Initial Laboratory Research Articles

Magnetic resonance imaging features of post-COVID-19 regional and invasive sino-nasal mucormycosis

BackgroundSino-nasal mucormycosis is an opportunistic, invasive fungal disease which has shown a rising trend in the setting of COVID-19. The objective of this study is to document and analyze demographic data, clinical presentation and MR imaging spectra for early detection and management of post-COVID-19 sino-nasal mucormycosis.ResultsSixty-two cases of sino-nasal mucormycosis were enrolled in this study; their mean age was 50.65 ± 8.25 years, with significant female predominance. Nine patients (14.5%) had active COVID-19 and 53 (85.5%) were recent COVID-19 cases. Sixty patients have not received COVID-19 vaccine. The mean duration from the initial COVID-19 laboratory confirmation to the detection of sino-nasal mucormycosis was 25.7 +/− 4.6 days. Thirty-five patients (56.5%) were kept in the hospital for COVID management and 4 of them received intensive care unit (ICU) treatment. Twenty-seven patients (43.5%) were treated in home isolation. Corticosteroids were administered in 48 cases (77.4%). Twenty-nine patients (46.8%) had been given oxygen for an average time of 11.2 ± 4.15 days. Diabetes was found in 56 cases (90.3%). The most common clinical symptoms were headache, seen in 52 patients (83.87%). The ethmoid sinus was the most common paranasal sinus involved in our study, seen in 47 cases (75.81%). In 36 cases (58%), multiple sinuses were involved. MRI staging according to the extent of regional involvement. Stage 1 seen in 2 cases (3.23%), stage 2 in 13 cases (20.97%), stage 3 in 35 cases (56.45%) and stage 4 in 12 cases (19.35%).ConclusionsMRI shows a spectrum of findings in sino-nasal mucormycosis. Imaging plays a major role in staging and assessing the extent of involvement and complications. In light of this, mortality and morbidity can be dramatically decreased with adequate evaluation and therapy.

Effectiveness and costs of a stepwise versus an all-in-one approach to diagnose mild bleeding disorders.

The diagnostic work-up of patients referred to the haematologist for bleeding evaluation is performed in a stepwise way: bleeding history and results of screening laboratory tests guide further diagnostic evaluation. This can be ineffective, time-consuming and burdensome for patients. To improve this strategy, the initial laboratory investigation can be extended. In a model-based approach, effectiveness and costs of a conventional stepwise versus a newly proposed all-in-one diagnostic approach for bleeding evaluation were evaluated and compared, using data from an observational patient cohort study, includingadult patients referred for bleeding evaluation. In the all-in-one approach, specialized platelet function tests, coagulation factors, and fibrinolysis tests were included in the initial investigation. Final diagnosis, hospital resource use and costs and patient burden were compared. A total of 150 patients were included. Compared to the stepwise approach, in the all-in-one approach, 19 additional patients reached a diagnosis and patient burden was lower, but total costs per patient were higher [€359, 95% bootstrapped confidence interval (BCI) 283-518, p= 0.001]. For bleeding evaluation of patients referred to the haematologist, an all-in-one diagnostic approach has a higher diagnostic yield and reduces patient burden, at a higher cost. This raises the question what costs justify the diagnosis of a bleeding disorder and a less burdensome diagnostic strategy.

Comparison of Procalcitonin With Commonly Used Biomarkers and Algorithms for Evaluating Suspected Pediatric Musculoskeletal Infection in the Emergency Department.

It is difficult to distinguish between children with infectious versus noninfectious conditions of the musculoskeletal system during initial evaluation. Clinical predictive algorithms potentially support this effort but not without limitations. Procalcitonin (PCT) has been proposed as a biomarker to help differentiate infection from noninfection. This study evaluates the adoption and utility of PCT during initial infection evaluations and assesses test characteristics of commonly used parameters and algorithms. PCT was introduced for initial laboratory evaluation of the suspected musculoskeletal infection. Prospective enrollment occurred from July 2020 to November 2021 with 3 cohorts established after a retrospective review of final diagnoses at the end of treatment: 1) deep infection, 2) superficial infection, and 3) noninfection. Univariate and multivariate logistic regression analysis of parameters and diagnoses was performed. Test characteristics of individual and aggregated parameters were assessed. Among 258 children evaluated, 188 (72.9%) had PCT drawn during the evaluation. An increase of PCT acquisition from 67.8% to 82.4% occurred over the study timeframe. Eighty-five children were prospectively studied, including those with deep infection (n=21); superficial infection (n=10), and noninfection (n=54). Test characteristics of parameters showed accuracy ranging from 48.2% to 85.9%. PCT >0.1ng/mL independently predicted deep infection in 84.7% of cases, outperforming white blood cell, C-reactive protein (CRP), and absolute neutrophil count. Using study thresholds for CRP, erythrocyte sedimentation rate, PCT, and Temp improved accuracy to 89.4%. PCT is a potentially useful biomarker during the initial assessment of children suspected to have a musculoskeletal infection. Systematic evaluation using a combination of parameters improves the accuracy of assessment and assists predictive judgment under uncertainty. PCT <0.1ng/mL, erythrocyte sedimentation rate <18 mm/hr, CRP <3.3mg/dL, and temperature <37.8°C should reasonably reassure clinicians that deep musculoskeletal infection is less likely, given the high negative predictive value and collective accuracy of these parameters. Level III - Retrospective cohort comparison.

