bluuebunny/crossref_metadata_2025 huggingface dataset:
S100A4-neutralizing monoclonal antibody 6B12 counteracts the established experimental skin fibrosis induced by bleomycin
Authors: Švec Xiao , Štorkánová Hana , Trinh-Minh Thuong , Tran Manh Cuong , Štorkánová Lenka , Hulejová Hana , Oreská Sabína , Heřmánková Barbora , Bečvář Radim , Pavelka Karel , Vencovský Jiří , Klingelhöfer Jörg , Hussain Rizwan I , Hallén Jonas , Šenolt Ladislav , Distler Jörg H W , Tomčík Michal
Published: June 2023

Objectives

Our previous studies have demonstrated that the Damage Associated Molecular Pattern (DAMP) protein, S100A4, is overexpressed in the involved skin and peripheral blood of patients with SSc. It is associated with skin and lung involvement, and disease activity. By contrast, lack of S100A4 prevented the development of experimental dermal fibrosis. Herein we aimed to evaluate the effect of murine anti-S100A4 mAb 6B12 in the treatment of preestablished experimental dermal fibrosis.

Methods

The effects of 6B12 were assessed at therapeutic dosages in a modified bleomycin-induced dermal fibrosis mouse model by evaluating fibrotic (dermal thickness, proliferation of myofibroblasts, hydroxyproline content, phosphorylated Smad3-positive cell count) and inflammatory (leukocytes infiltrating the lesional skin, systemic levels of selected cytokines and chemokines) outcomes, and transcriptional profiling (RNA sequencing).

Results

Treatment with 7.5 mg/kg 6B12 attenuated and might even reduce pre-existing dermal fibrosis induced by bleomycin as evidenced by reduction in dermal thickness, myofibroblast count and collagen content. These antifibrotic effects were mediated by the downregulation of TGF-β/Smad signalling and partially by reducing the number of leukocytes infiltrating the lesional skin and decrease in the systemic levels of IL-1α, eotaxin, CCL2 and CCL5. Moreover, transcriptional profiling demonstrated that 7.5 mg/kg 6B12 also modulated several profibrotic and proinflammatory processes relevant to the pathogenesis of SSc.

Conclusion

Targeting S100A4 by the 6B12 mAb demonstrated potent antifibrotic and anti-inflammatory effects on bleomycin-induced dermal fibrosis and provided further evidence for the vital role of S100A4 in the pathophysiology of SSc.
Responding to uncertainty in the COVID-19 pandemic: perspectives from Bavaria, Germany
Authors: Fiske Amelia , Lange Johannes , Buyx Alena , McLennan Stuart
Published: June 2023

The 2019 novel coronavirus (COVID-19) pandemic has created unprecedented challenges for policymakers and scientific experts charged with preventing the spread of the virus. In upending the usual mechanisms for political deliberation, the pandemic offers a window into the co-production of governmental policy decisions and scientific evidence. Taking the German state of Bavaria as a case study, this article draws on expert interviews with individuals directly involved in high-level pandemic decision-making to explore the changing relationships between policymakers and scientific experts. The challenges that emerged in the Bavarian context illustrate that while uncertainty has long been understood as constitutive of scientific knowledge, it became a stumbling block for policymakers due to newfound degrees of urgency and implications of decision-making in relation to the pandemic. In order to better address the emergent, evolving problems posed by public health crises, uncertainty must also be understood as formative in the work of policy.
New Technologies Provide Innovative Opportunities to Enhance Understanding of Major Virus Diseases Threatening Global Food Security
Authors: Kreuze Jan F. , Cuellar Wilmer J. , Kumar P. Lava , Boddupalli Prasanna , Omondi Aman B.
Published: June 2023

Plant viruses pose a continuous and serious threat to crop production worldwide, and globalization and climate change are exacerbating the establishment and rapid spread of new viruses. Simultaneously, developments in genome sequencing technology, nucleic acid amplification methods, and epidemiological modeling are providing plant health specialists with unprecedented opportunities to confront these major threats to the food security and livelihoods of millions of resource-constrained smallholders. In this perspective, we have used recent examples of integrated application of these technologies to enhance understanding of the emergence of plant viral diseases of key food security crops in low- and middle-income countries. We highlight how international funding and collaboration have enabled high-throughput sequencing-based surveillance approaches, targeted field and lab-based diagnostic tools, and modeling approaches that can be effectively used to support surveillance and preparedness against existing and emerging plant viral threats. The importance of national and international collaboration and the future role of CGIAR in further supporting these efforts, including building capabilities to make optimal use of these technologies in low- and middle-income countries, are discussed.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Long-term Radiographic and Clinical Outcomes After Selective Thoracic Fusion for Adolescent Idiopathic Scoliosis With Lenke 1C Curve
Authors: Park Se-Jun , Lee Chong-Suh , Park Jin-Sung , Ma Chang-Hyun , Shin Tae Soo , Jeon Chung-Youb
Published: June 2023

Background:

Despite the promising results with selective thoracic fusion (STF) in patients with adolescent idiopathic scoliosis (AIS) of the Lenke 1C curve, postoperative coronal imbalance and progression of the unfused lumbar curve have been concerns in long-term follow-up. In this study, we aimed to investigate the radiographic and clinical outcomes after STF for AIS with Lenke 1C curve with long-term follow-up.

Methods:

A total of 30 patients with AIS with Lenke 1C curves who underwent STF between 2005 and 2017 were included. Minimum follow-up duration was 5 years. Time-dependent changes in radiographic parameters were investigated preoperatively, immediately postoperatively, and at the last follow-up. In addition, radiographic adverse events such as coronal decompensation (CD), lumbar decompensation (LD), distal adding-on (DA) phenomenon, and trunk shift were evaluated at the last follow-up. The Scoliosis Research Society-22 score was used for clinical outcome evaluation.

