bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer
Authors: Yuan Yang , Zhang Shaohua , Wang Tao , Bian Li , Yan Min , Yin Yongmei , Song Yuhua , Wen Yi , Li Jianbin , Jiang Zefei
Published: April 2023

Background:

Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2– MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2– MBC.

Methods:

Patients with HR+/HER2– MBC were screened from the Chinese Society of Clinical Oncology Breast Cancer database between January 1st, 1996 and September 30th, 2018. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) of patients were analyzed.

Results:

Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs. 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs. 8.5 months; P <0.01; ET cohort vs. CT cohort: 14.0 vs. 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS.

Conclusions:

ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.
Bilateral Irreversible Amantadine-Related Corneal Edema Successfully Treated With Descemet Membrane Endothelial Keratoplasty (DMEK)
Authors: Sierra Patricia Beatriz , Sierra Mendoza Mariela
Published: April 2023

Corneal edema is a recognized adverse reaction of chronic amantadine hydrochloride use. Fortunately, it is usually reversible with prompt discontinuation of the medication. We report a case of a patient with schizoaffective disorder–bipolar treated with high doses of amantadine for drug-induced akathisia, who developed irreversible bilateral severe corneal edema, and was successfully treated with Descemet membrane endothelial keratoplasty (DMEK). This case highlights the importance of recognizing amantadine-induced endothelial toxicity and confirms the utility of DMEK in the treatment of the condition.
Class A capsid assembly modulator RG7907 clears HBV-infected hepatocytes through core-dependent hepatocyte death and proliferation
Authors: Kum Dieudonné Buh , Vanrusselt Hannah , Acosta Sanchez Abel , Taverniti Valerio , Verrier Eloi R. , Baumert Thomas F. , Liu Cheng , Deval Jerome , Corthout Nikky , Munck Sebastian , Beigelman Leonid , Blatt Lawrence M. , Symons Julian A. , Raboisson Pierre , Jekle Andreas , Vendeville Sandrine , Debing Yannick
Published: April 2023

Background and Aims:

Effective therapies leading to a functional cure for chronic hepatitis B are still lacking. Class A capsid assembly modulators (CAM-As) are an attractive modality to address this unmet medical need. CAM-As induce aggregation of the HBV core protein (HBc) and lead to sustained HBsAg reductions in a chronic hepatitis B mouse model. Here, we investigate the underlying mechanism of action for CAM-A compound RG7907.

Approach and Results:

RG7907 induced extensive HBc aggregation in vitro, in hepatoma cells, and in primary hepatocytes. In the adeno-associated virus (AAV)–HBV mouse model, the RG7907 treatment led to a pronounced reduction in serum HBsAg and HBeAg, concomitant with clearance of HBsAg, HBc, and AAV-HBV episome from the liver. Transient increases in alanine transaminase, hepatocyte apoptosis, and proliferation markers were observed. These processes were confirmed by RNA sequencing, which also uncovered a role for interferon alpha and gamma signaling, including the interferon-stimulated gene 15 (ISG15) pathway. Finally, the in vitro observation of CAM-A–induced HBc–dependent cell death through apoptosis established the link of HBc aggregation to in vivo loss of infected hepatocytes.

Conclusions:

Our study unravels a previously unknown mechanism of action for CAM-As such as RG7907 in which HBc aggregation induces cell death, resulting in hepatocyte proliferation and loss of covalently closed circular DNA or its equivalent, possibly assisted by an induced innate immune response. This represents a promising approach to attain a functional cure for chronic hepatitis B.
An International Survey on Grading, Diagnosis, and Management of Immune Effector Cell-Associated Hematotoxicity (ICAHT) Following CAR T-cell Therapy on Behalf of the EBMT and EHA
Authors: Rejeski Kai , Greco Raffaella , Onida Francesco , Sánchez-Ortega Isabel , Bonini Chiara , Sureda Anna , Gribben John G. , Yakoub-Agha Ibrahim , Subklewe Marion
Published: April 2023

Hematological toxicity represents the most common grade ≥3 toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, its underlying pathophysiology is incompletely understood and its grading and management remains ill-defined. To inform the forthcoming European Hematology Association/European Society for Blood and Marrow Transplantation (EHA/EBMT) guidelines on the management of “immune effector cell-associated hematotoxicity” (ICAHT), we undertook a survey of experienced clinicians using an online survey focusing on (1) grading, (2) risk-stratification and diagnostic work-up, (3) short-term, and (4) long-term management of ICAHT. There were 81 survey respondents across 18 countries. A high degree of variability was noted for cytopenia grading in regards to depth, duration, and time from CAR-T infusion. The majority of experts favored pre-CAR-T bone marrow studies, especially in case of a high-risk profile. Most respondents felt that the work-up for patients with severe hematotoxicity should rule-out viral infections (96%), substrate deficiency (80%), or coincident sHLH/MAS (serum ferritin, 92%), and should include bone marrow aspiration (86%) and/or biopsy (61%). Clinicians were divided as to whether the occurrence of coincident immunotoxicity should influence the decision to apply G-CSF, and when to initiate G-CSF support. In case of prolonged thrombocytopenia, most survey participants favored thrombopoietin agonists (86%). Conversely, autologous hematopoietic cell boosts represented the preferred choice for neutropenia (63%), although they were frequently not available and no consensus was reached regarding the optimal trigger point. These findings underline the current heterogeneity of practice patterns regarding ICAHT and invite the development of consensus guidelines, which may harmonize grading, establish standard operating procedures for diagnosis, and set management guidelines.
A CASE OF RETINAL ATHEROSCLEROTIC OXALOSIS DUE TO HYPEROXALURIA IN A PATIENT WITH SHORT GUT SYNDROME
Authors: Lee Stacey , Malbin Brett , Alfaro Cesar , Syeda Sarah , Lin Xihui
Published: April 2023