Characterization of collapsible gypsum sand soil with the presence of matric suction using a modified odometer apparatus

This study looks into the influence of matric suction on the volume change of gypsum sand soil in unsaturated conditions. The specimens were collected from Al-Najaf, Iraq, and included 14 and 29% gypsum. Three series of initial stress laboratory tests were utilized in a modified oedometer device. For each gypsum content, twelve remolded specimens were examined in unsaturated circumstances with the initial stress and applied stress using four matrices suction (30 kPa, 18 kPa, 9 kPa, and saturated state). Three tests were performed for each matric suctions with initial stresses, no initial load, 56 and 112 kPa, respectively. The findings exhibit a clear pattern of increase in the vertical strain as gypsum content rises and matric suction reduces under a variety of situations. The wetting process softens the gypsum components, which are significantly resulting in an increase in vertical strains.

To Repeat or Not Repeat, That Is the Question: Von Willebrand Testing in Adolescent Girls with Heavy Menstrual Bleeding

Heavy menstrual bleeding (HMB) is often the initial manifestation of a bleeding disorder in adolescent females. Von Willebrand disease (VWD) is the most common bleeding disorder, yet diagnosing VWD in HMB is challenging given that menstruation, acute illness, and physiologic stress all elevate von Willebrand factor (VWF) laboratory values. Thus, the interpretation of initial VWF results may be challenging, and the need for repeat VWF testing in this population may be unclear. The aims of this study were to understand VWD diagnostic testing patterns in adolescent females evaluated within the Texas Children's Hospital (TCH) network and to develop a prediction model to determine whether repeat testing was indicated based on initial VWF testing results. Female patients aged 9 to 21 years who had any VWF laboratory test over a 5-year period (January 1, 2017 through December 31, 2021) at a TCH facility (greater Houston metroplex) were identified. Data collection included patient demographics, VWF-related testing (antigen and activity [ristocetin cofactor or glycoprotein Ib]), factor VIII activity, hemoglobin concentration and serum ferritin. Both initial and subsequent laboratory evaluations were collected. The site of clinical testing was also identified, including both acute care settings (emergency department, inpatient, and critical care), and outpatient settings (adolescent medicine, gynecology, hematology, otolaryngology, other outpatient TCH primary care clinics). To ensure that subsequent laboratory testing was not mistaken as the initial testing within the cohort, patients who underwent VWF laboratory testing from 2010 to 2016 were excluded. VWF levels obtained after the administration of VWF replacement products were also removed from the data set. Based on the ASH ISTH NHF WFH 2021 guidelines on the diagnosis of VWD, and with the presumption that adolescents with HMB met the criteria for abnormal bleeding, we analyzed the need to repeat VWF testing to identify any patient with a low VWF antigen level consistent with Type 1 VWD, defined as <50%. A Bayesian linear regression model was developed to predict follow-up VWF antigen levels using the initial levels. Prediction intervals were analyzed to identify thresholds for patients who may not require retesting. This study was approved by the Baylor College of Medicine Institutional Review Board. A total of 6,125 adolescent females underwent VWD testing at a TCH facility during the study period; 1,204 (19.7%) had repeat VWF antigen values performed and were included in the analysis (TABLE). Of those, 1,037 subjects (86.1%) had normal VWF values (≥50%) on both initial and repeat testing. Seventy-five subjects (6.2%) had low VWF antigen values on both initial and repeat testing. Ninety-two subjects had discrepant initial and repeat testing. Forty-seven (3.9%) had low initial VWF antigen values that normalized on subsequent testing. Forty-five (3.7%) had normal initial VWF values that subsequently fell below 50%. Based on our prediction model, in subjects with initial VWF antigen values of ≥80% there was ≥97% probability of having normal repeat VWF values. Values of ≥100% carry a 99.4% probability of having normal repeat VWF testing (FIGURE). No association was identified between age and VWF antigen level. Subjects assessed in outpatient adolescent medicine or gynecology clinics were more likely to have low VWF values (on any testing) whereas subjects with normal values were more frequently assessed in the acute care settings (P<0.001). The median serum ferritin and hemoglobin values in the cohort were 13 ng/ml and 12.8 g/dl, respectively, without a significant difference between those with normal versus low VWF antigen values. Repeat testing in adolescent females whose initial VWF antigen testing values are 80% and higher is unlikely to identify more patients with VWF values below 50%. In this cohort, subjects undergoing hemostatic evaluation, presumably for HMB, by adolescent medicine or gynecology providers were more likely to identify abnormal VWD testing compared to the acute care setting. Iron deficiency screening should be considered for all adolescent females with HMB and not just those girls with a confirmed bleeding disorder. Additional studies are needed to determine the effects of iron deficiency and anemia on VWD laboratory testing in adolescent females with HMB and to validate the accuracy of the prediction model. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

