bluuebunny/crossref_metadata_2025 huggingface dataset:
81 Juvenile RHUPUS syndrome: a case reports
Authors: Gacem Ourida , Abba Kahina , Tenkout Khaoula , Abbas Salima , Guers Saliha , Chouli Mohamed , Achir Moussa , Ladj Mohamed Samir
Published: October 2022

Background

RHUPUS syndrome is a rare association with rheumatoid arthritis and systemic lupus erythematosus (SLE) in adult patients. Its pediatric presentation is very rare and underdiagnosed. The mechanism is not well understood yet, but most theories accepted a real overlap between SLE and juvenile idiopathic arthritis. In children. Patients with Rhupus have clinical symptoms of SLE with positive ANA, anti-DNA or anti Sm associated with clinical symptoms of JIA.

Objective

Illustrate an unusual presentation of lupus in children

Methods

we present a case of juvenile rhupus syndrome; we describe the clinical presentation, the serological results, the diagnostic criteria for SLE (ACR 1997) and JIA (ILLA 2001) and the treatment installed.

Case reports

We recently diagnosed Rhupus syndrome in an 11-year-old girl who presented with polyarthritis deformans of the bilateral joints of the wrists, hands and feet for 24 months. she also had an onset of profound asthenia, recurrent oral aphtosis and massive hair loss over the past few months. Initial investigation showed anaemia, increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Radiographic examinations showed juxtra-articular osteopenia and chronic synovitis of the wrists. The autoimmune assessment was contributory with a positive rheumatoid factor (RF), antinuclear antibodies (ANA) (1/1000) and positive anti-Sm antibodies. Anticardiolipin and anti-RNP antibodies were negative. Our patient met >4 ACR criteria for SLE classification. She was treated with methotrexate and hydroxychloroquine, under close medical supervision in order to watch for the appearance of other organic damage to lupus disease, in particular renal and neurological. This type of joint damage is considered to be either lupus joint damage, lupus with chronic arthritis, or overlapping lupus with JIA. Children with Rhupus initially present with JIA and later develop lupus. Previous reports have shown female predominance, polyarticular involvement, non-erosive arthritis, and years of diagnostic wandering. Our patient had polyarthritis deformans with a two-year delay in diagnosis of SLE.

Conclusion

Although rare, the infantile Rhupus syndrome must be evoked in front of a deforming arthropathy.
The role of B cells in the pathogenesis of systemic sclerosis: an update
Authors: Sakkas Lazaros I , Katsiari Christina G , Daoussis Dimitrios , Bogdanos Dimitrios P
Published: October 2022

The pathogenesis of SSc is incompletely understood, but several lines of evidence suggest that B cells are involved. Effector B (Beff) cells are hyperactivated and produce autoantibodies (autoAbs), and regulatory B cells (Bregs) are decreased, although a recent study reported a defect in central B cell tolerance. AutoAbs appear before fibrosis, and some have direct profibrotic effects, while others also induce microvasculopathy. Recently, a study found that B cells reactive to topo I with high affinity produce IL-6 and cause fibrosis in mice, whereas B cells with low affinity for topo I produce IL-10 and inhibit fibrosis. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, promoted B cells with low affinity for topo I and decreased fibrosis. These findings provide a rationale for innovative B cell–directed strategies for managing SSc, such as ibrutinib or chimeric antigen receptor T cells, particularly in the early inflammatory stage of the disease.
Similar effect of co-administration of methotrexate and folic acid for the treatment of arthritis compared to separate administration
Authors: Dalix Elisa , Maalouf Mathieu , Peyroche Sylvie , Vanden-Bossche Arnaud , Arthaud Charles-Antoine , Hodin Sophie , Müller Rüdiger B , Marotte Hubert
Published: October 2022

Objectives

MTX is the recommended first-line treatment for RA associated with folic acid (FA) to reduce side effects related to MTX. Here, we proposed to test a co-administration of MTX with FA in the rat adjuvant-induced arthritis (AIA) on efficacy.

Material and methods

AIA was induced in female Lewis rats and treated with MTX in three groups. The first group of rats received only MTX (n = 13), whereas the second received MTX and FA on the same day (n = 14). The third group received FA one day after MTX (n = 14). Arthritic index (AI), ankle circumference (AC), ankle microcomputed tomography, and blood tests assessed arthritis severity and MTX tolerance.

Results

AI and AC were similar in MTX groups at various time points. Bone erosion and bone loss parameters were similar in all groups. MTX-PG1 was found at similar levels in various MTX groups and correlated negatively with arthritis severity. Finally, haematology and metabolic parameters were found at a similar level in MTX groups.

Conclusion

Co-administration of MTX with FA on the same day did not reduce efficacy compared with FA application one day after MTX. Thus, co-administration of MTX and FA could be more convenient and improve compliance in patients.
Development of a scoring model for the Sharp/van der Heijde score using convolutional neural networks and its clinical application
Authors: Honda Suguru , Yano Koichiro , Tanaka Eiichi , Ikari Katsunori , Harigai Masayoshi
Published: October 2022

Objectives

To construct a predictive model for the Sharp/van der Heijde score (SHS) and assess its applicability in clinical research settings.

