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Residential fires are a significant cause for morbidity and mortality in the United States. Death is often the result of soot and smoke inhalation causing carbon monoxide (CO) toxicity. The approximate lethal level of carboxyhemoglobin (COHb) in healthy adults has been well described. However, a significant number of medical examiner cases involve infirmed decedents, often elderly, with complex cardiovascular disease burdens. It is well known that death in these cases will occur at sublethal levels of COHb; however, increased lethality has been largely documented via anecdotal experience and lacks quantification. Fifty-five cases were identified where death resulted from smoke and soot inhalation suffered in a residential fire. The control group, with no cardiovascular disease, had an age-adjusted mean COHb level of 61.6% at the time of death. Presence of hypertensive cardiovascular disease showed a 30% reduction in COHb (age-adjusted mean 43.2%), atherosclerotic disease showed a 33% reduction (age-adjusted mean 41.5%), and combined disease presentation accounted for 41% reduction (age-adjusted mean 36.3%). When controlling for age, atherosclerotic and hypertensive cardiovascular diseases were each associated with statistically significant decreases in COHb (p < 0.01). Increasing age was associated with decreased COHb levels at 2.8% per 10 years of life (p < 0.01), even when modeled with hypertensive and atherosclerotic disease. These findings carry important public health significance, as well as practical significance for the medical examiner when interpreting COHb levels in cases of suspected deaths due to smoke and soot inhalation.

We assess the utility of a Centers for Disease Control and Prevention (CDC) guidelines-based coronavirus disease 2019 (COVID-19) screening checklist for postmortem severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance, detailing the relationship between the histologic findings at autopsy and attribution of death to COVID-19.SARS-CoV-2 nasopharyngeal swabs were collected at the time of autopsy in all "checklist-positive" decedents. Additional "checklist-negative" decedents were randomly tested daily. Lung slides were blindly reviewed by 3 pathologists, assessing for the presence of diffuse alveolar damage (DAD) and other findings. Sixteen decedents had positive postmortem SARS-CoV-2 nasopharyngeal swabs and underwent complete autopsies. Seven decedents had positive screening checklists. Of these, 4 had DAD and 1 had COVID-19-associated thromboembolic disease. Of the 9 decedents with negative screening checklists, 2 had DAD, but only 1 was attributed to COVID-19; the other was likely drug related. Acute bronchopneumonia was the second most common finding, and aspiration was the likely etiology in cases without concomitant DAD. COVID-19-related DAD was identified more commonly in decedents who screened positive by CDC checklist, but false-negatives did occur. Medical examiner offices should maintain a low threshold for random testing of decedents even when COVID-19 is not suspected.

AIMS: Diffuse alveolar damage (DAD) is a ubiquitous finding in inpatient coronavirus disease 2019 (COVID-19)-related deaths, but recent reports have also described additional atypical findings, including vascular changes. An aim of this study was to assess lung autopsy findings in COVID-19 inpatients, and in untreated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive individuals who died in the community, in order to understand the relative impact of medical intervention on lung histology. Additionally, we aimed to investigate whether COVID-19 represents a unique histological variant of DAD by comparing the pathological findings with those of uninfected control patients. METHODS AND RESULTS: Lung sections from autopsy cases were reviewed by three pulmonary pathologists, including two who were blinded to patient cohort. The cohorts included four COVID-19 inpatients, four cases with postmortem SARS-CoV-2 diagnoses who died in the community, and eight SARS-CoV-2-negative control cases. DAD was present in all but one SARS-CoV-2-positive patient, who was asymptomatic and died in the community. Although SARS-CoV-2-positive patients were noted to have more focal perivascular inflammation/endothelialitis than control patients, there were no significant differences in the presence of hyaline membranes, fibrin thrombi, airspace organisation, and 'acute fibrinous and organising pneumonia'-like intra-alveolar fibrin deposition between the cohorts. Fibrinoid vessel wall necrosis, haemorrhage and capillaritis were not features of COVID-19-related DAD. CONCLUSIONS: DAD is the primary histological manifestation of severe lung disease in COVID-19 patients who die both in hospital and in the community, suggesting no contribution of hyperoxaemic mechanical ventilation to the histological changes. There are no distinctive morphological features with which to confidently differentiate COVID-19-related DAD from DAD due to other causes.