COVID-19 Associated Atypical Hemolytic Uremic Syndrome

Introduction: Atypical hemolytic uremic syndrome (atypical HUS) is a complement-mediated thrombotic microangiopathy (TMA) that affects multiple organs including the kidneys. We present a case of 37-year-old male with recent COVID-19 infection who presented with epistaxis. His blood work was consistent with TMA and acute kidney injury (AKI). Hemodialysis and plasmapheresis (PLEX) were initiated for presumed thrombotic thrombocytopenic purpura (TTP) but after excluding ADAMTS-13 deficiency, eculizumab was started for possible atypical HUS. Renal biopsy and genetic testing ultimately confirmed diagnosis of atypical HUS. Case presentation: A 37-year-old male with past medical history of recent COVID infection presented to the emergency room with complaint of epistaxis. Physical exam showed mild epistaxis from right naris and bilateral leg swelling. Initial laboratory findings were hemoglobin (Hb) 5 g/dL, platelets 70 B/L, Lactate dehydrogenase (LDH) 581 IU/L, haptoglobin < 10 mg/dL, creatinine (Cr) 36.80 mg/dL, blood urea nitrogen (BUN) 232 mg/dL, potassium (K) 6.6 mmol/L, calcium (Ca) 6 mg/dL and normal prothrombin time (PT) and partial thromboplastin time (PTT). Complement C3 levels were low but normal C4 levels. Peripheral blood smear showed schistocytes confirming TMA. He was started on both PLEX and hemodialysis (HD) along with prednisone 80 mg daily. PLEX was stopped on day 4 after normal ADAMTS-13 levels resulted, helping rule out TTP. Based on history and laboratory findings, diagnosis of atypical HUS was favored and eculizumab was started. He received meningococcal vaccine and prophylactic penicillin while on eculizumab. Hemodialysis was continued with eventual improvement of his labs to Hb 7, platelets 119, LDH 339, haptoglobin < 10, Cr 9.07, BUN 85, K 5.8, and Ca 8.0. He was discharged on bimonthly dose of eculizumab and hemodialysis three times a week. Two months later, his labs were Hb 10.4, platelets 184, LDH 490, haptoglobin < 10, Cr 11.60, BUN 82, K 5.2, and Ca 9.2. PT and PTT remained normal. Given persistence of laboratory findings, renal biopsy and genetic testing for complement proteins was done. Kidney biopsy showed diffuse global renal microangiopathy with negative C3. Genetic testing showed a heterozygous C3 variant, homozygous deletion of CFHR1-CFHR4, negative factor H autoantibodies (FHAA), and single nucleotide variant in C5 gene. Discussion: Atypical HUS is a disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and AKI. The complement system is a part of the immune system that enhances the ability of phagocytic cells to clear microbes and damaged cells. Atypical HUS is caused by dysregulation of the alternative complement pathway that leads to microvascular thrombosis. Various mutations in complement and its regulatory proteins have been discovered in atypical HUS patients. Heterozygous C3 variants result in persistently low C3 levels and cause severe disease. Most individuals with a homozygous deletion of CFHR1 and/or CFHR3, CFHR4 genes have a pathogenic role in the development of the anti-factor H autoantibodies. These autoantibodies interfere with the binding of CFH to the C3 convertase and are associated with defective CFH-dependent cell protection. Some case reports of COVID-19 patients showed that complement activation was significantly stronger in lung alveolar septa, hyaline membranes, and in alveolar lumina via the lectin and alternative complement pathways. Treatment of atypical HUS is symptomatic but in severe disease eculizumab or ravulizumab have roles by binding to the complement protein C5, inhibiting its cleavage to C5a and C5b, and preventing formation of terminal complement complex C5b-9. Patients on these therapies are at risk of meningococcal disease, thus it is recommended to get meningococcal vaccines and prophylactic penicillin for the duration of therapy. Our patient had homozygous deletion of CFHR1-CFHR4 genes with no factor H autoantibodies. However, he did have C3 variant with gain of function mutation which caused overt activation of alternative pathway as indicated by his low C3 levels with normal C4 levels. He responded partially to eculizumab and discussion on possible kidney transplant has been started.

Use of Clinical Decision Support to Improve the Laboratory Evaluation of Monoclonal Gammopathies

Introduction: Since its introduction in 2001, the serum free light chain (sFLC) assay has played an increasingly prominent role in the initial clinical evaluation of patients with suspected monoclonal gammopathies (MGs). This is primarily due to its superior sensitivity for detecting monoclonal proteins especially in light chain disease. In 2009, the International Myeloma Working Group (IMWG) recommended ordering the combination of an SPEP, sFLC and sIFE for initial screening for all MGs. However, there is still significant heterogeneity in sFLC ordering practices. A recent survey of over 700 clinical laboratories found that sFLC were included in the most common screening order sets for the initial evaluation of MGs in only 19.7% of centers. Methods: We performed a retrospective analysis of SPEP and sFLC ordering practices at our institution over a 6-year period (2014-2019). We then designed and implemented a clinical decision support (CDS) alert to improve compliance with IMWG's recommendations. The alert fires when a provider orders an SPEP without a concurrent sFLC order or result in the last 30 days and suggests the ordering of sFLC. We analyzed the impact on ordering practices and diagnostic outcomes over the course of a 10-month period. Results: Our retrospective analysis of over 90,000 SPEP results, associated sFLC orders, and ICD-10 codes revealed that many providers deviated from society guidelines for the use of sFLC in the initial laboratory evaluation of MGs. Prior to the alert 62.8% of all SPEP evaluations included sFLC testing, while post-implementation nearly 90% of evaluations included sFLC (Figure 1). When restricting our analysis to patients with no prior sFLC results, we found that the alert contributed to the clinical care of as many as 2,791 patients. Twenty nine percent (810/2,791) of these patients had an abnormal kappa/lambda ratio (rFLC). In 462 of these patients the rFLC was the only laboratory evidence of a monoclonal protein (Table 1). Moreover, within this population there were numerous instances of new diagnoses of multiple myeloma and other MGs. Conclusions: In the initial laboratory evaluation of MGs, a CDS alert was an effective tool to increase clinical practice compliance with society guidelines. More importantly, the alert prompted sFLC orders that contributed to the diagnosis of numerous MGs that may have been missed or warrant further investigation and follow up. This study will hopefully serve as a useful guide for other institutions addressing the gap between clinical practice and evidence-based guidelines. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Quotidian Fever in Secondary Hemophagocytic Lymphohistiocytosis Due to Diffuse Large B-Cell Lymphoma: A Case Report

