Abnormal Laboratory Values Research Articles

National Registry for Childhood Onset Scleroderma I: Insights from the first 341 juvenile localized scleroderma patients

Objectives: There is an under recognition of juvenile-onset localized scleroderma and its extracutaneous manifestations leading to delay in systemic treatment. Our study aims to address this gap by describing the demographics, presentation, associated family history, concurrent autoimmune disease, extracutaneous manifestations, laboratory evaluation, treatment, and course of disease in juvenile-onset localized scleroderma patients enrolled in the National Registry for Childhood Onset Scleroderma. Methods: Participants for this study were derived from the National Registry for Childhood Onset Scleroderma and included 341 patients with juvenile-onset localized scleroderma. Demographic, and prospectively collected outcome measures, such as the Localized Scleroderma Cutaneous Assessment Tool, physical exam findings, laboratory values, and patient-reported outcomes were reviewed. Results: Most patients were female (71%), Caucasian (94%), had a linear subtype (56%), and had the onset of disease at age 7.5 (±4.2) years, and diagnosis 1.9 (±2.6) years after symptom onset. Most patients experienced at least one extracutaneous manifestation (70%), most commonly musculoskeletal (57%), followed by neurological (46%), and ophthalmological (11%). Those with musculoskeletal extracutaneous manifestation have significantly abnormal inflammatory and antibody laboratory values. Of patients with 1-year follow-up, a majority were treated with systemic therapy and globally improved with significant reduction in both modified Localized Scleroderma Skin Index ( p < 0.001) and Localized Scleroderma Damage Index ( p = 0.001). Conclusion: The study highlights need for earlier recognition of juvenile-onset localized scleroderma after demonstrating the delay in diagnosis and frequent extracutaneous manifestations with significant disease burden in a juvenile-onset localized scleroderma cohort. The benefits of systemic treatment and full extracutaneous manifestation screening in juvenile-onset localized scleroderma is supported.

Glycyrrhizic acid induced acquired apparent mineralocorticoid excess syndrome with a hyperadrenergic state: a case report

BackgroundSyndrome of apparent mineralocorticoid excess (AME) is characterized by excessive MR stimulation despite low levels of aldosterone. 11Beta-hydroxysteroid dehydrogenase-2 (11βDSH-2) inactivates cortisol to cortisone, preventing cortisol-induced MR activation. Genetic defects in 11βDSH-2 cause AME through accumulation of cortisol in the distal nephron, leading to MR activation induced hypertension, hypokalemia and metabolic alkalosis. Acquired AME can occur due to the ingestion of glycyrrhizic acid, found in licorice root, which inhibits 11βDSH-2 and has additional effects on cortisol homeostasis through inhibition of 11βDSH-1.Case reportWe present a case of acquired AME with a hyperadrenergic symptoms induced by ingestion of Advanced Liver Support, a nutritional supplement produced by Advanced BioNutritionals(R), in a 65-year-old Caucasian female who presented with accelerated hypertension, hypokalemia, metabolic alkalosis and adrenergic symptoms. Cessation of the licorice-containing supplement resulted in complete resolution of the patient's hypertension, symptoms and abnormal lab values. To our knowledge this is the first reported case of AME from this supplement, and the first to describe accompanying hyperadrenergic symptoms.ConclusionsGlycyrrhizic acid is increasingly being found in unregulated nutritional supplements and has the potential to induce a reversable syndrome of AME. Acquired AME should be suspected in individuals who present with hypertension along with hypokalemia, metabolic alkalosis and low plasma renin and serum aldosterone levels.

Risk factors for readmission after sepsis and its association with mortality

BackgroundSepsis is associated with an approximately 20 % 30-day readmission rate and with subsequent mortality. ObjectivesTo determine the demographics, comorbidities that had been documented prior to sepsis onset, processes of care, commonly administered laboratory tests measured near discharge, and post-sepsis infections that may be associated with readmission and, secondarily, whether readmission is an independent risk factor for 90-day mortality. MethodsUsing a database of patients who met Sepsis-3 criteria divided into Construction and Validation groups, we used logistic regression to estimate the factors independently associated with readmission within 30 days after discharge and proportional hazard regression to estimate the factors independently associated with 90-day mortality. ResultsOf the 30,798 patients ≥ 18 years at our combined referral and community hospital and were discharged alive who met Sepsis-3 criteria between July 10, 2009 and September 7, 2019, 5943 (19 %) were readmitted within 30 days. Thirteen thousand, four hundred forty-four (44 %) of the patients were female, 25,293 (82 %) White, 3523 (11 %) Black, and the mean age was 59 ± 17 years. Among the readmitted patients, 894 (15 %) died within 90 days from the original discharge compared to 11 % (p < 0.001) who had not been readmitted. Seven comorbidities, five processes of care (presepsis platelet transfusion, postsepsis platelet transfusion, operation, ICU length of stay, and hospital length of stay), five culture results, two discharge laboratory values, and discharge location were associated with readmission. The model had good discrimination, 0.770 ± 0.004 (Construction Group) and 0.748 ± 0.006 (Validation Group) and good relevancy (area under the precision recall curve), 0.390 ± 0.004 (Construction group) and 0.476 ± 0.005 (Validation group). Readmission within 30 days was independently associated with a 56 % higher risk of death (HR=1.562, 95 % CI=1.434, 1.703, p < 0.001) within 90 days from discharge. ConclusionsComorbidities, abnormal laboratory values, processes of care, and post-sepsis onset culture results, but not demographic characteristics, were associated with 30-day readmission. Readmission was associated with 90-day mortality.

