Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.

Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T.

Trafficking through the blood-brain barrier is directed by core and outer surface components of layer-by-layer nanoparticles.

Drug-carrying nanoparticles are a promising strategy to deliver therapeutics into the brain, but their translation requires better characterization of interactions between nanomaterials and endothelial cells of the blood-brain barrier (BBB). Here, we use a library of 18 layer-by-layer electrostatically assembled nanoparticles (NPs) to independently assess the impact of NP core and surface materials on in vitro uptake, transport, and intracellular trafficking in brain endothelial cells. We demonstrate that NP core stiffness determines the magnitude of transport, while surface chemistry directs intracellular trafficking.

Toward a more patient-centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): Practical considerations from the International Consortium for MDS (icMDS).

Notable treatment advances have been made in recent years for patients with myelodysplastic syndromes/neoplasms (MDS), and several new drugs are under development. For example, the emerging availability of oral MDS therapies holds the promise of improving patients' health-related quality of life (HRQoL). Within this rapidly evolving landscape, the inclusion of HRQoL and other patient-reported outcomes (PROs) is critical to inform the benefit/risk assessment of new therapies or to assess whether patients live longer and better, for what will likely remain a largely incurable disease.

The Minimum Protein Staple? - Towards 'bio'-Baldwin's rules inter-phosphosite linking in the MEK1 activation loop.

In small molecule organic chemistry, the heuristic insight into ring-forming processes that was enabled by Baldwin's rules some 50 years ago proved a step-change in the role of mechanistically guided synthesis. It created a lens upon and marker of fundamental stereoelectronic and conformation-guided chemical processes. However, despite the widespread role of stereoelectronics and conformational control in Biology, no equivalent coherent exploitation of trapped, ring-forming processes yet exists in biomolecules.

Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic has affected a large portion of the global population, both physically and mentally. Current evidence suggests that the rapidly evolving coronavirus subvariants risk rendering vaccines and antibodies ineffective due to their potential to evade existing immunity, with enhanced transmission activity and higher reinfection rates that could lead to new outbreaks across the globe. The goal of viral management is to disrupt the viral life cycle as well as to relieve severe symptoms such as lung damage, cytokine storm, and organ failure.

Virtual planning and 3D-printed guides for mandibular reconstruction: Factors impacting accuracy.

Objectives: Examine accuracy and factors impacting accuracy for mandibular reconstruction with virtual surgical planning, 3D printed osteotomy guides and preoperatively bent mandibular reconstruction plate (VSP/3Dprinted-guide/plate).

Method: Retrospective review of osseous-free-flap mandibular reconstructions with VSP/3Dprinted-guide/plate between January 2015 and July 2020 at a single academic medical center.Patient demographics, disease, and treatment variables were extracted.

Developing a novel integrated geriatric palliative care consultation program for the emergency department.

With the aging of our population, older adults are living longer with multiple chronic conditions, frailty, and life-limiting illnesses, which creates specific challenges for emergency departments (EDs). Older adults and those with serious illnesses have high rates of ED use and hospitalization, and the emergency care they receive may be discordant with their goals and values. In response, new models of care delivery have begun to emerge to address both geriatric and palliative care needs in the ED.

Functional impact of androgen-targeted therapy on patients with castration-resistant prostate cancer.

Context: Second-generation androgen receptor inhibitors (ARIs) extend metastasis-free survival, prolong overall survival, and delay symptoms when added to androgen deprivation therapy for the treatment of castration-sensitive or castration-resistant prostate cancer (CRPC). However, ARIs may adversely impact physical and cognitive function, thereby decreasing quality of life and prognosis.

Objective: To evaluate the evidence regarding the potential effects of ARIs on physical and cognitive function and to contextualize how drug-related adverse effects may influence treatment decisions in CRPC.

Primary central nervous system lymphoma: Inter-compartmental progression.

