bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between popliteal artery wall thickness and structural progression in patients with symptomatic knee osteoarthritis
Authors: Wang Yuanyuan , Pontoh Ega Wirayoda , Hussain Sultana Monira , Lim Yuan Z , Jones Graeme , Hill Catherine L , Wluka Anita E , Tonkin Andrew , Ding Changhai , Cicuttini Flavia M
Published: August 2022

Objective

There is increasing evidence for the involvement of vascular disease in the pathogenesis of knee OA. Popliteal artery wall thickness can be used as a surrogate marker of atherosclerosis. We examined the association between popliteal artery wall thickness and knee cartilage volume in individuals with symptomatic knee OA.

Methods

This prospective cohort study analysed 176 participants from a randomized placebo-controlled trial examining the effect of atorvastatin on structural progression in knee OA. The participants underwent MRI of the study knee at baseline and 2-year follow-up. Popliteal artery wall thickness and tibial cartilage volume were measured from MRI using validated methods. The top quartile of the rate of tibial cartilage volume loss was defined as rapid progression.

Results

At baseline, every 10% increase in popliteal artery wall thickness was associated with 120.8 mm3 (95% CI 5.4, 236.2, P = 0.04) lower of medial tibial cartilage volume and 151.9 mm3 (95% CI 12.1, 291.7, P = 0.03) lower of lateral tibial cartilage volume. Longitudinally, for every 10% increase in popliteal artery wall thickness, the annual rate of medial tibial cartilage volume loss was increased by 1.14% (95% CI 0.09%, 2.20%, P = 0.03), and there was a 2.28-fold (95% CI 1.07, 4.83, P = 0.03) risk of rapid progression of medial tibial cartilage loss, adjusted for age, sex, BMI, tibial bone area, smoking, vigorous physical activity, and intervention group allocation.

Conclusion

The findings support a role for vascular pathology in the progression of knee OA. Targeting atherosclerosis has the potential to improve outcomes in knee OA.
Empowered Homeowners, Responsible Mothers: Promises and Pitfalls of Maternalist Housing Provision in Brazil’s Minha Casa Minha Vida Program
Authors: Koppelman Carter M
Published: August 2022

Brazil’s Minha Casa Minha Vida (MCMV) program was touted as a “pro-female” policy to promote women’s autonomy and empowerment through subsidized homeownership. However, its design and discourse constructed motherhood as the primary basis of women’s inclusion. This article examines the gendered effects of a maternalist housing program through ethnographic research in São Paulo, looking at both movement organizations using MCMV to provide housing for members, and everyday life among residents in an MCMV-subsidized housing complex. It finds that while many women felt empowered by inclusion in MCMV, the program also produced gendered exclusions and reinforced unequal gendered burdens. First, it selectively prioritized low-income mothers while excluding other groups of women as undeserving “single people.” Second, it primed beneficiaries to view state-subsidized housing as conditioned upon their responsibility for home and family, expanding maternal obligations to include the financial management of homeownership without easing gendered burdens of care.
Interactions of amyloid coaggregates with biomolecules and its relevance to neurodegeneration
Authors: Murakami Kazuma , Ono Kenjiro
Published: August 2022

The aggregation of amyloidogenic proteins is a pathological hallmark of various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In these diseases, oligomeric intermediates or toxic aggregates of amyloids cause neuronal damage and degeneration. Despite the substantial effort made over recent decades to implement therapeutic interventions, these neurodegenerative diseases are not yet understood at the molecular level. In many cases, multiple disease‐causing amyloids overlap in a sole pathological feature or a sole disease‐causing amyloid represents multiple pathological features. Various amyloid pathologies can coexist in the same brain with or without clinical presentation and may even occur in individuals without disease. From sparse data, speculation has arisen regarding the coaggregation of amyloids with disparate amyloid species and other biomolecules, which are the same characteristics that make diagnostics and drug development challenging. However, advances in research related to biomolecular condensates and structural analysis have been used to overcome some of these challenges. Considering the development of these resources and techniques, herein we review the cross‐seeding of amyloidosis, for example, involving the amyloids amyloid β, tau, α‐synuclein, and human islet amyloid polypeptide, and their cross‐inhibition by transthyretin and BRICHOS. The interplay of nucleic acid‐binding proteins, such as prions, TAR DNA‐binding protein 43, fused in sarcoma/translated in liposarcoma, and fragile X mental retardation polyglycine, with nucleic acids in the pathology of neurodegeneration are also described, and we thereby highlight the potential clinical applications in central nervous system therapy.
Feasibility of Emergency Department–based Fentanyl Test Strip Distribution
Authors: Lima Rafael A. , Karch Lydia B. , Lank Patrick M. , Allen Katherine C. , Kim Howard S.
Published: August 2022

Objectives

United States drug overdose deaths now overwhelmingly involve fentanyl and fentanyl analogs. The emergency department (ED) is an important setting to provide harm reduction for persons who use drugs, but ED-based fentanyl test strip distribution has not yet been described.

Methods

This is an observational study of patients with an opioid-related visit to an ED in downtown Chicago, Illinois. We offered fentanyl test strips alongside an existing take-home naloxone program and report on the number of patients who accepted fentanyl test strips. We assessed patient familiarity with fentanyl and fentanyl test strips during the index ED visit and attempted to contact patients 1 month after the ED visit to determine testing outcomes.