Vertebral compression fracture as the only presentation sign of acute lymphoblastic leukemia: a case report

BackgroundPathological fractures in acute lymphoblastic leukemia (ALL) are uncommon, but our case highlights the possibility of it being an unusual presentation even in the absence of abnormal laboratory values. The importance of recognizing such rare manifestations cannot be overstated, as early detection and appropriate management can significantly improve patient outcomes.Case presentationHere, we share a case study of a 7-year-old female patient who was diagnosed with acute lymphoblastic leukemia (ALL) after experiencing vertebral fractures. Interestingly, the patient was found to have osteoporosis before being diagnosed with ALL. This case highlights the importance of early diagnosis and prompt treatment to prevent complications and improve patient outcomes.ConclusionsIn short, discovering acute lymphoblastic leukemia can be challenging. It is important to remain vigilant in recognizing atypical signs to ensure early detection and the best possible outcome. We describe a case with ALL that was presented with compression vertebral fracture. This highlights the significance of imaging studies in pediatric cases, particularly for musculoskeletal abnormalities related to serious pathologies, most notably malignancies, which may be the only way to diagnose patients presenting with vague symptoms.

Idiopathic Calcinosis Cutis of the left great toe-A case report

Calcinosis cutis, a rare benign disorder, involves systemic calcium deposition in soft tissues, often linked with autoimmune and renal disorders. Pathophysiology varies among its five main types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Dystrophic calcification, the most common type, is associated with normal calcium and phosphorus levels and autoimmune diseases. Metastatic calcification, on the other hand, arises from abnormal serum calcium and phosphorus levels. Idiopathic calcification lacks underlying tissue damage or abnormal laboratory values. Iatrogenic calcification was triggered by calcium or phosphate-containing substances. Calciphylaxis involves vessel calcification and is linked to chronic renal failure and dialysis. A 19-year-old female presented with pain and swelling on her left great toe plantar aspect, diagnosed as unilateral idiopathic calcinosis cutis. A comprehensive diagnostic approach, including histopathological, radiological, and blood investigations, is crucial for effective management. The study aimed to highlight idiopathic cutaneous calcinosis, emphasizing its accurate diagnosis through clinical, pathological, and metabolic correlation. Surgical excision offers a complete cure for this rare condition, leading to an excellent prognosis.

Point-of-care lung ultrasound predicts hyperferritinemia and hospitalization, but not elevated troponin in SARS-CoV-2 viral pneumonitis in children

SARS-CoV-2 often causes viral pneumonitis, hyperferritinemia, elevations in D-dimer, lactate dehydrogenase (LDH), transaminases, troponin, CRP, and other inflammatory markers. Lung ultrasound is increasingly used to diagnose and stratify viral pneumonitis severity. We retrospectively reviewed 427 visits in patients aged 14 days to 21 years who had had a point-of-care lung ultrasound in our pediatric emergency department from 30/November/2019 to 14/August/2021. Lung ultrasounds were categorized using a 6-point ordinal scale. Lung ultrasound abnormalities predicted increased hospitalization with a threshold effect. Increasingly abnormal laboratory values were associated with decreased discharge from the ED and increased admission to the ward and ICU. Among patients SARS-CoV-2 positive patients ferritin, LDH, and transaminases, but not CRP or troponin were significantly associated with abnormalities on lung ultrasound and also with threshold effects. This effect was not demonstrated in SARS-CoV-2 negative patients. D-Dimer, CRP, and troponin were sometimes elevated even when the lung ultrasound was normal.

Circulating Nucleated Red Blood Cells: An Updated Reference Interval.

Nucleated red blood cells (nRBCs) are not identified in the peripheral blood in healthy individuals beyond the neonatal period. Their presence in children and adults is traditionally considered pathologic. Contemporary hematology analyzers measure nRBCs at very low levels compared to traditional manual morphometric methods. The original launch of the Sysmex XN analyzer in this study's clinical laboratory verified the previously used nRBC reference interval of 0.00 to 0.01 × 106/μL. However, nRBC results from apparently healthy patients were flagged as abnormal (high), subsequently causing patient anxiety and increased subspecialty referrals. To determine whether current reference intervals (RIs) for nRBCs were clinically relevant. We performed a prospective analysis of 405 300 specimens from nonhospitalized individuals who received a complete blood count. Applying inclusion/exclusion criteria produced a total specimen pool of 66 498. Of the 66 498 samples with otherwise normal complete blood count results from healthy, nonhospitalized individuals, 338 showed results outside the previously established RI; 336 of 66 498 (0.5%) had nRBC results greater than 0.01 × 106/μL. Two samples had nRBC values greater than 0.10 ×106/μL. Based on statistical analysis of our results, we concluded that the upper limit of the RI could be updated from 0.01 × 106/μL to 0.10 × 106/μL. Increasing the upper limit of normal for the nRBC RI should decrease patient consternation from an abnormal laboratory value and significantly decrease costs through reducing unnecessary follow up care, and without causing patient harm.

