bluuebunny/crossref_metadata_2025 huggingface dataset:
An Information-Theoretic Asset Pricing Model
Authors: Ghosh Anisha , Julliard Christian , Taylor Alex P
Published: January 2025

We show that a non-parametric estimate of the pricing kernel, extracted using an information-theoretic approach, delivers smaller out-of-sample pricing errors and a better cross-sectional fit than leading multi-factor models. The information stochastic discount factor (I-SDF) identifies sources of risk not captured by standard factors, generating very large annual alphas (20–37%) and Sharpe ratio (1.1). The I-SDF extracted from a wide cross-section of equity portfolios is highly positively skewed and leptokurtic, and implies that about a third of the observed risk premia represent compensation for 2.5% tail events. The I-SDF offers a powerful benchmark relative to which competing theories and investment strategies can be evaluated.
PLA2R autoantibodies, a multifaceted biomarker in nephrotic syndrome and membranous nephropathy
Authors: Ragy Omar , Abass Wessam , Kanigicherla Durga Anil K , Shinkins Bethany , Bestall Janine , King Natalie , Brenchley Paul , Smith Alison , Hamilton Patrick
Published: January 2025

Background and hypothesis

The PLA2R antibody test is a valuable first-line diagnostic tool for primary membranous nephropathy (MN), helping to identify PLA2R-related MN and potentially eliminating the need for a kidney biopsy in some individuals. By reducing the reliance on biopsies, the test streamlines diagnosis and improves patient care. However, determining the optimal PLA2R measurement method and cut-off is critical to maximising the benefits of the test and minimising any harms.

Methods

A systematic review and meta-analysis were performed to evaluate serum- and urine-based biomarkers for distinguishing between PLA2R-related MN and non-PLA2R MN. Searches were conducted in databases including Medline, Embase, Cochrane Library, Scopus, Web of Science, INAHTA, and ClinicalTrials.gov. The methodology followed Cochrane-recommended guidelines for systematic reviews and meta-analyses, and the QUADAS-2 tool was utilised to assess the overall risk of bias.

Results

Ninety one studies met the eligibility criteria for inclusion in the review. Of these, 38 studies reporting the accuracy of the PLA2R-Ab test using the EUROIMMUN ELISA method and 27 using the EUROIMMUN IF method were suitable for meta-analysis.. The pooled sensitivity and specificity of EUROIMMUN ELISA at a cut-off value of 20 RU/ml were 0.64 (95% CI: 0.56, 0.72) and 94.7% (95% CI: 90.5 - 97.1%),  respectively. The pooled sensitivity and specificity of EUROIMMUN IF at a threshold of 1:10 was 0.69 (95% CI: 0.637 – 0.739) and 0.98 (95% CI: 0.931 – 0.994), respectively. Risk of bias was higher for studies evaluating the IF compared to ELISA test. We also explored whether the timing of the index test had an impact on the pooled diagnostic accuracy results; no significant differences were found.

Conclusions

By evaluating the specificity and sensitivity of EUROIMMUN ELISA PLA2R-Ab and immunofluorescence (IF), we demonstrate that at ELISA levels ≥20 RU/mL, alongside thorough secondary screening, a kidney biopsy may be unnecessary. However, lower or negative levels still warrant a biopsy.
Electrochemical dendrite management via voltage-controlled rearrangement
Authors: Liu Zhexuan , Wu Xinru , Xiao Xiao , Xiao Zhiqiang , Fu Qingjin , Zheng Zhiyang , Zhong Xiongwei , Zheng Fengyi , Zhou Guangmin
Published: January 2025

The pursuit of advanced energy storage solutions has highlighted the potential of rechargeable batteries with metal anodes due to their high specific capacities and low redox potentials. However, the formation of metal dendrites remains a critical challenge, compromising both safety and operational stability. For zinc-based batteries (ZBs), traditional methods to suppress dendrite growth have shown limited success and often entail performance compromise. Here, we propose a novel strategy termed dendrite rearrangement (DR) that leverages the electrochemical self-discharge process to controllably address the dendrite issues. By temporarily increasing the input voltage within a single cycle, this strategy resets the cell stability without precipitating undesirable side reactions during normal operation. This pioneering technique extends operational lifespans to over three times their original duration, facilitating 80,000 cycles for Zn-ion hybrid capacitors and 3,000 hours for Zn symmetrical cells. Even in scaled-up pouch cells, Ah-level symmetrical cells demonstrate a cumulative capacity nearing 200,000 mAh, significantly surpassing that of reported metal symmetrical cells. Additionally, the electrolytic Zn-MnO2 battery demonstrates a high capacity approaching 10 Ah, setting a new benchmark among reported ZB devices. These results mark a significant advance towards resolving dendrite-related issues in metal anode batteries, paving the way for their sustainable development and potential commercialization.
Knee Anterior Laxity and Graft Maturation After Transphyseal Anterior Cruciate Ligament Reconstruction
Authors: Accadbled Franck , Lescot Timothé , Nicolaou Nicolas , Doumerc Jeremy , Cavaignac Etienne , Flumian Clara , Maupoint Estelle , Sales de Gauzy Jérôme
Published: January 2025

Background:

The failure rate of anterior cruciate ligament (ACL) reconstruction in children and adolescents is a significant concern. Of the multitude of clinical factors that contribute to this risk, delayed maturation and graft laxity are potentially related and modifiable elements. The aim was to investigate knee anterior laxity and graft maturation in children and adolescents. The ligamentization of the graft may be correlated with the residual laxity.

