Laboratory Monitoring Research Articles

Monte Carlo simulation of photo-peak efficiency response function and calculation of total efficiency for a NaI (Tl) scintillator detector

Abstract NaI (Tl) scintillation detectors are widely used in laboratories and in the field of gamma-ray spectrometry where detector efficiency is a key factor for successful quantitative γ ray analysis. In this work, Monte Carlo simulations using MCNPX code have been performed in order to evaluate energy resolution as a full width at half maximum (FWHM) of the peak and absolute efficiency of NaI detectors. Also, the detection efficiency and energy resolution for the NaI (Tl) scintillation detector of Tehran Research Reactor (TRR) pollution monitoring laboratory was measured. Simulation results were compared to experimental data and good agreement are obtained. In radioactive analyzing laboratory, precise determination of the detector efficiency according to any different gamma energy is a very important parameter whereas it uses in daily laboratory work.

CTNI-81. PROPOSAL FOR A PHASE IB PILOT CLINICAL TRIAL TO STUDY SAFETY AND IMPROVING ANTI-NEOPLASTIC ADVERSE EFFECTS BY ADDITION OF NATURAL MARINE PRODUCT FUCOIDAN TO THE STANDARD THERAPY FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (GBM)

Abstract INTRODUCTION GBM is the most aggressive primary brain tumor. Despite standard of care (SOC) with the Stupp protocol and tumor treating fields (TTFs), survival remains poor. In addition, SOC treatment is associated with 96% any adverse effects (AE) and 25% severe AEs (Chinot et al, NEJM 2014), which affects quality of life (QOL) and can lead to early treatment termination. Therefore, novel therapies are needed and minimization of chemoradiation-related AEs is crucial. Marine natural product, fucoidan, may have an important role in oncological management as tumor-directed therapy and as a protectant against chemoradiation-related AEs. Fucoidan is a seaweed-derived sulfated polysaccharide. Mounting evidence garnered from randomized clinical trials for colon, head and neck, and lung cancer patients suggests that fucoidan can improve certain AEs associated with chemoradiation. Furthermore, data gleaned from multiple studies have shown that fucoidan is tolerable with a good safety profile. HYPOTHESIS Fucoidan is safe in combination with chemoradiation and chemotherapy and improves treatment related AE profile. Fucoidan may improve survival outcome in GBM patients by augmenting cytotoxic effects, inhibiting angiogenesis, and improving the tolerability of SOC therapy. METHOD 12 newly diagnosed GBM patients will be enrolled. A Fucoidan-based product will be administered orally at the established dose for cancer patients daily with concurrent chemoradiation therapy and adjuvant chemotherapy over 6 months. Patients will be evaluated weekly to monthly for AEs and QOL scoring; laboratory and brain MRI monitoring will be performed per SOC guidelines. NK cell activity, proinflammatory cytokines, including interleukin (IL)-1β, will be measured. POTENTIAL OUTCOME This pilot study may establish a foundation for future larger randomized clinical trials to treat brain cancer more effectively by adding nature products.

CTNI-83. PROPOSAL FOR A PILOT PHASE 1B CLINICAL TRIAL WITH ADDITION OF NATURAL MARINE PRODUCT FUCOIDAN TO ANTI-NEOPLASTIC THERAPY FOR PATIENTS WITH RECURRENT GLIOBLASTOMA (RGBM) TO IMPROVE FATIGUE AND OTHER HEALTH-RELATED QUALITY OF LIFE (HRQOL) SYMPTOMS

