When non-Whiteness becomes a condition.

The term "benign ethnic neutropenia" describes the phenotype of having an absolute neutrophil count (ANC) <1500 cells/µL with no increased risk of infection. It is most commonly seen in those of African ancestry. In addition, ANC reference ranges from countries in Africa emphasize that ANC levels <1500 cells/µL are common and harmless. The lower ANC levels are driven by the Duffy null [Fy(a-b-)] phenotype, which is protective against malaria and seen in 80% to 100% of those of sub-Saharan African ancestry and <1% of those of European descent. Benign ethnic neutropenia is clinically insignificant, but the average ANC values differ from what are typically seen in those of European descent. Thus, the predominantly White American medical system has described this as a condition. This labeling implicitly indicates that common phenotypes in non-White populations are abnormal or wrong. We believe that it is important to examine and rectify practices in hematology that contribute to systemic racism.

Thrombosis-Related Loss of Arterial Lines in the First Wave of COVID-19 and Non-COVID-19 Intensive Care Unit Patients.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) can present with severe respiratory distress requiring intensive care unit (ICU)-level care. Such care often requires placement of an arterial line for monitoring of pulmonary disease progression, hemodynamics, and laboratory tests. During the first wave of the COVID-19 pandemic in March 2020, experienced physicians anecdotally reported multiple attempts, decreased insertion durations, and greater need for replacement of arterial lines in patients with COVID-19 due to persistent thrombosis. Because invasive procedures in patients with COVID-19 may increase the risk for caregiver infection, better defining difficulties in maintaining arterial lines in COVID-19 patients is important. We sought to explore the association between COVID-19 infection and arterial line thrombosis in critically ill patients. METHODS: In this primary exploratory analysis, a multivariable Fine-Gray subdistribution hazard model was used to retrospectively estimate the association between critically ill COVID-19 (versus sepsis/acute respiratory distress syndrome [ARDS]) patients and the risk of arterial line removal for thrombosis (with arterial line removal for any other reason treated as a competing risk). As a sensitivity analysis, we compared the number of arterial line clots per 1000 arterial line days between critically ill COVID-19 and sepsis/ARDS patients using multivariable negative binomial regression. RESULTS: We retrospectively identified 119 patients and 200 arterial line insertions in patients with COVID-19 and 54 patients and 68 arterial line insertions with non-COVID ARDS. Using a Fine-Gray subdistribution hazard model, we found the adjusted subdistribution hazard ratio (95% confidence interval [CI]) for arterial line clot to be 2.18 (1.06-4.46) for arterial lines placed in COVID-19 patients versus non-COVID-19 sepsis/ARDS patients ( P = .034). Patients with COVID-19 had 36.3 arterial line clots per 1000 arterial line days compared to 19.1 arterial line clots per 1000 arterial line days in patients without COVID-19 (adjusted incidence rate ratio [IRR] [95% CI], 1.78 [0.94-3.39]; P = .078). CONCLUSIONS: Our study suggests that arterial line complications due to thrombosis are more likely in COVID-19 patients and supports the need for further research on the association between COVID-19 and arterial line dysfunction requiring replacement.

A Massive Case of Cutaneous Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and extranodal involvement is seen in approximately 40% of cases. However, cases involving the skin and muscle are rare, and skin manifestations most commonly present as plaques, papules, small nodules, or ulcers. In this report, we discuss a case of a large exophytic mass involving skin, soft tissue, and muscle initially thought to be baso-squamous carcinoma subsequently identified as DLBCL and treated solely with chemotherapy. J Drugs Dermatol. 2023;22(12):1223-1224.     doi:10.36849/JDD.6936.

Persistence of Unequal Access to Classical Hematology Telemedicine Visits by Race and Other Demographics During the COVID-19 Pandemic.