Hemophagocytic lymphohistiocytosis (HLH) is a highly fatal syndrome characterized by excessive abnormal activation of the immune system. Fever is the most encountered clinical feature and is found in 100% of HLH cases (Al-Samkari & Berliner, 2018) Fever patterns can be an important clinical clue in certain diseases but have not been described in HLH. We report a 74-year-old Caucasian female patient who presented with fever, fatigue, and dyspnea on exertion of 2 months duration. On examination, she was found to be febrile, hypoxic, and disoriented. Initial laboratory workup was significant for normocytic anemia (6.3 g/dl) with severely elevated Ferritin (1501 µg/dL). Infectious and autoimmune workup was negative. Full body CT scan was negative for malignancy or lymphadenopathy but showed mild splenomegaly. The hospital course was complicated by worsening respiratory status despite empiric antibiotic treatment. She was noted to have persistent daily fever spikes in the early hours of the morning. This prompted workup for HLH which revealed rising serum ferritin, hypertriglyceridemia, elevated soluble IL-2 and low NK cell activity receptors, fulfilling the criteria of HLH. Bone marrow aspirate revealed clonal CD20 positive lymphocyte diagnostic of DLBCL as the trigger for HLH. The patient was started on HLH protocol and mini R-CHOP protocol with marked improvement in her symptoms and anemia. Little is known about the patterns of fever in HLH patients. Before this case, two other case reports described quotidian fever in HLH (Kouides et al., 2021; Henter et al., 2007). interestingly both were cases of secondary HLH. This case illustrates the possible association between HLH and quotidian fever and proposes the possibility of quotidian fever being a clinically important clue to secondary causes of HLH. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Updates on the Diagnosis and Treatment of Peripheral Autonomic Neuropathies.

Autonomic neuropathies are a complex group of disorders and result in diverse clinical manifestations that affect the cardiovascular, gastrointestinal, urogenital, and sudomotor systems. We focus this review on the diagnosis and treatment of peripheral autonomic neuropathies. We summarize the diagnostic tools and current treatment options that will help the clinician care for individuals with peripheral autonomic neuropathies. Autonomic neuropathies occur often in conjunction with somatic neuropathies but they can also occur in isolation. The autonomic reflex screen is a validated tool to assess sympathetic postganglionic sudomotor, cardiovascular sympathetic noradrenergic, and cardiac parasympathetic (i.e., cardiovagal) function. Initial laboratory evaluation for autonomic neuropathies includes fasting glucose or oral glucose tolerance test, thyroid function tests, kidney function tests, vitamin-B12, serum, and urine protein electrophoresis with immunofixation. Other laboratory tests should be guided by the clinical context. Reduced intraepidermal nerve density on skin biopsy is a finding, not a diagnosis. Skin biopsy can be helpful in selected individuals for the diagnosis of disorders affecting small nerve fibers; however, we strongly discourage the use of skin biopsy without clinical-physiological correlation. Ambulatory blood pressure monitoring may lead to early identification of patients with cardiovascular autonomic neuropathy in the primary care setting. Disease-modifying therapies should be used when available in combination with nonpharmacological management and symptomatic pharmacologic therapies. Autonomic function testing can guide the therapeutic decisions and document improvement with treatment. A systematic approach guided by the autonomic history and standardized autonomic function testing may help clinicians when identifying and/or counseling patients with autonomic neuropathies. Treatment should be individualized and disease-modifying therapies should be used when available.

CNSC-03. NEURONAL INTERMEDIATE FILAMENT (NIF) ANTIBODY POSITIVE PARANEOPLASTIC SYNDROME IN A PATIENT WITH METASTATIC NEUROENDOCRINE PANCREATIC CARCINOMA AND TREATMENT WITH IPILIMUMAB/NIVOLUMAB

Abstract Immune checkpoint inhibitors, such as ipilimumab (CTL-4) and nivolumab (PD-1) have shown effectiveness in many types of neoplasia. This combination has been used as salvage immunotherapy for high grade metastatic pancreatic carcinoma. Nevertheless, severe neurologic immune-mediated adverse effects can result from the use of this treatment. We present a case of a 64-year-old woman with metastatic neuroendocrine pancreatic carcinoma with abrupt left facial and oculomotor cranial nerve palsy as well spastic tetraplegia after one dose of ipilimumab/nivolumab. She had a history of sudden onset diplopia, fever and ground-level fall a few hours after her initial dose of immunotherapy. Initial laboratory assessment showed pronounced lymphocyte predominant leukocytosis and mild chronic hyponatremia. In the following hours, she developed right mydriasis, right sided fast phase nystagmus and right central facial paralysis along with weakness and spasticity in four extremities. Neuroimaging of brain, orbits and CTL spine showed enhancement of intra-orbital and intracranial optic nerves as well chiasm, linear enhancement from C4-C7 and cauda equina, as well as abnormal signal along thoracic spinal cord and conus medullaris. Routine EEG demonstrated non-etiology specific encephalopathy. Lumbar puncture had normal opening pressure, mild pleocytosis, hyper-proteinorrhachia and normal glucose. Viral panel and cytology in the CSF were negative, and myeline basic protein was elevated. She was treated with high dose steroids which improved overall strength and CN palsies. Twenty days after initial presentation, she suddenly developed hypotension, tachypnea, and altered cognition. The patient and family opted for comfort measures only. She passed away that same day. Late report of CSF antibody panels showed positive cell-based assay for heavy and light chain NIF with a titer of 1:512. This case emphasizes the importance of recognition of anti-body mediated paraneoplastic syndromes in patients treated with immunotherapy, their appropriate treatment and prognosis.