Abstract BACKGROUND Recurrent Glioblastoma (rGBM) has poor outcome with limited treatment options. rGBM causes significant fatigue and other health-related quality of life (HRQOL) symptoms secondary to tumor progression and anti-neoplastic therapies. More than 80% of brain tumor patients were found to experience fatigue during anti-neoplastic therapy and the incidence of cancer related fatigue may reach 89-94% among patients with rGBM. Therefore, improvement of fatigue and HRQOL in rGBM patients are crucial. Marine natural product, fucoidan, available as health supplement in the US, was found to play important roles in oncological management as supportive therapy against cancer and chemoradiation-related adverse effects and as a potential anti-neoplastic therapy. Fucoidan is a seaweed-derived sulfated polysaccharide. Data resulted from randomized clinical trials for colon, head and neck, and lung cancer patients suggest that fucoidan can improve cancer and chemotherapy or chemoradiation therapy related negative symptoms. In addition, Tachikawa et al. reported >50% tumor regression and increased natural killer (NK) cell activity in sarcoma-transplanted mice treated with Fucoidan. In Vitro anticancer investigation found that Fucoidan fractions clearly suppressed the growth of GBM U-251MG cancer cells. Multiple studies have also shown that fucoidan is tolerable with a good safety profile. METHOD 18 rGBM patients will be enrolled. Fucoidan based product will be administered orally at established dose for cancer patients daily with anti-neoplastic therapy over 6 months. Patients will be evaluated monthly for AEs and HRQOL score; laboratory and brain MRI monitoring will be performed per SOC guidelines. NK cell activity will be measured. POTENTIAL OUTCOME Fucoidan is safe and has good tolerability in combination with anti-neoplastic therapy for rGBM and improves fatigue and other HRQOL symptoms by ameliorating tumor progression and treatment related negative impact. Fucoidan may also improve survival in rGBM patients by improving the tolerability of anti-tumor therapy, augmenting cytotoxic effects, and inhibiting angiogenesis.

Nutritional, Metabolic, and Inflammatory Alterations in Children with Chylous Effusion in the Postoperative Period of Cardiac Surgery: A Descriptive Cohort

Objective: The occurrence of chylous effusion in children undergoing cardiac surgery is progressively increasing due to technical advances that have led to a rise in the number of surgeries. In this context, the objective was to describe the clinical profile of a cohort of patients at the time of chylous effusion diagnosis. Methods: A retrospective cohort analysis was conducted between January 2011 and July 2023, involving 23 patients, aged 0 to 18 years, treated at a quaternary university hospital in southeastern Brazil. Data were obtained from the follow-up records of the Multidisciplinary Nutritional Therapy Team (MNTT) for patients who received nutritional support after developing chylous effusion in the postoperative period of cardiac surgery. Results: The younger population predominated (median age of 6 months), with a high prevalence of malnutrition (60.9%). At the time of chylous effusion diagnosis, 83% had lymphopenia, and 74% had hypoalbuminemia. The longer the time elapsed after surgery for the onset of chylous effusion, the lower the HDL cholesterol, the lower the albumin levels, the greater the surgical complexity, the younger the patient, and the lower their weight. Hypocalcemia occurred in nearly half of the sample and hypophosphatemia in 26% of the analyzed cases. Conclusions: There was a notable presence of lymphopenia, hypoalbuminemia, and low HDL cholesterol, as well as a high incidence of mineral imbalances, particularly hypocalcemia and hypophosphatemia, which, if untreated, may lead to unfavorable outcomes. Therefore, clinical and laboratory monitoring of children in the postoperative period of cardiac surgery is important and can aid in the early diagnosis of chylous effusion and, consequently, in the timely initiation of treatment.

Multiyear high-temporal-resolution measurements of submicron aerosols at 13 French urban sites: data processing and chemical composition

Abstract. This paper presents a first comprehensive analysis of long-term measurements of atmospheric aerosol components from aerosol chemical speciation monitor (ACSM) and multiwavelength Aethalometer (AE33) instruments collected between 2015 and 2021 at 13 (sub)urban sites as part of the French CARA (Chemical Characterization of Particles) program. The datasets contain the mass concentrations of major chemical species within submicron aerosols (PM1), namely organic aerosols (OAs), nitrate (NO3-), ammonium (NH4+), sulfate (SO42-), non-sea-salt chloride (Cl−), and equivalent black carbon (eBC). Rigorous quality control, technical validation, and environmental evaluation processes were applied, adhering to both guidance from the French Reference Laboratory for Air Quality Monitoring (LCSQA) and the Aerosol, Clouds, and Trace Gases Research Infrastructure (ACTRIS) standard operating procedures. Key findings include geographical differences in the aerosol chemical composition, seasonal variations, and diel patterns, which are influenced by meteorological conditions, anthropogenic activities, and proximity to emission sources. Overall, OA dominates PM1 at each site (43 %–60 % of total mass), showing distinct seasonality with higher concentrations (i) in winter, due to enhanced residential heating emissions, and (ii) in summer, due to increased photochemistry favoring secondary aerosol formation. NO3 is the second most important contributor to PM1 (15 %–30 %), peaking in late winter and early spring, especially in northern France, and playing a significant role during pollution episodes. SO4 (8 %–14 %) and eBC (5 %–11 %) complement the major fine-aerosol species, with their relative contributions strongly influenced by the origin of air masses and the stability of meteorological conditions, respectively. A comparison with the 3D chemical transport model (CTM) CHIMERE shows high correlations between simulations and measurements, albeit with an OA concentration underestimation of 46 %–76 %. Regional discrepancies in NO3 concentration levels emphasize the importance of these datasets with respect to validating air quality models and tailoring air pollution mitigation strategies. The datasets can be found at https://doi.org/10.5281/zenodo.13318298 (Chebaicheb et al., 2024).

