract
Many potential applications of artificial intelligence involve making real-time decisions in physical systems while interacting with humans. Automobile racing represents an extreme example of these conditions; drivers must execute complex tactical manoeuvres to pass or block opponents while operating their vehicles at their traction limits
- Published
- 2021
40. Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections
- Author
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David A. Angulo, Barbara Alexander, Riina Rautemaa-Richardson, Ana Alastruey-Izquierdo, Martin Hoenigl, Ashraf S. Ibrahim, Mahmoud A. Ghannoum, Thomas R. King, Nkechi E. Azie, Thomas J. Walsh, and NIH - National Institute of Allergy and Infectious Diseases (NIAID) (Estados Unidos)
- Subjects
Microbiology (medical) ,Prevention ,ibrexafungerp ,Evaluation of treatments and therapeutic interventions ,Plant Science ,invasive fungal infection ,molds ,new antifungal agents ,Emerging Infectious Diseases ,Infectious Diseases ,Rare Diseases ,5.1 Pharmaceuticals ,6.1 Pharmaceuticals ,triterpenoid ,Development of treatments and therapeutic interventions ,Infection ,Ecology, Evolution, Behavior and Systematics - Abstract
Molds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited antifungal treatment options, and the opportunism of environmental molds renders patients at risk and especially vulnerable to invasive mold infections such as Aspergillus and members of the Order Mucorales. Currently, available antifungal drugs such as azoles and echinocandins, as well as combinations of the same, offer some degree of efficacy in the prevention and treatment of invasive mold infections, but their use is often limited by drug resistance mechanisms, toxicity, drug-drug interactions, and the relative paucity of oral treatment options. Clearly, there is a need for agents that are of a new class that provides adequate tissue penetration, can be administered orally, and have broad-spectrum efficacy against fungal infections, including those caused by invasive mold organisms. Ibrexafungerp, an orally bioavailable glucan synthase inhibitor, is the first in a new class of triterpenoid antifungals and shares a similar target to the well-established echinocandins. Ibrexafungerp has a very favorable pharmacokinetic profile for the treatment of fungal infections with excellent tissue penetration in organs targeted by molds, such as the lungs, liver, and skin. Ibrexafungerp has demonstrated in vitro activity against Aspergillus spp. as well as efficacy in animal models of invasive aspergillosis and mucormycosis. Furthermore, ibrexafungerp is approved for use in the USA for the treatment of women with vulvovaginal candidiasis. Ibrexafungerp is currently being evaluated in clinical trials as monotherapy or in combination with other antifungals for treating invasive fungal infections caused by yeasts and molds. Thus, ibrexafungerp offers promise as a new addition to the clinician's armamentarium against these difficult-to-treat infections. Experiments reported in this manuscript were funded by Scynexis and support for mucormycosis research was provided by the NIH/NIAID under Contract No. HHSN272201700039I (Task order A34-HHSN27200003). Sí
- Published
- 2022
41. Safety, Tolerability, and Population Pharmacokinetics of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients
- Author
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J. Christopher Day, Haydar Frangoul, Christopher Lademacher, Lara Danziger-Isakov, William J Muller, Inci Yildirim, Amit Desai, William J. Steinbach, Mark E. Jones, Julie Chu, Paul K. Sue, Laura L. Kovanda, Tempe K. Chen, Susan R. Rheingold, Dwight E Yin, Michael Neely, Thomas J. Walsh, Antonio Arrieta, Victoria A. Statler, Desiree Leiva Phillips, Kelley Micklus, Grace A. McComsey, and Kamal Hamed
- Subjects
0301 basic medicine ,Adolescent ,Pyridines ,030106 microbiology ,Administration, Oral ,Population pharmacokinetics ,Clinical Therapeutics ,Pharmacology ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,population pharmacokinetics ,Oral administration ,Nitriles ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Child ,invasive fungal infections ,business.industry ,isavuconazole ,Infant ,Safety tolerability ,Triazoles ,Prodrug ,Isavuconazonium ,triazole ,pediatric ,Infectious Diseases ,Tolerability ,Child, Preschool ,business ,medicine.drug - Abstract
Isavuconazole, administered as the water-soluble prodrug isavuconazonium sulfate, is a new triazole agent used to treat invasive fungal infections. This phase 1 study evaluated the pharmacokinetics (PK), safety, and tolerability of isavuconazole in 46 immunocompromised pediatric patients, stratified by age (1 to 80% and >76% of simulated pediatric patients following i.v. or oral administration, respectively. Intravenous and oral administration of isavuconazonium sulfate at the studied dosage of 10 mg/kg was well tolerated and resulted in exposure in pediatric patients similar to that in adults. (This study has been registered at ClinicalTrials.gov under identifier NCT03241550).
