Vulnerable Patient Research Articles

B-284 Evaluation of Bupivacaine Metabolite Interference With Norfentanyl in a Liquid Chromatography Tandem Mass Spectrometry Assay in Neonatal Urine

Abstract Background Bupivacaine is a local anesthetic commonly used when administering epidurals during labor and delivery. Bupivacaine metabolite, N-desbutylbupivacaine (NDB), has recently been shown to cause isobaric interference in common urine norfentanyl quantifier and qualifier multiple reaction monitoring (MRM) transitions. This can interfere with the detection of prenatal fentanyl exposure in this vulnerable patient population, which is especially concerning if fentanyl is unexpected. A recent review of urine fentanyl reporting at our institution identified that the number of urine norfentanyl results reported as an interference comment is increasing. A chromatographic review determined this is due to the presence of an unidentified peak co-eluting just before norfentanyl in both the qualifier and quantifier MRM transitions. Most of these samples are from neonates. This study aimed to determine if NDB is the cause of the interfering peak in the urine norfentanyl MRM transitions and evaluate if other specimen types are also affected. Methods NDB standards were prepared and tested using the routine urine fentanyl assay performed by LC-MS/MS in our laboratory, using norfentanyl MRM transitions 233.1 --> 84.1 and 233.1 --> 150.1. Chromatography results were compared to patients with the interference. A retrospective data pull was performed to identify neonatal patients with a urine fentanyl result who also had an umbilical cord or meconium testing requested. Referring centers with patients with the interference comment were contacted to determine neonatal urine collection practices and if bupivacaine was used in their labor and delivery departments. Results NDB produced the same chromatographic pattern observed in the patient samples with norfentanyl interference. This confirmed NDB as the source of the interference. Centers with high rates of NDB interference were contacted and confirmed bupivacaine was routinely administered during labor and delivery at their facilities. Retrospective data analysis identified 577 urine samples with either paired umbilical cord (547) or meconium (30) samples. Of those, 478/577 (82.8%) urine samples displayed NDB interference, and norfentanyl could not be reported due to interference; however, 59 samples were positive for parent fentanyl. Of the 478 urine samples with NDB interference, 455 had a matching cord sample, and 23 had a matching meconium sample. Further examination identified 34/455 (7.5%) cord samples with matching urine samples that had NDB interference were positive for fentanyl. This suggests umbilical cord samples may be useful in some cases to resolve whether a neonate was exposed to fentanyl if NDB interference is observed in urine. Of the 23 paired urine/meconium samples, no positive meconium samples were associated with a urine sample with NDB interference. Conclusions Bupivacaine metabolite is commonly seen in the urine of neonates if bupivacaine is administered as an epidural. Chromatographic separation of bupivacaine metabolite from norfentanyl should be evaluated, especially for centers that receive neonatal samples.

A-318 Validation of umbilical cord blood as an alternate sample type for quantitative in vitro detection of glucose-6-phosphate dehydrogenase in neonates

