bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bringing Calm to Antibiotic Stewardship: Customizing and Automating Antibiogram Creation at a Multi-Hospital Institution
Authors: Rogers John , Christensen Paul , Olsen Randy , Long Scott 
Published: October 2024

Abstract
We sought to automate antibiogram creation at our multi-hospital institution with custom features including transparency into data filtering, expanding the granularity to include multi-resistant organisms, and additional conditional formatting based on sensitivity percentages.
We automated creation of the antibiogram using a python framework with embedded SQL scripts. The sensitivity data for isolates from the prior year was retrieved from our lab information system. It was filtered to include only inpatient, emergency department, and observation patients across all seven hospitals in our system. Additionally, the data was filtered to only include the first organism per patient per year. Finally, organisms meeting specific sensitivity criteria (i.e. methicillin resistant Staphylococcus aureus) were included as separate rows beneath the parent organism. This data was inserted into an excel workbook with customized formatting to include the institutional logo, coloring based on sensitivity percentages, and customizable comments. Each of these steps are easily editable year-to-year to allow for changing requirements. At each step of filtering, the integrity of the data was extensively validated to make sure it was performing as intended.
The antibiograms are generated within a few minutes in a fully automated manner (Figure 1). These will be distributed systemwide after review by the Medical Microbiology directors and Antimicrobial Stewardship Committee in January of each year. The code was made in an easily editable, modular way such that requests for additional separation of organisms by sensitivity, removing drugs not pertinent to our formulary, and editing what organisms appear is easily managed by the informatics team on a year-to-year basis.
Optimizing Patient Care through Analysis of HIV-1 Genotyping: Insights into Test Ordering Strategies, Clinical Relevance, and Implications for Managing Drug Resistance
Authors: Simonyan Hayk , Dabash Abdelrahman , Yee Rebecca 
Published: October 2024

Abstract

Background
Antiretroviral resistance can lead to treatment failure and disease progression, especially in HIV patients. HIV-1 sequencing/genotyping tests (e.g., GenoSure) can be ordered by clinicians to detect HIV drug resistance (HIVDR). Here, we investigated our institution’s ordering practices, clinical relevance, and rates of HIVDR.

Methods
A total of 94 patients positive for HIV-1 between 01/2019-08/2021 were included (n=46 pre-COVID-19 prior to 03/11/2020; n=48 post-COVID-19). Patients’ charts were reviewed for demographics, laboratory results, clinical presentation, and antiviral management. Student t-test and Fisher exact test were used for statistical analyses.

Results
HIV-1 genotyping was ordered most by Medicine (67%), Surgery, (7%), Emergency medicine (6%), Neurology and Obstetrics & Gynecology (5% each). Only 70% of patients with GenoSure ordered and sent out had sufficient viral loads for genotyping. Among the patients with insufficient viral loads, the GenoSure test was most ordered by Medicine (68%), Surgery (9%) and Ob/Gyn (9%) departments. Our HIV patient population was predominantly male (70%) and had a mean age of 49 years (range: 25 to 90 years). Lower viral loads (1.8x105 vs. 3.4x105 copies/mL, p=0.05), CD4 counts (174 vs. 196 cells/mcL, p=0.7), CD8 counts (555 vs. 800 cells/mcL, p=0.04), and higher CD4/CD8 ratio (0.312 vs. 0.266, p=0.57) were seen in our post-COVID-19 patients. The overall prevalence of HIVDR was 20%. There was a 9% increase in HIVDR, predominantly in non-nucleotide reverse transcriptase inhibitors (NNRTI), after the COVID-19 pandemic. For example, higher resistance was documented for antiviral drugs Efavirenz (16%), Nevirapine (16%), and Rilpivirine (13%). Increased prevalence of mutations in G190A, K101, K103, and E138 positions which confer resistance to NNRTIs was seen. The GenoSure test results helped optimize antiviral therapy in 47.8% (42/88) of total cases, with an increase of 12.5% in patients from post-COVID-19 era. Infectious disease consultations led to more actionable changes (16% increase) and ordering of the updated version of the GenoSure test that includes integrase inhibitors (20% increase, p=0.005).