Material and methods

A prediction model for SHS was constructed in three steps using convolutional neural networks (CNN) and an in-house RA image database: orientation, detection and damage prediction. A predictive model for radiographic progression (ΔSHS >3/year) was developed using a graph convolutional network (GCN). A multiple regression model was used to assess the association between predicted SHS using the CNN model and clinical features.

Results

In the orientation and detection phases, 100% accuracy was achieved in the image orientation correction, and all predicted joint coordinates were within 10 pixels of the correct coordinates. In the damage prediction phase, the κ values between the model and expert 1 were 0.879 and 0.865 for erosion and joint space narrowing, respectively. Using a dataset scored by experts 1 and 2, a minimal overfitting was determined to the scoring by expert 1. High-titre RF was an independent risk factor of ΔSHS per year, as predicted by the CNN model in biologics users. The AUCs of the GCN model for predicting ΔSHS >3/year in patients with and without biologics at baseline were 0.753 and 0.734, respectively, superior to those of the other models. The RF titre was the most important feature in predicting ΔSHS >3/year in biologics users in the GCN model.

Conclusion

A high-performance scoring model for SHS that is applicable to clinical research was constructed.
Rapid cycle adaptation of a classroom-based intervention to promote equity in access to youth physical activity
Authors: Hasson Rebecca E , Eisman Andria B , Wassmann Amy , Martin Scott , Pugh Pamela , Winkelseth Kerry , Zernicke Ronald , Rabaut Lisa
Published: October 2022

Our objective was to systematically adapt Interrupting Prolonged sitting with ACTivity (InPACT), a classroom-based physical activity intervention, for home delivery to equitably increase access to structured youth physical activity opportunities during the COVID-19 pandemic. Key steps in the rapid-cycle research adaptation process included: (Step 1) identifying partner organizations; (Steps 2 and 3) engaging in problem and knowledge exploration to examine the problem from different perspectives; (Steps 4 and 5) initiating solution development and testing by selecting an intervention and adapting the format and content for home delivery. Using Rapid RE-AIM to guide online assessment and refinement of InPACT at Home; and (Step 6) utilizing dissemination strategies to extend the reach of the program. Core elements of the InPACT program that were retained included: the use of exercise videos, maintenance of the intervention dose, and teacher-led physical activities. Key adaptations included: utilization of physical education specialists to develop the exercise videos, incorporation of health messaging in videos, and utilization of dissemination strategies (intervention website) to reach K-12 students across the state. Intervention website reach included all 83 counties in Michigan, but goals were not met for website pageviews (5,147; 85% of goal) and video view duration (7 min 19 sec; 37% of goal). Accordingly, dissemination was expanded to include public television broadcasting (monthly viewers: 500,000) and videos were shortened to 8 minutes. Dissemination and implementation science frameworks guided the rapid adaptation of an existing intervention, InPACT, to equitably increase access to structured youth physical activity opportunities at home during the pandemic.
Opioid Use Patterns in a Statewide Adult Medicaid Population Undergoing Elective Lumbar Spine Surgery
Authors: Reitman Charles A. , Ward Ralph , Taber David J. , Moran William P. , McCauley Jenna , Basco William T. , Gebregziabher Mulugeta , Lockett Mark , Ball Sarah J.
Published: October 2022

Study Design.

Retrospective administrative database review

Objective.

Analyze patterns of opioid use in patients undergoing lumbar surgery and determine associated risk factors in a Medicaid population.

Summary of Background Data.

Opioid use in patients undergoing surgery for degenerative lumbar spine conditions is prevalent and impacts outcomes. There is limited information defining the scope of this problem in Medicaid patients.

Methods.

Longitudinal cohort study of adult South Carolina (SC) Medicaid patients undergoing lumbar surgery from 2014-2017. All patients had continuous SC Medicaid coverage for 15 consecutive months, including 6 months prior to and 9 months following surgery. The primary outcome was a longitudinal assessment of post-operative opioid use to determine trajectories and group-based membership using latent modeling. Univariate and multivariable modeling was conducted to assess risk factors for group-based trajectory modeling (GBTM) and chronic opioid use (COU).

Results.

A total of 1,455 surgeries met inclusion criteria. GBTM demonstrated patients fit into 5 groups; very low use (23.4%), rapid wean following surgery (18.8%), increasing use following surgery (12.9%), slow wean following surgery (12.6%) and sustained high use (32.2%). Variables predicting membership in high opioid use included pre-operative opioid use, younger age, longer length of stay, concomitant medications, and readmissions. More than three-quarters of patients were deemed COUs (76.4%). On bivariate analysis, patients with degenerative disc disease (DDD) were more likely to be COUs (24.8% vs. 18.6%; P=0.0168), more likely to take opioids prior to surgery (88.5% vs. 61.9%; P<0.001) and received higher amounts of opioids during the 30-days following surgery (mean MME 59.6 vs. 25.1; P<0.001).

Conclusions.