Results:

The mean age at the time of surgery was 13.8 years. The mean follow-up duration was 6.7 ± 0.8 years. The main thoracic curve significantly improved from 57 degrees to 23 degrees (60% correction), and the thoracolumbar/lumbar curve significantly improved from 47 degrees to 28 degrees (41% correction). Coronal balance was 15 mm after surgery but significantly improved to 10 mm at the last follow-up (P = 0.033). At the final follow-up, 11 patients (37%) sustained at least one of the radiographic adverse events: CD in 5 patients (17%), LD in 3 (10%), DA in 4 (13%), and trunk shift in 3 (10.%). However, there were no cases requiring revision surgery. In addition, there were no significant differences in any items or total Scoliosis Research Society-22 score between the patients with and without radiographic adverse events.

Conclusion:

STF in Lenke 1C curves showed an acceptable risk of adverse radiographic events such as CD, LD, DA, and trunk shift in long-term follow-up. We suggest that STF without fusion to the thoracolumbar/lumbar curve would be sufficient in treating AIS with Lenke 1C curve.

Level of Evidence:

Level III.
Modified Capsulorrhaphy Technique in Open Reduction of Developmental Dysplasia of the Hip
Authors: El-Sayed Mohamed M.H. , Hammad Mostafa E. , Khalifa Ahmed M. , Eltanahy Ahmed F. , Nada Abdullah A.
Published: June 2023

Background:

Neglected patients with developmental dysplasia of the hip (DDH) are not uncommon. Various treatment modalities have been used. Capsulorrhaphy is one of the most critical steps during the process of open reduction of DDH. Inadequate capsulorrhaphy technique can increase the failure rate of open reduction procedures. This study presented the clinical and radiographic results of using a new capsulorrhaphy technique.

Methods:

Between November 2005 and March 2018, 540 DDH in 462 patients were retrospectively reviewed. The mean age at surgery was 31 months. All patients underwent a modified capsulorrhaphy technique developed by the main author (with or without additional pelvic or femoral procedures). Postoperative patient assessment during the follow-up period was performed both clinically and radiologically.

Results:

Follow-up period ranged between 36 months and 12 years. Based on the modified McKay score, good and excellent outcomes were obtained in 90.3%. Functional results were better in younger age (less than 39 mo). Both acetabular index and lateral center edge angle showed significant improvement at 3 years follow-ups. Proximal femoral growth disturbance (PFGD) was encountered in 92 hips. Classes 2 and 3 did not affect the functional results, whereas patients with PFGD classes 4 and 5 had fair to poor functional outcomes. There were 12 hips with redislocation. Revision was done using the same capsulorrhaphy technique.

Conclusion:

Using the index technique of capsulorrhaphy in DDH surgery is safe, reliable, and yields good functional and radiologic outcomes with a relatively low complication rate.

Level of Evidence:

Level IV—therapeutic retrospective case series.
Defining the Incidence of Residual Acetabular Dysplasia After Successful Reduction With a Harness
Authors: Paranjape Chinmay S. , Bomar James D. , Upasani Vidyadhar V.
Published: June 2023

Background:

The purpose of this study was to evaluate the rate of residual acetabular dysplasia (RAD), defined as an acetabular index (AI) of >90th percentile of age and sex-matched controls, in a cohort of infants successfully treated with the Pavlik harness (PH).

Methods:

We retrospectively studied typically developing infants at a single center, with at least 1 dislocated hip, that was successfully treated with a PH and had a minimum of 48 months follow-up. Hip dislocation was defined as <30% femoral head coverage at rest on pretreatment ultrasound or IHDI grade 3 or 4 on the pretreatment radiograph.

Results:

Forty-six dislocated hips (41 infants) were studied (4 males and 37 females). Brace treatment was initiated at an average age of 1.8 months (range: 2 d to 9.3 mo) and was maintained for an average of 10.2 months (range: 2.3 to 24.9 mo). All hips achieved IHDI grade 1 reduction. Five of 46 hips (11%) had an AI >90th percentile at the conclusion of bracing. Average follow-up was 6.5 years (range: 4.0 to 15.2 y). We found a 30% incidence of RAD (14/46 hips) on final follow-up radiographs. Of these hips, 13/14 (93%) had AI <90th percentile at the end of brace treatment. Comparing children with and without RAD, there were no differences in age at the initial visit or brace initiation, total follow-up, femoral head coverage at the initial visit, alpha angle at the initial visit, or total time in the brace (P > 0.09).

Conclusion:

In a single-center cohort of infants with dislocated hips treated successfully with a PH, we observed a 30% incidence of RAD at a minimum 4.0-year follow-up. Normal acetabular morphology at the end of brace treatment did not result in normal acetabular morphology at the final follow-up in 13/41 hips (32%). We recommend that surgeons should pay close attention to the year-over-year change in both the AI and AI percentile.

Level of Evidence:

Level IV: case series.
Preferred Language Mediates Association Between Race, Ethnicity, and Delayed Presentation in Critically Ill Patients With COVID-19
Authors: Kelly Michael S. , Mohammed Adna , Okin Daniel , Alba George A. , Jesudasen Sirus J. , Flanagan Shelby , Dandawate Nupur A. , Gavralidis Alexander , Chang Leslie L. , Moin Emily E. , Witkin Alison S. , Hibbert Kathryn A. , Kadar Aran , Gordan Patrick L. , Bebell Lisa M. , Hauptman Marissa , Valeri Linda , Lai Peggy S.
Published: June 2023

IMPORTANCE:

Which social factors explain racial and ethnic disparities in COVID-19 access to care and outcomes remain unclear.

