bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncommon Presentation of Pulmonary Adenoid Cystic Carcinoma: A Case of Brain Metastasis in a Young Smoker
Authors: Liu J , Yeon S , Valyi-Nagy T , Garzon S
Published: October 2024

Introduction/Objective

Pulmonary adenoid cystic carcinoma (PACC) is a rare entity, accounting for only 0.04-0.2% lung cancers, and mainly originating from the small salivary glands in the tracheobronchial tree. Due to slow-growing pattern and unspecific symptoms, the diagnosis is often delayed. While metastasis in PACC is uncommon, reports of brain metastasis are exceedingly rare. We present a case of PACC with metastasis to the brain in a young smoker.

Methods/Case Report

A 29-year-old female with history of smoking presented with headache, hypersomnia, episodes of vomiting and falling. Physical examination revealed multiple palpable nodes on the mid head, left temporal and right parietal area, left shoulder area were found. CT scan demonstrated complex cystic mass with a mural nodule within the left cerebellar hemisphere, with displacement of the cerebellar tonsils, as well as a 7.4 cm left infrahilar mass with heterogenous enhancement. Patient underwent craniotomy with tumor resection and left lower lobe endobronchial biopsy.

Touch smear of the brain lesion showed clusters of hyperchromatic cells with myxoid like and hyalinized stroma. H&E stain showed cords of neoplastic cells embedded in a basophilic/myxoid stroma. Lung biopsy showed similar histological patterns. IHC stain showed the tumor cells were positive for epithelial and myoepithelial cells markers(CAM5.2, CK7, p63, Sox 10), retained INI1/BAF47 and BRG1 expression, negative for NUT and BCOR. Salivary Gland NGS Fusion Panel was performed and detected a MYBL1::NFIB [t(8;9)(8q13.1;9p23)] fusion alteration, which confirmed the diagnosis of adenoid cystic carcinoma. Considering no lesion was found in the patient’s head and neck, diagnosis of PACC was made.

Results (if a Case Study enter NA)

NA

Conclusion

PACC manifests three histologic subtypes: cribriform (most common), trabecular, and solid. In this case, brain and lung lesions exhibited similar patterns - nests of small, monomorphic cells within a myxoid-like and basophilic stroma background, consistent with trabecular pattern. Cytologically, densely packed cellular clusters were embedded in a myxoid like matrix.

Distinguishing PACC from other salivary gland tumors is challenging. Immunostains for epithelial and myoepithelial cells, along with morphology, aid in diagnosis. The MYB::NFIB fusion helps differentiate from other lung salivary gland malignancies, but is found in a lower percentage of PACC cases (~40%) compared to other primary adnoid cystic carcinoma (~85%).
An Economic Model for Rapid On-Site Evaluation (ROSE) Telecytology to Improve Remote Access and Pathology Practice
Authors: Petersen J M , Jhala A
Published: October 2024

Introduction/Objective

Rapid On-Site Evaluation (ROSE) is an integral part of the fine needle aspiration (FNA) procedure to inform on the diagnostic adequacy of the passes already taken. However, traditional ROSE is not accessible in rural areas and takes valuable cytopathologist time to travel to attend the procedure on site.

Telecytology has the promise to allow remote access with equivalent accuracy, though an economic benefit model based on the literature is sparse.

Methods/Case Report

Mean traditional ROSE times for cytopathologists and mean telecytology ROSE times from two institutions each from the literature were reviewed. The savings by telecytology ROSE was then modeled using the 2019 Medscape Physician Compensation Report (MPCR). Literature review of the nondiagnostic rate both with and without ROSE and costs reported from the University of Pennsylvania were used to model savings from increased accessibility of ROSE to remote settings by telecytology.

Results (if a Case Study enter NA)

Telecytopathologist traditional ROSE time (20.95 minutes and 56.2 minutes) and telecytology ROSE time (2.91 minutes and 7.5 minutes) was noted. The average pathologist salary per the 2019 MPCR was $120 per hour. The preceding corresponds to monetary savings of $26.90 to $106.58 per case. At one of the reviewed institutions, this would correspond to $23,672 to $93,790.40 in yearly savings. An average reported non- diagnostic rate of 20% (without ROSE with cost of $3,096 per FNA procedure) versus 0.98% (with ROSE with cost of $3327 per procedure) was noted, which if each non-diagnostic FNA results in a repeat procedure, leads to $32,186 in savings per 100 patients.

Conclusion

Telecytology has promise in not only improving economic efficiency of the ROSE procedure over traditional ROSE, but also in cost savings in remote settings that would otherwise not have access to ROSE at all. Therefore, there are economic savings that could be realized by improving access to telecytology across settings.
Don’t omit a urine culture when a urinalysis is suspicious for asymptomatic bacteriuria during pregnancy
Authors: Bergbower S B
Published: October 2024

Introduction/Objective

Investigation of a clinical problem using steps of evidence-based practice (EBP) led to the development of a recommendation submitted for Choosing Wisely consideration.

The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is between 2-15%. ASB may be a concern in pregnancy because of its capacity for association with adverse outcomes, namely preterm delivery, low birthweight, and possible progression to pyelonephritis. Screening and treatment may reduce the risks of adverse outcomes, but data is not current. A point-of-care urine dipstick is low cost and commonly used at routine obstetrician clinic visits to screen for ASB. The urinalysis dipstick is associated with high false-positive and false-negative rates as compared to the gold standard urine culture. Some providers make the decision to treat ASB given a positive urinalysis screen without ordering a follow-up culture. Such practice could lead to overtreatment of the patient and poor antibiotic stewardship.