Methods:

A single-center prospective study included skeletally immature patients treated with transphyseal ACL reconstruction using semitendinosus tendon autograft from 2017 to 2019. Participants were evaluated on 4 occasions: preoperatively, then at 6, 12, and 24 months with instrumented laximetry and MRI to analyze graft maturation according to the Signal-to-noise Quotient (SNQ) and Howell classification.

Results:

A total of 50 patients (33 boys and 17 girls), with a mean age of 13.2 years (range, 9 to 16) at the time of surgery, were included. Mean side-to-side knee anterior laxity decreased from 2.78 mm preoperatively to 1.59, 1.80, and 1.30 mm (at 6, 12, and 24 mo follow-up, respectively), P<0.05. No statistical difference was noted according to the follow-up or sex. SNQ was unchanged between 6 and 12 months, but a significant difference was demonstrated between 12 months and 24 months (P=0.008). There was no statistical correlation between laximetry and graft maturation.

Conclusions:

ACL graft ligamentization is delayed in children and adolescents and only occurs between 12 and 24 months postoperatively. Residual laximetry and MRI signal of the graft may become one of the multiple elements upon which to base the decision to return to sport.
Pediatric Bone Sarcoma Biopsy Tract Excision: Is it Safe to Resect Separately?
Authors: Eckhoff Michael D. , Strub Daryn R. , Utset-Ward Thomas J. , Wells Matthew E. , Scharschmidt Thomas J.
Published: January 2025

Background﻿:

Biopsy is an essential part of proper diagnostic workup in pediatric bone sarcomas impacting surgical planning, chemotherapeutic treatments, and prognostic determination. Two main biopsy techniques are currently used: closed biopsy (core needle or fine needle aspiration) and open biopsy. Historical oncologic teaching is for resection of the biopsy tract with the tumor specimen due to the theoretical risk for biopsy tract tumor contamination; however, this can restrict surgical planning and increase morbidity. This study evaluates oncologic outcomes at this institution, comparing open versus closed biopsy, and biopsy tract resection with or separate from the main tumor resection.

Methods:

Retrospective review of a single institution of all patients treated for bone sarcomas from 2006 through December 2021. Patient and tumor characteristics, biopsy technique, biopsy resection method, and oncologic outcomes were collected. Subgroup statistical analysis was performed comparing closed biopsy and open biopsy techniques, and biopsy tract resection with the main tumor or separately.

Results:

A total of 73 patients met the inclusion criteria, including 48 (65.8%) open biopsies and 25 closed biopsies [23 (31.5%) core needle biopsies and 2 (2.7%) fine needle aspirations]. Biopsy tract resection was performed with the main tumor in 36 (49.3%), separate in 37 (50.7%). There were no statistical differences in local recurrence, disease-free survival, metastatic progression, or overall survival between biopsy methodology analysis and biopsy tract removal methods.

Conclusion:

This study demonstrates the safety of both approaches for obtaining diagnostic tissues with low rates of biopsy tract seeding in both methods. In addition, it demonstrates that there is no difference in local recurrence, disease-free survival, metastatic progression, or overall survival between biopsy tract resection with or separate from the main tumor. Definitive surgical plan should not vary based on biopsy technique and biopsy tract management, but rather patient, tumor, institutional, and surgeon factors.

Level of Evidence:

Level III—retrospective chart review. The study was started after the patients were diagnosed and treated.
Unmasking High-Output Heart Failure: Beyond Conventional Paradigms
Authors: Shafi Irfan , Harmouch Khaled M. , Prakash Preeya , Kahe Farima , Ramappa Preeti , Afonso Luis
Published: January 2025

Heart failure (HF) poses a significant medical challenge, affecting millions of adults in the United States. High-output heart failure (HOHF) is a distinct subtype characterized by elevated cardiac output exceeding 8 L/min or a cardiac index >4 L/min/m². Patients with HOHF often present similarly to those with heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. However, the underlying pathophysiology differs; triggered by a progressive decline in systemic vascular resistance, the ensuing elevation of cardiac output eventually leads to left ventricular remodeling and HF. Failure to differentiate HOHF from other variant forms of HF has implications for management, particularly relating to the use of vasodilator medications with potentially deleterious consequences, ensuing from the unrestrained adoption of societal guideline-directed medical therapy recommendations. Despite its clinical importance, HOHF remains under-examined in literature, with limited recognition and understanding among clinicians. This review aims to provide a comprehensive analysis of knowledge surrounding HOHF, exploring its definition, etiopathology, and underlying pathophysiological mechanisms. Recognizing the challenges in diagnosing HOHF, we propose a novel diagnostic algorithm tailored to address the subtleties of this often-misdiagnosed variant of HF.
Interventional Cardiac Electrophysiology for the Management of Adults With Congenital Heart Disease
Authors: Kidess George G. , Brennan Matthew T. , Basit Jawad , Alraies M. Chadi
Published: January 2025