OBJECTIVES:

We hypothesized that preferred language mediates the association between race, ethnicity and delays to care.

DESIGN, SETTING AND PARTICIPANTS:

Multicenter, retrospective cohort study of adults with COVID-19 consecutively admitted to the ICU in three Massachusetts hospitals in 2020.

MAIN OUTCOME AND MEASURES:

Causal mediation analysis was performed to evaluate potential mediators including preferred language, insurance status, and neighborhood characteristics.

RESULTS:

Non-Hispanic White (NHW) patients (157/442, 36%) were more likely to speak English as their preferred language (78% vs. 13%), were less likely to be un- or under-insured (1% vs. 28%), lived in neighborhoods with lower social vulnerability index (SVI) than patients from racial and ethnic minority groups (SVI percentile 59 [28] vs. 74 [21]) but had more comorbidities (Charlson comorbidity index 4.6 [2.5] vs. 3.0 [2.5]), and were older (70 [13.2] vs. 58 [15.1] years). From symptom onset, NHW patients were admitted 1.67 [0.71–2.63] days earlier than patients from racial and ethnic minority groups (p < 0.01). Non-English preferred language was associated with delay to admission of 1.29 [0.40–2.18] days (p < 0.01). Preferred language mediated 63% of the total effect (p = 0.02) between race, ethnicity and days from symptom onset to hospital admission. Insurance status, social vulnerability, and distance to the hospital were not on the causal pathway between race, ethnicity and delay to admission.

CONCLUSIONS AND RELEVANCE:

Preferred language mediates the association between race, ethnicity and delays to presentation for critically ill patients with COVID-19, although our results are limited by possible collider stratification bias. Effective COVID-19 treatments require early diagnosis, and delays are associated with increased mortality. Further research on the role preferred language plays in racial and ethnic disparities may identify effective solutions for equitable care.
Postoperative Day 1 Discharge in Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction
Authors: Tapp Marion W. , Duet Mary L. , Steele Thomas N. , Gallagher Robert J. , Kogan Samuel , Calder Bennett W. , Robinson J. Michael
Published: June 2023

Background:

With high success rates of autologous breast reconstruction, the focus has shifted from flap survival to improved patient outcomes. Historically, a criticism of autologous breast reconstruction has been the length of hospital stay. Our institution has progressively shortened the length of stay after deep inferior epigastric artery perforator (DIEP) flap reconstruction and began discharging select patients on postoperative day 1 (POD1). The purpose of this study was to document our experience with POD1 discharges and to identify preoperative and intraoperative factors that may identify patients as candidates for earlier discharge.

Methods:

An institutional review board-approved, retrospective chart review of patients undergoing DIEP flap breast reconstruction from January 2019 to March 2022 at Atrium Health was completed, consisting of 510 patients and 846 DIEP flaps. Patient demographics, medical history, operative course, and postoperative complications were collected.

Results:

Twenty-three patients totaling 33 DIEP flaps were discharged on POD1. The POD1 group and the group of all other patients (POD2+) had no difference in age, ASA score, or comorbidities. BMI was significantly lower in the POD1 group (P = 0.039). Overall operative time was significantly lower in the POD1 group, and this remained true when differentiating into unilateral operations (P = 0.023) and bilateral operations (P = 0.01). No major complications occurred in those discharged on POD1.

Conclusions:

POD1 discharge after DIEP flap breast reconstruction is safe for select patients. Lower BMI and shorter operative times may be predictive in identifying patients as candidates for earlier discharge.
Single ethanol binge causes severe liver injury in mice fed Western diet
Authors: Yeh Yu-Te , Wu Xiangdong , Ma Yinyan , Ying Zhekang , He Ling , Xue Bingzhong , Shi Hang , Choi Youngshim , Yu Liqing
Published: June 2023

Background and Aims:

Alcohol-associated liver disease (ALD) and NAFLD often coexist in Western societies that consume energy-rich and cholesterol-containing Western diets. Increased rates of ALD mortality in young people in these societies are likely attributable to binge drinking. It is largely unknown how alcohol binge causes liver damage in the setting of Western diets.

Approach and Results:

In this study, we showed that a single ethanol binge (5 g/kg body weight) induced severe liver injury as shown by marked increases in serum activities of the 2 aminotransferases AST and ALT in C57BL/6J mice that have been fed a Western diet for 3 weeks. The Western diet plus binge ethanol-fed mice also displayed severe lipid droplet deposition and high contents of triglycerides and cholesterol in the liver, which were associated with increased lipogenic and reduced fatty acid oxidative gene expression. These animals had the highest Cxcl1 mRNA expression and myeloperoxidase (MPO)-positive neutrophils in the liver. Their hepatic ROS and lipid peroxidation were the highest, but their hepatic levels of mitochondrial oxidative phosphorylation proteins remained largely unaltered. Hepatic levels of several ER stress markers, including mRNAs for CHOP, ERO1A, ERO1B, BIM, and BIP, as well as Xbp1 splicing and proteins for BIP/GRP78 and IRE-α were also the highest in these animals. Interestingly, Western diet feeding for 3 weeks or ethanol binge dramatically increased hepatic caspase 3 cleavage, and the combination of the 2 did not further increase it. Thus, we successfully established a murine model of acute liver injury by mimicking human diets and binge drinking.

