bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of T-Cell Receptor-Based Adoptive Cell Therapy in Cutaneous Melanoma: A Meta-Analysis
Authors: Yarza Ramon , Bover Mateo , Herrera-Juarez Mercedes , Rey-Cardenas Macarena , Paz-Ares Luis , Lopez-Martin Jose A , Haanen John
Published: April 2023

Background

T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in cutaneous melanoma. We conducted a systematic review and meta-analysis aiming to assess the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma.

Methods

We searched through PubMed electronic database from its inception until May 21, 2022. Primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). We conducted logistic regression analyses to identify potential predictive factors for tumor response.

Results

From 187 patients, 50 showed an objective response (pooled ORR 28%; 95% CI, 20%-37%) and a pooled DCR of 38% (95% CI, 27%-50%). Median PFS was 2, 9 months (95% CI, 1.4-3.1). A trend toward higher PFS was demonstrated for patients treated with cancer/testis antigens targeting TCR-T cells (HR 0.91 95% CI, 0.64-1.3, P = .61) among whom, patients treated with NYESO-1 targeting TCR-T showed a significantly higher PFS (HR 0.63 95% CI, 0.64-0.98, P = .03). In addition, the number of infused cells was associated with a significantly higher likelihood of tumor response (OR 6.61; 95% CI, 1.68-21.6; P = .007).

Conclusion

TCR-T therapy shows promising results in terms of antitumor activity and survival similar to those reported for TILs with a significantly higher benefit for cancer/testis antigens targeting cells. Since TCR-based therapy shows advantages of great potential over classic ACT strategies, further research in solid cancers is warranted (PROSPERO ID CRD42022328011).
Restricted Composition is Information Compression
Authors: Bird Alexander
Published: April 2023

This paper proposes and examines an answer to the special composition question—complex objects compress information about their parts. I start by defending fastenation for material objects and then extract from fastenation the idea that the conjoinment of parts establishes correlations among the locations and motions of those parts. I move from this to the proposal that entities are parts of some object when that object allows for the efficient, if lossy, compression of information about those parts.
In person and virtual process mapping experiences to capture and explore variability in clinical practice: application to genetic referral pathways across seven Australian hospital networks
Authors: Morrow April , Steinberg Julia , Chan Priscilla , Tiernan Gabriella , Kennedy Elizabeth , Egoroff Natasha , Hilton Desiree , Sankey Lucien , Venchiarutti Rebecca , Hayward Anne , Pearn Amy , McKay Skye , Debono Deborah , Hogden Emily , Taylor Natalie
Published: April 2023

Genetic referral for Lynch syndrome (LS) exemplifies complex clinical pathways. Identifying target behaviours (TBs) for change and associated barriers requires structured group consultation activities with busy clinicians – consolidating implementation activities whilst retaining rigour is crucial. This study aimed to: i) use process mapping to gain in-depth understandings of site-specific LS testing and referral practices in Australian hospitals and support identification of TBs for change, ii) explore if barriers to identified TBs could be identified through process mapping focus-group data, and iii) demonstrate pandemic-induced transition from in-person to virtual group interactive process mapping methods.

LS clinical stakeholders attended interactive in-person or virtual focus groups to develop site-specific “process maps” visually representing referral pathways. Content analysis of transcriptions informed site-specific process maps, then clinical audit data was compared to highlight TBs for change. TBs were reviewed in follow-up focus groups. Secondary thematic analysis explored barriers to identified TBs, coded against the Theoretical Domains Framework (TDF). The transition from in-person to pandemic-induced virtual group interactive process mapping methods was documented.

Process mapping highlighted six key areas of clinical practice variation across sites and site-specific TBs for change were identified. Key barriers to identified TBs emerged, categorised to seven TDF domains.

Process mapping revealed variations in clinical practices surrounding LS referral between sites. Incorporating qualitative perspectives enhances process mapping by facilitating identification of TBs for change and barriers, providing a pathway to developing targeted interventions. Virtual process mapping activities produced detailed data and enabled comprehensive map development.
Uneven Returns to Nondegree Work Credentials for Older Workers
Authors: Zhang Tingting , Zhang Pidi
Published: April 2023

Using the U.S. Adult Training and Education Survey (N = 41,442), we examined the impact of acquiring nondegree work credentials at different ages on labor market outcomes, focusing on those close to retirement age. We examined two types of work credentials—occupational licenses and certifications. The majority of survey respondents, aged 16–66 years when surveyed, earned their most important credential, especially occupational licenses, at an early stage (before 35 years old). Although a significant share of older respondents held a work credential, fewer acquired a new credential close to retirement age. Results of multinominal logistic regression showed those obtaining a work credential close to retirement age (55–64 years old) were more likely to be in the labor force than noncredentialed respondents, but they were more likely to be underemployed or unemployed, controlling for demographic characteristics. Of those in the labor force, respondents earning a credential later (55–64 years old) were more likely to work part-time and have multiple jobs than noncredentialed respondents; those who earned a credential earlier (16–34 years old) were less likely to work part-time and more likely to work more hours weekly. Finally, among credential holders, older respondents thought work credentials earned at a younger age were more useful as a labor market signal; credentials earned later were less effective to gain or keep a job or to ensure marketability. Job-related effectiveness of occupational licenses decreased as the age when such credentials were earned increased, but certifications earned later were more likely viewed as a way to improve work skills than certifications earned at a younger age.
The Skill-Specific Automatability of Aging Workers and Its Impact on Retirement Decisions
Authors: Lee Zeewan
Published: April 2023

