bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Prior Hip or Knee Arthroplasty on Oswestry Disability Index Two Years after Elective Lumbar Surgery
Authors: Hambrecht Jan , Köhli Paul , Chiapparelli Erika , Amoroso Krizia , Duculan Roland , Zhu Jiaqi , Guven Ali E. , Evangelisti Gisberto , Burkhard Marco D. , Tsuchiya Koki , Shue Jennifer , Sama Andrew A. , Cammisa Frank P. , Girardi Federico P. , Mancuso Carol A. , Hughes Alexander P. 
Published: December 2024

Study Design.
Secondary analysis of prospective study.

Objective.
To analyze the impact of prior total knee arthroplasty (TKA), total hip arthroplasty (THA), or both on the Oswestry Disability Index (ODI) two years after elective lumbar surgery.

Background.
Degenerative conditions that cause pain and mobility loss significantly reduce quality of life. The rising prevalence of total joint arthroplasties (TJA) and spinal surgeries complicates treatment and may result in persistent postoperative symptoms. Understanding how these surgeries interact and how surgical history and underlying conditions influence postoperative outcomes is crucial.

Methods.
A secondary analysis was performed on a prospective study of patients undergoing lumbar surgery for degenerative conditions. Patients with a two-year ODI follow-up were included. ODI was prospectively assessed pre- and postoperatively. Patients without ODI-assessment were excluded. Differences in pre- and postoperative ODI were evaluated, and patients were categorized based on ODI-improvement. Statistical analyses included Mann-Whitney-U-test, univariable logistic regression, and multivariable logistic regression adjusted for age, sex, and BMI.

Results.
Overall, 385 patients (57% female, 65±10 y) were included. 46 patients (12%) had prior THA, 34 (9%) patients had prior TKA, and 11 (3%) patients had both. ODI-improvement was achieved in 91%. After adjusting for covariates, combined TKA and THA was significantly associated with postoperative ODI non-improvement (OR9.96, 95%CI 2.53-38.3, P=0.001). Prior TKA also tended to be a risk factor for ODI non-improvement, although not statistically significant (P=0.052) after adjusting for covariates.

Conclusion.
Patients with prior concomitant TKA and THA have higher odds of ODI non-improvement two years postoperatively, suggesting that concurrent musculoskeletal degeneration of the spine and lower extremities may negatively impact improvement after lumbar surgery. These results highlight the connection not only between the hip but also the knee and spine.
Sex Disparity in Extracorporeal Membrane Oxygenation Clinical Trial Enrollment
Authors: Damuth Emily , Baldwin Caitlin , Schmalbach Nicole , Green Adam , Puri Nitin , Jones Christopher W. 
Published: December 2024

OBJECTIVES:
Multiple studies have shown that extracorporeal membrane oxygenation (ECMO) is used clinically more often in men than women. Because clinical trials provide the basis for identifying patients who are likely to benefit from medical therapies, we hypothesized that sex-based imbalances in ECMO trial enrollment may both reflect and perpetuate these observed disparities. Our objective was to determine whether sex-based enrollment imbalances exist within the published ECMO clinical trial literature.

DESIGN:
Cross-sectional analysis.

SETTING:
Randomized controlled trials published between 2003 and 2023 that either tested ECMO as a treatment modality or tested another intervention among patients receiving ECMO.

PATIENTS:
Not applicable

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
We used the Cochrane Highly Sensitive Search Strategy to search PubMed for eligible trials. Data on participant demographics, trial characteristics, and journal information were abstracted for each publication. The primary outcome of interest was the proportion of male and female participants in each published trial. The initial literature search identified 774 articles. Of these, 31 were eligible for inclusion, and 28 provided data on the sex of study participants. Twenty-six of these 28 trials (93%) enrolled more men than women, and in aggregate women comprised 28% (95% CI, 26–30%) of all trial participants (551/1956 subjects). Trials involving extracorporeal cardiopulmonary resuscitation (ECPR) exhibited the largest sex-based enrollment differences (83% men) followed by venoarterial ECMO for cardiogenic shock (73% men). Among trials published in journals with impact factors of ten or higher 74% (95% CI, 72–76%) of participants were men. Only two trials (7%) provided data on the race or ethnicity of study participants.