Conclusions:

This simple Western diet plus single ethanol binge model recapitulates major hepatic phenotypes of ALD, including steatosis and steatohepatitis characterized by neutrophil infiltration, oxidative stress, and ER stress.
Rising alcohol-associated liver disease–related mortality rates in the United States from 1999 to 2022
Authors: Ilyas Fariha , Ali Hassam , Patel Pratik , Basuli Debargha , Giammarino Alexa , Satapathy Sanjaya K.
Published: June 2023

We examined trends in alcohol-associated liver disease (ALD)–related mortality in the United States from 1999 to 2022, focusing on sex, racial differences, and specific age groups. We analyzed age-adjusted mortality rates for ALD-related deaths using the CDC WONDER database and assessed differences between sex and racial groups. ALD-related mortality rates increased significantly between 1999 and 2022, with a more pronounced increase in females. White, Asian, Pacific Islander (AAPI), and American Indian or Alaska Native (AI/AN) groups showed significant uptrends in ALD-related mortality, while African Americans (AA) experienced a nonsignificant decline. Age-specific trends revealed substantial increases in crude mortality rates across various age groups, with the largest increase observed in the younger age groups of 25–34 years, with an average percent change of 11.12% from 2006 to 2022 (average annual percent change of 7.1% for the study period), and 35–44 years, which showed an average percent change of 17.2% from 2018 to 2022 (average annual percent change of 3.8% for the study period). This study reveals increased ALD-related mortality rates in the United States from 1999 to 2022, with disparities among sex, racial groups, and younger age groups. Continued monitoring and evidence-based interventions are needed to address the growing burden of ALD-related mortality, particularly in the younger population.
Preparing Clinicians for Roles in Academic Teaching: A Model for Clinical Associated Faculty Development
Authors: Bilyeu Catherine , Reilly Michelle , Niski Jessica
Published: June 2023

Background and Purpose.

Clinical associated faculty (CAF) are typically expert clinicians but novice educators, lacking professional development opportunities targeted to their unique needs. This can result in unnecessary variability in content delivery and potentially negative student learning outcomes. The purpose of this article is to describe the development, implementation, and evaluation of a faculty development program designed specifically for CAF.

Method/Model Description and Evaluation.

Thirty-two CAF completed a longitudinal faculty development program designed by faculty at the University of Colorado Doctor of Physical Therapy Program (CU). Content was driven by faculty development literature, core concepts of CU's Doctor of Physical Therapy (DPT) program, and key constructs for excellence in DPT education. Changes in teaching confidence were examined with a modified version of the Nurse Educator Skill Acquisition Assessment (NESAA) in pre-test/post-test design. Creighton University DPT Program (Creighton) adapted the faculty development program for their own CAF and similarly assessed change in teaching skill in 21 CAF using the NESAA. Additional data were collected through session evaluations and review of student course evaluations for both programs.

Outcomes.

At CU and Creighton, 28 and 21 participants, respectively, completed the CAF development program and all desired outcome measures. Outcomes revealed a significant increase (P < .05) on NESAA scores. In addition, results demonstrated decreased negative student comments related to teaching inconsistencies on course evaluations and an overall positive perception of the program by participants.

Discussion and Conclusion.

A CAF longitudinal faculty development program was developed and successfully implemented at 2 universities. This model could be used as a template by other DPT programs to address the existing faculty development gap and support the distinctive needs of CAF.
Foreign Body Granuloma Originating From the Lateral Process of Malleus: A Case Series of 19 Children
Authors: Mao Yanyan , Li Li , Yan Wenqing , Lu Yanqing , Li Wei , Zheng Jinfeng , Fan Zhaomin , Wang Haibo , Han Yuechen
Published: June 2023

Objective

A special presentation of foreign body granuloma originating from the lateral process of the malleus (FBGLP) was noted in the absence of a history of foreign body entry into the external auditory canal (EAC). This study reported the clinical features, pathology, and prognosis of patients with FBGLP.

Design

Retrospective study.

Setting

Shandong Provincial ENT Hospital.

Patients

Nineteen pediatric patients (age, 1–10 yr) with FBGLP.

Interventions

Clinical data were collected from January 2018 to January 2022.

Main Outcome Measures

Clinicopathologic characteristics of the patients were analyzed.

Results

All patients had an acute course, and were within 3 months of ineffective medical treatment. The most common symptoms were suppurative (57.9%) and hemorrhagic (42.1%) otorrhea. FBGLP imaging examinations demonstrated a soft mass blocking the EAC without bone destruction and occasionally concomitant effusion in the middle ear. The most common pathologic findings were foreign body granuloma (94.7%,18/19), granulation tissue (73.7%, 14/19), keratotic precipitate (73.7%, 14/19), calcium deposition (63.2%, 12/19), hair shafts (47.4%, 9/19), cholesterol crystals (5, 26.3%), and hemosiderin (15.8%, 3/19). Foreign body granuloma and granulation tissue showed higher expression levels of CD68 and cleaved caspase-3 than did the normal tympanic mucosa, whereas Ki-67 levels were similarly low in all tissues. The patients were followed up for 3 months to 4 years without recurrence.

Conclusion

FBGLP is caused by endogenous foreign particles in the ear. We recommend the trans-external auditory meatus approach for FBGLP surgical excision, as this shows promising outcomes.
How Did Adolescents With Cancer Experience the COVID-19 Pandemic? A Report From Italian Pediatric Hematology Oncology Association Centers
Authors: Zucchetti Giulia , Quarello Paola , Ferrari Andrea , Silva Matteo , Mercolini Federico , Sciarra Pierpaolo , Guido Antonella , Peruzzi Laura , Colavero Paolo , Montanaro Maria , Taormina Rino , Micheletti Maria V. , Solari Federica , Perillo Teresa , Paioli Anna , Canepa Monica , Migliozzi Camilla , Zuliani Livia , Solfa Valentina , Bertolotti Marina , Fagioli Franca
Published: June 2023

Purpose:

This study set out to evaluate the psychosocial effects of coronavirus disease 2019 (COVID-19) among adolescents with cancer, and whether these effects are significantly different among adolescents who were undergoing therapy or had completed it.