Determination of drought resistance of miniature rose varieties

ABSTRACT The researchers aimed to determine the effects of different irrigation levels on plant water consumption (ET), physiological, morphological and biomass traits of four different miniature rose varieties (Rosa Spp, cv. Mandarin, Orange Juwel, Zwergen Fee 09 and Zwergkönig 78). Four different irrigation levels (100% (control), 75%, 50%, 25%) were created in the experiment. The research was carried out at Çanakkale Onsekiz Mart University, Crop Stress Monitoring and Thermography Laboratory in 2020–2021. Water stress negatively affected the physiological and morphological traits measured in all four varieties. The six-month ET values of Mandarin, Orange Juwel, Zwergen Fee 09 and Zwerkönig 78 miniature rose varieties were 255.7–642.3 mm, 293.6–796.3 mm, 277.3–736.2 mm and 261.8–675.9 mm, respectively. Mandarin is more resistant to drought because its ET values are lower than other varieties.

Evidence-Informed Provision of Doxycycline Post-Exposure Prophylaxis for Prevention of Bacterial Sexually Transmitted Infections.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces the risk of bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. In the United States, doxy-PEP is in an early stage of integration into clinical practice, and national guidelines for its use were recently released. The goal of this manuscript is to provide practical guidance for clinicians who are considering or currently prescribing doxy-PEP. We address five clinical questions using post hoc analyses of data from the DoxyPEP randomized controlled trial and discuss the potential implications and limitations of each question with the goal of informing clinical practice and implementation of doxy-PEP programs. The questions address patient eligibility criteria for doxy-PEP, the expected benefit and associated doxy-PEP doses for the average patient, the initial number of doses prescribed, and laboratory monitoring of persons taking doxy-PEP.

MONITORING OF A SEVERE COVID-19 PATIENT WITH PNEUMOTHORAX COMPLICATIONS THROUGH RADIOLOGICAL AND LABORATORY DIAGNOSIS

Introduction: Monitoring and treatment of severely ill patients with the coronavirus disease who are on mechanical ventilation due to the severity of the disease with the development of many complications remains a challenge. The increased incidence of pneumothorax in Covid-19 patients on mechanical ventilation may be due to a combination of infection-induced parenchymal injury and infl ammatory response with additional positive pressure ventilation. Materials and methods: In our study, we report a case of a severe Covid-19 patient with a pneumothorax complication through radiological and laboratory diagnostics. The performed radiogram of the lungs was taken each time in the AP projection in a semi-sitting position. A digital mobile X-ray device was used for imaging. All laboratory parameters that were monitored in the patient are performed in the panel of standard routine controls for patients with Covid-19. Results: The radiogram was better as the administration of therapy and chest drain were eff ective. Biochemical and hematological parameters are performed, which indicate a decrease in the number in blood count and biochemistry. The patient spent a total of 80 days in the hospital. Conclusion: Survival of a severe form of Covid-19 infection with the complication of pneumothorax is very rare, but still possible, as shown in our case. A chest radiograph with laboratory monitoring of the condition is of great importance in establishing the diagnosis of Covid-19 infection, and in the fi nal assessment of the patient's condition upon discharge from the hospital. Keywords: Covid-19, mechanical ventilation, pneumothorax, radiological diagnostics, laboratory diagnostics.

