Laboratory Monitoring Research Articles

#2745 New strategies for capturing undiagnosed chronic kidney disease in patients at risk

Abstract Background and Aims Chronic Kidney Disease (CKD) is recognized as a health problem in the general population. The worldwide incidence of chronic kidney disease (CKD) is increasing, driven by aging populations and a higher prevalence of type 2 diabetes (T2D) and hypertension. The CKD is generally asymptomatic, and the diagnosis depends on the laboratory monitoring of the patients. The KDIGO consensus statement recommend the implementation of screening programs in patients at high risk of CKD development. We present the first results of a sentinel surveillance program of CKD in a healthcare area for detecting undiagnosed CKD in patients at risk. Method Our health department covers the metropolitan area of Valencia, attending 341, 972 citizens through 31 primary care centers. A CKD screening program has been established in this population based on a middleware clinical decision support (CDS) system “CDS-Ripple Down - Abbott Diagnostics” integrated in an electronic request system and in the electronic health records. When a general practitioner doctor order a lab test, the middleware CDS system detects high risk patients for CKD defined by age: >65 to <90, diabetes mellitus, hypertension, or obesity. Automatically, the system adds serum creatinine, estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR) and urine sediment analysis if it has not been requested (sentinel program). Then, the patients are classified into KDIGO stages based on eGFR and UACR and the CDS system detect those with progression (Fig. 1). Only patients with UACR > 300 mg/g, eGFR < 30 ml/min/1.73, or progression were referred to nephrology. A nephrologist then decides whether patients require a face-to-face visit or provides recommendations to primary care physicians. Results From 01/11/2023 to 31/12/2023, 4, 989 reports were generated by CDS-system corresponding to 122 laboratory test per day. 99, 33% were added by the sentinel program. 3, 970 (79.6%) patients did not have CKD (KDIGO G1-2 or UACR <30 mg/g), 887 (17.8%) patients CKD not suitable for referral to Nephrology (KDIGO 3 and UACR 30-300 mg/g without progression, and 130 (2, 6%) were referred to Nephrology. (Fig. 2) Patients referred to Nephrology had a median age of 79 years [IQR: 72-85], 68 (52, 3%) were women. Twenty-seven patients (20%) were classified as KDIGO G2 A3, 19 (14, 6%) as KDIGO G4 A1 and 18 (13, 8) as KDIGO G2 A2. Fifty-seven patients (43, 8%) have been scheduled to face-to-face at nephrology consultation (1.1% of the total sample), and 73 (56, 1%) have been referred to their primary care doctors with recommendations (1.5% of the total sample). Among the patients referred to Nephrology by the CDS system, the reasons for not scheduling a face-to-face visit in Nephrology were mild decrease in eGFR (n = 18), UACR A2 (n = 24), elderly patients with low Kidney Failure Risk Equation (n = 5), urological pathology (n = 10), dependent patient and/or palliative situation (n = 5) and other causes (n = 11). Conclusion A novel CKD automatic screening method for capturing undiagnosed CKD among patients at risk has been developed. After screening around 5 000 patients at risk in two months, 2.6% of them presented criteria for referral to Nephrology. Only 1.4% required face-to-face visit. If we continue at this screening rate, it is expected that half of our population at risk of developing CKD will have been screened in less than one year. Computer systems with algorithms programmed and improved by a multidisciplinary team can establish a sentinel route (reviewing patients medical records), interpreting analytical values (calculating progressions, KDIGO stages, KFRE risk...) and producing automatic interpretive reports that integrates all the elements of CKD clinical attention allowing us to carry out this population screening.

