Routine Clinical Use Research Articles

Personal protective equipment use among dental healthcare personnel during the coronavirus disease 2019 (COVID-19) pandemic and the impact of an educational video in clinical practice.

Dental healthcare personnel (DHCP) are at high risk of exposure to coronavirus disease 2019 (COVID-19). We sought to identify how DHCP changed their use of personal protective equipment (PPE) as a result of the COVID-19 pandemic, and to pilot an educational video designed to improve knowledge of proper PPE use. The study comprised 2 sets of semistructured qualitative interviews. The study was conducted in 8 dental clinics in a Midwestern metropolitan area. In total, 70 DHCP participated in the first set of interviews; 63 DHCP participated in the second set of interviews. In September-November 2020 and March-October 2021, we conducted 2 sets of semistructured interviews: (1) PPE use in the dental community during COVID-19, and (2) feedback on the utility of an educational donning and doffing video. Overall, 86% of DHCP reported having prior training. DHCP increased the use of PPE during COVID-19, specifically N95 respirators and face shields. DHCP reported real-world challenges to applying infection control methods, often resulting in PPE modification and reuse. DHCP reported double masking and sterilization methods to extend N95 respirator use. Additional challenges to PPE included shortages, comfort or discomfort, and compatibility with specialty dental equipment. DHCP found the educational video helpful and relevant to clinical practice. Fewer than half of DHCP reported exposure to a similar video. DHCP experienced significant challenges related to PPE access and routine use in dental clinics during the COVID-19 pandemic. An educational video improved awareness and uptake of appropriate PPE use among DHCP.

The P2X7 Receptor as a Mechanistic Biomarker for Epilepsy

Epilepsy, characterized by recurrent spontaneous seizures, is a heterogeneous group of brain diseases affecting over 70 million people worldwide. Major challenges in the management of epilepsy include its diagnosis and treatment. To date, video electroencephalogram (EEG) monitoring is the gold-standard diagnostic method, with no molecular biomarker in routine clinical use. Moreover, treatment based on anti-seizure medications (ASMs) remains ineffective in 30% of patients, and, even if seizure-suppressive, lacks disease-modifying potential. Current epilepsy research is, therefore, mainly focussed on the identification of new drugs with a different mechanism of action effective in patients not responding to current ASMs. The vast heterogeneity of epilepsy syndromes, including differences in underlying pathology, comorbidities and disease progression, represents, however, a particular challenge in drug discovery. Optimal treatment most likely requires the identification of new drug targets combined with diagnostic methods to identify patients in need of a specific treatment. Purinergic signalling via extracellularly released ATP is increasingly recognized to contribute to brain hyperexcitability and, consequently, drugs targeting this signalling system have been proposed as a new therapeutic strategy for epilepsy. Among the purinergic ATP receptors, the P2X7 receptor (P2X7R) has attracted particular attention as a novel target for epilepsy treatment, with P2X7Rs contributing to unresponsiveness to ASMs and drugs targeting the P2X7R modulating acute seizure severity and suppressing seizures during epilepsy. In addition, P2X7R expression has been reported to be altered in the brain and circulation in experimental models of epilepsy and patients, making it both a potential therapeutic and diagnostic target. The present review provides an update on the newest findings regarding P2X7R-based treatments for epilepsy and discusses the potential of P2X7R as a mechanistic biomarker.

Feasibility of using the Leap Motion Controller to administer conventional motor tests: a proof-of-concept study

Although upper-limb movement impairments are common, the primary tools for assessing and tracking impairments in clinical settings are limited. Markerless motion capture (MMC) technology has the potential to provide a large amount of quantitative, objective movement data in routine clinical use. Many past studies have focused on whether MMC are sufficiently accurate. However, another necessary step is to create meaningful clinical tests that can be administered via MMC in a robust manner. Four conventional upper-limb motor tests common in clinical assessments (visually guided movement, finger tapping, postural tremor, and reaction time) were modified so they can be administered via a particular MMC sensor, the Leap Motion Controller (LMC). In this proof-of-concept study, we administered these modified tests to 100 healthy subjects and present here the successes and challenges we encountered. Subjects generally found the LMC and the graphical user interfaces of the tests easy to use. The LMC recorded movement with sufficiently high sampling rate (>106 samples/s), and the rate of LMC malfunctions (mainly jumps in time or space) was low, so only 1.9% of data was discarded. However, administration of the tests also revealed some significant weaknesses. The visually guided movement test was easily implemented with the LMC; the modified reaction time test worked reasonably well with the LMC but is likely more easily implemented with other existing technologies; and the modified tremor and finger tapping tests did not work well because of the limited bandwidth of the LMC. Our findings highlight the need to develop and evaluate motor tests specifically suited for MMC. The real strength of MMC may not be in replicating conventional tests but rather in administering new tests or testing conditions not possible with conventional clinical tests or other technologies.

