bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemapheresis Clinic Scheduling Quality Improvement Project
Authors: Zaidi A , Allison D , Campbell-Lee S , Janiszewski S
Published: November 2023

Introduction/Objective

Outpatient (OP) Red blood cell exchange (RCE) therapy is used to treat patients with severe manifestations of sickle cell disease. Like any blood transfusion, a patient must have an active type and screen, drawn 24 to 72 hours prior to scheduled RCE procedure. UIH Hemapheresis clinic performs several types of apheresis procedures treating sickle cell disease, kidney transplant rejection and autoimmune disorders. Outpatient clinic staff perceived that most RCE procedures are scheduled disproportionately between Wednesday through Friday, which creates an unbalanced schedule that is lighter on Monday and Tuesday, and heavier Wednesday through Friday. The study's objective was to determine if there is a significant difference between the number of outpatient procedures scheduled on the different days of the week. If significant differences are identified, processes may be improved to schedule a more balanced OP clinic week. Potential benefits may include a more balanced patient to nursing staff ratios which can improve patient care and more efficient RBC utilization which can ease workload across multiple cross-functional departments such as nursing staff, reference labs and in-house blood bank staff.

Methods/Case Report

The UIH Epic Hemapheresis Clinic schedule was searched to identify how many total OP procedures, including RCE, were scheduled each day of the week between 01AUG2021 – 31JUL2022. Only OP procedures occurring in complete five-day weeks were included. Weekends and weeks having clinic closures for holidays were excluded

Results (if a Case Study enter NA)

Our study show that the lowest number of OP RCE (mean 1.4) and total number of OP procedures (mean 2.6) were on Monday. Wednesday is the busiest day with overall averaging 3.5 total procedures (Standard Deviation: 1.56). However, Friday is the most variable, with the largest SD for both RBCX (SD 1.4) and Total number of procedures (SD 1.7).

Conclusion

Contributing factors to low procedure volume on Monday are likely multifactorial. Some patients may prefer not to come to the hospital on Saturday for type and screen, while some may forget they need labs.

Transportation issues are another factor. One intervention the clinic has implemented is automatic appointment call reminders. Staff encourage patients or caregivers to sign up for the EPIC MyChart app which also notifies patients of upcoming appointments. Future studies need to be conducted to address other bottlenecks within the scheduling workflow and to determine ways to optimize patient appointment adherence.
An unbiased approach of individual tissue-specific autoantibody identification using Immunoprecipitation coupled to Mass-Spectrometry (IP-MS)
Authors: Arlt Friederike Antonia , Sánchez-Sendín Elisa , Kirchner Marieluise , De Haas Max-Pelgrom , Mertins Philipp , Pruess Harald
Published: November 2023

Background and aim

Autoreactive antibodies have gained increasing recognition in autoimmune diseases of the central nervous system (CNS) serving as disease drivers and / or biomarkers. Identification of novel autoantibodies therefore is crucial to optimize diagnostic work and therapy of these diseases as well as understanding their pathogenesis. Hence, we aimed to develop an unbiased strategy to identify patients’ individual main autoantibodies directed against brain epitopes.

Methods

We used murine tissue-based assays to screen patients’ sera and cerebrospinal fluids (CSFs) for autoreactive IgGs with known and unknown antibody targets. IgGs from autoreactive patients’ samples were coupled to magnetic beads and used as a bait to pull down potential targets from homogenized brain tissue of wildtype mice. After precipitation and several washes to reduce unspecific binding, beads were subjected to on-bead tryptic digestion followed by mass spectrometry based proteomic analyses using liquid chromatography tandem mass-spectrometry (LC-MS/MS). For antibody targets identification the fold change enrichment compared to a negative control or to all other pulldown samples, as well as the protein abundance was used. Antibody target validation was done via recombinant expression of the target protein in HEK-293 cells and neutralization with the respective antigen in tissue-based immunofluorescence assays.

Results

As proof of principle, we were able to identify Grin1 Caspr2, Trim46 and Nf-h [MOU1] as main targets of patients’ sera or CSF with autoimmune encephalopathy. All four antigens showed highest enrichment and/or highest protein abundance in the respective samples and have been confirmed in cell-based assays. In addition, we identified one novel anti-neuronal antibody target in serum and CSF of a patient showing a speckled staining of the granular cerebellar layer. Preabsorbance of the serum and CSF with the recombinant protein fully neutralized the signal of the tissue-based immunofluorescence.

Conclusions

Our IP-MS approach is suitable to identify the main autoantibody targets in patients’ serum and CSF within murine CNS tissue thereby providing an unbiased and scalable technique allowing for tissue-specific autoantibody determination.
Comparing Refrigeration to Immediate Room Temperature Testing for Uric Acid Monitoring in Rasburicase-Treated Patients
Authors: Lin Leo , Filtz Michael , Wilson Jeffrey , Errigo Roscoe , Sorenson Anh Nguyen , Zuromski Lauren , Young Brittany
Published: November 2023