Clinical characteristics of hospitalized male adolescents and young adults with atypical anorexia nervosa.

To describe the clinical characteristics of male adolescents and young adults hospitalized for medical complications of atypical anorexia nervosa (atypical AN) and to compare their clinical characteristics with females with atypical AN and males with anorexia nervosa (AN). A retrospective review of electronic medical records for patients with atypical AN and AN aged 9-25 admitted to the UCSF Eating Disorders Program from May 2012 to August 2020 was conducted. Among 21 males with atypical AN (mean age 15.1 ± 2.7, mean %mBMI 102.0 ± 11.8), medical complications evidenced by admission laboratory values included anemia (52.9%), vitamin D insufficiency/deficiency (52.6%), and zinc deficiency (31.6%). Compared with females with atypical AN (n = 69), males with atypical AN had longer length of stay (11.4 vs 8.4 days, p = .004), higher prescribed kcal at discharge (4114 vs 3045 kcal, p < .001), lower heart rate nadir (40.0 vs 45.8, p = .038), higher aspartate transaminase (AST, 37.9 vs 26.2 U/L, p = .032), higher alanine transaminase (ALT, 30.6 vs 18.3 U/L, p = .005), and higher rates of anemia (52.9% vs 19.4%, p = .005), with no differences in vitamin D, zinc, and vital signs. Compared with males with AN (n = 40), males with atypical AN had no significant differences in vital signs or laboratory assessments during the hospitalization. Atypical AN in males leads to significant medical comorbidity, and males with atypical AN require longer hospital stays compared to females with atypical AN. Rates of abnormal vital signs and abnormal serum laboratory values during hospital admissions do not differ in males with atypical AN compared to AN. Adolescent and young adult males with atypical anorexia nervosa experience significant medical complications. Males with atypical anorexia nervosa had longer hospitalizations and higher prescribed nutrition at discharge than females. Medical complications of atypical anorexia nervosa in male adolescents and young adults were generally equal to those of male adolescents and young adults with anorexia nervosa. Clinicians should be aware of unique medical complications of males with atypical anorexia nervosa.

Relationship Between Sleep Quality and Blood Pressure Pre Posterior Vitrectomy Patient

Background: Sleep patterns have the highest influence on the incidence of hypertension compared to other variables, namely age and gender. The delay in elective surgery was mostly due to medical factors and mostly due to acute changes in cardiovascular and respiratory functions, abnormal laboratory values and patients refusing surgery. In patients with eye disease, especially in the retina with a Posterior Vitrectomy surgery plan, patients often encounter comorbidities such as hypertension. Incidents of cancellation of elective eye surgery on the day of surgery at the National Eye Center of Cicendo Eye Hospital are also common, especially for reasons of hypertension. Objective: The purpose of this study was to determine the relationship between sleep quality and blood pressure of pre-Posterior Vitrectomy patients at the National Eye Center at Cicendo Eye Hospital, Bandung. Methods: The research method used in this research is analytic observational with cross sectional design. Sampling was carried out at the National Eye Center, Cicendo Eye Hospital, and Bandung. The sampling technique used purposive sampling with a total sample of 114 people. Statistical test with Chi Square Test using SPSS. Result: The results show a p value of 0.003 where the result is smaller than 0.05. From these results, it can be concluded that there is a relationship between the two variables, namely “Sleep Quality” with “Blood Pressure” pre-Posterior Vitrectomy patients at the National Eye Center of Cicendo Eye Hospital Bandung. Conclusion: There is a relationship between sleep quality and blood pressure in pre-posterior vitrectomy patients at the National Eye Centre at Cicendo Eye Hospital, Bandung.

COVID-stasis of Pregnancy: An Increased Prevalence of COVID-19 in Patients with Cholestasis.

To evaluate the relationship between intrahepatic cholestasis of pregnancy (ICP) and coronavirus disease 2019 (COVID-19). We performed a retrospective cohort study of pregnant women undergoing induction of labor (IOL) at a single institution between May 2020 to January 2021. Primary exposure was diagnosis of intrahepatic cholestasis of pregnancy (ICP). The primary outcome was the prevalence of COVID-19 as determined by reverse-transcriptase polymerase chain reaction testing on nasopharyngeal swabs for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) on routine admission testing. Secondary outcomes were abnormal laboratory values and adverse fetal outcomes. Logistic regression with log link analysis was performed comparing patients undergoing IOL for ICP compared with IOL for all other indications. The moderating effect of ethnicity was assessed by the interaction between ethnicity and ICP in a logistic regression model. The Wilcoxon rank-sum test and Fisher's exact test were performed for the secondary outcome analyses. Over the course of the study, 596 patients underwent IOL: 24 for ICP and 572 for other indications. The overall prevalence of COVID-19 positivity in the cohort was 5.5% (33 of 596). Those with ICP were more likely to test positive for COVID-19 compared with those with other IOL indications (29.2 vs. 4.5%, RR = 6.4, 95% CI: 2.8-12.5, p < 0.001). All patients with ICP who tested positive for COVID-19 were Hispanic. To analyze the moderating effect of ethnicity, the results of the logistic model found the interaction between ethnicity and ICP to not be significant (p = 0.991). In patients with ICP, the median AST (aspartate aminotransferase) was higher than those with COVID-19 (p = 0.0182). There were no adverse fetal outcomes in the ICP group. In this single-site retrospective cohort study, we demonstrated an increased prevalence of COVID-19 in those with ICP in general and among Hispanic patients specifically. Despite this difference, there was no increased risk of adverse fetal outcomes. · There is an increased prevalence of COVID-19 among Hispanic patients with ICP.. · The median AST of COVID-19-positive patients was significantly higher than COVID-19-negative patients.. · There was no increased risk of adverse fetal outcomes in with COVID-19 and ICP..