- Published
- 2021
42. YIA20-002: Racial Differences in Clinical Histopathological Features and Survival of Early- and Average-Onset Colorectal Cancer
- Author
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Ai Zhang, Deyali Chatterjee, Jie Liu, Jennifer Tappenden, Graham A. Colditz, Yin Cao, Thomas J. Walsh, Hanyu Chen, Xiaoyu Zong, and Ryan C. Fields
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Colorectal cancer ,Internal medicine ,medicine ,Racial differences ,business ,medicine.disease - Published
- 2020
43. Therapeutic drug monitoring of systemic antifungal agents: a pragmatic approach for adult and pediatric patients
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Shawn Mazur, Jamie John, Angela Loo, and Thomas J. Walsh
- Subjects
Adult ,medicine.medical_specialty ,Posaconazole ,Antifungal Agents ,Itraconazole ,Toxicology ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Therapeutic index ,Drug Development ,Amphotericin B ,medicine ,Humans ,Dosing ,Child ,Intensive care medicine ,Pharmacology ,Voriconazole ,medicine.diagnostic_test ,business.industry ,General Medicine ,Therapeutic drug monitoring ,030220 oncology & carcinogenesis ,Drug Monitoring ,business ,Invasive Fungal Infections ,Fluconazole ,medicine.drug - Abstract
Introduction: Therapeutic drug monitoring (TDM) has been shown to optimize the management of invasive fungal infections (IFIs), particularly for select antifungal agents with a well-defined exposure-response relationship and an unpredictable pharmacokinetic profile or a narrow therapeutic index. Select triazoles (itraconazole, voriconazole, and posaconazole) and flucytosine fulfill these criteria, while the echinocandins, fluconazole, isavuconazole, and amphotericin B generally do not do so. Given the morbidity and mortality associated with IFIs and the challenges surrounding the use of currently available antifungal agents, TDM plays an important role in therapy.Areas covered: This review seeks to describe the rationale for TDM of antifungal agents, summarize their pharmacokinetic and pharmacodynamic properties, identify treatment goals for efficacy and safety, and provide recommendations for optimal dosing and therapeutic monitoring strategies.Expert opinion: Several new antifungal agents are currently in development, including compounds from existing antifungal classes with enhanced pharmacokinetic or safety profiles as well as agents with novel targets for the treatment of IFIs. Given the predictable pharmacokinetics of these newly developed agents, use of routine TDM is not anticipated. However, expanded knowledge of exposure-response relationships of these compounds may yield a role for TDM to improve outcomes for adult and pediatric patients.
- Published
- 2019
44. Comparison of clinician and patient users of a mobile phone application to assess penile curvature in Peyronie’s disease
- Author
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Saneal Rajanahally, Thomas J. Walsh, George R. Schade, Marc J. Rogers, Hunter Wessells, Ryan S. Hsi, Wayne Brisbane, Lauren Trew, and Kevin A. Ostrowski
- Subjects
medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,Home environment ,business.industry ,Urology ,Girth measurements ,Gold standard ,030232 urology & nephrology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Disease severity ,Patient experience ,Physical therapy ,Medicine ,Pearson Correlation Test ,Penile curvature ,Peyronie's disease ,business - Abstract
Assessment of Peyronie’s disease with penile injection is invasive and uncomfortable. We developed a smartphone application (UWPEN) to assess penile angulation in the home environment. The purpose of this study was to compare clinician and patient measurements and assess the patient experience with UWPEN in a clinical setting. We prospectively enrolled patients with Peyronie’s disease undergoing intracavernosal injection of alprostadil. Penile angulation and narrowing were then assessed by patients and clinicians using UWPEN and compared to values obtained via a goniometer and a ruler (gold standard). Measurements were compared using the Pearson correlation test. Upon completion of measurements, patients were surveyed regarding the ease of use, confidence with use, and measurement preferences. Twenty patients were enrolled in the study; two patients were excluded for poor penile turgidity after a maximum dosage of intracavernosal alprostadil. Correlation between UWPEN and gold standard measurements by patients and clinicians was R = 0.55 (p = 0.01) and R = 0.87 (p
- Published
- 2019
45. Assessment of focused multivector ultraviolet disinfection withshadowless delivery using 5-point multisided sampling ofpatientcare equipment without manual-chemical disinfection