Abstract Background Detection of glucose-6-phosphate dehydrogenase (G6PD) deficiency provides important information for neonatal clinical management. G6PD newborn screening is recommended using umbilical cord blood specimens in vulnerable patient populations.1 Also, cord blood is used by many clinicians instead of peripheral blood for neonatal screening of G6PD.2 Use of cord blood is a modification to the FDA-approved Pointe Scientific G6PD kinetic-340 nm assay. The aim of this study was to validate cord blood as an alternate specimen type for the Pointe Scientific G6PD assay. Methods Hemoglobin (Hgb) results are from Sysmex XN 9100™ analyzers that use SLS methodology with photometric detection. G6PD results are from Roche cobas® c502 analyzers with Pointe Scientific kinetic method and spectrophotometric detection of activity, expressed as U/g Hgb. Neonatal blood specimens were obtained as paired samples from heel sticks and umbilical cord collected in EDTA lavender top tubes. Accuracy acceptance criteria was defined as Deming regression slope between 0.90 and 1.10, r-value of >0.90 and bias ±15% and mixing study recovery of ±10%. Precision (intra-assay and inter-assay), reportable range and linearity, carryover, and stability were established using cord blood samples or control materials sourced from Thermo Fisher Scientific or Sysmex. Reference intervals3, analytical sensitivity, specificity, and clinical validity were transferred to cord blood due to comparability with whole blood FDA-approved method. EP Evaluator software by Data Innovations® was used for calculations. Results Direct comparison of G6PD results (U/g Hgb) from 125 paired samples yielded a 0.9025 correlation coefficient, 1.024 Deming slope, and -0.25% bias. Mixing and recovery of admixed samples gave % recoveries of 102, 103, 101, 102, 100, and 100 for G6PD (U/g Hgb), and 102, 102, 101, 104, 99, and 105 for Hgb (g/dL). Intra-assay precision results were 2.4, 0.6, 0.8, 0.5, 0.4 % CV for G6PD and Hgb, respectively. Inter-assay precision results were 3.1, 3.3, 0.7, 0.7, 0.5 % CV for G6PD and Hgb, respectively. Reportable range and linearity evaluation resulted in a maximum deviation from target recovery of 4%, and a slope of 0.979 for a range of 50 - 2740 U/L, and reportable range for Hgb was confirmed as 0.1 - 26.0 g/dL using controls (1% maximum deviation and 0.991 slope). Carryover was -5.8 (mean concentration) for G6PD and 0% for Hgb after testing 21 replicates of pooled high and low samples in a defined order. Testing 3 samples in 3 replicates at each defined time interval defined stability as 1 week refrigerated or 72 hours room temperature for G6PD, and 3 days refrigerated or 1 day room temperature for Hgb. Conclusions Regression statistics and mixing-recovery studies demonstrated accuracy for detecting G6PD (U/g Hgb) and Hgb (g/dL) from EDTA cord blood. Additional performance characteristics were transferrable for this specimen type from the FDA-approved method for whole blood. Umbilical cord blood is an acceptable alternate specimen type for quantitative detection of G6PD (U/g Hgb) using Pointe Scientific with Sysmex XN-9100™ and Roche cobas® c502 instrumentation.

Wildfire exposures and in-hospital length of stay following lung cancer surgery.

311 Background: Wildfires pose substantial health and safety threats to patients recovering from lung cancer surgery. Without specific disaster preparedness guidelines, oncologists might resort to improvisational strategies, such as increasing the length of stay (LOS), a federal care quality measure with financial implication for hospitals, to better protect the health and safety of this medically vulnerable population. Methods: Individuals aged ≥18 years who received curative-intent lobectomy or pneumonectomy for stage I-III NSCLC between 2004 and 2021 were selected from the National Cancer Database. Exposure was defined as a Federal Emergency Management Agency (FEMA) Presidential Disaster Declaration in the county of the treatment facility between date of surgery and date of discharge from the hospital. Differences in the cumulative distribution function of LOS, defined as days between date of surgery and date of discharge from the hospital, were evaluated between exposed and propensity score matched unexposed patients, who were treated at the same facility but at a time when no disasters occurred, using the product-limit method and log-rank test. In sensitivity analysis, patients with discharge date equal to date of death (in-hospital mortality) were excluded, and the association was evaluated stratified by stage. Results: Patients exposed to a wildfire disaster declaration in the county of the treating facility had longer LOS (p<0.001) than unexposed patients (9.4days compared to 7.5 days, respectively) overall and for each of the stages (I-III) for which surgery is the recommended treatment modality. In sensitivity analysis, there were no in-hospital mortality difference between exposed and unexposed patients (10.8% and 10.5%, respectively, p=0.76). Excluding patients who died in the hospital did not change the main results. Conclusions: Patients whose facility is impacted by a wildfire disaster during recovery from lung cancer surgery have longer length of stay than similar patients treated at the same facility but at times when no disaster occurred. Future studies should evaluate whether extended hospital stay improves safety and quality of surgical care. Moreover, these findings should be considered for disaster preparedness guidelines tailored to vulnerable patient population.

Onasemnogene abeparvovec gene therapy for spinal muscular atrophy: A cohort study from the United Arab Emirates.