Research question

Is a urinalysis without culture sufficient for diagnosis and treatment of ASB during pregnancy?

Methods/Case Report

Laboratory Medicine Best Practices A-6 steps of Ask, Acquire, Appraise, Apply, Analyze, and Assess were utilized to develop an appropriate and relevant clinical question, collect literature, determine evidence value, assign ratings, implement into practice, and evaluate outcomes. During appraisal, six selected articles were graded according to study rating, practice, measures, and results, further including the final rating and effect size rating. Consistency and overall strength of the evidence were analyzed.

Results (if a Case Study enter NA)

Each evidence study demonstrated final ratings between 8 and 10, a rating of “Good,” and an effect size rating of “Substantial.” Consistency leads to a “High” overall strength among the body of evidence.

Conclusion

Obtain a urine culture if routine prenatal point-of-care dipstick urinalyses have findings consistent with asymptomatic bacteriuria. Urinalyses are limited as screening due to low sensitivity and specificity for bacteriuria. Positive urinalysis dipstick results should be neither the sole basis for diagnosis nor decision to treat.
Tracking Blood Product Wastage over a 6-year Period in Virginia Commonwealth University Medical Center
Authors: Liu L , Shemenski J , Zmanovskaia S , Sanford K
Published: October 2024

Introduction/Objective

Blood transfusions are a necessary practice for hospital emergency and surgical department. In emergent situations, blood components are in unmonitored settings during transit of critically ill patients. Any unused blood products are returned to the blood banks outside of a controlled temperature environment and are no longer viable to use. This study seeks to collect the average amount of blood products wasted in the Emergency and Surgery Department at Virginia Commonwealth University’s (VCU) Main Hospital. In addition, the study intends to highlight the budget that is impacted by these wasted blood units.

Methods/Case Report

Emergency Stock Records of VCU’s Hospital Emergency Department, Operating Room, Children’s Hospital of Richmond’s (CHoR) Emergency Department, and the CHoR’s Operating Room were collected and accumulated by the Transfusion Service’s Quality Assurance Coordinator. VCU’s Main Hospital Emergency Department monitors blood unit viability with a sensitive temperature indicator on each unit of blood stored in unmonitored refrigerators. Blood units above 10 degrees Celsius trigger the indicator and are required to be discarded. Our study collected a tally of these discarded units due to a triggered temperature indicator from 2018 to 2023. Acquisition cost per blood unit was estimated to be approximately $250 and overhead cost per unit was estimated to be $760.

Results (if a Case Study enter NA)

From 2018 to 2023, VCU’s health system wasted an average of 89.16 blood units per year due to the triggered temperature indicators, with a total of 535 units wasted over six years. The average annual cost of the wasted units totaled $90,058.33 per year ($22,291.67 and $67,766.67 in acquisition and overhead costs, respectively); cumulative cost over the 6 years amounted to $540,350 ($133,750 and $406,600 in acquisition and overhead costs, respectively).

Conclusion

With a notable number of resources and funding lost in the process due to blood unit wastage, an administrative discussion should focus on the use of high-level remote- controlled automated refrigerators in lieu of manual temperature indicator to reduce the expenditure and wastage of blood products.
Copy Number Analysis of Whole Exome Sequencing Data
Authors: Madubata Chinwe , Bi Xin , Pang Jiuhong , Gu Yue , Koganti Lahari , Liao Jun , Hsiao Susan , Aggarwal Vimla , Mansukhani Mahesh , Jobanputra Vaidehi
Published: October 2024

Background

Genetic alterations implicated in constitutional disorders range in size from single nucleotide substitutions to losses and gains of millions of bases. Whole exome sequencing (WES) captures many clinically relevant variants, but an analytic pipeline optimized for detection of small substitutions, insertions, and deletions may miss pathogenic copy number variants (CNVs). Historically, our laboratory performed separate cytogenetic tests to evaluate for larger genomic imbalances. Addition of copy number analysis to our WES pipeline could improve the assay’s diagnostic yield. This study describes part of our strategy to validate copy number analysis of our constitutional whole exome sequencing data.

Methods

We identified 18 CNV specimens that underwent both chromosomal microarray analysis (CMA) and WES between 2017 and 2023. Variants included 13 deletions (size range 14Kb-2Mb) and 5 duplications (size range 325Kb-10Mb). The standard method of constitutional copy number analysis in our clinical laboratory is CMA using the Affymetrix Cytoscan HD Array and analysis software. CNVs identified on CMA were reviewed with reference to the Database of Genomic Variants and multiple academic hospital databases. WES was performed on an Illumina sequencing system following capture-based library enrichment with the Integrated DNA Technologies xGen Exome Research, CNV Backbone, Human mtDNA Research, and Human ID Research Panel probes. CNVs identified on WES were called using the Broad Institute’s Genomic Analysis Toolkit (GATK) with a quality score cutoff of 120. Whole exome sequencing data was visualized on the Integrative Genomics Viewer.

