Unique Hemoglobinopathy Pattern Following Treatment with Voxelotor.

OBJECTIVE: Voxelotor, a FDA-approved drug for the treatment of patients with sickle cell disease (SCD), inhibits hemoglobin S (HbS) polymerization and increases total hemoglobin via hemolysis reduction. This drug has shown unique patterns in hemoglobin fractionation, affecting its interpretation. We aimed to evaluate whether these voxelotor-induced changes can be linked to improvement of hemolysis markers in pediatric patients on voxelotor. METHODS: A total of 15 patients (age 12 to 20 years; 40% females) on voxelotor were evaluated to compare changes in the hemoglobin fractionation by capillary electrophoresis, total hemoglobin, reticulocyte percentage (retic%), lactate dehydrogenase (LDH), and bilirubin measurements before and after the recorded date of voxelotor prescription. RESULTS: Hemoglobin fractionation showed changes in the profile of 60% (9/15) of the patients studied. Out of the 9 patients for which voxelotor showed changes in the hemoglobin fractionation, 44% (4/9) had an increase of >1 g/dL in their total hemoglobin after voxelotor treatment was started. Assessment of other hemolysis markers available showed decreased LDH (4/4), retic % (6/8), and bilirubin (3/4). CONCLUSIONS: Unique pattern of hemoglobin fractionation analysis following therapy with voxelotor has potential as a tool for the assessment of response and/or compliance to voxelotor for the treatment of SCD.

Comparison of random urine protein/creatinine ratio with 24-hour urine protein in suspected pre-eclampsia.

Introduction: Proteinuria is one of the classical criteria for the diagnosis of pre-eclampsia. The gold standard remains the measurement of 24-h urine protein which is time consuming and prone to preanalytical errors. Random urine protein creatinine ratio (UPCR) is endorsed by clinical practice guidelines as a faster alternative. The aim of this study was to evaluate the correlation between the 24-h urine protein excretion and UPCR in the identification of proteinuria in suspected preeclamptic patients. Method: A total of 51 women with suspected pre-eclampsia from the maternal fetal clinic of our institution were retrospectively studied. The correlation between the UPCR in random urine samples and protein excretion in the 24-h urine collection was determined by Deming Regression analysis and Pearson correlation on EP evaluator and SPSS respectively. Result: There was a significant positive correlation between the numerical values obtained by 24-h urine protein and the UPCR (R = 0.88, P < 0.001). Concordance analysis showed 81.1% positive agreement for proteinuria between methods (>300 mg/24hr and >0.3) and 71.4% negative agreement. The clinical sensitivity and specificity of the UPCR was 74% and 69% respectively. Conclusion: Overall, UPCR was well correlated with 24-h urine protein and could be an effective and compliant screening tool to indicate proteinuria in preeclamptic patients.

Pediatric vitamin D: Pseudo-hypervitaminosis.

BACKGROUND: Vitamin D toxicity is rare in pediatric population. Falsely elevated levels of 25-hydroxyvitamin D have been reported as a major challenge with immunoassay methods for quantifying vitamin D metabolites. CASE PRESENTATION AND METHOD: Here, we present two pediatric cases of falsely elevated 25-hydroxyvitamin D that resulted in unnecessary further testing. We also report significant same-day variation in the measurement of 25-hydroxyvitamin D using the Abbott i2000SR immunoassay. Samples were spun twice and their values were confirmed with the gold standard liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for confirmation. CONCLUSION: The addition of a centrifugation step prior to sample testing resolved the variation observed in the measurement of 25-hydroxyvitamin D levels. The patient samples were confirmed with instruments from a different vendor and LC-MS/MS. Re-centrifugation of samples resolved the variation in the 25-hydroxyvitamin D values.

Transition Readiness in Youth with Inflammatory Bowel Disease.

