Hypopigmented mycosis fungoides in childhood and adolescence: a long-term retrospective study.

Patients with hypopigmented mycosis fungoides (HMF) present at a younger age than those with classic MF. Our goal was to describe the clinical presentation, histopathologic features and long-term outcome in patients who developed HMF before the age of 21. It was observed that among 69 pediatric patients diagnosed with MF between 1992 and 2010, 50 had HMF. Thirty-five patients had clinical follow-up. There were 37 males and 32 females with a mean age of 13.6 years. Most patients were African American or Hispanic and presented with multiple hypopigmented patches. All biopsies showed epidermotropism of T-lymphocytes, whereas fibroplasia and lichenoid infiltrate were variable. All specimens tested were CD8+. Treatment modalities included topical steroids, narrow band ultraviolet B and psoralen and ultraviolet A. HMF patients were followed for <1-12 years. Most children responded to treatment, but recurrence rates were high. One patient progressed to plaque/tumor stage. Others did not progress; however, many were lost to follow-up. We present a large cohort of children with HMF and report on the features of disease and progression. A major difference in histology of HMF was lack of fibroplasia and lichenoid infiltrate, probably because of presentation in the early patch stage. Most patients have a waxing-and-waning course and relapse after discontinuation of therapy, requiring repetitive treatment.

Risk Estimation of Severe COVID-19 Based on Initial Biomarker Assessment Across Racial and Ethnic Groups.

CONTEXT.­: Disease courses in COVID-19 patients vary widely. Prediction of disease severity on initial diagnosis would aid appropriate therapy, but few studies include data from initial diagnosis. OBJECTIVE.­: To develop predictive models of COVID-19 severity based on demographic, clinical, and laboratory data collected at initial patient contact after diagnosis of COVID-19. DESIGN.­: We studied demographic data and clinical laboratory biomarkers at time of diagnosis, using backward logistic regression modeling to determine severe and mild outcomes. We used deidentified data from 14 147 patients who were diagnosed with COVID-19 by polymerase chain reaction SARS-CoV-2 testing at Montefiore Health System, from March 2020 to September 2021. We generated models predicting severe disease (death or more than 90 hospital days) versus mild disease (alive and fewer than 2 hospital days), starting with 58 variables, by backward stepwise logistic regression. RESULTS.­: Of the 14 147 patients, including Whites, Blacks, and Hispanics, 2546 (18%) patients had severe outcomes and 3395 (24%) had mild outcomes. The final number of patients per model varied from 445 to 755 because not all patients had all available variables. Four models (inclusive, receiver operating characteristic, specific, and sensitive) were identified as proficient in predicting patient outcomes. The parameters that remained in all models were age, albumin, diastolic blood pressure, ferritin, lactic dehydrogenase, socioeconomic status, procalcitonin, B-type natriuretic peptide, and platelet count. CONCLUSIONS.­: These findings suggest that the biomarkers found within the specific and sensitive models would be most useful to health care providers on their initial severity evaluation of COVID-19.

Elucidating the role of procalcitonin as a biomarker in hospitalized COVID-19 patients.

Our objectives were to evaluate the role of procalcitonin in identifying bacterial co-infections in hospitalized COVID-19 patients and quantify antibiotic prescribing during the 2020 pandemic surge. Hospitalized COVID-19 patients with both a procalcitonin test and blood or respiratory culture sent on admission were included in this retrospective study. Confirmed co-infection was determined by an infectious diseases specialist. In total, 819 patients were included; 335 (41%) had an elevated procalcitonin (>0.5 ng/mL) and of these, 42 (13%) had an initial bacterial co-infection. Positive predictive value of elevated procalcitonin for co-infection was 13% while the negative predictive value was 94%. Ninety-six percent of patients with an elevated procalcitonin received antibiotics (median 6 days of therapy), compared to 82% with low procalcitonin (median 4 days of therapy) (adjusted OR:3.3, P < 0.001). We observed elevated initial procalcitonin in many COVID patients without concurrent bacterial co-infections which potentially contributed to antibiotic over-prescribing.

Genomic surveillance of SARS-CoV-2 during the first year of the pandemic in the Bronx enabled clinical and epidemiological inference.