CONCLUSIONS:
Substantial sex-based disparity exists in published ECMO clinical trials. Underrepresentation of women relative to disease prevalence is most significant among trials utilizing venoarterial ECMO for cardiogenic shock and ECPR for cardiac arrest, limiting the applicability of findings from these trials for women.
Leishmaniasis Diagnosed in the United States Successfully Treated With Miltefosine
Authors: LaRocque Autumn , Zheng Vicky , Khambaty Mariam , Pfau Richard , Wheat Chikoti 
Published: December 2024

Abstract
Leishmaniasis is an infectious disease caused by the parasitic protozoa species Leishmania and is most often transmitted to humans through the bite of a sandfly. The most common manifestation is a cutaneous lesion. Leishmaniasis is endemic to many countries throughout the world but rarely diagnosed in the United States. Here, we report a 64-year-old man with initially undisclosed recent travel to Sudan, an endemic country, who returned to the United States with cutaneous lesions on his forehead and dorsal hand. After failing initial therapy, a biopsy showed amastigotes (the tissue stage of the parasite), chronic inflammation with numerous plasma cells, granulomatous features, focal necrobiosis, and neutrophilic debris, consistent with leishmaniasis. The lesions did not significantly improve with fluconazole, but miltefosine (100–200 mg daily) resulted in remission over an 8-week course. The purpose of this case report is to highlight the importance of including rare infectious organisms in the differential and briefly discuss diagnostic and treatment methods.
Angiosome-Guided Revascularization in Local Flap Reconstruction of the Foot and Ankle
Authors: Rohrich Rachel N. , Li Karen R. , Lava Christian X. , Akbari Cameron M. , Attinger Christopher E. 
Published: December 2024

Background
Among patients with critical limb ischemia and tissue loss, revascularization is an essential component for limb salvage. Local flaps of the foot and ankle remain a versatile tool in reconstructive limb salvage but is dependent on adequate arterial flow. In patients with arterial occlusive disease requiring revascularization, there is a lack of evidence in the current literature investigating on the necessity of direct arterial flow to the respective angiosome for local flaps reconstruction. Our study thereby compares the outcomes of direct (DR) and indirect (IR) revascularization for local flap success.

Methods
Patients who received endovascular revascularization (ER) prior to local flap reconstruction for chronic wounds in the foot and ankle were retrospectively reviewed. IR was performed in patients where DR could not be performed. DR was defined as an intervention on the same pedicle used for the local flap. IR was defined as an intervention performed on a different angiosome than the pedicle used for the local flap. Patient demographics, Charlson Comorbidity Index (CCI), angiographic details, postoperative complications, and long-term outcomes were collected.

Results
A total of 33 patients underwent 43 local flap reconstruction with preoperative ER: 58.1% (n = 25) received DR and 41.2% (n = 18) received IR. Patients had a mean CCI of 6.7 ± 1.8, with a high prevalence of diabetes mellitus (93.9%), peripheral arterial disease (90.9%), and end-stage renal disease (33.3%) with no significant differences between groups. In the immediate postoperative period (postoperative day 0 to 12), there were no significant differences in immediate flap success (DR: 100% vs IR: 88.9%, P = 0.169) or partial flap necrosis between (DR: 0.0% vs IR: 16.7%, P = 0.066). Rates of major complications from infection (DR: 28.2% vs IR: 22.2%, P = 0.736), ischemia (DR: 4.0% vs IR: 11.1%, P = 0.562), or dehiscence (DR: 8.0% vs IR: 16.7%, P = 0.634) requiring reoperation were similar between 2 groups. Overall limb salvage rate was 84.9%, and comparable between groups (DR: 78.6% vs IR: 89.5%, P = 0.628).