Rasburicase (Rb) is a uric acid (UA) degrading enzyme important for treating tumor lysis syndrome. Rb retains activity at room temperature (RT), so specimens collected for UA-level monitoring require cooling protocols: collecting samples in pre-chilled tubes, transporting on ice, centrifuging at 4°C, and testing within 4 hours. In our laboratory, specimens are tested within ~45 minutes of collection. Our clinical study objective was to determine if we could ease these pre-analytical requirements to improve compliance while maintaining accuracy. 50 pairs of specimens were transported and stored either on ice or at RT. All were tested at 3 time points post-collection: immediately upon arrival to the laboratory (~45 minutes), 90 minutes, and 135 minutes. Linear regression analysis of iced versus RT specimens showed a high correlation with R2= 0.99 (p< .0001) and bias of -2.4%, which indicate no clinical differences observed in UA concentrations between 1-12 mg/dL, at the immediate testing time point. UA levels did not significantly decrease in the iced specimens at any time point. However, UA levels had decreased by >10% in 16 of the 50 RT specimens after 90 minutes. Linear regression analysis of specimens tested immediately on ice versus RT specimens tested after 135 minutes yielded an R2= 0.84 (p< .0001) and bias of -17.5%. The best model from a stepwise regression was composed of the number of binned Rb half-lives (0-2 or >2) that had passed since the patients’ Rb infusion (Rb half-life= 1080 minutes; p< .0001) and the Rb dose (3 mg versus 6 mg, p< .0001), which explained ~50% of the UA variation (R2= 0.48, p< .0001). Keeping Rb dose constant, RT specimens tested within 0-2 half-lives post-infusion had an additional 24% average decrease in UA concentration compared to those tested after >2 half-lives. Similarly, keeping Rb half-life constant, RT specimens from patients given a 6-mg dose had an 18% decrease in UA concentration compared to patients given a 3-mg dose. Using a total allowable error (TEA) of 17% as a threshold, 96%, 60%, and 38% of RT specimens tested within 0-2 half-lives were within TEA at the immediate (45-minute), 90-minute, and 135-minute time points, respectively. In contrast, 100%, 96%, and 88% of RT specimens tested after >2 half-lives were within TEA at the immediate (45-minute), 90-minute, and 135-minute time points, respectively. UA concentrations are not clinically different in RT or iced specimens, as long as tested within ~45 minutes post-collection. Specimens tested within 2 Rb half-lives post-infusion have significantly decreased UA levels if kept at RT for >90 minutes. Laboratories that can test UA levels rapidly after specimen collection may be able to validate alternative pre-analytical methods to transporting and testing on ice.
Development and Validation of a Liquid Chromatography Mass Spectrometry Method to Measure Highly Concentrated Tacrolimus and Cyclosporine Specimens Prepared from Commercial Pharmaceutical Products to Assess Administration Through Feeding Tubes
Authors: Xiao Yi , Gabra Mari Ishak , Leung Edward
Published: November 2023

Background

Tacrolimus and cyclosporine are common immunosuppressive drugs used in the prevention and treatment of solid-organ transplant rejection (e.g., kidney, liver, heart). Other indications include several autoimmune diseases such as Crohn’s disease, autoimmune hepatitis, and rheumatoid arthritis. To prevent toxicity while achieving therapeutic efficacy, tacrolimus and cyclosporine in whole blood specimens are commonly measured in medical centers so that their dosages can be precisely adjusted. Different from adult patients, pediatric patients often require smaller doses and the use of feeding tubes for drug administration. In order to assess nonspecific adsorption by feeding tubes, we modified our in-house clinical method to measure highly concentrated tacrolimus and cyclosporine specimens prepared from clinical pharmaceutical products. Method: Highly concentrated tacrolimus and cyclosporine specimens were serially diluted with dimethyl sulfoxide (2,000 times for tacrolimus and 20,000 times for cyclosporine) before measurements by our clinical method using liquid chromatography mass spectrometry. The method for highly concentrated tacrolimus and cyclosporine was validated, with analytical measurement range determined with in-house prepared concentrated specimens at varying concentrations, precision (repeatability and reproducibility) assessed by multiple measurements of concentrated specimens at three different concentrations, accuracy assessed by recovery studies, and matrix effect assessed by post-column infusion and by matrix dilution with dimethyl sulfoxide.

Results

The method was linear from 10 ug/mL to 80 ug/mL for tacrolimus, and 1 mg/mL to 8 mg/mL for cyclosporine with r2 > 0.99. Repeatability and reproducibility were <10% CV. Minimal matrix effect was observed. Recovery studies using commercial calibrators to measure specimens prepared from reference materials and dimethyl sulfoxide identified no significant bias for tacrolimus but an average positive bias of 20% for cyclosporine, and a correction factor was used to finalize cyclosporine results for specimens prepared from clinical pharmaceutical products. The positive bias was eliminated when calibrators were prepared in dimethyl sulfoxide.

