Extended B-cell depletion beyond 6-months in patients receiving ocrelizumab or rituximab for CNS demyelinating disease.

OBJECTIVES: To investigate the duration of B-cell depletion in a cohort of patients receiving ocrelizumab or rituximab for multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD). METHODS: We retrospectively searched our database for patients diagnosed with MS or NMOSD, who were receiving ocrelizumab or rituximab and had available CD19 measurements. We collected demographic data, infusion doses, infusion dates, CD19 absolute counts and percentages, and their collection dates. We paired each infusion with the subsequent CD19 measurements recorded before the next infusion, discarding measurements done during a washout period of 30 days after each infusion. We applied three definitions for B-cell depletion, the most stringent of which was an absolute B-cell count ≤20 cells/uL. RESULTS: From 695 patients with demyelinating diseases in our database, over the period of January 1st 2010 to March 1st 2020, we identified 188 patients (178 with MS and 10 with NMOSD), who had received ocrelizumab or rituximab and had available CD19 measurements. 1054 CD19 measurements were captured. B-cell depletion, as defined above, was recorded as far out as 22.8 months after an ocrelizumab infusion, and 22.3 months after a rituximab infusion. Out of 90 B-cell measurements done ≥8 months (>210 days) after ocrelizumab infusion, 45(50%) measurements showed B-cell depletion. Similarly for rituximab, out of 113 measurements, 49(43%) showed B-cell depletion. CONCLUSIONS: This study demonstrates that B-cell depletion after ocrelizumab and rituximab continues beyond the traditional 6-month re-infusion interval in many patients. Our report provides data that can support clinical trials testing increasing the interval of re-infusion with ocrelizumab and rituximab beyond 6-months guided by B-cell measurements.

Nodule net: A centralized prospective lung nodule tracking and safety-net program.

BACKGROUND: Inadequate follow-up of suspicious lung nodules can result in diagnostic delays and potential progression to advanced lung cancer. In 2015, a multidisciplinary lung nodule management program, Nodule Net, was implemented to increase the timely follow-up rate. In this study, we sought to evaluate the effectiveness of the program. METHODS: 2398 chest CT reports were reviewed for the presence of a lung nodule. Baseline demographics, nodule characteristics, and follow-up recommendations were collected. For reports that did not include structured recommendations, Fleischner Society guidelines were applied if appropriate. The rate of follow-up imaging was recorded and compared with historical rates. RESULTS: Lung nodules were reported on 1367 (57%) of scans. Of the 632 participants with recommendations for follow-up, the Nodule Net nurse navigator was notified on 523 (83%). Of these, 408 (78%) completed follow-up, compared to 57/109 (52%) in those who were not reported to Nodule Net tracking system (risk ratio: 1.49, 95% CI: 1.24-1.79, p-value < 0.05). Out of these 408, nodule net outreach was required to prompt the follow-up in 116 (28%). Of these, a lung malignancy was diagnosed in 4 (4%). CONCLUSIONS: Management of lung nodules is a complex process. Implementation of a lung nodule tracking program led to a significant increase in the completion of recommended follow-up imaging compared with usual care. Developing a comprehensive lung nodule program using an automated software system rather than manual processes to refer and track incidental findings may further reduce barriers to completion of follow-up.

Qualitative emphysema and risk of COPD hospitalization in a multicenter CT lung cancer screening cohort study.

BACKGROUND: In the United States, 9 to 10 million Americans are estimated to be eligible for computed tomographic lung cancer screening (CTLS). Those meeting criteria for CTLS are at high-risk for numerous cardio-pulmonary co-morbidities. The objective of this study was to determine the association between qualitative emphysema identified on screening CTs and risk for hospital admission. STUDY DESIGN AND METHODS: We conducted a retrospective multicenter study from two CTLS cohorts: Lahey Hospital and Medical Center (LHMC) CTLS program, Burlington, MA and Mount Auburn Hospital (MAH) CTLS program, Cambridge, MA. CTLS exams were qualitatively scored by radiologists at time of screening for presence of emphysema. Multivariable Cox regression models were used to evaluate the association between CT qualitative emphysema and all-cause, COPD-related, and pneumonia-related hospital admission. RESULTS: We included 4673 participants from the LHMC cohort and 915 from the MAH cohort. 57% and 51.9% of the LHMC and MAH cohorts had presence of CT emphysema, respectively. In the LHMC cohort, the presence of emphysema was associated with all-cause hospital admission (HR 1.15, CI 1.07-1.23; p < 0.001) and COPD-related admission (HR 1.64; 95% CI 1.14-2.36; p = 0.007), but not with pneumonia-related admission (HR 1.52; 95% CI 1.27-1.83; p < 0.001). In the MAH cohort, the presence of emphysema was only associated with COPD-related admission (HR 2.05; 95% CI 1.07-3.95; p = 0.031). CONCLUSION: Qualitative CT assessment of emphysema is associated with COPD-related hospital admission in a CTLS population. Identification of emphysema on CLTS exams may provide an opportunity for prevention and early intervention to reduce admission risk.

Use of Dimensional Analysis in the X-, Y-, and Z-Axis to Predict Occurrence of Injury in Human Stampede.

BACKGROUND: Human stampedes (HS) may result in mass casualty incidents (MCI) that arise due to complex interactions between individuals, collective crowd, and space, which have yet to be described from a physics perspective. HS events were analyzed using basic physics principles to better understand the dynamic kinetic variables that give rise to HS. METHODS: A literature review was performed of medical and nonmedical sourced databases, Library of Congress databases, and online sources for the term human stampedes resulting in 25,123 references. Filters were applied to exclude nonhuman events. Retrieved references were reviewed for a predefined list of physics terms. Data collection involved recording frequency of each phrase and physics principle to give the final proportions of each predefined principle used a single-entry method for each of the 105 event reports analyzed. Data analysis was performed using the R statistics packages "tidyverse", "psych", "lubridate", and "Hmisc" with descriptive statistics used to describe the frequency of each observed variable. RESULTS: Of the 105 reports of HS resulting in injury or death reviewed, the following frequency of terms were found: density change in a limited capacity, 45%; XY-axis motion failure, 100%; loss of proxemics, 100%; deceleration with average velocity of zero, 90%; Z-axis displacement pathology (falls), 92%; associated structure with nozzle effect, 93%; and matched fluid dynamic of high pressure stagnation of mass gathering, 100%. CONCLUSIONS: Description or reference to principles of physics was seen in differing frequency in 105 reports. These include XY-axis motion failure of deceleration that leads to loss of human to human proxemics, and high stagnation pressure resulting in the Z-axis displacement effect (falls) causing injury and death. Real-time video-analysis monitoring of high capacity events or those with known nozzle effects for loss of proxemics and Z-axis displacement pathology offers the opportunity to prevent mortality from human stampedes.