Materials and Methods:

The AIEOP Adolescents Working Group and the AIEOP Psychosocial Working Group adapted a questionnaire, which was completed by 214 adolescent cancer patients (M
age=16.3 y, range: 15 to 19 y old) treated at 16 AIEOP centers in the North (38%), South (31%), and Center (31%) of Italy.

Results:

The results highlighted that fear of the virus is equally distributed among adolescent cancer patients, with patients being particularly concerned about their parents and families. The adolescents reported that had no difficulty in following individual safety measures: they used personal protective equipment and they were attentive to their own health and adhering to the rules imposed by doctors and the wider community. There are very few, limited differences between adolescents undergoing treatment (active group) and those who have completed treatment (follow-up group). The reminder of their own therapy experience triggered by the use of personal protective equipment, and the more common refusal to follow some restrictions were the only 2 behaviors by which the follow-up group differed significantly from the adolescents in the active group.

Conclusions:

Adolescents with cancer seem to have coped well with the pandemic: although they were very afraid of the virus for themselves and their families, and had to limit their social contact, they did comply with the restrictions. Their experience of cancer probably also had a positive effect in cultivating adolescents who are more responsible and resilient in emergency situations such as the pandemic.
Respiratory Failure Due to Idiopathic Pneumonia Syndrome in a Pediatric Patient After Recipient-derived Allogeneic Chimeric Antigen Receptor T-Cell Therapy
Authors: Zipper Rachelle , Loeb David M. , Lee Michelle A. , Oliver-Krasinski Jennifer , Liszewski Mark C. , Fraint Ellen
Published: June 2023

Idiopathic pneumonia syndrome (IPS) is a life-threatening complication of hematopoietic cell transplantation, but it is not clearly described following chimeric antigen receptor (CAR) T-cell therapy. We describe a child who developed IPS after receiving tisagenlecleucel for post–hematopoietic cell transplantation relapsed acute lymphoblastic leukemia and had a remarkable improvement after treatment with corticosteroids and etanercept. We discuss the implications of cytokine signaling in IPS and immunologic considerations of allogeneic CAR T cells. We anticipate that the incidence of IPS and other allogeneic phenomena will be observed more often as allogeneic CAR T cells are employed in more varied settings with more mismatched donors.
The Impact of Proactive Gastrostomy Tube Placement on Treatment-related Outcomes in Young Children With High-grade Central Nervous System Tumors
Authors: Kotch Chelsea , Elgarten Caitlin W. , McWhorter Jessica , Schmus Cynthia , Wilhelm Darielle , Li Yimei , Minturn Jane E.
Published: June 2023

Young children undergoing treatment with intensive chemotherapy for high-grade central nervous system (CNS) tumors are at risk for malnutrition, yet no guidelines exist for the placement of enteral tubes. Prior studies evaluated the impact of proactive gastrostomy tube (GT) placement with a narrow scope of outcomes, such as weight. To examine the impact of proactive GT on comprehensive treatment outcomes, we performed a single-center, retrospective study of children younger than 60 months of age with high-grade CNS tumors treated per CCG99703 or ACNS0334 between 2015 and 2022. Of 26 patients included, 9 (35%) underwent proactive GT, 8 (30%) had rescue GT, and 9 (35%) had a nasogastric tube (NGT). Clinically significant weight loss occurred in 47% of patients with NGT during induction compared with 22% with proactive GT (P = 0.274); however, between cohorts, there was no significant difference in antibiotic or parenteral nutrition utilization, weight loss at therapy completion, and duration of hospitalization. Therefore, proactive GT placement was modestly effective at preventing significant weight loss during induction, however, there was no clear benefit for hospitalization duration, antibiotic, or parental nutrition requirements compared with NGT. We recommend an individualized approach to GT placement for young children with CNS malignancies undergoing intensive chemotherapy.
Utility of a PAX2, PTEN, and β-catenin Panel in the Diagnosis of Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia in Endometrial Polyps
Authors: Lucas Elena , Niu Shuang , Aguilar Mitzi , Molberg Kyle , Carrick Kelley , Rivera-Colon Glorimar , Gwin Katja , Wang Yan , Zheng Wenxin , Castrillon Diego H. , Chen Hao
Published: June 2023

The diagnosis of atypical hyperplasia/endometrioid intraepithelial neoplasm (AH/EIN) within endometrial polyps (EMPs) often poses a diagnostic conundrum. Our previous studies demonstrated that a panel of immunohistochemical (IHC) markers consisting of PAX2, PTEN, and β-catenin can be effectively utilized for the identification of AH/EIN. A total of 105 AH/EIN within EMP were analyzed using the 3-marker panel. We also evaluated these cases for the presence of morules. Benign EMP (n=90) and AH/EIN unassociated with polyp (n=111) served as controls. Aberrant expression of PAX2, PTEN, or β-catenin was observed in AH/EIN in EMP in 64.8%, 39.0%, and 61.9% of cases, respectively. At least 1 IHC marker was abnormal in 92.4% of cases. Overall, 60% of AH/EIN in EMP demonstrated abnormal results for≥2 IHC markers. The prevalence of PAX2 aberrancy was significantly lower in AH/EIN in EMP than in nonpolyp AH/EIN (64.8% vs. 81.1%,P=0.007), but higher than in benign EMP (64.8% vs. 14.4%,P<0.00001). The prevalence of β-catenin aberrancy was significantly higher in AH/EIN in EMP than in nonpolyp AH/EIN (61.9% vs. 47.7%,P=0.037). All control benign EMP demonstrated normal expression of PTEN and β-catenin. Morules were present in 38.1% of AH/EIN in EMP versus 24.3% in nonpolyp AH/EIN, and absent in benign EMP. A strong positive association was found between β-catenin and morules (Φ=0.64). Overall, 90% cases of atypical polypoid adenomyoma (n=6) and mucinous papillary proliferation (n=4) showed IHC marker aberrancy. In conclusion, the 3-marker IHC panel (PAX2, PTEN, and β-catenin) is (1) a useful tool in the diagnosis of AH/EIN in EMP; (2) PAX2 loss should be interpreted with caution and in combination with morphology and other markers.
Intralabial Lip Compartments and Their Potential Clinical Relevance
Authors: Cotofana Sebastian , Hong Wei-Jin , Horne Julie , Harris Steven , Surek Christopher C. , Frank Konstantin , Alfertshofer Michael , Kattil Punnose K. , Sakuma Thais , Onishi Emy C. , Bertucci Vince , Green Jeremy B. , Smith Michael P. , Khan Amanda , Lowry Natalia
Published: June 2023