Image-derived input functions from dynamic 15O–water PET scans using penalised reconstruction

BackgroundQuantitative positron emission tomography (PET) scans of the brain typically require arterial blood sampling but this is complicated and logistically challenging. One solution to remove the need for arterial blood sampling is the use of image-derived input functions (IDIFs). Obtaining accurate IDIFs, however, has proved to be challenging, mainly due to the limited resolution of PET. Here, we employ penalised reconstruction alongside iterative thresholding methods and simple partial volume correction methods to produce IDIFs from a single PET scan, and subsequently, compare these to blood-sampled input curves (BSIFs) as ground truth. Retrospectively we used data from sixteen subjects with two dynamic 15O-labelled water PET scans and continuous arterial blood sampling: one baseline scan and another post-administration of acetazolamide.ResultsIDIFs and BSIFs agreed well in terms of the area under the curve of input curves when comparing peaks, tails and peak-to-tail ratios with R2 values of 0.95, 0.70 and 0.76, respectively. Grey matter cerebral blood flow (CBF) values showed good agreement with an average difference between the BSIF and IDIF CBF values of 2% ± and a coefficient of variation (CoV) of 7.3%.ConclusionOur results show promising results that a robust IDIF can be produced for dynamic 15O–water PET scans using only the dynamic PET scan images with no need for a corresponding MRI or complex analytical techniques and thereby making routine clinical use of quantitative CBF measurements with 15O–water feasible.

Inflammatory biomarkers in sebum for identifying skin damage in patients with a Stage I pressure ulcer in the pelvic region: A single centre observational, longitudinal cohort study with elderly patients.

Pressure Ulcers (PU) are a major burden for affected patients and healthcare providers. Current detection methods involve visual assessments of the skin by healthcare professionals. This has been shown to be subjective and unreliable, with challenges associated with identifying erythema in darker colour skin. Although there exists a number of promising non-invasive biophysical techniques such as ultrasound, capacitance measurements, and thermography, the present study focuses on directly measuring the changes in the inflammatory status of the skin and underlying tissues. Therefore, in this study, we aim to analyse inflammatory cytokines collected through non-invasive sampling techniques to detect early signs of skin damage. Thirty hospitalised patients presenting with Stage I PU were recruited to evaluate the inflammatory response of skin at the site of damage and an adjacent healthy control site. Sebutapes were collected over three sessions to investigate the temporal changes in the inflammatory response. The panel of cytokines investigated included high-abundance cytokines, namely, IL-1α and IL-1RA, and low abundance cytokines; IL-6, IL-8, TNF-α, INF-γ, IL-33, IL-1β and G-CSF. Spatial and temporal differences between sites were assessed and thresholds were used to determine the sensitivity and specificity of each biomarker. Theresultssuggest significant (P < .05) spatial changes in the inflammatory response, with upregulation of IL-1α, IL-8, and G-CSF as well as down-regulation of IL-1RA over the Stage I PU compared with the adjacent control site. There were no significant temporal differences between the three sessions. Selected cytokines, namely, IL-1α, IL-1RA, IL-8, G-CSF, and the ratio IL-1α/IL-1RA offered clear delineation in the classification of healthy and Stage-I PU skin sites, with receiver operating characteristic curves demonstrating high sensitivity and specificity. There were limited influences of intrinsic and extrinsic factors on the biomarker response. Inflammatory markers provided a high level of discrimination between the sites presenting with Stage I PU and an adjacent healthy skin site, in a cohort of elderly inpatients. Indeed, the ratio of IL-1α to IL-1RA provided the highest sensitivity and specificity, indicative that inflammatory homeostasis is affected at the PU site. There was a marginal influence of intrinsic and extrinsic factors, demonstrating the localised effects of the inflammation. Further studies are required to investigate the potential of inflammatory cytokines incorporated within Point of Care technologies, to support routine clinical use.

A unified classification approach rating clinical utility of protein biomarkers across neurologic diseases.

A major evolution from purely clinical diagnoses to biomarker supported clinical diagnosing has been occurring over the past years in neurology. High-throughput methods, such as next-generation sequencing and mass spectrometry-based proteomics along with improved neuroimaging methods, are accelerating this development. This calls for a consensus framework that is broadly applicable and provides a spot-on overview of the clinical validity of novel biomarkers. We propose a harmonized terminology and a uniform concept that stratifies biomarkers according to clinical context of use and evidence levels, adapted from existing frameworks in oncology with a strong focus on (epi)genetic markers and treatment context. We demonstrate that this framework allows for a consistent assessment of clinical validity across disease entities and that sufficient evidence for many clinical applications of protein biomarkers is lacking. Our framework may help to identify promising biomarker candidates and classify their applications by clinical context, aiming for routine clinical use of (protein) biomarkers in neurology.