Research regarding the effects of automation on labor supply often assesses the labor force as a whole and disregards specific effects on aging workers. In light of rapid technological changes in the labor market, we assess the linkage between the automatability of aging workers and their retirement decisions. Based on the theoretical model of task-based technological changes and drawing data from the Health and Retirement Study and O*NET 2000–2018, we create an automatability index based on workers’ primary skills. Using the index as our main explanatory variable in Cox proportional hazards models and logit models, we find that skill-specific automatability increases the retirement likelihood, both in terms of their expected and actual timing of retirement. This work provides empirical evidence that individuals’ automatability renders the notion of “working at old age” less viable, despite the financial and health benefits of staying in the labor force for an extended period. Our findings offer important insights on how to better promote productive aging, for instance, by offering retraining programs for older workers to harness their soft skills to reduce automatability in the labor market.
Incidence of Heterotopic Ossification at 10 years after Cervical Disc Replacement
Authors: Sheng Xia-Qing , Wu Ting-Kui , Liu Hao , Meng Yang
Published: April 2023

Study Design.

Systematic review and meta-analysis.

Objective.

This study aimed to assess the incidence of heterotopic ossification (HO) 10 years after cervical disc replacement (CDR).

Summary of Background Data.

HO is a common complication after CDR and may limit the range of motion (ROM) of the artificial disc. As HO usually progresses slowly, long-term follow-up is required to better understand its incidence. In recent years, the increasing number of original articles reporting 10 year outcomes give us the opportunity to better understand the long-term incidence of HO.

Methods.

We searched PubMed, Medline, Embase, and Cochrane Library databases to identify eligible studies. The incidence of HO was pooled and subgroup analysis was performed. Meta-regression analyses were conducted to identify factors contributing to heterogeneity.

Results.

Eleven studies with at least 10 years of follow-up comprising 1,140 patients who underwent CDR were included. The pooled incidence of overall HO was 70% (95% CI: 60–81%) at 10 years postoperatively, 60% (95% CI: 44–75%) at 5 or 6 years postoperatively, and 50% (95% CI: 27–72%) at 1 or 2 years postoperatively. The pooled incidence of severe HO (grade 3 or 4) was 37% (95% CI: 29–45%), and mild HO (grade 1 to 2) was 30% (95% CI: 17–44%) at 10 years of follow-up. Pooled ROM decreased from 8.59° before surgery to 7.40° 10 years after surgery. Subgroup analysis showed that HO incidence differed according to the prosthesis type. Earlier publication was associated with a higher pooled incidence of severe HO in the meta-regression analysis.

Conclusion.

This is the first meta-analysis providing detailed information on the pooled 10-year incidence of HO after CDR. The incidence ofHO appears to increase with the length of follow-up.

Level of Evidence.

III.
Novel Nomograms and Web-Based Tools Predicting Overall Survival and Cancer-specific Survival of Solitary Plasmacytoma of the Spine
Authors: Yang Sheng , Fan Guoxin , Feng Chaobo , Fan Yunshan , Xu Ningze , Zhou Hongmin , Wang Chuanfeng , Liao Xiang , He Shisheng
Published: April 2023

Study Design.

Retrospective analysis.

Objective.

This study aimed to establish nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in patients with solitary plasmacytoma of the spine (SPS).

Summary of Background Data.

SPS is a rare type of malignant spinal tumor. A systematic study of prognostic factors associated with survival can provide guidance to clinicians and patients. Consideration of other causes of death (OCOD) in CSS will improve clinical practicability.

Methods.

A total of 1078 patients extracted from the SEER database between 2000 and 2018 were analyzed. Patients were grouped into training and testing data sets (7:3). Factors associated with OS and CSS were identified by Cox regression and competing risk regression, respectively, for the establishment of nomograms on a training data set. The testing data set was used for the external validation of the performance of the nomograms using calibration curves, Brier’s scores, C-indexes, time-dependent receiver operating characteristic curves, and decision curve analysis (DCA).

Results.

Age and grade were identified as factors associated with both OS and CSS, along with marital status, radiation for OS, and chemotherapy for CSS. Heart disease, cerebrovascular disease, and diabetes mellitus were found to be the 3 most common causes of OCOD. The nomograms showed satisfactory agreement on calibration plots for both training and testing data sets. Integrated Brier score, C-index, and overall area under the curve on the testing data set were 0.162/0.717/0.789 and 0.173/0.709/0.756 for OS and CSS, respectively. DCA curves showed a good clinical net benefit. Nomogram-based web tools were developed for clinical application.

Conclusion.

This study provides evidence for risk factors and prognostication of survival in SPS patients. The novel nomograms and web-based tools we developed demonstrated good performance and might serve as accessory tools for clinical decision-making and SPS management.

Level of Evidence.