Results

14 out of 18 CNVs reported on CMA were also detected on WES with a quality score at or above 120 (78%). This includes 10 out of 13 deletions (77%) and 3 out of 5 duplications (60%). For both deletions and duplications, the size ranges of detected variants at or above the cutoff score and undetected variants overlapped. One duplication reported on CMA was detected on WES with a quality score below 120. Visualization of whole exome sequencing data showed variation in probe density that may have affected CNV calling.

Conclusions

The majority of CNVs reported after CMA (14/18, 78%) were also detected on WES data using a GATK quality score cutoff of 120. The data does not suggest an association between CNV size and detection by WES, although interpretation is limited by the small number of cases. Data visualization may be required to identify some CNVs. Future steps to characterize the limitations of copy number analysis of WES data include assessments of variance in probe density and read depth across the exome. Copy number analysis of WES data from cases with normal CMA results will also be performed for assay validation.
Estimation of Gestational Age-Specific Reference Intervals for Coagulation Assays in a Neonatal Intensive Care Unit Using Real-World Clinical Data
Authors: Spies Nicholas , Lalos Natasha , Vesoulis Zachary , Maucione Carly , Eby Charles , Dietzen Dennis , Roper Stephen
Published: October 2024

Interpretation of coagulation testing in neonates currently relies on reference intervals defined from adult cohorts. These likely do not reflect the normative values for neonates, in whom immature synthesis of vitamin K-dependent factors may contribute to this divergence. Direct reference interval estimation studies are difficult, particularly in neonatal populations; however, advances in indirect estimation may allow us to infer normative distributions from routinely collected clinical data. To accomplish this, initial coagulation testing results from all patients admitted to a level IV neonatal intensive care unit between 1/1/2018 - 1/1/2023 were extracted from the electronic health record and analyzed. Results prior to June 2021 were performed on the viscosity-based STA Compact Max (Diagnostica Stago. Parsippany, NJ, USA). Afterward, results were performed on a nephelometry-based ACL Top (Instrumentation Laboratory. Bedford, MA, USA). Specimens collected after transfusion of blood products were excluded. Prothrombin times (PT) and international normalized ratios (INR) were available for 1,117 neonates, while activated partial thromboplastin times (aPTT) were available for 790 neonates. The 95% confidence intervals (CI) of the median PT for extremely preterm, very preterm, preterm and term neonates were [19 - 21s], [18 - 22s], [17 - 19s] and [17 - 18s]. For INR, the CI were [1.6 - 1.8], [1.5 - 1.8], [1.4 - 1.6], and [1.4 - 1.5]. For aPTT, the CI were [51 - 61s], [47 - 58s], [45 - 50s], and [42 - 46s]. Indirect reference intervals (IRIs) were then estimated across gestational age groups (binning all patients delivered at less than 37 weeks into one preterm category) using refineR. The IRI for PT was 10 - 24s for preterm,10 - 22s for term, and 10 - 24s for all neonates. The IRI for INR was 0.7 - 2.1 for preterm, 0.8 - 1.8 for term, and 0.8 - 1.9 for all neonates. The IRI for aPTT was 24.5 - 68.4s for preterm, 24.7 - 58.2s for term, and 25 - 62.3s for all neonates. When compared to currently reported reference intervals, the lower limits of the IRI were similar to currently reported reference intervals; however, the upper limits of the IRIs were 1.3 - 1.8 times higher than current reference intervals. Theoretically, implementation of these IRIs would lead to a 3-fold decrease in the number of results flagged as abnormal. In conclusion, IRIs for coagulation assays estimated from neonates using routine clinical data show substantial divergence from current reference intervals in their upper limits, possibly due to the decreased factor concentrations seen prior to liver maturation. If implemented, these IRIs would substantially reduce the proportion of abnormal results. Future work will explore whether switching to these reference intervals could lead to a reduction in unnecessary transfusions or improved clinical outcomes.
Critical Value Reporting Performance Improvement Initiative: A Journey Towards Timely Patient Safety
Authors: Kuan Kevin , Forest Stefanie
Published: October 2024

Timely reporting of critical values serves as a quality indicator for the National Patient Safety Goal. Since the oncology inpatient unit at our institution has the highest number of critical values and often struggles to meet the targeted goal of timely results acknowledgement, this prompted a performance improvement initiative. By utilizing the Institute for Healthcare Improvement (IHI) Model for Improvement, the study aimed to decrease the time from specimen collection to acknowledgment of a complete blood count critical values (overall TAT). Three key metrics were monitored, including unit turnaround time (time from collection to receipt in laboratory; uTAT), laboratory turnaround time (time from receipt in laboratory to verified results) and timely critical value acknowledgment rate (% acknowledgement within 30 minutes). Quality improvement tools such as process maps and fishbone diagrams were employed, and two areas for improvement were identified. Firstly, it was observed that samples collected by the phlebotomists were delivered in batch to the laboratory via carts. However, samples collected by nurses were sent to the laboratory via a pneumatic tube. Hence, the uTAT varied drastically due to the different delivery methods. Secondly, the mode of alerting providers regarding critical values, which was via telephone calls from telecommunication staff, was deemed disruptive and redundant, as the providers often were already aware of the results from the electronic medical record (EPIC). Two multi-cycle Plan-Do-Study-Act (PDSA) interventions were implemented by a multidisciplinary team. The first focused on sending samples via pneumatic tube. The second PDSA intervention focused on a direct clinician acknowledgment of critical values within EPIC, by creating an auxiliary column on the EPIC patient list. Consequently, the overall TAT decreased from a median time of 167 minutes in July 2021 to 140 minutes by March 2022 in the oncology inpatient unit, with a sustained result (139 minutes) by October 2023. This reduction was driven by the standardization of pneumatic tube delivery system; the uTAT decreased from a median time of 104 minutes to 46 minutes by March 2022 and remained low at 52 minutes by January 2024. Notably, the rate of timely acknowledgment of critical value results worsened, dropping from 67% to as low as 51 % (March 2022) and improved to 64% by January 2024. It was realized that this unintended consequence was attributed to the decrease in uTAT, leading to more critical value results reported in early morning when there was less staffing. Despite the worsening in timely critical value acknowledgment, the overall TAT showed a discernible reduction. The application of IHI methodology played a pivotal role in expediting result reporting. Subsequent steps will focus on utilizing secure communication channels to augment the success rate of critical values acknowledgment within 30 minutes.
Evaluating RhD Assessment By Automated Methodology: A Potential ‘Blind Spot’ For RhD Variant Identification
Authors: Yurtsever Nalan , Tormey Chris , Bizzario Laurie , Lee Edward
Published: October 2024