Background:

Aesthetic soft-tissue filler injections for lip enhancement are popular and performed throughout the world. When injecting lips with a cannula, as the cannula is advanced, resistance is perceived in consistent locations, potentially indicating boundaries between intralabial compartments.

Objective:

We aimed to investigate whether intralabial compartments exist and, if so, to describe their volumes, location, boundaries, and dimensions.

Methods:

This cadaveric study investigated a total of 20 human body donors (13 male, seven female) with a mean (SD) age at death of 61.9 years (23.9) and body mass index of 24.3 kg/m2 (3.7). The investigated cohort included 11 White donors, eight Asian donors, and one Black donor. Dye injections simulating minimally invasive lip treatments were conducted.

Results:

Independent of sex or race, six anterior and six posterior compartments in the upper and lower lip were identified, for a total of 24 lip compartments. Compartment boundaries were formed by vertically oriented septations that were found in consistent locations. The anterior compartments had volumes ranging from 0.30 to 0.39 cc; the posterior compartment volume ranged from 0.44 to 0.52 cc. The compartment volumes were larger centrally and decreased gradually toward the oral commissure.

Conclusions:

The volume and size of each of 24 compartments contribute to the overall appearance and shape of the lips. To achieve a natural lip shape preserving aesthetic outcome it may be preferable to administer the volumizing product using a compartment-respecting injection approach.
Nutritional Recovery of Children With HIV and Severe Acute Malnutrition Attending an Outpatient Therapeutic Care Program
Authors: Mercedes Rebecca A. , Kasbaum Marie A. , George Paul E. , Tumweheire Enid G. , Scheurer Michael E. , Nabukeera-Barungi Nicolette
Published: June 2023

Background:

Despite significant morbidity and mortality from HIV and severe acute malnutrition (SAM) among children in sub-Saharan Africa, research is lacking in these children. We describe the proportion of children living with HIV with SAM achieving recovery, the factors associated with recovery, and time to recovery in an outpatient therapeutic care program.

Setting and Methods:

This is a retrospective observational study of children with SAM and HIV on antiretroviral therapy (6 months–15 years), enrolled in outpatient therapeutic care from 2015 to 2017 at a pediatric HIV clinic in Kampala, Uganda. SAM diagnosis and recovery by 120 days after enrollment were determined per World Health Organization guidelines. Cox-proportional hazards models were used to determine predictors of recovery.

Results:

Data from 166 patients were analyzed (mean age 5.4 years, SD 4.7). Outcomes showed 36.1% recovered, 15.6% were lost to follow-up, 2.4% died, and 45.8% failed. Average time to recovery was 59.9 days (SD 27.8). Patients 5 years or older were less likely to recover (crude hazard ratio [CHR] = 0.33, 95% CI: 0.18 to 0.58). In multivariate analysis, febrile patients were less likely to recover (adjusted hazard ratio = 0.53, 95% CI: 0.12 to 0.65). Patients with CD4 count of 200 or less at enrollment were less likely to recover (CHR = 0.46, 95% CI: 0.22 to 0.96).

Conclusions:

Despite treatment with antiretroviral therapy for children living with HIV, we observed poor rates of recovery from SAM, below the international target of >75%. Moreover, patients 5 years and older, fever, or low CD4 at diagnosis of SAM may require more intense therapy or closer monitoring than their counterparts.
Predictive Value of Radiographic and Magnetic Resonance Imaging Characteristics on Patient Outcomes in Confirmed Acute Osteomyelitis of the Extremities
Authors: Archer Holden , Ashikyan Oganes , Pezeshk Parham , Guirguis Mina , Gowda Prajwal , Hoang Diana , Xi Yin , Chhabra Avneesh
Published: June 2023

Objective

The aim of this study was to determine whether imaging characteristics on plain radiography, magnetic resonance imaging (MRI), and diffusion-weighted imaging are predictive of patient outcomes in cases of confirmed osteomyelitis (OM).

Materials and Methods

In this cross-sectional study, 3 experienced musculoskeletal radiologists evaluated pathologically proven cases of acute extremity OM and recorded imaging characteristics on plain radiographs, MRI, and diffusion-weighted imaging. These characteristics were then compared with the patient outcomes after a 3-year follow-up using length of stay, amputation-free survival, readmission-free survival, and overall survival using multivariate Cox regression analysis. Hazard ratio and corresponding 95% confidence intervals are reported. False discovery rate–adjusted P values were reported.

Results

For the 75 consecutive cases of OM in this study, multivariate Cox regression analysis adjusting for sex, race, age, body mass index, erythrocyte sedimentation rate, C-reactive protein, and white blood cell count showed no correlation among any of the recorded characteristics on imaging and patient outcomes. Despite the high sensitivity and specificity of MRI for diagnosing OM, there was no correlation between MRI characteristics and patient outcomes. Furthermore, patients with coexistent abscess of the soft tissue or bone with OM had comparable outcomes using the previously mentioned metrics of length of stay, amputation-free survival, readmission-free survival, and overall survival.