Conclusion

s: We have developed and validated a LC-MS/MS method for the measurement of highly concentrated tacrolimus and cyclosporine in specimens prepared from clinical pharmaceutical products. We hypothesize that one or more components in the commercial calibrators have contributed to the positive bias of cyclosporine in those specimens. Our method can be used to support studies that assess nonspecific adsorption by feeding tubes.
CytogeneticsTissue Fixation Significantly Impacts MLH1 Promoter Methylation Analysis: A Quality Improvement Study
Authors: Park Yongsang , Yeboah Bettie , Rosti Ozgur , Williams Eli , Fan Jinbo
Published: November 2023

MLH1 promoter methylation (MPM) analysis is an invaluable tool for distinguishing sporadic from inherited colorectal and endometrial cancers. At our institutional clinical genomics lab, we observed an unusually high failure rate of MPM testing in endometrial (EM) cancers. This triggered a quality improvement (QI) project to identify the underlying cause and improve the success rate of our MPM assay. We retrospectively identified all MPM cases (EM and non-endometrial (NEM) cancers) between January 2019 and October 2022 through querying our departmental database. The failure rates of these two groups were juxtaposed with the following variables: DNA concentration, performing technologists, operating surgeons, and specimen collection day (Monday through Saturday). A subsequent fishbone analysis was performed to evaluate the impact of specimen handling, fixation, and embedding procedure/timeline in the gross room and histology labs. We identified one-hundred thirty-one EM cases and eighty-two NEM cases that underwent MPM testing. Thirty-one EM cases (24%) and seven NEM cases (9%) failed, re-demonstrating the higher failure rate (X2=7.9, P-value=0.005) of EM cases. There was no significant difference in DNA concentration, performing technologists, and operating surgeons when compared to passed cases, however, a highly significant difference was seen concerning day of specimen collection (X2=53, P-value<0.0001). Most notably, all failed EM (n=31) and NEM cases (n=7) were collected on either Thursday or Friday (failure rate of 26% and 59%, respectively, 44% jointly). Our fishbone analysis revealed that specimens accessioned Thursday afternoon and Friday were fixed throughout the weekend before embedding on Monday, resulting in prolonged fixation (one extra day). This is consistent with previous studies’ conclusions showing DNA quality (but not quantity) significantly worsened with longer formalin fixation. Upon presenting these data to lab personnel, workflow changes were implemented. Cancer tissue that would have originally fixed over the weekend was instead processed on Saturday starting December 2022. This QI project revealed that prolonged formalin fixation of specimens over the weekend dramatically reduces the success rate of MPM analysis of EM cancer cases. Subsequently, we expanded our investigation to include other molecular assays at our institution that have returned similar results. Since the implementation of the revised workflow in December 2022, a preliminary prospective analysis showed the MLH1 failure rate of EM cancer tissues collected on Thursday and Friday has decreased from 44% to 11% in the past three months (December 2022 – February 2023). The current findings have important implications for the use of FFPE specimens in genetic analysis and highlight the need for careful consideration of fixation workflows, especially over the weekend, in sample processing protocols.
survex: an R package for explaining machine learning survival models
Authors: Spytek Mikołaj , Krzyziński Mateusz , Langbein Sophie Hanna , Baniecki Hubert , Wright Marvin N , Biecek Przemysław
Published: November 2023

Due to their flexibility and superior performance, machine learning models frequently complement and outperform traditional statistical survival models. However, their widespread adoption is hindered by a lack of user-friendly tools to explain their internal operations and prediction rationales. To tackle this issue, we introduce the survex R package, which provides a cohesive framework for explaining any survival model by applying explainable artificial intelligence techniques. The capabilities of the proposed software encompass understanding and diagnosing survival models, which can lead to their improvement. By revealing insights into the decision-making process, such as variable effects and importances, survex enables the assessment of model reliability and the detection of biases. Thus, transparency and responsibility may be promoted in sensitive areas, such as biomedical research and healthcare applications.

Availability and implementation

survex is available under the GPL3 public license at https://github.com/modeloriented/survex and on CRAN with documentation available at https://modeloriented.github.io/survex.
Miriam Toews’Women Talkingand the Embodied Life of Feminist Nonviolence
Authors: Glista Victoria
Published: November 2023

In Miriam Toews’ novel Women Talking (2018), the women of a remote Mennonite colony discover that they have been serially raped in their sleep, and so they meet to plot a nonhierarchical community of their own. I argue that this transformation relies on gestures, postures, and reorientations that spur liberatory new ways of perceiving and participating in the world; consequently, their bodily comportment is essential to revolutionary worldmaking, as well as to how we might approach the novel beyond its titular emphasis on speech. The women’s rechoreography of the colony’s norms also revivifies nonviolence as agonistic and egalitarian—a tentpole of the Mennonite faith. My reading works across the entanglement of movement and transformation in Women Talking before thinking through its rehearsal of bodily relations or set of gestural and postural ethics that ultimately dispose these women and survivors toward radical forms of care and interdependence, or what Judith Butler might call “aggressive nonviolence.”
A Core Outcome Set for Inflammatory Bowel Diseases: Development and Recommendations for Implementation in Clinical Practice Through an International Multi-stakeholder Consensus Process
Authors: Fierens Liselotte , Carney Nicholas , Novacek Gottfried , van der Woude C Janneke , Siegmund Britta , Casellas Francesc , Borruel Natalia , Huberts Anouk S , Sonnenberg Elena , Gerold Nathalie , Primas Christian , Hedin Charlotte R H , Stamm Tanja , Julsgaard Mette , Fiorino Gionata , Radice Simona , Zini Michela Luciana Luisa , Gross Evelyn , Sander Cornelia , Arijs Ingrid , Vakouftsi Vasiliki-Rafaela , Koltai Tunde , Charlafti Iliàs , Ferrante Marc
Published: November 2023

Background and Aims

Standardising health outcome measurements supports delivery of care and enables data-driven learning systems and secondary data use for research. As part of the Health Outcomes Observatory [H2O] initiative, and building on existing knowledge, a core outcome set [COS] for inflammatory bowel diseases [IBD] was defined through an international modified Delphi method.