Purpose:

To describe a severe case of crystalline retinopathy secondary to hyperoxaluria from short gut syndrome.

Methods:

Case report.

Results:

A 62-year-old Caucasian woman with short gut syndrome and end-stage renal disease from renal oxalosis presented with chronic bilateral vision loss. She had previously been treated for presumed occlusive vasculitis. Visual acuity on initial examination was 20/400 right eye and 20/100 left eye with an afferent pupillary defect of the right eye. Examination revealed attenuated retinal vasculature and diffuse crystalline infiltration of retinal arterial lumina and throughout the retinas bilaterally. Optical coherence tomography revealed inner retinal atrophy with crystalline deposition in the inner retinal layers. Fluorescein angiography demonstrated delayed vascular filling and dropout consistent with severe ischemic vasculopathy. It was concluded that the short-gut syndrome led to overabsorption of oxalate with subsequent hyperoxaluria leading to retinal atherosclerotic oxalosis.

Conclusion:

Retinal calcium oxalate deposits due to hyperoxaluria have been previously noted; however, this degree of severe retinal vascular infiltration has not been described. Our patient was receiving hemodialysis, which is associated with high rebound increases in systemic oxalate concentrations. It is important to keep hyperoxaluria in mind as a potential cause of retinopathy in patients with end-stage renal disease presenting with vision loss.
INCIDENCE OF AKREOS AO60 INTRAOCULAR LENS OPACIFICATION AFTER CONCURRENT OR SUBSEQUENT INTRAOCULAR OIL OR GAS USE
Authors: Padidam Sneha , Rougraff Nicholas , Melamud Alexander , Levinson Joshua D.
Published: April 2023

Purpose:

The purpose of this study was to report the incidence of opacification in a consecutive series of 10 eyes that underwent scleral-fixated Akreos AO60 placement with concurrent or subsequent contact with gas or silicone oil.

Methods:

This was a consecutive case series.

Results:

Three cases of intraocular lens (IOL) opacification were noted. Two cases of opacification occurred in patients who underwent subsequent retinal detachment repair with C3F8 and one with silicone oil. One patient underwent explanation of the lens because of visually significant opacification.

Conclusion:

Scleral fixation of the Akreos AO60 IOL is associated with risk of IOL opacification when exposed to intraocular tamponade. Although surgeons should consider the risk of opacification in patients at high risk of requiring intraocular tamponade, only 1 in 10 patients developed IOL opacification significant enough to require explantation.
RETINAL PIGMENT EPITHELIUM APERTURE PRECEDING COLLAPSE OF VASCULAR AND AVASCULAR PIGMENT EPITHELIAL DETACHMENTS SECONDARY TO AGE-RELATED MACULAR DEGENERATION
Authors: Girgis Jessica M. , Liu Yingna , Liang Michelle C. , Baumal Caroline R. , Duker Jay S. , Waheed Nadia K.
Published: April 2023

Purpose:

To describe retinal pigment epithelium (RPE) aperture preceding the collapse of RPE detachments (RPEDs) in eyes with neovascular and nonneovascular age-related macular degeneration (AMD).

Methods:

Medical records from five patients with RPE aperture associated with vascular and avascular RPEDs were reviewed between 2010 and 2021 at the New England Eye Center at Tufts Medical Center. Main outcome measures were analysis of RPE aperture characteristics and temporal course of RPED collapse.

Results:

Retinal pigment epithelium apertures were identified in six eyes from five women (mean age of 72.6 years). Two eyes had neovasacular AMD and four eyes had nonneovascular AMD. The RPE aperture initially appeared as a discontinuity at the apex of the RPED without rippling or retraction. Each aperture was associated with hypertransmission of optical coherence tomography signal into the choroid as well as hyperreflective foci. The mean time between the appearance of the RPE aperture and near-complete collapse of the RPED was 9 months. After RPED collapse, one eye developed choroidal neovascularization, three eyes progressed to geographic atrophy, one eye had recurrence of the RPED, and one eye remained unchanged.

Conclusion:

Retinal pigment epithelium aperture is a characteristic optical coherence tomography finding that can be observed in avascular or vascularized RPED secondary to AMD. Retinal pigment epithelium apertures precede RPED collapse, which are most likely to occur within 9 months of RPE aperture detection.
Slovenian Version of the Drug-Induced Extrapyramidal Symptoms Scale
Authors: Senica Nina , Aleksic Branko , Inada Toshiya , Iljes Anja Plemenitas , Zamuda Tilen , Kumperscak Hojka Gregoric
Published: April 2023

Aim

The Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) is a multidimensional rating scale for the assessment of drug-induced extrapyramidal symptoms (EPS), developed in 1994. It is suitable for evaluating EPS considering the degree of influence EPS has on daily activities and the subjective distress that it causes.