Utility of hydroxychloroquine laboratory monitoring in dermatologic and rheumatologic patients

Hydroxychloroquine (HCQ) is an immunomodulator used in dermatology and rheumatology. Side effects may be observed on routine monitoring studies before they become clinically apparent. The goal of this retrospective chart review was to assess laboratory abnormalities in dermatologic and rheumatologic patients taking HCQ. Medical records of patients prescribed HCQ were retrospectively reviewed. Demographics, reported side effects, and parameters on baseline and follow-up complete blood count (CBC) and comprehensive metabolic panel (CMP) were recorded and graded. Laboratory abnormalities were considered severe if they were grade 3 or greater according to Common Terminology Criteria for Adverse Events v3.0 and persistent if they continued beyond subsequent laboratory testing. Of 646 eligible charts, 289 had monitoring studies for review. There were 35 severe (grade 3 or 4, 35/289; 12%) adverse events that developed, as noted on CBC or CMP. Of these 35 severe adverse events, 25 self-corrected on subsequent testing, and 10 (10/289, 3%) across 9 patients were persistent, including glomerular filtration rate, alanine transferase, alkaline phosphatase, glucose, hemoglobin and lymphopenia abnormalities. Of these 10 abnormalities, 7/10 (70%) were unlikely due to hydroxychloroquine use according to the calculated Naranjo score for each patient. Severe laboratory abnormalities while taking hydroxychloroquine are rare, even in a population with a high rate of comorbidities. Among the abnormalities observed, the majority of them (70%) were likely due to disease progression or a medication other than hydroxychloroquine. CBC and CMP monitoring for the reason of observing abnormalities while on HCQ should be at the discretion of the prescribing physician.

Impact of a pharmacist-led oral chemotherapy monitoring clinic at the South Texas Veterans Health Care System.

As cancer treatments shift from traditional intravenous chemotherapy to inclusion of oral oncolytics, there is a critical need for structured oral chemotherapy monitoring and follow-up programs. To provide continuous care and minimize clinical gaps to Veterans receiving oral chemotherapy, the hematology/oncology clinical pharmacy practitioners designed and initiated a pilot, pharmacist-driven, Oral Chemotherapy Monitoring Clinic at the South Texas Veterans Health Care System supported by an oral chemotherapy certified pharmacy technician. A retrospective evaluation of patients receiving oral chemotherapy at the South Texas Veterans Health Care System was performed before (Phase I) and after (Phase II) pilot implementation to assess the impact of an Oral Chemotherapy Monitoring Clinic on compliance with drug-specific lab and symptom monitoring. Complete monitoring was defined as 100% of recommended labs and symptoms assessed per cycle, partial monitoring was <100%, but >0%, and incomplete monitoring was defined as 0%. The primary outcome assessed the proportion of patients receiving complete monitoring in Phase II compared to Phase I. Most patients were male (94%), with a median age of 72 years. The most common oncolytic was abiraterone acetate. Overall, drug-specific baseline and follow-up laboratory and symptom monitoring was complete at a statistically significantly higher rate in Phase II compared with Phase I (p-value < 0.01). A significantly higher portion of patients in the Phase II cohort had a clinical pharmacy practitioner intervention (44% vs. 90%; p < 0.01). Monitoring for Veterans receiving oral chemotherapy was optimized with clinical pharmacy practitioner and certified pharmacy technician involvement while simultaneously alleviating Oncologist and nurse oral chemotherapy workload.

ACUTE MYOCARDIAL INFARCTION DURING VRD CHEMOTHERAPY IN A PATIENT WITH MULTIPLE MYELOMA: A CLINICAL CASE

Acute myocardial infarction is a critical condition associated with significant morbidity and mortality rates. Myocardial infarction-related acute myocardial injury is characterized by a rapid elevation and subsequent decline in cardiac troponin concentration. According to the relevant data patients with multiple myeloma are in a high-risk category for venous and arterial thrombosis. Therefore, the incidence of cardiovascular complications, which include myocardial infarction, in these patients is higher than in the general population. The development of metaplastic anemia further compounds this risk by diminishing myocardial oxygen supply. Moreover, chemotherapy for oncohematological diseases carries the potential for cardiotoxic cardiovascular complications. Immunomodulator drugs like Thalidomide and Lenalidomide, frequently utilized in multiple myeloma treatment, have been associated with Lenalidomide-induced myocardial infarction—a prevalent adverse effect. The use of proteasome inhibitors such as Bortezomib and Carfilzomib poses an increased risk for myocardial infarction development. This clinical case presents an instance of acute myocardial infarction in a multiple myeloma patient during low cumulative chemotherapy dosage, comprising Lenalidomide and Bortezomib. It underscores the necessity for enhanced clinical, instrumental, and laboratory monitoring before each specific chemotherapy course in high-risk multiple myeloma patients. Such monitoring facilitates the early detection of chemotherapy-induced cardiotoxic effects, allowing for timely intervention and management.