Congenital heart disease (CHD) is the most common congenital anomaly in newborns. Advances in catheter and surgical techniques led to the majority of these patients surviving into adulthood, leading to evolving challenges due to the emergence of long-term complications such as arrhythmias. Interventional electrophysiology (EP) has had remarkable advances over the last few decades, and various techniques and devices have been explored to treat adult patients with CHD. This comprehensive review aims to summarize findings from recent studies exploring advances in the use of interventional electrophysiology to manage adult patients with CHD. While pacemaker therapy has some indications in adults with CHD, various long-term consequences include pacing-induced cardiomyopathy and complications requiring reintervention. Cardiac resynchronization therapy has shown promising results in some studies to treat CHD patients with heart failure, although further research to clarify guidelines is encouraged. Implantable cardiac defibrillators have demonstrated clear benefits in CHD patients and are indicated for primary prevention of sudden cardiac death, although selection criteria for secondary prevention of sudden cardiac death are uncertain. Catheter ablation has also been used for various atrial and ventricular arrhythmias in patients with CHD with high success rates, although the likelihood of success depends on patient characteristics and the type of arrhythmia, and multidisciplinary assessment is encouraged to improve the chance of successful therapy.
Rhinoplasty Septal Cartilage Harvest and Reconstruction: The 4 Clicks
Authors: Gimenez Alejandro R. , Borab Zachary , Fisher Sean , Rohrich Rod J.
Published: January 2025

Successful rhinoplasty relies on a deep understanding of nasal anatomy and precise nasal tip control for lasting functional and aesthetic outcomes. Structural grafts, like septal extension grafts, are instrumental in maintaining tip position and projection with minimal long-term changes. This article details a systematic technique to harvest septal cartilage that maximizes graft material and allows for effective septal deviation correction.
Monitoring response to prone positioning
Authors: Guérin Claude , Grasselli Giacomo
Published: January 2025

Purpose of review

The increasing use of prone position, in intubated patients with acute respiratory distress syndrome as well as in patients with acute hypoxemic respiratory failure receiving noninvasive respiratory support, mandates a better definition and monitoring of the response to the manoeuvre. This review will first discuss the definition of the response to prone positioning, which is still largely based on its effect on oxygenation. We will then address monitoring respiratory and hemodynamic responses to prone positioning in intubated patients. Finally, we will also discuss monitoring inspiratory effort in nonintubated patients with acute hypoxemic respiratory failure who breathe spontaneously and receive noninvasive respiratory support

Recent findings

The response to prone positioning should be enriched by data pertaining to lung protection beyond oxygenation. These include trans-pulmonary pressure, driving pressure, mechanical power, distribution of aeration and ventilation and assessment of potential for lung recruitment before the pronation.

The implications of present findings are to: better select those patients who will benefit from proning in physiological terms, better indicate the timing of onset and end of the sessions, and strengthen the relationship between physiological response and patient outcome.
Natural history of recovery and long-term outcome in critically ill patients with brain injury
Authors: Kanny Samantha , Giacino Joseph T.
Published: January 2025

Purpose of review

To increase knowledge of the natural history of recovery and long-term outcome following severe traumatic brain injury (sTBI).

Recent findings

Recovery of consciousness and complex behaviors that presage subsequent functional recovery frequently occurs well beyond the first 7 days after injury, which is typically the time period widely used in the ICU for prognostic decision-making and establishing goals of care for. Similarly, recovery of functional independence occurs between 1 and 10 years postinjury in a substantial proportion of patients who do not recover command-following during the acute hospitalization. Data from large, multicenter studies that systematically conduct long-term follow-up with well validated measures consistently indicate that the most common trajectory of recovery after 1 year postinjury is characterized by changes, not stability, in functional status.

Evidence from large multicenter studies with well characterized samples focusing on recovery trajectories beyond 1 year postinjury challenge conventional beliefs about outcome after sTBI. Signs of consciousness frequently emerge following discharge from the ICU setting and prediction of death and dependency within the first few weeks after injury is unreliable. Clinician knowledge of the frequency and time course to recovery of key behavioral milestones is central to evidence-based prognostic counseling.
Immunohistochemical Expression of PAX﻿8 in Central Nervous System Hemangioblastomas: A Potential Diagnostic Pitfall for Neuropathologists
Authors: Broggi Giuseppe , Farina Jessica , Barresi Valeria , Certo Francesco , Barbagallo Giuseppe Maria Vincenzo , Magro Gaetano , Caltabiano Rosario
Published: January 2025

The histologic differential diagnosis between intracranial hemangioblastoma (HB) and metastatic clear cell renal cell carcinoma may be challenging, especially considering that both tumors exhibit clear cell morphology and can be associated with vHL mutation and/or Von Hippel-Lindau syndrome. As the execution of immunohistochemical analyses is often mandatory, the expression of PAX8 has been traditionally considered a reliable marker of metastatic clear cell renal cell carcinoma, being consistently negative in intracranial HB. However, as in recent years, some cases of PAX8-positive HBs have been reported in the literature; we studied the expression of this antibody on a series of 23 intracranial HB, showing that about 40% of these tumors may express PAX8 and that this immunoreactivity is often focal and weak. We would like to emphasize that the possibility of a PAX8-positive intracranial HB does exist and must be taken into account by neuropathologists to avoid misdiagnoses; in this regard, a broader immunohistochemical panel also including CD10, Inhibin-α, PAX2, S100, and anti-﻿R﻿enal cell carcinoma (RCC) antibody﻿ is highly recommended.
Code Milk
Authors: Goli Shubhi G. , Sebok-Syer Stefanie S. , Halpern-Felsher Bonnie , Goyal Shuchi , Wang N. Ewen , Fang Andrea
Published: January 2025

Objectives:

The aim of the study is to characterize the lactation goals and practice of pediatric emergency medicine (PEM) fellows and to identify areas of improvement related to 1) policy awareness, 2) departmental culture and accommodations, and 3) lactation space and time.