Methods

Stakeholders rated 90 variables on a 9-point importance scale twice, allowing score modification based on feedback displayed per stakeholder group. Two consecutive consensus meetings were held to discuss results and formulate recommendations for measurement in clinical practice. Variables scoring 7 or higher by ≥80% of the participants, or based on consensus meeting agreement, were included in the final set.

Results

In total, 136 stakeholders (45 IBD patients [advocates], 74 health care professionals/researchers, 13 industry representatives, and four regulators) from 20 different countries participated. The final set includes 18 case-mix variables, three biomarkers [haemoglobin to detect anaemia, C-reactive protein and faecal calprotectin to detect inflammation] for completeness, and 28 outcomes (including 16 patient-reported outcomes [PROs] and one patient-reported experience). The PRO-2 and IBD-Control questionnaires were recommended to collect disease-specific PROs at every contact with an IBD practitioner, and the Subjective Health Experience model questionnaire, PROMIS Global Health and Self-Efficacy short form, to collect generic PROs annually.

Conclusions

A COS for IBD, including a recommendation for use in clinical practice, was defined. Implementation of this set will start in Vienna, Berlin, Barcelona, Leuven, and Rotterdam, empowering patients to better manage their care. Additional centres will follow worldwide.
Associations of omega-3 fatty acids vs. fenofibrate with adverse cardiovascular outcomes in people with metabolic syndrome: propensity matched cohort study
Authors: Kim Nam Hoon , Kim Ji Yoon , Choi Jimi , Kim Sin Gon
Published: November 2023

Aims

Omega-3 fatty acids and fenofibrates have shown some beneficial cardiovascular effects; however, their efficacy has not been compared. This study aimed to compare the effectiveness of currently available omega-3 fatty acids and fenofibrate for reducing major adverse cardiovascular events (MACE).

Methods and results

From a nationwide population-based cohort in South Korea (2008–2019), individuals with metabolic syndrome (≥30 years) who received statin with omega-3 fatty acids and those receiving statin with fenofibrate were matched by propensity score (n = 39 165 in both groups). The primary outcome was MACE, including ischaemic heart disease (IHD), ischaemic stroke (IS), and death from cardiovascular causes. The risk of MACE was lower [hazard ratio (HR), 0.79; 95% confidence interval (CI), 0.74–0.83] in the fenofibrate group than in the omega-3 fatty acid group. Fenofibrate was associated with a lower incidence of IHD (HR, 0.72; 95% CI, 0.67–0.77) and hospitalization for heart failure (HR, 0.90; 95% CI, 0.82–0.97), but not IS (HR, 0.90; 95% CI, 0.81–1.00) nor death from cardiovascular causes (HR, 1.07; 95% CI, 0.97–1.17). The beneficial effect of fenofibrate compared to omega-3 fatty acids was prominent in patients with preexisting atherosclerotic cardiovascular disease and those receiving lower doses of omega-3 fatty acids (≤2 g per day).

Conclusion

In a real-world setting, fenofibrate use was associated with a lower risk of MACE compared with low-dose omega-3 fatty acids when added to statins in people with metabolic syndrome.
The Danish-Norwegian randomized trial on beta-blocker therapy after myocardial infarction: Design, rationale, and baseline characteristics
Authors: Kristensen Anna Meta Dyrvig , Munkhaugen John , Halvorsen Sigrun , Olsen Michael Hecht , Bakken Arnhild , Sehested Thomas Steen Gyldenstierne , Ruddox Vidar , Lange Theis , Fagerland Morten Wang , Torp-Pedersen Christian , Prescott Eva , Atar Dan
Published: November 2023

Background and aims

The evidence for beta-blocker therapy after myocardial infarction (MI) is randomized trials conducted more than 30 years ago, and the continued efficacy has been questioned.

Design and methods

The ongoing Danish (DANBLOCK) and Norwegian (BETAMI) randomized beta-blocker trials are joined to evaluate the effectiveness and risks of long-term beta-blocker therapy after MI. Patients with normal or mildly reduced left ventricular ejection fraction (LVEF ≥ 40%) will be randomized to open-label treatment with beta-blockers or no such therapy. The event-driven trial will randomize ∼5700 patients and continue until 950 primary endpoints have occurred. As of July 2023, 5228 patients have been randomized. Of the first 4000 patients randomized, median age was 62 years, 79% were men, 48% had a ST-segment elevation myocardial infarction (STEMI), and 84% had a normal LVEF. The primary endpoint is a composite of adjudicated recurrent MI, incident heart failure (HF), coronary revascularization, ischaemic stroke, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest. The primary safety endpoint includes a composite of recurrent MI, HF, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest 30 days after randomization. Secondary endpoints include each of the components of the primary endpoint, patient-reported outcomes, and other clinical outcomes linked to beta-blocker therapy. The primary analysis will be conducted according to the intention-to-treat principle using a Cox proportional hazards regression model. End of follow-up is expected in December 2024.