Background: Unequal access to telemedicine services exacerbates health inequities and was evident at the start of the COVID-19 pandemic. We sought to explore whether unequal access persisted within a classical hematology division beyond the peak of COVID-19. Methods: Patient demographics by virtual visit type (telephone only [TO] or video only [VO]) between March 2020 and December 2021 were analyzed using adjusted odds ratio (aOR). Results: Of 8,207 patients, 18.4% had TO and 28.4% had VO visits. Fewer Black (21.8%; aOR 0.5 [0.4-0.62]), Hispanic or Latino (18.8%; 0.45 [0.34-0.59]), Spanish-speaking (7.6%; 0.32 [0.19-0.54]), high school (21.2%; 0.64 [0.52-0.78]), and older (24.2%) patients used VO compared with White (30.6%), English-speaking (29.5%), college (31%), postgraduate (34.9%), and younger (35.4%) patients. Conclusions: Groups that historically experience health inequities had fewer VO visits during and beyond the pandemic peak. Thus, there is a need to continue digital inclusion efforts to promote video access equity.

Enhanced dimethylarginine degradation improves coronary flow reserve and exercise tolerance in Duchenne muscular dystrophy carrier mice.

Duchenne muscular dystrophy (DMD) is an X-linked disease caused by null mutations in dystrophin and characterized by muscle degeneration. Cardiomyopathy is common and often prevalent at similar frequency in female DMD carriers irrespective of whether they manifest skeletal muscle disease. Impaired muscle nitric oxide (NO) production in DMD disrupts muscle blood flow regulation and exaggerates postexercise fatigue. We show that circulating levels of endogenous methylated arginines including asymmetric dimethylarginine (ADMA), which act as NO synthase inhibitors, are elevated by acute necrotic muscle damage and in chronically necrotic dystrophin-deficient mice. We therefore hypothesized that excessive ADMA impairs muscle NO production and diminishes exercise tolerance in DMD. We used transgenic expression of dimethylarginine dimethylaminohydrolase 1 (DDAH), which degrades methylated arginines, to investigate their contribution to exercise-induced fatigue in DMD. Although infusion of exogenous ADMA was sufficient to impair exercise performance in wild-type mice, transgenic DDAH expression did not rescue exercise-induced fatigue in dystrophin-deficient male mdx mice. Surprisingly, DDAH transgene expression did attenuate exercise-induced fatigue in dystrophin-heterozygous female mdx carrier mice. Improved exercise tolerance was associated with reduced heart weight and improved cardiac ß-adrenergic responsiveness in DDAH-transgenic mdx carriers. We conclude that DDAH overexpression increases exercise tolerance in female DMD carriers, possibly by limiting cardiac pathology and preserving the heart's responses to changes in physiological demand. Methylated arginine metabolism may be a new target to improve exercise tolerance and cardiac function in DMD carriers or act as an adjuvant to promote NO signaling alongside therapies that partially restore dystrophin expression in patients with DMD.NEW & NOTEWORTHY Duchenne muscular dystrophy (DMD) carriers are at risk for cardiomyopathy. The nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is released from damaged muscle in DMD and impairs exercise performance. Transgenic expression of dimethylarginine dimethylaminohydrolase to degrade ADMA prevents cardiac hypertrophy, improves cardiac function, and improves exercise tolerance in DMD carrier mice. These findings highlight the relevance of ADMA to muscular dystrophy and have important implications for therapies targeting nitric oxide in patients with DMD and DMD carriers.

Neutropenia Is an Underrecognized Finding in Pediatric Primary Immunodeficiency Diseases: An Analysis of the United States Immunodeficiency Network Registry.