Methods:

This study is a national, cross-sectional survey study of PEM fellows and program directors (PDs). Two surveys were developed via iterative review and distributed by the PEM-PD Survey Committee. Responses were collected anonymously via the Qualtrics survey platform. Data were summarized using descriptive statistics.

Results:

Survey responses from 60 PEM PDs (71%, 60/84) estimated that 67% (310/461) of their fellows had the ability to lactate. One hundred fifteen study-eligible fellows (37%) completed the survey. Most fellows (57%, 66/115) reported having lactated or expected to lactate during fellowship. Fellows reported an ideal lactation time of 11.5 months. Sixty-two percent (8/13) met their lactation goal and 42% (22/66) did not or did not know if they would meet their goal. Forty-three percent (50/115) of fellows and 57% (34/60) of PDs were aware of workplace lactation policies. Sixty-one percent (38/62) of fellows discussed a lactation plan with their PDs and 18% (7/39) reported their rotations upon returning to work were scheduled with lactation needs in mind. A dedicated lactation space was available to 67% (43/64) of fellows but used by 29% (11/28). Fellows lactated on average twice during an 8-hour shift, spending 7 minutes walking to and from their chosen lactation space and 21-minute pumping per session.

Conclusions:

PEM fellows are likely to have lactation needs during fellowship but receive inconsistent support from their programs. Based on our findings, we advocate for the creation of more visible and PEM-specific workplace lactation policies, planning with PDs pre-return to work, and improved availability and usability of designated lactation spaces. Further optimization may help support PEM fellows' personal, clinical, and academic productivity.
Fibromyalgia syndrome—a bodily distress disorder/somatic symptom disorder?
Authors: Häuser Winfried , Fitzcharles Mary-Ann , Henningsen Peter
Published: January 2025

Introduction:

The debate addressing the classification of chronic widespread pain as a physical disorder (fibromyalgia syndrome) [FMS] or a somatoform disorder according to psychiatric classification systems has continued for decades.

Objectives:

The review aims to line out the new perspectives introduced by the 11th version of the International Classification of Diseases (ICD 11) of the World Health Organization (WHO).

Methods:

Critical review of the classification criteria of fibromyalgia syndrome and bodily distress disorder in ICD 11.

Results:

Fibromyalgia syndrome has been eliminated from the chapter of diseases of the musculoskeletal system and is now included in a chapter “Symptoms, signs, clinical forms, and abnormal clinical and laboratory findings, not elsewhere classified“. Previously, the ICD-10 diagnosis of somatoform disorder was often used by mental health care disciplines instead of the label FMS. Somatoform disorders category has been eliminated as a diagnostic category in the ICD-11 and the 5th version Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (APA) and has been replaced with the new categories of bodily distress disorder (BDD) and somatic symptom disorder (SSD) respectively. For diagnosis, these latter mental disorders require at least one distressing somatic symptom (e.g. pain) plus positive psychobehavioral criteria, namely „excessive thoughts, feelings, or behaviours related to the somatic symptoms or associated health concerns“, without the condition that distressing somatic symptoms have to be medically unexplained.

Conclusion:

We argue that the psychobehavioral criteria of BDD/SSD are imprecisely defined and can be misinterpreted as for „Excessive health concerns“ which may occur due to the many uncertainties surrounding FMS or „Excessive time devoted to the symptoms“ which may be related to patient self-management strategies.
Gender differences in clinical presentations and sensory profiles in patients with fibromyalgia: implications of peripheral and central mechanisms
Authors: Liu Min , Harris Stephany , Andreou Anna P. , Bo Xuenong , Al-Kaisy Adnan
Published: January 2025

Introduction:

Fibromyalgia has a high female predominance and research work has been focussing mainly on women.

Objectives:

We aimed to answer (1) gender differences in pain scores and quality of life, (2) any gender-specific subgroups defined by quantitative sensory testing (QST), and (3) correlations of QST parameters with pain intensity and questionnaire scores.

Methods:

We evaluated clinical presentations and QST profiles from 38 male and 38 age-matched female patients.

Results:

Women reported significantly higher scores in average daily pain, daily sleep interference score, average weekly pain, weekly sleep interference score, and revised fibromyalgia impact questionnaire (rFIQ). Based on LOGA classification, L0G2, mechanical allodynia or hyperalgesia without abnormal sensory loss, was the most common QST subtype which accounted for 28.9% of men and 26.3% of women. Approximately 34.2% of men and 26.3% of women displayed loss of function of small fibres with an increased cold or warm detection threshold. Cold detection threshold was negatively correlated with pain intensity and functional impairment, suggesting a peripheral mechanism. Central sensitization, defined as allodynia and hyperalgesia to thermal or mechanical stimuli, was found in two-thirds of male and female patients. Mechanical pain sensitivity was positively correlated with the severity of pain and associated symptoms in women, but not men.