Most SC Medicaid patients undergoing lumbar elective lumbar spine surgery were using opioids pre-operatively and continued long-term use post-operatively at a higher rate than previously reported databases. Pre-operative and perioperative intake, DDD, multiple prescribers, depression and concomitant medications were significant risk factors.
LncRNA MSC-AS1, as an oncogene in melanoma, promotes the proliferation and glutaminolysis by regulating the miR-330-3p/YAP1 axis
Authors: Tian Tian , Luo Binjie , Shen Guoliang , Ji Geng
Published: October 2022

Melanoma is a kind of aggressive skin neoplasms with high mortality. The purpose of this present research was to investigate the effects and potential mechanisms of long-noncoding RNA (lncRNA) MSC antisense RNA 1 (MSC-AS1) in melanoma. MSC-AS1, miR-330-3p and YAP1 expression levels in melanoma tissues and cells were assessed by quantitative real-time polymerase chain reaction. Melanoma cells were evaluated using cell count kit-8, clone formation and ELISA in vitro. The relationship among MSC-AS1, YAP1 and miR-330-3p was validated by pull-down and luciferase reporter assays. Finally, the role of MSC-AS1 in vivo was determined by the xenograft model. Results showed that lncRNA MSC-AS1 was upregulated in melanoma tissues and cells. High expression of MAS-AS1 was positively correlated with a poor prognosis. Pull-down and luciferase reporter demonstrated that miR-330-3p specifically binds directly to YAP1 and MSC-AS1, respectively. MSC-AS1 promoted the expression of YAP1 by downregulating miR-330-3p. Functional experiments suggested that knockdown of MSC-AS1 suppressed the proliferation of melanoma cells and decreased the levels of glutamine, glutamate and α-ketoglutarate, glutaminase and glutamine transporter alanine-serine-cysteine transporter 2. Upregulation of miR-330-3p alleviated the promotion effect of MSC-AS1 overexpression on the proliferation and glutaminolysis of melanoma cells. The above changes could be reversed by YAP1 overexpression. In addition, knockdown of MSC-AS1 dramatically restrained the growth of melanoma cells in xenograft model. In conclusion, our results revealed that MSC-AS1 facilitated the proliferation and glutaminolysis of melanoma cells by regulating miR-330-3p/YAP1 pathway, suggesting that MSC-AS1 could provide a new idea for the treatment of melanoma.
Genotyping and Cytology Triage of High-Risk HPV DNA Positive Women for Detection of Cervical High-Grade Lesions
Authors: El-Zein Mariam , Bouten Sheila , Abdrabo Lina Sobhi , Siblini Aya , Louvanto Karolina , Franco Eduardo , Ferenczy Alex
Published: October 2022

Objective

A demonstration project of primary human papillomavirus (HPV) testing was initiated in 2011 among more than 23,000 women attending routine cervical cancer screening. We examined the additional diagnostic performance of HPV genotyping for detecting disease in women with abnormal cytology.

Methods

Women aged 30 to 65 years were originally screened for HPV using Hybrid Capture II test. Women with positive results were triaged using conventional cytology, and those with atypical squamous cells of undetermined significance or worse (≥ASC-US) were referred to colposcopy. We retrospectively genotyped (Roche cobas 4800 HPV system [Roche Molecular Systems Inc, Pleasanton, CA]) cervical specimens that were HPV+ with Hybrid Capture II test and extracted women's medical history postbaseline screening. We calculated positive predictive values (PPVs) and 95% confidence intervals (CIs) of triage tests to detect histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) within the first year of follow-up among women positive for HPV16, HPV18, and HPV16 and/or HPV18 as well as among those negative for HPVs 16 and 18.

Results

Of 1,396 HPV-positive women, 1,092 (78%) were classified as normal, 136 (10%) had CIN1, 80 (6%) had CIN2, 81 (6%) had CIN3, and 7 women had cancer throughout the entire follow-up period. Seventy CIN2+ cases were detected within the first year of follow-up. The PPV for detecting CIN2+ was 20.9% (63/239; 95% CI = 16.4–25.9) for ASC-US+ cytology. In women with ASC-US+, PPVs were 31.2% (24/77; 95% CI = 21.1–42.7) for HPV16+, 27.8% (5/18; 95% CI = 9.7–53.5) for HPV18+, 30.8% (28/91; 95% CI = 21.5–41.3) for HPV16+ and/or HPV18+ women, and 16.6% (35/211; 95% CI = 11.8–22.3) in women testing negative for HPVs 16 and 18.

Conclusion

Partial genotyping as an additional triage strategy to cytology can markedly improve clinical diagnostic performance.
Recurrence in Cervical High-Grade Squamous Intraepithelial Lesion: The Role of the Excised Endocervical Canal Length—Analysis of 2,427 Patients
Authors: Foggiatto Andresa Ines , de Carvalho Newton Sergio , Fonseca Fernanda Villar , Maestri Carlos Afonso
Published: October 2022

Objective

This study aimed to evaluate the influence of the excised canal length on relapse rates of cervical high-grade squamous intraepithelial lesion (HSIL) treated by loop electrosurgical excision procedure and to find a cut-off point, above which lower recurrence rates could be observed, with low probability of compromising future obstetric outcome, and the relationship with other individual factors related to HSIL recurrence.

Method

This was a retrospective cohort study of 2,427 women diagnosed with cervical intraepithelial neoplasia CIN2+ who underwent cervical conization using the high-frequency loop electrosurgical excision procedure surgery technique, to analyze the role of endocervical canal length associated with individual factors in the recurrent disease after CIN2+ treatment and determine a cut-off point for the excised canal length needed to decrease the risk of disease relapse.