3
An All-arthroscopic Technique of Repair of Substance Tears of the Triangular Fibrocartilage Complex in Symptomatic Patients
Authors: Choudhury Muntasir Mannan , Yap Robert Tze Jin , Chia Dawn Sinn Yi , Sajeev Suraj , Jiang Jackson Kian Hong
Published: April 2023

Substance tears of the triangular fibrocartilage complex (TFCC) can occur secondary to trauma of the wrist. On the dorsal periphery, they are considered Palmer 1B tears or Atzei class 1 tears. If along the radial side, they can manifest as a tear of the central disc, classified as a Palmar class 1A tear. If it involves the ligaments, it is stated as a pre-1D tear as per the new classification system by Luchetti and colleagues. Multiple excellent repair techniques exist in the current literature for dorsal peripheral tears and even for those in the substance of the TFCC, whereas there are successful evolving techniques of repair of avulsed tears and those involving the substance of the ligaments on the radial side adjacent to the sigmoid notch. Here, we describe our technique of repairing substance tears of the TFCC arthroscopically without the need for any specialized equipment apart from the basic arthroscopy set. The technique was conducted in a patient with a transverse substance tear on the radial side of the triangular fibrocartilage involving the central disc with complete resolution of symptoms. It is a simple technique, which can be used to repair class 1B peripheral tears and pre-1D tears in the substance of the TFCC.
Injury mechanism, risk factors and outcomes associated with blunt cardiac injury: a systematic review and meta-analysis
Authors: Jiang Yongjin , Zhou Gaoliang , Feng Jun , Ma Likun , Pan Jianyuan
Published: April 2023

Background and purpose:

Risk factors that could be used to assess early and further improve the positive predictive value of blunt cardiac injury (BCI) are still inconclusive. We conducted a meta-analysis to quantitatively analyze the injury mechanism, risk factors, and outcomes associated with BCI in trauma patients.

Methods:

This systematic review and meta-analysis were performed to gather data on trauma patients with blunt cardiac injury. PubMed, Web of Science, and EMBASE databases were searched for studies until 20th November 2021. A pooled meta-analysis of injury mechanisms, risk factors, and outcomes concerning BCI was conducted.

Results:

We screened 256 records from which 11 studies published from 2000 to 2019 reporting 68,039 patients with trauma were included. Motor vehicle crash was the main injury mechanism, accounting for 65.2% of the attributed mechanisms for BCI (pool P = 0.652 [0.595–0.709]). The pooled relative risks (RRs) revealed that patients with sternal fracture, shock on arrival, and history of cardiac disease were associated with increased risk of BCI (for sternal fracture: RR = 7.21 [95% confidence interval (CI) = 3.99–13.05]; for the shock on arrival: RR = 2.45, 95% CI = 2.12–2.84; for the history of cardiac disease: RR = 1.87, 95% CI = 1.11–3.16). A significant difference was observed in the length of stay between the BCI group compared to the no BCI group, 11.68 (95% CI = 8.79–14.58 days) vs. 20.46 (95% CI = 16.78–24.14 days). The risk of mortality was significantly higher in trauma patients with BCI as compared to those without BCI (RR = 1.70, 95% CI = 1.53–1.90).

Conclusions:

BCI was associated with increased mortality in our study. Patients also tended towards a longer length of stay. In addition to electrocardiogram and TnI, we recommend screening for BCI when trauma patients are in the presence of sternal fracture, shock, and a history of cardiac disease.
Keloidal Collagen May Be Produced Directly by αSMA-positive Cells: Morphological Analysis and Protein Shotgun Analysis
Authors: Kaku Chiemi , Ichinose Shizuko , Dohi Teruyuki , Tosa Mamiko , Ogawa Rei
Published: April 2023

Background:

Keloids are fibroproliferative lesions caused by abnormal dermal wound healing. Keloidal collagen (KC) is a pathognomic feature of keloids, but the mechanism by which it forms is unknown. This study aimed to evaluate the histopathology of KC and thereby gain clues into how it forms.

Methods:

The cross-sectional study cohort consisted of a convenience series of patients with keloids who underwent surgical excision. Skin pieces (3 mm2) were collected from the keloid center and nearby control skin. Histopathology was conducted with light and electron microscopy and immunohistochemistry. KC composition was analyzed with protein shotgun analysis.

Results:

Microscopic analyses revealed the ubiquitous close association between KC and αSMA-positive spindle-shaped cells that closely resembled myofibroblasts. Neither KC nor the spindle-shaped cells were observed in the control tissues. Compared with control skin, the collagen fibers in the KC were overall thinner, their diameter varied more, and their spacing was irregular. These features were particularly pronounced in the collagens in the vicinity of the spindle-shaped cells. Protein shotgun analysis did not reveal a specific collagen in KC but showed abnormally high abundance of collagens I, III, VI, XII, and XIV.

Conclusions:

These findings suggest that KC may be produced directly by myofibroblasts rather than simply being denatured collagen fibers. Because collagens VI and XII associate with myofibroblast differentiation, and collagen XIV associates with local mechanical stress, these collagens may reflect, and perhaps contribute to, the keloid-specific local conditions that lead to the formation of KC.
Characteristics of fibrotic-foci-like lung adenocarcinoma on 18F-FDG PET/computed tomography and HRCT
Authors: Zhang Jing , Jiang Yu-Meng , Xu Ao-Di , Lin Shuai , Fang Na , Wang Yan-Li
Published: April 2023

Purpose

To assess the characteristics of fibrotic-foci-like lung adenocarcinoma on 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) and high-resolution computed tomography (HRCT).