Method

This study to evaluate the interrater and test-retest reliability of the DIEPSS Slovenian version conducted at the University Medical Center Maribor in Slovenia in November 2018.

Results

Six raters performed the interrater assessment of 135 DIEPSS video clips with recordings of patients with EPS. A second assessment was then performed by 2 raters to evaluate the test-retest reliability, which was high (interclass correlation coefficients from 0.743 to 0.936).

Conclusions

The results for the Slovenian language version of the DIEPSS show high interrater and test-retest reliability, with high concordance rates for all evaluated items (interclass correlation coefficient > 0.8).
Does the Implementation of Multidisciplinary Developmental Care Rounds Increase the Utilization of Developmental Caregiving Interventions in the Neonatal Unit?
Authors: Muirhead Renee , Bates Amanda
Published: April 2023

Aims:

The aims of this project were to improve the utilization of developmental care practices in the neonatal unit and to increase opportunities for parental involvement in the planning and provision of caregiving.

Methods:

This implementation project was conducted in a 79-bed neonatal tertiary referral unit in Australia. A pre/postimplementation survey design was utilized. A preimplementation survey was conducted to collect data on staff's perceived perception of developmental care practices. Following analysis of the data, a process for multidisciplinary developmental care rounds was developed and then implemented across the neonatal unit. A postimplementation survey was then conducted to evaluate whether staff perceived any changes in developmental care practices. The project was conducted over 8 months.

Results:

A total of 97 surveys (pre: n = 46/post: n = 51) were received. Differences were demonstrated in staff's perceived perception of developmental care practices between the pre- and postimplementation periods in 6 themes of developmental care practice. Identified areas of improvement included the use of the 5-step dialogue, encouragement of parents to contribute to care planning, availability of a well-defined care plan for parents to visualize and document caregiving activities, increased use of swaddled bathing, side-lying position for nappy changes, consideration of infants sleep state before caregiving, and increased use of skin-to-skin therapy for management of procedural pain.

Conclusion:

Despite the majority of staff members who participated in both surveys acknowledging the importance of family-centered developmental care practice on neonatal outcomes, their use in clinical care is not always considered or practiced. Although it is reassuring to see improvements in several areas of developmental care postimplementation of the developmental care rounds, continued awareness and reinforcement of developmental neuroprotective caregiving strategies through initiatives such as a multidisciplinary care rounds are warranted.
Evaluation of Online Distant Synchronous Interprofessional Simulations
Authors: Perry Audrey , Andrighetti Tia
Published: April 2023

Introduction:

Formative interprofessional education is an accreditation standard for health professional student populations. This study examined the perception of midwifery students and obstetrics and gynecology (OB-GYN) residents participating in distance synchronous interprofessional simulation.

Methods:

Students participated in an interprofessional simulation in an interactive video conferencing environment. Participants were midwifery students and OB-GYN residents from unaffiliated, geographically distant educational programs. Students' feedback was collected with a survey after the simulation session.

Results:

Eighty-six percent of midwifery students strongly agreed they felt better prepared for team-based care in future practice after the simulation, whereas 59% of OB-GYN students strongly agreed. Seventy-seven percent of midwifery students strongly agreed they were more clear on the scope of practice of the other profession after the simulation, whereas 53% of OB-GYN students strongly agreed. Eighty-seven percent of midwifery students and 74% of OB-GYN residents strongly agreed the distance synchronous simulation was a positive learning experience.

Discussion:

This study demonstrated that midwifery students and OB-GYN residents valued the experience of distance synchronous interprofessional education. Most learners reported feeling better prepared for team-based care and gained a better understanding of each other's scope of practice. Distance synchronous simulations can increase midwifery students' and OB-GYN residents' access to interprofessional education.
Home monitoring in asthma: towards digital twins
Authors: Drummond David , Roukema Jolt , Pijnenburg Mariëlle
Published: April 2023

Purpose of review

We highlight the recent advances in home monitoring of patients with asthma, and show that these advances converge towards the implementation of digital twin systems.

Recent findings

Connected devices for asthma are increasingly numerous, reliable and effective: new electronic monitoring devices extend to nebulizers and spacers, are able to assess the quality of the inhalation technique, and to identify asthma attack triggers when they include a geolocation function; environmental data can be acquired from databases and refined by wearable air quality sensors; smartwatches are better validated. Connected devices are increasingly integrated into global monitoring systems. At the same time, machine learning techniques open up the possibility of using the large amount of data collected to obtain a holistic assessment of asthma patients, and social robots and virtual assistants can help patients in the daily management of their asthma.

Advances in the internet of things, machine learning techniques and digital patient support tools for asthma are paving the way for a new era of research on digital twins in asthma.
Overcoming social appearance anxiety among children affected by congenital physical differences
Authors: de Reviers Béatrice , de Vries Herman
Published: April 2023

Purpose of review

How can we effectively help children with congenital physical differences and their parents in adapting to their situation and overcome social appearance anxiety? How can we improve their self-efficacy in social situations and relationships, as well as increase their self-esteem and self-confidence, which are foundations of assertiveness?