We report a case of a 40-year-old female of Yemeni background who presented with abdominal pain. The pain started 14 months prior and was localized to the epigastrium, was precipitated by eating, and was of a burning and itching type. The pain occurred every 2 to 3 days, lasted for several minutes

1. Which species of Schistosoma does not stain acid fast positive? Answer: A. In Ziehl-Neelsen staining, all tissues and any microorganisms take on the carbol fuchsin stain. Cells lacking a lipid layer are decolorized by acids and lose the red color of carbol fuchsin. In acid-fast organisms, the

Sickle cell disease (SCD) is associated with a high prevalence of airway hyperreactivity (AHR) and chronic inflammation at a steady state in the absence of infection or acute sickle events; SCD patients have also been reported to have increased circulating leukotrienes (LT) (Setty et al, 2002; Jennings et al, 2008): both the pro-inflammatory LT-B4 and cysteinyl leukotrienes (cys-LTs; LT-C4, -D4 and -E4), known to promote AHR. We sought to explore the mechanisms of increased AHR in SCD. Five-lipoxygenase (5LO) is a key enzyme in LT-B4 and cysLT synthesis, we have recently reported that expression of 5LO is significantly increased in blood mononuclear cells (MNCs) in patients with SCD (Patel et al 2009). Zileuton is a specific inhibitor of 5LO that decreases LT production, is licensed for asthma and is now available in BID dosing (Zyflo CR, Cornerstone Therapeutics), but has never been tested in patients with SCD. We performed a phase 1 clinical trial to determine the safety and pharmacodynamics (PK) of twice daily administration of ZL (Zyflo CR, the study drug was provided by Cornerstone Therapeutics) in patients with SCD after obtaining an IND from the FDA. The primary objective of this study was to determine a safe and tolerable dose of ZL using a 3x3 dose escalation design of twice daily ZL for 6 weeks, with monitoring of blood counts, serum and urine chemistries, echo, EKG and clinical events. Patients 7-30 years of age with SCD at steady state that were not on hydroxyurea or chronic transfusions were enrolled. A total of 14 subjects were consented and screened for the ZL trial; 4 failed screening and 11 subjects received the study drug; 2 subjects were withdrawn due to acute sickle events. The 1200 mg BID dose that is approved for asthma was well tolerated by 3 patients; the dose was then escalated to 3000 mg/day. We found that 1800 mg alternating with 1200 mg of ZL was a safe and clinically well tolerated dose in 6 patients. No clinically significant changes of any of the clinical/laboratory safety parameters were observed from baseline values that were attributable to ZL. PK, another primary objective of this study was performed using a D-optimal sampling strategy (day 1 through week 6) and data analyzed by nonlinear mixed effects modeling (NONMEM). ZL plasma concentrations were determined by validated LC-MS/MS assay. The Cmax of ZL were 2445 ± 795 ng/ml and 2510 ± 489 ng/ml at 2400 mg/d and 3000 mg/d and the minimum zileuton exposure as measured by predose troughs were 445.0 ± 137.7 ng/ml and 703.7 ± 172.2 ng/ml at 2400 mg/d and 3000 mg/d respectively. PK details will be presented. The secondary objective was to determine the pharmacodynamics (PD) of ZL in patients with SCD. PD end points were 1. CysLT levels before and after ZL administration for 6 weeks, 2. circulating levels of inflammatory biomarkers: sVCAM, sICAM, IL-6, IL-13 and macrophage chemoattractant protein-1 (MCP-1), 3. Methacholine challenge test (MCT) for AHR and 4. fetal hemoglobin. MCT was negative in 5 of 9 of patients; It is to be noted that exclusion of patients on hydroxyurea and chronic transfusions excluded the majority of patients with moderate to severe SCD that predominantly have AHR; 4 patients had a positive MCT, 2 of them became negative after receiving ZL while there was no change in the other 2 patients. LT and inflammatory markers are under analysis. There was no increase in HbF, F cells/F-retics in any of the patients, unlike results reported in vitro in erythroid cultures (Haynes et al, Blood 2004). Our study shows the safety and PK of ZL in SCD and that a higher dose of ZL (than used for asthma) was safely tolerated by SCD patients with good compliance. This phase I trial may form the basis of a phase II/III trial of zileuton in SCD. Clinicaltrial.gov # NCT01136941. Disclosures: No relevant conflicts of interest to declare.

Reported are experiences and practical results from parallelizing the modular GCD algorithm for sparse multivariate polynomials. The strategy is to identify key computation steps in the sequential algorithm and implement them in parallel. The two major steps of the sequential algorithm—computing the GCD modulo several primes and applying the Chinese Remainder Algorithm on the integer coefficients—are easily partitioned into independent subtasks. The subtask of computing the GCD modulo one prime can be subdivided further. Several parallel strategies for the multivariate GCD modulo a prime are presented. Actual timings on a Sequent Balance with 26 processors are presented.