Material and methods

This was a retrospective study with 20 cases in the fibrotic-foci-like lung adenocarcinoma group; the control group was old fibrotic-foci of the lung with 20 cases. The following 18F-FDG PET/CT and HRCT features were evaluated: the maximum standardized uptake value (SUVmax); the tumor-to-background ratios of SUVmax (TBRmax); the long-to-short diameter ratio (L/S); anatomic location; location type; internal characteristics; marginal characteristics and surrounding structures. In the fibrotic-foci-like lung adenocarcinoma group, a comparison of 18F-FDG uptake between the metastatic group (n = 10) and the non-metastatic group (n = 10) was performed. Finally, the comparison of diagnostic accuracy for fibrotic-foci-like lung adenocarcinoma between 18F-FDG PET/CT and HRCT was performed.

Results

The SUVmax [2.6 (1.7–7.9) vs. 1.0 (0.7–1.4)], TBRmax [2.9 (2.1–9.9) vs. 1.3 (1.2– 1.7)], L/S [2.4 (1.7–3.8) vs. 4.0 (3.2–6.3)], ground-glass opacity (GGO) [13/20 (65.0%) vs. 4/20 (20.0%)], and vessel convergence [7/20 (35.0%) vs. 1/20 (5.0%)] were found to be statistically significant differences between the fibrotic-foci-like lung adenocarcinoma group and the old fibrotic-foci group (P < 0.05). SUVmax [7.9 (4.7–8.8) vs. 1.7 (1.2–2.2)] and TBRmax [9.9 (6.5–11.0) vs. 2.1 (1.6–2.9)] were found to be statistically significant differences between the metastatic group and the non-metastatic group (P < 0.05). 18F-FDG PET/CT showed the higher diagnostic accuracy for fibrotic-foci-like lung adenocarcinoma than HRCT [95.0% (19/20) vs. 65.0% (13/20), P < 0.05].

Conclusion

The specific characteristics of fibrotic-foci-like lung adenocarcinoma on 18F-FDG PET/CT and HRCT were high 18F-FDG uptake, GGO, and vessel convergence, which could be distinguished from old fibrotic-foci of the lung.
Examining the Evidence for Escalating Antimicrobial Regimens in Febrile Oncology and Hematopoietic Stem Cell Transplant Patients Admitted to the PICU: An Observational Study*
Authors: Prince Remi D. , Blumenthal Jennifer A. , Geva Alon
Published: April 2023

OBJECTIVES:

To examine whether escalating antimicrobial treatment in pediatric oncology and hematopoietic cell transplantation (HSCT) patients admitted to the PICU is supported by culture data or affects patient outcomes.

DESIGN:

Retrospective cross-sectional study.

SETTING:

Quaternary care PICU.

PATIENTS:

Patients younger than 18 years old who were admitted to the PICU at Boston Children’s Hospital from 2012 to 2017 with a diagnosis of cancer or who had received HSCT and who had suspected sepsis at the time of PICU admission.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of 791 PICU admissions for 544 patients that met inclusion criteria, 71 (9%) had escalation of antimicrobial therapy. Median Pediatric Logistic Organ Dysfunction (PELOD) score was higher in the escalation group (4 vs 3; p = 0.01). There were 14 admissions (20%) with a positive culture in the escalation group and 110 (15%) in the no escalation group (p = 0.31). In the escalation group, there were only 2 (3%) cultures with organisms resistant to the initial antimicrobial regimen, compared with 28 (4%) cultures with resistant organisms in the no escalation group (p = 1). Mortality in the escalation group was higher (17%) compared with the nonescalation group (5%; p < 0.001). The escalation group had more acute kidney injury (AKI) (25%) during treatment compared with the no escalation group (15%; p = 0.04), although this difference was not statistically significant when controlling for age, neutropenia, and PELOD-2 score (odds ratio, 1.75; 95% CI, 0.95–3.08; p = 0.06).

CONCLUSIONS:

Few patients who had escalation of antimicrobials proved on culture data to have an organism resistant to the initial antimicrobials, and more patients developed AKI during escalated treatment. While the escalation group likely represents a sicker population, whether some of these patients would be safer without escalation of antimicrobial therapy warrants further study.
Evaluating Demographic Data to Improve Confidence in Equity Analytics in a Children’s Hospital
Authors: Straus Anna M. , Hayes Alissa , Simon Jodi , Sims Andrea , Skerlong Karen , Wilmoth Michele , Bigham Michael T.
Published: April 2023

Introduction:

Healthcare institutions are placing greater emphasis on equitable care. To accurately track and validate equity metrics, Akron Children’s Hospital evaluated how key fields are collected, analyzed, and visualized throughout the organization. Standardized recommendations in this area vary, and this investigation provided specific ways to advance analytics in this field. In addition, the technical infrastructure needed a comprehensive evaluation to increase confidence in using demographic data.

Methods:

First, we reviewed how staff are trained to collect data at registration. Next, the electronic health record team standardized race and ethnicity fields with federal definitions. We found that fields were not consistently accessible across reporting tools. However, when present, all fields are sourced from the same electronic health record field. Finally, 6 months of encounters were analyzed and validated, with limitations to a seldom-populated Race 2 field.

Results:

We compared data, including and excluding null values, to provide concise recommendations for standard visualizations. We uncovered many consistencies and a few inconsistencies that informed the next steps.