OBJECTIVES: To examine readiness of adolescents and young adults (AYAs) with inflammatory bowel disease (IBD) to transition to adult care. STUDY DESIGN: A cross-sectional multicenter study evaluating transition readiness in individuals with IBD 16-19 years old prospectively recruited from 8 Canadian IBD centers using the validated ON Taking Responsibility for Adolescent to Adult Care (ON TRAC) questionnaire. Secondary aims included (1) screening for depression and anxiety using the 8-item Personal Health Questionnaire Depression Scale and The Screen for Child Anxiety Related Emotional Disorders questionnaires, respectively; (2) evaluating the association between depression and anxiety with readiness and disease activity; and (3) subjectively evaluating AYA readiness based on physician and parent assessments. RESULTS: In total, 186 participants (139 adolescent, 47 young adult) were enrolled, mean age 17.4 years (SD, 0.87). ON TRAC scores determined that 26.6% of AYAs at pediatric and 40.4% at adult centers reached the threshold of readiness. On multivariable linear regression analysis age was positively (P = .001) and disease remission negatively (P = .03) associated with ON TRAC scores. No statistically significant differences were determined across centers. A significant percentage of AYAs reported moderate-to-severe depression (21.7%) and generalized anxiety (36%); however, neither were significantly associated with ON TRAC scores. Notably, physician and parental assessment of AYA readiness correlated poorly with ON TRAC scores (⍴ = 0.11, ⍴ = 0.24, respectively). CONCLUSIONS: Assessment of transition readiness in AYAs with IBD highlighted that a large proportion do not have adequate knowledge or behavior skills needed for transition to adult care. This study infers that readiness assessment tools are essential during transition to identify deficits in knowledge and behavior skills that could be specifically targeted by the youth, caregivers, and multidisciplinary team.

The Impact of the COVID-19 Pandemic on IBD Care in Alberta: Patient and Provider Perspectives.

Objective: The COVID-19 pandemic necessitated changes in the delivery of ambulatory care for patients with inflammatory bowel disease (IBD), including transitioning many visits to virtual formats and delaying non-urgent assessments. We aimed to evaluate the impact of the COVID-19 pandemic on IBD patient care from health care providers' (HCP) and patients' perspectives. Methods: We administered a 42-question HCP survey and a 44-question patient survey, which evaluated HCP and patient experience and satisfaction with care delivery and delays in access to IBD care during the first wave of the COVID-19 pandemic. Results: Surveys were completed by 19.2% (24/125) HCPs and 25.8% (408/1581) patients. Overall, 82.7% of patients with IBD maintained their care without disruption. The majority of patients were satisfied with a transition to virtual care. All HCPs were willing to use virtual care in the future; however, 60% (14/24) of HCPs reported that virtual care was not equivalent to in-person visits. Patients reported concerns around access to health resources, the uncertainty of IBD-specific care, and fear and stress due to employment uncertainty and safety. Providers also reported concerns about patient safety, patient education, adequate remuneration and challenges with providing care for new patients on virtual platforms. Conclusion: While some delays in health care delivery occurred during the first wave of the pandemic, both patients and HCPs were satisfied with a transition to new models of care delivery. These models may remain in place post-pandemic and allow for flexibility in care delivery that is acceptable to both patients and HCPs.

ChatGPT-Exploring Its Role in Clinical Chemistry.

OBJECTIVE: To evaluate the utility of artificial intelligence-powered language models (ChatGPT 3.5 and GPT-4) compared to trainees and clinical chemists in responding to common laboratory questions in the broad area of Clinical Chemistry. METHODS: 35 questions from real-life case scenarios, clinical consultations, and clinical chemistry testing questions were used to evaluate ChatGPT 3.5, and GPT-4 alongside clinical chemistry trainees (residents/fellows) and clinical chemistry faculty. The responses were scored based on category and based on years of experience. RESULTS: The Senior Chemistry Faculty demonstrated superior accuracy with 100% of correct responses compared to 90.5%, 82.9%, and 71.4% of correct responses from the junior chemistry faculty, fellows, and residents respectively. They all outperformed both ChatGPT 3.5 and GPT-4 which generated 60% and 71.4% correct responses respectively. Of the sub-categories examined, ChatGPT 3.5 achieved 100% accuracy in endocrinology while GPT-4 did not achieve 100% accuracy in any subcategory. GPT-4 was overall better than ChatGPT 3.5 by generating similar correct responses as residents (71.4%) but performed poorly to human participants when both partially correct and incorrect indices were considered. CONCLUSION: Despite all the advances in AI-powered language models, ChatGPT 3.5 and GPT-4 cannot replace a trained pathologist in answering clinical chemistry questions. Caution should be observed by people, especially those not trained in clinical chemistry, to interpret test results using chatbots.

Validation of atovaquone plasma levels by liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring in pediatric patients.