BACKGROUND: The frequency of neutropenia in pediatric primary immunodeficiency disorders (PIDDs) is unknown and potentially underappreciated. Our study aimed to determine the overall frequency and severity of neutropenia in children diagnosed with a PIDD entered in the United States Immunodeficiency Network (USIDNET) patient registry. PROCEDURE: Neutropenia data and demographic/clinical information from 1145 patients younger than 21 years of age was obtained from the USIDNET registry. RESULTS: Neutropenia is more common in PIDD patients entered within the USIDNET registry than previously appreciated. There was a >10% occurrence rate of neutropenia in all broad primary immunodeficiency categories as well as in nearly all individual PIDDs. Neutropenia frequency was greater in African American pediatric PIDD patients than in white or Asian patients. The degree of neutropenia did not associate with mortality in pediatric patients with a PIDD. CONCLUSION: Although our study did not assess the frequency of PIDD in patients presenting with neutropenia, the possibility of a primary immune disorder should be considered in patients with idiopathic neutropenia.

Provider Perceptions of Quality of Life, Neurocognition, Physical Well-being, and Psychosocial Health in Patients with Primary Immunodeficiency/Immune Dysregulation Conditions.

PURPOSE: Both pediatric and adult patients with a primary immunodeficiency/immune dysregulation (PID/PIDR) diagnosis report inferior quality of life (QOL) and patient-reported outcomes (PROs) as compared with their healthy peers. Recognition of the negative impact on QOL and PROs provides an opportunity for clinicians to intervene with supportive measures. However, provider perceptions of PID/PIDR patients' quality of life, physical well-being, psychosocial health and neurocognition, and access to supportive resources have yet to be systematically evaluated. METHODS: We report specialty providers' perception of the QOL and psychosocial and physical well-being of their pediatric and adult patients with PID/PIDR through the utilization of an online survey assessing QOL and the impact of disease or its associated treatment on their physical well-being, mental health, social relationships, neurocognition, and work/school performance. RESULTS: Clinicians trended towards believing adult PID/PIDR patients had worse overall QOL than children with PID/PIDR. Providers additionally identified their adult patients' QOL to be more deleteriously affected by co-morbidities than their pediatric patients. Clinicians distinguished anxiety and social relationships as the psychosocial aspects most often affected by a complex immunological diagnosis in all patients. Of physical health considerations, energy, rather than mobility or pain, was perceived to be more negatively influenced by PID/PIDR in both adult and pediatric patients. CONCLUSIONS: Knowledge of these clinician perceptions can affect communication of findings with patients, as well as ongoing management, and thus, it is important to understand these fully to improve healthcare delivery to, and clinical management of, these patients.

Development of Duffy Null-Specific Absolute Neutrophil Count Reference Ranges.

This study establishes a Duffy null phenotype­specific absolute neutrophil count reference range to optimize care and improve health equity.

Development of a Hematology-General Medicine Hybrid Team to Improve Care of Patients With Sickle Cell Disease.

PROBLEM: Approximately 100,000 individuals in the United States have sickle cell disease (SCD). These individuals face multiple barriers to equitable care. At Brigham and Women's Hospital, existing health inequities for these patients were compounded by admitting, rounding, and team structures that assigned patients with SCD to multiple medicine teams with a hematologist attending, leading to delays in patient care and gaps in residents' hematology knowledge. APPROACH: A hematology-general medicine hybrid team was created in September 2021 to enhance trainee knowledge, skill, and confidence in managing hematology conditions and improve the quality of care delivered to individuals with SCD. This allowed for regionalization of patients with classical hematology conditions to specific hospital floors under the care of one team with a hematologist as the attending of record. OUTCOMES: From October 1, 2021, to January 11, 2022, the majority (745/824, 90%) of in-hospital days for patients with a primary hematology diagnosis were under the care of the hematology-general medicine hybrid team. Regionalization to the home floor of the hybrid team was achieved on 331 (40%) of these 824 hospital days, consistent with regionalization rates for other teams. From October 1, 2021, to September 30, 2022, there were 128 unique patients with SCD admitted over 511 encounters and cared for by approximately 78 residents and 12 medical students. Feedback from residents reported improved knowledge in the management of hematology conditions, especially SCD. NEXT STEPS: The authors are working on a comprehensive analysis of the hybrid team's impact on trainee skill and confidence in managing SCD. The authors believe that this model can be replicated at other institutions to optimize trainee education, consolidate care, and address implicit bias against patients with SCD, even with the hematology attending as a consultant instead of as the attending of record.