Results

We offered fentanyl test strips to 23 consecutive ED patients (mean age, 39.8 years; male, 73.9%) with an opioid-related ED visit (87.0% for opioid overdose). Sixteen patients (69.5%) had heard of fentanyl, and 2 (8.7%) had prior experience using fentanyl test strips. Eighteen patients (78.2%) accepted the fentanyl test strips, 2 of which left the test strips behind in the ED alongside their take-home naloxone kit. Of the 16 total patients who departed with fentanyl test strips, we were able to reach 3 (18.8%) by phone 1 month after their ED visit; 9 had disconnected or wrong numbers listed. All 3 patients reported a positive fentanyl test strip result; tested substances included heroin, alprazolam, and cocaine.

Conclusions

This report demonstrates the feasibility and acceptability of ED fentanyl test strip distribution among patients with opioid-related ED visits.
Comprehensive Prediction Model, Including Genetic Testing, for the Outcomes of Cochlear Implantation
Authors: Han Ji Hyuk , Kim Sung Huhn , Moon In Seok , Joo Sun Young , Kim Jung Ah , Gee Heon Yung , Jung Jinsei , Choi Jae Young
Published: August 2022

Objectives:

Despite growing interest in the genetic contribution to cochlear implant (CI) outcomes, only a few studies with limited samples have examined the association of CI outcomes with genetic etiologies. We analyzed CI outcomes using known predictors and genetic testing results to obtain a comprehensive understanding of the impact of genetic etiologies.

Design:

We retrospectively reviewed the medical records and images of patients who underwent cochlear implantation and genetic testing at a single tertiary medical institution, between May 2008 and December 2020. After excluding those whose speech test results were unavailable, and those in whom the implant was removed due to complications, such as infection or device failure, 203 patients were included in this study. The participants were categorized into adult (≥19 years), child (2–18 years), and infant (<24 months) groups. Outcomes were measured based on categories of auditory perception, monosyllable, disyllable, and sentence scores. For the infant group, the Infant–Toddler Meaningful Auditory Integration Scale score was used.

Results:

Among the 203 participants, a causative genetic variant was identified in 117 (57.6%) individuals. The presence of a causative variant was significantly associated with better CI outcomes in the infant group (β = 0.23; 95% confidence interval, 0.01 to 0.47; p = 0.044), but not in the child and adult groups. In the genetically confirmed patients without cochlear malformation, genetic variants involving the spiral ganglion was a poor prognostic factor in the child group (β = −57.24; 95% confidence interval, −90.63 to −23.75; p = 0.004).

Conclusions:

The presence of known genetic etiology of hearing loss was associated with better CI outcomes in the infant group, but not in the child and adult groups. A neural-type genetic variant was a poor prognostic factor in the genetically diagnosed child subgroup without cochlear malformation. Careful genetic counseling should be performed before cochlear implantation.
Sex differences in normal and malignant hematopoiesis
Authors: Cui Xiaojing , Zhao Xinghui , Liang Ying
Published: August 2022

Introduction:

Hematopoiesis is a continuous and well-regulated process requiring both the capacity for self-renewal and the potential for differentiation of hematopoietic stem cells.

Results:

Multiple studies indicate that sex hormones exert significant effects on not only hematopoietic stem and progenitor cells, but also the development of hematopoietic lineages, resulting in sexual dimorphisms in normal hematopoiesis. Hematologic malignancies comprise a wide variety of cancers affecting the blood, bone marrow, and lymphatic system, such as leukemia, lymphoma, myeloma, myelodysplastic syndrome, and myeloproliferative diseases. Overall, males are at greater risk and have worse prognosis for most of these malignancies compared with females.

Conclusion:

A better understanding of the differences between male and female could be of substantial value in research as well as clinical management.
Modern Surgical Techniques for Treatment of Chronic Lateral Ankle Instability
Authors: Kukadia Saanchi K. , Murphy Conor I. , Shah Henal , Drakos Mark C.
Published: August 2022

Ankle sprains are among the most common injuries sustained during sports and physical activity. Around 2 million ankle sprains occur per year with ~85% of them being lateral ankle sprains. Lateral ankle sprains involve damage to the lateral ligamentous complex of the ankle. Patients with a history of lateral ankle sprains are at a 3.5× greater risk of re-injury than those who do not have a history of lateral ankle sprain. Repeated damage to the lateral ligamentous complex can result in the development of chronic lateral ankle instability (CLAI). CLAI can be managed conservatively or surgically. Given the frequency with which sprains occur, and the relative infrequency of symptoms requiring an operation, 80 to 85% of patients can be managed conservatively with good results and minimal disability. However, even with conservative treatment, a 56 to 74% recurrence rate of ankle sprain has been reported. Patients with CLAI who continue to display persistent symptoms after rehabilitation through conservative measures may require surgical intervention. These surgical techniques include direct ligament repair, anatomic reconstruction, and nonanatomic reconstruction. In this chapter we will discuss these procedures, along with their implications and associated risks. We offer different surgical techniques to manage CLAI and available outcome data.