Spinal muscular atrophy (SMA) manifests with progressive motor neuron degeneration, leading to muscle weakness. Onasemnogene abeparvovec is a US Food and Drug Administration-approved gene replacement therapy for SMA. This study aimed to present short-term data of children in the United Arab Emirates (UAE) treated with onasemnogene abeparvovec, particularly in the context of children requiring invasive ventilatory support via tracheostomy. A retrospective analysis was performed on 60 children who received onasemnogene abeparvovec. All these children received corticosteroids. They were followed up for up to 3 months. Motor function assessments were performed before and after the gene therapy. Comprehensive clinical evaluations, including pulmonary functions, were performed at baseline and the 3-month mark. Forty-three percent were male, and the mean age at the time of infusion was 29.6 months (SD ± 17.2). The mean weight was 10.1 kg (SD 2.6). All children demonstrated marked improvements in motor function within 3 months of gene therapy administration. No adverse effects attributable to corticosteroid therapy were observed. Positive clinical outcomes, including increased ventilator-free intervals, reduced antibiotic dependency, and fewer hospital admissions, were reported among children with invasive ventilation via tracheostomy. This study demonstrates the favorable tolerability and promising responses to onasemnogene abeparvovec in invasively ventilated pediatric patients. Early improvements in motor function, as observed within 3 months post-treatment, suggest its potential as a viable therapeutic option for this vulnerable patient population.

Sarcopenia influences clinical outcome in hospitalized patients with peripheral artery disease aged 75 years and older

ObjectivesSarcopenia represents a relevant comorbidity in patients with peripheral artery disease (PAD). However, only few studies exist assessing the clinical burden of sarcopenia in PAD. MethodsAll hospitalizations of patients aged ≥75 years who were admitted due to PAD within 2005-2020 in Germany were included in the study and stratified for sarcopenia. Temporal trends and the impact of sarcopenia on treatment procedures as well as adverse in-hospital events were investigated. ResultsOverall, 1,166,848 hospitalization-cases of patients admitted due to PAD (median age 81.0 [78.0-85.0] years; 49.5% female sex) were included, of which 2109 (0.2%) were coded with sarcopenia. Prevalence of sarcopenia in these patients increased during the observational period from 0.05% in 2005 to 0.34% in 2020 (β 2.61 [95%CI 2.42 to 2.80], P<0.001). Sarcopenic PAD patients were more often female (52.1% vs. 49.5%, P=0.015), obese (6.6% vs. 5.5%, P=0.021) and revealed higher prevalences of comorbidities (Charlson comorbidity index, 7.00 [6.00-9.00] vs. 6.00 [5.00-7.00], P<0.001). Sarcopenia was associated with reduced usage of reperfusion treatments (endovascular intervention: OR 0.409 [95%CI 0.358-0.466], P<0.001; surgical revascularization: OR 0.705 [95%CI 0.617-0.805],P<0.001), but higher conduction of amputation (OR 1.365 [95%CI 1.231-1.514], P<0.001) and higher rates of major adverse cardiovascular and cerebrovascular events (OR 1.313 [95%CI 1.141-1.512], P<0.001) and in-hospital death (OR 1.229 [95%CI 1.052-1.436], P=0.009). ConclusionsSarcopenia is an under-recognized condition in PAD patients of high clinical relevance causing a crucial disease burden. Awareness of the ailment needs to be increased in daily clinical practice to identify sarcopenia and improve clinical outcome of this vulnerable patient group.

Evaluation of treatment-related problems in hemodialysis patients in Egypt: a prospective observational study

BackgroundHemodialysis (HD) patients often have multiple comorbidities, leading to care from various prescribers and a complex medication regimen. Patients on HD are particularly vulnerable to treatment-related problems (TRPs). This study aimed to evaluate the impact of the lack of clinical pharmacy services on HD care by assessing the types and frequencies of TRPs encountered in HD units.Patients and methodsThis was a prospective observational study. Data were collected from medical records and medication reconciliation of HD patients attending to a large Hospital specialized in Nephrology and Urology at the Minia region in Egypt. The frequencies and percentages of demographic data were calculated. Standard multiple regression analysis was conducted to assess predictors of TRPs.ResultsA total of 103 patients were included. The mean age was 47.6 ± 15.1 years; patients had been on HD for 5.95 ± 5.04 years, had 2.47 ± 0.57 comorbidities and took 7.02 ± 1.35 different medications. Within the included patients, 121 TRPs were identified. The most common TRPs were the need for more frequent monitoring, followed by inappropriate dose/dosing frequency and the need for additional therapy (33.9%, 26.2%, and 15.5%, respectively). We did not identify any predictors of TRP in this study.ConclusionIn the Minia HD population of Egypt, TRPs affected 75% of the patients. Therefore, involving clinical pharmacy services to tailor the optimal management plan for each patient is crucial to reduce the frequency of TRPs in this vulnerable patient population.

