Late events after anti-CD19 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

Background: The short-term complications from chimeric antigen receptor T-cell therapy (CART) are well characterized, but the long-term complications still need to be further investigated. Therefore, herein, we will review the currently available literature published on the late adverse events following CART. Methods: We reviewed published data available from pivotal trials and real-world experiences with anti-CD19 CART (CART19) for adults with lymphoma. We defined late events as occurring or persisting beyond 1 month after CART infusion. We focused our literature review on the following late-event outcomes post-CART19: cytopenia, immune reconstitution, infections, and subsequent malignancies. Results: Grade 3-4 cytopenia beyond 30 days occurs in 30%-40% of patients and beyond 90 days in 3%-22% of patients and is usually managed with growth-factor and transfusion support, along with neutropenic prophylaxis. B-cell aplasia and hypogammaglobulinemia are expected on-target off-tumor effects of CART19, 44%-53% of patients have IgG < 400 mg/dL, and approximately 27%-38% of patients receive intravenous immunoglobulin (IVIG) replacement. Infections beyond the initial month from CART19 are not frequent and rarely severe, but they are more prevalent and severe when patients receive subsequent therapies post-CART19 for their underlying disease. Late neurotoxicity and neurocognitive impairment are uncommon, and other causes should be considered. T-cell lymphoma (TCL) after CART is an extremely rare event and not necessarily related to CAR transgene. Myeloid neoplasm is not rare post-CART, but unclear causality given heavily pretreated patient population is already at risk for therapy-related myeloid neoplasm. Conclusion: CART19 is associated with clinically significant long-term effects such as prolonged cytopenia, hypogammaglobulinemia, and infections that warrant clinical surveillance, but they are mostly manageable with a low risk of non-relapse mortality. The risk of subsequent malignancies post-CART19 seems low, and the relationship with CART19 and/or prior therapies is unclear; but regardless of the possible causality, this should not impact the current benefit-risk ratio of CART19 for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).

The role of body mass index in survivorship and clinical outcomes in total shoulder arthroplasty.

BACKGROUND: Increased body mass index (BMI) is a potential risk factor for poorer outcomes and complications. However, the influence of BMI on the long-term outcomes of anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) remains to be fully elucidated. METHODS: Institutional records were queried to identify patients who underwent primary total shoulder arthroplasty (TSA) between 2009 and 2020 with a minimum of 2 years of clinical follow-up. Retrospective review was performed to collect demographic characteristics; comorbidity status; and range-of-motion and strength measurements in forward elevation, external rotation, and internal rotation. Patients were contacted by telephone to provide patient-reported outcomes (PROs). Patients were stratified into 3 cohorts by BMI: underweight or normal weight (U/NW, BMI ≤25 kg/m2), overweight (OW, BMI >25 to ≤30 kg/m2), and obese (BMI >30 kg/m2). RESULTS: Among 466 TSA patients, 245 underwent aTSA whereas 221 underwent rTSA. In the aTSA cohort, 40 patients were classified as U/NW; 72, as OW; and 133, as obese. Comparatively, the rTSA cohort was composed of 33 U/NW, 79 OW, and 209 obese patients. Patients in the aTSA and rTSA cohorts had an average follow-up period of 5.8 ± 3.2 years and 4.5 ± 2.3 years, respectively. No differences in age at surgery were found in the aTSA group (U/NW vs. obese, 65.2 ± 7.9 years vs. 61.9 ± 8.9 years; P = .133); however, in the rTSA cohort, BMI was found to be inversely related to age at surgery (U/NW vs. obese, 72.4 ± 8.8 years vs. 65.7 ± 8.3 years; P < .001). Across all BMI cohorts, patients saw great improvements in range of motion and strength. Postoperative PROs after TSA did not vary by BMI in terms of Single Assessment Numeric Evaluation, Simple Shoulder Test, visual analog scale pain, and American Shoulder and Elbow Surgeons scores. There was no significant difference in survival rates at 10-year follow-up in the aTSA cohort (U/NW vs. obese, 95.8% vs. 93.2%; P = .753) or rTSA cohort (U/NW vs. obese, 94.7% vs. 94.5%; P = .791). CONCLUSION: With dramatic improvements in range of motion, minimal differences in PROs, and high rates of implant survival, TSA is a safe and effective treatment option for all patients, including overweight and obese patients.

Particulate matter and Alzheimer's disease: an intimate connection.

The environmental role in disease progression has been appreciated for decades; however, understanding how airborne toxicant exposure can affect organs beyond the lungs is an underappreciated area of scientific inquiry. Particulate matter (PM) includes various gases, liquids, and particles in suspension and is produced by industrial activities such as fossil fuel combustion and natural events including wildfires and volcanic eruptions. Although agencies have attempted to reduce acceptable airborne particulate levels, with urbanization and population growth, these policies have been only moderately effective in mitigating disease progression. A growing area of research is focused on the role of PM exposure in the progression of Alzheimer's disease (AD). This review will summarize the knowns and unknowns of this expanding field.

A Proof-of-Concept, Two-Tiered Approach for Ricin Detection Using Ambient Mass Spectrometry.

Ricin is a naturally occurring, highly potent toxin native to castor bean plants that has recently been used as a biological weapon in cases of bioterrorism and suicide attempts. Difficulties with direct detection arise from large heterogeneities in ricin glycosylation, which leads to markedly different bioactivity, and the fact that carefully developed and laborious sample preparation steps are required to maintaining the activity of the protein during analysis. Herein, we present an alternative, two-tiered approach to identify the presence of ricin by detecting ricinoleic acid and ricinine, which are co-extracted with the protein. This direct mass spectrometric-based technique takes as little as 2 minutes, and we determined its sensitivity to be in the parts-per-trillion range. Our method is applicable to paper substrates from suspected contaminated envelopes and biofluids from at-risk patients. The fact that prior sample preparations are not needed in this procedure means that analysis can be performed in the field for emergency cases.

Microsampling with cotton thread: Storage and ultra-sensitive analysis by thread spray mass Spectrometry.

Storage and quantitative analysis of small volumes of biofluids are challenging, especially when low concentrations of analytes are to be detected in the presence of complex matrices. In this study, we describe an integrated thread-based approach for stabilizing small blood volumes in the dry-state at room temperature, while also offering direct analysis capabilities via thread spray mass spectrometry. The analytical merits of this novel microsampling platform was demonstrated via the direct analysis of diazepam and cocaine in dried blood samples stored for 42 days. In-situ in-capillary blood processing from hydrophobic threads enabled limits of detection as low as parts-per-quadrillion to be reached. We validated this ultra-sensitivity by analyzing small tissue-like residues collected after pushing a thread through the sample once. The implications of this sample collection, storage, and analysis platform can be extensive with direct applications in forensics and clinical studies.