Conclusion
We have implemented stringent clinical criteria including pathologist approval and changed our electronic health record ordering system to ensure GenoSure is appropriately ordered. Diagnostic stewardship of sequencing tests needs to be implemented to ensure actionable clinical changes in the right patient population and to control testing costs. Additionally, our findings revealed increased HIVDR in our patient population post-COVID-19. Continued surveillance and collaboration with antimicrobial stewardship are critical to managing HIVDR and improving patient outcomes, particularly given the significant strain that the COVID-19 pandemic has placed on our healthcare system.
Clinical Test Comparison for Improved Diagnosis of Mucormycosis
Authors: Haas Allison , Hanson Kimberly 
Published: October 2024

Abstract
Mucormycosis is a rapidly progressive and invasive fungal infection caused by members of the order Mucorales. Proper treatment relies on a timely diagnosis. However, traditional fungal culture takes several days to weeks and has low sensitivity for recovering Mucorales, as these organisms are sensitive to specimen preparation, including tissue homogenization, and low storage temperatures. More rapid and sensitive diagnostic methods are needed to promptly detect infection. Our laboratory previously developed a real-time PCR assay that detects the most common genera associated with mucormycosis to help improve diagnosis. The assay was analytically validated for a variety of specimen types including serum, tissue (both fresh and FFPE), respiratory secretions and body fluids. Little is known about the agreement between our laboratory developed PCR and other detection methods such as culture or sequencing. We reviewed 6 years of laboratory data to assess overall PCR positivity rate, positivity rate across sample types, and agreement with culture and/or pan-fungal sequencing. We also calculated turnaround time to results to gauge the diagnostic value of Mucorales PCR. Test comparisons with fungal culture and/or pan-fungal sequencing were performed if testing was ordered within 30 days of each other. In our study, we reviewed 3,804 total PCR orders for 2,195 patients. The overall positivity rate of Mucorales PCR orders was 3.81% and varied among different sample types, with fresh tissue and body fluid having the highest positivity rates (18.11% total tissue (33.3% lung tissue) and 10.94% all body fluid (12.5% pleural fluid)) and sputum and CSF having the lowest positivity rates (&lt;1% positivity for both). In a cohort of 428 patients with fungal culture and/or sequencing also performed, 29 patients tested positive for Mucorales by at least one method. PCR detected Mucorales on average 7.83 days sooner than fungal culture (average time to positive result: 3.65 vs. 11.47 days). In patients with culture- or sequencing-confirmed Mucorales infection, PCR had a 100% agreement when comparing shared samples from the same source and collection time. Mucorales PCR was also able to detect infection in 10 (34.5%) other patients who were culture-negative for Mucorales. Our findings suggest that PCR could be a valuable diagnostic tool for suspected mucormycosis, especially tissue invasive disease. PCR increased case detection by 34.5% with a faster turnaround time than culture with lesser cost than sequencing. The main limitation of our study was lack of access to patient information to assess pretest probability of Mucormycosis.
Detection of Enteroviruses in a Pediatric Oncology Patient Population
Authors: Asowata Osaretin , McMillen Tracy , Jani Krupa , Clark Brenden , Babady Esther 
Published: October 2024