Conclusions
DR and IR achieve similar rates of limb salvage and flap success after local flap reconstruction. A multidisciplinary vasculo-plastic approach that incorporates preoperative arteriogram and revascularization should be utilized for this highly comorbid patient population to achieve optimal success and limb salvage.
An Epidemiological Survey of Hand Burn Injuries Admitted to a Large Burn Center in the New York City Metropolitan Area
Authors: Salingaros Sophia , Chang Philip H. , Houng Abraham P. , Jacoby Adam 
Published: December 2024

Background
Hand form and function play a vital role in daily living, and even minor trauma can significantly impair quality of life. There is a current paucity of data regarding hand burn patient and injury characteristics, particularly in urban areas in the United States. As the field of hand surgery expands, a demographic understanding of patients with severe injury potentially requiring surgical management is imperative. The aim of this study was to define the epidemiological characteristics of burn injuries involving the hand that were admitted to a large New York City burn center.

Methods
A retrospective review of the electronic health record was conducted to identify all patients admitted to our burn center with burn injury involving the hand from August 2020 to December 2023. Patient demographics, injury etiology and characteristics, and hospital course details were recorded and analyzed.

Results
We identified 96 admitted patients with 140 hand burn injuries, with a patient median age of 38 years. Female patients presented to the hospital significantly later after initial injury than male patients and were more likely to suffer from flame-related injury. The median length of stay for initial admission was 17.5 days, with longer length of stay associated with hypertension comorbidity. Patients experiencing homelessness demonstrated higher rates of psychiatric disorder, substance use, and current smoking. Length of follow-up was positively correlated with estimated household income. Compared to the general city population, the patient cohort was made up of a lower percentage of “White alone” and “Asian alone” race categories and higher percentage of persons experiencing homelessness.

Conclusions
We report the clinical and social characteristics of burn patients with hand involvement admitted to a large urban burn center. Hand burn injuries have distinct risk factors and morbidity implications, and consideration for higher-risk groups is imperative for optimal prevention, acute management, and long-term support.
Application of TFPI2 in Sepsis Severity Prediction
Authors: Song Kaiyuan , Wu Yongbin , Song Ruoyu , Zhou Jiankang , Tan Sichuang , Xiao Lan , Zhang Huali , Tan Sipin 
Published: December 2024

Abstract

Introduction
Infection and coagulation dysfunction are two major features of sepsis, and TFPI2 exhibits both antimicrobial and anticoagulant properties. This study aims to evaluate whether TFPI2 is associated with the severity of sepsis, thereby determining its potential value in sepsis diagnosis and prognosis.

Methods
Serum TFPI2 concentrations were measured and compared among 32 healthy controls, 16 ICU non-sepsis patients, and 106 ICU sepsis patients. Correlation analysis was performed between various indicators and TFPI2 levels in sepsis patients. Logistic regression analysis and ROC curves were used to assess the value of TFPI2 in predicting 28-day mortality in sepsis.

Results
Sepsis patients exhibited markedly elevated serum TFPI2 levels compared to both healthy individuals and ICU patients without sepsis. Serum TFPI2 levels were significantly correlated with sepsis severity indicators such as SOFA, APACHE II, Lac, coagulation markers including ISTH-DIC and SIC scores, and platelet count. Univariate and multivariate logistic regression analyses revealed that TFPI2 is an independent risk factor for 28-day mortality in sepsis. The ROC curve showed that TFPI2 has a significant predictive value for 28-day mortality in sepsis, with an AUC of 0.832 and an optimal cutoff value of 8.316.

Conclusions
This study indicates that serum TFPI2 levels hold promise as a biomarker for predicting the severity of sepsis.
FUNCTIONAL IMMUNOPHENOTYPING FOR PRECISION THERAPIES IN SEPSIS
Authors: Rao Mahil , McGonagill Patrick W. , Brackenridge Scott , Remy Kenneth E. , Caldwell Charles C. , Hotchkiss Richard S. , Moldawer Lyle L. , Griffith Thomas S. , Badovinac Vladimir P. 
Published: December 2024

ABSTRACT
Sepsis remains a significant cause of morbidity and mortality worldwide. Although many more patients are surviving the acute event, a substantial number enters a state of persistent inflammation and immunosuppression, rendering them more vulnerable to infections. Modulating the host immune response has been a focus of sepsis research for the past 50 years, yet novel therapies have been few and far between. Although many septic patients have similar clinical phenotypes, pathways affected by the septic event differ not only between individuals but also within an individual over the course of illness. These differences ultimately impact overall immune function and response to treatment. Defining the immune state, or endotype, of an individual is critical to understanding which patients will respond to a particular therapy. In this review, we highlight current approaches to define the immune endotype and propose that these technologies may be used to “prescreen” individuals to determine which therapies are most likely to be beneficial.
Exploring the Potential of BEND7 as an Immunomodulatory Biomarker in Sepsis through Integrative Genomic and Transcriptomic Analysis
Authors: Ren Chao , Liu Yuyang , Ding Zhangna , Yang Zhanyu , Wan Tao , Zhang Ning , Chen Junyi , Feng Hui , Liu Qi 
Published: December 2024