Pattern of Adverse Drug Reactions and Performed Monitoring Laboratory-Tests in Patients Receiving Anti Tuberculosis Treatment in an Endemic Region, Zabol

Background: Efficient anti TB treatment considered crucial globally. Anti TB drugs can cause various adverse drug reactions (ADRs). Clinical and laboratory monitoring will decrease rate of these ADRs, improve patient safety as well as drug adherence and treatment outcome. Methods: In this cross-sectional study total of 136 newly diagnosed TB patients were included. All patients received standard anti-TB 4 drug regimen. Predesigned data collection forms were used to gather patient’s lab data as well as clinical symptoms they experienced during treatment course. Monthly follow up visits or phone calls were also performed by investigators and all health issues were recorded. Results: The majority of our patients aged over 70-year-old. About 54% of them were female. We recorded at least one ADR in 80.8% of patients, and hepatic-gastrointestinal (GI) ADRs ranked first (64.7%). Although ADRs were more common in women and patients over 70-year-old, but there was no statistically significant relationship between sex or age and rate of ADRs (P> 0.05). We also observed that recommended baseline laboratory tests for monitoring anti TB treatment was not performed in any of our patients, except complete blood count (CBC) that was performed in 11 cases. This led to diagnoses of anemia and thrombocytopenia in one case. Conclusion: The majority of our patients experienced ADR. Recommended drug monitoring tests that could guarantee safe and effective treatment were not performed routinely in our TB management centres. These facts highlighted the importance of improving surveillance system for TB management based on national standards.

The value of ultrasound for monitoring disease activity in giant cell arteritis

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in the elderly. Although the diagnosis of GCA has improved, monitoring its disease activity remains challenging due to the lack of validated tools and biomarkers. The current reliance on assessing symptoms, physical signs, and inflammatory markers during disease follow-up presents limitations, notably the nonspecific nature of GCA-related symptoms and the suppressive impact of IL-6 inhibitors on inflammatory markers. Therefore, recent attention has shifted toward acknowledging imaging as a monitoring tool, particularly ultrasound, given its widespread accessibility, cost-effectiveness, and well-established role in GCA diagnosis. Research on this topic has found that ultrasound characteristics, including the number of affected arterial segments and halo size, are associated with laboratory markers and treatment response, underscoring the ultrasound’s potential as a monitoring tool for GCA. It has also been demonstrated that ultrasound abnormalities progress differently throughout the disease course, depending on the type of arterial involvement, with vessel wall changes in the axillary arteries resolving more slowly than those in the temporal arteries. Nevertheless, there are still no studies comparing the added value of regular ultrasounds for monitoring disease activity to clinical and laboratory monitoring alone; hence, this imaging modality is not yet recommended for patients with GCA in clinical and biochemical remission. This narrative review aims to synthesize the main research findings of key studies addressing the role of ultrasound for monitoring disease activity in GCA, with a focus on the pattern of arterial involvement. It highlights the potential of ultrasound, particularly halo sign assessment, for evaluating disease progression but notes that further validation and standardization of protocols are needed to improve accuracy and enable routine use.

Important practical aspects in the management of patients with shot bowel syndrome and intestinal failure

Short bowel syndrome is a gastrointestinal disorder resulting from massive resection of the small intestine. The most common causes of resection are acute mesenteric ischemia, Crohn’s disease, abdominal trauma, adhesive intestinal obstruction, intestinal malignancies, and radiation enteritis. Short bowel syndrome with intestinal failure is characterized by severe malabsorption-m aldigestion accompanied by abdominal pain, diarrhea, dehydration, and progression of protein-energy malnutrition. Many patients with SBS develop long-term clinical complications over time due to altered bowel anatomy and physiology or various therapeutic interventions such as parenteral nutrition and central venous catheterization. This review focuses on the most important aspects of diagnosis, treatment, and prevention of several complications that can occur in this patient population, including macronutrient and micronutrient imbalances, diarrhea, fluid and electrolyte imbalances, metabolic bone disease, biliary disorders, bacterial overgrowth in the small intestine, and complications related to venous access. The main therapeutic strategies for SBS with intestinal failure are: special diet, enteral nutritional support with semi-elemental mixtures, parenteral nutrition, oral rehydration, antimicrobal and antidiarrheal drugs, enzymes. Administration of glucagon-like peptide 2 analog, teduglutide, is clinically effective in reducing dependence on parenteral nutrition and improving quality of life. Management of patients with SBS with intestinal failure is a complex long-term process which requires dynamic clinical and laboratory monitoring.