Neurotrophins and vascular endothelial growth factor in oral fluid of elderly patients: diagnostic value for chronic periodontitis and oral lichen planus

Objective. To evaluate the vascular endothelial growth factor A and brain-derived neurotrophic factor in the oral fluid of mature and elderly patients with chronic periodontitis and oral lichen planus. Materials and methods. The study involved 56 participants. The control group consisted of healthy volunteers aged 18–44 (n=10). The comparison group included relatively healthy elderly people aged 60–74 (n=12). The distinguished groups of patients with age-associated dental diseases included: moderate chronic periodontitis mature patients of 45–59 years (n=10) and elderly patients (n=14), as well as elderly patients with oral lichen planus (n=10). The patients underwent dental examination. The content of neurotrophins and vascular endothelial growth factor A in saliva (BDNF/ NGF beta/ VEGF-A Human ProcartaPlex Simplex Kit, Invitrogen, USA) was determined by the multiparametric fluorescence analysis with magnetic microspheres (xMAP, Luminex 200, USA) in compliance with the manufacturer protocol. Results. The groups reveal no differences in the level of brain-derived neurotrophic factor and nerve growth factor beta. The elderly patients with oral lichen planus were found to obtain the highest angiogenesis factor, which diagnostic value was assessed by ROC-analysis. The test appears moderately accurate (AUC=0.875). Conclusion. Vascular endothelial growth factor A can be considered for laboratory monitoring of elderly patients with oral lichen planus.

Paracentesis - haemodynamic effects of large-volume paracentesis (LVP)

Introduction: Ascites is one of the manifestations of acute decompensation of liver cirrhosis. Study results in recent years indicate that liver cirrhosis is a systemic inflammation and leads to altered haemodynamics in addition to organ complications. The haemodynamic effects of paracentesis on the disturbed circulation must therefore be reconsidered. Methods: Observational study of 21 patients who underwent haemodynamic and laboratory monitoring before, under and up to 48 hours after paracentesis with albumin substitution using noninvasive haemodynamic monitoring (esCCO TM System®, Nihon Kohden, Japan).

Flushing in children with cutaneous mastocytosis

Introduction. Flushing is a subjective feeling of warmth that is accompanied by redness of the skin on any part of the body, but mainly on the face, neck and upper trunk. Episodic flushing with other symptoms associated with mast cell mediators can be observed in 30–50% of children with cutaneous mastocytosis (CM).Aim. To analyze the frequency of flushing in children with various clinical forms of cutaneous mastocytosis. To study serum tryptase levels in children with flushing.Materials and methods. The study included data from 275 children aged from 6 months to 17 years inclusive, who were undergoing outpatient treatment and observation at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology from March 2022 until January 2024. The concentration of tryptase in the blood was determined by immunofluo-rescence on a three-dimensional porous solid phase (ImmunoCAP technology, Pharmacia Diagnostics AB, Sweden). Polarization and immersion dermatoscopy with 20x magnification were performed.Results. Flushings were observed in 17.5% of patients out of 275 observed children with CM. The level of tryptase more than 15 µg/l was determined in 20.8% of children with flushing, above 11.0 µg/l – in 37.5%. Tryptase levels were higher than 8.0 µg/L in 22 (45.8%) patients. In 25.0% of patients with flushing, tryptase levels did not exceed 5 µg/L. The severity of the vascular pattern in lesions and apparently healthy skin was characteristic of patients with frequent or prolonged flushing and tryptase levels above 8.0 µg/L.Conclusion. This study was the first in the Russian Federation to demonstrate the prevalence of flushing in children with various clinical forms of cutaneous mastocytosis. The results showed that the assessment of serum tryptase levels should be performed in all children with flushing, regardless of the clinical form of mastocytosis, including those with isolated and multiple skin mastocytomas. Clinical laboratory and dermatoscopic monitoring are important for the development of individual therapeutic tactics and prevention of mediator reactions and anaphylaxis.