ABSTRACT

Background
Sepsis is a life-threatening condition driven by a dysregulated immune response to infection. Identifying the genetic factors underlying sepsis pathogenesis remains a major challenge in developing effective treatments.

Methods
The Summary-data-based Mendelian Randomization method was used to integrate genome-wide association study and expression quantitative trait loci data to identify sepsis-related genes. These genes were intersected with prognostic gene sets from Gene Expression Omnibus transcriptomic datasets and validated using an independent dataset. Comprehensive single-cell RNA sequencing analysis, including cell clustering, differential expression analysis, cell-cell communication mapping, and pseudotime trajectory analysis, was performed to explore the roles of the identified genes within the sepsis microenvironment.

Results
Intersection of Summary-data-based Mendelian Randomization and Gene Expression Omnibus gene sets, followed by validation, identified two risk genes and five protective genes as significantly differentially expressed. The risk gene BEND7, predominantly expressed in platelets, was further analyzed using single-cell RNA sequencing, revealing strong interactions with immune cells, particularly monocytes and neutrophils, via the intercellular adhesion molecule signaling pathway. Functional enrichment analysis suggested that BEND7-positive platelets play a role in immune modulation and platelet activation.

Conclusion
BEND7 was identified as a platelet-specific gene involved in immune regulation during sepsis. Targeting BEND7-positive platelets may present new therapeutic opportunities in sepsis management.
Long-term functional recovery after rib fractures: The impact of frailty
Authors: Rafaqat Wardah , Panossian Vahe S. , Yi Alisha , Heindel Patrick , Abiad May , Ilkhani Saba , Heyman Annie , Garvey Shannon , Anderson Geoffrey A. , Sanchez Sabrina E. , Herrera-Escobar Juan P. , Hwabejire John O. 
Published: December 2024

BACKGROUND
Previous studies have shown that patients with rib fractures experience long-term functional limitations. However, the specific predictors of these worse long-term functional limitations remain under-characterized.

METHODS
We conducted a prospective cohort study including patients ≥18 years with an injury severity score ≥9 and isolated chest injury. Patients included had ≥1 rib fracture and were admitted between July 2015 and May 2019 at one of three Level I trauma centers present in our region. We performed stepwise regression analysis to identify predictors of new functional limitations, i.e., limitations that patients developed postinjury in an activity of daily living. Patients were contacted between 5 and 12 months postinjury to inquire about functional limitations. We assessed frailty using the mFI-5 tool, and a score of 1 was considered moderate frailty, while >1 was considered severe frailty.

RESULTS
Among 279 included patients, 74 (26.5%) developed new functional limitations. The majority of patients had a displaced fracture [118 (42.3%)] and ≥3 rib fractures [237 (84.9%)]. A proportion of patients had superior rib fractures [105 (37.6%)], concomitant clavicular, scapular, or sternal fractures [64 (22.9%)], flail chest [37 (13.3%)], moderate frailty [106 (38.0%)], and severe frailty [57 (20.4%)]. Severe frailty and discharge to a skilled nursing facility, rehabilitation facility, or other location as opposed to home were predictors of new functional limitations.