Development of a Pipeline for Removing Allergy Labels in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Penicillin allergy is reported by 10% to 20 % of patients, but when evaluated only 1% to 2% may have a true allergy. Patients undergoing hematopoietic stem cell transplantation (HSCT) have a high likelihood of requiring beta-lactam antibiotics due to increased infection risk, which can be limited by a penicillin allergy label. When a penicillin allergy is recorded, alternatives are needed, including more expensive broader-spectrum antibiotics, with increases in drug-resistant bacteria, longer hospital stays, higher expenditures, and increases in nosocomial infections, such as Clostridium difficile colitis. This group of patients already undergoes extensive pretreatment testing and would especially benefit from allergy delabeling. This study aimed to develop a self-sustaining, low-cost pipeline between an HSCT clinic and an allergy clinic to identify and successfully delabel low-risk patients who endorse an allergy to penicillin, amoxicillin, amoxicillin-clavulanate, piperacillin-tazobactam, or ampicillin before admission to the hospital. We developed a survey to triage allergy risk, identified key stakeholders in building the pipeline, and underwent 4 plan, do, study, act (PDSA) cycles. Changes were made in each of the PDSA cycles to minimize cost and uncompensated provider time, as well as to increase patient retention throughout the pipeline by increasing appointment availability and decreasing reliance on patients to independently progress through the pathway. Of the 410 patients with planned HSCT who were screened over 11 months, 89 (21.7%) were listed as having a penicillin and/or beta lactam allergy. All but 1 (66 of 67; 98.5%) of the participants completed the survey accurately when confirmed by an allergist, and the survey was 100% accurate in predicting delabeling success in low-risk patients. Of eligible patients, 43.8% (n = 39) were successfully delabeled before their transplant date, and 97.4% of these (n = 38) have undergone HSCT to date. This pipeline is maintained by approximately 5 hours of work per week (1 hour of allergy physician time, 4 hours of nurse and/or clinical coordinator time), with no other direct costs. There is an estimated direct savings of at least $1914.93 per patient delabeled. We successfully designed and implemented a pipeline between the HSCT clinic and the allergy clinic as a quality improvement initiative to identify and address high rates of reported beta-lactam allergies. We identified and addressed patient-based factors, logistical, temporal, and financial barriers that impacted patient retention and sustainability. This model is expected to yield significant and sustained cost savings for the healthcare system as well as to improve patient outcomes, and this hypothesis is currently undergoing formal analysis. We anticipate that this model can be used to create a similar pipeline in other healthcare systems for HSCT recipients, as well as patients in other clinical settings, such as oncology and chimeric antigen receptor T cell therapy.

The Conundrum of Anticoagulation for Hospitalized Patients with Covid-19.

Thrombosis in patients with coronavirus disease 2019 (Covid-19) is driven by complex interactions between immune, complement, fibrinolytic, endothelial, and coagulation systems.1 In addition to venous thromboembolism (VTE), microthrombi have also been implicated in contributing to end-organ damage, such as acute respiratory distress syndrome and kidney dysfunction, as well as to overall mortality.1 As available therapies, variants, and vaccines have evolved, so have reported rates of VTE attributable to Covid-19.

Laboratory-based inequity in thrombosis and hemostasis: review of the evidence.

