Tagraxofusp followed by combined azacitidine and venetoclax in blastic plasmacytoid dendritic cell neoplasm: A case report and literature review.

INTRODUCTION: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy that originates from plasmacytoid dendritic cells. It can involve skin, bone marrow, and/or lymph nodes. There is no consensus recommendation regarding treatment especially in the relapsed setting. Tagraxofusp, a CD123 directed agent, was recently approved by the Food and Drug Administration to treat BPDCN. We report a case of an elderly patient with diagnosis of BPDCN who was treated initially with tagraxofusp followed by azacitidine and venetoclax combination on relapse. CASE REPORT: A 79 year old male presented with violaceous skin lesions. He had no other symptoms. Biopsy of these lesions was consistent with a diagnosis of BPDCN. Further testing showed no extracutaneous involvement.Management and outcome: Tagraxofusp was started at full dose (12 mcg/kg). This dose was not tolerated well. Patient could only tolerate the lowest dose (5 mcg/kg). Toxicities included elevated liver function tests, hyperglycemia, capillary leak syndrome, and pancreatitis. Dose escalation on progression was not possible due to side effects. Treatment was switched to venetoclax and azacitidine. Combination treatment was tolerated very well and patient showed major cutaneous response after 5 cycles and continues to do well. DISCUSSION: Tagraxofusp is a novel therapy that needs more real-world experience. This case describes the clinical course of an elderly patient on tagraxofusp. We also review the literature of azacytidine/venetoclax combination as a potential yet tolerable treatment option for this rare disease entity. This is the fourth case in literature to be treated with this combination.

The Anniston Community Health Survey.

As part of our continued effort to highlight innovative approaches to improve the health and environment of communities, the Journal is pleased to publish regular columns from the Agency for Toxic Substances and Disease Registry (ATSDR) at the Centers for Disease Control and Prevention (CDC). ATSDR serves the public by using the best science, taking responsive public health actions, and providing trusted health information to prevent harmful exposures and diseases related to toxic substances. The purpose of this column is to inform readers of ATSDR's activities and initiatives to better understand the relationship between exposure to hazardous substances in the environment, its impact on human health, and how to protect public health. The conclusions of this column are those of the author(s) and do not necessarily represent the official position of ATSDR or CDC. Caroline Cusack is an epidemiologist at ATSDR. Marian Pavuk is a lead epidemiologist at ATSDR. Nina Dutton and Tara Serio are Oak Ridge Institute for Science and Education (ORISE) fellows at ATSDR. Eric Yang is currently a statistical analyst at Aspen Dental Management, Inc.

Finding inhabited settlements and tracking vaccination progress: the application of satellite imagery analysis to guide the immunization response to confirmation of previously-undetected, ongoing endemic wild poliovirus transmission in Borno State, Nigeria.

BACKGROUND: Four wild polio-virus cases were reported in Borno State, Nigeria 2016, 1 year after Nigeria had been removed from the list of polio endemic countries by the World Health Organization. Resulting from Nigeria's decade long conflict with Boko Haram, health officials had been unable to access as much as 60% of the settlements in Borno, hindering vaccination and surveillance efforts. This lack of accessibility made it difficult for the government to assess the current population distribution within Borno. This study aimed to use high resolution, visible band satellite imagery to assess the habitation of inaccessible villages in Borno State. METHODS: Using high resolution (31-50 cm) imagery from DigitalGlobe, analysts evaluated the habitation status of settlements in Borno State identified by Nigeria's Vaccination Tracking System. The analysts looked at imagery of each settlement and, using vegetation (overgrowth vs. cleared) as a proxy for human habitation, classified settlements into three categories: inhabited, partially abandoned, and abandoned. Analysts also classified the intact percentage of each settlement starting at 0% (totally destroyed since last assessment) and increasing in 25% intervals through 100% (completely intact but not expanded) up to 200+% (more than doubled in size) by looking for destroyed buildings. These assessments were then used to adjust previously established population estimates for each settlement. These new population distributions were compared to vaccination efforts to determine the number of children under 5 unreached by vaccination teams. RESULTS: Of the 11,927 settlements assessed 3203 were assessed as abandoned (1892 of those completely destroyed), 662 as partially abandoned, and 8062 as fully inhabited as of December of 2017. Comparing the derived population estimates from the new assessments to previous assessment and the activities of vaccination teams shows that an estimated 180,155 of the 337,411 under five children who were unreached in 2016 were reached in 2017 (70.5% through vaccination efforts in previously inaccessible areas, 29.5% through displacement to accessible areas). CONCLUSIONS: This study's methodology provides important planning and situation awareness information to health workers in Borno, Nigeria, and may serve as a model for future data gathering efforts in inaccessible regions.