The Bronx was an early epicenter of the COVID-19 pandemic in the USA. We conducted temporal genomic surveillance of SARS-CoV-2 genomes across the Bronx from March-October 2020. Although the local structure of SARS-CoV-2 lineages mirrored those of New York City and New York State, temporal sampling revealed a dynamic and changing landscape of SARS-CoV-2 genomic diversity. Mapping the trajectories of variants, we found that while some became 'endemic' to the Bronx, other, novel variants rose in prevalence in the late summer/early fall. Geographically resolved genomes enabled us to distinguish between cases of reinfection and persistent infection in two pediatric patients. We propose that limited, targeted, temporal genomic surveillance has clinical and epidemiological utility in managing the ongoing COVID pandemic. One sentence summary: Temporally and geographically resolved sequencing of SARS-CoV-2 genotypes enabled surveillance of novel genotypes, identification of endemic viral variants, and clinical inferences, in the first wave of the COVID-19 pandemic in the Bronx.

Efficacy of booster doses in augmenting waning immune responses to COVID-19 vaccine in patients with cancer.

Anti-COVID-19 immunity dynamics were assessed in patients with cancer in a prospective clinical trial. Waning of immunity was detected 4-6 months post-vaccination with significant increases in anti-spike IgG titers after booster dosing, and 56% of seronegative patients seroconverted post-booster vaccination. Prior anti-CD20/BTK inhibitor therapy was associated with reduced vaccine efficacy.

Genomic surveillance of SARS-CoV-2 during the first year of the pandemic in the Bronx enabled clinical and epidemiological inference.

The Bronx was an early epicenter of the COVID-19 pandemic in the USA. We conducted temporal genomic surveillance of 104 SARS-CoV-2 genomes across the Bronx from March October 2020. Although the local structure of SARS-CoV-2 lineages mirrored those of New York City and New York State, temporal sampling revealed a dynamic and changing landscape of SARS-CoV-2 genomic diversity. Mapping the trajectories of mutations, we found that while some became 'endemic' to the Bronx, other, novel mutations rose in prevalence in the late summer/early fall. Geographically resolved genomes enabled us to distinguish between cases of reinfection and persistent infection in two pediatric patients. We propose that limited, targeted, temporal genomic surveillance has clinical and epidemiological utility in managing the ongoing COVID pandemic.

Alpha- and beta-synucleins are new diagnostic tools for acute erythroid leukemia and acute megakaryoblastic leukemia.

α-Synuclein is a key component of the Lewy body, a large globular protein complex that forms in the nervous system of patients with Parkinson disease and other dementias [1-3]. Since α-synuclein also occurs in megakaryocytic and erythroid lineages [4-7], we wondered what role synucleins had in the hematopoietic system. Therefore, we studied the expression of α-, ß-, and γ-synucleins in a comprehensive panel of patient bone marrows and leukemic cell lines. We observed under expression of α-synuclein in the megakaryocytes of myeloproliferative neoplasm (MPN), but not normal reactive marrow (NRM) or myelodysplastic syndrome (MDS). Conversely, we observed over expression of ß-synuclein in the blasts of megakaryoblastic leukemias (MegL), but not acute myeloid leukemia (AML) or erythroleukemia (EryL), suggesting that α- and ß-synucleins could be useful adjunct markers for the early detection of MDS and the differential diagnosis of EryL and MegL from other AMLs.

Systemic mastocytosis in a child with t(8;21) acute myeloid leukemia.

Mastocytosis is primarily limited to the cutaneous variant in pediatric patients. Systemic mastocytosis (SM) has been associated with t(8;21) acute myeloid leukemia (AML) in adults. We provide the first report of a child with t(8;21) AML, diagnosed with asymptomatic SM following four cycles of chemotherapy. Unlike most adults with SM/AML, she was not found to have a c-KIT (D816V) mutation. SM persisted in the bone marrow after completion of chemotherapy, and her AML relapsed 9 months off-treatment. Although she achieved a second remission, mastocytosis persists in the marrow. Pediatric patients with t(8;21) AML/SM may represent a high-risk group despite favorable cytogenetics.