- Author
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Wladyslaw Kowalski, Thomas J. Walsh, Donna Armellino, and Vidmantas Petraitis
- Subjects
Sampling protocol ,Surface Properties ,Ultraviolet Rays ,Epidemiology ,Colony Count, Microbial ,Chemical disinfection ,Patient care ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,Infection control ,030212 general & internal medicine ,Cross Infection ,0303 health sciences ,Waste management ,030306 microbiology ,business.industry ,Health Policy ,Public Health, Environmental and Occupational Health ,Sampling (statistics) ,Ultraviolet germicidal irradiation ,Disinfection ,Treatment Outcome ,Infectious Diseases ,Equipment and Supplies ,business - Abstract
The aim of this study was to evaluate the performance of a focused multivector ultraviolet (FMUV) system employing shadowless delivery with a 90-second disinfection cycle for patient care equipment inside and outside the operating room (OR) suite without manual-chemical disinfection.A 5-point multisided sampling protocol was utilized to measure the microbial burden on objects inside and outside the OR environment in a 3-phase nonrandomized observational study. Surface sampling was performed pre- and postdisinfection in between cases (IBCs) to assess the performance of manual-chemical disinfection. FMUV system performance was separately assessed pre- and postdisinfection before the first case and IBCs. Additionally, visibly clean high-touch objects were sampled outside the OR, and the microbial burden reductions after FMUV disinfection were quantified without manual-chemical disinfection.Manual-chemical disinfection reduced the active microbial burden on sampled objects IBCs by 52.8%-90.9% (P.05). FMUV reduced the active microbial burden by 92%-97.7% (P.0001) before the firstcase and IBCs combined, and 96.3%-99.6% (P.0001) on objects outside the OR without chemical disinfection.Five-point multisided sampling proved effective for assessing disinfection performance on all exterior sides of equipment. FMUV produced significant overall reductions of the microbial burden on patient care equipment in all study phases and independent of manual cleaning and chemical disinfection.
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- 2019
46. Nonmuscle Invasive Bladder Cancer Influences Physical Health Related Quality of Life and Urinary Incontinence
- Author
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George R. Schade, Jonathan L. Wright, Wayne Brisbane, John L. Gore, Brian Winters, Thomas J. Walsh, and Sarah K. Holt
- Subjects
Male ,medicine.medical_specialty ,Urology ,Population ,030232 urology & nephrology ,Urinary incontinence ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,Bayesian multivariate linear regression ,Epidemiology ,medicine ,Humans ,Neoplasm Invasiveness ,education ,Aged ,education.field_of_study ,Bladder cancer ,business.industry ,medicine.disease ,Urinary function ,Confidence interval ,Urinary Incontinence ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,medicine.symptom ,business - Abstract
To evaluate the effects of nonmuscle invasive bladder cancer (NMIBC) on health-related quality of life (HRQOL) and urinary function within patients diagnosed with NMIBC as compared to the general population.Using the Surveillance, Epidemiology, and End Results-Medicare Health Outcome Survey (SEER-MHOS) database (1998-2013), 325 patients diagnosed with NMIBC with baseline and postdiagnosis MHOS surveys were propensity-matched 1:5 to noncancer controls (NCC). Multivariate linear regression analysis compared NMIBC patients with matched NCC in terms of physical component summary (PCS), mental component summary (MCS), and health domain scales. Changes in urinary function were assessed using χPatients diagnosed with NMIBC experienced significant decline in PCS vs NCC (-3.0, 95% confidence interval [CI -4.1, -2.0] vs -1.5, 95%CI [-2.0, -1.0], P = .01), while the observed decline in MCS was not significantly different (P = .09) between groups. On sub-analysis, the significant decline in PCS was confined to patients with high-risk NMIBC (P = .01). NMIBC patients had significantly greater decline in role physical (P = .04), general health (P = .04) and role emotional (P0.01) health domain scales. NMIBC patients were more likely to report worsened urinary leakage, require physician intervention, and receive new treatment for urinary leakage (P values all.01).NMIBC diagnosis was associated with significant decreases in physical HRQOL and urinary function compared with NCC. Further study focused on NMIBC patients, and the inherent HRQOL factors to this diagnosis is needed to assess where improvements can be made in treating this patient population.