Conclusions:

The results informed 7 recommendations to align Akron Children’s Hospital’s advancement in analytics for health equity data: standardize race and ethnicity fields across all reporting tools, add Child Opportunity Index 2.0 to the enterprise data warehouse, utilize data at the time of the patient’s encounter, include null fields (patient refused, unknown, and not specified) in analysis, increase reporting capabilities for social determinants of health (SDOH), standardize multiracial data visualizations, and optimize reliable upstream data collection to increase reliability for all health equity measures.
Recognizing Nonaccidental Trauma in a Pediatric Tertiary Hospital: A Quality Improvement Imperative
Authors: Greene H. Michelle , Letson Megan M. , Spencer Sandra P. , Dolan Kevin , Foster Jeanette , Crichton Kristin G.
Published: April 2023

Introduction:

Abusive injuries can go unrecognized or improperly managed by medical providers. This study sought to standardize the nonaccidental trauma (NAT) workup and improve NAT evaluation completion for children <7 months with concerning injuries in the pediatric emergency department (PED) and inpatient settings at an urban, tertiary care children’s hospital.

Methods:

The quality improvement (QI) team created hospital guidelines for suspected NAT, including age-based recommendations (care bundle). The team embedded an order for NAT evaluation into the electronic health record (EHR). The QI team provided education on child abuse identification and evaluation across the hospital. Hospital providers received written guides focused on enhancing communication with families. Outcome measures included monthly NAT bundle use and cases between incomplete bundles in children with suspicious injuries. Chart review of incomplete bundles helped accurately identify patients who needed NAT bundles and improved accurate NAT bundle completion for appropriate patients.

Results:

Appropriate NAT bundle completion increased from 31% during the baseline period in January 2019 to 100% in April 2020 and remained at 100% for the remainder of the study period, ending June 2021. The number of patients between missed bundles was 11 from August 2019 until March 2020, when it increased to 583. There were no missed bundles from March 2020 through June 2021.

Conclusions:

Standardizing NAT evaluation and creating a NAT care bundle to facilitate the appropriate evaluation preceded an increase in appropriate bundle completion in patients <7 months old with possible NAT in the PED and inpatient units.
Determinants of Blood Culture Use in Critically Ill Children: A Multicenter Qualitative Study
Authors: Woods-Hill Charlotte Z. , Nelson Maria N. , Eriksen Whitney , Rendle Katharine A. , Beidas Rinad S. , Bonafide Christopher P. , Brajcich Michelle R. , Milstone Aaron M. , Shea Judy A.
Published: April 2023

Introduction:

Blood cultures are fundamental in diagnosing and treating sepsis in the pediatric intensive care unit (PICU), but practices vary widely. Overuse can lead to false positive results and unnecessary antibiotics. Specific factors underlying decisions about blood culture use and overuse are unknown. Therefore, we aimed to identify perceived determinants of blood culture use in the PICU.

Methods:

We conducted semistructured interviews of clinicians (M.D., D.O., R.N., N.P., P.A.) from 6 PICUs who had participated in a quality improvement collaborative about blood culture practices. We developed interview questions by combining elements of the Consolidated Framework for Implementation Research and behavioral economics. We conducted telephone interviews, open-coded the transcripts, and used modified content analysis to determine key themes and mapped themes to elements of Consolidated Framework for Implementation Research and behavioral economics.

Results:

We reached thematic saturation in 24 interviews. Seven core themes emerged across 3 Consolidated Framework for Implementation Research domains: individual characteristics [personal belief in the importance of blood cultures, the perception that blood cultures are a low-risk test]; inner setting [adherence to site-specific usual practices, site-specific overall approach to PICU care (collaborative versus hierarchical), influence of non-PICU clinicians on blood culture decisions]; and outer setting [patient-specific risk factors, sepsis guidelines]. In addition, outcome bias, default bias, and loss aversion emerged as salient behavioral economics concepts.

Conclusions:

Determinants of blood culture use include individual clinician characteristics, inner setting, and outer setting, as well as default bias, outcome bias, and loss aversion. These determinants will now inform the development of candidate strategies to optimize culture practices.
Gram-positive bacteria increase breast implant related complications: Prospective analysis of 100 revised implants.
Authors: Flores Tonatiuh , Kerschbaumer Celina , Jaklin Florian J. , Rohrbacher Alexander , Weber Michael , Luft Matthias , Aspöck Christoph , Ströbele Barbara , Kitzwögerer Melitta , Lumenta David B. , Bergmeister Konstantin D. , Schrögendorfer Klaus F.
Published: April 2023

Background:

Breast implant-related complications can be reduced by strict antiseptic precautions during insertion, but bacteria can often be found on implant surfaces on the occasion of revision surgery. We prospectively analyzed the association of bacteria found on breast implant surfaces with implant-related complications in breast implant revision cases.

Methods:

We analyzed a total of 100 breast implant revisions in in 66 patients between August 2018 and January 2021. Capsular swabs and capsular samples were taken intraoperatively. Analyses upon the occurrence of bacteria and the occurrence of implant-related complications were performed. Additionally, correlations between bacterial contaminated breast implant surfaces and implant-related complications were performed.