CRISPR-Cas12a-mediated colorimetric aptasensor of netilmicin based on enzymes-assisted signal amplification and nanozyme employing a rationally truncated aptamer

Netilmicin (NET) is a typical veterinary antibiotic used in aquaculture and animal husbandry, but its excessive accumulation poses a serious threat to the ecological environment and human health. Therefore, a novel and highly sensitive Crispr-Cas12a-mediated colorimetric aptasensor was developed by combining the enzyme-assisted signal amplification strategy and magnetic NMOF-Pt nanozyme composite material (NPSM) for the visual detection of veterinary antibiotic residues in real samples. A high-affinity truncated aptamer (N-20) targeting NET was evolved from a parental aptamer sequence with the help of comprehensive recognition mechanism studies. Subsequently, N-20 was elaborately designed into the isothermal enzyme-assisted strand displacement amplification reaction. The amplified products (Act-DNAs) activated the trans-cleavage activity in the Crispr Cas12a system. The NMOF-Pt nanozyme was released from NPSM after cleaving the single chain of DNA (ssDNA). The quantity of released nanozyme was positively correlated with the amount of NET to quantitatively achieve the detection with the linear range and limits of detection (LOD) of about 0.003–30 ng/mL and 1.15 pg/mL, respectively. This method was successfully applied to detect NET in Lake water, milk and pork samples with satisfactory recoveries ranging from 89.9 % to 104.3 %. The constructed aptasensor demonstrated superior analytical performance and exhibited enormous application prospects in food supervision, environment monitoring, and medical laboratory science.

Precocious Puberty and GnRH Analogs: Current Treatment Practices and Perspectives among US Pediatric Endocrinologists.

Gonadotropin releasing hormone analogs (GnRHas) are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. The Drugs and Therapeutics Subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the USA. The survey consisted of four main subsections: (1) description of clinical practice; (2) self-assessment of knowledge base of pediatric and adult GnRHa formulations; (3) current practice for treating central precocious puberty (CPP); and (4) utilization of healthcare resources. There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the 3-month preparation, and the histrelin implant (Supprelin®) (88%, 96%, and 91%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) (65%) and 6-month subcutaneous leuprolide (Fensolvi®) (45%). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44%), but in practice, respondents reported a higher percentage of patients treated with the 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (64%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. The survey indicated there is more familiarity with older, shorter acting GnRHas, which are prescribed in greater numbers than newer, longer acting formulations. There is lack of consensus on the need for central nervous system (CNS) imaging in girls presenting with CPP between 6 and 8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability, there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.

Clinical Practice Patterns in Sickle Cell Disease Treatment: Disease-modifying and Potentially Curative Therapies.

Therapeutic options for sickle cell disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. This study aimed to describe practice patterns for pediatric hematologists regarding the use of disease-modifying and potentially curative therapies for SCD. A 9-section, cross-sectional electronic survey was disseminated during a 3-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology/Oncology Hemoglobinopathy Special Interest Group (ASPHO HSIG). A total of 88 physician members of the ASPHO HSIG were surveyed. Ninety percent of respondents (72/80) start hydroxyurea routinely in patients with HbSS and HbSβ 0 thalassemia, regardless of disease severity. Laboratory monitoring was recommended every 3 months for stable dosing in 63.8% (51/80). New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68.5% (37/54) or crizanlizumab 93.1% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin in 65.1% (43/66) of cases. Matched sibling transplant was considered for any disease severity by 55.1% (38/69). Gene therapy trials are offered on-site by 29% (20/69). Our study demonstrated the enhanced utilization of hydroxyurea while revealing the unexplored potential of other disease-modifying therapies in SCD. These findings underscore the importance of continued knowledge acquisition about the long-term efficacy of new medical therapies and addressing barriers to the use of proven therapies and guide the development of future studies of optimal SCD management.

Risk and timing of isotretinoin-related laboratory disturbances: a population-based study.

