tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of the Panobinostat-Bortezomib-Dexamethasone Combination in Relapsed or Relapsed/Refractory Multiple Myeloma: Results from the Randomized Panorama 3 Study
Authors: Jacob P. Laubach, Fredrik Schjesvold, Mário Mariz, Meletios A Dimopoulos, Ewa Lech-Marańda, Ivan Spicka, Vania T. M. Hungria, Tatiana Shelekhova, Andre Abdo, Lutz Jacobasch, Chantana Polprasert, Roman Hajek, Arpad Illes, Tomasz Wróbel, Anna Sureda Balari, Meral Beksac, Iara Goncalves, Joan Bladé Creixenti, S. Vincent Rajkumar, Ajai Chari, Sagar Lonial, Andrew Spencer, Pierre Maison-Blanche, Philippe Moreau, Paul G. Richardson, Jesus F. San-Miguel
Journal: Blood (2020)
Identification of Predictive Markers of Severe and Prolonged Neutropenia after CD19-Specific CAR T-Cell Treatment in Patients with Relapsed/Refractory B-Cell Malignancies
Authors: Kai Rejeski, Carolina Berger, Liv Jentzsch, Semjon Willier, Viktoria Blumenberg, Veit Buecklein, Christoph Faul, Christian Schmidt, Michael von Bergwelt, Tobias Feuchtinger, Wolfgang Bethge, Francis A. Ayuk, Marion Subklewe
Journal: Blood (2020)
First Line Treatment with Hydroxyurea in Patients with Policitemia Vera: Evaluation of Efficacy in the Current Clinical Practice Beyond ELN Criteria
Authors: Roberto Latagliata, Massimo Breccia, Ambra Di Veroli, Giulia Benevolo, Elena M Elli, Francesco Cavazzini, Gianni Binotto, Alessia Tieghi, Mario Tiribelli, Florian H. Heidel, Massimiliano Bonifacio, Novella Pugliese, Giovanni Caocci, Monica Crugnola, Francesco Mendicino, Enrica Antonia Martino, Alessandra D'Addio, Simona Tomassetti, Bruno Martino, Daniela Bartoletti, Giuseppe Auteri, Lucia Catani, Rossella Stella, Fabio D'Amore, Luigi Scaffidi, Nicola Polverelli, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto Massimo Lemoli, Nicola Vianelli, Michele Cavo, Giuseppe A. Palumbo, Francesca Palandri
Journal: Blood (2020)
Prognostic Value of Delta Lymphocyte Index (DLIx) in Patients with Large B-Cell Lymphoma (LBCL) Treated with Chimeric Antigen Receptor (CAR) T-Cell Therapy
Authors: Paolo Strati, Haleigh Mistry, Brittany Pulsifer, Luis Fayad, Sairah Ahmed, Hun Ju Lee, Swami P. Iyer, Ranjit Nair, Loretta J. Nastoupil, Simrit Parmar, Maria Alma Rodriguez, Felipe Samaniego, Raphael Eric Steiner, Michael Wang, Chelsea C. Pinnix, Bouthaina S. Dabaja, Mansoor Noorani, Catherine M. Claussen, Elizabeth J. Shpall, Partow Kebriaei, Chris R. Flowers, Jason R. Westin, Sattva S. Neelapu
Journal: Blood (2020)
Expert Variant Curation Combined with <i>in-Silico</i> analysis for Clinical Interpretation of <i>BCL2</i> variants in Resistance to BCL2 Inhibitors in Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma
Authors: Matthew McCoy, Shruti Rao, Shannon Cosgrove, Subha Madhavan, Shashikant Kulkarni, Xinjie Xu, Rashmi Kanagal-Shamanna
Journal: Blood (2020)
AB0184 Misdiagnosis of insufficiency fractures in patients with inflammatory joint disease
Authors: D Schapira, D Militianu, Y Braun-Moscovici, AM Nahir
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Insufficiency fractures may occur in patients with long-standing inflammatory joint diseases (IJD). Activity of the disease, immobilisation and prolonged corticosteroid treatment are the main predisposing factors. In most cases the fractures are easily diagnosed, in others the diagnosis is delayed, as they may mimic exacerbation of the underlying disease or other pathological conditions. <h3>Objectives</h3> To evaluate the clinical profile of patients with initially misdiagnosed insufficiency fractures and to investigate the causes of the diagnostic delay. <h3>Methods</h3> The files of 12 patients with IJD who were referred for presumed exacerbation of the rheumatic disease and were subsequently diagnosed as suffering from insufficiency fractures were reviewed and relevant parameters were analysed. <h3>Results</h3> Most of the patients were aged (mean 68.5 years) and were suffering from IJD for long periods of time (mean 16.6 years). All of them received prolonged corticosteroid therapy (mean 9.5 years) in doses up to 15 mg prednisone a day). Five patients had previous insufficiency fractures. The new fractures were located in the distal tibia, femoral neck, head of humerus, lesser trochanter of the femur, sacrum, pubic rami, acetabulum and metatarsus. The initial diagnosis was: acute synovitis (8 patients), trochanteric bursitis (1), radiculopathy (1), tendinitis (1) and avascular necrosis of bone (1). The diagnostic delay was one to eight weeks (mean 2.7). In seven patients the correct diagnosis was reached by initial radiographs and in five by bone scintigraphy and CT. Treatment with bed rest, non weight bearing, NSAID (all patients) and calcitonin (7 cases) resulted in partial (8 patients) or complete recovery (4 patients). <h3>Conclusion</h3> Insufficiency fractures can mimic disease activity or other musculoskeletal pathological conditions in patients with IJD. Clinician's awareness may prevent unnecessary investigations and therapy. <h3>References</h3> Lingg GM, Soltesz I, Kessler S, Dreher R. Insufficiency and stress fractures of the long bones occuring in patients with rheumatoid arthritis and other inflammatory diseases, with a contribution on the possibilities of computed tomography. Eur J Radiol. 1997;26:54–63 Alonso-Bartolome P, Martinez-Taboada VM, Blanco R, Rodriguez-Valverde V. Insufficiency fractures of the distal tibia and fibula. Semin Arthritis Rheum. 1999;28:413–20
Performance and clinical utility of supervised machine-learning approaches in detecting familial hypercholesterolaemia in primary care
Authors: Ralph K. Akyea, Nadeem Qureshi, Joe Kai, Stephen F. Weng
Journal: npj Digital Medicine (2020)

Familial hypercholesterolaemia (FH) is a common inherited disorder, causing lifelong elevated low-density lipoprotein cholesterol (LDL-C). Most individuals with FH remain undiagnosed, precluding opportunities to prevent premature heart disease and death. Some machine-learning approaches improve detection of FH in electronic health records, though clinical impact is under-explored. We assessed performance of an array of machine-learning approaches for enhancing detection of FH, and their clinical utility, within a large primary care population. A retrospective cohort study was done using routine primary care clinical records of 4,027,775 individuals from the United Kingdom with total cholesterol measured from 1 January 1999 to 25 June 2019. Predictive accuracy of five common machine-learning algorithms (logistic regression, random forest, gradient boosting machines, neural networks and ensemble learning) were assessed for detecting FH. Predictive accuracy was assessed by area under the receiver operating curves (AUC) and expected vs observed calibration slope; with clinical utility assessed by expected case-review workload and likelihood ratios. There were 7928 incident diagnoses of FH. In addition to known clinical features of FH (raised total cholesterol or LDL-C and family history of premature coronary heart disease), machine-learning (ML) algorithms identified features such as raised triglycerides which reduced the likelihood of FH. Apart from logistic regression (AUC, 0.81), all four other ML approaches had similarly high predictive accuracy (AUC > 0.89). Calibration slope ranged from 0.997 for gradient boosting machines to 1.857 for logistic regression. Among those screened, high probability cases requiring clinical review varied from 0.73% using ensemble learning to 10.16% using deep learning, but with positive predictive values of 15.5% and 2.8% respectively. Ensemble learning exhibited a dominant positive likelihood ratio (45.5) compared to all other ML models (7.0-14.4). Machine-learning models show similar high accuracy in detecting FH, offering opportunities to increase diagnosis. However, the clinical case-finding workload required for yield of cases will differ substantially between models.