Results:

Implant-related complications (perforation, rupture, capsular contraction) were observed in 42 implant sites; in eight unilateral and 34 bilateral cases. In total 16 swabs showed positive bacterial growth, 10 of which were associated with a breast implant-related complication (X
2 = x.yz, p = 0.006). The most common implant-based complication at contaminated prosthetics was implant rupture. The association of contaminated breast implants and implant rupture was statistically significant.

Conclusion:

We identified a correlation between implant complications and gram-positive bacteria found on breast implant surfaces. The most common implant-based complication seen at simultaneously positive samples was implant rupture in 50% of our cases. Here, no capsular contraction or other complications were seen.
Patient-perceived hand function measured can predict treatment for Dupuytren’s disease
Authors: van den Berge Bente A. , Blom Paula C.A. , Werker Paul M.N. , Broekstra Dieuwke C.
Published: April 2023

Background:

Web based patient-reported outcome measures (PROMs) could aid surgeons to remotely assess the need for examination and subsequent treatment of Dupuytren’s disease (DD) patients. We studied whether the Unité Rhumatologique des affections de la Main (URAM) and the Michigan Hand Questionnaire (MHQ) could predict DD treatment.

Methods:

In this prospective cohort study, we compared MHQ and URAM scores of treated patients with untreated patients. For the treatment group, we selected a score closest to one year before treatment. For controls we randomly selected a score. Additionally, we tested the predictive value of a one-year change score between 15 months and 6 weeks before treatment. The primary outcome measure was DD treatment.

The predictive value was determined using the Area Under the Curve (AUC). An AUC >0.70 was considered as good predictive ability, 0.70-0.50 as poor predictive ability and <0.50 as no predictive ability.

Results:

We included 141 patients for the MHQ analysis and 145 patients for the URAM analysis. The AUC of the MHQ and URAM scores measured one year before treatment were 0.80 (95% CI 0.71-0.88) and 0.75 (95% CI 0.68-0.82), respectively. The one-year change score resulted in an AUC of <0.60 for both questionnaires.

Conclusions:

Our results show that both the MHQ and URAM score measured around one year before treatment can predict treatment for DD. If future studies show that telemonitoring of DD patients with PROMs is also cost-effective, web-based PROMs could optimise patient care and treatment effectiveness of DD.
Clinical outcomes of upper extremity nerve transfers in neuralgic amyotrophy
Authors: Solaja Ogi , Baergen Allison K. , Head Linden K. , Wolff Gerald K. , Boyd Kirsty U.
Published: April 2023

Neuralgic amyotrophy (NA) is a disease affecting peripheral nerves. Historically, treatment has been conservative as the natural course of the disease was thought to be self-limiting. Recent work has demonstrated that as many as two-thirds of those affected suffer from persistent pain, fatigue, or weakness. At our centre, supercharge end-to-side (SETS) nerve transfers are commonly performed in patients with NA to optimize motor recovery while allowing for native axonal regrowth. We describe the technique and clinical outcomes of patients with NA affecting the anterior interosseous nerve (AIN) who were treated with SETS nerve transfer from extensor carpi radialis brevis (ECRB) to AIN. Ten patients (90% male, mean age 51.3 ± 9.7 years) underwent ECRB to AIN nerve transfer at a mean of 6.4 ± 1.4 months following onset of symptoms. Mean postoperative follow-up duration was 14.8 ± 3.2 months. Preoperatively, all patients demonstrated clinically significant weakness in the flexor pollicis longus (FPL), flexor digitorum profundus muscle to the index finger (FDP2), or both. FPL strength improved from a median Medical Research Council (MRC) grade of 1.5 to 4 (p = 0.011) and FDP2 strength improved from a median MRC of 1 to 5 (p = 0.016). A postoperative MRC grade of 4- or greater was achieved in 9 of 10 (90%) FPL and 10 of 10 (100%) FDP muscles. This is the first report of SETS nerve transfer for the treatment of NA. The outcomes of this work suggest that SETS nerve transfers may be an option to optimize the motor outcomes in patients with NA.
The Deep Fascia of the Head and Neck Revisited: Relationship with the Facial Nerve and Implications for Rhytidectomy
Authors: Minelli Lennert , van der Lei Berend , Mendelson Bryan C.
Published: April 2023

Background:

The deep fascia is important in face-lift surgery, as it is relied on for protection of the facial nerve during surgical dissection. Lack of consistency with the term may be attributable to the term deep fascia having two different meanings. It is a specific type of connective tissue, classically thin, fibrous, and flat, whereas in the description of the layers of the face and neck, the deep fascia layer includes all the connective tissue deep to the superficial fascia layer. This cadaver study was undertaken to clarify the layered anatomy of the face and neck and its relationship with the facial nerve branches.

Methods:

Preliminary dissections and macrosectioning, followed by a conclusive series of standardized layered dissections, histologic analysis, and sheet plastination, were performed on 50 cadaver heads.

Results:

The deep fascia is thin in convex areas of the face and neck, and thicker in concave areas; it is interspersed with deep fat. The facial nerve branches, after emerging from the parotid gland, are embedded within the deep fascia, not deep to it. They transition from deep within the deep fascia at specific locations to course in the most superficial part of the deep fascia where they underlie their target superficial fascia muscles and are at risk from deep plane face-lift dissection.