Conclusion

The combined BETAMI–DANBLOCK trial will have the potential to affect current clinical practice for beta-blocker therapy in patients with normal or mildly reduced LVEF after MI.
Inonotus obliquus sclerotia epidermis were different from internal tissues in compound composition, antioxidant activity, and associated fungi
Authors: Zhang Yijia , Liu Qiao , Sun Yong , Jiang Jihong
Published: November 2023

Inonotus obliquus is a medicinal fungus with potential for use in various health applications. To better utilize this fungus, this study focused on epidermis and internal tissues of five sclerotia from different regions in Jilin, Inner Mongolia, and Heilongjiang, examining their polyphenols, polysaccharides, flavonoids, and total triterpenes contents. And evaluated the extracts from sclerotia for their total antioxidant capacity and scavenging ability of DPPH free radicals. The study also isolated the associated fungi from the epidermis and internal tissues of three sclerotia. Results revealed that the polyphenol content was higher in the epidermis than in internal tissue of every sclerotium. However, flavonoid and total triterpenoid content was lower in the epidermis of every sclerotium. The polysaccharide content was no significant in different parts of three sclerotia, but the epidermal polysaccharide content in two sclerotia was significantly higher than in internal tissues. The internal tissue extracts from tested sclerotia exhibited better scavenging ability of DPPH free radicals than those from the epidermis. There was no significant difference in total antioxidant capacity among different parts of three sclerotia, and the internal tissues' total antioxidant capacity in two sclerotia was higher than the epidermis. The number and species of associated fungi in the internal tissues were far less than that in the epidermis. The study suggests separating the epidermis and internal tissue for medicinal use. The research provides insights into the bioactive components and associated fungi of I. obliquus to inform its practical application in medicine.
Therapeutic drug monitoring of ceftazidime/avibactam: why one leg is not enough to run
Authors: Gatti Milo , Viale Pierluigi , Pea Federico
Published: November 2023

Background

Therapeutic drug monitoring (TDM) is becoming an increasingly recommended approach for assessing optimal pharmacokinetic/pharmacodynamic (PK/PD) target attainment of ceftazidime/avibactam. Some authors hypothesized that the PK/PD target attainment of ceftazidime/avibactam could be assessed by means of the TDM of solely ceftazidime, since avibactam concentrations might be extrapolated based on the fixed 4:1 ceftazidime-to-avibactam ratio present in the vial. The reliability of this hypothesis could be called into question if a wide interindividual variability in the ceftazidime-to-avibactam ratio would exist among patients. This study aimed to assess the distribution of the individual ceftazidime-to-avibactam ratios in relation to renal function in a cohort of adult patients who were treated with continuous infusion ceftazidime/avibactam and underwent TDM of both ceftazidime and avibactam.

Methods

Individual ceftazidime-to-avibactam ratio was calculated at each TDM assessment. Receiving operating characteristics (ROC) curve analysis was performed for testing the potential impact of renal function on ceftazidime-to-avibactam ratio variability.

Results

A total of 188 TDM assessments were collected from 107 patients. The ceftazidime-to-avibactam ratios ranged from 1.29:1 to 13.46:1. Seventy-seven out of 188 ceftazidime-to-avibactam ratios (41.0%) were >5:1, and 36 (19.1%) were >6:1. Patients without renal dysfunction had significantly higher proportions of ceftazidime-to-avibactam ratio >5:1 (59.3% versus 23.8%; P < 0.001) and >6:1 (32.1% versus 6.3%; P < 0.001) compared with those with mild-to-severe renal dysfunction.

Conclusions

The findings may strengthen the contention that for properly assessing the PK/PD target attainment of ceftazidime/avibactam, both ceftazidime and avibactam concentrations should be measured, given the unpredictability of the ceftazidime-to-avibactam ratio occurring among patients.
Biochemical Alterations Associated With the Severity of COVID-19 in Sub-Saharan Black African Individuals
Authors: Moukambi Lydie Armelle , Kande Yatara Marisca , Lendoye Elisabeth , Padzys Guy-Stéphane , Ndeboko Benedict , Maloupazoa Siawaya Anicet Christel , Nzoghe Amandine Mveang , Oliveira Stéphane , Ivala Mendome Yannick , Biyie Bi Ngoghe Prudence , Mvoundza Ndjindji Ofilia , Avome Houechenou Rotimi Myrabelle , Leboueny Marielle , Djoba Siawaya Joel Fleury
Published: November 2023

Background

Biochemical markers are essential in the monitoring and the clinical care of patients as they inform clinicians. Here, we characterized biochemical alterations in sub-Saharan Black African individuals with COVID-19.

Methods

The study includes COVID-19 patients cared for at the Akanda Army Hospital in Libreville (Gabon). A total of 2237 patient records were extracted and reviewed. Patients were classified based on hospital admission (intensive care unit [ICU], internal medicine ward, and outpatient).

