John Mark Sloan

Background: Duffy‐null associated neutrophil count (DANC) causes neutropenia without clinical sequelae. 25%–50% of people of African ancestry in the United States are thought to have Fy(a‐b‐) status and are often erroneously identified as having pathologically low neutrophil counts. Results: We performed a retrospective chart review of new neutropenia referrals to the Hematology Clinic at Boston Medical Center (BMC) to evaluate diagnostic patterns for Fy(a‐b‐) status. 103 new referrals for neutropenia were made from 1/2020 to 2/2022, of which 78 were included for further analysis. DANC was the etiology for low neutrophil count in 64.1%, 82% of whom were African American or Black or were born in an African or Caribbean country. 66% of these patients underwent confirmatory blood bank testing, and 97% of patients tested were confirmed to have Fy(a‐b‐) status. The average cost of a laboratory visit for patients with typical neutrophil count with Fy(a‐b‐) status was on average lower, but not negligible, than those without ($363.82 vs. $737.93; p < 0.005). These patients were also statistically less likely to have a follow‐up appointment ( p = 0.039). Conclusions: Expanded use of serological Fy(a,b) antigen testing for patients with chronic, asymptomatic neutropenia could reduce the cost of care and referrals to the hematology clinic.

Venous thromboembolism (VTE) risk is increased in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). A key question was whether increased intensity of anticoagulation would help prevent VTE and improve patient outcomes, including transfer to the intensive care unit (ICU) and mortality. At the start of the coronavirus disease‐19 (COVID‐19) pandemic, our institution, Boston Medical Center, instituted a VTE risk stratification protocol based on patients’ initial D‐dimer levels, medical history, and presence of thrombosis to determine whether they should receive standard‐dose prophylaxis, high‐dose prophylaxis, or therapeutic anticoagulation. We performed a retrospective observational cohort study examining the association of degree of anticoagulation with outcomes in 915 hospitalized COVID‐19 patients hospitalized initially on the general inpatient wards between March 1,^, 2020, and June 1, 2020. Patients directly hospitalized in the ICU were excluded. Most, 813 patients (89%), in our cohort were on standard‐dose prophylaxis; 32 patients (3.5%) received high‐dose prophylaxis; 70 patients (7.7%), were treated with therapeutic anticoagulation. VTE occurred in 45 patients (4.9%), and the overall in‐hospital mortality rate was 5.4% (49 deaths). On multivariable analysis of clinical outcomes in relation to type of anticoagulation, in the high‐dose prophylaxis group, there was a trend towards increased in‐hospital mortality (odds ratio 2.4 (0.8–7.5, 95% CI)) and increased ICU transfer (odds ratio 2.2 (0.9‐5.7, 95% CI)). Our results suggest that patients receiving high‐dose prophylaxis had more severe disease that was not mitigated by intermediate‐dose anticoagulation.

The systemic inflammatory response seen in patients with severe COVID-19 shares many similarities with the changes observed in hemophagocytic lymphohistiocytosis (HLH); a disease characterized by excessive immune activation. Many patients with severe COVID qualify for a diagnosis of HLH. Etoposide, an inhibitor of topoisomerase II is used to control inflammation in HLH. This randomized, open-label, single center phase II trial attempted to determine whether etoposide can be used to blunt the inflammatory response in severe COVID. This trial was closed early after eight patients were randomized. This underpowered trial did not meet its primary endpoint of improvement in pulmonary status by two categories on an 8 point ordinal scale of respiratory function. There were not significant differences in secondary outcomes including overall survival at 30 days, cumulative incidence of grade 2 through 4 adverse events during hospitalization, duration of hospitalization, duration of ventilation and improvement in oxygenation or paO2/FIO2 ratio or improvement in inflammatory markers associated with cytokine storm. A high rate of grade 3 myelosuppression was noted in this critically ill population despite dose reduction, a toxicity which will limit future attempts to explore the utility of etoposide for virally-driven cytokine storm or HLH.