Level of Evidence:

Diagnostic level 4, case series
Clinical Characteristics and Outcomes of Gastritis Associated With Immune Checkpoint Inhibitors: Scoping Review
Authors: Obeidat Adham , Silangcruz Krixie , Kozai Landon , Wien Eric , Fujiwara Yu , Nishimura Yoshito
Published: August 2022

Among immune-related adverse events associated with immune checkpoint inhibitors, immune-mediated gastritis (IMG) has been rarely described in the literature and has not yet been well characterized. This scoping review aimed to characterize IMG in terms of precipitating agents, clinical presentations, and prognosis. After the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including “gastritis,” “immune checkpoint inhibitor,” and “immune-related adverse event” from their inception to December 28, 2021. Twenty-two articles, including 5 observational studies and 17 case reports and case series, were included. Nivolumab, pembrolizumab, and combination therapy with those and cytotoxic T-lymphocyte-associated antigen-4 inhibitor (ipilimumab) were commonly used in those with IMG. 59.8% had epigastric pain, and 50% had erosive gastritis. 87.5% had Common Terminology Criteria for Adverse Events (CTCAE) grade 3 gastritis, and 91.2% received corticosteroids. Recurrence was noted in 16.7%, and only 1 expiration was noted. 4.3% had positive helicobacter pylori and cytomegalovirus from the gastric specimen. Similar to immune-related colitis, patients with IMG may have a favorable prognosis with a better response to immune checkpoint inhibitors if treated appropriately. The diagnosis of IMG is made by exclusion, and a thorough workup is necessary to rule out concurrent helicobacter pylori and cytomegalovirus involvement. Further studies are critical for a better understanding of this complication.
Activation of GPR75 Signaling Pathway Contributes to the Effect of a 20-HETE Mimetic, 5,14-HEDGE, to Prevent Hypotensive and Tachycardic Responses to Lipopolysaccharide in a Rat Model of Septic Shock
Authors: Tunctan Bahar , Senol Sefika Pinar , Temiz-Resitoglu Meryem , Yilmaz Dilsah Ezgi , Guden Demet Sinem , Bahceli Omer , Horat Mehmet Furkan , Sahan-Firat Seyhan , Sari Ayse Nihal , Falck John R. , Anugu Raghunath Reddy , Malik Kafait U.
Published: August 2022

The orphan receptor, G protein–coupled receptor (GPR) 75, which has been shown to mediate various effects of 20-hydroxyeicosatetraenoic acid (20-HETE), is considered as a therapeutic target in the treatment of cardiovascular diseases in which changes in the production of 20-HETE play a key role in their pathogenesis. Our previous studies showed that 20-HETE mimetic, N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE), protects against vascular hyporeactivity, hypotension, tachycardia, and arterial inflammation induced by lipopolysaccharide (LPS) in rats. This study tested the hypothesis that the GPR75 signaling pathway mediates these effects of 5,14-HEDGE in response to systemic exposure to LPS. Mean arterial pressure reduced by 33 mm Hg, and heart rate increased by 102 beats/min at 4 hours following LPS injection. Coimmunoprecipitation studies demonstrated that (1) the dissociation of GPR75/Gαq/11 and GPR kinase interactor 1 (GIT1)/protein kinase C (PKC) α, the association of GPR75/GIT1, large conductance voltage and calcium-activated potassium subunit β (MaxiKβ)/PKCα, MaxiKβ/proto-oncogene tyrosine-protein kinase (c-Src), and epidermal growth factor receptor (EGFR)/c-Src, MaxiKβ, and EGFR tyrosine phosphorylation were decreased, and (2) the association of GIT1/c-Src was increased in the arterial tissues of rats treated with LPS. The LPS-induced changes were prevented by 5,14-HEDGE. N-[20-Hydroxyeicosa-6(Z),15(Z)-dienoyl]glycine, a 20-HETE antagonist, reversed the effects of 5,14-HEDGE in the arterial tissues of LPS-treated rats. Thus, similar to 20-HETE, by binding to GPR75 and activating the Gαq/11/PKCα/MaxiKβ, GIT1/PKCα/MaxiKβ, GIT1/c-Src/MaxiKβ, and GIT1/c-Src/EGFR signaling pathways, 5,14-HEDGE may exert its protective effects against LPS-induced hypotension and tachycardia associated with vascular hyporeactivity and arterial inflammation.
miR-133a—A Potential Target for Improving Cardiac Mitochondrial Health and Regeneration After Injury
Authors: Puthanveetil Prasanth , O'Hagan Kathleen P.
Published: August 2022

The various roles of muscle secretory factors and myokines have been well studied, but in recent decades, the role of myocyte-specific microRNAs (myomiRs) has gained momentum. These myomiRs are known to play regulatory roles in muscle health in general, both skeletal muscle and cardiac muscle. In this review, we have focused on the significance of a myomiR termed miR-133a in cardiovascular health. The available literature supports the claim that miR-133a could be helpful in the healing process of muscle tissue after injury. The protective function could be due to its regulatory effect on muscle or stem cell mitochondrial function. In this review, we have shed light on the protective mechanisms offered by miR-133a. Most of the beneficial effects are due to the presence of miR-133a in circulation or tissue-specific expression. We have also reviewed the potential mechanisms by which miR-133a could interact with cell surface receptors and also transcriptional mechanisms by which they offer cardioprotection and regeneration. Understanding these mechanisms will help in finding an ideal strategy to repair cardiac tissue after injury.
Turn Up the HETE on Septic Shock
Authors: Thomas Kirby , Strong Luke , Fan Fan , Roman Richard J.
Published: August 2022