Results

In 2,427 cases, the relapse rate of HSIL treated was 12%. Compromised margins of conization, HIV+, and endocervical canal length were related directly to relapses (p < .001). The cut-off point, by receiver operating characteristic curve, to calculate the endocervical canal length related to relapses was 1.25 cm of canal excised. Canal length of less than 1.25 cm increased the recurrence rate 2.5 times. Compromised margins and HIV+ increased recurrence rates by more than 5 times.

Conclusion

Cervical HSIL recurrence was directly related to the endocervical canal length: excised canal length of 1.25 cm or more decreases recurrence rate; HIV and compromised margins increase the chance of recurrence by more than 5 times.
Vascular stiffening and endothelial dysfunction in atherosclerosis
Authors: Hooglugt Aukie , Klatt Olivia , Huveneers Stephan
Published: October 2022

Purpose of review

Aging is an important risk factor for cardiovascular disease and is associated with increased vessel wall stiffness. Pathophysiological stiffening, notably in arteries, disturbs the integrity of the vascular endothelium and promotes permeability and transmigration of immune cells, thereby driving the development of atherosclerosis and related vascular diseases. Effective therapeutic strategies for arterial stiffening are still lacking.

Recent findings

Here, we overview the literature on age-related arterial stiffening, from patient-derived data to preclinical in-vivo and in-vitro findings. First, we overview the common techniques that are used to measure stiffness and discuss the observed stiffness values in atherosclerosis and aging. Next, the endothelial response to stiffening and possibilities to attenuate this response are discussed.

Future research that will define the endothelial contribution to stiffness-related cardiovascular disease may provide new targets for intervention to restore endothelial function in atherosclerosis and complement the use of currently applied lipid-lowering, antihypertensive, and anti-inflammatory drugs.
The Change in the Fibrosis-4 Index for the Assessment of Liver Fibrosis After Pancreaticoduodenectomy
Authors: Tani Masaji , Maehira Hiromitsu , Iida Hiroya , Mori Haruki , Miyake Toru , Nitta Nobuhito
Published: October 2022

Objectives

Nonalcoholic fatty liver is a complication of pancreaticoduodenectomy (PD); however, liver fibrosis after PD is not well documented. Therefore, we estimated the hepatic fibrotic index of nonalcoholic fatty liver after PD.

Methods

We retrospectively examined the electronic medical records of patients who had underwent PD and had computed tomography (CT) records preoperatively and 6 months postoperatively between 2011 and 2019 at the Shiga University of Medical Science Hospital.

Results

Overall, 115 patients were enrolled. After 6 months from PD, body mass index significantly decreased from 21.90 to 19.57 kg/m2 (−10.6%). The Fibrosis-4 (FIB-4) index significantly increased from 1.756 to 2.384 (P < 0.001). The FIB-4 grade significantly worsened. Contrarily, neither the albumin-bilirubin (ALBI) score nor the ALBI grade demonstrated significant differences. The CT attenuation value significantly decreased (P < 0.001) from 57.6 to 49.5. Multivariate analysis predicted a high preoperative FIB-4 index, high ALBI index, and hypo-CT attenuation value (<30 HU) as risk factors for a high postoperative FIB-4 index.

Conclusions

The FIB-4 index worsened when the follow-up period was only 6 months, regardless of the eternalness in the ALBI score. Liver fibrosis should be assessed using the FIB-4 index for a long-term survivorship after PD.
Recruitment and Retention Strategies for the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study
Authors: Yazici Cemal , Dyer Anne-Marie , Conwell Darwin L. , Afghani Elham , Andersen Dana K. , Basina Marina , Bellin Melena D. , Boone Leslie R. , Casu Anna , Easler Jeffrey J. , Greenbaum Carla J. , Hart Phil A. , Jeon Christie Y. , Lee Peter J. , Meier Shelby , Papachristou Georgios I. , Raja-Khan Nazia T. , Saeed Zeb I. , Serrano Jose , Yadav Dhiraj , Fogel Evan L. ,   on behalf of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC)
Published: October 2022

Recruitment and retention of patients with acute pancreatitis (AP) in clinical studies can be challenging. While some obstacles are similar to other clinical conditions, some are unique to AP. Identifying potential barriers early and developing targeted solutions can help optimize recruitment and retention in AP studies. Such pre-emptive and detailed planning can help prospective, longitudinal studies focus on exocrine and endocrine complications of AP in accurately measuring outcomes. This article highlights the challenges in recruitment and retention strategies in AP studies and reviews available resources to create opportunities to address them. We describe the multifaceted approach used by the Recruitment and Retention Committee of the Type 1 Diabetes in Acute Pancreatitis Consortium, which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study.
Standard Operating Procedures for Biospecimen Collection, Processing, and Storage
Authors: Wasserfall Clive , Dyer Anne-Marie , Speake Cate , Andersen Dana K. , Baab Kendall Thomas , Bellin Melena D. , Broach James R. , Campbell-Thompson Martha , Chinchilli Vernon M. , Lee Peter J. , Park Walter G. , Pratley Richard E. , Saloman Jami L. , Sims Emily K. , Tang Gong , Yadav Dhiraj , Yazici Cemal , Conwell Darwin L. ,   on behalf of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC)
Published: October 2022