CONCLUSION
In our population, frailty, not injury characteristics, predicted new long-term functional limitations in patients with rib fractures. Frail patients may benefit from additional inpatient and discharge resources for improved long-term outcomes.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level III.
PANGENOMES AID ACCURATE DETECTION OF LARGE INSERTION AND DELETIONS FROM GENE PANEL DATA: THE CASE OF CARDIOMYOPATHIES
Authors: Mazzarotto Francesco , Kalay Özem , Arslan Elif , Cinquina Valeria , Turgut Deniz , Buchan Rachel J , Allouba Mona , Bertini Valeria , Halawa Sarah , Theotokis Pantazis , Budak Gungor , Girolami Francesca , Peldova Petra , Bonaventura Jiri , Aguib Yasmine , Colombi Marina , Olivotto Iacopo , Gennarelli Massimo , Macek Milan , Pelo Elisabetta , Ritelli Marco , Yacoub Magdi , Barton Paul JR , Tetikol H Serhat , Walsh Roddy , Ware James S , Jain Amit 
Published: December 2024

ABSTRACTGene panels represent a widely used strategy for genetic testing in a vast range of Mendelian disorders. While this approach aids reliable bioinformatic detection of short coding variants, it fails to detect most larger variants. Recent studies have recommended the adoption of pangenomes to augment detection of large variants from targeted sequencing, potentially providing diagnostic laboratories with the possibility to streamline diagnostic work-ups and reduce costs.Here, we analyze a large-scale cohort comprising 1,952 cardiomyopathy cases and 1,805 technically matched controls and show that a pangenome-based workflow, GRAF, conjugates higher precision and recall (F1 score 0.86) compared with conventional orthogonal methods (F1 0-0.57) in detecting potentially pathogenic ≥20bp variants from short-read panel data.Our results indicate that pangenome-based workflows aid precise and cost-effective detection of large variants from targeted sequencing data in the clinical context. This will be particularly relevant for conditions in which these variants explain a high proportion of the disease burden.
Association of Polygenic Risk Scores for Neurodevelopmental Traits and Psychiatric Conditions with Incontinence and Constipation in Children and Young People
Authors: Bastiani Oliver , Dardani Christina , Burrows Kimberley , Christensen Jane Hvarregaard , Joinson Carol 
Published: December 2024

AbstractObservational studies report prospective associations of neurodevelopmental and psychiatric traits with paediatric incontinence and constipation, but unmeasured and residual confounding may limit observational measures. Here, we use a prospective birth cohort study to investigate whether common variant genetic liability for a range of neurodevelopmental and psychiatric conditions are associated with paediatric incontinence and constipation. We used data from 7,857 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) with data on genotype, incontinence, and constipation, and calculated Polygenic risk scores (PRS) for neurodevelopmental traits (ADHD, autism, intelligence) and psychiatric conditions (anxiety, depression, and OCD). Incontinence subtypes (daytime urinary incontinence [DUI], enuresis [any bedwetting and enuresis subtypes: monosymptomatic, non-monosymptomatic], faecal incontinence), and constipation, were assessed by parental reports at age 9 years and self-reports at age 14. PRS for ADHD (OR=1.14, 95% CI, 1.01-1.29, unadjustedp=0.040) and depression (OR=1.09, 95% CI, 1.00–1.20, unadjustedp=0.063) were associated with DUI at age 9. PRS for autism (OR=1.19, 95% CI, 1.02-1.41, unadjustedp=0.032) and intelligence (OR=1.17, 95%, 0.99-1.38, unadjustedp=.06l) were associated with DUI at age 14. PRS for ADHD (OR=1.13, 95% CI, 1.03-1.24, unadjustedp=0.008) were associated with constipation at age 9. Within enuresis subtypes, PRS for autism were associated with MNE at age 9 (OR=1.15, 95% CI, 1.03–1.28, unadjustedp=0.012), but not NMNE (OR=0.93, 95% CI, 0.79–1.18, unadjustedp=0.335). No associations survived false discovery rate adjustment. The findings add to existing evidence that common variant genetic liability for neurodevelopmental traits and psychiatric conditions could be associated with paediatric incontinence and constipation.Key pointsQuestionAre common variant genetic liabilities for neurodevelopmental and psychiatric conditions associated with paediatric incontinence and constipation in a population-based cohort?FindingsWe found some evidence that polygenic risk scores (PRS) for ADHD, autism, intelligence, and depression may be associated with daytime urinary incontinence. PRS for ADHD were also associated with constipation and enuresis and PRS for autism and depression were weakly associated with constipation. None of the associations survived adjustment for false discovery rate.MeaningCommon variant genetic liabilities for ADHD, autism, intelligence, and depression could be risk factors for developing paediatric incontinence and constipation.