Septic shock is life-threatening organ dysfunction due to a dysregulated response to infection. It is a leading cause of death caused by the excessive release of cytokines and inflammatory mediators in response to bacterial endotoxins. It produces hypotension refractory to vasoconstrictors leading to tissue hypoperfusion and multiple organ failure. Despite intensive investigation, there still are no specific pharmacologic treatments. Current therapy relies on supportive care, including antibiotics, fluid resuscitation, corticosteroids, and pressor agents. This commentary summarizes little-known previous observations that inhibition of vascular 20-hydroxyeicosatetraenoic acid (20-HETE) by nitric oxide plays a key role in sepsis. It also highlights the new and exciting current report by Tunctan et al (2022) in this issue of Journal of Cardiovascular Pharmacology that administration of a 20-HETE mimetic can prevent lipopolysaccharide-induced vascular hyporeactivity, hypotension, and tachycardia in rats by activating the recently discovered GPR75/20-HETE receptor. Overall, these results provide a compelling case for initiating 20-HETE clinical trials to prevent hypotension, multiple organ failure, and death in septic shock.
Visual simulations of presbyopic corrections through cataract opacification
Authors: Barcala Xoana , Zaytouny Amal , Rego-Lorca Daniela , Sanchez-Quiros Julia , Sanchez-Jean Ruben , Martinez-de-la-Casa Jose Maria , Dorronsoro Carlos , Marcos Susana
Published: August 2022

Purpose:

To study the viability of visual simulation of presbyopic corrections in patients with cataract, the effect and impact of the cataract on the perceived visual quality of the different simulated presbyopic corrections pre- and post-operatively.

Setting:

San Carlos Clinical Hospital, Madrid, Spain

Design:

Observational, non-interventional, pilot study, early feasibility of the device being studied.

Methods:

Cataract patients were tested pre-operatively (n=24) and post-operatively (n=15) after bilateral implantation of monofocal intraocular lenses. The degree of cataract was evaluated objectively with the Ocular Scattering Index (OSI). Visual acuity (VA) and perceived visual quality of natural scene images (Multifocal Acceptance Score) were measured before and after cataract surgery at far (4 m), intermediate (64 cm) and near distance (40 cm) with four binocular presbyopic corrections (single vision, bifocal, monovision and modified-monovision) simulated with a binocular Simultaneous Vision simulator based on temporal multiplexing.

Results:

VA was significantly correlated with OSI (r=-0.71, p<0.0005), although the visual degradation at far for each correction was constant and not correlated with OSI. The visual benefit at near distance provided by the presbyopic correction was noticeable (23.3±27.6% across corrections) for OSI<5. The individual perceptual scores were highly correlated pre-operatively vs post-operatively (r=0.64, p<0.0005) for all corrections and distances.

Conclusions:

Visual simulations of IOLs are an excellent tool to explore prospective post-operative vision. The high correlation in the perceptual scores pre- and post-cataract surgery demonstrates that SimVis Gekko can be used in cataractous patients to guide the selection of the optimal correction for a patient.
Firefighters’ Health Knowledge, Cardiovascular Disease Risk Factors, and Sociodemographic Characteristics as Predictors of Firefighters Attitudes Toward Health
Authors: Ras Jaron , Leach Lloyd
Published: August 2022

Objective

The aim of the study is to determine the predictors of firefighters’ attitudes toward health based on firefighters’ knowledge cardiovascular disease (CVD) risk factors and sociodemographic characteristics.

Methods

The study used a web-based cross-sectional, descriptive, and correlational research design. Convenience sampling was used to recruit 110 firefighters, males, and females, aged 18 to 65 years.

Results

Firefighters’ health knowledge, age group 30 to 39 years, and having CVD risk factors present were significant predictors of firefighters’ attitudes toward regular aerobic exercise (P < 0.05). Firefighters’ health knowledge was a significant predictor of firefighters liking exercise to look physically fit, and health knowledge and the age group 20 to 29 and 30 to 39 years were significant predictors of firefighters liking exercise to be fit for firefighting (P < 0.05).

Conclusions

Health knowledge, age group, years of experience, and having CVD risk factors present were significant predictors of firefighters’ attitudes toward health.
Comorbid Vulvar Lichen Sclerosus and High-Grade Squamous Intraepithelial Lesions: A Management Conundrum
Authors: Janke Monica J. , DeBlanc Jennie , Kobernik Emily K. , Skala Stephanie L. , Hiles Guadalupe Lorenzatti , Kelly Rebeca , Welch Kathryn C.
Published: August 2022

Objective

This study aimed to determine if treating lichen sclerosus (LS) with high-potency topical corticosteroids (TCS) increases the risk of high-grade squamous intraepithelial lesion (HSIL) recurrence in patients with comorbid vulvar LS and HSIL.

Methods

This is a retrospective study of patients with comorbid vulvar LS and HSIL treated with TCS between 2015 and 2020. Patients with clinically diagnosed or biopsy-proven LS and biopsy-proven HSIL of the vulva were included. Clinical data included demographics, tobacco use, immune-modifying conditions, specimen pathology, treatment types, and HSIL recurrence. Bivariate analysis was performed to compare demographic and clinical characteristics between patients with and without HSIL recurrence.

Results

Twenty-six patients with comorbid LS and HSIL were identified. The median age was 66.0 years and median time in treatment for LS was 5.5 years. Thirteen (50%) had recurrence of HSIL and 13 (50%) did not have recurrence. Exposure to high-potency TCS was present in 20 (77%) patients, with 17 (65%) having use of more than 1-year duration and 9 (35%) having use at the time of HSIL diagnosis. When comparing the groups with and without HSIL recurrence, there was no significant difference in high-potency TCS exposure, duration of use, or use at time of HSIL diagnosis.