- Published
- 2019
47. Prophylactic rituximab prevents EBV PTLD in haplo-cord transplant recipients at high risk
- Author
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Koen van Besien, Michael J. Satlin, Maxwell A. Brown, Hanna Rennert, Adrienne A. Phillips, Thomas J. Walsh, Tsiporah B. Shore, Adriana C Rossi, Usama Gergis, Jingmei Hsu, Sebastian Mayer, Danielle Guarneri, Catherine B. Small, Lizamarie Bachier-Rodriguez, Amrita Singh, and Rosemary Soave
- Subjects
Adult ,Male ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Cancer Research ,Transplantation Conditioning ,Allogeneic transplantation ,Cord ,New York ,Lymphoproliferative disorders ,medicine.disease_cause ,Virus ,Young Adult ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,medicine ,Humans ,Aged ,business.industry ,Histocompatibility Testing ,Incidence ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Epstein–Barr virus ,Lymphoproliferative Disorders ,Transplant Recipients ,Survival Rate ,surgical procedures, operative ,Oncology ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Transplantation, Haploidentical ,Immunology ,Female ,Virus Activation ,Rituximab ,Cord Blood Stem Cell Transplantation ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Epstein-Barr virus (EBV) reactivation and post-transplant lymphoproliferative disorders (PTLD) are common and potentially fatal complications after allogeneic transplantation with mismatched donors and T-cell depletion. Haplo-cord transplantation combines a mismatched UCB graft with third-party cells. Conditioning involves thymoglobulin. EBV reactivation and PTLD were common in initial patients. As of March 2017, we administered a prophylactic dose of rituximab 375 mg/m
- Published
- 2019
48. The expanding use of matrix-assisted laser desorption/ionization-time of flight mass spectroscopy in the diagnosis of patients with mycotic diseases
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Matthew W. McCarthy and Thomas J. Walsh
- Subjects
0301 basic medicine ,Materials science ,Fungi ,Analytical chemistry ,Matrix assisted laser desorption ionization time of flight ,Mass spectrometry ,Laser ,Pathology and Forensic Medicine ,law.invention ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Molecular Diagnostic Techniques ,Mycoses ,law ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,030220 oncology & carcinogenesis ,Desorption ,Genetics ,Humans ,Molecular Medicine ,Molecular Biology - Abstract
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a powerful new tool to identify human fungal pathogens and has radically altered the diagnostic mycology workflow at many medical centers around the world. Areas covered: While most experience is with the identification of yeasts, including species of Candida and Cryptococcus, there is ongoing work investigating the role of MALDI-TOF MS to detect molds, including species of Aspergillus, Fusarium, Scedosporium, and Mucormyctes as well as thermally dimorphic fungi. Expert commentary: In this paper, we review the current knowledge about this important new platform and examine how its expanding use may impact molecular diagnostics and patient care in the years ahead.