Uncertainty surrounds the optimal routine laboratory monitoring in acne patients treated with isotretinoin. Our aim was to evaluate the risk of mild and severe laboratory abnormalities in patients with acne starting isotretinoin versus oral antibiotic treatment. A global population-based retrospective cohort study assigned two groups of patients with acne-prescribed isotretinoin (n = 79,012) and oral antibiotics (n = 79,012). Comprehensive propensity-score matching was conducted. Compared to acne patients treated with oral antibiotics, those under isotretinoin demonstrated an increased risk of grade ≥3 hypertriglyceridemia (hazard ratio [HR], 7.85; 95% confidence interval [CI], 5.58-11.05; P < 0.001) and grade ≥3 elevated aspartate transaminase (AST) levels (HR, 1.45; 95% CI, 1.13-1.85; P = 0.003) within the initial 3 months of treatment. The absolute risk of these abnormalities among isotretinoin initiators was 0.4% and 0.2%, respectively. The risk difference of these findings was clinically marginal: 3 and 1 additional cases per 1,000 patients starting isotretinoin, respectively. There was no significant risk of grade ≥3 impairment in cholesterol, alanine transaminase, gamma-glutamyl transferase, or creatinine levels under isotretinoin. Most laboratory abnormalities were documented 1-3 months after drug initiation in time-stratified analysis. Isotretinoin is associated with a clinically marginal increased risk of severe hypertriglyceridemia and hypertransaminasemia. Routine blood testing should be performed 1-3 months after commencing therapy.

Abstract PS15-03: Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, plus palbociclib in ER–positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: phase 1b cohort

Abstract Background: Vepdegestrant (ARV-471) is an oral PROTAC ER degrader. In a phase 1/2 study (NCT04072952), vepdegestrant monotherapy had a favorable safety profile and encouraging clinical activity, and showed robust ER degradation. The phase 1b cohort of this study is evaluating vepdegestrant in combination with the cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (palbo). In xenograft models, vepdegestrant plus palbo showed substantially greater tumor growth inhibition vs fulvestrant plus palbo, supporting investigation in patients with breast cancer. Methods: Eligible patients for the phase 1b combination cohort had ER+/HER2- locally advanced/metastatic breast cancer and had received ≥1 prior endocrine therapy and ≤2 chemotherapy regimens for advanced disease; prior CDK4/6 inhibitor treatment was permitted. Vepdegestrant was given orally once daily (QD) continuously at doses of 180 mg (n=2), 200 mg (n=21), 400 mg (n=3), or 500 mg (n=20); palbo 125 mg was given orally QD for 21 days followed by 7 days off treatment in 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) in the first cycle and safety (adverse events [AEs] and laboratory abnormalities). Enrollment in these 4 dose levels is complete; we report data as of June 6, 2023. Results: Across 46 patients in the phase 1b cohort, 45 (97.8%) patients were female with a median age of 62.0 y (range: 29–78). Patients had received a median of 4 prior therapies (range: 1–11) in any setting, including 87.0% prior CDK4/6 inhibitors (78.3% prior palbo), 80.4% prior fulvestrant, and 76.1% prior chemotherapy (45.7% in the metastatic setting). There were no DLTs. Treatment-emergent AEs (TEAEs) leading to dose reductions or discontinuation of vepdegestrant occurred in 5 and 4 patients, respectively. TEAEs leading to dose reductions or discontinuation of palbo occurred in 34 and 8 patients, respectively. Grade 3/4 treatment-related AEs (TRAEs) to either vepdegestrant or palbo in ≥10% of patients were neutropenia (89.1%), decreased white blood cell count (15.2%), and decreased platelet count (10.9%); there were no grade 5 TRAEs and no patients had febrile neutropenia. The clinical benefit rate (rate of confirmed complete response, partial response, or stable disease ≥24 wks) in patients treated with vepdegestrant plus palbo was 63.0% (95% CI: 47.5–76.8). The objective response rate in evaluable patients with measurable disease at baseline (n=31) was 41.9% (95% CI: 24.5–60.9). Pharmacokinetics (PK) showed dose-dependent exposure for vepdegestrant, consistent with data for vepdegestrant administered as monotherapy; palbo exposure was similar across dose levels of vepdegestrant and modestly higher compared with historical palbo PK data. Circulating tumor DNA levels were evaluated in patients who received vepdegestrant 200 mg QD plus palbo and demonstrated substantial and sustained decreases in ESR1 mutant allele fraction across multiple treatment cycles. Conclusions: The combination of vepdegestrant plus palbo showed promising clinical activity in heavily pretreated patients with ER+/HER2- advanced breast cancer who had received extensive prior treatment. The safety profile of vepdegestrant plus palbo was generally consistent with the known safety profiles of the 2 agents except for an increased occurrence of grade 3/4 neutropenia, which was readily managed with laboratory monitoring and dose reductions of palbo. There is an ongoing study lead-in to the global VERITAC-3 study (NCT05909397) that is evaluating 2 doses of palbo (100 mg and 75 mg) in combination with vepdegestrant 200 mg QD to determine the recommended phase 3 combination to compare with letrozole plus palbo as first-line treatment for ER+/HER2- advanced breast cancer. Citation Format: Erika Hamilton, Rinath Jeselsohn, Sara Hurvitz, Dejan Juric, Hyo Han, Melinda Telli, George Zahrah, Rita Nanda, Yuanyuan Zhang, Weiwei Tan, Elizabeth Duperret, Eric Zhi, Cecile Mather, Anne Schott. Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, plus palbociclib in ER–positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: phase 1b cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS15-03.