Conclusions

High-potency TCS use for the treatment of LS did not seem to increase the risk of HSIL recurrence in patients with comorbid vulvar LS and HSIL. This suggests that high-potency TCS can be appropriately used for the treatment of LS even when HPV-associated disease is present.
Monoclonal Antibodies for First-Line Treatment of Metastatic Colorectal Cancer
Authors: Liao Pei-Fei , Wu Ta-Wei , Peng Tzu-Rong
Published: August 2022

Background:

In addition to discontinuing treatment at disease progression, cumulative toxicity limitations and genetic mutations play important roles in chemotherapy choice in metastatic colorectal cancer (mCRC). However, in recent years, targeted therapies, such as immune checkpoint inhibitors or monoclonal antibodies (MoAbs), have been used with chemotherapy to improve clinical outcomes in patients with mCRC.

Areas of Uncertainty:

Approximately 15% of patients with CRC would be eligible for further targeted therapy with immune checkpoint inhibitors based on genetic testing, but most patients with CRC would not qualify, especially Kirsten rat sarcoma wild-type. Therefore, adding MoAb is only an option for most patients until disease progression or unacceptable toxicity occurs. However, the results are not consistent with the combination of MoAb and different chemotherapy bases. In addition, most results from combining MoAb with different chemotherapy bases are not consistent.

Data Sources:

This meta-analysis includes published of the PubMed and Embase databases, limited to English literature, and patients were treated with MoAb combination. Randomized control trials conducted published up to May 2021 were considered for inclusion.

Therapeutic Advances:

Fluoropyrimidine-based chemotherapy has been the backbone of palliative therapy for mCRC, with demonstrated benefits. This article will review the efficacy and safety of randomized control trials comparing different MoAb with fluoropyrimidine-based chemotherapy as first-line therapy for patients with mCRC, particularly in Kirsten rat sarcoma wild-type.

Conclusion:

This meta-analysis revealed that MoAb plus chemotherapy has better progression-free survival and objective response rate than chemotherapy alone. However, treatment-related serious adverse events (grade ≥ 3) should be considered, particularly severe rash, diarrhea, and hypertension.
Comparison of 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT in patients with non-small cell lung cancer
Authors: Can Canan , Kepenek Ferat , Kömek Halil , Gündoğan Cihan , Kaplan İhsan , Taşdemir Bekir , Güzel Yunus , Agüloğlu Nurşin , Karaoğlan Hüseyin
Published: August 2022

Aim

In this study, we aimed to compare the diagnostic accuracy of 18F−fluorodeoxyglucose (18F-FDG) and Gallium-68 labeled fibroblast activator protein inhibitor (68Ga-FAPI)-04 PET/CT in the tumor–node–metastasis (TNM) staging of patients with nonsmall cell lung cancer (NSCLC) and investigate whether adenocarcinoma (ADC) and squamous cell cancer (SCC) exhibit different uptake patterns on 68Ga-FAPI-04 PET/CT.

Materials and method

Twenty-nine patients with a histopathologically-confirmed diagnosis of NSCLC, who had no history of previous radiation therapy or chemotherapy and underwent 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT imaging between January 2021 and December 2021 were included in this retrospective study. Staging was performed using the 8th edition of the TNM staging system on both 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT images. Standardized uptake value (SUV)max and tumor-to-background ratios (TBR) were calculated on primary lesions and metastases.

Results

There was no statistically significant difference in primary lesions in terms of SUVmax and TBR values. However, 68Ga-FAPI-04 PET/CT was significantly superior to 18F-FDG PET/CT in terms of the number of lymph nodes and bone metastases revealed. The SUVmax and TBR values of lymph nodes, hepatic lesions and bone lesions were significantly higher on 68Ga-FAPI-04 PET/CT than on 18F-FDG PET/CT. 68Ga-FAPI-04 PET/CT changed the disease stage of three patients (10.9%). The diagnostic accuracy of 68Ga-FAPI-04 PET/CT was 100%, whereas the diagnostic accuracy of 18F-FDG PET/CT was 89.6% (P = 0.250).

Conclusion

Although 68Ga-FAPI-04 PET/CT detected more lesions and higher diagnostic accuracy than 18F-FDG PET/CT in NSCLC, neither method was statistically superior to each other in terms of diagnostic accuracy in TNM staging.
Clinical Outcomes of Patients with Osteosarcoma Experiencing Relapse or Progression: A Single-institute Experience
Authors: Umeda Katsutsugu , Sakamoto Akio , Noguchi Takashi , Uchihara Yoshinori , Kobushi Hirokazu , Akazawa Ryo , Ogata Hideto , Saida Satoshi , Kato Itaru , Hiramatsu Hidefumi , Uto Megumi , Mizowaki Takashi , Haga Hironori , Date Hiroshi , Okamoto Takeshi , Watanabe Kenichiro , Adachi Souichi , Toguchida Junya , Matsuda Shuichi , Takita Junko
Published: August 2022

Background:

Patients with osteosarcoma who experience relapse or progression [R/P] have a poor prognosis.

Methods:

Data from 30 patients who experienced R/P among 59 with a diagnosis of high-grade osteosarcoma, who were younger than 40 years old between 2000 and 2019, were retrospectively analyzed to identify prognostic and therapeutic factors influencing their outcomes.

Results:

The 5-year overall survival [OS] rates after the last R/P of patients experiencing first [n=30], second [n=14], and third [n=9] R/P were 50.3%, 51.3%, and 46.7%, respectively. Multivariate analysis did not identify any independent risk factors affecting OS. The 5-year PFS rate of the 30 patients after first R/P was 22.4%, and multivariate analysis identified histologic subtype and curative local surgery as independent risk factors influencing PFS. Long [>6 mo] partial response was observed in three patients treated using temozolomide+etoposide, irinotecan+carboplatin, or regorafenib.