Conclusion:

There was a marked gender difference in reported pain and quality of life. We have confirmed that central sensitization is a major mechanism for women. Our data suggested an important role of small fibre pathology in both men and women.
Improvement in Temple Hollowing with VYC-20L Hyaluronic Acid Filler: A Multicenter, Randomized Controlled Trial of Safety and Effectiveness
Authors: Montes José Raúl , Hooper Deirdre , Jones Derek , Biesman Brian , Baumann Leslie , Beer Kenneth , Yoelin Steve , Leung Kelly , Chawla Smita
Published: January 2025

Background:

Temple hollowing is characterized by the reduction of volume in the temporal fossa, which can result in a skeletonized look and contribute to an aged appearance. This study aimed to evaluate the safety and effectiveness of the VYC-20L injectable gel for improvement of temple hollowing.

Methods:

Adults with minimal, moderate, or severe temple hollows were randomized 2:1 to receive VYC-20L or no treatment. Participants were followed for 13 months for safety and effectiveness assessments. Treatment effectiveness was assessed by blinded evaluating investigators using the validated Allergan Temple Hollowing Scale (ATHS) and the Global Aesthetic Improvement Scale (GAIS), and by participants using GAIS, FACE-Q scales, and patient satisfaction questionnaires. Adverse events and injection site responses (ISRs) were monitored.

Results:

At Month 3, 80.4% of the treatment group vs 13.5% of the untreated control group achieved a ≥1-grade improvement in both temples on the ATHS (P < 0.0001). The ATHS responder rate remained high throughout Month 13. The GAIS responder rates at Month 3 (responses of Improved or Much improved) were high in the treatment group, as assessed by the blinded evaluating investigator (83.8%) and participants (92.9%). Furthermore, satisfaction with Facial Appearance and Temples on the FACE-Q questionnaires increased significantly from baseline (both P < 0.0001). Adverse events and ISRs were mostly mild and consistent with the known safety profile of fillers.

Conclusions:

VYC-20L treatment showed favorable safety and effectiveness results in restoring temple volume, with significant aesthetic improvement and high participant satisfaction. Treatment effects lasted for over a year.
Using Transorbital Sonography for Assessing Traumatic Brain Injury in Patients With Periorbital Hematoma
Authors: Bao Yi-Ping , Shen Tian-Yu , Lou Zi-Wei , Zhou Yang , Zhang Ling
Published: January 2025

Objective:

The aim of this study is to assess the comparative effectiveness of transorbital sonography (TOS) and the pupillary penlight visual assessment method in patients with traumatic brain injury (TBI) and periorbital hematoma.

Methods:

A total of 140 patients with traumatic brain injury (TBI), meeting the inclusion and exclusion criteria, were selected from a tertiary hospital in Zhejiang Province between January 2022 and December 2023. Pupillary function in all patients was assessed using both TOS and the pupillary penlight visual assessment method on the first, third, and seventh day after admission. The stability and consistency of the measurement results were compared. Stability was determined using the coefficient of variation, whereas consistency was assessed using the intraclass correlation coefficient.

Results:

The coefficients of variation for the pupillary transverse diameter values measured by TOS were 29.84% (left) and 29.55% (right) on day 1, 27.81% (left) and 26.88% (right) on day 3, and 26.80% (left) and 25.51% (right) on day 7. These values were consistently lower than those obtained through the pupillary penlight visual assessment method, indicating superior stability with the TOS measurement. In addition, the intraclass correlation coefficient analysis demonstrated consistency between the 2 methods, with values ranging from 0.562 to 0.809 (P<0.05), indicating good consistency.

Conclusion:

TOS represents an innovative tool for neurological assessment. It has been validated that the presence or absence of eyelid edema does not compromise the accuracy of ultrasound-based pupillary function measurements. The 2 methods of measurement exhibit good consistency, with the TOS method demonstrating superior stability in monitoring data. This approach provides a more accurate means of assessing pupillary function in patients with TBI who have periorbital hematoma or facial swelling, particularly when opening the eyelid is challenging, thereby addressing a significant clinical nursing challenge.
Surgical Opioid Stewardship: From the Epidemic Through the Pandemic and Beyond
Authors: Podder Sourav K , Koeneman Scott , Fagenson Alexander M , Schleider Christine , Philp Matthew M , Noonan Kristin M , Braun Pamela A , Smith Meghan , Cowan Scott W , Pitt Henry A ,   for the Pennsylvania New Jersey – Surgical Opioid Stewardship
Published: January 2025

Background:

In response to the opioid epidemic, prescribing guidelines and statewide surgical opioid management programs were initiated in 2018-19. This analysis aims to document the sustainability of a regional opioid stewardship consortium through the pandemic and beyond.

Study Design:

From September 2019 through August 2023, 15 NSQIP hospitals in two states gathered opioid-specific variables on patients undergoing 12 procedures. Operations were performed by seven specialties including general surgery, gynecology, orthopedic surgery, neurosurgery, surgical oncology, urology, and vascular surgery. Data were gathered on preoperative opioid use, intraoperative opioids and blocks, opioid avoidance strategies and discharge opioid prescriptions. Cochran-Armitage trend and Wald tests were utilized to assess temporal effects with p values <0.001 considered significant.

Results:

Among 18,325 patients who underwent surgery, 54% were women, with a median age of 60 years. The percentage of patients taking opioids preoperatively decreased significantly (p<0.001) in the overall cohort from 17% to 10%. The utilization of intraoperative blocks also increased significantly (p<0.001) among all patients from 21% to 27%. The utilization of opioid avoidance strategies was maintained in the majority of the patients (68-70%) and the percentage of postoperative opioid prescriptions on discharge remained the same (81%) over the four-year study period.