Abstract
Enteroviruses are responsible for around 10 to 15 million infections and tens of thousands of hospitalizations annually. Infants, children, and people with weakened immune systems are more likely to get hospitalized and can have serious complications from enterovirus infection. Non-polio enteroviruses like EV-D68 can cause mild to severe symptoms like wheezing, difficulty breathing and acute flaccid myelitis (AFM). Therefore, it is crucial to continue to monitor the prevalence of enteroviruses, especially those that can potentially cause severe symptoms like EV-D68. This study focused on determining the prevalence of enteroviruses in a pediatric oncology patient population. Residual Nasopharyngeal swabs (NPS) specimens, collected from pediatric patients (&lt;18 years old) presenting to a cancer hospital in New York between September 2022 and December 2022, and September 2023 and December 2023 for cancer care were included in the study. Rhinovirus/Enterovirus (RV/EV) was detected using the BioFire FilmArray Respiratory Panel (bioMerieux, Inc.) or the ePlex Respiratory Pathogen Panel (GenMark/Roche Molecular). For Enterovirus identification, RNA was extracted from the RV/EV positive NPS using the KingFisher™ Flex Magnetic Particle Processors (Thermo Scientific, USA), followed by RT-PCR in the ABI 7500 Fast real-time PCR instrument (ThermoFisher, USA) for enteroviruses and EV-D68 using pan-Enterovirus and EV-D68 specific primers, respectively. A total of 880 and 694 NPS samples from patients &lt;18 years old were tested during the study period in 2022 and 2023, respectively. Of these, 238 (238/880; 27%) and 225 (225/694; 32%) RV/EV positives NPS were detected in 2022 and 2023 respectively. A total of 370 (370/463; 80%) RV/EV positive samples (182 samples from 2022 and 188 samples from 2023) were selected for additional testing and 14 samples (14/370; 4%) were positive for Enteroviruses. Of note, EV-D68 was not detected. In this study, we report a high prevalence of RV/EV which is consistent with the higher detection rate in the fall seasons, when our samples were collected. The low prevalence of EV suggests a high prevalence of RV, although this was not tested. Despite a nationwide surge in the USA in 2022, there was no EV-D68 circulating in these patients. Further analysis, using Whole genome sequencing of the enteroviruses detected in this study will provide additional information on specific circulating Enterovirus genotypes.
Determination of Citrate Content of Commonly Transfused Blood Products
Authors: Mehr Noah , Simon Richard , Carll Timothy 
Published: October 2024

Abstract

Background
Citrate is a calcium-chelating anion used as an anticoagulant in the collection and manufacturing of blood products for transfusion. Overwhelming of normal hepatic catabolism of infused citrate, such as in liver failure or in massive transfusion, may cause citrate toxicity. Resultant hypocalcemia, impaired coagulation, and metabolic alkalosis results in increased patient mortality and morbidity. The citrate load per blood product unit is rarely known to the transfusionist, precluding precise calcium repletion. Manufacturing data of citrate content is available, but it is unreliable and often contradictory. The aim of this project is to directly measure the citrate concentrations of common blood products including packed red blood cells (pRBCs), plasma, and apheresis platelets.

Methods
Blood products (or samples thereof) were obtained, centrifuged, and assayed using a benchtop enzymatic citrate assay (Sigma-Aldrich). This technique generates a chromogenic product detectable via spectrophotometry at 570nm via conversion of citrate to a pyruvate intermediate. Blood products were serially diluted to the assay’s concentration measurement range based on estimations from the product manufacturing processes. Validation studies were performed to verify no significant interference from native pyruvate or from hemolysis at the dilutions used. All samples were run with a paired reference standard. Product type, storage duration, volume, and anticoagulant/preservative solution were recorded.

Results
Preliminary testing was performed on eleven pRBC units, twelve apheresis platelet units, and four whole blood(WB)-derived plasma. Measured citrate content of AS-1 and AS-5 units ranged from 43.56 - 114.5 mg while that of AS-3 units ranged from 327.23 – 816.82 mg, compared to manufacturing estimates of 188 mg and 883 mg, respectively. Measured citrate content of apheresis platelets ranged from 822-1533 mg compared to manufacturing estimates of 805 mg. Measured citrate content of WB-derived plasma also exceeded the manufacturing estimate of 1201 mg. Interference from pyruvate and hemolysis were insignificant at the dilutions used for testing. Validation of pRBC segment sampling is ongoing.