Clinical utility and impact of a diagnostic oncology clinic.

74 Background: Oncologists have expertise in the work-up and management of patients with a suspected diagnosis of cancer. Patients diagnosed with cancer during acute care hospitalization often have poorer outcomes than those diagnosed as outpatients. For these patients, time to appropriate cancer diagnosis, management of cancer-related symptoms, and timely initiation of treatment are key to improved outcomes. Outpatient new diagnosis clinics may improve patient outcomes by improving access to subspecialty care. Methods: Patients seen by the inpatient oncology consult service over a two-month period (8/1/23-8/31/23 and 10/1/23-10/31/23) were included in this analysis. Inpatient management of disease was defined as an invasive procedure to treat the disease or a complication of the disease, initiation of systemic anti-neoplastic treatment, or radiation therapy. Surveys regarding perceived barriers to timely outpatient oncology care were distributed to oncology fellows and attendings. A Diagnostic Oncology Clinic (DOC) was started 2/1/2024 with the goal to decrease time to first outpatient oncology by a median of 12 days to less than 10 days, decrease hospital length of stay (LOS), improve outpatient management of cancer related symptoms, and improve time to treatment. Results: A total of 95 patients were evaluated. 74 (78%) of patients had a new diagnosis of cancer. Most patients had gastrointestinal cancer (n = 40, 42%) or thoracic cancer (n = 24, 25%). 51 patients (53.7%) had metastatic disease. 48 patients (50.5%) had an ECOG performance status of 0 or 1 at the time of consultation. The median hospital LOS was 11 days (IQR, 5-19). 13 patients (13.7%) had an inpatient PET scan and 43 patients (45.3%) required inpatient management of their disease or disease-related complication. 57 patients (60%) were discharged home, 21 (22%) to an extended care facility, and 17 (18%) expired or transitioned to hospice. 35 patients (37%) were seen as new outpatients with a median time to visit of 12 days (IQR 7-20). The median time to initiation of anti-neoplastic therapy as an outpatient was 24 days (IQR 18-33). There were 29 survey respondents corresponding to a response rate of 69%. 16 (55%) felt that about half the time or less patients will have timely follow-up with an oncologist after discharge, and 19 (65%) felt half the time or less patients will have appropriate cancer-related symptom management after discharge. Conclusions: Most patients seen by the inpatient oncology consult service with a new diagnosis of cancer have advanced and symptomatic disease. Historically, there has been significant time to outpatient care and cancer-specific management led by an oncologist. Creation of a diagnostic oncology clinic may shift some diagnostic testing and symptom management from the inpatient to outpatient setting, decrease time to first outpatient visit, and improve provider workflow for a vulnerable patient population. Analysis of this intervention is ongoing.

Comprehensive secondary analysis of thrombotic events in pediatric patients receiving extracorporeal membrane oxygenation: A prospective cohort study.

This study aims to describe laboratory and clinical factors associated with thrombotic events during prolonged pediatric extracorporeal membrane oxygenation. A secondary analysis of a multi-center prospective study performed between 2012 and 2014. Patients under the age of 19years that received extracorporeal membrane oxygenation for at least 4days of therapy were included (n = 385). Univariable analysis and binomial regression were performed to evaluate predictive factors of single and multiple thrombotic events. A posteriori scoring tool was created to categorize thrombotic event severity. Over 39% of children receiving prolonged ECMO experienced a thrombotic event (TE). Binomial regression demonstrated an association between higher transfused platelet volume (mL/kg) (OR 1.04, CI: 95% 1.01-1.06, p = 0.003), Anti-Xa (OR 5.38, CI: 95% 1.22-23.8, p = 0.026) and aPTT (OR 1.01, CI: 95% 1.00-1.02, p = 0.032) the day prior to TE. Patients experiencing multiple TEs were associated with higher platelet transfusion volume (mL/kg) (OR 1.08, CI: 95% 1.05-1.12, p =< 0.001), antithrombin III (OR 1.03, CI: 95% 1.01-1.04, p = 0.001) and aPTT (OR 1.02, CI: 95% 1.01-1.03, p = 0.009). Patients experiencing multiple thrombotic events had a higher risk of 28-day mortality based on a cumulative clot severity score >4 (OR 2.37 (CI: 95% 1.32-4.24). Current lab tests show limited sensitivity to predict these events the day prior in a vulnerable patient group, leading to potential ECMO circuit failures. Patients with multiple thrombotic events during ECMO therapy face increased mortality risks, highlighting the need for dynamic reporting tools like clot severity scores and detailed documentation of interventions to enhance understanding and improve outcomes.