Recent findings

Several studies have examined the coping skills variability between children. Researchers have attempted to identify the discriminating factors of these differences. Standardized programmes combining Cognitive Behavioural Therapy (CBT) and Social Skills Training (SST) have been developed, but recent studies question their effectiveness. Research is now focusing on third-wave CBT that is promoted actively despite insufficient evidence.

Close examination of the mechanisms by which children develop social appearance anxiety shows that exposure and assertiveness training are key therapeutic tools. As with any other type of social anxiety, exposure allows these children to experience and learn positive, value-enhancing social relationships, in spite of their differences. SST creates a well tolerated exposure environment for whichever kind of curiosity the child may encounter. Therapeutic support requires continued individualized readjustment and a complete understanding of the child's personal history, the complex system in which they are developing, and the mechanisms involved. We suggest to formulate for each child a personalized ‘Global Theory’, which integrates history and detailed functional analyses.
Predictors of Central Vascular Access Device Bloodstream Infections in Patients With Acute Leukemia and Neutropenia
Authors: Joslyn Delight , Saber Deborah A. , Miles Patricia
Published: April 2023

Central vascular access devices (CVADs) are standard for the treatment of leukemia. The objectives of this study were to examine predictors for central line-associated bloodstream infection (CLABSI) and causative microorganisms. A retrospective case/control design was used to examine electronic health records (EHRs) of patients with acute leukemia, a CVAD, and neutropenia. Variables were examined for differences between those who developed bacteremia (cases: n = 10) and those who did not (controls: n = 13). Variables included conditions of health (eg, patient history, laboratory results at the time of nadir, nutritional intake during hospitalization, and CVAD care practices). Fisher exact and Mann-Whitney U tests were used for comparison. Nine organisms were identified, including viridans group streptococci (20%) and Escherichia coli (20%). No statistical differences in variables were found between groups. However, over 50% of the nutritional intake data was missing due to lack of documentation. These findings indicate that further study is needed to examine barriers for electronic documentation. The data collection site found opportunities to improve patient care that included education regarding the daily care of CVADs, collaboration with nutritional services to ensure accurate assessments, and coordination with clinical information systems to improve clinical documentation compliance.
Nursing Practices and Sensitive Outcomes Related to Peripheral Intravenous Catheterization in Portugal
Authors: Santos-Costa Paulo , Paiva-Santos Filipe , Sousa Liliana B. , Bernardes Rafael A. , Ventura Filipa , Salgueiro-Oliveira Anabela , Parreira Pedro , Vieira Margarida , Graveto João
Published: April 2023

Implementation of evidence-based practice (EBP) is essential for ensuring high-quality nursing care. In Portugal, nurses are responsible for care delivery to patients who require peripheral intravenous access. However, recent authors emphasized the predominance of a culture based on outdated professional vascular access practices in Portuguese clinical settings. Thus, the aim of this study was to map the studies conducted in Portugal on peripheral intravenous catheterization. A scoping review was conducted based on the Joanna Briggs Institute recommendations, with a strategy adapted to different scientific databases/registers. Independent reviewers selected, extracted, and synthesized the data. Of the 2128 studies found, 26 were included in this review, published between 2010 and 2022.

Previous research shows that Portuguese nurses' implementation of EBP was found to be relatively low overall, while most studies did not attempt to embed EBP change into routine care. Although nurses are responsible for implementing EBP at an individual patient level, the studies conducted in Portugal report nonstandardized practices among professionals, with significant deviations from recent evidence. This reality, combined with Portugal's absence of government-endorsed evidence-based standards for peripheral intravenous catheter (PIVC) insertion and treatment and vascular access teams, may explain the country's unacceptably high incidence of PIVC-related complications reported over the last decade.
Challenges with Breastfeeding
Authors: Mahurin-Smith Jamie
Published: April 2023

Background and Significance:

Breastfeeding problems are common; however, health care providers vary widely in their ability to address them effectively.

Purpose:

The purpose of this study was to identify the relative frequencies of common breastfeeding challenges and their associations with maternal well-being.

Study Design and Methods:

Women completed an online survey in which they described breastfeeding problems. Factor analysis was used to identify problems that co-occurred frequently, as well as the problems most strongly associated with maternal distress, maternal perceptions of greater severity, and postpartum depression or postpartum anxiety.

Results:

There were 535 responses to the online survey; of these, 457 answered the question about the nature of their breastfeeding difficulties. Pain with breastfeeding was the most common breastfeeding problem. Difficulties with milk supply and milk intake were most strongly associated with heightened maternal distress and perceptions of severity.

Clinical Implications:

Coordinated care for breastfeeding dyads, in which providers acknowledge the complex and reciprocal nature of many breastfeeding problems, has the potential to improve maternal satisfaction with breastfeeding as well as breastfeeding metrics.
The Role of Nurses in Fetal Cardiology Programs
Authors: Butler Mary , McArthur Erin C.
Published: April 2023

Background:

Fetal cardiology programs are evolving quickly and include multiple interdisciplinary health care professionals whose roles could benefit from clear definition. Nurses provide an essential function in this field; however, descriptions or definitions of nursing practice, education and knowledge requirements, and responsibilities are limited and vary across institutions and disciplines.