Conclusion
Varying guidelines exist for the correction of hypocalcemia during ongoing trauma resuscitation; however, guidance is limited regarding repletion by specific blood product. Our investigation affirms significant heterogeneity in pRBC citrate concentrations by collection method and identifies lower citrate concentrations than expected. This may be due to citrate metabolism by RBCs during storage. Platelet and FFP products contain significantly greater citrate masses by comparison, with a high degree of variation observed due to inherent product volume variability. Further sampling and testing are ongoing to establish reliable expected citrate loads for commonly transfused blood products.
Impact of a New Departmental Awards Program on Faculty Engagement and Promotion
Authors: Guarner Jeannette , Bradley Kyle , Neish Andy , Lewis Melinda , Hanley Krisztina 
Published: October 2024

Abstract

Background
Many academic institutions recognize contributions to individual departments by awarding faculty departmental awards for their achievement in service, teaching and scholarship. Before 2019, our department had teaching awards chosen by residents, but there were no awards given to the faculty by peers for academic accomplishments. The objective of this abstract is to present the impact of the newly implemented departmental awards on the promotion and academic advancement of our faculty.

Design
Based on the already established awards in other departments within the School of Medicine a committee of six faculty members proposed six annual awards: Educator Impact, Outstanding Service, Outstanding Citizenship, Mentoring, and Basic and Clinical Science Publications. The committee defined activities and eligibility for each award category (for example, faculty could not receive the same award within 3 years). The categories and eligibility criteria are distributed to all faculty (around 120) each year. The first call for nominations occurred in 2019. Assessment of the awards program included the number of nominators and nominees each year and the impact on recipients’ academic advancement and recognition.

Results
In 2019, 17 faculty nominated 16 other faculty for the six awards. These numbers grew steadily, and by 2023, 42 faculty nominated 28 other faculty for the awards. The awards have been included in the curriculum vitae of five faculty who have been promoted to either the Associate Professor or Professor level and six faculty inducted into our institution’s Clinical Distinctions program. During the five years this awards program has existed, two faculty received two awards in different categories, whereas the remaining 26 awardees each received one award. Anecdotes from faculty during this time have been overwhelmingly positive.

Conclusion
Based on the increased engagement of faculty nominating their peers and the overall impact of the awards on faculty promotion and clinical distinction recognition, the new departmental awards program has been very successful.
Two Concurrent Cases of NAIT in Pregnant Sisters
Authors: Costa Victoria , Hilbert Timothy 
Published: October 2024

Abstract
Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal antibodies directed against fetal platelet antigens inherited from the father. Approximately 80% of cases of NAIT are attributed to antibodies against human platelet antigen (HPA)-1a and less commonly to antibodies against HPA-5b. We present two cases of possible NAIT attributed to anti-HPA-5b that were identified in sisters requiring concurrent management.
Patient #1 is a 32-year-old G9P4044 woman with one pregnancy complicated by intrauterine growth retardation and partial placental abruption, another pregnancy complicated by fetal anomaly (intracerebral hemorrhage) status post termination of pregnancy at 23 weeks’ gestation and three miscarriages (one with chromosomal abnormality). The patient is homozygous for HPA-1a and HPA-5a, and the partner is homozygous for HPA-5b. HPA-5b antibodies and HLA antibodies were identified in the patient’s serum. Deemed at high risk for subsequent NAIT, she was started on intravenous immunoglobulin twice weekly and steroids during her second trimester until delivery. The patient underwent weekly fetal sonograms during pregnancy which were normal. The patient’s platelet counts were stable. The patient refused caesarean delivery. At 38 weeks’ gestation, the patient gave birth to a healthy female via normal spontaneous vaginal delivery. HPA-5b negative platelets were procured from our blood supplier, but neither the mother nor neonate required transfusion. The neonate showed no signs of bleeding and had normal platelet counts. Ultrasound imaging of the head was unremarkable. The patient and neonate were discharged home.
Patient #2 is a 33-year-old G13P6156 woman with a prior pregnancy complicated by stillbirth at 32 weeks’ gestation. Considering her personal and family history, HPA testing was performed and HPA-5b antibodies were identified in the patient’s serum. The patient’s partner is heterozygous for HPA-5b. Crossmatched platelets were procured from our blood supplier. The patient refused caesarean delivery. The patient gave birth at 37 weeks’ gestation to a healthy male via normal spontaneous vaginal delivery. The fetus had mild thrombocytopenia (107 x 103/uL), with no bleeding or bruising identified. Neither the mother nor neonate required transfusion. The patient and neonate were discharged home. Ultrasound imaging of the head was unremarkable, and his thrombocytopenia resolved.
While some studies postulate that anti-HPA-5b identification may be coincidental rather contributory to the disease process, these cases re-emphasize the importance of obtaining pregnancy, neonatal and family history to best risk stratify patients and determine management from both the clinical and transfusion medicine perspectives. If transfusion is needed, transfusion options include HPA negative platelets, crossmatched platelets and random donor platelets depending on clinical urgency and platelet availability.
A maternal germline mutator phenotype in a family affected by heritable colorectal cancer
Authors: Young Candice L , Beichman Annabel C , Mas Ponte David , Hemker Shelby L , Zhu Luke , Kitzman Jacob O , Shirts Brian H , Harris Kelley 
Published: October 2024