Does the number of pages received per hour affect resident productivity?

Workflow interruptions are common for emergency physicians and are shown to have downstream consequences such as patient dissatisfaction, delay in clinical response, and increase in medical error. However, the impact of passive interruptions on physician productivity is unclear and has not been well studied. We sought to evaluate if the number of pages received per hour significantly affects the number of patients seen per hour. Retrospective data was collected on resident physician (RP) emergency department shifts from July 1st, 2021 to June 30th, 2022 at an academic medical center with an annual census of 55,000 patients. A total of 2865 RP shifts were collected among the 26 postgraduate year (PGY) 1 and PGY2 residents. For each RP shift, we identified the number of pages received per hour and the number of new patients seen per hour. Pages consist of any transmitted message that was sent to the RP's personal pager, which includes both automatic (eg, bed assignments, abnormal lab values) and personalized pages from other healthcare practicioners(eg, nursing, consultants). Data were analyzed using Poisson regression controlling for clustering at the physician level to determine if the number of patients seen per hour is significantly affected by the number of pages (divided into quartiles) received. We found the number of pages received per hour did not decrease the number of patients seen per hour. Contrary to our hypothesis, there was a strong positive relationship between the number of pages received per hour and the number of patients seen by RPs in that hour and subsequent hours. During the middle of a shift (hours 3, 4, and 5), RPs receiving pages in the third and fourth quartile (top 50% of pages) saw significantly more patients during that same hour and the next hour (p<0.001). The number of pages received by RPs per hour did not decrease the number of patients seen per hour. When RPs receive a higher number of pages, there is a positive association with the number of patients they see in that hour and subsequent hours. Further studies will be needed to determine whether the content of pages affects resident productivity.

AKATSUKI 48-Week Interim Analysis: Emicizumab and Immune Tolerance Induction in People with Hemophilia A and Factor VIII Inhibitors

Background: Immune tolerance induction (ITI) therapy, for the eradication of factor (F)VIII inhibitors, is indicated for people with hemophilia A (PwHA) with FVIII inhibitors. There are limited data regarding the safety of emicizumab treatment in combination with ITI, particularly regarding thrombotic events (TEs). This study, conducted in Japan, aims to evaluate the safety profile of emicizumab during and immediately after ITI. Methods: AKATSUKI is a Phase IV, open-label, non-randomized, interventional, multicenter study; the methods have been previously published (Matsushita et al. BMJ Open 2022). PwHA with FVIII inhibitors received an approved dose of emicizumab and ITI therapy. Any standard half-life (SHL) FVIII concentrate could be used for ITI, with a dosing regimen of 50IU/kg, three times a week; when using an extended half-life (EHL) FVIII concentrate, 50IU/kg twice a week was permitted. Those who achieved ITI partial success received prophylaxis with emicizumab and a FVIII concentrate starting from the date of their next study visit following investigator confirmation of partial success. Any FVIII concentrate could be used for post-ITI maintenance therapy, given as 50IU/kg once a week for the first 24 weeks followed by 50IU/kg once every 2 weeks for the next 24 weeks, followed by discontinuation of the FVIII concentrate at the investigator's discretion. The primary endpoint was evaluation of adverse events (AEs), with a key focus on TEs, and abnormal laboratory values over time during and immediately after ITI. The main secondary endpoints included number of treated bleeds and the proportion of participants meeting ITI success criteria. Partial success was achieved on the same date that the participant's blood sample showed normal FVIII recovery in addition to the participant receiving a negative FVIII inhibitor titer. Normalized FVIII recovery was defined as a FVIII recovery rate of ≥66% of the predicted value on two consecutive occasions ≥2 weeks apart, and a negative FVIII inhibitor titer was defined as achieving FVIII inhibitor levels of &amp;lt;0.6 BU/mL on two consecutive occasions ≥2 weeks apart. Results: Twelve participants, all of whom were male (median [range] age 2.5 [1-54] years) were included in this interim analysis (evaluation period, median [range]: 437.5 days [224-749]. Data cut-off date: December 22, 2022). Prior to the study, participants had received emicizumab (n=11), ITI (n=9), or both (n=7), and the median (range) duration of ITI in combination with emicizumab was 203.0 (7-1,002) days. Three participants used a SHL FVIII product for their ITI treatment regimen, and nine participants used an EHL FVIII product. Additional baseline characteristics are presented in Table 1. Overall, 30 AEs occurred, none of which were considered emicizumab- or FVIII concentrate-related. Two participants each experienced one serious AE: one case of pneumonia, initially caused by transmission of a viral infection, and one wound hemorrhage, which was recorded as accidental; both recovered. No participants experienced a TE. Three participants reported a total of 10 treated bleeds, all of which were categorized as traumatic and were treated with recombinant activated FVII. At data cut-off, one participant had achieved partial ITI success, having reached a negative inhibitor titer at Week 5 and normalized FVIII recovery by Week 17. This participant was then treated with emicizumab and FVIII concentrate (50IU/kg once a week). No bleeds or AEs were reported for this participant during the observational period. The changes in FVIII inhibitor titer across the study for all participants are presented in Figure 1. Conclusions: At this 48-week interim analysis, no new safety concerns or TEs were reported in PwHA receiving emicizumab and ITI. This study continues to evaluate the safety of emicizumab in conjunction with, and following, ITI therapy in PwHA with FVIII inhibitors.