Conclusions:

OS rate in the patients with osteosarcoma experiencing R/P included in this study was markedly higher than that reported previously, mainly due to the surgical total removal of tumors, even after subsequent R/P. The recent establishment of salvage chemotherapy or molecular targeted therapy may also increase survival rates in a subgroup of patients.
Autoimmune Myelofibrosis in a 12-Year-old Male With Monosomy 7, Systemic Lupus Erythematous and Lupus Nephritis: A Case Report and Review of the Literature
Authors: Español María G. , Ehlayel Abdulla M. , Alicea Marrero Minelys M. , Gardner Renee V. , Velez María C.
Published: August 2022

Complete or partial loss of chromosome 7 is a common and well-known cytogenetic abnormality associated with preleukemic myelodysplasia and myeloid leukemia but not with autoimmune myelofibrosis. Detection of this molecular change represents poor prognosis. When malignant transformation occurs, the condition tends to be chemotherapy-resistant requiring haematopoietic stem cell transplantation (HSCT) to obtain a cure. Disappearance after immunosuppressive therapy has been documented in children with hematological disorders but not in association with cyclophosphamide and systemic lupus erythematous.We present the interesting case of a 12-year-old male with monosomy 7, systemic lupus erythematous, and lupus nephritis with the resolution of the monosomy 7 and autoimmune myelofibrosis after treatment with cyclophosphamide, along with a review of the literature.
Roles of Vitamin-K-dependent Factors Protein S and GAS6 With TAM Receptors and HMGB1 in Pediatric COVID-19 Disease
Authors: Şik Nihan , Duman Murat , Küme Tuncay , Gürsoy Doruk Özlem , Yilmaz Durgül , Ören Hale
Published: August 2022

Objective:

This study was designed to evaluate serum high-mobility group box 1 (HMGB1), protein S (PS), growth arrest-specific gene 6 (GAS6), and TAM receptor (TYRO3, AXL, and MERTK) levels in children with COVID-19 disease.

Methods:

A prospective case-control study was conducted in our pediatric emergency department and 57 patients with SARS-CoV-2 polymerase chain reaction (PCR) positivity, 6 patients with multisystem inflammatory syndrome in children (MIS-C), and 17 healthy children were included. Demographic data, clinical findings, laboratory and radiologic data, the need for hospitalization, and prognosis were recorded. Serum HMGB1, PS, GAS6, and TAM receptor levels were studied by enzyme-linked immunosorbent assay method.

Results:

While SARS-CoV-2 PCR-positive patients and healthy controls were similar in terms of gender and age, GAS6 and MERTK levels were significantly lower in SARS-CoV-2 PCR-positive patients compared with healthy controls. Among SARS-CoV-2 PCR-positive patients, no difference was found in terms of serum markers in those with and without gastrointestinal or respiratory system symptoms. However, in patients with respiratory distress at admission, PS and TYRO3 levels were significantly lower. AXL levels were lower in patients diagnosed with MIS-C compared with healthy controls. Activated partial thromboplastin time was negatively correlated with HMGB1, PS, GAS6, and AXL levels.

Conclusion:

Our results suggest that such measurements may be informative and warranted in children with COVID-19 who show evidence of coagulopathy and respiratory distress. Further studies are needed to clarify the roles of these markers in diagnosis, to predict clinical severity, and to evaluate their roles in treatment approaches for COVID-19 disease.
Prelicensure Virtual Clinical Practicum to Improve Quality and Safety Education for Nurses Competencies
Authors: Halstead Valerie , Letourneau Rayna
Published: August 2022

Fluctuating prelicensure educational experiences during the COVID-19 pandemic may result in new nurses entering professional practice without necessary competencies to provide optimal patient care. A virtual clinical practicum was an effective strategy to increase nursing students’ confidence across six Quality and Safety Education for Nurses competencies. Importantly, nursing professional development practitioners may utilize this virtual clinical program during onboarding or as part of ongoing career development for nurses across a variety of healthcare systems.
Traumatic Diaphragmatic Injuries at Medicolegal Autopsy
Authors: van Wyk Charmaine , Hlaise Keven Khazamula , Blumenthal Ryan
Published: August 2022

Introduction

Traumatic diaphragmatic injuries (TDIs) are relatively rare. The forensic literature pertaining to TDIs consists mainly of case studies, suggesting little attention to these injuries during autopsies and research.

Materials and Methods

This prospective study was conducted at the Ga-Rankuwa Forensic Pathology Services mortuary over a 1-year period. We included all cases who had a full medicolegal autopsy, as prescribed by the relevant South African legislation (Inquest Act 58 of 1959). All diaphragms were examined by a forensic medical practitioner performing the autopsy.

Results

Nine hundred ninety-nine cases were analyzed; of these, 71 cases with TDIs were identified. The incidence of TDI was, therefore, determined to be 7.11%. A total of 60.56% involved the right hemidiaphragm, 19.72% the left hemidiaphragm, and 19.72% were present bilaterally. A total of 85.92% were present in men and 14.08% in women. Blunt force trauma comprised 33.80%, and penetrative trauma 61.97%. Most were associated with severe injuries. A total of 12.68% had organ herniation through the defects present.