Abstract
Variation in DNA repair genes can increase cancer risk by elevating the rate of oncogenic mutation. Defects in one such gene, MUTYH, are known to elevate the incidence of colorectal cancer in a recessive Mendelian manner. Recent evidence has also linked MUTYH to a mutator phenotype affecting normal somatic cells as well as the female germline. Here, we use whole-genome sequencing to measure germline de novo mutation rates in a large extended family containing both mothers and fathers who are affected by pathogenic MUTYH variation. By developing novel methodology that uses siblings as “surrogate parents” to identify de novo mutations, we were able to include mutation data from several children whose parents were unavailable for sequencing. In the children of mothers affected by the pathogenic MUTYH genotype p.Y179C/V234M, we identify an elevation of the C&gt;A mutation rate that is weaker than mutator effects previously reported to be caused by other pathogenic MUTYH genotypes, suggesting that mutation rates in normal tissues may be useful for classifying cancer-associated variation along a continuum of severity. Surprisingly, we detect no significant elevation of the C&gt;A mutation rate in children born to a father with the same MUTYH genotype, and we similarly find that the mutator effect of the mouse homolog Mutyh appears to be localized to embryonic development, not the spermatocytes. Our results suggest that maternal MUTYH variants can cause germline mutations by attenuating the repair of oxidative DNA damage in the early embryo.
Busy Ethic: A Validation of a Popular Concept
Authors: van Solinge Hanna , Ekerdt David J , Henkens Kène 
Published: October 2024

Abstract

Background and Objectives
The busy ethic for retirement, as proposed by Ekerdt (1986), is a prescriptive norm that esteems an occupied, active lifestyle. This research is a first attempt to measure the busy ethic in a standardized way and apply it to a population-based sample. Objectives are: to examine whether a busy ethic is affirmed by retirees; to test busy ethic endorsement by different segments of the retired population; and to examine whether endorsement is associated with selected activities.

Research Design and Methods
We developed a scale measuring the busy ethic for a survey among 1,143 Dutch retirees. We tested two sets of hypotheses about social factors that might explain subscription to a busy norm: a hypothesis about modernization (i.e., individual autonomy from social control) that would reduce busy ethic endorsement and a hypothesis about differential exposure to expectations.

Results
Greater consent to the busy ethic was associated with circumstances that enable active lifestyles (perceived income adequacy, self-reported health), that raise one’s social value (education), and that entail more social connectedness (religious service attendance). Busy ethic agreement was positively associated with engagement in paid work, productive social activities, and group recreation.

Discussion and Implications
We found substantial endorsement of the importance of activity for oneself and others. The idealization of a busy retirement as a good retirement may be a seeming way for retirees to defer old age. At the same time, a prescriptive norm of activation may put strain on older adults who are less capable of conforming.