Purpose:

To conduct an integrative review summarizing the literature to determine the role of nurses in fetal cardiology programs.

Methods:

We conducted an integrative review as per Whittemore and Knafl's (2005) methodology of current literature to reveal strengths and opportunities in describing nursing practice as fetal cardiology nurses. The search strategy included five electronic databases: CINAHL, Medline, PsycINFO, Web of Science, and Google Scholar. Peer-reviewed English-language articles discussing nursing practices in fetal cardiology published between 2015 and 2022 were selected. Data extraction and analysis were completed on a final sample of 26 articles.

Results:

Four themes were identified on fetal cardiac nursing practice from nursing and medical perspectives: multidisciplinary key team member, psychosocial family support and counselor, coordinator or navigator, and role description.

Clinical Implications:

More discussion in the literature is needed to better understand and define fetal cardiac nursing practice. Although most experts agree nurses are an important member of the interdisciplinary fetal cardiology team, their roles and educational requirements are poorly described and defined. Quality metrics and benchmarks are needed to ensure safe and effective fetal cardiology care.
Psychometric Testing of a Tool to Assess Midwifery Clinical Educator Skill Acquisition
Authors: Sebach Aaron M.
Published: April 2023

Background:

Midwifery clinical educators balance expertise in clinical practice and academia.

Purpose:

The purpose of this cross-sectional study was to assess midwifery clinical educator skill acquisition and psychometric properties of the Academic Clinical Nurse Educator Skill Acquisition Tool (ACNESAT) with midwifery clinical educators.

Methods:

A convenience sample of 143 educators completed the 40-item ACNESAT aligned with the National League for Nursing academic clinical nurse educator competencies.

Results:

Participants reported extreme confidence overall with ACNESAT items (M = 168.99, SD = 23.61), highest confidence with Ensures Safe Care is Delivered by Learners in the Clinical Setting (M = 4.51, SD = 0.659), and lowest with Applies Theory to Clinical Practice During Clinical Nursing Education Experiences (M = 4.01, SD = 0.934).

Conclusions:

Academic leaders are empowered to utilize the ACNESAT to personalize clinical educator orientation programs with targeted professional development activities.
Calcified Chondroid Mesenchymal Neoplasm
Authors: Kallen Michael E. , Michal Michael , Meyer Anders , Suster David I. , Olson Nicholas J. , Charville Gregory W. , Perret Raul , Gross John M.
Published: April 2023

Calcified chondroid mesenchymal neoplasm is a term proposed for tumors with a spectrum of morphologic features, including cartilage/chondroid matrix formation, that frequently harbor FN1 gene fusions. We report a series of 33 cases of putative calcified chondroid mesenchymal neoplasms, mostly referred for expert consultation out of concern for malignancy. Patients included 17 males and 16 females, with a mean age of 51.3 years. Anatomic locations include the hands and fingers, feet and toes, head and neck, and temporomandibular joint; 1 patient presented with multifocal disease. Radiologic review showed soft tissue masses with variable internal calcification, which occasionally scalloped bone but in all cases appeared indolent/benign. Tumors had a mean gross size of 2.1 cm and a homogenous rubbery to fibrous/gritty tan-white cut surface. Histology demonstrated multinodular architecture with a prominent chondroid matrix and increased cellularity towards the periphery of the nodules. The tumor cells were polygonal with eccentric nuclei and bland cytologic features and showed a variable amount of increased spindled / fibroblastic forms in the perinodular septa. The majority of cases had notable grungy and/or lacy calcifications. A subset of cases demonstrated at least focal areas of increased cellularity and osteoclast-like giant cells. Herein, we confirm the distinct morphologic and clinicopathologic features associated with this entity with the largest series to date, with a focus on practical diagnostic separation from similar chondroid neoplasms. Awareness of these features is critical in avoiding pitfalls, including a malignant diagnosis of chondrosarcoma.
Centrifugal or Roller Blood Pumps for Neonatal Venovenous Extracorporeal Membrane Oxygenation: Extracorporeal Life Support Organization Database Comparison of Mortality and Morbidity
Authors: Ündar Akif , Kunselman Allen R. , Barbaro Ryan P. , Alexander Peta , Patel Krishna , Thomas Neal J.
Published: April 2023

OBJECTIVES:

To investigate outcomes associated with conventional roller or centrifugal pumps during neonatal venovenous extracorporeal membrane oxygenation (ECMO). Our primary hypothesis is that in comparison with conventional roller-pump support, centrifugal pump use is associated with greater odds of survival. Our secondary hypothesis is that centrifugal pump use is associated with lesser odds of complications.

DESIGN:

Retrospective cohort identified using the Extracorporeal Life Support Organization (ELSO) registry 2016 to 2020 dataset.

SETTING:

All ECMO centers reporting to the ELSO registry.