Results

One thousand six hundred seventy-one were included in the study. ICU patients were significantly older than non-ICU hospitalized patients (P < 0.001) and outpatients (P < 0.0001). Hyperglycemic patients had 6.4 odds of being in ICU (P < 0.0001). Patients with abnormally high urea had 54.7 odds of being in ICU (P < 0.0001). Patients with abnormally high aspartate aminotransferase (AST) (>33 IU/L) had 3.5 odds of being in ICU (P < 0.0001). Hyperlactatemia (>246 IU/L) odds in ICU patients were 14 (P < 0.0001). The odds of abnormally high alkaline phosphatase (ALP) (>147 IU/L) in ICU patients were 4.6 (P < 0.0001). Odds for hypochloremia (<98 mmol/L) were 1.6 in ICU (P < 0.05). Dysnatremia patients (<135 or >145 mmol/L) had 9.5 odds of being found in ICU patients (P < 0.0001). The odds of potassium imbalance (<3.6 or >5 mmol/L) in ICU patients were 12.2 (P < 0.0001).

Conclusions

COVID-19-associated biochemical alterations observed in the Black African population are similar to those observed in other populations, and the association between COVID-19 severity, hyperglycemia, and multi-organ affection is confirmed.
Prevention of motor ascending branch of the rectus femoris injuries in Bernese periacetabular osteotomy: a cadaveric study
Authors: Lara Joaquín , Garín Alan , Abara Selim , del Río Javier , Besomi Javier , Herrera Cristhián , Cancino Jaime , Villegas Diego , Tobar Carlos
Published: November 2023

The Bernese periacetabular osteotomy (PAO) is a surgical procedure used to treat hip dysplasia in young adults, but it carries the risk of neurological complications, including injury to the motor ascending branch of the rectus femoris (MABRF). This study aimed to describe anatomical considerations to prevent MABRF injuries during PAO. A cadaveric study was conducted on seven specimens. The original and modified PAO approaches were used, with and without disinsertion of the rectus femoris muscle origin. The femoral nerve was dissected in all specimens from the endopelvic position to the MABRF origin (T-point). The average distance from the anterosuperior iliac spine to the T-point was 10.2 ± 0.4 cm. To protect the MABRF, a safety zone was identified for the osteotome placement during the ischial cut. The osteotome was slid over the joint capsule, deflecting the iliocapsularis muscle medially and distally. This manoeuvre shields the MABRF with the iliocapsularis muscle, reducing the risk of neurological injury. Both the original and modified PAO approaches were considered safe techniques with low risk to the rectus femoris innervation. These findings offer valuable insights for surgeons performing PAO, emphasizing the significance of understanding anatomical relationships and implementing protective measures to enhance patient outcomes and minimize complications. In conclusion, implementing these anatomical considerations can help prevent MABRF injuries during PAO, contributing to safer and more successful surgical interventions for hip dysplasia in young adults.
The McMaster osteotomy—a novel surgical treatment to chronic slipped capital femoral epiphysis: description of surgical technique and case study
Authors: Li Zhi , Qiu Reva Y , Khurshed Abdulaziz , Alomran Dana , Williams Dale S , Ayeni Olufemi R , Kishta Waleed
Published: November 2023

Slipped capital femoral epiphysis (SCFE) is a common adolescent hip disorder that can lead to complex proximal femur deformities and devastating consequences such as avascular necrosis, femoroacetabular impingement syndrome and early-onset osteoarthritis. Existing surgical techniques are often insufficient to fully address the constellation of multiplanar deformities in patients with severe SCFE. Therefore, the McMaster Osteotomy, a novel intertrochanteric proximal femur osteotomy, was developed to improve anatomic correction and hip mechanics in patients with chronic SCFE. The McMaster Osteotomy was implemented in two patients (A: 16-year-old male, B: 17-year-old female) with proximal femur deformities due to chronic SCFE. Surgical planning was facilitated with a 3D-printed pelvic model generated from a CT scan of a patient with the SCFE deformity. Patient B also underwent concurrent arthroscopic osteochondroplasty and labral repair. Pre- and post-operative function and radiographic measurements were recorded. Post-operatively, patient A’s neck-shaft angle improved from 125° to 136°, Southwick angle from 52° to 33°, neck length from 66 mm to 80 mm and hip internal rotation from 5° to 25°. Patient B’s post-operative neck-shaft angle improved from 122° to 136°, Southwick angle from 25° to 15°, neck length from 76 mm to 84 mm, hip internal rotation from 5° to 20° and alpha angle from 87.6° to 44.3°. Both patients are pain-free and have obtained full union of their osteotomies. The McMaster Osteotomy is a versatile technique that can produce a more anatomic reconstruction of hip anatomy and restoration of abductor mechanics. As an extracapsular technique, the risk of femoral head avascular necrosis is minimized.
Questionnaire-based scoring system for screening moderate-to-vigorous physical activity in middle-aged Japanese workers
Authors: Adachi Takuji , Ashikawa Hironobu , Funaki Kuya , Kondo Takaaki , Yamada Sumio
Published: November 2023

Objectives: Currently available questionnaires have limited ability to measure physical activity (PA) using accelerometers as a gold standard. This study aimed to develop a PA questionnaire for middle-aged Japanese workers and propose a PA scoring system for predicting low moderate-to-vigorous PA (MVPA).

Methods: A total of 428 participants (median age 49 years; 75.8% men) participated in a 7-day PA measurement using an accelerometer and a questionnaire. The association between questionnaire responses and low MVPA (<150 min/wk) was assessed by logistic regression analysis. A score was assigned to each response based on the correlation coefficients of the multivariate model. The ability of the sum score to predict low MVPA was assessed using the area under the receiver operating characteristic curve (AUC).