Paradoxical Findings in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with C5 Inhibitors: Suboptimal Disease Control Perceived As Satisfactory

Introduction: The introduction of C5 inhibitors (C5i) for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) has resulted in lower morbidity and mortality rates. However up to 86% of patients still experience anemia and fatigue in 63% of them which may impact their quality of life (QoL). The SATURNO study aimed to assess PNH patient and physician satisfaction with C5i treatment, along with the impact of the disease and clinical outcomes. Methods: A multicenter, observational, cross-sectional study conducted in PNH patients receiving C5i treatment for at least 3 months in Spain. Key clinical and laboratory data were collected, including red blood cells (RBC) transfusions, hemolytic crisis, hemoglobin (Hb), haptoglobin (Hp), lactate dehydrogenase (LDH), absolute reticulocyte count (ARC) and bilirubin. Patient satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM) and Visual Analog Scale (VAS). Physician satisfaction was measured using the TSQM general item and VAS. Fatigue and QoL were evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), respectively. The Work Productivity and Activity Impairment questionnaire (WPAI) was also used. Results: A total of 56 patients and 13 physicians participated in the study. Median (IQR) age of patients was 54.0 (44.5; 63.5) years, 35.7% were female and median (IQR) duration of treatment with C5i was 6.6 (3.3; 11.6) years. Overall, 94.6% of patients and 90.6% of physicians reported to be satisfied, very satisfied, or extremely satisfied with the treatment. Mean (SD) VAS score for patient satisfaction was 9.0 (1.2) and for physicians 7.9 (1.7) out of 10. Mean (SD) EORTC QLQ-C30 score was 71.7 (21.7) out of 100. Mean (SD) FACIT-F score was 39.7 (10.6) out of 52 and fatigue was reported by 55.2% of patients. Clinical and laboratory parameters showed a significant proportion of patients exhibiting abnormal values. Hb and Hp were below the normal ranges in 67.9% and 65.1% of patients, respectively, whereas elevated LDH, ARC and indirect bilirubin were observed in 50.0%, 83.0% and 75.9% of them, respectively. In the last 12 months, 30.9% of patients had received at least one RBC transfusion, with a mean (SD) number of 8.6 (8.4) RBC transfusions, and 33.9% experienced at least one hemolytic crisis with a mean (SD) of 4.9 (9.4). Work productivity assessment revealed that 60.7% of patients were currently unemployed, a mean (SD) percentage of absenteeism of 5.7% (12.4) and presenteeism of 23.8% (26.0). Overall mean (SD) percentage of work productivity impairment was 25.6% (27.3). Activity impairment was reported by 36.4% (28.3) of patients. Conclusions: The SATURNO study showed that although patients and physicians reported satisfaction with C5i treatment, this might be challenged. A substantial number of PNH patients treated with C5i still experience anemia, fatigue and abnormal laboratory values, indicative of ongoing hemolysis and suboptimal control. Moreover, patients with PNH had affected work productivity and a proportion of them were experiencing activity impairment. These findings highlight the need for comprehensive management strategies to address the impact of the disease on patients with PNH receiving C5i treatment.

Association between Race and Social Deprivation in Patients with Hematologic Malignancies

Background: Recent therapeutic advances including biologics, immunomodulators, and cellular therapies have transformed management paradigms for hematologic malignancies. Nevertheless, disparities exist in terms of access to care, and non-White individuals are historically underrepresented in clinical trials. As it remains unknown whether there are inequalities in care related to adverse events of these therapeutic approaches, in this study we explored whether racial and social differences are related to outcomes of patients with hematologic malignancies. Methods: This was a retrospective chart review from January 2011 to December 2021 that included adult patients across our cancer center network with diagnostic codes for malignant neoplasms of lymphoid, myeloid, and hematopoietic origin who were receiving an immunologic therapy at the time of an emergency department visit. Data were compared according to White and non-White individuals. The non-White group comprised of Black or African American, Asian Indian, Chinese, Asian, or unspecified/other. Differences in continuous variables between groups were assessed using the Wilcoxon rank-sum test, and Chi-square or Fisher's exact test was used to compare categorical variables. Outcomes included time to admission, length of stay within the hospital, ICU admissions, and differences in social deprivation index (SDI). SDI is a composite measure of a geographic region's socioeconomic variation in health outcomes based on demographic characteristics collected by the U.S Census Bureau (www.census.gov/programs-surveys/acs). Higher SDI scores indicate more severe social deprivation. Results: 180 patients were identified with 142 patients meeting inclusion criteria. Among these, 43% were non-White patients. The median age for the White group was 71.6 and for the non-White group 65.8 (P=.001). The most common immunotherapies were lenalidomide (50%), pomalidomide (19.7%), daratumumab (12.7%), methotrexate (9.9%), and rituximab (8.5%). The main chief complaint that was statistically different between the two groups was musculoskeletal complaints; the incidence among the White group was 8.6% and 29.5% among the non-White group (P=0.001). Other reasons for presentation included neurological complaints (21)%, infection/sepsis (16%), respiratory issues (12%), and abnormal laboratory values (3.5%). There were no differences in time to hospitalization for White versus non-White patients (5 versus 6 hours, P=0.12). Differences in ICU admissions, 30 day-readmissions, and length of stay were also not statistically significant between the two groups. However, the median SDI for the White group was statically greater among the non-White group (p&amp;lt;0.001). Discussion: In this retrospective study, non-White patients with hematologic malignancies were found to have greater social deprivation than White patients, however this did not impact inpatient metrics. We found that non-White patients with hematologic malignancies were more likely to originate from socially disadvantaged backgrounds, although there were no differences in hospitalization outcomes among the two groups. Results suggest that social determinants may impact factors unrelated to access to acute care in patients with hematologic therapies receiving immunologic therapies.