Differences in methods for biospecimen collection, processing, and storage can yield considerable variability and error. Therefore, best practices for standard operating procedures are critical for successful discovery, development, and validation of disease biomarkers. Here, we describe standard operating procedures developed for biospecimen collection during the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) Study within the Type 1 Diabetes in Acute Pancreatitis Consortium. Notably, these protocols were developed using an integrative process based on prior consortium experience and with input from working groups with expertise in immunology, pancreatitis, and diabetes. Publication and adoption consistent biospecimen protocols will inform future studies and allow for better comparisons across different metabolic research efforts.
Rationale and Design for the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study
Authors: Hart Phil A. , Papachristou Georgios I. , Park Walter G. , Dyer Anne-Marie , Chinchilli Vernon M. , Afghani Elham , Akshintala Venkata S. , Andersen Dana K. , Buxbaum James L. , Conwell Darwin L. , Dungan Kathleen M. , Easler Jeffrey J. , Fogel Evan L. , Greenbaum Carla J. , Kalyani Rita R. , Korc Murray , Kozarek Richard , Laughlin Maren R. , Lee Peter J. , Maranki Jennifer L. , Pandol Stephen J. , Phillips Anna Evans , Serrano Jose , Singh Vikesh K. , Speake Cate , Tirkes Temel , Toledo Frederico G.S. , Trikudanathan Guru , Vege Santhi Swaroop , Wang Ming , Yazici Cemal , Zaheer Atif , Forsmark Christopher E. , Bellin Melena D. , Yadav Dhiraj ,   on behalf of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC)
Published: October 2022

Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study.
Design and Rationale for the Use of Magnetic Resonance Imaging Biomarkers to Predict Diabetes After Acute Pancreatitis in the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study
Authors: Tirkes Temel , Chinchilli Vernon M. , Bagci Ulas , Parker Jason G. , Zhao Xuandong , Dasyam Anil K. , Feranec Nicholas , Grajo Joseph R. , Shah Zarine K. , Poullos Peter D. , Spilseth Benjamin , Zaheer Atif , Xie Karen L. , Wachsman Ashley M. , Campbell-Thompson Martha , Conwell Darwin L. , Fogel Evan L. , Forsmark Christopher E. , Hart Phil A. , Pandol Stephen J. , Park Walter G. , Pratley Richard E. , Yazici Cemal , Laughlin Maren R. , Andersen Dana K. , Serrano Jose , Bellin Melena D. , Yadav Dhiraj ,   on behalf of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC)
Published: October 2022

This core component of the Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM) study will examine the hypothesis that advanced magnetic resonance imaging (MRI) techniques can reflect underlying pathophysiologic changes and provide imaging biomarkers that predict diabetes mellitus (DM) after acute pancreatitis (AP). A subset of participants in the DREAM study will enroll and undergo serial MRI examinations using a specific research protocol. The aim of the study is to differentiate at-risk individuals from those who remain euglycemic by identifying parenchymal features after AP. Performing longitudinal MRI will enable us to observe and understand the natural history of post-AP DM. We will compare MRI parameters obtained by interrogating tissue properties in euglycemic, prediabetic, and incident diabetes subjects and correlate them with metabolic, genetic, and immunological phenotypes. Differentiating imaging parameters will be combined to develop a quantitative composite risk score. This composite risk score will potentially have the ability to monitor the risk of DM in clinical practice or trials. We will use artificial intelligence, specifically deep learning, algorithms to optimize the predictive ability of MRI. In addition to the research MRI, the DREAM study will also correlate clinical computed tomography and MRI scans with DM development.
Telomere Attrition in Intraductal Papillary Mucinous Neoplasms of the Pancreas Associated With Carcinogenesis and Aging
Authors: Miki Atsushi , Matsuda Yoko , Aida Junko , Watanabe Jun , Sanada Yukihiro , Sakuma Yasunaru , Lefor Alan K. , Fukushima Noriyoshi , Sata Naohiro , Arai Tomio , Takubo Kaiyo , Ishiwata Toshiyuki
Published: October 2022

Objectives

It is challenging to preoperatively distinguish malignant and benign forms of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The aims of this study were to investigate whether telomere length is associated with pathological grade of IPMNs and age and to clarify the utility of telomere length as a marker to identify malignant IPMNs.

Methods

Pancreas tissue was obtained from 28 patients after resection. We measured the telomere lengths of tumor cells in IPMNs and normal duct cells by quantitative fluorescence in situ hybridization. The association of normalized telomere-centromere ratio (NTCR) to pathological grade of IPMNs and age were determined.

Results

The NTCR showed a gradual decrease with increasing pathological grade of IPMNs. The NTCR in intermediate- and high-grade dysplasia and adenocarcinoma lesions was significantly shorter than in normal pancreatic ducts (P < 0.05). In multivariate analysis, telomere length was most associated with carcinogenesis. When the cutoff value of NTCR was set to 0.74, the sensitivity for detection of high-grade dysplasia and adenocarcinoma was 82.8%, with a specificity of 87.5%.