Conclusions:

The deep fascia layer is a multilamellar fibrofatty layer of variable thickness, which includes the deep fat in which the facial nerve branches are embedded. In deep plane face-lift surgery, dissection must be performed in the most superficial level of this deep fascia layer.
EFFECTS OF BACTERIAL LIPOPOLYSACCHARIDE AND SHIGA TOXIN ON INDUCED PLURIPOTENT STEM CELL-DERIVED MESENCHYMAL STEM CELLS
Authors: Martire-Greco Daiana , La Greca Alejandro , Castillo Montañez Luis , Biani Celeste , Lombardi Antonella , Birnberg-Weiss Federico , Norris Alessandra , Sacerdoti Flavia , Amaral María Marta , Rodrigues-Rodriguez Nahuel , Pittaluga Jose Ramón , Furmento Verónica Alejandra , Landoni Verónica Inés , Miriuka Santiago Gabriel , Luzzani Carlos , Fernández Gabriela Cristina
Published: April 2023

Background: Mesenchymal stem cells (MSCs) can be activated by different bacterial toxins. Lipopolysaccharides and Shiga Toxin (Stx) are the main toxins necessary for hemolytic uremic syndrome development. The main etiological event in this disease is endothelial damage that causes glomerular destruction. Considering the repairing properties of MSC, we aimed to study the response of MSC derived from induced pluripotent stem cells (iPSC-MSC) to LPS and/or Stx and its effect on the restoration of injured endothelial cells. Methods: iPSC-MSC were treated with LPS and or/Stx for 24 h and secretion of cytokines, adhesion, and migration were measured in response to these toxins. In addition, conditioned media from treated iPSC-MSC were collected and used for proteomics analysis and evaluation of endothelial cell healing and tubulogenesis using human microvascular endothelial cells 1 as a source of endothelial cells. Results: The results obtained showed that LPS induced a proinflammatory profile on iPSC-MSC, whereas Stx effects were less evident, even though cells expressed the Gb3 receptor. Moreover, LPS induced on iPSC-MSC an increment in migration and adhesion to a gelatin substrate. Addition of conditioned media of iPSC-MSC treated with LPS + Stx, decreased the capacity of human microvascular endothelial cells 1 to close a wound, and did not favor tubulogenesis. Proteomic analysis of iPSC-MSC treated with LPS and/or Stx revealed specific protein secretion patterns that support the functional results described. Conclusions: iPSC-MSC activated by LPS acquired a proinflammatory profile that induces migration and adhesion to extracellular matrix proteins but the addition of Stx did not activate any repair program to ameliorate endothelial damage, indicating that the use of iPSC-MSC to regenerate endothelial injury caused by LPS and/or Stx in hemolytic uremic syndrome could not be the best option to consider to regenerate a tissue injury.
Safety and Effectiveness of Cladribine in Multiple Sclerosis: Real-World Clinical Experience From 5 Tertiary Hospitals in Portugal
Authors: Santos Mónica , Sequeira João , Abreu Pedro , Guerreiro Rui , Santos Mariana , Ferreira João , Brum Marisa , Ladeira Filipa , Leitão Lia , Dias Rafael , Sá Maria José , Salgado Vasco , Capela Carlos , de Sá João
Published: April 2023

Objectives

Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe for very active multiple sclerosis (MS) with relapses. Aims were to assess the safety and effectiveness of cladribine in real-world setting, during treatment follow-up.

Methods

This was a multicentric, longitudinal, observational study with retrospective and prospective data collection of clinical, laboratory, and imaging data. This interim analysis reports data from July 1, 2018 (study onset), to March 31, 2021.

Results

A total of 182 patients were enrolled: 68.7% were female; mean age at onset was 30.1 ± 10.0 years, and mean age at first cycle of cladribine treatment was 41.1 ± 12.1; 88.5% were diagnosed with relapse-remitting MS and 11.5% with secondary progressive MS. Mean disease duration at cladribine start was 8.9 ± 7.7 years. Most patients (86.1%) were not naive, and median number of previous disease-modifying therapies was 2 (interquartile range, 1–3). At 12 months, we observed no significant Expanded Disability Status Scale score worsening (P= 0.843, Mann-WhitneyUtest) and a significantly lower annualized relapse rate (0.9 at baseline to 0.2; 78% reduction). Cladribine treatment discontinuation was registered in 8% of patients, mainly (69.2%) due to disease activity persistence. Most frequent adverse reactions were lymphocytopenia (55%), infections (25.2%), and fatigue (10.7%). Serious adverse effects were reported in 3.3%. No patient has discontinued cladribine treatment because of adverse effects.

Conclusion

Our study confirms the clinical efficacy and the safety profile of cladribine for treating MS patients with a long-term active disease in the real-world setting. Our data contribute to the body of knowledge of the clinical management of MS patients and the improvement of related clinical outcomes.
A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults
Authors: Devinney Michael J. , Wong Megan K. , Wright Mary Cooter , Marcantonio Edward R. , Terrando Niccolò , Browndyke Jeffrey N. , Whitson Heather E. , Cohen Harvey J. , Nackley Andrea G. , Klein Marguerita E. , Ely E. Wesley , Mathew Joseph P. , Berger Miles ,   the MADCO-PC & INTUIT Study Groups
Published: April 2023

Objective

Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.

Methods

Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR).