Shifting Treatment Patterns and Clinical Outcomes in Veterans Diagnosed with Waldenstrom Macroglobulinemia from 2006 to 2018
Authors: Hsu-Chih Chien, Deborah Kay Morreall, Vikas Patil, Kelli M Rasmussen, Christina Yong, Catherine Li, Zachary R Burningham, Brian C Sauer, Ahmad S Halwani
Journal: Blood (2020)
Spotlight on microRNAs in allergy and asthma
Authors: Julie Weidner, Sabine Bartel, Ayse Kılıç, Ulrich M. Zissler, Harald Renz, Jürgen Schwarze, Carsten B. Schmidt‐Weber, Tania Maes, Ana Rebane, Susanne Krauss‐Etschmann, Madeleine Rådinger
Journal: Allergy (2020)

Abstract In past 10 years, microRNAs (miRNAs) have gained scientific attention due to their importance in the pathophysiology of allergic diseases and their potential as biomarkers in liquid biopsies. They act as master post‐transcriptional regulators that control most cellular processes. As one miRNA can target several mRNAs, often within the same pathway, dysregulated expression of miRNAs may alter particular cellular responses and contribute, or lead, to the development of various diseases. In this review, we give an overview of the current research on miRNAs in allergic diseases, including atopic dermatitis, allergic rhinitis, and asthma. Specifically, we discuss how individual miRNAs function in the regulation of immune responses in epithelial cells and specialized immune cells in response to different environmental factors and respiratory viruses. In addition, we review insights obtained from experiments with murine models of allergic airway and skin inflammation and offer an overview of studies focusing on miRNA discovery using profiling techniques and bioinformatic modeling of the network effect of multiple miRNAs. In conclusion, we highlight the importance of research into miRNA function in allergy and asthma to improve our knowledge of the molecular mechanisms involved in the pathogenesis of this heterogeneous group of diseases.
Abstract MP103: Methylglyoxal Modifications on Myofilament Proteins Caused by Diabetes Block Heart Failure Drug Targets Through Changing Tropomyosin Position
Authors: Maria Papadaki, Theerachat Kampaengsri, Samantha Barrick, Stuart Campbell, Michael Greenberg, Jonathan A Kirk
Journal: Circulation Research (2020)

We previously discovered methylglyoxal (MG), a glycolysis byproduct, modifies arginine and lysine residues on myofilament proteins to a greater extent in patients with diabetes and heart failure than non-failing controls. These modifications reduced myofilament calcium sensitivity (pCa 50 ), maximal calcium activated force (F max ) and cross-bridge cycling dynamics. We hypothesized that compensating for these modifications might slow or halt the development of diabetic cardiomyopathy. We attempted to pharmacologically compensate for the negative functional effects of MG using omecamtiv mecarbil (OM), a myosin activator currently in clinical trials. As reported previously, we found that OM increased pCa 50 and decreased F max in normal myocytes. However, in myocytes pretreated with MG, OM had no effect of pCa 50 but still decreased F max . These data suggest OM may have less, or potentially detrimental effects in diabetic patients.To understand why MG might block the actions of sarcomere drug targets, we aimed to further elucidate the molecular mechanisms of MG. We utilized a computer model of sarcomere contraction to predict what molecular effects of MG would explain the functional data we collected. The model predicted a simultaneous increase in cross-bridge detachment rate and a decrease in the closed-to-blocked tropomyosin transition rate could explain the data. Stopped flow experiments measuring myofilament kinetics indicated a decreased transition rate between “closed” and “blocked” tropomyosin state but did not indicate a difference in the cross-bridge detachment rate upon treatment with MG. This finding further explained the observation that MG blocks OM’s effects - since a myosin activator would not necessarily be effective if MG affected tropomyosin position on actin. We hypothesize that a residue we found to be modified by MG on actin, K291 would be important for the molecular mechanism observed, since it is located in a critical position for the interaction between actin and tropomyosin. In this study, we have elucidated the mechanism of MG’s detrimental myofilament impact and found that that these modifications reduce the efficacy of OM. This mechanistic understanding will help drive future identification of therapeutic targets.