Kidney Replacement Therapies in Advanced Heart Failure - Timing, Modalities, and Clinical Considerations.

Acute kidney dysfunction is commonly encountered in advanced heart failure and carries significant prognostic implications, often leading to poorer outcomes and increased mortality. It can alter the course of decision making for left ventricular assist device (LVAD) and cardiac transplantation candidacy. Kidney replacement therapies (KRT) offer a critical intervention in this context but require careful consideration of timing, various types of KRT modalities, individual patient preferences and circumstances. This review discusses the intricacies of KRT in advanced heart failure, examining how to optimize timing and choose among the various KRT modalities. It also provides a detailed discussion on the unique clinical scenarios that clinicians may face when treating this vulnerable patient group.

Clinical outcomes of peripherally inserted central catheters in patients with gastroenterological diseases: Report of a 9-year experience.

Peripherally inserted central catheters (PICCs) are safe and useful alternatives to centrally inserted central catheters (CICCs). Several studies have investigated the effectiveness and safety of PICCs; however, few have focused on their use in patients with gastroenterological diseases. In the present study, we evaluated the outcomes of patients with gastroenterological diseases who received PICCs and identified the risk factors associated with central line-associated blood stream infection (CLABSI). We retrospectively examined hospitalized patients at our institution who received PICCs between 2015 and 2023. We evaluated the data on their clinical characteristics, complications, and outcomes. Furthermore, we investigated the risk factors for CLABSIs. A total of 405 patients were included (262 men and 143 women). The median age was 71 (range, 15-94) years. The vessels were inserted in the basilic, cephalic, and brachial veins in 366 (90%), 22 (6%), and 17 (4%) patients, respectively. The median procedure time was 32 [6-149] min. The median dwell time was 16 [0-188] days. CLABSI, catheter occlusions, phlebitis, and exit-site skin infection occurred in 14 (3.5%; 1.77/1000 catheter days), 6 (1.5%; 0.76/1000 catheter days), 3 (0.7%; 0.38/1000 catheter days), and 1 (0.2%; 0.13/1000 catheter days) patients, respectively. There was no case of deep vein thrombosis or pulmonary thrombosis due to PICC placement. Multivariate analysis performed using a Cox's proportional hazard regression model revealed that patients with gastroenterological malignancies had an independently higher risk for CLABSIs (odds ratio [OR]: 3.25, 95% confidence interval [CI]: 1.05-10.05, p = 0.041) and that older age (⩾70 years) tended to be associated with CLABSIs (OR: 3.61, 95% CI: 0.98-13.32, p = 0.054). Gastroenterological malignancies and older age were associated with a higher risk of CLABSIs. Rigorous catheter management is crucial for preventing complications, particularly in vulnerable patient subgroups.

Adrenal Insufficiency in Patients with Beta Thalassemia: A Meta-Analysis

Background and Objectives: Adrenal insufficiency (AI) can be a significant concern in patients with transfusion-dependent homozygous beta thalassemia (bThal) due to the chronic disease burden and frequent blood transfusions that these patients require. The prevalence of AI in this population remains unclear, with studies often lacking control groups for comparison. This meta-analysis aimed to estimate the proportion of patients with transfusion-dependent bThal who exhibit evidence of AI. Materials and Methods: A systematic review following PRISMA guidelines identified 19 studies for analysis. Results: Despite the variability in the diagnostic methods used to ascertain AI, the meta-analysis revealed that approximately one-third of patients had evidence of AI, with the prevalence rising to 50% in studies focused on adults with bThal. Conclusions: These findings suggest an increased risk of AI in patients with bThal compared to the general population. Clinicians should consider tailored management strategies, including glucocorticoid coverage during surgical procedures, to mitigate the risk of adrenal crises in this vulnerable patient group. Further research is needed to optimize adrenal surveillance and management in patients with bThal.

