bluuebunny/crossref_metadata_2025 huggingface dataset:
Efgartigimod restores muscle function in a humanized mouse model of immune-mediated necrotizing myopathy
Authors: Julien Sarah , van der Woning Bas , De Ceuninck Leentje , Briand Emma , Jaworski Thara , Roussel Gaëlle , Zoubaïri Rachid , Allenbach Yves , Benveniste Olivier , Drouot Laurent , Boyer Olivier
Published: June 2023

Objective

Immune-mediated necrotizing myopathies (IMNMs) are severe forms of myositis often associated with pathogenic anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies (aAbs). Efgartigimod is an engineered human IgG1 Fc fragment that antagonizes the neonatal Fc receptor (FcRn), thereby preventing recycling and promoting lysosomal degradation of IgG, including aAbs. We evaluated the therapeutic effects of IgG reduction by efgartigimod in a humanized murine model of IMNM.

Methods

Disease was induced in C5-deficient (C5def) or Rag2-deficient (Rag2–/–) mice receiving co-injections of anti-HMGCR+ IgG from an IMNM patient and human complement. C5def mice were treated in a preventive setting with s.c. injections of efgartigimod and Rag2–/– mice in a curative setting after disease was induced by anti-HMGCR+ IgG injections. Anti-HMGCR aAbs levels were monitored in mouse serum and muscle tissue. Histological analysis was performed on muscle sections. Muscle force was assessed by grip test or measurement of gastrocnemius strength upon electrostimulation.

Results

Administration of efgartigimod rapidly reduced total IgG levels, including the level of pathogenic anti-HMGCR aAbs, in both serum (P < 0.0001) and muscle (P < 0.001). In the preventive setting, efgartigimod prevented myofibre necrosis (P < 0.05), thus precluding loss of muscle strength (P < 0.05). In the therapeutic setting, efgartigimod prevented further necrosis and allowed muscle fibre regeneration (P < 0.05). Hence, muscle strength returned to normal (P < 0.01).

Conclusion

Efgartigimod reduces circulating IgG levels, including pathogenic anti-HMGCR+ IgG aAbs, in a humanized mouse model of IMNM, preventing further necrosis and allowing muscle fibre regeneration. These results support investigating the therapeutic efficacy of efgartigimod through a clinical trial in IMNM patients.
A Social Network Analysis of Influences on Residents’ Value-Based Decisions
Authors: Bock Lotte A. , Westra Daan , Noben Cindy Y.G. , Essers Brigitte A.B. , van Mook Walther N.K.A.
Published: June 2023

Purpose

To ensure a value-based health care system, it is becoming increasingly important that residents are trained in making value-based decisions. This study explored the social network influencing residents’ value-based decisions.

Method

To explore the social network influencing residents’ value-based decisions, the authors used a semistructured individual and mini-group interviewing approach and participatory visual mapping. In total, 17 residents across 13 different specialties were interviewed from the southeastern postgraduate medical education and training region of the Netherlands, May–November 2021. Two researchers independently coded the transcribed data using an integrated inductive thematic approach. Subsequently, social network analysis was used to visualize the results.

Results

Residents indicated that their value-based decisions were influenced by direct actors who influenced decisions related to patients and indirect actors who shaped decisions related to patients without directly modifying them. Different interaction-aspects (i.e., personal, situational, and institutional) further affected residents’ ability to make value-based decisions. Thus, residents’ value-based decisions were a product of the interplay between various interactions with actors and different interaction-aspects. Residents defined value-based decisions differently, even within an interview.

Conclusions

These results suggest residents’ value-based decisions are influenced by a multitude of actors, including hierarchically superior colleagues who can directly alter decisions and patients (and their families) and nurses with whom residents consider it important to maintain good relationships. In addition, more experienced actors, mainly from the medical and nursing profession, contribute most to learning. Furthermore, residents’ value-based decisions are deeply underpinned by the hidden curriculum. However, many senior physicians may not have received sufficient training in the concept of value-based health care. Consequently, an approach of formally educating residents in value-based health care will likely have limited effects unless social influences in day-to-day clinical settings reinforce its importance.
Acquire, Curate, Diversify: Staying Current With Key Medical Education Literature
Authors: Chen Fei , Chen Weichao , Isaak Robert , Xu Shenmeng
Published: June 2023

Rapid technological advancement has led to increasingly convenient and affordable access to academic publications while also contributing to information overload.We recommend the following strategies for clinicians and researchers to effectively stay current with themedical education literaturemost applicable to their areas of focus.1,2
Only 1% of Total Knee Arthroplasty Clinical Trials Report Patient Opioid Use Before or After Surgery
Authors: Crane Patricia , Morris John , Egan William , Young Jodi L. , Nova Vitalina , Rhon Daniel I.
Published: June 2023

Objectives:

Many clinical trials report significant improvements in osteoarthritis-related pain and function after total knee arthroplasty (TKA). Opioids are commonly prescribed for pain management of knee osteoarthritis and also perioperative pain after surgery. The extent of persistent opioid use after TKA is unknown. Because up to 20% of individuals have poor outcomes after TKA and prior opioid use is a risk factor for future opioid use, treatment effects from TKA clinical trials would be better understood by assessing opioid use data from trial participants. The purpose of this review was to determine the proportion of participants in TKA trials with opioid use before surgery and persistent use after surgery and how well clinical trials capture and report these variables.