Results: Five questionnaire items were used for measuring PA scores (range: 0-50; higher scores indicated a higher probability of low MVPA). The AUC was 0.741 (95% CI, 0.689-0.792), and the sensitivity and specificity at the optimal cut-off value were 66.7% and 68.2%, respectively. This predictive ability was slightly increased by body mass index (AUC 0.745 [95% CI, 0.693-0.796]; sensitivity 69.9%; specificity 66.9%). These predictive values were greater than those of conventional questionnaires used in health checkups in Japan (P < .05).

Conclusions: This questionnaire-based PA scoring system showed moderate accuracy in predicting low MVPA. It is useful for screening physically inactive workers and promoting PA.
Clinical Outcomes of Human Rhinovirus/Enterovirus Infection in Pediatric Hemopoietic Cell Transplant Patients
Authors: Castejon-Ramirez Sandra , Chaisavaneeyakorn Sujittra , Ferrolino Jose A , Allison Kim J , Peterson Megan , Dallas Ronald H , Suliman Ali , Hayden Randall T , Maron Gabriela , Hijano Diego R
Published: November 2023

Background

Respiratory viral infections are common among pediatric transplant patients, with human rhinovirus (HRV) being the most frequent. In pediatric patients undergoing hemopoietic cell transplant (HCT), infection with HRV has been associated with progression to lower respiratory tract infection (LRTI) and adverse outcomes. We describe the clinical presentation and outcomes of HRV infection in children undergoing HCT.

Methods

Single-center retrospective study. HCT recipients who were positive for HRV/EV (HRV+) or negative for any respiratory virus (VN) by BioFire® FilmArray® panel between October 2014 and December 2017, were included. Primary outcomes were progression to LRTI, ICU admission, all-cause mortality at 3 and 6 months, and respiratory event-related mortality at 6 months.

Results

227 patients (160 allogeneic HCT) were included. Of all patients, 108/227 (47.6%) were HRV+. From all HRV+, 95/108 (88%) were symptomatic and 68/107 (63.6%) of the diagnosis were made pretransplant. The median age of HRV+ was significantly lower than VN patients (5 vs 10 years). Cough and rhinorrhea were more frequently observed in HRV+ (53.7 and 60% vs 19.8 and 22.8%, respectively). No differences were found between both groups pretransplant and overall in rates progression to LRTI, ICU admission, mechanical ventilation, all-cause within 3 and 6 months, and mortality related with respiratory failure. No significant association was found between the severity of respiratory disease and the type of conditioning, type of transplant, or absolute lymphocyte count.

Conclusions

HRV infection is frequently detected in HCT recipients but is not associated with severity of respiratory disease, need for intensive care unit or mortality, including those diagnosed before transplant, suggesting that delaying HCT in this scenario may not be needed. Multicenter larger studies are required to confirm these findings.
Film dialogue and R-stylo
Authors: Salt Barry
Published: November 2023

The dialogue of a large number of American feature films of the last 30 years is analysed with the stylometric tools contained in the R-stylo package. Various interesting results showing the capabilities and restrictions of this statistical package emerge.
Music Therapy in Shelters for People Who Are Unhoused: A Scoping Review
Authors: Gregory Dianne , Hernandez Flor , Beach Christopher
Published: November 2023

A scoping review of publications pertaining to music therapy interventions with people who are unhoused and living in shelters was implemented to determine if the available evidence supports professional advocacy and program development with this underserved population at the present time. Searches using EBSCOHost, PsycINFO, ProQuest, and search engines for music therapy journals resulted in 294 publications. Specification of inclusion criteria (population-context-concept) resulted in 13 articles for review to determine the types of evidence, key characteristics of participants and interventions, and gaps and limitations in the literature. An overview of therapists’ descriptions of their sessions’ goals, interventions, and recommendations, combined with information from shelter staff and former participants, provides practical information for interventions and future research. However, the diversity within the small collection of articles prevents generalizations and provides only a glance at possibilities, not a foundation, for professional advocacy and program development.
Journey to kidney transplantation: patient dynamics, suspensions, transplantation and deaths in the Australian kidney transplant waitlist
Authors: De La Mata Nicole L , Khou Victor , Hedley James A , Kelly Patrick J , Morton Rachael L , Wyburn Kate , Webster Angela C
Published: November 2023

Background

People on the kidney waitlist are less informed about potential suspensions. Disparities may exist among those who are suspended and who return to the waitlist. We evaluated the patient journey after entering the waitlist, including suspensions and outcomes, and factors associated with these transitions.

Methods

We included all incident patients waitlisted for their first transplant from deceased donors in Australia from 2006 to 2019. We described all clinical transitions after entering the waitlist. We predicted the restricted mean survival time (unadjusted and adjusted) until first transplant by the number of prior suspensions. We evaluated factors associated with transitions using flexible survival models and clinical endpoints using Cox models.

