Citations

Tandem mass spectrometry (MS/MS) is the most universal platform currently available for the analysis of enzymatic activities and biomarkers in dried blood spots (DBS) for applications in newborn screening (NBS). Among the MS/MS applications in NBS, the most common is flow-injection analysis (FIA-) MS/MS, where the sample is introduced as a bolus injection into the mass spectrometer without the prior fractionation of analytes. Liquid chromatography combined with MS/MS (LC-MS/MS) has been employed for second-tier tests to reduce the false-positive rate associated with several nonspecific screening markers, beginning two decades ago. More recently, LC-MS/MS has been applied to primary screening for new conditions for which FIA-MS/MS or other methods, including genomic screening, are not yet adequate. In addition to providing a list of the currently used LC-MS/MS-based assays for NBS, the authors share their experience regarding the maintenance requirements of LC-MS/MS vs. FIA-MS/MS systems. The consensus is that the maintenance of LC-MS/MS and FIA-MS/MS instrumentation is similar, and LC-MS/MS has the advantage of allowing for a larger number of diseases to be screened for in a multiplex, cost-effective fashion with a high throughput and an adequate turnaround time.

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible. One recent therapeutic breakthrough is that all BPDCNs express CD123 (IL3Rα) and that this accessible surface marker can be pharmacologically targeted. The first-in-class agent for BPDCN, tagraxofusp, which targets CD123, was approved in December 2018 in the United States for patients with BPDCN aged ≥2 years. Despite favorable response rates in the frontline setting, many patients still relapse in the setting of monotherapy, and outcomes in patients with relapsed/refractory BPDCN remain dismal. Therefore, novel approaches targeting both CD123 and other targets are actively being investigated. To begin to formally address the state of the field, we formed a new collaborative initiative, the North American BPDCN Consortium (NABC). This group of experts, which includes a multidisciplinary panel of hematologists/oncologists, hematopoietic stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists, was tasked with defining the current standard of care in the field and identifying the most important research questions and future directions in BPDCN. The position findings of the NABC’s inaugural meetings are presented herein.

AbstractThe poor generalizability of clinical research data due to the enrollment of highly educated, non‐Latinx White participants hampers the development of therapies for Alzheimer's disease (AD). Black and Latinx older adults have a greater risk for dementia, yet it is unclear how health‐care disparities and sociocultural factors influence potential AD therapies and prognosis. Low enrollment of under‐represented populations may be attributable to several factors including greater exclusion due to higher rates of comorbidities, lower access to AD clinics, and the legacy of unethical treatment in medical research. This perspective outlines solutions tested in the Brain Health Registry (BHR) and the Alzheimer's Disease Neuroimaging Initiative (ADNI), including culturally‐informed digital research methods, community‐engaged research strategies, leadership from under‐represented communities, and the reduction of exclusion criteria based on comorbidities. Our successes demonstrate that it is possible to increase the inclusion and engagement of under‐represented populations into US‐based clinical studies, thereby increasing the generalizability of their results.

Background: Medicare Advantage (MA) plans are popular among Medicare-eligible patients, but little is known about MA in lower-extremity total joint arthroplasty (TJA). The purpose of this study was to describe trends in MA utilization and analyze differences in patient characteristics and postoperative outcomes between patients undergoing primary TJA using traditional Medicare (TM) or MA plans. Methods: Patients ≥65 years of age who underwent primary total knee or total hip arthroplasty were identified using the Premier Healthcare Database. Patients were categorized into TM and MA cohorts. Data from 2004 to 2020 were used to describe trends in insurance coverage. Data from 2015 to 2020 were used to identify differences in patient characteristics and postoperative complications using ICD-10 codes. Multivariate analyses were performed using 2015 to 2020 data to account for potential confounders. Results: From 2004 to 2020, the proportion of patients with MA increased from 7.9% to 34.4%, while those with TM decreased from 83.7% to 54.0%. Of the 697,317 patients who underwent primary elective TJA from 2015 to 2020, 471,439 (67.6%) had TM coverage and 225,878 (32.4%) had MA coverage. The cohorts were similar in terms of age and sex. However, a higher proportion of Black patients (8.29% compared with 4.62%; p < 0.001) and a lower proportion of White patients (84.0% compared with 89.2%; p < 0.001) were enrolled in MA compared with TM. After controlling for confounders, patients with MA had higher odds of surgical site infection (adjusted odds ratio [aOR]: 1.15; 95% confidence interval [CI]: 1.04 to 1.47; p = 0.031), periprosthetic joint infection (aOR: 1.10; 95% CI: 1.03 to 1.18; p = 0.006), stroke (aOR: 1.15; 95% CI: 1.02 to 1.31; p = 0.026), and acute kidney injury (aOR: 1.08; 95% CI: 1.04 to 1.11; p < 0.001), but lower odds of urinary tract infection (aOR: 0.94; 95% CI: 0.90 to 0.98; p = 0.003). Conclusions: From 2004 to 2020, the number of patients utilizing MA increased markedly such that 1 in 3 were covered by MA in 2020. From 2015 to 2020, patients who were non-White were more likely to have MA than TM, and the MA group had a higher rate of several postoperative complications compared with the TM group. As TM claims data inform health-care policy and clinical decisions, this change portends future challenges, including limitations in arthroplasty registry research, an increase in the administrative burden of surgeons, and a potential worsening of social disparities in health care.

Introduction: The COVID-19 pandemic has disproportionally affected historically marginalized populations and their access to resources and healthcare. In times of crisis, authentic community engagement is more important than ever. This study was Phase 1 of a larger 3-phase study to conduct timely community-engaged research with community members to understand the disproportionate impact of COVID-19 on historically underserved communities. The objective of this work was to conduct key informant (KI) interviews (1) to understand community organizations perspectives about the role that large academic health centers play as they interface with community organizations to support their work, (2) to leverage KI’s expertise to identify needs and assets within the community, and (3) to inform both Phase 2 (focus group qualitative research) and Phase 3 (survey) of the broader study. Methods: A total of 24 key informants were identified through purposeful sampling and one-on-one semi-structured interviews were conducted across 4 states using video conferencing. Results: Barriers to access and lack of transparency were highlighted as major issues requiring reform—in particular, aggressive billing practices and insurance barriers exacerbated local distrust of medical institutions. KIs recognized the health institution’s support for testing and vaccination during the COVID-19 pandemic, but noted other significant gaps in care, especially regarding mental health support. Although communication with the health institution was consistent for some KIs, others experienced unsustained communication efforts that hindered cooperation and relationship building. Conclusions: Leaders in the community as key stakeholders can provide unique insights into the challenges and potential solutions required to promote health equity, and foster understanding between local communities and healthcare institutions.

AbstractDiabetes insipidus is characterized by polyuria due to an inability to auto‐regulate water balance resulting in dangerous metabolic derangements. Intraoperative anesthetics have been increasingly identified as a cause of diabetes insipidus in adult patients; however, it is rare in pediatrics. We present a case of a 16‐year‐old male undergoing resection of a recurrent left juvenile nasopharyngeal angiofibroma who experienced intraoperative polyuria concerning diabetes insipidus. Urine output drastically decreased following discontinuation of dexmedetomidine with complete resolution within 24 h. We conclude that this case of transient diabetes insipidus was associated with dexmedetomidine administration.

AbstractExtended‐release liposomal bupivacaine is frequently used in surgical infiltration for postoperative pain control. The manufacturer recommends against subsequent local anesthetics within 96 hours. We administered epidural bupivacaine one day after local liposomal bupivacaine infiltration for staged hemipelvectomy without symptoms of LAST. Further pharmacokinetic and clinical safety studies are needed.