Conclusions

Telomere shortening occurs with carcinogenesis and aging. A significant reduction of telomere length in IPMNs may be useful for surgical decision making.
Organoids
Authors: Navarro-Serer Bernat , Wood Laura D.
Published: October 2022

Pancreatic cancer is one of the most lethal cancer types, estimated to become the second leading cause of cancer-related deaths in the United States in 2030. The use of 3-dimensional culture systems has greatly expanded over the past few years, providing a valuable tool for the study of pancreatic cancer. In this review, we highlight some of the preclinical in vitro and in vivo models used in pancreatic cancer research, each with its own advantages and disadvantages, and focus on one of the recently used 3-dimensional culture models: organoids. Organoids are multicellular units derived from tissue samples and embedded within extracellular matrix gels after mechanical and enzymatic digestion. We define organoids, differentiate them from other 3-dimensional culture systems such as spheroids, and describe some applications of this model that have recently advanced our understanding of pancreatic cancer and its tumor microenvironment. Organoids have provided valuable insights into pancreatic cancer progression, heterogeneity, and invasion, and they have enabled the creation of biobanks, providing a platform for drug screening. In addition, we discuss some of the future directions and challenges in this model when addressing research questions.
Helping Patients Understand Pancreatic Cancer Using Animated Pancreas Patient Education With Visual Formats of Learning
Authors: Munigala Satish , Gardner Timothy B. , O'Reilly Eileen M. , Fernández-del Castillo Carlos , Ko Andrew H. , Pleskow Douglas , Vollmer Charles M. , Searle Nicholas A. , Bakelman David , Holt Jane M. , Gelrud Andres
Published: October 2022

Objectives

Patient education and resources that address barriers to health literacy to improve understanding in pancreatic cancer are limited. We evaluated the impact and outcomes benefits of Animated Pancreas Patient (APP) cancer educational modules (APP website and YouTube).

Methods

A retrospective study of APP metrics and utilization data from September 2013 to February 2021 was conducted. We evaluated audience reach and calculated top views by media type (animation/expert video/patient video/slideshow) and top retention videos from the modules.

Results

During the study period, APP had 4,551,079 views worldwide of which 2,757,064 unique visitors or 60% were from the United States. Of these, 54% were patients, 17% were family members or caregivers, 16% were health care providers, and 13% were other. The most popular topic viewed among the animations was “Understanding Clinical Trials” (n = 182,217), and the most common expert video viewed was “What are the different stages of pancreatic cancer?” (n = 15,357).

Conclusions

Pancreatic cancer patient education using APP's visual formats of learning demonstrated a wide reach and had a significant impact on improved understanding among patients, families, and caregivers. Continued efforts should be made to provide patient resources that address health literacy, better quality of life and improved health outcomes in pancreatic cancer.
Reducing Inpatient Psychiatric Unit Denials
Authors: Baum Gwen , Sullivan Michaela , Kohne Lisa , Seaberry Colette , Powers Taryn
Published: October 2022

Purpose of Project:

The purpose of the inpatient psychiatric unit denials reduction project was to establish a taskforce to analyze denials data for root cause and identify an effective solution to prevent denials through improved provider documentation.

Primary Practice Setting:

The development and implementation of the project occurred at Stanford Health Care, a nonprofit Level 1 trauma hospital, with a 29-bed inpatient psychiatric unit containing both open and secured levels of care. The project was led by the Utilization/Denials Management team, which is subteam within the Case Management Department. Team members are Nurse Case Managers specializing in the management of denials and appeals, data analysis and trending of denials, denial avoidance, and reduction of financial risk.

Methodology:

Denials data analysis revealed the Psychiatry Service Line was responsible for over 70% of payer denials within the Length of Stay Write-offs category. In early 2019, the Utilization/Denials Management team initiated a quality improvement project using A3 Lean Approach methodology and evidence-based practice to guide the implementation. The partnership and collaboration included Case Management, Revenue Cycle, Clinical Documentation Improvement, Technology and Digital Solutions, and Psychiatry Service Line leadership that had an interest in reducing payer denials.

Results:

Outcomes measured for the project were based on denials data for (fiscal year) FY19, the preintervention period, compared to FY20 and FY21, the postintervention period. From FY19 to FY20, revenue loss decreased by 42%. The downward trend continued from FY20 to FY21 with a recorded decrease by 69%.

Implications for Case Management Practice:

The most important implication of the project was improved physician documentation and medical necessity supporting the severity and intensity of inpatient psychiatric level of care, and medical justification for the inpatient stay not only to prevent medical necessity denials but to accurately reflect the care that was provided. High-quality documentation correlates to the high quality of care being provided. This project is far reaching not only for psychiatric units but also reproducible for other acute hospital service lines. Case Management is a multidisciplinary role, and this work is most meaningful for a Nurse Case Manager engaged in care coordination, including utilization and denials management.
Objective evaluation of face-lift outcomes through a new composite photo-numerical scale: The face and neck lift Objective Photo-Numerical Assessment Scale
Authors: La Padula Simone , Coiante Edoardo , Pizza Chiara , D’Andrea Francesco , Rega Umberto , Hersant Barbara , Meningaud Jean Paul
Published: October 2022

Background:

Success or failure of plastic surgery procedures relies on cosmetic results. Understanding the objective perception of favourable aesthetic results is critical to ensure patient satisfaction. The aim of this study was to develop and to validate a new facial rating scale that could objectively assess face and neck lift outcomes: The face and neck li
ft Objective Photo-Numerical Assessment Scale.