Evaluation of Safety and Efficacy of Ruxolitinib in Patients with Pediatric Lymphoproliferative Disorders

Introduction. Pediatric lymphoproliferative disorders (PLPD) encompass a wide spectrum of immune dysregulation conditions with heterogeneous clinical presentation and lab abnormalities. The underlying mechanisms of PLPD are diverse, including dysregulated differentiation of immune cell populations, aberrant recruitment of lymphocyte populations, and/or retention and pathologic survival of lymphocytes. Many PLPD are associated with inborn or acquired genetic factors impacting immune function. Standardized measures to characterize clinical and biological factors in PLPD patients and responses to therapy are lacking. One common feature in PLPD patients is activating IFNg signaling. Ruxolitinib is a drug that blocks hyperactivated IFNg signaling through the JAK-STAT pathway. The goal of this study is to describe the clinical responses of PLPD patients to ruxolitinib. Methods. Medical charts were reviewed to identify patients with PLPD treated with ruxolitnib at Texas Children's Hospital over a 7-year period. Clinical manifestations (recurrent fever, fatigue, lymphadenopathy, recurrent infections, pulmonary disease, endocrinopathy, enteropathy, hepatosplenomegaly, arthritis, CNS symptoms, atopy, dysphagia, underweight), lab values of complete blood count and pathologic inflammation markers (CXCL9, ferritin, sIL2R, IL-18, CD163, neopterin) were categorized with a severity system indicating: 0 no clinical signs and normal lab values; 1 mild to moderate symptoms and abnormal lab values; 2 severe symptoms, highly abnormal lab values (table 1). Total score was computed before and during the addition of ruxolitinib. Complete response (CR) represented a reduction of the total score to 0. Partial response (PR) signified reduction of criteria score ≥ 30% from the baseline with no progression or manifestation of new symptoms. Progression of the disease or improvement &amp;lt; 30% was marked as no response (NR). Results. Chart review identified 19 children and young adults with PLPD who received treatment with ruxolitinib (median age 8.5 years; range 1.2 to 21.6 years). Underlying disease states driving PLPD included HLH, inborn errors of immunity, juvenile rheumatoid arthritis, macrophage activation syndrome, malignant atrophic papulosis of Degos, Aicardi-Goutierres Syndrome, and T-cell large granular lymphocytic leukemia.Genetic variants known or predicted to be damaging were identified in 15 cases (79%), including STAT1, STAT3, TREX1, OFD1, NLRP12, NLRP4, UNC13, PRF1, AP3D1 and mosaic genome-wide paternal uniparental disomy. While 79% of patients received ruxolitinib in combination with other immune suppressants, 21% received only ruxolitinib out of which half received it as front-line therapy. Based on the PLPD Scoring System, overall response rate to ruxolitinib was 73.7%, with 5.3% achieving CR, and 68.4% PR. Overall survival on this study was 84.2% with median 11 months follow-up (range: 0.5 month to 7.1 years). Three patients died due to uncontrolled disease progression. Six patients in whom hematopoietic cell transplant was deemed essential for cure survived to conditioning. Toxicities potentially related to ruxolitinib included grades 1 to 4 cytopenias and grade 1 elevated liver enzymes. Conclusion. PLPD represents a population with overall poor outcomes. We developed standardized staging and response metrics to characterize extent of immune dysregulation and response to therapy. Ruxolitinib represents a potential “precision” therapeutic intervention for patients with pathologic IFNg pathway activation. Ruxolitinib was well-tolerated in this high risk population, and was associated with positive responses in the majority of patients. This study supports expansion of prospective studies to validate the PLPD Scoring System and to optimize therapeutic strategies to manage immune dysregulation, including ruxolitinib.