Conclusions

Our study revealed that TDIs were more common than initially reported. The right side was more often involved in our study than in other studies. Diaphragmatic injuries were observed in 21.46% of all penetrative trauma cases received in a year.
PRAME Expression in Cancer. A Systematic Immunohistochemical Study of >5800 Epithelial and Nonepithelial Tumors
Authors: Kaczorowski Maciej , Chłopek Małgorzata , Kruczak Anna , Ryś Janusz , Lasota Jerzy , Miettinen Markku
Published: August 2022

Preferentially expressed antigen in melanoma (PRAME) is considered a useful marker in the differential diagnosis between malignant melanoma and its melanocytic mimics. Recently PRAME expression was documented in nonmelanocytic tumors, but much of the data are based on mRNA studies. This investigation evaluated PRAME expression in the spectrum of normal tissues and >5800 human tumors using immunohistochemistry and EP461 monoclonal antibody. In normal tissues, PRAME was expressed in the testis and proliferative endometrium. In tumors, PRAME was variably expressed in malignancies of different lineages. Among epithelial tumors, >50% of PRAME-positive lesions were found among endometrial carcinomas (82%), uterine serous carcinomas (82%), uterine carcinosarcomas (60%), ovarian clear cell carcinomas (90%), ovarian serous carcinomas (63%), adenoid cystic carcinomas (81%), seminomas (78%), thymic carcinomas (75%), and basal cell carcinomas (62%). In mesenchymal and neuroectodermal malignancies, PRAME was frequently expressed in synovial sarcoma (71%), myxoid liposarcoma (76%), neuroblastoma (61%) and metastatic melanoma (87%). Also, PRAME was consistently expressed in 4 melanomas that lacked all melanoma markers including S100 protein and SOX10 but harbored typical for melanoma BRAF or NRAS driver mutations. However, strong and diffuse PRAME immunoreactivity was seen in many types of nonmelanocytic poorly differentiated carcinomas and sarcomas. Based on this study, PRAME is a relatively unspecific immunohistochemical marker, which limits its use in diagnostic surgical pathology. However, immunohistochemistry is a reliable and unexpensive method useful in detecting PRAME-positive malignancies for potential immunotherapy.
Everolimus is Safe as a Second-/Third-Line Therapy in Pediatric Autoimmune Hepatitis
Authors: Jannone Giulia , Scheers Isabelle , Smets Françoise , Stephenne Xavier , M Sokal Etienne
Published: August 2022

Objectives:

Autoimmune hepatitis (AIH) can lead to progressive fibrosis in patients refractory to conventional therapy with prednisolone and azathioprine. The use of mammalian target of rapamycin (mTOR) inhibitors has recently emerged in refractory AIH, but no data have been published about everolimus in pediatric AIH to date. Our aim was to share our experience about everolimus as a second-/third-line therapy in pediatric AIH.

Methods:

Pretransplant AIH patients aged 0–18 years who received everolimus therapy from 2014 to 2021 were retrospectively identified. All patients underwent regular plasma monitoring of everolimus trough levels to avoid toxicity and assess adherence. Special attention was paid to the clinical and biochemical occurrence of everolimus-related adverse events.

Results:

We report six difficult-to-treat AIH patients who received everolimus therapy for 8–46 months (median 28 months). No side effects were reported when everolimus plasma trough levels were in the therapeutic range. Liver transaminases improved in 5 of 6 patients at everolimus introduction and significantly decreased at the last follow-up (FU) in our cohort (P < 0.05). None of our patients achieved complete biochemical remission at the last FU and 3 of 6 admitted to have suboptimal adherence to therapy.

Conclusions:

Our data bring preliminary safety for the use of everolimus as a second-/third-line therapy in pediatric AIH. Although liver transaminases improved in our cohort, prospective studies are needed to determine if everolimus can induce long-term remission.
Framework for Training in Minimally Invasive Pancreatic Surgery: An International Delphi Consensus Study
Authors: Korrel Maarten , Lof Sanne , Alseidi Adnan A , Asbun Horacio J , Boggi Ugo , Hogg Melissa E , Jang Jin-young , Nakamura Masafumi , Besselink Marc G , Abu Hilal Mohammad ,   for the International Consortium on Minimally Invasive Pancreatic Surgery (I-MIPS)
Published: August 2022

BACKGROUND:

Previous reports suggest that structured training in minimally invasive pancreatic surgery (MIPS) can ensure a safe implementation into standard practice. Although some training programs have been constructed, worldwide consensus on fundamental items of these training programs is lacking. This study aimed to determine items for a structured MIPS training program using the Delphi consensus methodology.

STUDY DESIGN:

The study process consisted of 2 Delphi rounds among international experts in MIPS, identified by a literature review. The study committee developed a list of items for 3 key domains of MIPS training: (1) framework, (2) centers and surgeons eligible for training, and (3) surgeons eligible as proctor. The experts rated these items on a scale from 1 (not important) to 5 (very important). A Cronbach’s α of 0.70 or greater was defined as the cut-off value to achieve consensus. Each item that achieved 80% or greater of expert votes was considered as fundamental for a training program in MIPS.

RESULTS:

Both Delphi study rounds were completed by all invited experts in MIPS, with a median experience of 20 years in MIPS. Experts included surgeons from 31 cities in 13 countries across 4 continents. Consensus was reached on 38 fundamental items for the framework of training (16 of 35 items, Cronbach’s α = 0.72), centers and surgeons eligible for training (19 of 30 items, Cronbach’s α = 0.87), and surgeons eligible as proctor (3 of 10 items, Cronbach’s α = 0.89). Center eligibility for MIPS included a minimum annual volume of 10 distal pancreatectomies and 50 pancreatoduodenectomies.