Background: Patients with cancer undergoing cytotoxic chemotherapy face an elevated risk of developing serious infection as a consequence of their treatment, which lowers their white blood cell count and, more specifically, their absolute neutrophil count. This condition is known as neutropenia. Neutropenia accompanied by a fever is referred to as febrile neutropenia, a common side effect of chemotherapy with a high mortality rate. The timely detection of severe neutropenia (<500 absolute neutrophil count/μL) is critical in detecting and managing febrile neutropenia. Current methods rely on blood draws, which limit them to clinical settings and do not allow frequent or portable monitoring. In this study, we demonstrated the usability of PointCheck, a noninvasive device for neutropenia screening, in a simulated home environment without clinical supervision. PointCheck automatically performs microscopy through the skin of the finger to image the blood flowing through superficial microcapillaries and enables the remote monitoring of neutropenia status, without requiring venipuncture. Objective: This study aimed to evaluate the usability of PointCheck, a noninvasive optical technology for screening severe neutropenia, with the goal of identifying potential user interface, functionality, and design issues from the perspective of untrained users. Methods: We conducted a multicenter study using quantitative and qualitative approaches to evaluate the usability of PointCheck across 154 untrained participants. We used a mixed method approach to gather usability data through user testing observations, a short-answer qualitative questionnaire, and a standardized quantitative System Usability Scale (SUS) survey to assess perceived usability and satisfaction. Results: Of the 154 participants, we found that 108 (70.1%) scored above 80.8 on the SUS across all sites, with a mean SUS score of 86.1 across all sites. Furthermore, the SUS results indicated that, out of the 151 users who completed the SUS survey, 145 (96%) found that they learned how to use PointCheck very quickly, and 141 (93.4%) felt very confident when using the device. Conclusions: We have shown that PointCheck, a novel technology for noninvasive, home-based neutropenia detection, can be safely and effectively operated by first-time users. In a simulated home environment, these users found it easy to use, with a mean SUS score of 86.1, indicating an excellent perception of usability and placing this device within the top tenth percentile of systems evaluated for usability by the SUS. Trial Registration: ClinicalTrials.gov NCT04448314; https://clinicaltrials.gov/ct2/show/NCT04448314 (Hospital Universitario 12 de Octubre registration) and NCT04448301; https://clinicaltrials.gov/ct2/show/NCT04448301 (Boston Medical Center registration)

High‐dose melphalan and stem cell transplantation (HDM/SCT) is an effective treatment for selected patients with AL amyloidosis. We report the long‐term outcomes of 648 patients with AL amyloidosis treated with HDM/SCT over 25 years. Hematologic CR was achieved by 39% of patients. The median duration of hematologic CR was 12.3 years, and 45% of patients with a hematologic CR had no evidence of a recurrent plasma cell dyscrasia at 15 years after HDM/SCT. With a median follow‐up interval of 8 years, the median event‐free survival (EFS) and overall survival (OS) were 3.3 and 7.6 years, respectively. Patients with a hematologic CR had a median OS of 15 years, and 30% of these patients survived >20 years. On multivariable analysis, dFLC >180 mg/L and BM plasma cells >10% were independently associated with shorter EFS, whereas BNP >81 pg/mL, troponin I > 0.1 ng/mL, and serum creatinine >2.0 mg/dL were independently associated with shorter OS. We developed a prognostic score for EFS, which incorporated dFLC >180 mg/L and BMPC% >10% as adverse risk factors. Patients with low‐risk (0 factors), intermediate‐risk (1 factor), and high‐risk (2 factors) disease had median EFS estimates of 5.3, 2.8, and 1.0 years, respectively (p < .001). The 100‐day treatment‐related mortality rate was 3% in the latest treatment period (2012–2021), and the 25‐year risk of t‐MDS/AML was 3%. We conclude that HDM/SCT induces durable hematologic responses and prolonged survival with improved safety in selected patients with AL amyloidosis.

BACKGROUND Cancer patients undergoing cytotoxic chemotherapy face an elevated risk of developing serious infection as a consequence of their treatment, which lowers their white blood cell (WBC) count and, more specifically, their absolute neutrophil count (ANC). This condition is known as neutropenia. Neutropenia accompanied by a fever is referred to as febrile neutropenia (FN), a common side effect of chemotherapy with a high mortality rate. Timely detection of severe neutropenia (ANC < 500/μL) is critical in detecting and managing FN. Current methods rely on blood draws, which limit them to clinical settings and do not allow frequent or portable monitoring. In this study, we demonstrate the usability of PointCheck™, a non-invasive device for neutropenia screening, in a simulated home environment without clinical supervision. PointCheck™ automatically performs microscopy through the skin of the finger to image the blood flowing through superficial microcapillaries, and enables remote monitoring of neutropenia status, without requiring venipuncture. OBJECTIVE This study aims to evaluate the usability of PointCheck™, a non-invasive optical technology for screening severe neutropenia, with the goal of identifying potential User Interface (UI), functionality, and design issues from the perspective of untrained users. METHODS We conducted a multi-center study using quantitative and qualitative approaches to evaluate the usability of PointCheck™ across N=154 untrained participants. We used a mixed-method approach to gather usability data through user testing observations, a short-answer qualitative questionnaire, and a standardized quantitative System Usability Scale (SUS) survey to assess user experience and satisfaction. RESULTS We found that N=108 (70.1%) of participants scored above 80.8 on the SUS across all sites, with a mean SUS score of 86.1 across all sites. Furthermore, the SUS results indicated that N=145 (96.0%) of users who completed the SUS survey found they learned how to use PointCheck™ very quickly, and N= 141 (93.0%) felt very confident using the device. CONCLUSIONS We have shown that PointCheck™, a novel technology for non-invasive, home-based neutropenia detection, can be safely and effectively operated by first-time users. In a simulated home environment, these users found it easy to use, with a mean SUS score of 86.1, indicating excellent perception of user experience and placing this device within the top 10th percentile of systems evaluated for usability by the SUS. CLINICALTRIAL ClinicalTrials.gov: H12O: NCT04448314 https://clinicaltrials.gov/ct2/show/NCT04448314 BMC: NCT04448301 https://clinicaltrials.gov/ct2/show/NCT04448301