PATIENTS:

All neonates (≤ 28 d) supported with venovenous ECMO and cannulated via right internal jugular vein using dual-lumen venovenous cannulas and polymethyl pentene membrane oxygenators.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 612 neonates (centrifugal, n = 340; conventional roller, n = 272) were included in the analysis. Using a multivariable logistic regression model, centrifugal pump use—as opposed to roller pump use—was associated with lesser odds of survival (odds ratio [OR], 0.53; 95% CI, 0.33–0.84; p < 0.008). Thrombosis and clots in the circuit components were also associated with lesser odds of survival (OR, 0.28; 95% CI, 0.16–0.60; p < 0.001). We failed to show that hemolysis was an independent variable for survival (OR, 0.60; 95% CI, 0.31–1.19; p = 0.14). The primary diagnosis of neonatal aspiration/meconium aspiration is associated with more than seven-fold greater odds of survival (OR, 7.57; 95% CI, 4.02–15.74; p < 0.001).

CONCLUSIONS:

Contrary to our hypotheses, conventional roller pump use was associated with greater odds of survival. While thrombosis and clots in circuit components were independent variables for lesser odds of survival, further research is needed better to understand the use of centrifugal pumps in neonatal practice.
Textured versus Smooth Tissue Expanders: a Comparison of Complications in 3,526 Breast Reconstructions
Authors: Nelson Jonas A. , Rubenstein Robyn N. , Vorstenbosch Joshua , Haglich Kathryn , Poulton Richard T. , McGriff De’von , Stern Carrie S. , Coriddi Michelle , Cordeiro Peter G. , McCarthy Colleen M. , Disa Joseph J. , Mehrara Babak J. , Matros Evan
Published: April 2023

Background:

Increased understanding of breast implant-associated anaplastic large cell lymphoma(BIA-ALCL) has led to a shift away from textured breast devices. Few small studies have compared the complication rates of textured and smooth tissue expanders(TEs). The aim of this study was to compare complication profiles in patients undergoing two-stage post-mastectomy breast reconstruction with either textured or smooth TEs.

Methods:

We performed a retrospective review of female patients who underwent immediate breast reconstruction with textured or smooth TEs from 2018 to 2020 at our institution. Rates of seroma, infection/cellulitis, malposition/rotation, exposure, and TE loss were analyzed in the overall cohort and subgroups undergoing prepectoral and subpectoral TE placement. A propensity score matched analysis was used to decrease the effects of confounders comparing textured and smooth TEs.

Results:

We analyzed 3,526 TEs(1,456 textured; 2,070 smooth). More frequent use of acellular dermal matrix(ADM), SPY angiography, and prepectoral TE placement was noted in the smooth TE cohort(p<0.001). Univariate analysis suggested higher rates of infection/cellulitis, malposition/rotation, and exposure in smooth TEs(all p<0.01). Rates of TE loss did not differ. After propensity matching, no differences were noted in infection or TE loss. Prepectoral smooth expanders had increased rates of malposition/rotation.

Conclusions:

TE surface type did not affect rates of TE loss, though increased rates of expander malposition were noted in the smooth prepectoral cohort. Further research is needed to examine BIA-ALCL risk with temporary textured TE exposure to improve decision-making.
Two-Stage Implant-Based Breast Reconstruction Using Intraoperative Fluorescence Imaging: A Propensity Score-Matched Analysis
Authors: Escandón Joseph M. , Christiano Jose G. , Gooch Jessica C. , Olzinski Ann Therese , Prieto Peter A. , Skinner Kristin A. , Langstein Howard N. , Manrique Oscar J.
Published: April 2023

Background:

Limited comparability between study groups can generate significant selection and observer bias when evaluating the efficacy of SPY system and fluorescence imaging for implant-based breast reconstruction (IBBR). Herein, we compared the surgical outcomes and complications during the first stage of reconstruction between reconstructions intraoperatively evaluated with fluorescence imaging using the SPY system and clinical assessment using a matched analysis.

Methods:

We conducted a retrospective review of patients undergoing total mastectomy and immediate two-stage IBBR with TEs during January 2011 and December 2020. The rate of complication, time for TE-to-implant exchange, and time to start radiotherapy were compared between groups (intraoperative fluorescence imaging versus clinical assessment) using a propensity score-matched analysis.

Results:

After propensity score matching, 198 reconstructions were evaluated. Ninety-nine reconstructions in each group. The median time for TE-to-implant exchange (140-days versus-185 days p=0.476) and time to initiate adjuvant radiotherapy (144-days versus 98-days,p=0.199) were comparable between groups. The 30-day rate of wound-related complications (21% versus 9%, p=0.017) and 30-day rate of wound-related unplanned interventions were significantly higher in reconstructions evaluated with clinical assessment when compared to SPY system (16% versus 5%, p=0.011). A higher 30-day rate of seroma (19% versus 14%, p=0.041) and hematoma (8% versus 0%, p=0.004) were found in reconstructions intraoperatively assessed with SPY.