Conclusion:

From 2019 to 2023, the percentage of patients taking opioids preoperatively decreased significantly, and the utilization of intraoperative blocks also increased significantly. The PENNJ-SOS program played a key role in combatting the opioid crisis over the four years of data collection, adapting effectively to the challenges posed by the Coronavirus Disease 2019 pandemic.
Impact of a 7-Gene Predictive Biosignature on Adjuvant Radiation Therapy Recommendations in Patients Undergoing Breast-Conserving Surgery for Ductal Carcinoma in Situ
Authors: Margenthaler Julie A , Zoberi Imran , Thomas Maria , Kennard Kaitlyn
Published: January 2025

Background:

Breast conservation therapy for patients with DCIS includes breast conserving surgery (BCS) with post-operative radiotherapy (RT). Because RT does not impact overall survival, identifying women who do not benefit from RT would allow de-escalation of therapy. We evaluated the impact of a novel 7-gene DCIS biosignature on adjuvant radiation recommendations for patients undergoing BCS for DCIS.

Methods:

7-gene biosignature was evaluated in women diagnosed with DCIS between 2019-2022. 7-gene biosignature is reported as a “decision score” (DS) and categorical risk groups. RT recommendation before and after 7-gene biosignature was identified through retrospective chart review after IRB approval. The impact of DCISionRT on RT recommendations was assessed using McNemar’s test. The 7-gene biosignature decision score (DS) was compared between treatment types by t-test.

Results:

101 patients underwent BCS for DCIS. Of those, 24 (24%) met RTOG 9804 criteria and 45 (45%) had nuclear grade 3 DCIS. Prior to 7-gene biosignature testing, all 101 patients were recommended RT; after testing, 35 patients omitted RT, corresponding to a 35% decision change (p<0.0001). Patients who ultimately omitted radiation had a significantly lower decision score (DS median 0.9) versus those who received RT (DS median 3.7) (p<0.0001). There were 22 of 39 patients (56%) with DS<2 and 11 of 40 patients (28%) with DS 2-4 who were not treated with RT. More patients with DS>4 (20/22, 91%) were treated with RT than DS<2, p<0.001, and patients with DS>4 were treated with an increased RT dose, p=.028.

Conclusions:

7-gene biosignature test resulted in a 35% reduction in patients treated with adjuvant RT. Patients with higher decision scores were more likely to receive RT and to receive a greater RT dose.
Comparison of Partial Endoscopic vs Surgical Fundoplication after Hiatal Hernia Repair
Authors: Hodgens Brian , Godwin George , Rhodes Marvin , Korver Isaac , Abshier Chase , Boyd Cooper , Jorgensen Brynne , Sunkavalli Madhu , Blackhurst Dawn , Kothari Shanu
Published: January 2025

Background:

The concomitant hiatal hernia repair with endoscopic fundoplication (c-TIF) is a novel anti-reflux procedure that addresses the hiatus and the gastro-esophageal flap valve for surgical candidates with GERD. We aim to compare the outcomes of a hiatal hernia repair with endoscopic fundoplication (TIF) vs surgical partial fundoplication (anterior and posterior) with regards to quality-of-life scores at 12 months after surgery.

Study Design:

Following IRB approval, a prospectively maintained anti-reflux database was retrospectively reviewed to identify patients who underwent a c-TIF procedure or a surgical hiatal hernia repair with partial fundoplication. The primary endpoint was QoL scores at 2, 6, and 12 months from surgery with attention to bloating and dysphagia scores. Secondary endpoints were PPI use, 30-day outcomes, OR time and costs, re-operation within 1 year. The three groups were compared using analysis of variance for continuous variables and Pearson’s Chi-square test for categorical variables. P-values < 0.05 were considered indicative of statistical significance.

Results:

Demographics between groups were similar except for age, PPI use, and presenting symptoms. There was no difference between the three groups with regards to post-operative QoL scores, PPI use, dysphagia, or bloating. All three types of fundoplication are associated with significant improvement of all symptom types and 65-80% of patients are no longer using a PPI at 12 months.

Conclusion:

There are no differences in outcomes between the c-TIF and a surgical partial fundoplication. QoL scores significantly decrease with all partial fundoplications and there are no differences in dysphagia or bloating between the three types of fundoplication. Long term data is necessary to see if either technique provides superior control of symptoms while minimizing dysphagia and bloating.
Impact of Massive Transfusion Activation on Time to Delivery of the First Cooler and Patient Survival: A Study of 4,313 Consecutive Activations
Authors: Van Gent Jan-Michael , Bavishi Devi , Clements Thomas W , Dickey James B , Hobbs Rhonda , Bai Yu , Kao Lillian S , Cotton Bryan A
Published: January 2025

Background:

In 2012, TQIP guidelines for massive transfusion protocols (MTP) recommended delivery of blood product coolers within 15 minutes. Subsequent work found that every minute delay in cooler arrival was associated with a 5% increased risk of mortality. We sought to assess the impact and sustainability of quality improvement (QI) interventions on time to MTP cooler delivery and their association with trauma patient survival.

Study Design:

In 2009, a quality improvement (QI) process was initiated to improve MTP activation and delivery of blood (QI #1). In 2012, TQIP Best Practice Guidelines were implemented at our facility (QI #2). In 2016, we implemented measures to activate our MTP based off prehospital ABC score >1 or any prehospital blood transfusion (QI #3). All patients receiving MTP from 01/2009 and 12/2022 were included. Patients were compared by year and their respective QI interventions. Primary outcome was time from MTP activation to delivery of the first cooler. A regression model was then constructed to evaluate time to first cooler on outcomes.