Materials and Methods:

A systematic review of the literature (5 databases: CINAHL Cochrane CENTRAL, Embase, PubMed, and Web of Science) was conducted to assess the reporting of opioid use in TKA clinical trials. All opioid use was extracted, both prior and postoperatively. Long-term opioid use was determined using 4 different contemporary definitions to increase the sensitivity of the assessment.

Results:

The search produced 24,252 titles and abstracts, and 324 met the final inclusion criteria. Only 4 of the 324 trials (1.2%) reported any type of opioid use; 1 identified prior opioid use, and none reported long-term opioid use after surgery. Only 1% of TKA clinical trials in the past 15 years reported any opioid use.

Discussion:

Based on available research, it is not possible to determine if TKA is effective in reducing reliance on opioids for pain management. It also highlights the need to better track and report prior and long-term opioid use as a core outcome in future TKA trials.
Construction and Evaluation of Clinical Prediction Model for Immunotherapy-related Adverse Events and Clinical Benefit in Cancer Patients Receiving Immune Checkpoint Inhibitors Based on Serum Cytokine Levels
Authors: Zhao Ni , Jiang Aimin , Shang Xiao , Zhao Fumei , Wang Ruoxuan , Fu Xiao , Ruan Zhiping , Liang Xuan , Tian Tao , Yao Yu , Li Chunli
Published: June 2023

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape of cancer therapy. This study aimed to develop novel risk classifiers to predict the risk of immune-related adverse events (irAEs) and the probability of clinical benefits. Patients with cancer who received ICIs from the First Affiliated Hospital of Xi ‘an Jiaotong University from November 2020 to October 2022 were recruited and followed up. Logistic regression analyses were performed to identify independent predictive factors for irAEs and clinical response. Two nomograms were developed to predict the irAEs and clinical responses of these individuals, with a receiver operating characteristic curve to assess their predictive ability. Decision curve analysis was performed to estimate the clinical utility of the nomogram. This study included 583 patients with cancer. Among them, 111 (19.0%) developed irAEs. Duration of treatment (DOT)>3 cycles, hepatic-metastases, IL2>2.225 pg/mL, and IL8>7.39 pg/mL were correlated with higher irAEs risk. A total of 347 patients were included in the final efficacy analysis, with an overall clinical benefit rate of 39.7%. DOT>3 cycles, nonhepatic-metastases, and irAEs and IL8>7.39 pg/mL were independent predictive factors of clinical benefit. Ultimately, 2 nomograms were successfully established to predict the probability of irAEs and their clinical benefits. Ultimately, 2 nomograms were successfully established to predict the probability of irAEs and clinical benefits. The receiver operating characteristic curves yielded acceptable nomogram performance. Calibration curves and decision curve analysis supported the hypothesis that nomograms could provide more significant net clinical benefits to these patients. Specific baseline plasma cytokines were closely correlated with irAEs and clinical responses in these individuals.
Machine learning in basic scientific research on oral diseases
Authors: Yin Cheng , Yan Bin
Published: June 2023

The growing complexity and increasing scale of biological data have led scientists to develop novel analytical methods in bioinformatics. Machine learning is a predictive model to learn from a particular dataset, analyze it, and make predictions. However, the technology is complex and relatively new, especially in the basic research on oral diseases. This review surveys machine learning in the research on oral diseases. Articles were extracted from PubMed. Results, key concepts, techniques, benefits, and challenges of machine learning in the basic research on oral diseases are summarized. Future trends are predicted for forthcoming research.
Progress in clinical application of computer-assisted orthopedic surgery
Authors: Shen Huaqiao , Liu Hongwei
Published: June 2023

With the rapid development of computer technology, new materials, 5G communication, artificial intelligence and robot technology, computer-assisted orthopaedic surgery (CAOS) technology has obtained an unprecedented opportunity for development, which has greatly promoted the personalized, accurate and minimally invasive process of orthopedic surgery. Compared with traditional orthopedic surgery, CAOS has significant advantages in implementing accurate surgery, shortening operation time, reducing patient trauma and reducing intraoperative X-ray radiation exposure. However, with the increasing medical needs of patients and the increasing medical costs, the technology of computer-assisted orthopedic surgery still needs to be improved. This paper mainly summarizes the current situation of clinical application of computer-assisted orthopedic surgery, focusing on following four aspects: broken bone splicing and restoration technology, 3D printing guide plate assisted orthopedic surgery, computer-assisted navigation in orthopedic surgery and orthopedic surgery robot technology. At the same time, the problems and difficulties existing in CAOS are discussed, and the author's own views on the future development of computer-assisted orthopedic surgery are put forward.
Effectiveness of Telehealth Cardiac Rehabilitation Programs on Health Outcomes of Patients With Coronary Heart Diseases
Authors: Shi Wendan , Green Heidi , Sikhosana Nqobile , Fernandez Ritin
Published: June 2023

Purpose:

The aim of this study was to conduct an umbrella review summarizing the evidence from existing systematic reviews of telehealth cardiac rehabilitation (CR) on health outcomes of patients with coronary heart disease (CHD).

Review Methods:

An umbrella review of systematic reviews was undertaken in accordance with the PRISMA and JBI guidelines. A systematic search was conducted in Medline, APA PsycINFO, Embase, CINAHL, Web of Science, Cochrane database of systematic reviews, JBI evidence synthesis, Epistemonikos, and PROSPERO, searching for systematic reviews published from 1990 to current and was limited to the language source of English and Chinese. Outcomes of interest were health behaviors and modifiable CHD risk factors, psychosocial outcomes, and other secondary outcomes. Study quality was appraised using the JBI checklist for systematic reviews. A narrative analysis was conducted, and meta-analysis results were synthesized.