Conclusion:

After matching, reconstructions evaluated with fluorescence imaging exhibited a lower incidence of early wound-related complications when compared to clinical evaluation alone. Nonetheless, the wise pattern for mastectomy was found to be the only independent predictor associated with early wound-related complications.
Injectable Cartilage Microtissue Regenerated by Autologous Chondrocytes for Nasal Augmentation: A 5-Year Follow-Up Study
Authors: Li Dan , Yin Zongqi , Liu Yu , Li Xin , Dong Wei , Zhang Chen , Ma Jiguang , Zhou Guangdong , Zhang Yixin , Cao Yilin
Published: April 2023

Background:

A lack of ideal filling materials is a critical limitation in current rhinoplasty. Cartilage sheet regeneration by autologous chondrocytes is expected to provide an ideal source of material. However, the inability to perform minimally invasive transplantation of cartilage sheets has greatly limited the clinical application of this material. In this article, the authors propose the concept of injectable cartilage microtissue (ICM) based on cartilage sheet technology, with the aim of achieving minimally invasive augmentation rhinoplasty in clinical practice.

Methods:

Approximately 1.0 cm2 of posterior auricular cartilage was collected from 28 patients. Isolated chondrocytes were expanded, then used to construct autologous cartilage sheets by high-density seeding and in vitro culture in chondrogenic medium with cytokines (eg, transforming growth factor beta-1 and insulin-like growth factor-1) for 3 weeks. Next, ICM was prepared by granulation of the cartilage sheets; it was then injected into a subcutaneous pocket for rhinoplasty.

Results:

ICM was successfully prepared in all patients, and its implantation efficiently raised the nasal dorsum. Magnetic resonance imaging confirmed that regenerative tissue was present at the injection site; histologic examinations demonstrated mature cartilage formation with typical cartilage lacunae and abundant cartilage-specific deposition of extracellular matrix. Excellent or good postoperative patient satisfaction results were achieved in 83.3% of patients over 5 years of follow-up. Obvious absorption of grafts occurred in only two patients (8.3%).

Conclusions:

These results demonstrated that ICM could facilitate stable cartilage regeneration and long-term maintenance in the human body; the implantation of ICM enabled natural augmentation of the depressed nasal dorsum.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Indole-3-Propionic acid, A Gut Microbiota Metabolite, Protects Against the Development of Postoperative Delirium
Authors: Zhou Xue , Wu Xinbo , Wu Yan , Yang Liuyue , Shi Eleanor , Ding Weihua , Chen Liang , Shi Xu , Feng Xia , Su Chienwen , You Zerong , Xia Jianguo , Chen Cynthia , Yeliseyev Vladimir , Bry Lynn , Xia Suyun , Huang Peigen , Meng Jiawei , Houle Timothy , Akeju Oluwaseun , Mao Jianren , Gerszten Robert , Chen Qian , Xie Zhongcong , Shen Shiqian
Published: April 2023

Objective:

Determine preoperative gut microbiota metabolites that may be associated with postoperative delirium (POD) development in patients and further study in rodents.

Summary Background Data:

POD occurs in 9-50% of older patients undergoing anesthesia/surgery but lacks effective treatments or prevention. High throughput metabolomics using liquid chromatography with tandem mass spectrometry have accelerated disease-related biomarkers discovery. We performed metabolomic studies in humans to identify potential metabolite biomarkers linked to POD and examined potential mechanisms in rodents.

Methods:

We performed a prospective observational cohort study to examine the metabolomic changes that were associated with the development of POD. Then the gut microbiota-related metabolomic changes were recapitulated by gut microbiota perturbation in rodents. POD was assessed in mice using a battery of behavioral tests including novel objective test, Y maze test, open field test, and buried food test. The mechanisms through which gut microbiota-related metabolomic changes influenced POD were examined using chemogenetics.

Results:

IPA is a gut microbiota metabolite that belongs to the indole family. Baseline plasma levels of IPA were significantly inversely correlated with the onset of POD in 103 (17 cases) human individuals. This relationship was validated in preclinical mouse models for POD: reducing IPA levels through gut microbiota perturbation promoted POD-like behavior. More importantly, IPA administration deterred POD-like behavior. Colonization of germ-free mice with mutant Clostridium sporogenes that did not produce IPA promoted POD-like behavior. Chemogenetic studies revealed that the protective effect of IPA in mice was mediated, in part, by peroxisome proliferator-activated receptor gamma coactivator 1-alpha in hippocampal interneurons.

Conclusions:

Gut microbiota-derived IPA is an important molecule implicated in the pathogenesis of POD, which could potentially be harnessed for POD prevention. (270 words)
Ethanol depresses neurons in the lateral parabrachial nucleus by potentiating pre- and postsynaptic GABAA receptors
Authors: Liu Shengjun , Xia Rongping , Hong Zongyuan , Li Jing , Wang Fang , Jiang Junjie , Wang Facai , Shen Bingxiang
Published: April 2023