Polyserositis as a Unique Presentation of Isolated Myeloid Sarcoma: A Case Report.

BACKGROUND: Myeloid Sarcoma (MS) are tumors containing myeloid blasts occurring in a location other than the bone marrow, including lymph nodes, skin, and soft tissues. MS presenting as polyserositis however is very rare, with only a few cases in the literature. CASE REPORT: A 20-year-old male presented with cough, shortness of breath and was found to have left upper lobe consolidation, left pleural effusion, pericardial effusion, and a large anterior mediastinal mass. A transthoracic echocardiogram showed pericardial effusion with tamponade physiology. He underwent emergent pericardiocentesis and thoracentesis. The fluid studies showed flow cytometry findings consistent with MS/ acute myeloid leukemia (AML) phenotype. A bone marrow aspirate and biopsy were unremarkable and showed no immunophenotypic findings diagnostic of acute leukemia or a lymphoproliferative disorder. Cytogenetics was negative for AML abnormalities per FISH analysis. Videoassisted thoracoscopy surgery (VATS) with biopsy of the mediastinal mass, pericardium, and left upper lobe of the lung was consistent with MS. He was treated with induction cytarabine and idarubicin, and a follow up PET-CT scan showed complete remission. He is currently day 200 + post stem cell transplant with no evidence of disease recurrence. CONCLUSION: To the best of our knowledge, this is the first case of isolated myeloid sarcoma presenting as polyserositis, without prior leukemia/ bone marrow involvement. Hence, fluid studies should involve cytometry analysis and MS should be entertained as a differential for polyserositis, even without a history of prior leukemia. Timely diagnosis can expedite aggressive chemotherapy required for a potentially life-threatening disease.

Using search-constrained inverse distance weight modeling for near real-time riverine flood modeling: Harris County, Texas, USA before, during, and after Hurricane Harvey.

Flooding poses a serious public health hazard throughout the world. Flood modeling is an important tool for emergency preparedness and response, but some common methods require a high degree of expertise or may be unworkable due to poor data quality or data availability issues. The conceptually simple method of inverse distance weight modeling offers an alternative. Using stream gauges as inputs, this study interpolated stream elevation via inverse distance weight modeling under 15 different model input parameter scenarios for Harris County, Texas, USA, from August 25th to September 15th, 2017 (before, during, and after Hurricane Harvey inundated the county). A digital elevation model was used to identify areas where modeled stream elevation exceeded ground elevation, indicating flooding. Imagery and observed high water marks were used to validate the models' outputs. There was a high degree of agreement (between 79 and 88%) between imagery and model outputs of parameterizations visually validated. Quantitative validations based on high water marks were also positive, with a Nash-Sutcliffe efficiency of in excess of .6 for all parameterizations relative to a Nash-Sutcliffe efficiency of the benchmark of 0.56. Inverse distance weight modeling offers a simple, accurate method for first-order estimations of riverine flooding in near real-time using readily available data, and outputs are robust to some alterations to input parameters.

Readiness for an Increase in Congenital Zika Virus Infections in the United States: Geographic Distance to Pediatric Subspecialist Care.