- Published
- 2019
49. Fungal Endophthalmitis after Intravitreal Injections of Triamcinolone Contaminated by a Compounding Pharmacy: Five-Year Follow-up of 23 Patients
- Author
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Elaine M. Tran, Kent W. Small, Christine A. Garabetian, Thomas J. Walsh, Jessica Avetisjan, and Fadi Shaya
- Subjects
Adult ,Male ,Fungal meningitis ,medicine.medical_specialty ,Triamcinolone acetonide ,Visual acuity ,genetic structures ,Drug Compounding ,Visual Acuity ,Triamcinolone Acetonide ,03 medical and health sciences ,0302 clinical medicine ,Endophthalmitis ,Ophthalmology ,medicine ,Humans ,Aged ,Retrospective Studies ,030304 developmental biology ,Aged, 80 and over ,Voriconazole ,0303 health sciences ,biology ,business.industry ,Middle Aged ,Eye infection ,medicine.disease ,Bipolaris ,biology.organism_classification ,eye diseases ,Methylprednisolone ,Intravitreal Injections ,030221 ophthalmology & optometry ,Female ,medicine.symptom ,Drug Contamination ,business ,Eye Infections, Fungal ,Follow-Up Studies ,medicine.drug - Abstract
Purpose To report the 5-year outcome of an outbreak of Bipolaris hawaiiensis fungal endophthalmitis caused by contamination of intravitreal triamcinolone from Franck’s Compounding Pharmacy in Ocala, Florida. Design Retrospective case series. Participants Twenty-three patients (n = 25 eyes). Methods Data was collected from the practice of a single retina specialist in Los Angeles (K.W.S) and a retina practice in New York City. Intravitreal injections of triamcinolone obtained from a single lot were subsequently found to be contaminated with Bipolaris hawaiiensis. Main Outcome Measures Visual acuity; presence of vitreous cells, anterior chamber cells, or both; and detection of fungi or fungal elements in samples obtained by vitreous needle aspiration or vitreous biopsy. Results Fungal endophthalmitis developed in 92% (23/25) of eyes. Despite aggressive local and systemic long-term therapy, severe visual loss resulted in the majority of treated eyes and the enucleated eyes showed evidence of hyphae. Conclusions These reported cases of Bipolaris hawaiiensis endophthalmitis provide important messages for clinicians and regulatory agencies. First, patients treated with high-dose, long-term, orally administered voriconazole appeared to achieve better outcomes in treatment of Bipolaris endophthalmitis. Second, treated eyes may still show signs of deterioration, indicating the potential survival of causative organisms or fibrosis encapsulating the ciliary body, leading to hypotony. Third, several parallels can be drawn between this outbreak and the fungal meningitis outbreak after Exserohilum rostratum contamination of methylprednisolone by the New England Compounding Center.
- Published
- 2019
50. 992. Oral Ibrexafungerp Outcomes in Patients with Oropharyngeal and Esophageal Candidiasis from an Interim Analysis of a Phase 3 Open-label Study (FURI)
- Author
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Jose A Vazquez, Oliver Cornely, Philipp Koehler, Riina Rautemaa-Richardson, Rohit Bazaz, G Marshall Lyon, Francisco M Marty, Isabel H Gonzalez-Bocco, Rachel Miller, Thomas J Walsh, Peter Pappas, Todd P McCarty, John W Sanders, Caryn Morse, Luis Ostrosky-Zeichner, Robert Krause, Jürgen Prattes, Andrej Spec, David Andes, Oliver Witzke, Nkechi Azie, and David A Angulo
- Subjects
Infectious Diseases ,Oncology ,education - Abstract
Background Candida albicans is the predominant organism causing esophageal candidiasis (EC) and oropharyngel candidiasis (OPC). These infections may arise from subjects colonized with Candida who are predisposed due to illness, debility or a local reduction in host resistance to an overgrowth of their own indigenous flora. Patients with mucocutaneous Candida infections can be treated in the outpatient setting, yet there are limited oral treatment options available for patients who are unresponsive to or who are intolerant to currently available antifungals. Oral ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor antifungal with activity against Candida species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp (FURI; NCT03059992) is ongoing for the treatment of patients intolerant of or with fungal disease refractory to standard antifungal therapy. Table 1. FURI Outcomes in OPC and EC Methods FURI subjects were eligible for enrollment if they had proven or probable severe mucocutaneous candidiasis, invasive candidiasis, invasive aspergillosis, or other fungal diseases with evidence of treatment failure, intolerance, or toxicity related to a currently approved standard-of-care antifungal treatment or if they were unable to receive an approved oral antifungal option (e.g., susceptibility of the