Prosthesis applications and challenges in children with earthquake-related amputations

BackgroundAmputations are among the most important traumatic injuries caused by earthquakes. However, data on amputee children and prosthesis application is quite limited in the literature. The aim of the study is to evaluate the injury-related data, stump problems, prosthesis application, difficulties and complications experienced with prosthesis during follow-up of children with 2023 Kahramanmaraş earthquake-related limb loss. Patients and methodsSociodemographic and injury-related data, pre-amputation and post-amputation interventions, prosthesis application, current prosthetic problems, and revision surgeries of the amputee children were recorded. ResultsMedian age of patients (n = 102) admitted to our center was 13.0 years. 67.6 % of patients had one or more concomitant injuries. Median time and number of amputations were 4 (0–57) days and 1 (1–4), respectively. Of the total 120 amputations, 67.5 % (n = 81) were lower extremity amputations. Most common amputation levels were transtibial (29.1 %, n = 35), transfemoral (22.5 %, n = 27), and transhumeral (15.8 %, n = 19). Most amputees (56.8 %) underwent revision surgery after initial amputation. Median duration of time from amputation to prosthesis application was 184 (28–314) days. For 25 prostheses, a socket revision was required. Six patients had surgical revision of the stumps to allow prosthetic fit and mobility (due to bone overgrowth, soft tissue failure, heterotopic ossification). ConclusionLimited healthcare facilities, surgeries performed under emergency conditions, accompanying multiple traumas, inadequate follow-up conditions, and additional difficulties arising from the pediatric patient group lead to difficulties in the care of pediatric amputee patients. Our results will guide the care of this vulnerable patient population in the event of a similar unfortunate disaster.

Prevalence and Outcomes of Candida auris Infections in a Tertiary Hospital in the United Arab Emirates (UAE).

Background Candida auris (C. auris) is an emerging serious threat to healthcare settings, with an average mortality of 45% in cases of bloodstream infections. This study aimed to determine the prevalence of C. auris in a single center in the UAEduring the year 2022 and understand risk factors related to poor outcomes. Methods This retrospective cohort chart review at Al-Qassimi Hospital encompassed all confirmed Candida infections, including C. auris, from January to December 2022. The study involved male and female patients aged 13 years and older, using comprehensive data extracted from the hospital's electronic healthcare records. The analysis included clinical, laboratory, and epidemiological data. Adhering to the 2011 Declaration of Helsinki and Good Pharmacoepidemiology Practices, the study received Institutional Review Board approval, with informed consent waived due to its retrospective design. Data were summarized using appropriate statistical methods, including the unpaired t-test, Mann-Whitney U test, Chi-square test, and Fisher exact test. A significance level of 95% (p<0.05) was maintained throughout the statistical analyses. Results Of the 75 confirmed Candidainfections, 53 (70.7%) were C. auris-positive cases.About 23 (43.4%) of the C. auris group were above 65 years old. Most cases of C. auris group were hospital-acquired (49, 92.5%). The highest number of positive cases were found in urine samples. The demographic and clinical profiles of the C. auris and non-auris groups candidemia were largely similar, except for differences in antifungal use history and ICU requirements. Notably, the C. auris group had a significantly lower history of antifungal use and a lower ICU requirement compared to the non-auris group. The study also highlighted the higher mortality rate associated with candidemia. While mortality was higher in the non-auris group, the difference was not statistically significant. Conclusions The findings of the study suggest that while C. auris poses a serious threat, particularly in hospital settings; the clinical and demographic factors influencing its spread and impact are complex and warrant further investigation. Understanding these factors is crucial for developing effective strategies to prevent and manage C. auris infections, particularly in vulnerable patient populations.

Abstract B135: Association of residential economic and racial segregation with metastatic disease at diagnosis in pediatric patients with solid tumors