Rhabdomyolysis, Acute Kidney Injury, and Mortality in Ebola Virus Disease: Retrospective Analysis of Cases From the Eastern Democratic Republic of the Congo, 2019.

Skeletal muscle injury in Ebola virus disease (EVD) has been reported, but its association with morbidity and mortality remains poorly defined. This retrospective study included patients admitted to 2 EVD treatment units over an 8-month period in 2019 during an EVD epidemic in the Democratic Republic of the Congo. An overall 333 patients (median age, 30 years; 58% female) had at least 1 creatine kinase (CK) measurement (n = 2229; median, 5/patient [IQR, 1-11]). Among patients, 271 (81%) had an elevated CK level (>380 U/L); 202 (61%) had rhabdomyolysis (CK >1000 IU/L); and 45 (14%) had severe rhabdomyolysis (≥5000 U/L). Among survivors, the maximum CK level was a median 1600 (IQR, 550-3400), peaking 3.4 days after admission (IQR, 2.3-5.5) and decreasing thereafter. Among fatal cases, the CK rose monotonically until death, with a median maximum CK level of 2900 U/L (IQR, 1500-4900). Rhabdomyolysis at admission was an independent predictor of acute kidney injury (adjusted odds ratio, 2.2 [95% CI, 1.2-3.8]; P = .0065) and mortality (adjusted hazard ratio, 1.7 [95% CI, 1.03-2.9]; P = .037). Rhabdomyolysis is associated with acute kidney injury and mortality in patients with EVD. These findings may inform clinical practice by identifying laboratory monitoring priorities and highlighting the importance of fluid management.

Evaluation of the First Three Years of Treatment of Children with Congenital Hypothyroidism Identified through the Alberta Newborn Screening Program.

The effectiveness of newborn screening (NBS) for congenital hypothyroidism (CH) relies on timely screening, confirmation of diagnosis, and initiation and ongoing monitoring of treatment. The objective of this study was to ascertain the extent to which infants with CH have received timely and appropriate management within the first 3 years of life, following diagnosis through NBS in Alberta, Canada. Deidentified laboratory data were extracted between 1 April 2014 and 31 March 2019 from Alberta Health administrative databases for infants born in this time frame. Time to lab collection was anchored from date of birth. Timeliness was assessed as the frequency of monitoring of Thyroid Stimulating Hormone (TSH) and appropriateness as the frequency of children maintaining biochemical euthyroidism. Among 160 term infants, 95% had confirmation of diagnosis by 16 days of age. The cohort had a median of 2 (range 0-5) TSH measurements performed in the time interval from 0 to 1 month, 4 (0-12) from 1 to 6 months, 2 (0-10) from 6 to 12 months, and 7 (0-21) from 12 to 36 months. Approximately half were still biochemically hypothyroid (TSH > 7 mU/L) at 1 month of age. After becoming euthyroid, at least some period of hypo- (60%) or hyperthyroidism (TSH < 0.2 mU/L) (39%) was experienced. More work needs to be performed to discern factors contributing to prolonged periods of hypothyroidism or infrequent lab monitoring.

Isotretinoin's Effect on Fasting Lipid Profile in Acne Patients.