Radiation-Based Approaches As an Alternative to Stem Cell Transplant for Relapsed/Refractory Classical Hodgkin Lymphoma: A Multicenter Retrospective Analysis
Authors: Meredith I. Larose, Steven M. Bair, Shwetha Manjunath, Jordan Carter, Andrew M. Evens, Krista Isaac, Craig A. Portell, Sayan Chowdhury, Narendranath Epperla, Jordan Intrator, Tatyana A. Feldman, Hayder Saeed, Leidy Isenalumhe, Daniel J. Landsburg, Sunita Dwivedy Nasta, James N. Gerson, Stefan K. Barta, Elise A. Chong, Stephen J. Schuster, Ima Paydar, John Plastaras, Jakub Svoboda
Journal: Blood (2020)
Defibrotide: Real World Experience for Management of Veno-Occlusive Disease/ Sinusoidal Obstructive Syndrome after Hematopoietic Stem Cell Transplantation
Authors: Mary Nauffal, Haesook T. Kim, Paul G. Richardson, Robert J. Soiffer, Joseph H. Antin, Corey Cutler, Sarah Nikiforow, Mahasweta Gooptu, John Koreth, Roman M Shapiro, Rizwan Romee, Vincent T. Ho
Journal: Blood (2020)
Symptom Burden and Quality of Life in High-Risk Essential Thrombocythemia and Polycythemia Vera Patients Receiving Hydroxyurea or Pegylated Interferon Alfa-2a: Results of Myeloproliferative Neoplasms Research Consortium (MPN-RC) 111 and 112 Trials
Authors: Gina L. Mazza, Carolyn Mead-Harvey, John Mascarenhas, Abdulraheem Yacoub, Ronald Hoffman, Heidi E. Kosiorek, Josef T. Prchal, Richard T. Silver, Tiziano Barbui, Amylou C. Dueck, Ruben Mesa
Journal: Blood (2020)
Abstract MP164: Electrophysiologic Conservation of Epicardial Conduction Dynamics After Myocardial Infarction in Newborn Piglets
Authors: Hanjay Wang, Terrence Pong, Haley Lucian, Joy Aparicio-Valenzuela, Yuko Tada, Sasank Sakhamuri, Sam W Baker, Nicholas A Tran, Michael J Paulsen, Yuanjia Zhu, Anson M LEE, Y. Joseph Woo
Journal: Circulation Research (2020)

Introduction: Newborn piglets reportedly exhibit natural heart regeneration after myocardial infarction (MI). However, the electrophysiologic properties of this regenerated muscle have not been examined. We hypothesized that epicardial electrical conduction is preserved after MI in newborn piglets. Methods: Yorkshire-Landrace piglets underwent left anterior descending coronary artery ligation on postnatal day 1 (P1, n=4) or postnatal day 7 (P7, n=7), infarcting the anteroseptal left ventricle through which the Purkinje conduction system passes. After 7 weeks, cardiac magnetic resonance imaging (MRI) was performed with late gadolinium enhancement for fibrosis analysis. Epicardial conduction mapping was performed using custom 3D-printed, 256-channel high-resolution mapping arrays (Fig 1A). Age- and weight-matched healthy pigs served as controls (n=7). Data are expressed as mean±SD. Results: MRI analysis revealed significant differences between the control, P1, and P7 groups in ejection fraction (47.6±3.1% vs 37.6±3.3% vs 30.2±6.6%, p&lt;0.001, Fig 1B) and the degree of transmural anteroseptal LV scar (0.0±0.0% vs 9.1±5.4% vs 15.4±4.2%, p&lt;0.001), respectively. Evidence of infarcted myocardium was identified with high-resolution mapping in the P1 and P7 piglets (black arrows, Fig 1C-F). Epicardial electrical conduction was preserved in control and all P1 pigs (Figs 1C-D), whereas variable conduction block or aberrant propagation were observed in all P7 pigs (Fig 1E-F, p=0.001). Conclusion: P1 piglets exhibited incomplete natural cardiac regeneration after MI but nevertheless demonstrated electrophysiologic conservation of epicardial conduction dynamics.