Background

Automated blood typing platforms are ideal for blood donor centers, given their broad recognition of RhD antigen variants, resulting in products from such donors to be labeled as RhD positive. However, this ‘blind spot’ for variants may be problematic for hospital-based transfusion services, since RhD variants may require provision of RhD- RBC units and Rh immune globulin. The extent to which automated methods accurately characterize variant D antigen expression is not known. As such, the objective of our study was to assess D typing results, as well as RHD genotyping, among two automated testing platforms at our facility.

Methods

The study site is a single tertiary care center with analysis done from 12/2020-1/2024. At our facility, all females <60 years of age with RhD antigen testing results of ≤2+ agglutination (0-4+ scale) via automated methods [solid phase testing 12/20-4/22 (Neo, Immucor, Norcross, GA) and gel testing 5/22-1/24 (Erytra, Grifols, Emeryville, CA)] are assessed by a tube RhD antigen test (Grifols reagents). If tube testing confirms a ≤2+ result (0-4+ scale), molecular variant D analysis is performed (Versiti, Milwaukee, WI). Patients typed as Rh negative with anti-D antibodies, or those with inconsistent D typing, are also subjected to genetic D testing. The Wilcoxon matched pairs signed rank test was employed for comparative data (P< 0.05 was deemed significant).

Results

Amongst tested patients, 73 demonstrated ≤2+ agglutination via an automated typing method, leading to variant D genetic analysis. Of these, 71% (n=52) harbored variant D antigens. Within this subgroup, 29 (56%) subjects exhibited variants associated with potential allo-anti-D development (n=5 partial D variants; n=24 weak D variants). Notably, 4 patients with partial D and 1 with weak D demonstrated allo-anti-D antibodies. Of 23 patients with variant D who underwent automated gel testing, 20 concurrent tube testing results were available. Gel testing revealed significantly stronger agglutination compared to tube testing (p < 0.001). In contrast, for paired solid phase and tube testing (n=11), there was no statistically significant difference in agglutination strength (p = 0.28).

Conclusion

Automated testing, particularly gel-based platforms, exhibits reduced sensitivity to RhD antigen variant identification when compared to tube testing, placing subsets of patients potentially at risk for forming allo-anti-D. Implementing protocols for verification of D status could enhance the sensitivity of variant D detection for facilities that largely rely on automated methods for antigen typing.
Conformal Prediction and Large Language Models for Medical Coding
Authors: Snyder Christopher , Brodsky Victor
Published: October 2024

The assignment of current procedure terminology (CPT) codes to medical events is a highly cumbersome, logistic challenge for many healthcare organizations, as well as a significant contributor to medical expenses. Improvement in the allocation of medical resources and expenses dedicated to such tasks can be achieved through automation. However, because of the complex nature of medical records, automation of procedure terminologies is just now developing with the advent of machine learning methods. In this study, we develop a fine-tuned large language model (LLaMA-3B) as a high-reliability predictor for CPT codes. As input, we use 2018 pathology report text data, including gross report, microscopic description, brief medical history, and final diagnosis. We define our dataset with the top five most common technical component CPT codes, which account for 85% of all samples. As a (meta) predictor of the veracity of the large language model itself, we use the prediction’s softmax scalar value of the classification model, borrowing from similar recent approaches in conformal prediction. Specifically, the validation set, which is distinct from both the train and test set, is used to establish a prediction threshold below which the model withholds judgement. We show that, by fine tuning an off-the-shelf language model on pathology report text alone, we can achieve 95% prediction accuracy of the top 5 most common CPT codes on our dataset. We also then demonstrate the utility of combining large language models with conformal prediction. The two in combination raise our accuracy to 99.5% when we allow the model to abstain on making a prediction on 30% of the data, as is determined by a separate threshold on the scalar value of the predictor from the aforementioned validation set. We therefore present a highly flexible model for medical coding, which is simultaneously provably-reliable. Large language models can as such serve as a powerful tool for overcoming challenges in medical billing, thereby improving healthcare efficiency and reducing medical costs.
The Predictive Value of sFlt-1/PlGF Ratio for Postpartum Preeclampsia
Authors: Li Yaxin , Cagino Kristen , Yee Jim , Andy Caroline , Grossman Tracy , Zhao Zhen
Published: October 2024

Background

Preeclampsia (PE) is a leading cause of maternal mortality, affecting 5% to 8% of pregnancies worldwide. Postpartum PE typically develops within the first 48 hours and can occur up to 6 weeks after childbirth and requires immediate clinical management. However, overdiagnosis may lead to unnecessary hospital admissions and overuse of medical resources. The ratio of soluble fms like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) has been evaluated as a tool to predict PE, but its utility in the postpartum setting is yet to be established.