Postoperative outcomes of resectable periampullary cancer accompanied by obstructive jaundice with and without preoperative endoscopic biliary drainage.

Preoperative biliary drainage (PBD) is useful in resectable periampullary cancer with obstructive jaundice. Whether it is better than direct surgery (DS) in terms of postoperative complications and mortality is controversial. All cases of successful pancreaticoduodenectomy (PD) in patients with periampullary cancer with obstructive jaundice performed between January 2016 and January 2021 were retrospectively reviewed. Endoscopic PBD was performed; data pertaining to serum bilirubin level, procedural technique, and duration before surgery were obtained. The incidence of postoperative complications and survival rate were compared between the PBD and DS group. A total of 104 patients (PBD, n = 58; DS, n = 46) underwent curative PD. The mean age was 63.8 ± 10 years and 53 (51%) were male. Age, body mass index (BMI), sex, Eastern Cooperative Oncology Group status, presence of comorbid disease, initial laboratory results, and pathological diagnoses were not significantly different between the two groups. The incidence of postoperative complications was 58.6% in the PBD group while 73.9% in the DS group (relative risk [RR] 1.26, 95% confidence interval [CI] 0.92, 1.73, p=0.155) and the difference was not significant except in bile leakage (RR 8.83, 95% CI 1.26, 61.79, p = 0.021) and intraoperative bleeding (RR 3.97, 95% CI 0.88, 17.85, p = 0.049) which were higher in the DS group. The one-year survival rate was slightly less in the DS group but the difference was not statistically significant. The independent predictors for death within 1-year were intraoperative bleeding and preoperative total bilirubin > 14.6 mg/dL. PBD in resectable malignant distal biliary obstruction showed no benefit in terms of 1-year survival over DS approach. But it demonstrated the benefit of lower risks of intraoperative bleeding, and bile leakage. Additionally, the level of pre-operative bilirubin level of over 14.6 mg/dL and having intraoperative bleeding were associated with a lower 1-year survival in such patients. Overall, PBD may be not necessary for all resectable periampullary cancer patients, but there might be a role in those with severely jaundice (>14.6 mg/dL), as it helps lower risk of intraoperative bleeding, and might lead to a better survival outcome.

Incidence of Heparin Induced Thrombocytopenia (HIT) in patients with severe COVID-19

Abstract Introduction To prevent and treat thrombotic complications in patients hospitalized with severe COVID-19 infection, anticoagulation treatments primarily with heparin and low molecular weight heparin have been recommended. Heparin-induced thrombocytopenia (HIT) is a rare but conceivably fatal reaction to heparin that is characterized by a sudden drop in platelet count accompanied by new onset of thrombosis 4-10 days after heparin exposure. The purpose of this retrospective study was to investigate the prevalence of thrombocytopenia and HIT in hospitalized COVID-19 patients, as well as their association with mortality. Methods 3,672 plasma samples were collected from patients admitted to the first wave of COVID-19 in our institution at New York City (March to May 2020). All patients admitted with a platelet count of less than 150 k/ul were assigned to the thrombocytopenic group. In addition, two groups with similar demographics and normal platelet counts were randomly selected based on discharge outcome: alive vs. deceased (n= 88 per group). PF4 IgG Elisa and heparin neutralization were carried out in accordance with the manufacturer's instructions. A positive HIT result required an optical density (OD) greater than 0.4 and heparin neutralization greater than 50%. Statistical analysis was done in R studio (V.1.4.1717) to analyze demographics (age, gender, ethnicity), initial laboratory data, anticoagulation on admission, and thrombosis. Results Only 86 of the 3,672 (2.3%) patients admitted had thrombocytopenia. Only 1 of the 86 patients tested positive for HIT (1.1% ). 4 cases of the non-survivors (4.5%) tested positive for HIT compared to none of the survivors in the two groups with normal platelet counts. One of these 4 cases had a history of thrombosis (DVT). Interestingly, the PF4 Elisa ODs in non-survivors were significantly higher than in survivors (0.09 vs. 0.06, p-value&amp;lt; 0.001). Although the platelet count did not differ significantly between the two groups, the mean platelet volume (MPV) on admission and its maximum peak during hospitalization were significantly higher in non-survivors than in survivors. Conclusions We only found HIT positive cases among non-survivors, implying that HIT is associated with COVID severity. The incidence of HIT in severe COVID-19 patients appears to be higher than the pre-COVID-19 historical rates of HIT in hospitalized patients (&amp;lt;1%). Although thrombocytopenia is relatively uncommon in COVID-19 patients, the MPV was significantly higher in non-survivors, suggesting that platelet activation and destruction may explain the higher rate of HIT in COVID-19.

Abstract 10966: Autoimmune Limbic Encephalitis Mimicking Inferior Myocardial Infarction on ECG

Case Presentation: A 64 year-old man was brought to the emergency department (ED) after being found down, awake, but unresponsive by family. In the ED, he denied chest pain and shortness of breath. His past medical history included coronary artery disease status-post coronary artery bypass grafting, heart failure with reduced ejection fraction, and paroxysmal atrial fibrillation. On physical exam, he was hemodynamically stable, oriented to self and place with no other significant neurological findings. The field and ED electrocardiograms (ECGs) (Figure 1) were consistent with an acute inferior ST elevation myocardial infarction (STEMI). The patient underwent emergent coronary angiography via left heart catheterization which showed no acute lesions requiring intervention. Initial pertinent lab work included a peak troponin-I of 0.095 ng/mL and serum sodium of 126 mmol/L. Collateral information revealed that the patient has progressive memory loss and intermittent episodes of hand tremors with non-purposeful eye movements. He also had a witnessed faciobrachial dystonic seizure, which is pathognomonic for Leucine-rich, Glioma Inactivated-1 (LGI-1) autoimmune encephalitis. Serum and CSF analyses were positive for LGI-1 IgG antibodies, confirming the diagnosis. The patient was treated with high-dose steroids, IVIG, and valproic acid with improvement in seizure activity and cognitive status, and discharged on prednisone and levetiracetam. Discussion: Per review of the current literature, central nervous system pathology may induce sympathetic overactivity causing transient myocardial injury, referred to as neurogenic stunned myocardium. This can manifest as left ventricular dysfunction, myocardial injury, and/or ECG changes consistent with myocardial infarction. This case presentation highlights an example of a seizure leading to neurogenic stunned myocardium with an ECG showing an acute inferior STEMI.