Material and Methods:

One thousand Caucasian patients were included in our study and assessed. To validate our scale the inter-rater reliability and the test-retest reliability were analysed. The Rasch model was used as part of the scale validation process.

Results:

Eleven scales for face and neck lift outcomes assessment were developed. All scales exceeded criteria for acceptability, reliability and validity. The inter and intra-rater reliabilities were good with a substantial or virtually perfect inter-rater reliability for the total score (p=0.15).

Conclusion:

Our results allowed us to validate the face and neck lift Objective Photo-Numerical Assessment Scale as a reliable and reproducible tool to assess face and neck lift outcomes. This scale could be also considered as an important new metrics to be used in facial rejuvenation surgery clinical research.
Traditional versus laterally extended upper blepharoplasty skin excisions: objective and patient reported outcomes
Authors: Hollander Maria H.J. , Contini Mark , Delli Konstantina , Vissink Arjan , Schepers Rutger H. , Jansma Johan , Schortinghuis Jurjen
Published: October 2022

Background:

Different skin excision shapes may result in different aesthetic outcomes when performing an upper blepharoplasty.

Methods:

Two skin-only excision shapes were objectively and subjectively evaluated in 28 matched patients: the laterally extended skin excision (A) and traditional elliptical skin excision (B). The pretarsal show, lateral eyebrow height, amount of scarring (Patient and Observer Scar Assessment Scale), and patient reported aesthetic results (FACE-Q questionnaires) were scored and compared at 6 and 12 months postoperatively.

Results:

In both groups, the pretarsal show improved significantly after the blepharoplasty. The homogeneity of the pretarsal show improved significantly in the lateral extension group (A), together with a slightly more pretarsal show (0.5–0.8 mm at central pupil region) at 6 and 12 months follow up compared to group B (p=0.004). A trend was observed in the Exocanthion45°(EX-EX45) measurement where group A showed 0.6mm more pretarsal show at 6 months postoperative. The homogeneity of the pretarsal show had significantly improved in group A 12 months after the blepharoplasty, but not in group B. No other significant differences were observed between the groups regarding the pretarsal show measurements or FACE-Q scores. Both groups showed descent of the lateral eyebrow, but this was only significant in group B. Group B showed 1.4 to 2.0mm more descent compared to group A. Both groups’ scarring and adverse effects scores were low and did not differ.

Conclusion:

Both excision shapes result in positive aesthetic results, but the laterally extended skin excision technique is accompanied by a slightly more favourable outcome.
Resistant herpes simplex virus infections – who, when, and what's new?
Authors: Kotton Benjamin D. , Kotton Camille N.
Published: October 2022

Purpose of review

This review summarizes the literature on acyclovir resistant herpes infections and the most recent data pertinent to diagnosis and treatment in the immunocompromised patient population.

Recent findings

Although fairly rare, acyclovir resistant herpes infections can be challenging to diagnose. Clinicians should be aware of this entity when facing refractory herpes infections. With updated diagnostics, the diagnosis is usually made through viral culture and sequencing. Therapeutic choices depend on the extent of disease. Topical therapy may be appropriate for mucocutaneous disease. Intravenous antiviral therapies such as foscarnet and cidofovir may be necessary for disseminated, ophthalmologic, central nervous system, or visceral disease. Experimental therapies such as pritelivir are in clinical trials.

Immunosuppressed patients are at risk for developing acyclovir-resistant herpes, which can be challenging to diagnose and treat, although emerging therapeutic options look promising.
A Computer-based Analysis for Identification and Quantification of Small Airway Disease in Lung Computed Tomography Images
Authors: Mahdavi Mohammad Mehdi Baradaran , Arabfard Masoud , Rafati Mehravar , Ghanei Mostafa
Published: October 2022

Computed tomography (CT) imaging is being increasingly used in clinical practice for detailed characterization of lung diseases. Respiratory diseases involve various components of the lung, including the small airways. Evaluation of small airway disease on CT images is challenging as the airways cannot be visualized directly by a CT scanner. Small airway disease can manifest as pulmonary air trapping (AT). Although AT may be sometimes seen as mosaic attenuation on expiratory CT images, it is difficult to identify diffuse AT visually. Computer technology advances over the past decades have provided methods for objective quantification of small airway disease on CT images. Quantitative CT (QCT) methods are being rapidly developed to quantify underlying lung diseases with greater precision than subjective visual assessment of CT images. A growing body of evidence suggests that QCT methods can be practical tools in the clinical setting to identify and quantify abnormal regions of the lung accurately and reproducibly. This review aimed to describe the available methods for the identification and quantification of small airway disease on CT images and to discuss the challenges of implementing QCT metrics in clinical care for patients with small airway disease.
Building an Optimal Pediatric Trauma Program
Authors: Upperman Jeffrey S.
Published: October 2022

In this brief review, I suggest a framework for the ideal pediatric trauma program. I provide a trauma program construct devised by the American College of Surgeons. I expand on this design by offering some concepts around how trauma programs can maximize their effectiveness in care, education, and research. This review was a preamble for a minisymposium focused on pediatric hemorrhagic shock and resuscitation.