Methods

In this study, we conducted a non-interventional, prospective study at NewYork-Presbysterian-Weill Cornell Hospital, measuring serum sFlt-1 and PlGF levels using Elecsys® and cobas e411 analyzer. The primary aim was to determine the predictive accuracy of the sFlt-1/PlGF ratio in postpartum PE, focusing on its sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) using a cutoff 38, as established in the PROGNOSIS study.

Results

Among 47 participants, 9 (19.1%) developed postpartum PE. The sFlt-1/PlGF ratio was significantly higher for the women who developed PE (55.9, IQR, 48.6-196.2) than for women without PE (19.9, IQR, 5.8-29.1). There was no significant difference in age, first-trimester body-mass index (BMI), gestational week of delivery, smoking status and nulliparous between PE and non-PE groups. Moreover, the sFlt-1/PlGF ratio at 38 cutoff point had a sensitivity of 77.8% (95% CI, 45.0-93.7) and a specificity of 81.6% (95% CI, 66.6-90.8), with a PPV of 50.0% (95% CI, 33.9-66.1). Notably, it demonstrated a high NPV of 93.9% (95% CI, 80.4-98.3).

Conclusion

Our findings suggest that the sFlt-1/PlGF ratio may be used as a predictor of postpartum PE, highlighting its significance in managing postpartum PE.
A Closer Look at the Newer GP1bM Assay Sheds Light on Unusual Findings
Authors: Asif Maryam , Tun Theingi , Sabath Daniel
Published: October 2024

Von Willibrand disease (VWD) is the most common inherited bleeding disorder. The 2021 Guidelines on VWD diagnosis recommend newer assays measuring the platelet-binding activity of von Willebrand factor (VWF), such as VWF: GPIbM and VWF: GPIbR, over the traditional ristocetin cofactor assay (VWF: RCo). Among these newer assays, the GP1bM INNOVANCE VWF Ac assay obtained de novo FDA approval in October 2022. Its ristocetin-independent activity distinguishes it from other assays. Our laboratory conducted a comprehensive validation on the Stago StaR-Max platform, utilizing Siemens Standard Plasma for calibration. The VWF activity measured by the GP1bM assay was compared with the existing VWF: Ab assay (IL, HemosIL® von Willebrand Factor Activity). The validation studies revealed a good correlation between the two assays. Since implementing the GP1bM assay in October 2023, our attention has been drawn to at least four cases exhibiting unexpectedly high activity levels compared to VWF antigen levels. On average, the activity-to-antigen ratio was 1.9. Notably, all these cases showed the presence of all multimers (low, intermediate, and high). Despite extensive investigation, encompassing considerations like heterophile antibody interference using scantibodies, retesting with different lot numbers of Innovance VWF Ac reagent, and rerunning tests at an outside laboratory, the cause of this anomaly remains elusive. A notable variable lies in the platform disparity between Siemens and Stago. Given the recent introduction of this assay, it has yet to gain widespread adoption in laboratories, resulting in a limited understanding of its practical variations. While recent studies affirm the overall superior performance of newer assays compared to the ristocetin cofactor assay, intricate details of each assay remain less explored. The novelty of the GP1bM assay and its limited usage in laboratories underscore the potential emergence of stable outliers as it becomes more widely adopted. The peculiar cases in our study pose an enigma as to why the reported activity is approximately double the antigen level. As laboratories increasingly embrace and integrate the GP1bM assay, a more complete understanding of its potential variations is expected to unfold. This may elucidate the mysteries surrounding these peculiar cases and ensure the assay’s robust interpretation in clinical settings.
Pediatric safety profile of low titer O whole blood with increasing Anti-A and Anti-B titers
Authors: Addams Joel , Stewart Collin , Conrad Hope
Published: October 2024

Objectives

To add additional evidence to the safety of using low-titer O whole blood (LTOWB) in the massively hemorrhaging pediatric population, even with increasing allowance of anti-A and anti-B titers, up to 200.

Methods

A retrospective review from December 2021 to March 2023 of the blood bank and surgical massive transfusion protocols was performed with IRB approval to identify patients less than 18 years old who had received LTOWB as part of trauma resuscitation. In addition to patient characteristics, volume of LTOWB and other components were assessed, as well as Day 1-3 of serum potassium, creatinine, and total bilirubin. Wilcoxon rank-sum tests were performed to compare continuous variables and Fisher’s exact tests were performed to compare categorical variables between group O blood groups patients and non-O blood group patients.