OBJECTIVE: The study's purpose was to investigate readiness for an increase in the congenital Zika infection (CZI) by describing the distribution of pediatric subspecialists needed for the care of children with CZI. METHODS: We applied county-level subspecialist counts to US maps, overlaying the geocoded locations of children's hospitals to assess the correlation of hospital and subspecialist locations. We calculated travel distance from census tract centroids to the nearest in-state children's hospital by state (with/without > 100 reported adult Zika virus cases) and by regions corresponding to the likely local Zika virus transmission area and to the full range of the mosquito vector. Travel distance percentiles reflect the population of children 100 miles. CONCLUSION: The travel distance to pediatric subspecialty care varies widely by state and is likely to be an access barrier in some areas, particularly states bordering the Gulf of Mexico, which may have increasing numbers of CZI cases. (Disaster Med Public Health Preparedness. 2019;13:476-486).

Polychlorinated biphenyls, indicators of thyroid function and thyroid autoantibodies in the Anniston Community Health Survey I (ACHS-I).

In this study, we examined associations between serum concentrations of 35 polychlorinated biphenyl (PCB) congeners, pesticides, and indicators of thyroid function in participants of the Anniston Community Health Survey (ACHS). Study subjects lived in the vicinity of a former PCB production facility and had PCB concentrations 2 to 3 times higher than similar age and race groups from the general population. We investigated associations among serum levels of thyroid hormones (thyroxin [T4], free thyroxin [fT4], triiodothyronine [T3], thyroid stimulation hormone [TSH]) and auto-antibodies (thyroglobulin antibody [TgAb] or thyroperoxidase antibody [TPOAb]) and combined indicators of thyroid function with the sum of PCBs, varying PCB groups, individual PCB congeners, and 8 pesticides. Logistic and linear regression models were adjusted for log10 transformed total lipids, age, sex, ethnicity, BMI, smoking, and family history of thyroid disease. We also performed analyses stratified by ethnicity and sex. Linear regression showed inverse associations between TT3 and thyroid-like PCBs (sum of PCBs 28, 52, 74, 101, 105, and 118; p = .0004), two pesticides (hexachlorobenzene, and pp'-DDE), and individual congeners (PCBs 74, 105). Null associations were observed between PCBs, pesticides, TSH, TT4, and fT4. Logistic regression analyses did not provide support for TT3 findings and found no association with other thyroid hormones, antibodies, or combined indicator of thyroid function. These results suggest there is little evidence that these chemicals have any major clinical effect on thyroid function in this highly PCB exposed population.

Liver Disease in a Residential Cohort With Elevated Polychlorinated Biphenyl Exposures.

Endocrine and metabolism disrupting chemicals (EDCs/MDCs) have been associated with environmental liver diseases including toxicant-associated steatohepatitis (TASH). TASH has previously been characterized by hepatocellular necrosis, disrupted intermediary metabolism, and liver inflammation. Polychlorinated biphenyls (PCBs) are environmental EDCs/MDCs associated with the genesis and progression of steatohepatitis in animal models and human liver injury in epidemiology studies. The cross-sectional Anniston Community Health Survey (ACHS) investigates ortho-substituted PCB exposures and health effects near a former PCB manufacturing complex. The rates of obesity, diabetes, and dyslipidemia were previously determined to be high in ACHS. In this study, 738 ACHS participants were categorized by liver disease status using the serum cytokeratin 18 biomarker. Associations between PCB exposures and mechanistic biomarkers of intermediary metabolism, inflammation, and hepatocyte death were determined. The liver disease prevalence was high (60.2%), and 80.7% of these individuals were categorized as having TASH. Sex and race/ethnicity differences were noted. TASH was associated with increased exposures to specific PCB congeners, insulin resistance, dyslipidemia, proinflammatory cytokines, and liver necrosis. These findings are consistent with PCB-related steatohepatitis. ΣPCBs was inversely associated with insulin resistance/production, leptin, and hepatocyte apoptosis, while other adipocytokines were increased. This is possibly the largest environmental liver disease study applying mechanistic biomarkers ever performed and the most comprehensive analysis of PCBs and adipocytokines. It provides insight into the mechanisms of PCB-related endocrine and metabolic disruption in liver disease and diabetes. In the future, associations between additional exposures and liver disease biomarkers will be evaluated in the ACHS and follow-up ACHS-II studies.