From 1301 identified reviews, 13 systematic reviews (10 meta-analyses) comprised 132 primary studies conducted in 28 countries. All the included reviews have high quality, with scores ranging 73-100%. Findings to the health outcomes remained inconclusive, except solid evidence was found in the significant improvement in physical activity (PA) levels and behaviors from telehealth interventions, exercise capacity from mobile health (m-health) only and web-based only interventions, and medication adherence from m-health interventions. Telehealth CR programs, work adjunct or in addition to traditional CR and standard care, are effective in improving health behaviors and modifiable CHD risk factors, particularly in PA. In addition, it does not increase the incidence in terms of mortality, adverse events, hospital readmission, and revascularization.
Urate-lowering drugs for chronic kidney disease with asymptomatic hyperuricemia and hypertension: a randomized trial
Authors: Kohagura Kentaro , Satoh Atsushi , Kochi Masako , Nakamura Takuto , Zamami Ryo , Tana Takeshi , Kinjyo Kazushi , Funakoshi Ryo , Yamazato Masanobu , Ishida Akio , Sakima Atsushi , Iseki Kunitoshi , Arima Hisatomi , Ohya Yusuke
Published: June 2023

Introduction:

Xanthine oxidase (XO) inhibitors may slow down chronic kidney disease (CKD) progression. The comparative effectiveness of the different urate-lowering drugs is unknown. The aim of this study was to determine whether urate-lowering therapy with an XO inhibitor (febuxostat) and that with a uricosuric drug (benzbromarone) are comparable in slowing renal function decline in patients with CKD complicated with hypertension and hyperuricemia.

Methods:

This study was an open-label randomized parallel-group clinical trial of 95 patients with stage G3 CKD in Japan. The patients had hypertension and hyperuricemia without a history of gout. They were randomized to receive febuxostat (n = 47; febuxostat group) or benzbromarone (n = 48; benzbromarone group) and titrated to reduce their serum urate level to <6.0 mg/dl. The primary end-point was change in estimated glomerular filtration rate (eGFR) from baseline to 52 weeks. The secondary end-points included changes in uric acid level, blood pressure, urinary albumin-to-creatinine ratio, and XO activity.

Results:

Of the 95 patients, 88 (92.6%) completed the trial. There were no significant differences in change in eGFR (in ml/min/1.73 m2) between the febuxostat [−0.23, 95% confidence interval (CI), −2.00 to 1.55] and benzbromarone (−2.18, 95% CI, −3.84 to −0.52) groups (difference, 1.95; 95% CI, −0.48 to 4.38; P = 0.115) nor in the secondary end-points, except for XO activity. Febuxostat significantly reduced XO activity (P = 0.010). There were no significant differences in primary and secondary outcomes between the groups. A decrease in eGFR was significantly less in the febuxostat group than that of the benzbromarone group in the CKDG3a, but not in CKDG3b, in the subgroup analysis. There were no adverse effects specific to either drug.

Conclusions:

No significant differences were found in the effects of febuxostat and benzbromarone in renal function decline in stage G3 CKD complicated with hyperuricemia and hypertension.
Interactive Effects of Ayahuasca and Cannabidiol in Social Cognition in Healthy Volunteers
Authors: Rossi Giordano Novak , Rocha Juliana Mendes , Osório Flávia L. , Bouso José Carlos , Ona Genis , Silveira Gabriela de Oliveira , Yonamine Mauricio , Bertozi Giuliana , Crevelin Eduardo José , Queiroz Maria Eugênia , Crippa José Alexandre S. , Hallak Jaime E. Cecílio , dos Santos Rafael G.
Published: June 2023

Background

Serotonergic hallucinogens and cannabinoids may alter the recognition of emotions in facial expressions (REFE). Cannabidiol (CBD) attenuates the psychoactive effects of the cannabinoid-1 agonist tetrahydrocannabinol. Ayahuasca is a dimethyltryptamine-containing hallucinogenic decoction. It is unknown if CBD may moderate and attenuate the effects of ayahuasca on REFE.

Procedures

Seventeen healthy volunteers participated in a 1-week preliminary parallel-arm, randomized controlled trial for 18 months. Volunteers received a placebo or 600 mg of oral CBD followed by oral ayahuasca (1 mL/kg) 90 minutes later. Primary outcomes included REFE and empathy tasks (coprimary outcome). Tasks were performed at baseline and 6.5 hours, 1 and 7 days after the interventions. Secondary outcome measures included subjective effects, tolerability, and biochemical assessments.

Results

Significant reductions (all P values <0.05) only in reaction times were observed in the 2 tasks in both groups, without between-group differences. Furthermore, significant reductions in anxiety, sedation, cognitive deterioration, and discomfort were observed in both groups, without between-group differences. Ayahuasca, with or without CBD, was well tolerated, producing mainly nausea and gastrointestinal discomfort. No clinically significant effects were observed on cardiovascular measurements and liver enzymes.