Abstract 13860: Heart Failure With Preserved Ejection Fraction Induced by Amyloid Light Chain Amyloidosis: A Case Report

Introduction: Cardiac amyloidosis is a clinical disorder defined as an extracellular deposition of protein in the heart. Typically, signs and symptoms of heart failure develop in the advanced disease. High index of suspicion is required for the diagnosis of this disorder. Results: A 62 years old male came to the cardiology clinic due to lower extremity edema, fatigue, dyspnea on exertion. He had a 3 month history of progressive lower leg edema. On physical examination he had a positive S4; lung sounds were diminished and there was dullness to percussion over the lower two thirds; and bilateral lower extremity edema. Hospital admission was decided for management of decompensated heart failure. On admission, the surface ECG showed normal sinus rhythm with low QRS voltage in the limb leads, a RBBB and LPFB. Initial laboratory reported elevated NT-proBNP: 13,816 pg/mL. Chest x-ray demonstrated right interstitial infiltration and bilateral pleural effusion. The echocardiogram revealed severe concentric hypertrophy of the left ventricle, an apical sparing left ventricle longitudinal strain, and an ejection fraction of 68%. A cardiac MRI showed concentric biventricular hypertrophy associated with extensive diffuse late gadolinium enhancement, suggestive of cardiac amyloidosis. Screening resulted in a Perugini score of 1 on Tc-PYP scintigraphy, elevated Kappa and Lambda light chains on serum, and kidney biopsy positive for amyloidosis. Hematology-oncology consultation was done and a daratumumab-CyBorD protocol was started. Conclusions: This case elucidated a stepwise diagnostic approach of cardiac amyloidosis in a patient presenting with signs and symptoms of heart failure. Amyloid AL cardiac amyloidosis and its repercussions are severe because it not only compromises by being infiltrative but also by its toxic capacity. A high index of suspicion and a multidisciplinary approach is needed in order to improve quality of life and prolong survival.

Initial Laboratory Values Can Predict Mortality in Burn Patients.

There are several burn scores used to predict mortality in burn patients. However, minimal data exists on the role of laboratory values in risk stratification. We hypothesized that laboratory derangements seen on admission can predict mortality in burn patients. A retrospective chart review was conducted on burn patients admitted to a busy Level 1 Trauma and Burn Center from 2013 to 2019. Data analysis included patients with partial or full thickness burns and a total body surface area (TBSA) burn greater than 15%. Exclusion criteria included patients presenting with electrical burns, non-thermal conditions (Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, or soft tissue infections) or patients with significant polytrauma. 112 patients were included in the analysis. Admission phosphate, creatinine, albumin, and glucose levels were associated with mortality. There was a difference in serum phosphate (3.48 and 6.04 mg/dL), creatinine (0.85 and 1.13 mg/dL), albumin (3.26 and 2.3 mg/dL), and glucose (138 and 233 mmol/L) levels for survivors and non-survivors; respectively. There were increased mortality rates seen in patients presenting with abnormal serum levels compared to normal serum levels (Phosphate: 7.5% vs. 53.3%, creatinine: 13.5% vs. 38.9%, albumin: 38.5% vs. 8.10% and glucose: 10.1% vs. 31.6% (normal vs. abnormal; respectively)). Serum sodium, potassium, and hemoglobin levels had no association with mortality. Specific laboratory derangements seen on admission are associated with an increased risk for mortality. This can be used as a framework for future studies in risk stratification of burn victims.

Young patient with thunderclap headache, seizure activity, and fixed eye deviation.