Results

Of 207 patients (median age 68, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24-hours after surgery (median postoperative change 0.28, [IQR] [-0.48-1.24]; Wilcoxon p=0.001). Preoperative to 24-hour postoperative change in CPAR was greater among patients who developed delirium vs those who did not (median [IQR] 1.31 [0.004, 2.34] vs 0.19 [-0.55, 1.08]; p=0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24-hour postoperative change in CPAR was independently associated with delirium incidence (per CPAR increase of 1, OR = 1.30, [95% CI 1.03-1.63]; p=0.026) and increased hospital length of stay (IRR = 1.15 [95% CI 1.09-1.22]; p<0.001)

Interpretation

Postoperative increases in blood-brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay.
Daily rhythms, demographics and health: findings from a nationally representative survey
Authors: Ujma Péter P. , Horváth Csenge G. , Bódizs Róbert
Published: April 2023

The timing of daily activity in humans have been associated with various demographic and health-related factors, but the possibly complex patterns of confounding and interaction between these has not been systematically explored. We use data from Hungarostudy 2021, a nationally representative survey of 7000 Hungarians to assess the relationship between self- reported chronotype, social jetlag (using the Munich Chronotype Questionnaire), demographic variables and self-reported health and demographic variables, including ethnic and sexual minority membership. Supporting the validity of self-reports, participants with later chronotypes reported the lowest daytime sleepiness at a later clock time. We found that older age, female sex, a more eastward and southward geographical position, residence in a smaller settlement, less education and income, religiousness and cohabiting with small children were associated with an earlier chronotype. Younger age, higher education and income, and cohabiting with small children were associated with increased social jetlag. Of the 48 health-related variables surveyed, the relationship with both chronotype and social jetlag were mostly accounted for by age, sex, and socioeconomic effects, but we identified alcohol consumption, smoking, and physical activity as predictors of both social jetlag and chronotype, while a number of disorders were either positively or negatively associated with chronotype and social jetlag. Our findings from a large, nationally representative sample indicate that both biological and social factors influence chronotype and identified both demographic and health-related variables as risk factors for social jetlag. Our results, however, do not support a causal relationship between light exposure and mental health.
Development of Comorbidity Index for In-hospital Mortality for Patients Underwent Coronary Artery Revascularization
Authors: Li Renxi
Published: April 2023

Background

For myocardial revascularization, coronary artery bypass grafting (CAGB) and percutaneous coronary intervention (PCI) are two common modalities but with high in-hospital mortality. A comorbidity index is useful to predict mortality or can be used with other covariates to develop point-scoring systems. This study aimed to develop specific comorbidity indices for patients who underwent coronary artery revascularization.

Methods

Patients who underwent CABG or PCI were identified in the National Inpatient Sample database between Q4 2015-2020. Patients of age<40 were excluded for congenital heart defects. Patients were randomly sampled into experimental (70%) and validation (30%) groups. Thirty-eight Elixhauser comorbidities were identified and included in multivariable regression to predict in-hospital mortality. Weight for each comorbidity was assigned and single indices, Li CABG Mortality Index (LCMI) and Li PCI Mortality Index (LPMI), were developed.

Results

Mortality prediction by LCMI approached adequacy (c-statistic=0.691, 95% CI=0.682-0.701) and was comparable to multivariable regression with comorbidities (c-statistic=0.685, 95% CI=0.675-0.694). LCMI prediction performed significantly better than Elixhauser Comorbidity Index (ECI) (c-statistic=0.621, 95% CI=0.611-0.631) and can be further improved by adjusting age (c-statistic=0.721, 95% CI=0.712-0.730).

LPMI moderately predicted in-hospital mortality (c-statistic=0.666, 95% CI=0.660-0.672) and performed significantly better than ECI (c-statistic=0.610, 95% CI=0.604-0.616). LPMI performed better than the all-comorbidity multivariable regression (c-statistic=0.658, 95% CI=0.652-0.663). After age adjustment, LPMI prediction was significantly increased and was approaching adequacy (c-statistic=0.695, 95% CI=0.690-0.701).

Conclusions

LCMI and LPMI effectively predicted in-hospital mortality. These indices were validated and performed superior to ECI. The adjustment of age increased their predictive power to adequacy, implicating potential clinical application.
Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking
Authors: Liu Lihong , Casner Ryan G. , Guo Yicheng , Wang Qian , Iketani Sho , Chan Jasper Fuk-Woo , Yu Jian , Dadonaite Bernadeta , Nair Manoj S. , Mohri Hiroshi , Reddem Eswar R. , Yuan Shuofeng , Poon Vincent Kwok-Man , Chan Chris Chung-Sing , Yuen Kwok-Yung , Sheng Zizhang , Huang Yaoxing , Bloom Jesse D. , Shapiro Lawrence , Ho David D.
Published: April 2023

SARS-CoV-2 continues to evolve and evade most existing neutralizing antibodies, including all clinically authorized antibodies. We have isolated and characterized two human monoclonal antibodies, 12-16 and 12-19, which exhibited neutralizing activities against all SARS-CoV-2 variants tested, including BQ.1.1 and XBB.1.5. They also blocked infection in hamsters challenged with Omicron BA.1 intranasally. Structural analyses revealed both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, revealing a previously unrecognized site of vulnerability on SARS-CoV-2 spike. These antibodies prevent viral receptor engagement by locking the receptor-binding domain of spike in the down conformation, revealing a novel mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but the responsible mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.