Results

Only ten patients were identified under 18 years of age who had received LTOWB during trauma resuscitation, with five being blood group O and five non-O. Patient characteristics were similar between the two groups; however, only 10% were female and 10% self-reported as Black or African American. Age in the non-O group was 15 +/- 3.0 and 16.2 +/- 1.3 in the O group, p=0.75. Weight was 56.16 kg +/- 7.17 in the non-O group and 64.02+/- 14.23 in the O group, p=0.35. LTOWB transfused was 10.46 mL/kg +/- 2.42 in the non-O group and 10.32 +/- 6.53 in the O group, p=0.25. Potassium, creatinine, and total bilirubin were similar on Days 1-3 in both groups, except a single high total bilirubin in the non-O group, and this value normalized on Day 3.

Conclusion

A small data set was extracted from the available massive transfusion protocol data, reflecting the small amount of pediatric patients requiring massive transfusion for trauma compared to adults. Moreover, the predominance of males requiring massive transfusion for trauma corresponds with general trauma trends in the United States. These data reflect and are similar to previous safety reviews of pediatric trauma patients receiving LTOWB. This retrospective review records, however, a time period when the titer of anti-A and anti-B had been relaxed to 200 (rather than 50 in previous studies). This study, although small, reflects an additional Level I trauma site delivering LTOWB at potentially higher titers without negative sequelae in potassium, creatinine, or total bilirubin. With upcoming randomized controlled trials, such as Massive Transfusion in Children (MATIC-2), these data continue to reassure that the practice of using LTOWB is likely safe during the resuscitation period.
Updating Pediatric Reference Ranges at Seattle Children’s Hospital Using an Indirect Approach
Authors: Pape Ari , Dickerson Jane
Published: October 2024

Background

The aim of this project was to evaluate the accuracy of historical reference ranges at our institution. Our population of interest is children (<18 years old) within a large city. Ideally, reference intervals are determined using the direct method by performing studies on healthy volunteers. However, this approach has many challenges including being resource intensive, and, particularly in the pediatric population, difficulty in obtaining the required number of healthy volunteers for every age range. Given these challenges, a second approach, the indirect approach, has also been utilized to update reference ranges. This approach uses retrospective data analysis on data that was not specifically collected for evaluation of a reference range. Abnormal values are filtered out using a variety of methods.

Methods

For our project we pulled all outpatient data between 10/3/2020 and 06/30/2023 for the following analytes: albumin, ALP, AST, ALT, BUN, calcium, chloride, CO2, conjugated bilirubin, delta bilirubin, potassium, sodium, total bilirubin, total protein, and unconjugated bilirubin. We limited each patient to their first result for each analyte on the basis that analytes being measured more than once are more likely to be abnormal, and to limit bias. We also pulled the age (in days) and legal sex for each patient. The Tukey method was used to exclude outliers on the assumption that most data points would be normal, so any outliers would represent abnormal values from potentially not healthy patients. For each analyte and every age range the frequency of each value was plotted and the percentage of values within the current reference range, 2.5th percentile, and 97.5th percentile were calculated. A reference range was considered accurately representative of the normal population at our institution if the percentage of values within the reference range was greater than or equal to 80%.

Results

The “in range” percentage for albumin, ALT, BUN, calcium, chloride, conjugated bilirubin, delta bilirubin, creatinine, and total bilirubin was greater than 80% for all age ranges tested. Potassium, sodium, and unconjugated bilirubin each had one age range where the percent “in range” was less than 80% (2 days – 3 months, < 1 week, and < 1 month respectively), however the sample number for these age ranges was considered too low to make any significant conclusions (n=273, n=11, and n=21 respectively). ALP, AST, CO2, and total protein each had at least one age range where the percent “in range” was less than 80% and a substantial number of data points was available. In these cases, we proposed changing the reference interval to the calculated 2.5th and 97.5th percentiles based on our retrospective data analysis or verifying an externally validated pediatric reference interval from the CALIPER study.
Assessing Alkaline Phosphatase Reference Intervals Using Gamma-Glutamyl Transferase as a Surrogate for Normal Liver Function
Authors: Brown Hannah , Spies Nicholas , Farnsworth Christopher
Published: October 2024

Limited studies assess reference intervals (RIs) for hepatic enzymes, particularly for alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). In the US, ALP and GGT RIs were established on Roche assays using a European cohort of ≤ 450 patients that may not reflect population variance. Further, age- and sex-specific variation in ALP and GGT may warrant tiered RIs, but evidence to justify this approach is limited. We aimed to evaluate the manufacturer’s RIs by comparing them to indirectly estimated RIs (IRIs). 217,333 AST, ALT, ALP, and GGT results (Roche c702) performed between 1/1/2019-12/31/2022 on outpatients ≥21 years were extracted from the laboratory information system. The first ALP for each patient was identified, and the earliest AST, ALT, and GGT drawn within 7 days was included. This approach was repeated for GGT. Concordance and correlation were calculated using Weighted Cohen’s Kappa and Spearman’s rank correlation coefficient respectively. {refineR} was applied to patients with “normal” liver function (defined as normal AST, ALT for all IRIs, plus normal GGT for ALP IRIs, and ALP for GGT IRIs). IRIs were estimated for all males, all females, females ≤50, and females >50 years and compared to the method specific manufacturer RI (ALP: 40-129 Units/L for males and 35-104 Units/L for females; GGT: 8-61 Units/L for males and 5-36 Units/L for females). Of the 71,783 outpatients, 54.9% were female, 74% self-identified as white and 19% as black. The median age was 58 (IQR: 43-68 years), the median ALP concentration was 77 (62-97 Units/L), and the median GGT concentration was 28 (17-57 Units/L). A moderate agreement (Kappa = 0.48, 95% confidence interval: 0.46-0.51) and positive correlation (r = 0.51; p<0.0001) between ALP and GGT was observed. For ALP and GGT, no significant differences were observed between the lower limit of the IRIs and the current RI. The upper limit of estimated IRIs was 132 [95% confidence interval: 117-147 Units/L] for patients with normal AST/ALT/GGT (n = 1596). For males, the sex-specific upper limit was 120 [101-140 Units/L] and for females, was 123 [110-136 Units/L]. Age stratified upper limits for females were 120 [101-140 Units/L], and 109 [97-121 Units/L] for ≤50 and >50 years, respectively. The upper limit for all patients with normal AST/ALT/ALP (n = 2,446) was 62 [55-70 Units/L]. For males, all females, females ≤50 and >50 years was 58 [46-69 Units/L], 40 [39-51 Units/L], 31 [23-39 Units/L], and 56 [41-71 Units/L]. Manufacturer RIs agreed well with the IRIs for most subsets, but differed for ALP IRIs of all females with normal hepatobilliary function and in GGT for all females and females >50 years. Further investigation of the impact of preselecting patient populations on IRIs and a direct RI study on select patient subsets is worth investigation.
Long-term Functional and Aesthetic Outcomes of Labiaplasty: A Review of the Literature
Authors: McGrattan Meghan , Majeed Amna , Hanna Steven A
Published: October 2024