1670. It Is Likely Not HSV: Decreasing Empiric Acyclovir Use In Low-Risk Infants

Abstract Background Neonatal HSV infection is a rare but potentially devastating disease. Institutional practices regarding which neonates must be treated empirically with acyclovir varies. While some centers elect to treat all neonates presenting with fever or hypothermia, some treat only those considered at risk. Our goal was to decrease empiric acyclovir use in low-risk neonates admitted to the Infectious Disease (ID) ward. Methods Quality improvement initiative aimed to decrease acyclovir exposure in neonates 15 to 28 days old hospitalized on the ID ward for fever/hypothermia without a focus, risk factors, or clinical signs for HSV (Figure 1). Interventions included development of a risk stratification algorithm (Figure 2), consensus building among Emergency Medicine and ID providers, and order set implementation. We reviewed all neonates with HSV infections for delayed acyclovir initiation as a balancing measure. The pre-study baseline period was 2019 to 2020, and the study period was 2020, to March 31, 2023. Control charts were used to assess the interventions.Figure 1Key Driver Diagram.Figure 2Risk stratification algorithm for HSV empiric treatment in low-risk infants. Results The mean acyclovir use per quarter in neonates who met low risk criteria decreased from 79% during the baseline period (7/2019-6/2020) to 30% in the post-intervention period (7/2020-3/2023) (p = &amp;lt; 0.0001) (Figure 3). Most common reasons why patients failed low risk criteria were: CSF pleocytosis in the setting of a traumatic LP, minimally abnormal lab values (slightly increased ALT, slightly decreased platelets), no LP in well-appearing patient and alternative fever etiology (URI symptoms with positive respiratory infection array). There were no cases of delayed acyclovir initiation in patients with HSV disease. Only one patient with HSV disease fell within the age range but was admitted to the ICU following cardiac arrest and appropriately started on acyclovir therapy.Figure 3Control chart of empiric acyclovir use in low-risk infants. Conclusion Our algorithm, targeted to limit empiric acyclovir therapy in neonates with fever/hypothermia without a focus at low risk for HSV, led to a significant decrease in acyclovir exposure sustained for &amp;gt; 2 years after implementation. Interestingly, it also led to decreased in acyclovir use in patients who failed low risk criteria, but this did not result in missed diagnosis of HSV disease, likely because our algorithm was conservative and HSV infection is rare. Disclosures All Authors: No reported disclosures

A Rare Case of Unilateral Lymphadenopathy: Unicentric Castleman Disease

Background Castleman Disease (CD) involves a group of disorders characterized by an enlargement of lymphoid follicles with capillary proliferation. The disorders are largely separated into unicentric (UCD) or multicentric (MCD) depending on the number of involved lymph nodes. MCD has been linked to HHV8 or immunosuppression secondary to HIV, while UCD has been thought to be driven by a clonal neoplastic process, likely from the follicular dendritic cell. Case Presentation A 14-year-old female with ADHD, OCD, and autism spectrum disorder (ASD) presents to clinic with a 2-year history of a right-sided neck mass. There was no history of trauma or illness around the time of the mass being noted and the mass has not changed significantly in size for the past two years. An excisional biopsy was attempted but, due to excessive vascularity around the mass, was ultimately deferred. Following subsequent MRI and CT scans, a core needle biopsy was performed, revealing lymphoid tissue with regressed follicles and focal hyalinization without signs of malignancy. PET/CT scans at this time showed increased metabolic activity confined to the right-sided neck mass without any increased metabolic activity in the other lymph nodes of the head and neck. Eventually, the 7 cm diameter mass was excised; pathology studies revealed distorted architecture with hyaline deposits in the germinal centers and sclerotic blood vessels penetrating the germinal centers consistent with the hypervascular variant of Castleman Disease. Pre- and post-operative labs such as the C-reactive protein, immunoglobulin counts, and protein electrophoresis panels were all within normal limits. Furthermore, post-operative PET/CT scans showed no metabolically active foci indicating that the lesion was indeed unicentric Castleman Disease. After the excision of the mass, the patient continues to do well without any further surgeries or complications. Discussion Differentiation between UCD and MCD requires imaging, often with a CT scan, to establish the number and locality of the affected lymph nodes. UCD often presents with one bulky lymph node or multiple enlarged lymph nodes within the same region, whereas MCD tends to be smaller lymph nodes spread over multiple regions. MCD is also more often associated with B symptoms and abnormal lab values such as elevated CRP or ESR along with abnormal protein levels. Other subtypes exist, thought to be driven primarily by cytokines like VEGF and IL-12 similar to other neoplasms. The hypervascular type, more commonly associated with UCD, consists of fibrous bands running through lymphoid follicles with regressed germinal centers while the plasmacytic type, found more often in MCD, consists of sheets of plasma cells and hyperplastic germinal centers. Lastly, mixed type has features of both the main types. Preferred treatment for resectable UCD is surgery with treatments for unresectable UCD involving observation (if asymptomatic) or a combination of rituximab and steroids with anti-IL6 monoclonal antibody treatment (such as tocilizumab) followed by surgery or radiation therapy. Similarly, MCD is often treated with rituximab, steroids, and tocilizumab. Conclusion Due to the presence or absence of other signs and symptoms, Castleman Disease is often difficult to diagnose without a biopsy. Further studies into the etiologies of CD, including possible associations with other neoplastic or immunosuppressed states, are needed to develop better criteria for diagnosing the disease. Developing standardized patient registries with information on disease progression as well as proper follow-up for patients after treatment are vital to diagnosing, treating, and providing surveillance for patients with Castleman Disease.