Conclusions

There was no evidence of interactive effects between ayahuasca and CBD. The safety of separate and concomitant drug intake suggests that both drugs could be applied to clinical populations with anxiety disorders and in further trials with larger samples to confirm findings.
Clinical Recommendations for Augmentation Agents in Obsessive-Compulsive Disorder Partially Responsive to Serotonin Reuptake Inhibitors
Authors: Gautam Mohan
Published: June 2023

Background

Obsessive-compulsive disorder (OCD) affects 2% to 3% of adults worldwide. Although serotonin reuptake inhibitors (SRIs) reliably demonstrate efficacy for this condition, 40% to 60% of patients only achieve partial recovery. The purpose of this systematic review was to assess the efficacy of other agents that may be used as augmentation agents for patients who are partial responders to SRI monotherapy.

Methods

Using PRISMA-P guidelines, PubMed and Embase were searched using the randomized controlled trial (RCT) filter and the key word “obsessive-compulsive disorder.” To be considered for analysis, a potential augmentation agent needed to have at least 2 RCTs. This review specifically analyzes the effect of each augmentation agent on OCD symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale.

Results

The augmentation agents analyzed in this review are d-cycloserine (2 RCTs), memantine (4 RCTs), N-acetylcysteine (5 RCTs), lamotrigine (2 RCTs), topiramate (3 RCTs), riluzole (2 RCTs), ondansetron (2 RCTs), celecoxib (2 RCTs), aripiprazole (5 RCTs), risperidone (7 RCTs), quetiapine (9 RCTs), and olanzapine (3 RCTs).

Implications

The augmentation agents most supported by this review for OCD that is only a partial response to SRI monotherapy are lamotrigine, memantine, and aripiprazole. If an antipsychotic must be used and aripiprazole is not tolerated, risperidone may be considered as an alternative. Unlike the SRI class effect for OCD symptom reduction, augmentation agents demonstrate considerable intraclass variability.
To Compare the Effects of a Standard Versus Hydrophilic Polymer Coated Airway Stent in a Porcine Model
Authors: Cho Roy Joseph , Kadowaki Koji , Seelig Davis , Glumac Daniel E. , Kent Leslie A. , Hunter Ryan C. , MacIver Robroy H. , Peterson Gregory K. , Pandey Vidhu , Tanahashi Kazuhiro
Published: June 2023

Background:

Stent encrustation with debris and mucostasis is a significant cause of airway injury and comorbidity, leading to ~25% of stent exchanges (1–3). Previous work from our group has shown that the experimental coating can reduce mucous adhesion in bench testing and demonstrated a signal for reducing airway injury and mucostasis in a feasibility study.

Objectives:

The aim of this study is to continue our inquiry in a randomized, single-blinded multi-animal trial to investigate the degree of airway injury and mucostasis using silicone stents with and without this specialized coating.

Methods:

We modified commercially available silicone stents with a hydrophilic polymer from Toray Industries. We conducted an in vivo survival study in 6 mainstem airways (3 coated and 3 uncoated) of 3 pigs to compare the degree of airway injury and mucostasis between coated versus noncoated stented airways. Both stents were randomized to either left or right mainstem bronchus. The pathologist was blinded to the stent type.

Results:

We implanted a total of six 14×15 mm silicone stents (1 per mainstem bronchi) into 3 pigs. All animals survived to termination at 4 weeks. All stents were intact; however, 1 uncoated stent migrated out. On average, all the coated stents demonstrated reduced pathology and tissue injury scores (75 vs. 68.3, respectively). The average total dried mucous weight was slightly higher in the coated stents (0.07 g vs. 0.05 g; respectively).

Conclusion:

Coated stents had lower airway injury compared with uncoated stents in this study. Of all the stents, 1 uncoated stent migrated out and was not included in the dried mucous weight totals. This could explain the slightly higher mucous weight in the coated stents. Nevertheless, this current study demonstrates promising results in lowering airway injury in stents incorporated with the hydrophilic coating, and future studies, including a larger number of subjects, would be needed to corroborate our findings.
Efficacy of Prophylactic Post-Operative Antibiotics in Tissue Expander-Based Breast Reconstruction: A Propensity Score-Matched Analysis
Authors: Sergesketter Amanda R. , Langdell Hannah C. , Shammas Ronnie L. , Geng Yisong , Atia Andrew N. , Rezak Kristen , Sisk Geoffroy C. , Hollenbeck Scott T. , Phillips Brett T.
Published: June 2023

BACKGROUND:

Conflicting evidence exists regarding the utility of prophylactic post-operative antibiotics in tissue expander-based breast reconstruction. This study evaluated risk of surgical site infection between patients receiving 24 hours of perioperative antibiotics alone versus prolonged post-operative antibiotics within a propensity score-matched cohort.

METHODS:

Patients undergoing tissue expander-based breast reconstruction receiving 24 hours of perioperative antibiotics alone were propensity score-matched 1:3 to patients receiving post-operative antibiotics based on demographics, comorbidities, and treatment factors. Incidence of surgical site infection was compared based on duration of antibiotic prophylaxis.

RESULTS:

Of a total of 431 patients undergoing tissue expander-based breast reconstruction, post-operative antibiotics were prescribed in 77.2%. Within this cohort, 348 were included for propensity matching (No Antibiotics: 87 patients; Antibiotics: 261 patients). After propensity score matching, there was no significant difference in incidence of infection requiring intravenous (No Antibiotics: 6.9%; Antibiotics: 4.6%; p=0.35) or oral antibiotics (No Antibiotics: 11.5%; Antibiotics: 16.1%; p=0.16). In addition, rates of unplanned reoperation (p=0.88) and 30-day readmission (p=0.19) were similar. After multivariate adjustment, prescription of post-operative antibiotics was not associated with a reduction in surgical site infection (OR 0.5; 95% CI -0.3-1.3; p=0.23).