Background: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS. Methods: Atovaquone was extracted from a 10 µL volume of K2-EDTA human plasma using a solution consisting of ACN: EtOH: DMF (8:1:1 v:v:v), separated using reverse-phase chromatography, and detected using a SCIEX 5500 QTrap MS system. LC-MS/MS assay performance was evaluated for precision, accuracy, carryover, sensitivity, specificity, linearity, and interferences. Results: Atovaquone and its deuterated internal standard were analyzed using a gradient chromatographic method that had an overall cycle-time of 7.4 min per injection, and retention times of 4.3 min. Atovaquone was measured over a dynamic concentration range of 0.63 - 80 µM with a deviation within ≤ ± 5.1 % of the target value. Intra- and inter-assay precision were ≤ 2.7 % and ≤ 8.4 %, respectively. Dilutional, carryover, and interference studies were also within acceptable limits. Conclusions: Our studies have shown that our LC-MS/MS-based method is both reliable and robust for the quantification of plasma atovaquone concentrations and can be used to determine the effective dose of atovaquone for pediatric patients treated for AML.

Outcomes in Patients with Inflammatory Bowel Disease Transitioning from Pediatric to Adult Care: A Scoping Review.

PURPOSE: Approximately 25% of inflammatory bowel disease (IBD) patients are diagnosed in childhood and the incidence is increasing. Thus, more patients will transition to adult care in the future. Within the literature, transition readiness has been deemed important to achieving a successful transition; however, it is unclear what outcomes define success. This scoping review aims to summarize the literature on outcomes surrounding transition from pediatric to adult care in patients with IBD. METHODS: A scoping review was conducted with the following steps: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting the data, (5) collating, summarizing, and reporting results, and (6) consultation with an additional researcher. Studies were identified from 5 databases and were included in part if (1) IBD was a disease of interest, (2) referred to transition as the movement and adjustment from pediatric to adult care, and (3) evaluated patient outcomes up to 5 years after first adult appointment and/or defined a successful or unsuccessful transition. RESULTS: Twenty-six peer-reviewed studies were included. Four studies defined transition success, while 2 studies defined an unsuccessful transition. Transition outcomes were categorized into these 6 themes: being comfortable in adult care (n = 4); health care utilization (n = 19); disease management (n = 15); knowledge (n = 5); quality of life (n = 6); self-efficacy (n = 7). CONCLUSIONS: Most studies evaluated transition outcomes by themes of health care utilization (n = 19) and disease management (n = 15). Future research should focus on engaging patients along with providers in order to create a consensus on indicators of transition success.

Performance evaluation of the XT MicroSlide assay pairs on the Vitros XT 7600 compared to VITROS single microslide assays on Vitros 5600.

Objectives: Pediatric hospitals are always challenged by specimen volumes and thus any innovation in this realm is very welcome. With the introduction of Microslide assay pairs, we aimed to evaluate the analytical performance of the Vitros XT MicroSlide assay pairs on the Vitros XT 7600 compared to single MicroSlides. Design: Performance characteristics included within-run precision, analytical measurable range, method comparison, and interference verification. We compared six XT MicroSlide pairs on the Vitros XT 7600 with twelve corresponding single slide assays on the Vitros 5600 system. Results: The XT MicroSlides on Vitros XT 7600 demonstrated excellent precision, equivalent analytical measurable range, and strong method correlation with single slide assays on Vitros 5600 for most of the assays tested. Within-run CVs of the analytes ranged between 0.32% and 2.93% with between-run CV of less than 8.8% and linearity for all analytes was within the manufacturer's specified range. Interference studies showed comparable effects of hemolysis, lipemia, and bilirubin on both instruments. Conclusions: The XT MicroSlides are comparable to the single MicroSlide assays with improved efficiency, turnaround times and lower sample volumes.

True hyponatremia in the setting of pegasparagase-induced hypertriglyceridemia: A case report.

Pegasparagase (PEG-Asparaginase) induced hypertriglyceridemia is rare in the treatment of lymphoblastic lymphoma in children. We present a case of PEG-asparaginase induced hypertriglyceridemia that was incidentally identified and suspicion of its interference with sodium measurement in the clinical laboratory. The use of a direct ion selective method clarified the presence of true hyponatremia. The patient was treated with an oral Fenofibrate therapy which resolved the hypertriglyceridemia. This case highlights that PEG-asparaginanse and Olazanpine can induce hypertriglyceridemia in acute lymphoblastic leukemia and it may be useful to obtain baseline triglyceride measurements for these patients.