Vertebrate endocrine disruptors induce sex-reversal in blue mussels

Mollusks are the second most diverse animal phylum, yet little is known about their endocrinology or how they respond to endocrine disrupting compound (EDC) pollution. Characteristic effects of endocrine disruption are reproductive impairment, skewed sex ratios, development of opposite sex characteristics, and population decline. However, whether classical vertebrate EDCs, such as steroid hormone-like chemicals and inhibitors of steroidogenesis, exert effects on mollusks is controversial. In the blue mussel, Mytilus edulis, EDC exposure is correlated with feminized sex ratios in wild and laboratory mussels, but sex reversal has not been confirmed. Here, we describe a non-destructive qPCR assay to identify the sex of M. edulis allowing identification of males and females prior to experimentation. We exposed male mussels to 17α-ethinylestradiol and female mussels to ketoconazole, EDCs that mimic vertebrate steroid hormones or inhibit their biosynthesis. Both chemicals changed the sex of individual mussels, interfered with gonadal development, and disrupted gene expression of the sex differentiation pathway. Impacts from ketoconazole treatment, including changes in steroid levels, confirmed a role for steroidogenesis and steroid-like hormones in mollusk endocrinology. The present study expands the possibilities for laboratory and field monitoring of mollusk species and provides key insights into endocrine disruption and sexual differentiation in bivalves.

Post Artesunate Delayed Hemolysis in Pediatric Patients in the United States

Abstract Background Malaria continues to pose a major threat to global public health, causing millions of infections and hundreds of thousands of deaths each year. Intravenous artesunate is the current first line therapy for severe malaria and has substantially reduced its mortality. Some patients develop severe delayed hemolysis after artesunate therapy, a phenomenon termed post artesunate delayed hemolysis (PADH). A recent study of U.S. adults treated with artesunate found that 2.7% of patients experienced PADH and 56% of those patients required blood transfusion. Thus, the U.S. Food and Drug Administration recommends that patients treated with artesunate receive weekly post-treatment monitoring of hemoglobin and hemolytic markers for four weeks after therapy. While PADH in adults frequently requires blood transfusion, the frequency and severity of PADH in pediatric patients in non-endemic countries is not known. Understanding the risk of PADH in pediatric patients is essential to determine appropriate monitoring for this condition. Methods Multicenter Retrospective Chart Review To estimate rates of PADH in pediatric patients (0-18 years of age), we used ICD-10 diagnosis codes to identify patients treated for malaria at seven hospitals (The Children’s Hospital of Philadelphia, Riley Hospital for Children, Texas Children’s Hospital, Seattle Children’s Hospital, UCSF Benioff Children’s Hospital, NYU Langone Medical Center, and Bellevue Hospital), between April 2017 and July 2022. We reviewed post-discharge laboratory values and clinic visits to identify patients with laboratory findings of PADH and determine clinical outcomes. Pediatric Health Information System (PHIS) Database Review To estimate rates of severe PADH requiring repeat emergency room visit or hospitalization, we used ICD-10 diagnosis codes to identify patients who were treated for malaria with artesunate between January 2019 and July 2023 in a database of 49 children’s hospitals (PHIS). We reviewed patient visits within eight weeks of treatment to identify patients with repeat presentations related to anemia or hemolysis. Results In our retrospective chart review, four of seventeen patients (25%) treated with artesunate had laboratory evidence of PADH. None of these patients were symptomatic and none required readmission or medical intervention. Haptoglobin levels remained low in most patients up to four weeks after treatment, regardless of the presence of PADH, and lactate dehydrogenase (LDH) levels slowly declined over this period. We identified 92 patients in the PHIS database who were treated with artesunate. Of these, three patients (3.3%) had a repeat presentation within four weeks with one or more diagnosis suggestive of new onset anemia. Repeat presentations occurred 5-13 days after initial admission for malaria. Conclusion PADH is common in US pediatric patients treated with artesunate for severe malaria. However, severe hemolysis requiring repeat emergency room visit or readmission is rare. We find that haptoglobin and LDH levels were not useful as initial screening labs for PADH in pediatric patients. Together, our findings call into question the utility of weekly laboratory monitoring, as opposed to symptom-based monitoring, to identify pediatric patients at risk of readmission for PADH. Additional studies are necessary to determine which patients would benefit from weekly laboratory monitoring and which can be monitored clinically.

Bivalirudin anticoagulation for an infant with heparin resistance on ECMO: A case report.