CONCLUSIONS:

Within a propensity-matched cohort accounting for patient comorbidities and receipt of adjuvant therapies, prescription of post-operative antibiotics after tissue expander-based breast reconstruction conferred no improvement in rates of tissue expander infection, reoperation, or unplanned healthcare utilization. This data underscores the need for multi-center, prospective randomized trials on the utility of antibiotic prophylaxis in tissue expander-based breast reconstruction.
“Quantifying the Impact of Prepectoral Implant Conversion on Patient Satisfaction and Quality of Life”
Authors: Seitz Allison J. , MacKenzie Ethan L. , Edalatpour Armin , Janssen David A. , Doubek III William G. , Afifi Ahmed M.
Published: June 2023

Background:

Conversion of subpectoral reconstruction to the prepectoral plane has been increasing in popularity. However, there is a paucity of research assessing patient-reported outcomes following this operation. The primary aim of this study is to examine patient-reported outcomes following conversion of implants from the subpectoral to prepectoral plane through utilization of the BREAST-Q.

Methods:

We retrospectively examined patients who underwent subpectoral to prepectoral implant conversion by three surgeons at two separate centers from 2017-2021. Patient demographics, primary indication for the conversion, surgical characteristics, postoperative outcomes, and BREAST-Qs were obtained.

Results:

Sixty-eight breasts in 39 patients underwent implant conversion. The most common primary indications for implant conversion were chronic pain (41%), animation deformity (30%), and cosmetic concerns (27%). Average BREAST-Q scores improved significantly preoperatively to postoperatively in all the domains measured (“satisfaction with breasts”, “satisfaction with implants”, “physical well-being,” “psychosocial well-being,” and “sexual well-being”) (p<0.01). When examined by primary indication, all cohorts had significant preoperative to postoperative score improvement in “satisfaction with breasts” (p<0.001) and “physical well-being” (p<0.01) domains. Fifteen breasts (22%) developed postoperative complications, with implant loss in 9% of breasts.

Conclusions

:Conversion of subpectoral implants to the prepectoral plane significantly improves BREAST-Q outcomes in all aspects, including patient satisfaction with breasts and implants, as well as psychosocial, physical, and sexual well-being. Implant conversion to the prepectoral plane in now becoming our primary solution to most patients with chronic pain, animation deformity or cosmetic concerns after subpectoral reconstruction.
The Delay Procedure in Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction
Authors: Beugels Jop , Levine Joshua L. , Vasile Julie V. , Craigie James E. , Allen Robert J.
Published: June 2023

Background:

The delay procedure in deep inferior epigastric artery perforator (DIEP) flap breast reconstruction, in which the reduced-caliber choke vessels play a major role, can provide more well-perfused tissue than a standard DIEP flap. The aim of this study was to review the authors’ experience with this technique, evaluate the indications, and analyze the surgical outcomes.

Methods:

A retrospective study was conducted of all consecutive DIEP delay procedures performed between March of 2019 and June of 2021. Patient demographic characteristics, operative details, and complications were registered. Patients had preoperative imaging by magnetic resonance angiography to select dominant perforators. The surgical technique involves a two-stage operation. During the first operation, the flaps were pedicled on a dominant perforator and a lateral skin bridge extending toward the lateral flank and lumbar fat; in a second stage, the flap was harvested and transferred.

Results:

A total of 82 extended DIEP delay procedures were performed to reconstruct 154 breasts. The majority were bilateral breast reconstructions (87.8%). The delay procedure was used for 38 primary reconstructions (46.3%) and 32 tertiary reconstructions (39.0%). The primary indication was the need for additional volume (79.3%), followed by extensive abdominal scarring and liposuction. After the first operation, seroma was the most frequently observed complication (7.3%). After the second operation, three total flap losses (1.9%) were observed.

Conclusions:

The delay procedure in DIEP flap breast reconstruction results in the harvest of a good amount of abdominal tissue by adding a preliminary procedure. This technique can convert cases previously considered unsuitable into suitable candidates for abdominal-based breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Association Between Payer Type and Risk of Persistent Opioid Use after Surgery
Authors: Srinivasan Sudharsan , Gunaseelan Vidhya , Jankulov Alexandra , Chua Kao-Ping , Englesbe Michael , Waljee Jennifer , Bicket Mark , Brummett Chad M.
Published: June 2023

Objective:

To assess whether the risk of persistent opioid use after surgery varies by payer type.

Background:

Persistent opioid use is associated with increased healthcare utilization and risk of opioid use disorder, opioid overdose, and mortality. Most research assessing the risk of persistent opioid use has focused on privately insured patients. Whether this risk varies by payer type is poorly understood.

Methods:

This cross-sectional analysis of the Michigan Surgical Quality Collaborative database examined adults aged 18-64 years undergoing surgical procedures across 70 hospitals between January 1, 2017, and October 31, 2019. The primary outcome was persistent opioid use, defined a priori as 1+ opioid prescription fulfillment at (1) an additional opioid prescription fulfillment after an initial postoperative fulfillment in the perioperative period or at least one fulfillment in the 4-90 days after discharge and (2) at least one opioid prescription fulfillment in the 91-180 days after discharge. The association between this outcome and payer type was evaluated using logistic regression, adjusting for patient and procedure characteristics.