Results

Of 8466 patients waitlisted and followed over 45 757.4 person-years (median 4.8 years), 6741 (80%) were transplanted, 381 (5%) died waiting and 1344 (16%) were still waiting. A total of 3127 (37%) people were suspended at least once. Predicted mean time from waitlist to transplant was 3.0 years [95% confidence interval (CI) 2.8–3.2] when suspended versus 1.9 years (95% CI 1.8–1.9) when never suspended. Prior suspension increased the likelihood of further suspensions 4.2-fold (95% CI 3.8–4.6) and returning to the waitlist by 50% (95% CI 36–65) but decreased the likelihood of transplantation by 29% (95% CI 62–82). Death risk while waiting was increased 12-fold (95% CI 8.0–18.3) when currently suspended. Australian non-Indigenous males were 13% [hazard ratio (HR) 1.13 (95% CI 1.04–1.23)] and Asian males 23% [HR 1.23 (95% CI 1.06–1.42)] more likely to return to the waitlist compared with females of the same ethnicity.

Conclusion

The waitlist journey was not straightforward. Suspension was common, impacted the chance of transplantation and meant waiting an average of 1 year longer until transplant. We have provided estimates for and factors associated with suspension, relisting and outcomes after waitlisting to support more informed discussions. This evidence is critical to further understand drivers of inequitable access to transplantation.
Inhibition of the glucocorticoid receptor attenuates proteinuric kidney diseases in multiple species
Authors: Stamellou Eleni , Agrawal Shipra , Siegerist Florian , Buse Marc , Kuppe Christoph , Lange Tim , Buhl Eva Miriam , Alam Jessica , Strieder Thiago , Boor Peter , Ostendorf Tammo , Gröne Hermann-Josef , Floege Jürgen , Smoyer William E , Endlich Nicole , Moeller Marcus J
Published: November 2023

Background

Glucocorticoids are the treatment of choice for proteinuric patients with minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS). Immunosuppressive as well as direct effects on podocytes are believed to mediate their actions. In this study, we analyzed the anti-proteinuric effects of inhibition of the glucocorticoid receptor (GR) in glomerular epithelial cells, including podocytes.

Methods

We employed genetic and pharmacological approaches to inhibit the GR. Genetically, we used Pax8-Cre/GRfl/fl mice to specifically inactivate the GR in kidney epithelial cells. Pharmacologically, we utilized a glucocorticoid antagonist called mifepristone.

Results

Genetic inactivation of GR, specifically in kidney epithelial cells, using Pax8-Cre/GRfl/fl mice, ameliorated proteinuria following protein overload. We further tested the effects of pharmacological GR inhibition in three models and species: the puromycin aminonucleoside–induced nephrosis model in rats, the protein overload model in mice and the inducible transgenic NTR/MTZ zebrafish larvae with specific and reversible podocyte injury. In all three models, both pharmacological GR activation and inhibition consistently and significantly ameliorated proteinuria. Additionally, we translated our findings to humans, where three nephrotic adult patients with MCD or primary FSGS with contraindications or insufficient responses to corticosteroids were treated with mifepristone. This treatment resulted in a clinically relevant reduction of proteinuria.

Conclusions

Thus, across multiple species and proteinuria models, both genetic and pharmacological GR inhibition was at least as effective as pronounced GR activation. While the mechanism remains perplexing, GR inhibition may be a novel and targeted therapeutic approach to treat glomerular proteinuria potentially bypassing adverse actions of steroids.
Using a Health Information Exchange to Characterize Changes in HIV Viral Load Suppression and Disparities During the COVID-19 Pandemic in New York City
Authors: Tucker Emma , Reyes Nieva Harry , Schiffer Kayla , Yin Michael T , Castor Delivette , Gordon Peter , Elhadad Noémie , Zucker Jason
Published: November 2023

Background

HIV viral suppression requires sustained engagement in care. The COVID-19 pandemic challenged care accessibility for many people living with HIV (PLWH). We used health information exchange data to evaluate the effect of pandemic-related disruptions in HIV care on viral load suppression (VLS) and to examine racial/ethnic disparities in VLS.

Methods

We performed a retrospective observational cohort study of PLWH using data from a regional health information exchange in the New York City region between 1 January 2018 and 31 December 2022. We established 2 cohorts: PLWH who received HIV care in 2020 (cohort A) and PLWH who did not receive HIV care in 2020 (cohort B). We categorized HIV VLS outcomes as suppressed or not suppressed and calculated the prevalence of VLS between 2018 and 2022. We compared proportions using chi-square tests and used unadjusted and adjusted logistic regression to estimate the association among variables, including race/ethnicity, cohort, and VLS.

Results

Of 5 301 578 patients, 34 611 met our inclusion criteria for PLWH, 11 653 for cohort A, and 3141 for cohort B. In 2019, cohort B had a lower prevalence of VLS than cohort A (86% vs 89%, P < .001). Between 2019 and 2021, VLS dropped significantly among cohort B (86% to 81%, P < .001) while staying constant in cohort A (89% to 89%, P = .62). By 2022, members of cohort B were less likely than cohort A to be receiving HIV care in New York City (74% vs 88%, P < .001). Within both cohorts, Black and Hispanic patients had lower odds of VLS than White patients.

Conclusions

In New York City, VLS remained high among PLWH who continued to receive care in 2020 and dropped among PLWH who did not receive care. VLS was lower among Black and Hispanic patients even after controlling for receipt of care.