To determine the isotretinoin's effect on fasting lipid profile in patients with acne. Observational study. Place and Duration of the Study: Outpatient Department of Dermatology, Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan, from 22nd June to 21st December 2022. Patients of clinically moderate and severe acne were selected and prescribed a dose of 0.5mg /kg cap isotretinoin for 6 months. They were advised to get a fasting lipid profile at the baseline and then after two months of isotretinoin therapy. National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 grading system and Adult Treatment Panel III were used for the grading of abnormalities. McNemar Bowker test was used to assess the difference in variables [serum triglycerides (TGs), cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL)] at the baseline and after 2 months follow-up. A total of 214 patients were evaluated. After 2 months of isotretinoin therapy, TGs and cholesterol levels were elevated to higher grade in 2% of the patients. Likewise in 1% of patients, LDL levels rised to higher grade. Moreover, HDL levels declined to lower grade in 2% of the patients taking isotretinoin. Insignificant alterations in the various serum lipid parameters were observed in acne patients during isotretinoin therapy. It is advisable to obtain a baseline fasting lipid profile in all acne patients on isotretinoin and repeated in those with baseline abnormal levels and in patients with a clinical sign of metabolic syndrome and a family history of dyslipidemias. Acne, Hyperlipidemias, Isotretinoin, Laboratory monitoring.

3D Printed Lung Phantom for Individual Monitoring.

The Human Monitoring Laboratory, Health Canada (HML), has used a 3D printer to re-engineer its Lawrence Livermore National Laboratory (LLNL) foam lung sets (manufactured by Radiology Support Devices, Inc., Long Beach, CA). The foam sets are currently the HML standard for calibrating and performance testing lung-counting systems in Canada. This paper describes the process of creating and validating new 3D-printed lung sets modeled from one of the HML's existing RSD foam sets. The existing sets were custom made, making them costly and difficult to obtain or replace. Also, after many years of use, the HML has found that they are prone to wear and tear. When used with planar inserts containing various isotopes, the blank sets can become contaminated and are difficult to clean. Using 3D printing, the HML has created new blank lung sets that are nearly identical copies of the originals and are inexpensive and easily manufactured. Measurements using natural uranium (Nat U), 241Am, and 152Eu planar lung inserts were performed to compare obtained efficiencies at a wide range of energies using the original RSD foam sets and the 3D-printed ones. Both the foam and the 3D-printed lung sets were counted using the LLNL chest phantom positioned in the same counting geometry in the lung counting system. Biases, all below 15%, were obtained between the foam and the 3D-printed sets for energies above 40 KeV. Based on these results, as well as cost benefits and ease of use, the HML has decided to replace its original RSD foam lung set with the 3D-printed version for its lung performance testing program.

Optimizing the Positioning of Detectors for Improved Counting Efficiencies Using Monte Carlo Simulations.

The Human Monitoring Laboratory (HML) at Health Canada updated its whole-body counter with four new electrically cooled HPGe detectors. To optimize the counting efficiency of the new system, Monte Carlo simulation was used to model the whole-body counter using a reference BOMAB male phantom. The resulting modeled counting efficiencies showed that the best position to install the four new detectors could be obtained without performing laborious real measurements, thereby reducing the cost of preparing the BOMAB phantoms and reconfiguring the detector arrays in multiple geometries, saving time and energy.

ЭКСПЛУАТАЦИЯ СТАЛЬНЫХ ПОКРЫТИЙ УНИКАЛЬНЫХ СООРУЖЕНИЙ.