Level of Evidence

IV
Multicompartmental traumatic injury and the microbiome: Shift to a pathobiome
Authors: Munley Jennifer A. , Kelly Lauren S. , Pons Erick E. , Kannan Kolenkode B. , Coldwell Preston S. , Whitley Elizabeth M. , Gillies Gwendolyn S. , Efron Philip A. , Nagpal Ravinder , Mohr Alicia M.
Published: October 2022

BACKGROUND

Previous animal models have demonstrated altered gut microbiome after mild traumatic injury; however, the impact of injury severity and critical illness is unknown. We hypothesized that a rodent model of severe multicompartmental injuries and chronic stress would demonstrate microbiome alterations toward a “pathobiome” characterized by an overabundance of pathogenic organisms, which would persist 1 week after injury.

METHODS

Male Sprague-Dawley rats (n = 8 per group) were subjected to either multiple injuries (PT) (lung contusion, hemorrhagic shock, cecectomy, and bifemoral pseudofractures), PT plus daily chronic restraint stress for 2 hours (PT/CS), or naive controls. Fecal microbiome was measured on days 0, 3, and 7 using high-throughput 16S rRNA sequencing and Quantitative Insights Into Microbial Ecology 2 bioinformatics analysis. Microbial α diversity was assessed using Chao1 and Shannon indices, and β diversity with principle coordinate analysis. Intestinal permeability was evaluated by plasma occludin; ileum and descending colon tissues were reviewed for injury. Analyses were performed in GraphPad (GraphPad Software, La Jolla, CA) and R (R Foundation for Statistical Computing, Vienna, Austria), with significance defined as p < 0.05.

RESULTS

There were significant alterations in β diversity at day 3 and between all groups. By day 3, both PT and PT/CS demonstrated significantly depleted bacterial diversity (Chao1) (p = 0.01 and p = 0.001, respectively) versus naive, which persisted up to day 7 in PT/CS only (p = 0.001). Anaerostipes and Rothia dominated PT and Lactobacillus bloomed in PT/CS cohorts by day 7. Plasma occludin was significantly elevated in PT/CS compared with naive (p = 0.04), and descending colon of both PT and PT/CS showed significantly higher injury compared with naive (p = 0.005, p = 0.006).

CONCLUSIONS

Multiple injuries with and without chronic stress induces significant alterations in microbiome diversity and composition within 3 days; these changes are more prominent and persist for 1 week postinjury with stress. This rapid and persistent transition to a “pathobiome” phenotype represents a critical phenomenon that may influence outcomes after severe trauma and critical illness.
Survivorship
Authors: Livingston David H.
Published: October 2022

This address challenges the trauma community and each trauma center to develop a dedicated outpatient center for trauma survivors, delivering patient-centered, high-quality physical and behavioral health care as well as social support for patients and caregivers.
Venous thromboembolism risk after spinal cord injury: A secondary analysis of the CLOTT study
Authors: Godat Laura N. , Haut Elliott R. , Moore Ernest E. , Knudson M. Margaret , Costantini Todd W.
Published: October 2022

INTRODUCTION

Patients with spinal cord injury (SCI) are at high risk of venous thromboembolism (VTE). Pharmacologic VTE prophylaxis (VTEppx) is frequently delayed in patients with SCI because of concerns for bleeding risk. Here, we hypothesized that delaying VTEppx until >48 hours would be associated with increased risk of thrombotic events.

METHODS

This is a secondary analysis of the 2018 to 2020 prospective, observational, cohort Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) study of patients aged 18 to 40 years, at 17 US level 1 trauma centers. Patients admitted for >48 hours with documented SCI were evaluated. Timing of initiation of VTEppx, rates of thrombotic events (deep vein thrombosis [DVT] and pulmonary embolism [PE]), and missed VTEppx doses were analyzed. The primary outcome was VTE (DVT + PE).

RESULTS

There were 343 patients with SCI. The mean ± SD age was 29.0 ± 6.6 years, 77.3% were male, and 78.7% sustained blunt mechanism. Thrombotic events occurred in 33 patients (9.6%): 30 DVTs (8.7%) and 3 PEs (0.9%). Venous thromboembolism prophylaxis started at ≤24 hours in 21.3% of patients and 49.3% at ≤48 hours. The rate of VTE for patients started on VTEppx ≤48 hours was 7.1% versus 12.1% if started after 48 hours (p = 0.119). After adjusting for differences in risk factors between cohorts, starting ≤48 hours was independently associated with fewer VTEs (odds ratio, 0.45; 95% confidence interval, 0.101–0.978; p = 0.044). Unfractionated heparin was associated with a VTE rate of 21.0% versus 7.5% in those receiving enoxaparin as prophylaxis (p = 0.003). Missed doses of VTEppx were common (29.7%) and associated with increased thrombotic events, although this was not significant on multivariate analysis.

CONCLUSION

Rates of thrombotic events in patients with SCI are high. Prompt initiation of VTEppx with enoxaparin and efforts aimed at avoiding missed doses are critical to limit thrombotic events in these high-risk patients.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.