The concept of normal in hematology, similar to that in other areas of medicine, is anchored to the perspective of those setting the standard. This means that several laboratory reference intervals and approaches to the conditions of thrombosis and hemostasis are influenced by the vantage point of those in power. Structural inequity, including systemic racism and sexism, can lead to inappropriate normalization of disease states, such as anemia or iron deficiency, or delayed diagnoses, such as in von Willebrand disease. This review will focus on how laboratory reference intervals perpetuate the cycles of inequity in care of patients with disorders of thrombosis and hemostasis. We provide examples and case studies in maternal mortality as well as in disorders such as von Willebrand disease and iron deficiency, question physiology versus pathophysiology, acknowledge the distinction between social constructs and biologic influence, and highlight opportunities for much-needed restructuring in areas such as defining anemia and iron deficiency.

Absolute neutrophil count by Duffy status among healthy Black and African American adults.

Many people of African ancestry have lower absolute neutrophil counts (ANCs) without increased risk for infection. This is associated with the Duffy-null phenotype (nonexpression of the Duffy antigen on red blood cells), which is commonly found in those of African descent. Currently, there are no studies that compare the ANC of individuals with Duffy-null phenotype to those with Duffy non-null phenotypes within a self-identified Black population. The aim of this study was to assess the impact of Duffy status on ANCs based on complete blood counts with differential and Duffy testing in a healthy population of self-identified Black individuals at a single primary care center. This study found that 66.7% (80 of 120) of Black individuals have the Duffy-null phenotype and that there is a significant difference in ANCs between Duffy-null and Duffy non-null individuals (median, 2820 cells per µL vs 5005 cells per µL; P < .001). Additionally, 19 of 80 (23.8%) Duffy-null individuals had an ANC of <2000 cells per µL compared with no (0) Duffy non-null individuals. The Duffy-null phenotype is clinically insignificant; however, inappropriate reference ranges can propagate systemic racism. Therefore, we advocate for the development of Duffy-null-specific ANC reference ranges as well as replacing the term benign ethnic neutropenia with Duffy-nullassociated neutrophil count.

Quality of life and patient-reported outcomes in chronic severe neutropenia conditions.

Quality of life (QOL) and patient-reported outcomes (PROs) assessments in immunodeficiency patients, including those with chronic severe neutropenia conditions, are imperative to determining modifiable health-related features to optimize care. We present the largest study to date of QOL in those with chronic severe neutropenia conditions with further evaluation of patient provider satisfaction and patient-reported outcome measures. Subjects completed electronic surveys assessing QOL, PROs, and patient provider satisfaction. There is a significantly negative impact of a chronic severe neutropenia disorder on QOL, fatigue, physical function, cognitive function and pain in adult patients when compared to controls. Children with a chronic neutropenia condition had comparable QOL to controls, but reported fewer depressive symptoms, improved mobility, and stronger self-reported peer relationships. Adults had worse scores for QOL, depression and fatigue when compared to children. Adult and pediatric chronic severe neutropenia patients or their caregivers felt that their medical provider was compassionate, trustworthy, and accessible. However, less than 50% of adult patients agreed their clinician had excellent expertise in white blood cell disorders. Chronic neutropenia complexly affect QOL and PROs. An analysis of these parameters allows for targeted interventions to improve patient psychosocial, physical and neurocognitive health.

Impact of sickle cell trait on morbidity and mortality from SARS-CoV-2 infection.

The COVID-19 pandemic has highlighted racial health disparities within the United States. Although social determinants of health are the most likely drivers of this disparity, it is possible that genetic traits enriched in the black population like sickle cell trait (SCT) could worsen the morbidity and mortality of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients admitted for SARS-CoV-2 infection who identified as black or African American were included in the study (n = 166). Blood remnants were tested for SCT, and clinical data were abstracted from the chart. There was no difference in mortality between those with SCT and those without. There was no difference in respiratory complications between groups, but those without SCT had a much higher burden of chronic lung disease (P = .004). Those with SCT had higher creatinine on admission (P = .004), but no difference in in-hospital renal complications (P = .532). Notably, 12% of the cohort had SCT, which is higher than the expected 7.31% (P = .025). Our study did not show any evidence of increased end organ damage, morbidity, or mortality from SARS-CoV-2 infection among patients with SCT but did show differences in admission creatinine and preexisting lung disease.

