Zumberg, Marc S

Abstract Hereditary hemorrhagic telangiectasia (HHT) results in recurrent severe epistaxis, chronic gastrointestinal bleeding, and other morbid manifestations. Pomalidomide was recently demonstrated to be efficacious for bleeding in HHT in the landmark PATH-HHT trial. Given that the vascular remodeling that results in bleeding improvement may require several months, characteristics associated with treatment response would be invaluable to plan treatment. Using data from PATH-HHT (NCT03910244), we identified characteristics associated with change from baseline in Epistaxis Severity Score (ESS; a well-validated 10-point HHT bleeding scale and the trial’s primary end point) using multivariable-adjusted repeated-measures models. Characteristics associated with a better response to pomalidomide at weeks 16 to 24 of the trial included a higher (more severe) baseline ESS (change from baseline, −0.76 [95% confidence interval (CI), −0.99 to −0.54] points per 1-point higher baseline score, P< .001) and concomitant antifibrinolytic therapy (−0.73 [95% CI, −1.48 to 0.01] vs no therapy, P = .05). Characteristics associated with a less robust response were older age (0.29 [95% CI, 0.05-0.53] per 10 years older, P = .02) and underlying ACVRL1 germ line mutation (0.62 [95% CI, −0.04 to 1.27] vs ENG, SMAD4, or mutation not known, P = .06]. Characteristics notably associated with placebo response (placebo effect) were patient-reported outcome measures, such that those experiencing more severe disease at baseline had less placebo effect. In conclusion, several baseline patient and disease characteristics were associated with pomalidomide response, findings that may help guide patient selection for the use of pomalidomide in HHT. This trial was registered at www.Clinicaltrials.gov as NCT03910244.

Abstract Systems-based hematology (SBH) is an emerging discipline focused on optimizing care delivery for patients with hematologic disorders within complex health care systems. Despite its growing importance, the field lacks a formal definition, standardized curriculum, and clear career pathway, hindering widespread adoption and training of future SBH experts. We sought to define core principles, competencies, challenges, and future directions of SBH to identify foundational components for a potential educational curriculum. Semistructured interviews were conducted with 8 SBH experts. Expert participants were identified through their committee involvement with the American Society of Hematology. Five overarching themes emerged: (1) The accidental expert: SBH careers have developed organically and reactively in response to pressing institutional needs, not through formal training; (2) Defining the unseen: experts define the field pragmatically by its function and roles; (3) The SBH toolkit: success requires a hybrid skillset combining clinical hematology expertise with health systems science (HSS) principles; (4) The architect's dilemma: the field's growth is hindered by interdependent challenges of building a curriculum, awareness, and securing resources; and (5) Charting the future: the discipline is poised for growth, driven by increasing health care complexity and specialization. SBH represents the nexus of HSS principles and hematology care. Formalizing SBH requires a multipronged approach, including developing a standardized curriculum that equips learners with a hybrid skillset, creating clear value for health systems and patients, and fostering a community of practice through professional societies. These findings provide a foundational framework for developing educational resources and institutional support necessary to continue advancing SBH.