Conclusion

Neither radiography nor MRI features predict patient outcomes in extremity OM.
Deep Abscess Formation After Head and Neck Free Flap Reconstruction: A Critical Appraisal of Current Guidelines for Prophylactic Antibiotics in Head and Neck Surgery
Authors: van Mierlo Auke , Vaassen Lauretta , van Mens Suzan , Kessler Peter
Published: June 2023

Postoperative infections have a major impact on patient recovery, especially when a second surgical procedure is required. In this study, 342 cases from a retrospective cohort of patients undergoing microvascular free flap reconstruction of head and neck defects, were evaluated with respect to the development of deep abscesses. Two different perioperative antibiotic prophylaxis protocols based on amoxicillin-clavulanate and cefazolin with metronidazole were compared. Streptococcus anginosus was found to be the causative pathogen for the development of abscesses in the head and neck region in all cases in this series. An association for the development of abscesses was found with the use of osteosynthesis material and the use of cefazolin with metronidazole.
Efficacy of Immediate Lymphatic Reconstruction to Decrease Incidence of Breast Cancer-related Lymphedema
Authors: Coriddi Michelle , Dayan Joseph , Bloomfield Emily , McGrath Leslie , Diwan Richard , Monge Jasmine , Gutierrez Julia , Brown Stav , Boe Lillian , Mehrara Babak
Published: June 2023

Objective:

To conduct a randomized controlled trial (RCT) on the efficacy of immediate lymphatic reconstruction (ILR) for decreasing the incidence of breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND).

Background:

Despite encouraging results in small studies, an appropriately powered RCT on ILR has not been performed.

Methods:

Women undergoing ALND for breast cancer were randomized in the operating room 1:1 to either ILR, if technically feasible, or no ILR (control). The ILR group underwent lymphatic anastomosis to a regional vein using microsurgical techniques; control group had no repair and cut lymphatics were ligated. Relative volume change (RVC), bioimpedance, quality of life (QoL), and compression use were evaluated at baseline and every 6 months postoperatively up to 24 months. Indocyanine green (ICG) lymphography was performed at baseline and 12 and 24 months postoperatively. The primary outcome was the incidence of BCRL, defined as ≥10% RVC from baseline in the affected extremity at 12-, 18-, or 24-month follow-up.

Results:

Of 72 patients randomized to ILR and 72 to control from January 2020 to March 2023, our preliminary analysis includes 99 patients with 12-month follow-up, 70 with 18-month follow-up, and 40 with 24-month follow-up. The cumulative incidence of BCRL was 9.5% in the ILR group and 32% in the control group (P=0.014). The ILR group had lower bioimpedance values, decreased compression usage, better lymphatic function on ICG lymphography, and better QoL than the control group.

Conclusions:

Preliminary results of our RCT show that ILR after ALND decreases BCRL incidence. Our goal is to finish the accrual of 174 patients with 24-month follow-up.
Endoscopic Ultrasound–guided Versus Percutaneous Transhepatic Biliary Drainage After Failed ERCP: A Systematic Review and Meta-analysis
Authors: Giri Suprabhat , Seth Vishal , Afzalpurkar Shivaraj , Angadi Sumaswi , Jearth Vaneet , Sundaram Sridhar
Published: June 2023

Background:

Endoscopic retrograde cholangiopancreatography (ERCP) may fail to achieve biliary drainage in 5% to 10% of cases. Endoscopic ultrasound–guided biliary drainage (EUS-BD) and percutaneous transhepatic biliary drainage (PTBD) are alternative therapeutic options in such cases. The present meta-analysis aimed to compare the efficacy and safety of EUS-BD and PTBD for biliary decompression after failed ERCP.

Methods:

A comprehensive search of literature from inception to September 2022 was done of 3 databases for studies comparing EUS-BD and PTBD for biliary drainage after failed ERCP. Odds ratios (ORs) with 95% CIs were calculated for all the dichotomous outcomes. Continuous variables were analyzed using mean difference (MD).

Results:

A total of 24 studies were included in the final analysis. Technical success was comparable between EUS-BD and PTBD (OR=1.12, 0.67-1.88). EUS-BD was associated with a higher clinical success rate (OR=2.55, 1.63-4.56) and lower odds of adverse events (OR=0.41, 0.29-0.59) compared with PTBD. The incidence of major adverse events (OR=0.66, 0.31-1.42) and procedure-related mortality (OR=0.43, 0.17-1.11) were similar between the groups. EUS-BD was associated with lower odds of reintervention with an OR of 0.20 (0.10-0.38). The duration of hospitalization (MD: −4.89, −7.73 to −2.05) and total treatment cost (MD: −1355.46, −2029.75 to −681.17) were significantly lower with EUS-BD.

Conclusions:

EUS-BD may be preferred over PTBD in patients with biliary obstruction after failed ERCP where appropriate expertise is available. Further trials are required to validate the findings of the study.
Artificial intelligence versus surgeon gestalt in predicting risk of emergency general surgery
Authors: El Moheb Mohamad , Gebran Anthony , Maurer Lydia R. , Naar Leon , El Hechi Majed , Breen Kerry , Dorken-Gallastegi Ander , Sinyard Robert , Bertsimas Dimitris , Velmahos George , Kaafarani Haytham M.A.
Published: June 2023

BACKGROUND

Artificial intelligence (AI) risk prediction algorithms such as the smartphone-available Predictive OpTimal Trees in Emergency Surgery Risk (POTTER) for emergency general surgery (EGS) are superior to traditional risk calculators because they account for complex nonlinear interactions between variables, but how they compare to surgeons’ gestalt remains unknown. Herein, we sought to: (1) compare POTTER to surgeons’ surgical risk estimation and (2) assess how POTTER influences surgeons' risk estimation.