Mater Artium Necessitas: The Birth of a COVID-19 Command Center.

In February of 2020, New York City was unprepared for the COVID-19 pandemic. Cases of SARS-CoV-2 infection appeared and spread rapidly. Hospitals had to repurpose staff and establish diagnostic testing for this new viral infection. In the background of the usual respiratory pathogen testing performed in the clinical laboratory, SARS-CoV-2 testing at the Montefiore Medical System grew exponentially, from none to hundreds per day within the first week of testing. The job of appropriately routing SARS-CoV-2 viral specimens became overwhelming. Additional staff was required to triage these specimens to multiple in-house testing platforms as well as external reference laboratories. Since medical school classes and many research laboratories shut down at the Albert Einstein College of Medicine and students were eager to help fight the pandemic, we seized the opportunity to engage and train senior MD-PhD students to assist in triaging specimens. This volunteer force enabled us to establish the "Pathology Command Center," staffed by these students as well as residents and furloughed dental associates. The Pathology Command Center staff were tasked with the accessioning and routing of specimens, answering questions from clinical teams, and updating ever evolving protocols developed in collaboration with a team of Infectious Disease clinicians. Many lessons were learned during this process, including how best to restructure an accessioning department and how to properly onboard students and repurpose staff while establishing safeguards for their well-being during these unprecedented times. In this article, we share some of our challenges, successes, and what we ultimately learned as an organization.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Qualitative Immunoglobulin G Assays: The Value of Numeric Reporting.

CONTEXT.­: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) testing is used for serosurveillance and will be important to evaluate vaccination status. Given the urgency to release coronavirus disease 2019 (COVID-19) serology tests, most manufacturers have developed qualitative tests. OBJECTIVE.­: To evaluate clinical performance of 6 different SARS-CoV-2 IgG assays and their quantitative results to better elucidate the clinical role of serology testing in COVID-19. DESIGN.­: Six SARS-CoV-2 IgG assays were tested using remnant specimens from 190 patients. Sensitivity and specificity were evaluated for each assay with the current manufacturer's cutoff and a lower cutoff. A numeric result analysis and discrepancy analysis were performed. RESULTS.­: Specificity was higher than 93% for all assays, and sensitivity was higher than 80% for all assays (≥7 days post-polymerase chain reaction testing). Inpatients with more severe disease had higher numeric values compared with health care workers with mild or moderate disease. Several discrepant serology results were those just below the manufacturers' cutoff. CONCLUSIONS.­: Severe acute respiratory syndrome coronavirus 2 IgG antibody testing can aid in the diagnosis of COVID-19, especially with negative polymerase chain reaction. Quantitative COVID-19 IgG results are important to better understand the immunologic response and disease course of this novel virus and to assess immunity as part of future vaccination programs.

Seroconversion rates following COVID-19 vaccination among patients with cancer.

As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. On comparison with solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematologic malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than with mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies.

Laboratory and clinical predictors of 30-day survival for patients on Extracorporeal Membrane Oxygenation (ECMO): 8-Year experience at Albert Einstein College of Medicine, Montefiore Medical Center.

PURPOSE: Survival of patients on ECMO has remained stable in every population. Laboratory values predictors of survival are required to improve patient care. MATERIALS AND METHODS: Clinical Looking Glass software was used to assess Electronic Medical Records (EMRs) of patients at Albert Einstein College of Medicine, Montefiore Medical Center (2007-2014). RESULTS: Our population comprises of 166 adults and was divided in survivors and non-survivors, within 30days. Indications for ECMO were cardiac (65%), respiratory (25%) and infectious diseases (<10%). Eighty six patients (51.8%) survived the procedure. Gender, body weight, ejection fraction, diastolic blood pressure, and socio-economic status did not differ among survivors and non-survivors. In contrast, younger patients (45yo vs 55yo, p=0.0001) and higher systolic blood pressure (115mmHg vs 103mmHg, p=0.025) have favorable outcome. Univariate analysis shows that pre-cannulation values for creatinine (p=0.0003), chloride (p=0.009), bicarbonate (p=0.015) and pH (p=0.03) have prognostic value. Post-cannulation aPTT, pH, platelet and lymphocyte counts also have discriminative power. Notably, multiple logistic regressions for Multivariate Analysis identified chloride (OR 1.07; 95% CI 1.02-1.13; p=0.004), pH (OR 3.35; 95% CI 1.89-5.9; p<0.0001) and aPTT (OR 0.98; 95% CI 0.976-0.998; p=0.024) as independent risk factors for 30-day mortality. These results imply that pre-existing renal conditions and hemostatic dysregulation contribute to poor outcome. Finally, patients on VV-ECMO have increase odds of survival (OR 1.88; 95% CI 1.06-3.34; p=0.029). CONCLUSIONS: Laboratory markers identified herein may guide the management of patients on ECMO.