organism) and a continued IV antifungal therapy was clinically undesirable or unfeasible. Results An independent Data Review Committee (DRC) provided an assessment of treatment response for 74 subjects enrolled in the FURI study from 22 centers in US, UK and EU treated with ibrexafungerp for mucocutaneous or invasive fungal infections from 2016- 2020. A total 32 subjects (43.2%) had mucocutaneous candidiasis and 24 subjects were diagnosed with OPC or EC. The percent of patients who were determined to have a complete response (CR) or partial response (PR) was 62.5%, stable disease (SD), 20.8%, and progression of disease, 16.7%. Table 1 shows outcomes by EC and OPC as determined by the DRC. Conclusion Analysis of 24 EC and OPC patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging mucocutaneous fungal disease and limited treatment options. Disclosures Oliver Cornely, Prof., Actelion (Consultant, Grant/Research Support)Al-Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Consultant)Amplyx (Consultant, Grant/Research Support)Astellas (Consultant, Grant/Research Support)Basilea (Consultant, Grant/Research Support)Biocon (Consultant)Biosys (Consultant)Cidara (Consultant, Grant/Research Support)CoRe Consulting (Consultant)Da Volterra (Consultant, Grant/Research Support)DFG (German Research Foundation) (Grant/Research Support)Entasis (Consultant)F2G (Consultant, Grant/Research Support)German Federal Ministry of Research and Education (Grant/Research Support)Gilead (Consultant, Grant/Research Support)Grupo Biotoscana (Consultant)Immunic (Grant/Research Support)IQVIA (Consultant)Janssen (Grant/Research Support)Matinas (Consultant)Medicines Company (Grant/Research Support)MedPace (Consultant, Grant/Research Support)Melinta Therapeutics (Grant/Research Support)Menarini (Consultant)Merck/MSD (Consultant, Grant/Research Support)Molecular Partners (Consultant)MSG-ERC (Consultant)Mylan (Consultant)Nabriva (Consultant)Noxxon (Consultant)Octapharma (Consultant)Paratek (Consultant)Pfizer (Consultant, Grant/Research Support)PSI (Consultant)Roche Diagnostics (Consultant)Scynexis (Consultant, Grant/Research Support)Seres (Consultant)Shionogi (Consultant)Wiley (Blackwell) (Other Financial or Material Support) Philipp Koehler, MD, Ambu GmbH (Consultant, Speaker’s Bureau)Astellas Pharma (Speaker’s Bureau)Euopean Confederation of Medical Mycology (Speaker’s Bureau)German Federal Ministry of Research and Education (Grant/Research Support)Gilead (Consultant, Speaker’s Bureau)MSD (Speaker’s Bureau)Noxxon N.V. (Consultant)Pfizer (Speaker’s Bureau)State of North Rhine-Westphalia, Germany (Grant/Research Support) Riina Rautemaa-Richardson, DDS, PhD, FRCPath, SCYNEXIS, Inc. (Scientific Research Study Investigator) G. Marshall Lyon, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Francisco M. Marty, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Rachel Miller, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Thomas J. Walsh, MD, PhD (hon), Scynexis (Consultant, Grant/Research Support)Shionogi (Consultant, Grant/Research Support) Peter Pappas, MD, Astellas (Grant/Research Support)Cidara (Grant/Research Support, Advisor or Review Panel member)Mayne (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support)SCYNEXIS, Inc. (Consultant, Grant/Research Support) Todd P. McCarty, MD, Cidara (Grant/Research Support)GenMark (Grant/Research Support, Other Financial or Material Support, Honoraria for Research Presentation)T2 Biosystems (Consultant) Caryn Morse, MD, Chimerix (Scientific Research Study Investigator)Covis Pharma (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator)Ridgeback Biotherapeutics (Scientific Research Study Investigator)Roche (Scientific Research Study Investigator)SCYNEXIS, Inc. (Scientific Research Study Investigator)Theratechnologies (Advisor or Review Panel member)Viiv (Advisor or Review Panel member) Luis Ostrosky-Zeichner, MD, Amplyx (Consultant)Cidara (Consultant)F2G (Consultant)Gilead (Grant/Research Support, Speaker’s Bureau)Pfizer (Scientific Research Study Investigator, Speaker’s Bureau)Scynexis (Grant/Research Support, Scientific Research Study Investigator)Viracor (Consultant) Jürgen Prattes, Dr, AbbVie Inc. (Shareholder)Gilead (Speaker’s Bureau)MSD (Grant/Research Support)Novo Nordisk (Shareholder)Pfizer (Advisor or Review Panel member)Stryker (Shareholder) Andrej Spec, MD, MSCI, SCYNEXIS, Inc. (Consultant, Scientific Research Study Investigator) David Andes, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Oliver Witzke, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Nkechi Azie, MD, SCYNEXIS, Inc. (Employee, Shareholder) David A. Angulo, MD, SCYNEXIS, Inc. (Employee, Shareholder)
- Published
- 2021
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