CONCLUSION:

Consensus among worldwide experts in MIPS was reached on fundamental items for the framework of training and criteria for participating surgeons and centers. These items act as a guideline and intend to improve training, proctoring, and safe worldwide dissemination of MIPS.
Do plasmids containing heavy metal resistance genes play a role in neonatal sepsis and invasive disease caused by Klebsiella pneumoniae and Klebsiella variicola?
Authors: Turton Jane F. , Perry Claire , Claxton Alleyna
Published: August 2022

Introduction.

Klebsiella

species are some of those most implicated in neonatal sepsis. However, many isolates from infections appear unremarkable; they are generally susceptible to antibiotics and often of sporadic types not associated with virulence.

Hypothesis/Gap Statement. Investigation is needed to identify if such isolates have virulence characteristics.

Aim. To sequence multiple isolates of a range of types from cases of neonatal invasive disease to identify elements that may explain their virulence, and to determine if such elements are more common among these isolates than generally.

Methodology. In total, 14 isolates of

K. pneumoniae

/

K. variicola

belonging to 13 distinct types from blood or CSF from neonatal infections were sequenced using long-read nanopore technology. PCR assays were used to screen a general set of isolates for heavy metal resistance genes arsC, silS and merR.

Results. Overall, 12/14 isolates carried one or more plasmids. Ten carried a large plasmid (186 to 310 kb) containing heavy metal resistance genes associated with hypervirulence plasmids, with most (nine) carrying genes for resistance to copper, silver and one other heavy metal (arsenic, tellurite or mercury), but lacking the genes encoding capsule-upregulation and siderophores. Most isolates (9/14) lacked any additional antibiotic resistance genes other than those intrinsic in the species. However, a representative of an outbreak strain carried a plasmid containing bla
CTX-M-15, qnrS1, aac3_IIa, dfrA17, sul1, mph(A), tet(A), bla
TEM1B and aadA5, but no heavy metal resistance genes. arsC, silS and merR were widely found among 100 further isolates screened, with most carbapenemase-gene-positive isolates (20/27) carrying at least one.

Conclusion. Plasmids containing heavy metal resistance genes were a striking feature of isolates from neonatal sepsis but are widely found. They share elements in common with virulence and antibiotic resistance plasmids, perhaps providing a basis from which such plasmids evolve.
A long-term prospective cohort study of seriously injured older trauma patients
Authors: Ibitoye Sarah , Bridgeman-Rutledge Lily , Carter Ben , Braude Philip
Published: August 2022

A protocol for a prospective observational cohort study to investigate the effect of frailty on long-term outcomes in older adults admitted with trauma. Patients aged 65 years and older admitted to the Severn Major Trauma Centre at North Bristol NHS Trust in England between November 2018 and September 2019, will be followed up at 4-years. The objective is to determine if there is an association between Clinical Frailty Scale and mortality at 4 years after admission to hospital with a traumatic injury. The primary outcome will be mortality as measured by time from hospital admission to death. Analyses will be adjusted for other factors shown to be associated with mortality, using a mixed-effects multivariable Cox proportional hazards model.

Protocol Version

Signature Page

The undersigned confirm that the following protocol has been agreed and accepted and that the Chief Investigator agrees to conduct the study in compliance with the approved protocol and will adhere to the principles outlined in the Declaration of Helsinki, the Sponsor’s SOPs, and other regulatory requirements.

I agree to ensure that the confidential information contained in this document will not be used for any other purpose other than the evaluation or conduct of the investigation without the prior written consent of the Sponsor

I also confirm that I will make the findings of the study publicly available through publication or other dissemination tools without any unnecessary delay and that an honest, accurate and transparent account of the study will be given; and that any discrepancies from the study as planned in this protocol will be explained.

Chief Investigator

Key Study Contacts

Study Summary

Funding and Support in Kind

Roles and Responsibilities

Protocol Contributors

Study Flow Chart
Performance of the Cue COVID-19 Molecular Test for Point of Care: Insights from a multi-site clinic service model
Authors: Rebbapragada Anu , Cariazo Lane , Elchuk David , Abdelrahman Hossam , Pham Dang , Joseph Nirochile , Gouzenkova Elena , Gill Harpreet , Blecher Peter
Published: August 2022

The COVID-19 pandemic highlighted the critical need for rapid and accurate molecular diagnostic testing. The Cue COVID-19 Point of Care Test (Cue POCT) is a nucleic acid amplification test (NAAT), authorized by Health Canada and FDA as a POCT for SARS-CoV-2 detection. Cue POCT was deployed at a network of clinics in Ontario, Canada with n=13,848 patrons tested between July 17, 2021 to January 31, 2022. The clinical performance and operational experience with Cue POCT was examined for this testing population composed mostly of asymptomatic individuals (93.7%). A head-to-head prospective clinical verification was performed between July 17 to October 4 for all POCT service clients (n= 3037) with paired COVID-19 testing by Cue and RT-PCR. Prospective verification demonstrated a clinical sensitivity of 100% and clinical specificity of 99.4% for Cue COVID-19 POCT. The lack of false negatives and low false positive rate (0.64%), underscores the high accuracy (99.4%) of Cue POCT to provide rapid PCR quality results. Low error rates (cancellation rate of 0% and invalid rate of 0.63%) with the current software version were additionally noted. Together these findings highlight the value of accurate molecular COVID-19 POCT in a distributed service delivery model to rapidly detect cases in the community with the potential to curb transmission in high exposure settings (i.e. in-flight, congregate workplace and social events). The insights gleaned from this operational implementation are readily transferable to future POCT diagnostic services.