COMPOSER Part 4: An Optimized Dosing Strategy for Crovalimab in the Treatment of Complement Inhibitor-Naïve or -Experienced Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Regis Peffault De Latour, Simona Sica, Julia Ramos, Jules Hernández-Sánchez, Jin Seok Kim, Anna Kiialainen, Sung-Soo Yoon, Sasha Sreckovic, Antoine Soubret, Haruhiko Ninomiya, Alexandre Sostelly, Jens Panse, Simon Buatois, Hubert Schrezenmeier, Ido Paz-Priel, Jun-ichi Nishimura, Alexander Röth
Journal: Blood (2020)
Indoleamine 2,3-Dioxygenase Mediates Survival of Chronic Lymphocytic Leukemia B Cells through Aryl Hydrocarbon Receptor By Inducing Mcl1
Authors: Claudio Giacinto Atene, Rossana Maffei, Stefania Fiorcari, Silvia Martinelli, Patrizia Zucchini, Monica Maccaferri, Giulia Debbia, Leonardo Potenza, Mario Luppi, Roberto Marasca
Journal: Blood (2020)
Efficacy and Safety of Biosimilar Romiplostim in Immune Thrombocytopenic Purpura : Single Centre Retrospective Data Analysis
Authors: Seema S. Bhatwadekar, Shubhangi Vishwas Deshpande, Shweta Vikas Khadse, Devashri Jani, Ujjwala Lakhmapurkar, Pina Vasoya, Saloni Shah, Aangi Jayesh Shah, Bijal Shah, Devenkumar Desai
Journal: Blood (2020)
Profiling T-Cell Receptor Diversity and Dynamics during Lymphoma Immunotherapy Using Cell-Free DNA (cfDNA)
Authors: Navika D Shukla, Alexander F. M. Craig, Brian Sworder, David M. Kurtz, Charles Macaulay, Andrea Garofalo, Matthew J. Frank, Stefan Alig, George Duran, Youn H. Kim, James Zehnder, Crystal L. Mackall, David B. Miklos, Maximilian Diehn, Michael S. Khodadoust, Ash A. Alizadeh
Journal: Blood (2020)
Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis
Authors: Roy M Fleischmann, Ricardo Blanco, Stephen Hall, Glen T D Thomson, Filip E Van den Bosch, Cristiano Zerbini, Louis Bessette, Jeffrey Enejosa, Yihan Li, Yanna Song, Ryan DeMasi, In-Ho Song
Journal: Annals of the Rheumatic Diseases (2020)

Objectives To evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy. Methods SELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts (‘non-responders’) and at week 26 based on Clinical Disease Activity Index (CDAI) &gt;10 (‘incomplete-responders’) without washout. Results A total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups. Conclusions These observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.