Results:

Among 40,071 patients included, mean age was 45.3 years (SD 12.3), 24,853 (62%) were female, 9,430 (23.5%) were Medicaid-insured, 26,760 (66.8%) were privately insured, and 3,889 (9.7%) were covered by other payer types. The rate of POU was 11.5% and 5.6% for Medicaid-insured and privately insured patients, respectively (average marginal effect for Medicaid: 2.9% (95% CI 2.3%-3.6%)).

Conclusions:

Persistent opioid use remains common among individuals undergoing surgery, and higher among patients with Medicaid insurance. Strategies to optimize postoperative recovery should focus on adequate pain management for all patients and consider tailored pathways for those at risk.
Novel Gene-Modified Mesenchymal Stem Cell Therapy Reverses Impaired Wound Healing in Ischemic Limbs
Authors: Huerta Carlos Theodore , Ortiz Yulexi Y. , Li Yan , Ribieras Antoine J. , Voza Francesca , Le Nga , Dodson Caroline , Wang Gaofeng , Vazquez-Padron Roberto I. , Liu Zhao-Jun , Velazquez Omaida C.
Published: June 2023

Objective:

Here we report a new method to increase therapeutic potential of mesenchymal stem/stromal cells (MSCs) for ischemic wound healing. We tested biologic effects of MSCs modified with E-selectin, a cell-adhesion molecule capable of inducing post-natal neovascularization, on a translational murine model.

Summary Background Data:

Tissue loss significantly worsens the risk of extremity amputation for patients with chronic limb-threatening ischemia (CLTI). MSCs-based therapeutics hold major promise for wound healing and therapeutic angiogenesis, but unmodified MSCs demonstrate only modest benefits.

Methods:

Bone marrow cells harvested from FVB/ROSA26SormTmG donor mice were transduced with E-selectin-GFP/AAV-DJ or GFP/AAV-DJ (control). Ischemic wounds were created via a 4 mm punch biopsy in the ipsilateral limb after femoral artery ligation in recipient FVB mice and subsequently injected with PBS or 1×10^6 donor MSCGFP or MSCE-selectin-GFP. Wound closure was monitored daily for 7 postoperative days (POD), and tissues were harvested for molecular and histological analysis and immunofluorescence. Whole-body DiI perfusion and confocal microscopy was utilized to evaluate wound angiogenesis.

Results:

Unmodified MSCs do not express E-selectin, and MSCE-selectin-GFP gain stronger MSC phenotype yet maintain trilineage differentiation and colony-forming capability. MSCE-selectin-GFP therapy accelerates wound healing compared to MSCGFP and PBS treatment. Engrafted MSCE-selectin-GFP manifest stronger survival and viability in wounds at POD 7. Ischemic wounds treated with MSCE-selectin-GFP exhibit more abundant collagen deposition, and enhanced angiogenic response.

Conclusion:

We establish a novel method to potentiate regenerative and pro-angiogenic capability of MSCs by modification with E-selectin/AAV. This innovative therapy carries potential as a platform worthy of future clinical studies.
Patient-controlled analgesia for the management of adults with acute trauma in the emergency department: A systematic review and meta-analysis
Authors: Sim Guek Gwee , See Amanda Huimin , Quah Li Juan Joy
Published: June 2023

BACKGROUND

Patient-controlled analgesia (PCA) has potential as a form of analgesia for trauma patients in the emergency department (ED). The objective of this review was to evaluate the effectiveness and safety of PCA for the management of adults with acute traumatic pain in the ED. The hypothesis was that PCA can effectively treat acute trauma pain in adults in the ED, with minimal adverse outcomes and better patient satisfaction compared with non-PCA modalities.

METHODS

MEDLINE (PubMed), Embase, SCOPUS, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception date to December 13, 2022. Randomized controlled trials involving adults presenting to the ED with acute traumatic pain who received intravenous (IV) analgesia via PCA compared with other modalities were included. The Cochrane Risk of Bias tool and the Grading of Recommendation, Assessment, Development, and Evaluation approach were used to assess the quality of included studies.

RESULTS

A total of 1,368 publications were screened, with 3 studies involving 382 patients meeting the eligibility criteria. All three studies compared PCA IV morphine with clinician-titrated IV morphine boluses. For the primary outcome of pain relief, the pooled estimate was in favor of PCA with a standard mean difference of −0.36 (95% confidence interval, −0.87 to 0.16). There were mixed results concerning patient satisfaction. Adverse event rates were low overall. The evidence from all three studies was graded as low-quality because of a high risk of bias from lack of blinding.

CONCLUSION

This study did not demonstrate a significant improvement in pain relief or patient satisfaction using PCA for trauma in the ED. Clinicians wishing to use PCA to treat acute trauma pain in adult patients in the ED are advised to consider the available resources in their own practice settings and to implement protocols for monitoring and responding to potential adverse events.