The incidence of female genital cosmetic surgery (FGCS), and specifically labiaplasty, is on the rise. Common motivators for labiaplasty include hygiene concerns, functional impairment, difficulties with physical or sexual activity, and dissatisfaction with genital appearance, among others. However, there have been few reports on long-term functional and aesthetic outcomes and complications of labiaplasty. The aim of this literature review was to report on long-term outcomes of labiaplasty, defined as ≥1 year postoperatively, to inform safety and efficacy recommendations for the procedure. A comprehensive literature review was conducted on PubMed (National Institutes of Health, Bethesda, MD) and Embase (Elsevier, Amsterdam, the Netherlands) from inception to December 1, 2023, following PRISMA guidelines. Articles were selected according to predetermined eligibility criteria. A manual search was performed to identify additional relevant studies. Nine studies reported on the long-term postoperative complications associated with labiaplasty, with a cumulative total of 748 patients. The most commonly reported complications included postoperative asymmetry (n = 45, 6.02%), scarring (n = 14, 1.87%), and the need for revisional surgery (n = 42, 5.61%). Of note, the majority of patients (n = 621 of 748) were reported to not have any postoperative complications. In the 7 studies that reported on psychological outcomes associated with labiaplasty, all reported sustained improvement in genital appearance scores as well as aesthetic and sexual satisfaction over the long term.

Level of Evidence: 3 (Therapeutic)
Anti-symmetric framework for balanced learning of protein–protein interactions
Authors: Tang Tao , Li Tianyang , Li Weizhuo , Cao Xiaofeng , Liu Yuansheng , Zeng Xiangxiang
Published: October 2024

Motivation

Protein–protein interactions (PPIs) are essential for the regulation and facilitation of virtually all biological processes. Computational tools, particularly those based on deep learning, are preferred for the efficient prediction of PPIs. Despite recent progress, two challenges remain unresolved: (i) the imbalanced nature of PPI characteristics is often ignored and (ii) there exists a high computational cost associated with capturing long-range dependencies within protein data, typically exhibiting quadratic complexity relative to the length of the protein sequence.

Result

Here, we propose an anti-symmetric graph learning model, BaPPI, for the balanced prediction of PPIs and extrapolation of the involved patterns in PPI network. In BaPPI, the contextualized information of protein data is efficiently handled by an attention-free mechanism formed by recurrent convolution operator. The anti-symmetric graph convolutional network is employed to model the uneven distribution within PPI networks, aiming to learn a more robust and balanced representation of the relationships between proteins. Ultimately, the model is updated using asymmetric loss. The experimental results on classical baseline datasets demonstrate that BaPPI outperforms four state-of-the-art PPI prediction methods. In terms of Micro-F1, BaPPI exceeds the second-best method by 6.5% on SHS27K and 5.3% on SHS148K. Further analysis of the generalization ability and patterns of predicted PPIs also demonstrates our model’s generalizability and robustness to the imbalanced nature of PPI datasets.

Availability and implementation

The source code of this work is publicly available at https://github.com/ttan6729/BaPPI.
Optimizing Western blotting immunodetection: Streamlining antibody cocktails for reduced protocol time and enhanced multiplexing applications
Authors: Yamani L Z , Alsamman Khaldoon , El-Masry Omar S
Published: October 2024

Adaptive, rather than innate, immunity relies mainly on antigen–antibody recognition. This recognition is driven by the binding of specific antibody paratopes to distinct epitopes found on antigens. This interaction is pivotal for immune responses that have been re-purposed for diagnostic and therapeutic purposes. This article focuses on Western blotting, an in vitro technique performed for protein immunodetection. Traditionally, this technique requires separate incubations of both primary and secondary antibodies, for which these antibodies recognize different antigen epitopes (conventional method). We propose a modified protocol combining both antibodies, involving a single incubation step that reduces time and conserves reagents (non-conventional/improved method). This improved protocol will enhance efficiency without compromising detection accuracy. It will support multiplexing, enabling the simultaneous detection of multiple proteins. Despite the positive results found by applying available antibodies, further optimization is required for a more thorough evaluation, to ensure that all antibodies consistently yield successful results in every detection attempt for broader use. Our findings indicate that the tested antibody cocktails remained stable over time, which suggests potential for commercialization of this modified Western blot protocol with a wide scope towards multiplex diagnostic application.
Colorectal cancer prevalence in faecal immunochemical test non-returners: potential for health inequality in symptomatic referral pathways
Authors: Gerrard Adam D , Coxon Jonty , Maeda Yasuko , Theodoratou Evropi , Dunlop Malcolm G , Din Farhat V N
Published: October 2024