Abstract Background: Disparities in pediatric cancer outcomes by race and ethnicity may be influenced by neighborhood characteristics, particularly residential economic and racial segregation. Prior to a new cancer diagnosis, pediatric patients are vulnerable to structural barriers embedded in their neighborhoods. In particular, residential economic and racial segregation may impede access to initial care for early cancer detection, increasing the likelihood of presenting with distant metastatic disease at diagnosis that can translate to excess morbidity and mortality. This study assesses the association of residential economic and racial segregation as measured by the Index of Concentration at the Extremes (ICE) with the likelihood of presenting with distant metastatic disease (as compared to local or locoregional disease) among children newly diagnosed with cancer. Methods: We studied a cohort of pediatric patients diagnosed with solid tumors at Children’s Healthcare of Atlanta between 2010 and 2016. Patients’ ZIP codes were linked to the ICE, which was constructed at the ZIP code level using American Community Survey 2012-2016 five-year estimates. The ICE was categorized into tertile 1 (most deprived) through tertile 3 (most privileged). Multivariable logistic regression models were used to assess the association between residential economic and racial segregation, defined by tertiles of the ICE, and the likelihood of presenting with distant metastatic disease, as determined by initial cancer staging. All models adjusted for patient- and disease-level covariates, including age, sex at birth, health insurance type, and cancer type. Results: Among 829 patients identified in our analytic sample, 27.6% had distant metastatic disease at diagnosis. Living in the most deprived (ICE tertile 1) versus the most privileged (ICE tertiles 2/3) neighborhoods was significantly associated with a higher likelihood of presenting with distant metastatic disease at diagnosis (adjusted odds ratio [OR] = 1.46; 95% confidence interval [CI] = 1.03 to 2.07; p=0.03). Additionally, non-Hispanic Black patients living in the most deprived neighborhoods were more likely to have distant metastatic disease at diagnosis compared to non-Hispanic White patients living in the most privileged neighborhoods (adjusted OR = 1.83; 95% CI = 1.15 to 2.92; p=0.002). Conclusion: This study provides new insights into how residential economic and racial segregation is associated with metastatic disease at diagnosis among children presenting with a new solid tumor. Our findings highlight the need for geographically targeted interventions to improve community care, resource allocation and investment, and public policies aimed at supporting this vulnerable patient population. Citation Format: Alexandra Cathcart, Sharon M. Castellino, Lu Zhang, Karen Wasilewski-Masker, Andrew L. Hong, Heeju Sohn, Xu Ji. Association of residential economic and racial segregation with metastatic disease at diagnosis in pediatric patients with solid tumors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B135.

Efficacy of late-onset antiviral treatment in immunocompromised hosts with persistent SARS-CoV-2 infection.

Four years after the onset of the global coronavirus disease 2019 (COVID-19) pandemic, the immunocompromised are at greatest risk of developing life-threatening severe disease. However, specific treatment plans for this most vulnerable patient group have not yet been developed. Employing a CD4+ and CD8+ T cell-depleted immunocompromised mouse model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we explored therapeutic options of persistent infections with standard-of-care paxlovid, molnupiravir, and the experimental therapeutic 4'-fluorouridine (4'-FlU). Late-onset treatment initiated 14 days after infection was efficacious, but only 4'-FlU was rapidly sterilizing. No treatment-experienced viral variants with reduced susceptibility to the drugs emerged, albeit virus replication rebounded in animals of the paxlovid group after treatment end. This study supports the use of direct-acting antivirals (DAAs) for late-onset management of persistent SARS-CoV-2 infection in immunocompromised hosts. However, treatment courses likely require to be extended for maximal therapeutic benefit, calling for appropriately powered clinical trials to meet the specific needs of this patient group.

Paediatric formulations-part of the repurposing concept?

The lack of available appropriate paediatric formulations is a significant challenge for optimal treatment in children. The resulting manipulation of adult medicines implies risk of medication errors, inaccurate dosing, and unacceptable dosage forms resulting in non-compliance. This represents significant unmet needs for a large and vulnerable patient group. Currently, the repurposing discussions seems only to a limited degree to cover the aspects of paediatric off-label use of adult medicines, including reformulation strategies to cover unmet needs for suitable formulations in the youngest age groups. Similarly, limited focus seems to be put on incentives in this specific area of repurposing. This paper will discuss the role of reformulation for paediatric needs as part of the repurposing concept, and potential factors contributing to barriers to incentivise the development of new formulations for children.

Vaccination Rates in Patients with Chronic Inflammatory Skin Diseases and Immunomodulatory Systemic Therapies-Vaccinations against SARS-CoV-2, Influenza Virus or Varicella Zoster Virus.