Extracorporeal membrane oxygenation (ECMO) technology in the field of intense care for children in China has developed rapidly, and it has become a key strategy for the rescue treatment of critically ill children and an advanced extracorporeal life support system. Compared with adults and children, neonatal respiratory disease with ECMO support has the best prognosis, with an average survival rate of 74%. Bleeding and thrombotic events during ECMO are common, morbid, and potentially lethal. Therefore, how to balance the coagulation state is the key to ECMO management. A full-term male infant (2h 5min) was hospitalized for respiratory distress and cyanosis. With a history of premature rupture of membranes (>7 hours) and a birth weight of 3000 g, the patient had Apgar scores of 7, 8, and 9 at 1, 5, and 10 minutes, respectively. This infant has the indication of extracorporeal membrane lung support. After full communication, venoarterial-ECMO was performed, and intravenous infusion of heparin was used for anticoagulation management. We encountered an unreliable heparin monitoring in an infant on ECMO, which considered as heparin resistance. Subsequently, we switched the anticoagulant from heparin to bivalirudin and managed by using multiple laboratory tests including activated clotting time (ACT) and activated partial thromboplastin time. The phenomenon of inconsistent monitoring results occurred later. To help the clinic to adjust the anticoagulation dose accurately, we adopted additional tests such as thrombin-antithrombin complex (TAT) and fibrin/fibrinogen degradation products and applied comparison of thrombela stogram (TEG)-ACT with anticoagulated specimens and bedside non-anticoagulated ACT, then recommended clinicians to use activated partial thromboplastin time combined with TAT. In collaboration with other symptomatic supportive treatments, the ECMO flow was gradually reduced, the respiratory and circulatory functions were stable after reducing the flow rate, there was no bleeding tendency, and the ECMO was finally evacuated. Due to the unique physiological characteristics of newborns, the hemostatic changes differ significantly from those in adults. Precise monitoring of anticoagulation becomes a critical and challenging task. Bivalirudin can be effectively used for anticoagulation management in neonatal ECMO; however, due to its unique characteristics, precise dose adjustment poses a challenge. Selecting the optimal laboratory monitoring indicators is crucial in this regard. In some cases, bedside ACT may not be the optimal anticoagulation monitoring parameter, and when necessary, comparative analysis can be conducted using anticoagulant-sample ACTs such as thrombela stogram-ACT. Traditional markers such as D-dimer/fibrinogen degradation products and newer indicators like TAT can reflect the activation of coagulation and assist in monitoring the anticoagulation effect, especially when there is conflicting information among the monitoring parameters.

Re-evaluating the necessity of routine laboratory monitoring during isotretinoin therapy for acne.

In this letter, we discuss the topic of necessity of routine laboratory monitoring during isotretinoin treatment for acne. According to Park and colleagues, it is advisable to monitor the levels of triglycerides, alanine aminotransferase, and aspartate aminotransferase every 5 to 6 months. Additionally, the levels of total cholesterol and low-density lipoprotein should be checked within the first two months of treatment. Isotretinoin is a commonly prescribed agent mainly used to treat acne. Despite its high effectiveness, it necessitates regular monitoring of laboratory parameters due to its side effect profile. Currently, there remains a lack of consensus on the appropriate frequency for monitoring these parameters during treatment with isotretinoin. This letter will provide insight into this complex and controversial topic. Based on existing literature, we concluded that the incidence of changes in lipid and liver aminotransferase levels during isotretinoin treatment for acne was low and likely clinically insignificant. For generally healthy people, we recommend testing lipid and liver profiles once at baseline and a second time at the peak dosage. However, frequent testing might still be beneficial in certain populations of patients.