Results:

During the study period, 52,328 trauma patients were admitted, with 4,313 MTP trauma activations. With each subsequent QI intervention, time to first MTP cooler and mortality both decreased, while injury severity increased. Multivariate regression noted that when time to first cooler could be kept to 8 minutes or less, mortality was reduced by 35% (OR 0.64, 95% C.I. 0.44-0.92; p=0.019).

Conclusion:

With increased MTP activations, delivery of the first cooler was faster and mortality improved. Keeping cooler times under 8 minutes was associated with increased survival. The measurement and monitoring of “Door-to-cooler” time should be considered as a metric to assess performance and delivery of institutional MTP.
Southern Surgical Association: Leadership Pre and Post Flexner’s Report
Authors: Holman William L
Published: January 2025

Preface:

The Joseph M Donald Endowment for the Archival Collection of the Southern Surgical Association is named for the 73rd President Elect of the Southern Surgical Association (Figure 1), who died in 1961 at age 57 before he had the opportunity to deliver his Presidential Address. Dr Donald’s career as a surgeon in Birmingham began in 1931 after the completion of his residency at the Mayo Clinic. He was one of four generations of Donalds to serve Alabama as physicians. Joe practiced General Surgery at three hospitals in Birmingham, including work as voluntary faculty at University Hospital under Dr James Mason and later Dr Champ Lyons.

Dr Donald interrupted his practice to serve in the European Theater with the US Army Medical Corps during the Second World War. He was a Governor and Regent of the American College of Surgeons (ACS) and a leader in the Alabama Chapter of the ACS. Two of his sons, Joseph, Jr and Thomas trained as surgeons. From 1854 until the present, twenty-four Donald or Donald-related physicians have practiced in Alabama (personal communication, Dr Thomas T Donald). The present talk is dedicated to the memory of Dr Joseph Marion Donald and his contributions to the field of surgery.
Reducing blood culture contamination: an environmental imperative
Authors: Gregg Sophie , Purcell Niamh , Doyle Maeve , Chan Grace
Published: January 2025

Abstract
Blood culture (BC) investigation remains the gold standard for diagnosis of bloodstream infections. However, BC contamination can have clinical implications for the patient, cost implications for service providers and less well documented, environmental impacts. Efforts to reduce BC contamination are a longstanding theme in quality improvement initiatives in emergency departments and hospitals, prompted by the hospital costs, healthcare inefficiencies and antimicrobial stewardship efforts.  The WHO global analysis of health care waste in the context of COVID-19, has reported that tens of thousands of tonnes of extra medical waste was produced from the response to the COVID-19 pandemic, basing its estimates on the quantity of personal protective equipment (PPE). Additionally, recent literature has also shown increased BC contamination rates during the COVID-19 pandemic. Our study reviews the trend of BC contamination during the COVID-19 pandemic in our institution’s Emergency Department.  We further discuss some of the potential implications of BC contamination, including potential environmental, economic and efficiency implications.
ACUTE BIPHENOTYPIC LEUKEMIA: A CASE REPORT AT THE MOHAMMED V MILITARY TRAINING HOSPITAL IN RABAT
Authors: laatiris hamid , Essahli khadija , Elfaiz mouna , bennai nadia , baidada ilyass , zahid hafid
Published: January 2025

Acute biphenotypic leukemias (BAL) are characterized by the co-expression, on the same blasts, of membrane or cytoplasmic molecules belonging to at least two cellular lineages (B lymphoid, T lymphoid, or myeloid). However, their terminology remains inconsistent, with varied designations such as "mixed leukemias," "hybrid leukemias," "My+ALL," or "Ly+AML." A more precise term would be "chimeric leukemias," distinct from biclonal leukemias or those with aberrant expression of specific markers.
We present here a case of acute biphenotypic leukemia, emphasizing the importance of combining hematological cytology and immunophenotyping for an accurate diagnosis.
The patient, a 23-year-old male with a history of chronic smoking, presented with physical fatigue associated with headaches, dizziness, and a general deterioration of health. Additionally, an anemic syndrome characterized by mucocutaneous pallor was observed.
Hypoxia-inducible factor 2α promotes protective Th2 cell responses during intestinal helminth infection
Authors: Labuda Jasmine C. , Olsen Tayla M. , Verma Sheenam , Kimmel Samantha , Edwards Thomas H. , Dufort Matthew J. , Harrison Oliver J.
Published: January 2025

Th2 cells must sense and adapt to the tissue milieu in order to provide protective host immunity and tissue repair. Here, we examined the mechanisms promoting Th2 cell differentiation and function within the small intestinal lamina propria. Single cell RNA-seq analyses of CD4+T cells from the small intestinal lamina propria of helminth infected mice revealed high expression of the geneEpas1, encoding the transcription factor hypoxia-inducible factor 2a (HIF2α).In vitro, exposure to hypoxia or genetic HIF2α activation promoted Th2 cell differentiation, even under non-polarizing conditions. In mice, HIF2α activation in CD4+T cells promoted intestinal Th2 cell accumulation in the absence of infection, and HIF2α-deficiency impaired CD4+T cell-mediated host immunity to intestinal helminth infection. Our findings identified hypoxia, and the oxygen-regulated transcription factor Hypoxia-Inducible Factor 2α (HIF2α), as key regulators of Th2 cell differentiation and function within the small intestine.
EEG correlates of active removal from working memory
Authors: Shan Jiangang , Postle Bradley R.
Published: January 2025