Lenalidomide Plus Hypomethylating Agent as a Treatment Option in Acute Myeloid Leukemia With Recurrent Genetic Abnormalities-AML With inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM.

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous clonal hematopoietic neoplasm. The cytogenetic changes associated with AML affect the response rate and survival and are one of the most important independent prognostic factors. AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM accounts for 1% to 2% of all forms of AML and has been associated with a younger age at diagnosis, a poor response to standard induction chemotherapy, and very poor long-term prognosis. PATIENTS AND METHODS: We performed a single-center, retrospective cohort study comparing the outcomes with hypomethylating agent (HMA) plus lenalidomide to those with standard intensive induction therapies for newly diagnosed and relapsed/refractory AML with inv(3). RESULTS: Of the 15 patients, 4 (26.7%) had received lenalidomide and HMA as primary therapy. The overall response rate (ORR) was 100% for the 4 patients who had received lenalidomide with HMA as first-line induction therapy. The ORR was 27.3% (3 of 11) for the patients who had received other induction regimens (P = .0256). The duration of response for first induction therapy was an average of 7.4 months after lenalidomide plus an HMA and a mean of 1.5 months after induction with other chemotherapy regimen (P = .057). The ORR for induction and reinduction therapy was also assessed, with an ORR of 21.4% (6 of 28) for alternative chemotherapy regimens and an ORR of 75% (6 of 8) for induction and reinduction with lenalidomide plus HMA (P = .0046). CONCLUSIONS: The high ORR and reasonable duration of response could allow for potentially curative allogeneic hematopoietic cell transplantation for these patients with high-risk AML. Our initial data suggest that lenalidomide plus HMA is a promising approach for patients with AML with inv(3).

Clinical characteristics, HIV status, and molecular biomarkers in squamous cell carcinoma of the conjunctiva in Ghana.

BACKGROUND AND AIMS: Conjunctival squamous cell carcinoma (CSCC) varies in incidence geographically from 0 to 1 case per 100 000 per year globally. Additionally, the incidence of CSCC is known to increase 49% for every 10° decrease in latitude. Since the onset of the AIDS epidemic, there has been a trend of increasing incidence of CSCC in Africa, and despite relatively stable levels of ultraviolet (UV) exposure, there is an observed 12 times greater risk of developing CSCC when individuals are infected with HIV. In this study, we aim to analyze the clinical characteristics and biomarkers of CSCC in Ghana. METHODS: In this study, a registry review of patients from January 2011 to May 2016 with CSCC at Komfo-Anokye Teaching Hospital in Kumasi, Ghana, was performed (n = 64). Tumor blocks of the CSCC were analyzed for the expression of various biomarkers. RESULTS: In this study, the median age of onset of CSCC is 46.5 years old (range of 20-90 y old). Fifty one and a half percent (n = 33) of the cohort is female. There is a low rate of smoking and alcohol use in our CSCC cohort. Thirty-nine percent (n = 12) of Ghanaian men with CSCC are HIV-, while only 12% (n = 4) of women are HIV-. Fifteen patients had metastasis to lymph nodes or other tissues, and we observed a statistically significant relationship between HIV infection and metastasis (P = 0.027, chi-squared test). We observed no statistically significant relationship between known prognostic CSCC biomarkers and HIV status, age, or tumor stage. CONCLUSION: Better characterization of CSCC could have a profound impact on the prevention, early identification, and treatment of CSCC in Africa. A retrospective chart analysis and collection of tumor samples can be challenging in this region due to methods of record keeping and stigma attached to clinical data such as HIV testing and smoking and alcohol use. As a result, in this study, data were often incomplete leading to inconclusive results and analysis that should be interpreted with caution. Future studies should consider a prospective study design that gathers clinical data in a standardized format and ensures fresh tissue from CSCC tumors.