There is limited understanding of the inter-compartmental progression and treatment outcomes of primary central nervous system lymphoma (PCNSL). In this multicenter retrospective cohort study on 234 patients with PCNSL (median age: 62.5 years [18-92]; median follow-up 35 months [0.

A nonrandomized phase I and biomarker trial of regorafenib in advanced myeloid malignancies.

We conducted a single-center, open-label, dose escalation, and expansion phase I trial of the antiangiogenic multikinase inhibitor regorafenib in patients with advanced myeloid neoplasms. We enrolled 16 patients with relapsed/refractory acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), chronic myelomonocytic leukemia (CMML), or myelodysplastic syndrome (MDS). A 3 + 3 dose escalation design was used with two planned dose levels (120 or 160 mg daily) and one de-escalation level (80 mg daily).

Heal the Healers: A pilot study evaluating the feasibility, acceptability, and exploratory efficacy of a Transcendental Meditation intervention for emergency clinicians during the coronavirus disease 2019 pandemic.

Objective: Emergency clinicians face elevated rates of burnout that result in poor outcomes for clinicians, patients, and health systems. The objective of this single-arm pilot study was to evaluate the feasibility of a Transcendental Meditation (TM) intervention for emergency clinicians during the coronavirus disease 2019 (COVID-19) pandemic and to explore the potential effectiveness in improving burnout, sleep, and psychological health.

Methods: Emergency clinicians (physicians, nurses, and physician-assistants) from 2 urban hospitals were recruited to participate in TM instruction (8 individual or group in-person and remote sessions) for 3 months.

Engineering serendipity: When does knowledge sharing lead to knowledge production?

Research Summary: We investigate how knowledge similarity between two individuals is systematically related to the likelihood that a serendipitous encounter results in knowledge production. We conduct a field experiment at a medical research symposium, where we exogenously varied opportunities for face-to-face encounters among 15,817 scientist-pairs. Our data include direct observations of interaction patterns collected using sociometric badges, and detailed, longitudinal data of the scientists' postsymposium publication records over 6 years.

Addition of rituximab in relapsed/refractory chronic lymphocytic leukemia after progression on venetoclax monotherapy.

Venetoclax is approved as monotherapy and in combination with rituximab for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Two Phase 1 studies (M12-175 [NCT01328626]; M13-365 [NCT01682616]) were conducted in which patients who initially responded and then progressed on venetoclax monotherapy could receive added rituximab. Ten patients were evaluated (M12-175, n = 8; M13-365, n = 2), and five (50%) responded again upon addition of rituximab, including three complete and two partial responses.

Circulating tumor cell analysis in locally advanced and metastatic squamous cell carcinoma of the head and neck.

Background: Circulating tumors cells (CTCs) are considered an early step towards metastasis and have been linked to poor prognosis in several types of cancer. CTCs in squamous cell carcinoma of the head and neck (SCCHN) have an unclear role.

Methods: In this prospective study, patients with locally advanced or metastatic SCCHN had CTC counts assessed before starting systemic treatment using the CellSearch System.

Longitudinal health-related quality of life in first-line treated patients with chronic lymphocytic leukemia: Results from the Connect CLL Registry.

Health-related quality of life (HRQoL) in patients with chronic lymphocytic leukemia (CLL) is important in guiding treatment decisions. However, the impact of CLL treatment initiation on HRQoL is unclear. We assessed HRQoL using the FACT-Leu and EQ-5D-3L questionnaires in the Connect CLL Registry, a large, US-based, multicenter, prospective observational study of CLL patients enrolled between 2010 and 2014, prior to the introduction of novel therapies.

Anticoagulation after intracranial hemorrhage in brain tumors: Risk of recurrent hemorrhage and venous thromboembolism.

Background: Intracranial hemorrhage (ICH) is a common and often devastating outcome in patients with brain tumors. Despite this, there is little evidence to guide anticoagulation management following an initial ICH event.

Objectives: To analyze the risk of recurrent hemorrhagic and thrombotic outcomes after an initial ICH event in patients with brain tumors and prior venous thromboembolism (VTE).