The national guidelines and the Standing Committee on Vaccination (STIKO) of the Robert Koch Institute (RKI) in Germany support preventive vaccinations for patients under immunomodulatory treatments. Retrospective analysis of data from patients with chronic inflammatory skin diseases from December 2021 to December 2022 with a focus on preventive vaccinations against influenza virus, varicella zoster virus, or SARS-CoV-2. Patients with chronic inflammatory skin diseases were referred to our university outpatient's clinic for recommendations of systemic therapy. Vaccinations against influenza virus, varicella zoster virus, or SARS-CoV-2 were documented in 7365 analyzed patient files. A total of 79.7% were completely vaccinated against SARS-CoV-2, 49.7% patients were vaccinated against the influenza virus, and only 9.2% were completely vaccinated against varicella zoster virus. In our patients who came for counselling before or during systemic treatment, vaccination rates against SARS-CoV-2, varicella zoster virus, or influenza virus were low. Patients age 60 and above had higher rates than the average German population of the same age, but still no satisfying protection. We suggest informing patients about preventive vaccination before and during systemic immunomodulatory treatments and emphasize the need for active communication in this vulnerable patient group.

Do not forget about transplant patients during disasters.

The frequency of natural disasters and man-made conflicts has risen significantly in the past two decades, coinciding with an increase in kidney transplant recipients globally. This review addresses the critical need for disaster preparedness to mitigate the severe impacts on this vulnerable patient cohort. Kidney transplant recipients are highly dependent on robust healthcare infrastructures for ongoing care, including specialized medical staff, advanced diagnostics, and a consistent supply of immunosuppressive medications. Disasters disrupt these essential services, leading to increased risks of organ rejection, infections, and other medical complications. Strategies at various levels, from government to individual patients, can help maintain care continuity during such crises. Effective disaster preparedness plans involving strategic medication stockpiling, emergency communication systems, and patient education are crucial to support kidney transplant recipients. By implementing these measures, healthcare systems can better protect the health and well being of transplant patients during and after disasters.

Current Advances and Challenges in the Management of Cutaneous Squamous Cell Carcinoma in Immunosuppressed Patients.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and poses a significant risk to immunosuppressed patients, such as solid organ transplant recipients and those with hematopoietic malignancies, who are up to 100 times more likely to develop cSCC compared with the general population. This review summarizes the current state of treatment for cSCC in immunosuppressed patients, focusing on prevention, prophylaxis, surgical and non-surgical treatments, and emerging therapies. Preventative measures, including high-SPF sunscreen and prophylactic retinoids, are crucial for reducing cSCC incidence in these patients. Adjusting immunosuppressive regimens, particularly favoring mTOR inhibitors over calcineurin inhibitors, has been shown to lower cSCC risk. Surgical excision and Mohs micrographic surgery remain the primary treatments, with adjuvant radiation therapy recommended for high-risk cases. Traditional chemotherapy and targeted therapies like EGFR inhibitors have been utilized, though their efficacy varies. Immunotherapy, particularly with agents like cemiplimab and pembrolizumab, has shown promise, but its use in immunosuppressed patients requires further investigation due to potential risks of organ rejection and exacerbation of underlying conditions. Treatment of cSCC in immunosuppressed patients is multifaceted, involving preventive strategies, tailored surgical approaches, and cautious use of systemic therapies. While immunotherapy has emerged as a promising option, its application in immunosuppressed populations necessitates further research to optimize safety and efficacy. Future studies should focus on the integration of personalized medicine and combination therapies to improve outcomes for this vulnerable patient group.

COVID-19 and Cancer Care: A Review and Practical Guide to Caring for Cancer Patients in the Era of COVID-19.

COVID-19, a novel infectious disease caused by the emergence of the SARS-CoV-2 virus in 2020, has had a profound impact on healthcare, both at the individual and population level. The impact at the population level was felt most acutely during the emergency phase of the pandemic, with hospital capacity issues leading to widespread disruptions and delays in the delivery of healthcare services such as screening programs and elective surgeries. While hospitals are no longer being acutely overwhelmed by COVID-19 patients, the impact of the virus on vulnerable patient populations such as cancer patients continues to be of ongoing consequence. Cancer patients remain at high risk of hospitalization, ICU admission, and death due to COVID-19, even in the era of vaccination. Infection prevention and risk mitigation strategies such air quality control, masking, testing, vaccination, and treatment should therefore be integrated into the usual care and counseling of cancer patients moving forward to avoid preventable morbidity and mortality from this infection and ensure the safety of this vulnerable cohort as they navigate their cancer diagnosis and treatment in the era of COVID-19.