Incidence, Risk Factors, and Outcomes of Viral Reactivations in Alternative Donor Haematopoietic Stem Cell Transplant
Authors: Vinodhini M, Anant Gokarn, Sachin Punatar, Sumeet Prakash Mirgh, Akanksha Chichra, Vijay Shirure, Avinash Bonda, Lingaraj Nayak, Bhausaheb Bagal, Vivek Bhat, Sanjay Biswas, Sadhana Kannan, Libin J Mathew, Rachana Tripathi, Shesheer Kumar, Tapan Saikia, Navin Khattry
Journal: Blood (2020)
Gut Bacterial Diversity Associates with Efficacy of Anti-CD19 CAR T-Cell Therapy in Patients with Large B-Cell Lymphoma
Authors: Neeraj Saini, Chia-Chi Chang, Paolo Strati, Loretta J. Nastoupil, Jason Westin, Ranjit Nair, Luis Fayad, Sairah Ahmed, Hun Ju Lee, Swaminathan P Iyer, Raphael Eric Steiner, Uri Greenbaum, Partow Kebriaei, Elizabeth J. Shpall, Nitin Jain, Michael R Green, Nadim J Ajami, Christopher Flowers, Richard E. Champlin, Jennifer Wargo, Sattva S. Neelapu, Robert R. Jenq
Journal: Blood (2020)
Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health
Authors: Abudukadier Abulizi, Rebecca L. Cardone, Romana Stark, Sophie L. Lewandowski, Xiaojian Zhao, Joelle Hillion, Lingjun Ma, Raghav Sehgal, Tiago C. Alves, Craig Thomas, Charles Kung, Bei Wang, Stephan Siebel, Zane B. Andrews, Graeme F. Mason, Jesse Rinehart, Matthew J. Merrins, Richard G. Kibbey
Journal: Cell Metabolism (2020)
First-in-Human Phase I Trial of Adoptive Immunotherapy with <i>Ex Vivo</i> Expanded and Activated Γδ T Cells Following Haploidentical Bone Marrow Transplantation and Post-BMT Cyclophosphamide
Authors: Lawrence S. Lamb, Melissa Jo Beelen, Samantha Langford Youngblood, Rupal Soder, Sunil Abhyankar, Joseph P. McGuirk
Journal: Blood (2020)
Chromosomal Translocation t(11;14) Induced By the Cre-Loxp System in Normal B Cell-Derived Ips Cells for the Study of Myeloma-Initiating Cells
Authors: Misaki Sugai, Naohiro Tsuyama, Yu Abe, Yusuke Azami, Kenichi Kudo, Akinobu Ota, Sivasundaram Karnan, Moe Muramatsu, Tomonari Shigemura, Megumi Sasatani, Yuko Hashimoto, Kenji Kamiya, Ichiro Hanamura, Takayuki Ikezoe, Masafumi Onodera, Akira Sakai
Journal: Blood (2020)
The Pyruvate Kinase Activator Mitapivat Ameliorates Anemia and Prevents Iron Overload in a Mouse Model of Hereditary Spherocytosis
Authors: Alessandro Mattè, Wilson Anand, Enrica Federti, Charles Kung, Penelope A. Kosinski, Veronica Riccardi, Iana Iatcenko, Lenny Dang, Christophe Leboeuf, Anne Janin, Carlo Brugnara, Mohandas Narla, Lucia De Franceschi
Journal: Blood (2020)
Sputum microbiota in adults with CF associates with response to inhaled tobramycin
Authors: Alya Heirali, Christina Thornton, Nicole Acosta, Ranjani Somayaji, Isabelle Laforest Lapointe, Douglas Storey, Harvey Rabin, Barbara Waddell, Laura Rossi, Marie Claire Arrieta, Michael Surette, Michael D Parkins
Journal: Thorax (2020)

Inhaled tobramycin powder/solution (TIP/S) use has resulted in improved clinical outcomes in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa. However, TIP/S effect on the CF sputum microbiome has not been explored. We hypothesised that TIP/S has additional 'off-target' effects beyond merely P. aeruginosa and that baseline microbiome prior to initiation of therapy is associated with subsequent patient response.We drew sputum samples from a prospectively collected biobank. Patients were included if they had one sputum sample in the 18 months before and after TIP/S. Bacterial 16S rRNA gene profiling was used to characterise the sputum microbiome.Forty-one patients met our inclusion criteria and 151 sputum samples were assessed. At baseline, median age was 30.4 years (IQR 24.2-35.2) and forced expiratory volume in 1 (FEV1) second was 57% predicted (IQR 44-74). Nineteen patients were defined a priori as responders having no net decrease in FEV1 in the year following TIP/S. No significant changes were observed in key microbiome metrics of alpha (within-sample) or beta (between-sample) diversity for samples collected before and after TIP/S. However, significant beta-diversity (Bray-Curtis) differences were noted at baseline between patients based on response status. Notably, responders were observed to have a higher abundance of Staphylococcus in pretherapy baseline samples.Our longitudinal study demonstrates that the sputum microbiome of patients with CF is relatively stable following inhaled tobramycin over many months. Intriguingly, our findings suggest that baseline microbiome may associate with patient response to TIP/S-suggesting the sputum microbiome could be used to personalise therapy.