THU410 Retrospective Review Of Adults Patients With Suspected Or Confirmed Hypophosphatasia At The Penn Bone Center

Abstract Disclosure: R. Tran: None. C. Hvisdas: None. M. Riordan: None. L. Novotny: None. S. Kallish: None. K. Patel: None. M. Al Mukaddam: None. Abstract: Hypophosphatasia (HPP) is a rare inherited genetic disorder that affects the mineralization of bones and teeth. HPP is the result of a pathogenic variant involving the tissue nonspecific alkaline phosphatase (ALPL) gene. The clinical presentations of HPP greatly vary from serious perinatal manifestations (respiratory failure, seizures, and death) to mild manifestations in adulthood. In adults, hallmark signs and symptoms include early loss of primary or secondary teeth, osteoporosis, osteomalacia, recurring metatarsal stress fractures, and abnormal laboratory values, such as low alkaline phosphatase (ALP), elevated phosphoethanolamine, and elevated vitamin B6.The treatment and follow up of adults with HPP are not clearly described. This retrospective study characterizes 43 patients referred to the Penn Bone Center for suspected HPP. Twelve of the 43 patients had a confirmed HPP diagnosis based on both clinical presentations and evidence of variant in the ALPL gene. The twelve patients consisted of both female and male adults between the ages of 24 to 74. In addition, the patients had abnormal ALP levels, ranging between less than 5 to 38 units per liter (normal range: 38 to 126 U/L). Six of these patients had previous or current use of asfotase alfa with variable treatment response. Two patients decided to stop treatment due to lack of clinical benefit or worsening of symptoms while on asfotase alfa therapy. Biochemical and bone mineral density follow-up while on therapy has not been shown to be helpful in monitoring treatment response. Asfotase alfa is a subcutaneously administered synthetic human alkaline phosphatase that was approved by the Federal Drug Administration (FDA) in 2015 for treatment of perinatal/infantile- and juvenile-onset hypophosphatasia. However, the efficacy of treatment in adults remain unclear at this time. Further research is required to better define the natural progression of mild or adult-onset hypophosphatasia and the patients who would benefit from enzyme therapy. Presentation: Thursday, June 15, 2023

Increased adherence to ACOG diagnostic guidelines for HDP following a workshop in Bolivia, a LMIC

ObjectivesHypertensive disorders of pregnancy (HDP) exert a heavy mortality burden in low- to middle-income countries (LMIC). ACOG revised HDP diagnostic guidelines to improve identifying pregnancies at greatest risk but whether they are used in LMIC is unknown. Study designWe held a workshop to review ACOG guidelines in La Paz, Bolivia (BO) and then reviewed prenatal, labor and delivery records for all HDP diagnoses and twice as many controls at its three largest delivery sites during the year before and the nine months after a workshop (n = 1376 cases, 2851 controls during the two periods). Main outcome measuresHDP diagnoses, maternal, and infant characteristics. ResultsBolivian and ACOG criteria identified similar frequencies of gestational hypertension (GH) or eclampsia, but preeclampsia with severe features (sPE) was under- and preeclampsia without severe features (PE) over-reported during both periods. Increases occurred after the workshop in testing for proteinuria and the detection of abnormal laboratory values and severe hypertension in HDP women. Any adverse maternal outcome occurred more frequently after the workshop in women with BO PE or sPE diagnoses who met ACOG sPE criteria. ConclusionsUtilization of ACOG guidelines increased following the workshop and improved identification of PE or sPE pregnancies with adverse maternal outcomes. Continued use of a CLAP perinatal form recognizing HELLP as the only kind of sPE resulted in under-reporting of sPE. FundingNIH TW010797, HD088590, HL138181.

Adverse drug events in Chinese elder inpatients: a retrospective review for evaluating the efficiency of the Global Trigger Tool.

Elderly patients frequently experience a high incidence of adverse drug events (ADEs) due to the coexistence of multiple diseases, the combination of various medications, poor medication compliance, and other factors. Global Trigger Tool (GTT) is a new method for identifying ADEs, introducing the concept of a trigger, that is, clues including abnormal laboratory values, reversal drugs, and clinical symptoms that may suggest ADEs, and specifically locating information related to ADEs in the medical record to identify ADEs. The aim of this study was to establish a GTT-based trigger tool for adverse medication events in elderly patients and to investigate the risk variables associated with such events. The triggers were identified by reviewing the frequency of ADEs in elderly patients in Sichuan, China, retrieving relevant literature, and consulting experts. A retrospective analysis was carried out to identify adverse medication occurrences among 480 elderly inpatients in Sichuan People's Hospital. A total of 56 ADEs were detected in 51 patients (10.62%), 13.04 per 1,000 patient days, and 11.67 per 100 admissions. The overall positive predictive value (PPV) of the triggers was 23.84, and 94.64% of ADEs caused temporary injury. Gastrointestinal system injury (27.87%) and metabolic and nutritional disorders (24.53%) were the primary organ-systems affected by ADEs. The majority of ADEs were caused by drugs used to treat cardiovascular diseases. 71.43% of ADE occurred within 2 days of administration and the risk factor analysis of ADE revealed that the number of medicines had a significant correlation. This study demonstrated GTT's value as a tool for ADEs detection in elderly inpatients in China. It enhances the level of medication management and comprehensively reflects the situation of ADE of the elderly.