8557 Osteitis Fibrosa Cystica as the Initial Manifestation of Severe Primary Hyperparathyroidism: A Case Report

Abstract Disclosure: L.A. Robles Gomez: None. G. Gill: None. A. Vincent, DO: None. A. Mahmoud, MD: None. Introduction: Osteitis fibrosa cystica (OFC) is a pathognomonic yet uncommon finding of hyperparathyroidism seen in less than 2% of patients with primary hyperparathyroidism in Western countries. We present a case of infrequent finding of late-stage severe hyperthyroidism with asymptomatic hypercalcemia and incidental findings of osteolytic bone lesions. Clinical Case: A 28-year-old female with a history of PCOS, fatigue, and chronic abdominal pain presents to the clinic after recent work-up during an ED visit demonstrated incidental findings of osteolytic bone lesions in the setting of mild hypercalcemia. Physical examination was relatively unremarkable except for mild tenderness to palpation on the right lower quadrant. Laboratory significant calcium 10.7 mg/dl (8.6-10.2 mg/dL), albumin 3.6 g/dL, Creatinine 0.56 mg/dL, GFR 127 mL/min, Alkaline phosphatase 187 IU/L (37-127 IU/L), AST 24 IU/L, ALT 45 IU/L, Intact PTH and calcium: PTH 413 pg/mL (15-65 pg/mL), Calcium 11.5 (8.7-10.4 mg/dL), Bone Specific Alkaline Phosphatase: 54.5 mcg/L (4.7-17.8 mcg/L), Phosphorus 2.1 mg/dL (2.4-4.8 mg/dL), Magnesium 1.7 mg/dL (1.5-2.5 mg/dL), Vitamin D 25 10 mg/mL (20-100 ng/mL), TSH 2.12 uIU/mL (0.46-5.05 uIU/mL). CT abdomen pelvis w/o contrast with multiple predominantly lytic expansile bone lesions, mainly in the pelvis, with the most extensive 6.2 cm lesion in the superior, posterior right ilium, the anterior acetabulum, and the posterior right ischium. A prior CT done in 2018 showed a similar distribution of lytic lesions. The patient denied any previous personal or family history of hypercalcemia or parathyroid abnormalities despite a review of prior outside records revealed abnormal labs dating back to 2018 with intact PTH 406 pg/mL, calcium 10.3 mg/dL, Ionized calcium 10.7 mg/dl (3.30-6.0 mg/dL), albumin 3.3g/dL, alkaline phosphatase 288 IU/L. The patient denied prior symptomatology of hypercalcemia, including renal stones, or prior treatment for hypercalcemia. Further work-up was ordered, and the patient was referred to endocrine surgery for management. Conclusion: Osteitis fibrosa cystica (OFC) has become a rare manifestation of primary hyperparathyroidism (PHPT) due to early diagnosis of hypercalcemia by routine lab monitoring. Skeletal findings typically seen on PHPT can vary from bone reabsorption-acroosteolysis, subchondral bone resorption, brown tumors, salt-and-pepper skull, and osteopenia. Subchondral reabsorption around specific joints commonly affects pubic symphysis and sacroiliac joints, as seen in our patient. The mechanism is due to PTH-mediated osteoclastic absorption of bone and surrounding cartilage. Due to the rare presentation of PHPT with associated osteitis fibrosa cystica, diagnosis requires a high degree of clinical suspicion, as delayed diagnosis can lead to avoided manifestation, as described by our report. Presentation: 6/3/2024

Performance Capabilities of a Mobile Laboratory for Supporting Immunological Monitoring in Natural Plague Foci

Performance Capabilities of a Mobile Laboratory for Supporting Immunological Monitoring in Natural Plague Foci

B-162 Evaluation of two commercially available stable isotope labeled whole-protein infliximab as internal standard for a clinical infliximab LC-MS/MS assay