As a psychoactive substance, ethanol is widely used in people’s life. However, the neuronal mechanisms underlying its sedative effect remain unclear. In this study, we investigated the effects of ethanol on the lateral parabrachial nucleus (LPB), which is a novel component related to sedation. Coronal brain slices (280 μm thick) containing the LPB were prepared from C57BL/6J mice. The spontaneous firing and membrane potential of LPB neurons, and GABAergic transmission onto these neurons were recorded using whole-cell patch-clamp recordings. Drugs were applied through superfusion. The LPB neurons exhibited a regular spontaneous discharge at a rate of 1.5–3 Hz without burst firing. Brief superfusion of ethanol (30, 60, and 120 mM) concentration-dependently and reversibly suppressed the spontaneous firing of the neurons in LPB. In addition, when synaptic transmission was blocked by tetrodotoxin (TTX) (1 μM), ethanol (120 mM) caused hyperpolarization of the membrane potential. Furthermore, superfusion of ethanol markedly increased the frequency and amplitude of spontaneous and miniature inhibitory postsynaptic currents, which were abolished in the presence of the GABAA receptor (GABAA-R) antagonist picrotoxin (100 μM). In addition, the inhibitory effect of ethanol on the firing rate of LPB neurons was completely abolished by picrotoxin. Ethanol inhibits the excitability of LPB neurons in mouse slices, possibly via potentiating GABAergic transmission onto the neurons at pre- and postsynaptic sites.
Salinimicrobium profundisediminis sp. nov., isolated from deep-sea sediment of the Mariana Trench
Authors: An Yu , Wang Ming-Chen , Su Xiao-Yan , Fan Shen , Lu Jie , Wan Jin-Jian , Xin Yu , Zhang Yu-Zhong , Zhang Xi-Ying , Fu Hui-Hui
Published: April 2023

A Gram-stain-negative, aerobic, rod-shaped, non-gliding bacterial strain, designated as MT39T, was isolated from a deep-sea sediment sample collected from the Mariana Trench. Strain MT39T grew optimally at 35°C and pH 7.0, and could tolerate up to 10% (w/v) NaCl. The strain was positive for catalase and negative for oxidase. The genome of strain MT39T was 4 033 307 bp, with a 41.1 mol % genomic G+C content and 3514 coding sequences. Phylogenetic analysis based on 16S rRNA gene sequences placed strain MT39T within the genus

Salinimicrobium

, showing the highest 16S rRNA gene sequence similarity to Salinimicrobium terrea CGMCC 1.6308T (98.1%). The average nucleotide identity and in silico DNA–DNA hybridization values between strain MT39T and the type strains of seven

Salinimicrobium

species were all less than the threshold values to discriminate bacterial species, indicating that strain MT39T is affiliated with a novel species within the genus. The major cellular fatty acids of strain MT39T were iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0 3-OH. Polar lipids of strain MT39T included phosphatidylethanolamine, one unidentified aminolipid and four unidentified lipids. Menaquinone-6 was the only respiratory quinone in strain MT39T. On the basis of the polyphasic data present in this study, strain MT39T represents a novel species of the genus

Salinimicrobium

, for which the name Salinimicrobium profundisediminis sp. nov. is proposed, with type strain being MT39T (=MCCC 1K07832T=KCTC 92381T).
Lesion-specific suppression of YAP/TAZ by biomimetic nanodrug ameliorates atherosclerosis development
Authors: Huang Hui-Chun , Wang Ting-Yun , Rousseau Joshua , Mungaray Michelle , Michaud Chamonix , Plaisier Christopher , Chen Zhen Bouman , Wang Kuei-Chun
Published: April 2023

Atherosclerosis, characterized by the buildup of lipid-rich plaque on the vessel wall, is the primary cause of myocardial infarction and ischemic stroke. Recent studies have demonstrated that dysregulation of yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) contributes to plaque development, making YAP/TAZ potential therapeutic targets. However, systemic modulation of YAP/TAZ expression or activities risks serious off-target effects, limiting clinical applicability. To address the challenge, this study develops monocyte membrane-coated nanoparticles (MoNP) as a drug delivery vehicle targeting activated endothelium lining the plaque surface and utilizes MoNP to deliver verteporfin (VP), a potent YAP/TAZ inhibitor, for lesion-specific treatment of atherosclerosis. The results reveal that MoNP significantly enhance payload delivery to inflamed endothelial cells (EC) while avoiding phagocytic cells, and preferentially accumulate in atherosclerotic regions. MoNP-mediated delivery of VP substantially reduces YAP/TAZ expression, suppressing inflammatory gene expression and macrophage infiltration in cultured EC and mouse arteries exposed to atherogenic stimuli. Importantly, this lesion-targeted VP nanodrug effectively decreases plaque development in mice without causing noticeable histopathological changes in major organs. Collectively, these findings demonstrate a plaque-targeted and pathway-specific biomimetic nanodrug, potentially leading to safer and more effective treatments for atherosclerosis.
Structure determination of a DNA crystal by MicroED
Authors: Haymaker Alison , Bardin Andrey A. , Gonen Tamir , Martynowycz Michael W. , Nannenga Brent L.
Published: April 2023

Microcrystal electron diffraction (MicroED) is a powerful tool for determining high-resolution structures of microcrystals from a diverse array of biomolecular, chemical, and material samples. In this study, we apply MicroED to DNA crystals, which have not been previously analyzed using this technique. We utilized the d(CGCGCG)2DNA duplex as a model sample and employed cryo-FIB milling to create thin lamella for diffraction data collection. The MicroED data collection and subsequent processing resulted in a 1.10 Å resolution structure of the d(CGCGCG)2DNA, demonstrating the successful application of cryo-FIB milling and MicroED to the investigation of nucleic acid crystals.