SARS-CoV-2 anti-spike antibodies after vaccination in pediatric heart transplantation: A first report.

BACKGROUND: BACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant. METHODS: We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center. RESULTS: Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28 of 40 (70%) post-HTx recipients (median antibody level 10.9 AU/ml). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a known pre-vaccination SARS-CoV-2 viral infection had a detectable SARS-CoV-2 Anti-Spike IgG. All 12 vaccinated pre-HTx patients had a detectable antibody (median antibody level 11.6 AU/ml) including 5 patients that maintained detectable antibodies post-HTx. There were no cases of myocarditis among the total of 17 pre-HTx and 81 post-HTx patients that underwent SARS-CoV-2 vaccination. CONCLUSION: Our data suggest that a significant proportion of pediatric HTx recipients have no detectable antibody response after SARS-CoV-2 vaccination and support the recommendation to complete the vaccination series prior to HTx in those pediatric patients waiting for HTx.

Polysomnography shows sleep fragmentation in patients with inactive inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), classified as Crohn's disease or ulcerative colitis, is a chronic inflammatory condition that affects the gastrointestinal tract. Fatigue is a common symptom of IBD, even in periods of inactive disease; however, the cause of this fatigue is unknown. Studies have suggested that altered sleep patterns may be associated with the fatigue experienced by IBD patients. The aim of our study was to assess the sleep quality of patients with inactive IBD who report fatigue. METHODS: We conducted a prospective observational pilot study that examined IBD outpatients with inactive disease who had complaints of fatigue. Upon enrolment, patients underwent Level 1 diagnostic polysomnography for one night to measure objective sleep parameters. Patients were also asked to complete 3 validated questionnaires to assess fatigue, depression levels, and subjective sleep quality. RESULTS: Fifteen patients (7 with CD, 8 with UC) were enrolled in the study; their mean age was 38.6±11.6 years. IBD patients had a mean spontaneous arousal index of 20.0±9.7 arousals /h. Patients spent an average of 6.6%, 60.4%, 15.2%, and 17.9% of their total sleep time in stages N1, N2, N3 and rapid-eye-movement sleep, respectively. Four (26.7%) patients had obstructive sleep apnea, and 7 (46.7%) patients experienced periodic limb movements of sleep. CONCLUSIONS: Patients with IBD experienced altered sleep patterns and high rates of sleep fragmentation. Further research is needed to determine how poor sleep quality can be treated in patients with IBD.

The Investigation of Lipoxygenases as Therapeutic Targets in Malignant Pleural Mesothelioma.

Advanced malignant pleural mesothelioma (MPM) has an extremely poor prognosis with limited chemotherapy options, therefore the identification of new therapeutic targets would aid in disease management. Arachidonic acid is metabolised by cyclooxygenase and lipoxygenase enzymes. The lipoxygenase isoenzymes 5-LOX and 12-LOX have been implicated in carcinogenesis. We aimed to examine 5-LOX and 12-LOX protein expression in a large retrospective series of mesothelioma samples. Further to this, the in vitro cytotoxic effects of lipoxygenase pathway inhibitors were investigated in mesothelioma cells. Archival samples from 83 patients with MPM were examined by immunohistochemistry for expression of the 5-LOX and 12-LOX proteins. The MTS assay was used to assess cell viability following 72 h treatment with the lipoxygenase pathway inhibitors baicalein, licofelone, MK-886 and zileuton in the MPM cell lines NCI-H2052, NCI-H2452 and MSTO-211H. Positive 12-LOX protein expression was recorded in 69/83 (83%) and positive 5-LOX expression was observed in 56/77 (73%) of MPM tissue samples. Co-expression of 5-LOX with 12-LOX was seen in 46/78 (58%) of MPM samples. Positive expression of 5-LOX, 12-LOX and COX-2 proteins was identified in the NCI-H2052, NCI-H2452 and MSTO-211H MPM cell lines. Baicalein (12-LOX and 15-LOX inhibitor) was effective in 3/3 MPM cell lines at low concentrations with an IC50 range of 9.6 µM to 20.7 µM. We have demonstrated that the 5-LOX and 12-LOX proteins are expressed in a significant proportion of MPM samples (73% and 83% respectively) and may represent novel therapeutic targets in this disease. We have demonstrated that the inhibition of the LOX pathway using baicalein may be effective as a novel treatment for MPM, however further human pharmacokinetic studies are required in order to establish whether the concentration used in vitro is clinically achievable.