Abstract Background Liquid chromatography tandem mass spectrometry (LC-MS/MS) based quantitation of infliximab has been successfully introduced in the clinical laboratory for therapeutic drug monitoring in recent years. Although stable isotope labeled (SIL)-peptide or non-labeled analog protein internal standards have been utilized, SIL-whole protein infliximab is generally considered to be the ideal internal standard for the correction of variations during sample preparation and analysis. In this study, we compared two commercially available SIL infliximab proteins, Sigma SILu™MAb and Promise Proteomics, for use in a clinical infliximab assay. Methods Both labeled infliximab proteins incorporate [13C6, 15N4]-arginine and [13C6, 15N2]-lysine in their sequence and are designed for use as an internal standard for LC-MS/MS based quantitative analysis of infliximab. For the comparison of their performance, a laboratory-developed LC-MS/MS clinical method was utilized. Linearity at 6 levels in triplicate with Remicade and 3 biosimilars (-abda, -axxq, and -dyyb), intra-assay precision at 2 levels (n=10/level), and method comparison (n=15) experiments were performed using each labeled infliximab as the internal standard. For sample preparation, internal standard was mixed with the serum sample, followed by protein precipitation with ammonium sulfate, protein denaturation, and tryptic digestion. The peptides YASESMSGIPSR (YASE) from infliximab and YASESMSGIPSR [13C6, 15N4] (SIL-YASE) from labeled infliximab were monitored by LC-MS/MS (Transcend TLX and TSQ Atlis, Thermo Scientific) and utilized for the quantitation of infliximab. Results For the linearity experiment (1-50 µg/mL), while utilizing the Promise Proteomics internal standard to assay had an accuracy range of 103.4% to 114.1% for Remicade, 100.6% to 108.2% for Infliximab-axxq, 103.0% to 110.9% for Infliximab-abda, 102.7% to 108.3% for Infliximab-dyyb. For the Sigma SILu™Mab SIL infliximab, the accuracy range was 92.1% to 99.6% for Remicade, 94.5% to 107.2% for Infliximab-axxq, 99.0% to 104.2% for Infliximab-abda, and 105.1% to 112.0% for Infliximab-dyyb. The mean overall error for Remicade and biosimilars was 0.203 µg/mL (2.0%) for Sigma SILu™Mab SIL infliximab and 0.193 µg/mL (2.0%) for Promise Proteomics internal standardization. Intra-day precision using each SIL infliximab was evaluated with Remicade at low and high levels (5 and 20 µg/mL). Using Promise Proteomics, the coefficient of variation (CV) was 2.8 and 2.2%, while using Sigma SILu™Mab the precision was 6.8 and 6.5% for the low and high levels, respectively. The regression analysis for the method comparison experiment had a correlation coefficient (r) of 0.9996 with a slope of 1.050 (95% confidence interval, 1.030-1.070) and intercept of -0.318 (95% confidence interval, -0.842 to 0.205). Conclusions The mean overall error for the linearity experiment was the same using Sigma SILu™Mab or Promise Proteomics as the internal standard. The Promise Proteomics product demonstrated a lower intra-assay CV compared to the Sigma SILu™Mab. The 2 products displayed a strong correlation during the method comparison experiment. Both Sigma SILu™Mab and Promise Proteomics labeled standards showed acceptable performance as an internal standard for LC-MS/MS based quantitative analysis of infliximab. Having both products available increases the robustness of LC-MS/MS clinical assays in the event of supply issues.

Considering best practice standards for routine whole-genome sequencing for TB care and control.

TB is a priority pathogen for the application of whole-genome sequencing (WGS) into routine public health practice. In low-incidence settings, a growing number of services have begun to incorporate routine WGS into standard practice. The increasing availability of real-time genomic information supports a variety of aspects of the public health response, including the detection of drug resistance, monitoring of laboratory and clinical practices, contact tracing investigations and active case finding. Optimal structures and approaches are needed to support the rapid translation of genomic information into practice and to evaluate outcomes and impact. In this consensus paper, we outline the elements needed to systemically incorporate routine WGS into the TB public health response, including the sustainability of services, multidisciplinary team models and monitoring and evaluation frameworks. If integrated in an efficient and thoughtful manner, routine WGS has the potential to significantly improve clinical TB care for individuals and the overall public health response.

Outcomes of the American Board of Dermatology focused Practice Improvement program 2016-2023

BackgroundBoard-certified dermatologists experience diverse practice gaps. ObjectiveIdentify the top self-selected focused Practice Improvement (fPI) modules completed over time by board-certified dermatologists during the program’s first 8 years. MethodsCohort study of dermatologists certified by American Board of Dermatology (ABD) completing fPI modules from 2016 to 2023. This descriptive analysis reports modules completed by topic, subspecialty, relevance, and self-reported changes to subsequent patient care related to modules. Results19143 fPI modules were completed by 7378 unique ABD diplomates, representing 48.8% of all current ABD-certified dermatologists (n = 15118). Modules were rated relevant by 18917 participants (99%). Care gaps requiring improvement efforts and performance remeasurement occurred in 2919 (15.2%) completed modules. Acne and medication-related laboratory monitoring were popular topics requiring improvement. Diplomates reported care improvements resulting from completing modules in 8397 instances (43.9%), and improved patient outcomes in at least one patient 5310 times (27.7%). Finally, diplomates stated they would recommend fPI modules to peers 18633 (97.3%) times. LimitationsDermatologists who started but did not complete modules would not have rated the module. Attribution bias on care impact is possible and potentially overestimated. ConclusionThe ABD fPI program is helping board-certified dermatologists identify and improve gaps in care with reported patient outcome improvements.