A novel 2-stage approach that detects complement activation in patients with antiphospholipid antibody syndrome.

INTRODUCTION: The antiphospholipid syndrome (APS) is marked by autoantibodies that recognize anionic phospholipids in a cofactor-dependent manner. A role for complement has been implicated in the pathophysiology, however, elevations of complement activation markers have not been consistently demonstrated in clinical studies. We therefore designed a proof-of-principle study to determine whether complement activation might be detectable in APS by first exposing plasmas to phospholipid vesicles. METHODS: We examined complement activation markers in patients with APS, non-APS thrombosis, systemic lupus erythematosus, cancer, patients with antiphospholipid antibodies without thrombosis (APL) and healthy controls. Direct measurements of plasma C5a and sC5b-9 levels were compared to levels that were generated in normal serum by phospholipid vesicles that had been pre-incubated with the same plasmas. We then determined the effects of the C5 inhibitor, eculizumab, examined the complement pathways involved, and determined whether the effects could be reproduced with purified IgGs and ß2-glycoprotein I (ß2GPI). RESULTS: Plasma levels of C5a and sC5b-9 were higher, but not significantly increased in APS patients compared to healthy controls. In contrast, phospholipid vesicles pre-incubated with APS plasmas generated significantly higher levels than healthy controls and the other groups, except for APL patients. Complement activation was abrogated by addition of eculizumab. The results with substrate sera indicated that the alternative and classical/lectin pathways were involved. The results were reproducible with purified IgGs and ß2GPI. CONCLUSION: This proof-of-principle study confirms a role for complement in APS and opens the possibility of monitoring complement activation by including phospholipid vesicles in assay systems.

Dos and don'ts in diagnosing antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombotic tendency that is identified by the presence of abnormal antiphospholipid laboratory tests in patients who have a history of vascular thrombosis and/or pregnancy complications including recurrent spontaneous miscarriages and a group of other complications due to placental insufficiency. Diagnostic testing for APS is often problematic because of many misconceptions regarding these empirically derived assays. This chapter is intended to provide hematology-oncology consultants with practical information about the uses and limitations of assays used to diagnose APS.

Spectrin isoforms: differential expression in normal hematopoiesis and alterations in neoplastic bone marrow disorders.

Spectrins are large, rod-like, multifunctional molecules that participate in maintaining cell structure, signal transmission, and DNA repair. Because little is known about the role of spectrins in normal hematopoiesis and leukemogenesis, we immunohistochemically stained bone marrow biopsy specimens from 81 patients for αI, αII, ßI, and ßII spectrin isoforms in normal reactive marrow (NRM), myelodysplastic syndrome, myeloproliferative neoplasm, acute myeloid leukemia (AML) with well-characterized cytogenetic abnormalities, acute erythroid leukemia (EryL), and acute megakaryoblastic leukemia (MegL). In NRM, spectrin isoforms were differentially expressed according to cell lineage: αI and ßI in erythroid precursors; αII and ßII in granulocytes; and ßI and ßII in megakaryocytes. In contrast, 18 (44%) of 41 AMLs lacked αII spectrin and/or aberrantly expressed ßI spectrin (P = .0398; Fisher exact test) and 5 (100%) of 5 EryLs expressed ßII spectrin but lacked ßI spectrin. The frequent loss and/or gain of spectrin isoforms in AMLs suggests a possible role for spectrin in leukemogenesis.