The removal of no-longer-relevant information from visual working memory (WM) is important for the functioning of WM, given its severe capacity limitation. Previously, with an “ABC-retrocuing” WM task, we have shown that removing information can be accomplished in different ways: by simply withdrawing attention from the newly irrelevant memory item (IMI; i.e., via “passive removal”); or by or “actively” removing the IMI from WM (Shan and Postle, 2022). Here, to investigate the neural mechanisms behind active removal, we recorded electroencephalogram (EEG) signals from human subjects (both sexes) performing the ABC-retrocuing task. Specifically, we tested the hijacked adaptation model, which posits that active removal is accomplished by a top-down-triggered down-modulation of the gain of perceptual circuits, such that sensory channels tuned to the to-be-removed information become less sensitive. Behaviorally, analyses revealed that, relative to passive removal, active removal produced a decline in the familiarity landscape centered on the IMI. Neurally, we focused on two epochs of the task, corresponding to the triggering, and to the consequence, of active removal. With regard to triggering, we observed a stronger anterior-to-posterior traveling wave for active versus passive removal. With regard to the consequence(s) of removal, the response to a task-irrelevant “ping” was reduced for active removal, as assessed with ERP and with posterior-to-anterior traveling waves, suggesting that active removal led to decreased excitability in perceptual circuits centered on the IMI.

Significance Statement

The removal of no-longer-relevant information from working memory is critical for the flexible control of behavior. However, to our knowledge, the only explicit accounts of this operation describe the simple withdrawal of attention from that information (i.e., “passive removal”). Here, with measurements of behavior and electroencephalography (EEG), we provide evidence for a specific mechanism for the active removal of information from WM–hijacked adaptation–via the top-down triggering of an adaptation-like down-regulation of gain of the perceptual circuits tuned to the to-be-removed information. These results may have implications for disorders of mental health, including rumination, intrusion of negative thoughts, and hallucination.
CocycleHunter: cohomology-based circular gene set enrichment and genetic phase estimation in single-cell RNA-seq data
Authors: Maggs Kelly , Youssef Markus , Pulver Cyril , Isma Jovan , Nguyên Tâm J. , Karthaus Wouter , Hess Kathryn , Dotto G. Paolo
Published: January 2025

In this paper we introduce cocycle hunter (cHunter), a tool for identifying and exploiting diverse circular structure in single-cell RNAseq data. Our method is based on persistent cohomology in dimension one, which we use to define a system of statistically enriching gene sets for circular structure. We also develop a powerful, cohomology-based technique for estimating the phase of genes exhibiting cyclic expression patterns. We validate our method on synthetic RNA transcription models, as well as real datasets studying the cell cycle, tissue re-generation and senescence in diverse experimental conditions. Our work points towards cocycles as pervasive mathematical structures of the transcriptional program.
Astrocyte and mitochondrial footprints in brain-derived extracellular vesicles predict tau pathology
Authors: Espourteille Jeanne , Barve Aatmika , Zufferey Valentin , Leroux Elodie , Perbet Romain , Bagard Severine , Caillierez Raphaelle , Maurage Claude Alain , Toni Nicolas , Buee Luc , Colin Morvane , Richetin Kevin
Published: January 2025

Tauopathies are neurodegenerative disorders characterized by abnormal tau aggregation, with primary 3R (e.g., Picks disease, PiD) and 4R (e.g., progressive supranuclear palsy, PSP) variants posing a significant diagnostic challenge. Here, we examined brain-derived extracellular vesicles (BD-EVs) isolated from the prefrontal cortex of PiD (3R), PSP (4R), and non-demented controls (CTRL) to determine if these vesicles reflect disease-specific proteomic signatures. We found that while tau pathology does not substantially alter BD-EV concentration or the enrichment of core vesicular markers, it does influence their size distribution and protein cargo. BD-EV samples from PiD patients exhibited a greater abundance of small vesicles and distinct protein profiles when compared to PSP and CTRL. Weighted Gene Co-expression Network Analysis (WGCNA) identified four key protein modules to account for variance between patient groups Endoplasmic Reticulum, Mitochondria, Microtubules, and Trivalent Inorganic Cation Transport. In PiD, astrocyte-derived mitochondrial proteins were significantly elevated, whereas neuronal microtubule-related proteins were diminished relative to both PSP and CTRL. Notably, changes in the mitochondrion and microtubule modules enhanced the detection of PiD pathology. Cellular origin annotation revealed a marked shift in BD-EV composition: PiD samples exhibited an increased astrocytic signature, while both PiD and PSP showed a reduction in neuronal proteins compared to CTRL. Crucially, the enrichment of astrocytic mitochondrial and endoplasmic reticulum proteins, alongside reduced neuronal proteins, correlated strongly with the severity of tau pathology (AT8-stained aggregates) in patient brains. These findings demonstrate that BD-EVs capture tau isoform-specific cellular and molecular alterations, offering a window into disease mechanisms at the neuron-glia interface. By linking distinct protein signatures and their cellular origins to tau pathology severity, our results highlight the potential of BD-EV profiling as a biomarker strategy for distinguishing between and monitoring the progression of 3R and 4R tauopathies.