Background

This study aimed to describe the faecal immunochemical test non-return rate of those referred with high-risk symptoms of colorectal cancer from primary care, and the clinical outcomes of the ‘non-returners’.

Methods

From January 2019 to July 2021, patients referred to secondary care with symptoms suspicious of colorectal cancer and a referral priority of urgent or urgent suspicion of cancer were sent a faecal immunochemical test. All patients were investigated regardless of faecal immunochemical test return or result. Demographics and clinical outcomes such as colorectal cancer prevalence were compared between those who returned a faecal immunochemical test and non-returners.

Results

Of 7345 patients included in the study, 874 (11.9%) did not return a faecal immunochemical test. Non-returner characteristics included male sex (P = 0.040), younger age (median age 57 versus 65 years, P < 0.001), per rectal bleeding (P < 0.001) and lower socioeconomic status (median Scottish Index of Multiple Deprivation, 6 versus 7, P < 0.001) compared with those who returned a faecal immunochemical test. Of 6294 patients undergoing colorectal investigation, there was a greater prevalence of colorectal cancer (5.4% versus 3.6% P = 0.032) and significant bowel pathology than in the non-returners (15.3% versus 9.8%, P < 0.001). With a median follow-up of 25 months, the colorectal cancer prevalence for the entire 7345 cohort was equal between those who returned and did not return a faecal immunochemical test (3.2% versus 3.8%, P = 0.108). Of note, the non-returners diagnosed with colorectal cancer were younger (median age 64 versus 73 years, P < 0.001) and from a lower socioeconomic area (median Scottish Index of Multiple Deprivation 4 versus 7, P = 0.015) than faecal immunochemical test returners.

Conclusion

Patients referred to secondary care, with symptoms suspicious of colorectal cancer, that did not return a faecal immunochemical test had a similar colorectal cancer prevalence to those that returned the test.
The diagnostic complexities of reactive angioendotheliomatosis
Authors: Gelson-Thomas Amelia S I , Bridgewater Kalina , Vilenchik Victoria , Wright Beth , Oxley Jon , Garty Florence , Singh Kiran , Woodrow Sarah , Keith Daniel
Published: October 2024

The presented letter discusses the diagnostic challenges posed by reactive angioendotheliomatosis (RAE) due to its similarities to other conditions. The authors delve into four cases of RAE, highlighting diverse clinical presentations and emphasizing the importance of accurate differentiation of this condition. This is crucial in aiding early diagnosis and optimizing outcomes for patients with RAE.
Artificial intelligence evaluation of electrocardiographic characteristics and interval changes in transgender patients on gender-affirming hormone therapy
Authors: Adel Fadi W , Sang Philip , Walsh Connor , Maheshwari Arvind , Cummings Paige , Attia Zachi , Mangold Kathryn , Davidge-Pitts Caroline , Lopez-Jimenez Francisco , Friedman Paul , Noseworthy Peter A , Mankad Rekha
Published: October 2024

Aims

Gender-affirming hormone therapy (GAHT) is used by some transgender individuals (TG), who comprise 1.4% of US population. However, the effects of GAHT on electrocardiogram (ECG) remain unknown. The objective is to assess the effects of GAHT on ECG changes in TG.

Methods and results

Twelve-lead ECGs of TG on GAHT at the Mayo Clinic were inspected using a validated artificial intelligence (AI) algorithm. The algorithm assigns a patient’s ECG male pattern probability on a scale of 0 (female) to 1 (male). In the primary analysis, done separately for transgender women (TGW) and transgender men (TGM), 12-lead ECGs were used to estimate the male pattern probability before and after GAHT. In a subanalysis, only patients with both pre- and post-GAHT EGCs were included. Further, the autopopulated PR, QRS, and QTc intervals were compared before and after GAHT. Among TGW (n = 86), the probability (mean ± SD) of an ECG male pattern was 0.84 ± 0.25 in the pre-GAHT group, and it was lowered to 0.59 ± 0.36 in the post-GAHT group (n = 173, P < 7.8 × 10−10). Conversely, among TGM, male pattern probability was 0.16 ± 0.28 (n = 47) in the pre-GAHT group, and it was higher at 0.41 ± 0.38 in the post-GAHT group (n = 53, P < 2.4×10−4). The trend persisted in the subanalysis. Furthermore, both the PR (P = 5.68 × 10−4) and QTc intervals (P = 6.65×10−6) prolonged among TGW. Among TGM, the QTc interval shortened (P = 4.8 × 10−2).

Conclusion

Among TG, GAHT is associated with ECG changes trending towards gender congruence, as determined by the AI algorithm and ECG intervals. Prospective studies are warranted to understand GAHT effects on cardiac structure and function.