LEVEL OF EVIDENCE

Systematic Review/Meta-Analyses; Level III.
Correlation analysis of salivary cytokines and hormones with resiliency
Authors: Wong Cheyenne , Patel Sagar , LaPorta Anthony , Towne Francina , Gubler Kelly Dean , Bartone Paul , Ryznar Rebecca
Published: June 2023

BACKGROUND

Frequent exposure to acute stress increases risk of suicide, posttraumatic stress disorder, and other stress-related disorders. Neuroendocrine and immunologic dysregulation associated with stress may underlie predispositions to psychological disorders and inflammatory disease processes in individuals, such as first-responders and other healthcare professionals, who function in high stress situations. The Hardiness Resilience Gauge (HRG) can be used to psychometrically measure resilience, a psychological modifier of the stress response. Using the HRG alongside salivary biomarker profiling, may help to identify low resilience phenotypes and allow mitigation and early therapeutic interventions. There is a paucity of knowledge regarding biomarkers of resilience. This study aims to evaluate the relationship between factors of resilience with salivary biomarker levels and fluctuations during and following acute stress.

METHODS

Sixty-three first responders underwent a standardized stress-inducing training exercise, providing salivary samples before (prestress), immediately after (post-stress), and 1 hour after the event (recovery). The HRG was administered before (initial) and after (final) the event. Multiplex ELISA panels quantified 42 cytokines and 6 hormones from the samples, which were analyzed for relationships to psychometric factors of resilience measured by the HRG.

RESULTS

Several biomarkers correlated with psychological resilience following the acute stress event. The HRG scores correlated (p < 0.05) with a select set of biomarkers with moderate-to-strong correlations (|r| > 0.3). These included EGF, GROα, PDGFAA, TGFα, VEGFA, interleukin (IL)1Ra, TNFα, IL18, cortisol, FGF2, IL13, IL15, and IL6. Interestingly, fluctuations of EGF, GROα, and PDGFAA in post-stress compared with recovery were positively correlated with factors of resilience, which were negatively correlated from the pre-stress to post-stress period.

CONCLUSION

This exploratory analysis discovered a small subset of salivary biomarkers that are significantly correlated with acute stress and resilience. Further investigation of their specific roles in acute stress and associations with resiliency phenotypes is warranted.
ABO blood type and functional neurological outcome in patients with severe traumatic brain injury
Authors: Esnault Pierre , Houcinat Nazim , de Malleray Hilaire , Quere Pierre-Louis , Cardinale Michael , D'aranda Erwan , Joubert Christophe , Dagain Arnaud , Goutorbe Philippe , Meaudre Eric
Published: June 2023

BACKGROUND

The ABO blood system has been involved in the pathogenesis of several diseases, including coagulopathy and bleeding complications. In trauma patients, blood type A has been associated with acute respiratory distress syndrome, and recently, blood type O has been associated with all-cause mortality. The purpose of this study was to assess the association between ABO blood types and long-term functional outcomes in critically ill patients with severe traumatic brain injury (TBI).

METHODS

We conducted a single-center, retrospective, observational study including all patients admitted to the intensive care unit with severe TBI (defined as a Glasgow Coma Scale score of ≤8) between January 2007 and December 2018. Patient characteristics and outcomes were extracted from a prospective registry of all intubated patients admitted to the intensive care unit for TBI. ABO blood types were retrospectively retrieved from patient medical records. The association between ABO blood type (A, B, AB, and O) and unfavorable functional outcome (defined by a Glasgow Outcome Scale score between 1 and 3) 6 months after injury was assessed in univariate and multivariate analysis.

RESULTS

A total of 333 patients meeting the inclusion criteria were included. There were 151 type O (46%), 131 type A (39%), 37 type B (11%), and 12 type AB patients (4%). No significant differences in baseline demographic, clinical, or biological characteristics were observed between blood types. The prevalence of unfavorable outcome was significantly different between the four groups. After adjustment for confounders, blood type O was significantly associated with unfavorable outcome at 6 months (odds ratio, 1.97; confidence interval [1.03–3.80]; p = 0.042). The prevalence of coagulopathy or progressive hemorrhagic injury was not statistically different between blood types (p = 0.575 and p = 0.813, respectively).

CONCLUSION

Blood type O appears to be associated with unfavorable long-term functional outcome in critically ill patients with severe TBI. Further studies are needed to detail the mechanism underlying this relationship.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Optimal dose of cryoprecipitate in massive transfusion following trauma
Authors: Dorken-Gallastegi Ander , Bokenkamp Mary , Argandykov Dias , Mendoza April E. , Hwabejire John O. , Saillant Noelle , Fagenholz Peter J. , Kaafarani Haytham M.A. , Velmahos George C. , Parks Jonathan J.
Published: June 2023

BACKGROUND

While cryoprecipitate (Cryo) is commonly included in massive transfusion protocols for hemorrhagic shock, the optimal dose of Cryo transfusion remains unknown. We evaluated the optimal red blood cell (RBC) to RBC to Cryo ratio during resuscitation in massively transfused trauma patients.

METHODS

Adult patients in the American College of Surgeon Trauma Quality Improvement Program (2013–2019) receiving massive transfusion (≥4 U of RBCs, ≥1 U of fresh frozen plasma, and ≥1 U of platelets within 4 hours) were included. A unit of Cryo was defined as a pooled unit of 100 mL. The RBC:Cryo ratio was calculated for blood products transfused within 4 hours of presentation. The association between RBC:Cryo and 24-hour mortality was analyzed with multivariable logistic regression adjusting for the volume of RBC, plasma and platelet transfusions, global and regional injury severity, and other relevant variables.