A 39-year-old female with a history of iron deficiency anemia presented to the emergency department (ED) with a 3-hour history of severe headache followed by acute-onset projectile non-bilious, non-bloody vomiting, acute mental status change, and seizure-like activity. The onset of the headache was spontaneous and described as the worst headache of her life. Vomiting and seizure-like activity began several hours after the onset of headache, and emergency medical services (EMS) were called at that time. The patient was found to be unresponsive by EMS. Upon arrival to the ED, the physical examination was notable for fixed left eye deviation, intermittent withdrawal from noxious stimuli, and spells of sustained clonus in the lower extremities greater on the left than the right. The patient was given 2-mg intravenous lorazepam with minimal improvement in the tonic–clonic activity. The patient was hemodynamically stable and had an oxygen saturation of 98% on room air. Initial laboratory test results were significant for anemia (hemoglobin = 5.2 g/dL, hematocrit = 21%) and elevated platelets (426.5). Computed tomography (CT) of the head, CT angiogram of the head and neck, CT venogram of the head, and urgent neurology consult were obtained immediately after arrival to the ED. The patient continued to decline after CT and was intubated for airway protection. Imaging was suggestive of acute venous sinus thrombosis extending from the superior sagittal sinus to the right cranial jugular vein with no definite intracranial hemorrhage (Figures 1 and 2) and bilateral segmental and subsegmental pulmonary emboli (Figure 3). This case describes a typical presentation of cerebral venous sinus thrombosis (CVST). CVSTs are more commonly seen in women aged 30–50 years.1 Commonly, sinus thrombosis can lead to subarachnoid hemorrhage with a subsequent “thunderclap” headache that can lead to neurological symptoms.3 Neurology evaluated the patient in the ED, and the patient was taken to the operating room for an aspiration thrombectomy and started on a continuous heparin infusion. The patient had gradual improvement of symptoms after 1 week of inpatient care in the neurology intensive care unit. At discharge, she was started on indefinite anticoagulation and levetiracetam for seizure prophylaxis. Further workup showed no evidence of hypercoagulability, no recent trauma, and no oral contraceptive use. CVST is defined as occlusion of dural sinuses leading to decreased venous flow, an increase in intracranial pressure, decreased cerebral perfusion pressures, and dilation of the cerebral veins. Continued hypoperfusion can result in ischemic tissue damage, resulting in acute neurologic symptoms such as seizures, headaches, altered mental status, and increased intracranial pressure. Without treatment, the thrombus can damage vessel walls, increasing the chances of vessel rupture, leading to subarachnoid hemorrhages and decreased cerebrospinal fluid outflow.1 Common risk factors for CVSTs include recent trauma, malignancy, thrombophilia, infection, obesity, oral contraceptive use, and increased estrogen states such as pregnancy.2

PREHOSPITAL CRYSTALLOID RESUSCITATION: PRACTICE VARIATION AND ASSOCIATIONS WITH CLINICAL OUTCOMES.

Introduction: Although resuscitation guidelines for injured patients favor blood products, crystalloid resuscitation remains a mainstay in prehospital care. Our understanding of contemporary prehospital crystalloid (PHC) practices and their relationship with clinical outcomes is limited. Methods: The Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial data set was used for this investigation. We sought to identify factors associated with PHC volume variation and hypothesized that higher PHC volume is associated with worse coagulopathy and a higher risk of acute respiratory distress syndrome (ARDS) but a lower risk of acute kidney injury (AKI). Subjects were divided into groups that received <1,000 mL PHC (PHC<1,000) and ≥1,000 mL PHC (PHC≥1,000); initial laboratory values and outcomes (ARDS and AKI risk) were summarized with medians and interquartile ranges or percentages and compared using Wilcoxon rank-sum tests and chi-square tests. The primary outcome was ARDS risk. Multivariable regression was used to characterize the association of each 500 mL aliquot of PHC with initial laboratory values and clinical outcomes. Results: PHC volume among study subjects (n = 680) varied (median, 0.3 L; interquartile range, 0-0.9 L) with weak associations demonstrated among prehospital hemodynamics, intubation, Glasgow Coma Score, and Injury Severity Score (0.008 ≤ R2 ≤ 0.09); prehospital time and enrollment site explained more variation in PHC volume with R2 values of 0.2 and 0.54, respectively. Compared with PHC<1,000, PHC≥1,000 had higher INR, PT, PTT, and base deficit and lower hematocrit and platelets. The proportion of ARDS in the PHC≥1,000 group was higher than PHC<1,000 (21% vs. 12%, P < 0.01), whereas the rate of AKI was similar between groups (23% vs. 23%, P = 0.9). In regression analyses, each 500 mL of PHC was associated with increased INR and PTT, and decreased hematocrit and platelet count (P < 0.05). Each 500 mL of PHC was associated with increased ARDS risk and decreased AKI risk (P < 0.05). Conclusion: PHC administration correlates poorly with prehospital hemodynamics and injury characteristics. Increased PHC volume is associated with greater anemia, coagulopathy, and increased risk of ARDS, although it may be protective against AKI.

PMON318 Nephrogenic syndrome of inappropriate antidiuresis in a 19 months old child with gross developmental delay

Abstract Case report 19 months old African American boy with nonsignificant past medical history presented with inability to walk, hypotonia chewing difficulties and speech delay. Initial laboratory evaluations demonstrated serum hyponatremia of 120-129 mEq/dl, low serum osmolality 261 mosm/kg (normal serum osmolality 275-295 mosm/kg) with inappropriately high urine osmolality 445 mosm/kg) (normal urine osmolality 300-1000 mosm/kg). Blood work for thyroid, adrenal, and pituitary function was unremarkable. Vasopressin level of 2.4 pg/ml (normal 0.0 - 4.7 pg/mL) did not support the diagnosis of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH). Fludrocortisone challenge test ruled out aldosterone deficiency with insufficient decrease in urine sodium and no response in serum sodium. Renal ultrasound and brain MRI were normal. Genetic testing revealed AVPR2 X-linked mutation c.409C&amp;gt;T p.R137C, consistent with nephrogenic syndrome of inappropriate antidiuresis (NSIAD). The patient was discharged on sodium chloride tablets 2g every 8 hours and remained stable, asymptomatic. One month after discharge patient showed significant neurological improvement. Discussion Sodium is known to play a significant role in growth and maturation of the whole body, especially of the nervous system. Moderate (120-129 mEq/L) to severe (&amp;lt;120 mEq/L) hyponatremia can present with nausea, malaise, headache, lethargy, motor and speech delay, seizures and even death due to brain herniation. Normal fluid and electrolyte balance is achieved by the thirst mechanism and free water excretion in kidneys. This is mediated by Vasopressin, which acts through V2R receptor in distal renal collecting duct. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia. Reset osmostat syndrome with a congenitally low serum osmolality threshold is one of the rare disorders on the differential. Hereditary nephrogenic syndrome of inappropriate antidiuresis is very rare mutation in vasopressin receptor, which clinically resembles SIADH except for normal/low vasopressin levels in set of hyponatremia. It causes gain of function and inappropriately high water retention. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PMON129 Pituitary Adenoma Co-Secreting GH, Prolactin and ACTH