Currently, employees of the Laboratory for Standardization, Reconstruction and Monitoring of Unique Buildings and Structures of the Department of Metal Structures of the V.A. Kucherenko Central Research Institute are preparing to print the standard of the organization STO 36554501-073-2023 “Technical operation of steel structures for coatings of unique buildings and Structures” in accordance with Federal Law No. 162-FZ dated June 29, 2015 “On Standardization in the Russian Federation Federation”. This SRT 36554501-073-2023 is compiled taking into account the requirements of Federal Laws: dated December 27, 2002 No. 184-FZ “On Technical Regulation”; No. 123-FZ dated June 22, 2008 “Technical Regulations on Fire Safety Requirements” and No. 384-FZ dated December 30, 2009 “Technical Regulations on the Safety of Buildings and Structures”. SRT 36554501-073-2023 applies to steel structures of unique coatings, including including large-span buildings and structures for maintenance, ensuring the safe functioning of buildings and structures. The standard provides an explanation of the concept of “unique buildings and structures”: these include buildings and structures with a height exceeding 100 m, or with a span of more than 100 m, or with a console departure of more than 20 m, or, if the depth of the underground part, relative to the planning mark of the ground, is more than 15 m, or structures where structures and structural schemes are used with the use of non-standard or specially developed calculation methods, or requiring verification on physical models, as well as sports and entertainment, religious buildings, exhibition pavilions, public buildings, shopping and entertainment complexes with an estimated stay of more than 1,000 people inside or more than 10,000 people near the facility. The article presents the materials that served as the basis for the creation of a service station for the operation of steel structures in the coatings of unique structures.

Diagnosis and Intensive Care in Children’s Diabetic Acidosis: an Interdisciplinary Viewpoint

Diabetic ketoacidosis (DKA) is the main cause of death and disability in children with type I diabetes mellitus (T1DM). Children’s mortality from T1DM reaches 1% in developed countries and 13% in developing countries. The main cause of death in DKA is cerebral edema, clinical manifestations of which develop in 0.5–0.9% of children with DKA, while mortality riches 24%.Objective. Developing recommendations to prevent life-threatening complications of children with DKA using analysis of literature data and consolidated opinion of experts on the issues of intensive care in children with T1DM.Materials and methods. We analyzed and discussed studies in diagnosis and treatment of DKA in children with type 1 diabetes and 1200 literature sources since January 1970, published in Russian peer-reviewed scientific journals and international publications presented in the online repository Medline (Pubmed). The search for publications was carried out using the keywords: «children», «DKA», «DM1», «dehydration», «cerebral edema».Results. We considered issues of epidemiology, pathogenesis, clinical manifestations, diagnosis, intensive care for DKA, as well as clinical and diagnosis, treatment, prevention of cerebral edema issues in children. Limitations of the study were the small number of modern studies with a high level of evidence (randomized controlled trials, meta-analyses) over the past 5 years on DKA in children.Conclusion. Taking into account the national and international experience, joint recommendations on a consensus format were developed and formulated for the diagnosis of DKA, its leading complications and treatment recommendations for children with T1DM and DKA. Timely and accurate diagnosis of DKA, intensive therapy options based on proven therapeutic efficacy, laboratory and clinical monitoring are warranted to interrupt the DKA pathogenesis, prevent the development of life-threatening conditions, and improve treatment outcomes for children with DKA.

Projection of Interspecific Competition (PIC) Matrices: A Conceptual Framework for Inclusion in Population Risk Assessments.

Accounting for intraspecific and interspecific competition when assessing the effects of chemical and nonchemical stressors is an important uncertainty in ecological risk assessments. We developed novel projection of interspecific competition (PIC) matrices that allow for analysis of population dynamics of two or more species exposed to a given stressor(s) that compete for shared resources within a landscape. We demonstrate the application of PIC matrices to investigate the population dynamics of two hypothetical fish species that compete with one another and have differences in net reproductive rate and intrinsic rate of population increase. Population status predictions were made under scenarios that included exposure to a chemical stressor that reduced fecundity for one or both species. The results of our simulations demonstrated that measures obtained from the life table and Leslie matrix of an organism, including net reproductive rate and intrinsic rate of increase, can result in erroneous conclusions of population status and viability in the absence of a consideration of resource limitation and interspecific competition. This modeling approach can be used in conjunction with field monitoring efforts and/or laboratory testing to link effects due to stressors to possible outcomes within an ecosystem. In addition, PIC matrices could be combined with adverse outcome pathways to allow for ecosystem projection based on taxonomic conservation of molecular targets of chemicals to predict the likelihood of relative cross-species susceptibility. Overall, the present study shows how PIC matrices can integrate effects across the life cycles of multiple species, provide a linkage between endpoints observed in individual and population-level responses, and project outcomes at the community level for multiple generations for multiple species that compete for limited resources. Environ Toxicol Chem 2024;43:1406-1422. Published 2024. This article is a U.S. Government work and is in the public domain in the USA.