RESULTS

The study cohort included 12,916 patients. Among those who received Cryo (n = 5,511 [42.7%]), the median RBC and Cryo transfusion volume within 4 hours was 11 U (interquartile range, 7–19 U) and 2 U (interquartile range, 1–3 U), respectively. Compared with no Cryo administration, only RBC:Cryo ratios ≤8:1 were associated with a significant survival benefit, while lower doses of Cryo (RBC:Cryo >8:1) were not associated with decreased 24-hour mortality. Compared with the maximum dose of Cryo administration (RBC:Cryo, 1:1–2:1), there was no difference in 24-hour mortality up to RBC:Cryo of 7:1 to 8:1, whereas lower doses of Cryo (RBC:Cryo, >8:1) were associated with significantly increased 24-hour mortality.

CONCLUSION

One pooled unit of Cryo (100 mL) per 7 to 8 U of RBCs could be the optimal dose of Cryo in trauma resuscitation that provides a significant survival benefit while avoiding unnecessary blood product transfusions.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level IV.
Rapid clearing CT-001 restored hemostasis in mice with coagulopathy induced by activated protein C
Authors: Sim Derek S. , Mallari Cornell R. , Bauzon Maxine , Hermiston Terry W.
Published: June 2023

BACKGROUND

Activated protein C (APC) is one of the mechanisms contributing to coagulopathy, which is associated with high mortality. The counteraction of the APC pathway could help ameliorate bleeding. However, patients also transform frequently from a hemorrhagic state to a prothrombotic state at a later time. Therefore, a prohemostatic therapeutic intervention should take this thrombotic risk into consideration.

OBJECTIVES

CT-001 is a novel factor VIIa (FVIIa) with enhanced activity and desialylated N-glycans for rapid clearance. We assessed CT-001 clearance in multiple species and its ability to reverse APC-mediated coagulopathic blood loss.

METHODS

The N-glycans on CT-001 were characterized by liquid chromatography–mass spectrometry. Three species were used to evaluate the pharmacokinetics of the molecule. The potency and efficacy of CT-001 under APC pathway–induced coagulopathic conditions were assessed by coagulation assays and bleeding models.

RESULTS

The N-glycosylation sites of CT-001 had high occupancy of desialylated N-glycans. CT-001 exhibited 5 to 16 times higher plasma clearance in human tissue factor knockin mice, rats, and cynomolgus monkeys than wildtype FVIIa. CT-001 corrected the activated partial thromboplastin time and thrombin generation of coagulopathic plasma to normal in in vitro studies. In an APC-mediated saphenous vein bleeding model, 3 mg/kg of CT-001 reduced bleeding time in comparison with wildtype FVIIa. The correction of bleeding by CT-001 was also observed in a coagulopathic tail amputation severe hemorrhage mouse model. The efficacy of CT-001 is independent of the presence of tranexamic acid, and the combination of CT-001 and tranexamic acid does not lead to increased thrombogenicity.

CONCLUSION

CT-001 corrected APC pathway–mediated coagulopathic conditions in preclinical studies and could be a potentially safe and effective procoagulant agent for addressing APC-mediated bleeding.
Long-term physical and mental health outcomes of pediatric firearm-injured victims: A prospective cohort study
Authors: Haasz Maya , Dulchavsky Alexandria , Stevens Jenny , Nolan Margo , Leonard Jan , Phillips Ryan , Knoepke Christopher , Schroeppel Thomas , Zuk Jeannie , Abbey William , Ambroggio Lilliam
Published: June 2023

BACKGROUND

Firearms are a leading cause of injury among US youth. There is little research describing outcomes after pediatric firearm injuries, particularly past 1 year.

OBJECTIVE

This study aimed to assess long-term physical and mental health outcomes among nonfatal firearm versus motor vehicle collision (MVC)–injured victims and versus a standard population.

METHODS

We retrospectively identified firearm and MVC-injured pediatric patients seen at one of our four trauma centers (January 2008 to October 2020) and prospectively assessed outcomes using validated patient-reported outcome measures. Eligible patients were English speaking, injured ≥5 months before study start, younger than 18 years at time of injury, and 8 years or older at study start. All firearm patients were included; MVC patients were matched 1:1 with firearm patients for Injury Severity Score (dichotomized <15 or ≥15), age range (±1 year), and year of injury. We conducted structured interviews of patients and parents using validated tools (Patient-Reported Outcomes Measurement Information System tools, Children's Impact of Event Scale for younger than 18 years and parent proxies). Patient-Reported Outcomes Measurement Information System scores are reported on a T score metric (mean [SD], 50 [10]); higher scores indicate more of the measured domain. We used paired t tests, Wilcoxon signed-rank tests, and McNemar's test to compare demographics, clinical characteristics, and outcomes.

RESULTS

There were 24 participants in each of the MVC and firearm-injured groups. Compared with MVC-injured patients, firearm-injured patients younger than 18 years had similar scores, and firearm-injured patients 18 years or older had higher anxiety scores (59.4 [8.3] vs. 51.2 [9.4]). Compared with a standard population, patients younger than 18 years had worse global health scores (mean [SD], 43.4 [9.7]), and participants 18 years or older reported increased fatigue (mean [SD], 61.1 [3.3]) and anxiety (mean [SD], 59.4 [8.3]).

CONCLUSION

Long-term effects of firearm-injured patients were poorer than matched MVC and the standard population in few domains. Further study in a larger, prospectively recruited cohort is warranted to better characterize physical and mental health outcomes.