STUDY DESIGN

A total of 150 patients who underwent EGS at a large quaternary care center between May 2018 and May 2019 were prospectively followed up for 30-day postoperative outcomes (mortality, septic shock, ventilator dependence, bleeding requiring transfusion, pneumonia), and clinical cases were systematically created representing their initial presentation. POTTER's outcome predictions for each case were also recorded. Thirty acute care surgeons with diverse practice settings and levels of experience were then randomized into two groups: 15 surgeons (SURG) were asked to predict the outcomes without access to POTTER's predictions while the remaining 15 (SURG-POTTER) were asked to predict the same outcomes after interacting with POTTER. Comparing to actual patient outcomes, the area under the curve (AUC) methodology was used to assess the predictive performance of (1) POTTER versus SURG, and (2) SURG versus SURG-POTTER.

RESULTS

POTTER outperformed SURG in predicting all outcomes (mortality—AUC: 0.880 vs. 0.841; ventilator dependence—AUC: 0.928 vs. 0.833; bleeding—AUC: 0.832 vs. 0.735; pneumonia—AUC: 0.837 vs. 0.753) except septic shock (AUC: 0.816 vs. 0.820). SURG-POTTER outperformed SURG in predicting mortality (AUC: 0.870 vs. 0.841), bleeding (AUC: 0.811 vs. 0.735), pneumonia (AUC: 0.803 vs. 0.753) but not septic shock (AUC: 0.712 vs. 0.820) or ventilator dependence (AUC: 0.834 vs. 0.833).

CONCLUSION

The AI risk calculator POTTER outperformed surgeons' gestalt in predicting the postoperative mortality and outcomes of EGS patients, and when used, improved the individual surgeons' risk prediction. Artificial intelligence algorithms, such as POTTER, could prove useful as a bedside adjunct to surgeons when preoperatively counseling patients.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level II.
Mini-incision Right Hepatectomy for Living Donor Hepatectomy
Authors: Park Jeong-Ik , Jung Dong-Hwan , Moon Deok-Bog , Ahn Chul-Soo , Yoon Young-In , Kang Woo-Hyung , Na Byeong-Gon , Ha Su-Min , Kim Sang-Hoon , Kim Minjae , Kim Sung-Min , Yang Geunhyeok , Oh Rak-Kyun , Hwang Shin , Lee Sung-Gyu
Published: June 2023

Background.

The application of a minimally invasive technique to graft procurement in living donor liver transplantation has minimized skin incisions and led to early recovery in donor hepatectomy while ensuring donor safety. This study aimed to evaluate the safety and feasibility of mini-incision living donor right hepatectomy compared with conventional open surgery.

Methods.

The study population consisted of 448 consecutive living donors who underwent living donor right hepatectomy performed by a single surgeon between January 2015 and December 2019. According to the incision type, the donors were divided into 2 groups: a right subcostal mini-incision group (M group: n = 187) and a conventional J-shaped incision group (C group: n = 261). A propensity score matching analysis was conducted to overcome bias.

Results.

The estimated graft volume and measured graft weight were significantly lower in the M group (P = 0.000). The total of 17 (3.8%) postoperative complications were identified. The readmission rate and overall postoperative complication rate of donors was not significantly different between the groups. The biliary complication rates in the recipients were 12.6% and 8.6% in the C group and M group, respectively (P = 0.219). Hepatic artery thrombosis requiring revision developed in 2 patients (0.8%) in the C group and 7 patients (3.7%) in the M group (P = 0.038). After propensity score matching, these complications were not significantly different between the groups.

Conclusions.

Mini-incision living donor right hepatectomy shows comparable biliary complications to open surgery and is considered a safe and feasible operative technique.
T-B Collaboration in Autoimmunity, Infection, and Transplantation
Authors: DiToro Daniel , Murakami Naoka , Pillai Shiv
Published: June 2023

We have attempted here to provide an up-to-date review of the collaboration between helper T cells and B cells in response to protein and glycoprotein antigens. This collaboration is essential as it not only protects from many pathogens but also contributes to a litany of autoimmune and immune-mediated diseases.
Fifty shades of greenbeard: robust evolution of altruism based on similarity of complex phenotypes
Authors: Båvik Linnéa M. , Mehta Rohan S. , Weissman Daniel B.
Published: June 2023

We study the evolution of altruistic behaviour under a model where individuals choose to cooperate by comparing a set of continuous phenotype tags. Individuals play a donation game and only donate to other individuals that are sufficiently similar to themselves in a multidimensional phenotype space. We find the generic maintenance of robust altruism when phenotypes are multidimensional. Selection for altruism is driven by the coevolution of individual strategy and phenotype; altruism levels shape the distribution of individuals in phenotype space. Low donation rates induce a phenotype distribution that renders the population vulnerable to the invasion of altruists, whereas high donation rates prime a population for cheater invasion, resulting in cyclic dynamics that maintain substantial levels of altruism. Altruism is therefore robust to invasion by cheaters in the long term in this model. Furthermore, the shape of the phenotype distribution in high phenotypic dimension allows altruists to better resist the invasion by cheaters, and as a result the amount of donation increases with increasing phenotype dimension. We also generalize previous results in the regime of weak selection to two competing strategies in continuous phenotype space, and show that success under weak selection is crucial to success under strong selection in our model. Our results support the viability of a simple similarity-based mechanism for altruism in a well-mixed population.