Abstract Background Pituitary adenomas co-secreting GH, Prolactin and ACTH are rare. Clinical Case A 38-year-old male with a past medical history of depression and type 2 diabetes mellitus was seen in the endocrinology clinic for an evaluation of acromegaly. In the preceding four years, the patient had experienced an enlargement of his hands and feet, hyperhidrosis, development of an underbite, snoring, daytime somnolence, erectile dysfunction, headaches, and blurry vision. His visual fields were normal. Physical exam: BP 137/85, BMI 39 kg/m2. He had coarse facial features, acral changes of his hands and feet, and wide spacing of his teeth. There was a notable absence of facial plethora, abdominal obesity with thin extremities, proximal muscle weakness, purple abdominal striae, and galactorrhea. Initial laboratory results: GH 16.9 ng/mL (0.05-3 ng/ml), IGF-1 1,109 ng/mL (82-242 ng/mL), Prolactin (PRL) 96.9 ng/ml (5-20 ng/ml), testosterone 34 ng/dL (200-1000 ng/dL), LH 2.3 miu/ml (1.4–12 miu/ml), FSH 4.8 miu/ml (1.5-12 miu /ml), ACTH 197.6 pg/mL (7.2- 63.3 pg/mL), 0800 cortisol 16.2 ug/dL (5-29 ug/dL), 24-hour urine free cortisol 56.84 mcg (3.5-40 mcg), HS salivary cortisol 0.242 (&amp;lt;0.359 ug/dL), overnight 1 mg Dexamethasone suppression test cortisol 6.9 mcg/dL (&amp;lt; 1.8 mcg/dL), normal Free T4 and TSH, and A1c 9.7%. A pituitary MRI revealed a 3.9 cm lobulated, intra and supra-sellar mass with mass effect on the optic chiasm and 75% encasement of the left supra-clinoid internal carotid artery. Neurosurgery performed an endoscopic, endonasal partial resection of the pituitary tumor. The histology was diagnostic of an adenoma, and immunohistochemical staining was positive for GH and PRL, but not ACTH. Post-op lab results: GH 1.07 ng/ml, IGF-1 353 ng/ml, PRL 9.6 ng/ml, testosterone 41 ng/dL, ACTH 68.2 pg/ml, cortisol 4.5 ug/dL, 24-hr urine free cortisol 8 mcg, HbA1c 5.7%. Discussion The intent of this case presentation is to report the rare finding of a pituitary tumor co-secreting GH, ACTH, and Prolactin. The diagnosis of acromegaly was confirmed by significant elevations of GH and IGF-1. The diagnosis of subclinical Cushing's disease was confirmed by elevated ACTH level, 24-hr urine free cortisol, and failed dexamethasone suppression test. The elevated PRL may have been due to tumor PRL secretion or stalk effect. The reduction of these parameters after surgery corroborated the presence of pleurihormonal secretion. This patient's findings support screening for co-secretion of multiple pituitary hormones in patients with acromegaly. Reference Pleurihormonal ACTH-GH Adenoma: Case Report and Systematic Literature Review World Neurosurg 2018 114: 158-164 Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PSUN249 Starvation Ketoacidosis as the Presenting Finding of Glycogen Storage Disorder Type III

Abstract A 30-year woman with a history of heart transplantation and a history of post-transplant diabetes mellitus presents with severe euglycemic ketoacidosis. Initial concern was for diabetes related ketoacidosis given history of diabetes however blood glucose was within goal range in the absence of pregnancy and use of sodium glucose transporter type 2 inhibitor use. Initial laboratory evaluation showed a serum glucose of 177 mg/dL, a serum beta hydroxybutyrate of greater than 12.66 mmol/L, serum lactate of 0.6 mmol/L, with a calculated anion gap of greater than 30 mmol/L. C-peptide levels were repeatedly normal and appropriate for blood glucose level ranging between 2.8 ng/mL and 7.5 ng/mL ruling out insulin deficiency as causative. It was discovered that the patient had intentionally fasted for greater than 18 hours and thus had not used the premixed insulin regimen prescribed. Metabolic disturbance corrected with a dextrose and insulin infusion. Evaluation for inborn error of metabolism showed: acylcarnitine panel returned normal making an inborn error of fatty acid metabolism unlikely. The mitochondrial DNA mutation panel was negative for point mutations or deletions. Further testing for urinary organic acids did not reveal elevation of 3-hydroxybutyric acid suggesting SCOT enzyme levels were sufficient in our patient. Review of pathology records for heart transplantation completed for idiopathic cardiomyopathy 20 years prior to this presentation showed high levels of glycogen deposition prompting evaluation for glycogen storage disorders. Results revealed a heterozygous abnormality at exon 9 of the AGL gene; AGL gene c.1139A&amp;gt;G (p.Glu380Gly). This is not a reported pathologic mutation, and given the heterozygosity of the mutation in this autosomal recessive condition, it is felt that either environmental factors or the presence of other unrecognized genetic mutations allowed for the phenotypic expression of GSDIII with euglycemic starvation ketoacidosis. The patient was treated with dietary counseling regarding ketone suppression with basal insulin during periods of fasting and preference to avoid periods of prolonged fasting with frequent carbohydrate-containing meals. Conclusion This case represents a novel, potentially pathologic defect in the AGL gene. This finding should prompt further investigations into genetic variabilities that may lead to this phenotypic expression. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.