Stem Cells In IVF: Hope or Hype?

Perhaps the most obvious link to IVF and stem cells is the development of human Embryonic Stem Cells (hESC) from the inner cell mass of human embryos [4]. Whilst hESC are pluripotent and therefore an excellent candidate for gamete production, very little progress has been made because of the legal, ethical, moral, and religious objections to creating hESC which requires the destruction of a viable human embryo [5]. Induced Pluripotent Stem Cells (iPSC) have a similar history when it comes to IVF. These are somatic cells (e.g., skin cells) which are ‘transformed’ into pluripotent stem cells by the introduction of various genes [6]. These iPSC are pluripotent and autologous, so they have the ability, in theory, to be able to carry out gametogenesis in patients undergoing fertility treatment [7]. The problems with the routine clinical use of iPSC in fertility treatment is the cost but most importantly ongoing safety concerns about iPSC because of the genes needed to be inserted to convert a somatic cell into a stem cell [8]. Mesenchymal stem cells (MSC) can be obtained from adipose tissue, bone marrow, the umbilical cord and even inside teeth [9]. These MSC stem cells can produce bone, connective tissue and adipose tissue and there are some data suggesting that MSC may be useful in premature ovarian failure [10]. The drawbacks of using MSC in the treatment of infertility are the cost and the standardization of MSC to ensure safety and efficacy [11]. All these stem cell types have their problems when considering their use in the treatment of infertility. It may be many years, if ever, before they come to routine clinical practice in the treatment of infertility.

Noninferiority of Artificial Intelligence–Assisted Analysis of Ki-67 and Estrogen/Progesterone Receptor in Breast Cancer Routine Diagnostics

Image analysis assistance with artificial intelligence (AI) has become one of the great promises over recent years in pathology, with many scientific studies being published each year. Nonetheless, and perhaps surprisingly, only few image AI systems are already in routine clinical use. A major reason for this is the missing validation of the robustness of many AI systems: beyond a narrow context, the large variability in digital images due to differences in preanalytical laboratory procedures, staining procedures, and scanners can be challenging for the subsequent image analysis. Resulting faulty AI analysis may bias the pathologist and contribute to incorrect diagnoses and, therefore, may lead to inappropriate therapy or prognosis. In this study, a pretrained AI assistance tool for the quantification of Ki-67, estrogen receptor (ER), and progesterone receptor (PR) in breast cancer was evaluated within a realistic study set representative of clinical routine on a total of 204 slides (72 Ki-67, 66 ER, and 66 PR slides). This represents the cohort with the largest image variance for AI tool evaluation to date, including 3 staining systems, 5 whole-slide scanners, and 1 microscope camera. These routine cases were collected without manual preselection and analyzed by 10 participant pathologists from 8 sites. Agreement rates for individual pathologists were found to be 87.6% for Ki-67 and 89.4% for ER/PR, respectively, between scoring with and without the assistance of the AI tool regarding clinical categories. Individual AI analysis results were confirmed by the majority of pathologists in 95.8% of Ki-67 cases and 93.2% of ER/PR cases. The statistical analysis provides evidence for high interobserver variance between pathologists (Krippendorff's α, 0.69) in conventional immunohistochemical quantification. Pathologist agreement increased slightly when using AI support (Krippendorff α, 0.72). Agreement rates of pathologist scores with and without AI assistance provide evidence for the reliability of immunohistochemical scoring with the support of the investigated AI tool under a large number of environmental variables that influence the quality of the diagnosed tissue images.

Derivation and validation of a novel risk score to predict need for haemostatic intervention in acute upper gastrointestinal bleeding (London Haemostat Score)

BackgroundAcute upper gastrointestinal bleeding (AUGIB) is a common medical emergency, which takes up considerable healthcare resources. However, only approximately 20%–30% of bleeds require urgent haemostatic intervention. Current standard of care...

Creating a brief form of the Supervisory Working Alliance Inventory in the Chinese cultural context using multilevel factor analyses.

The aim of this study was to examine the multilevel factor structure of the Supervisory Working Alliance Inventory (SWAI; Efstation et al., 1990) and shorten it for routine clinical use in the Chinese cultural context. Participants were 203 (Sample 1) and 97 (Sample 2) beginning counseling trainees from a master's level training program in China. They were given the SWAI after every supervision session, and a subset of Sample 1 trainees also completed measures of their counseling self-efficacy before every client session. With Sample 1, multilevel exploratory factory analysis (M-EFA) showed that for the original 19-item version of SWAI, two factors emerged on the within-trainee level (Rapport and Client Focus) as proposed in Efstation et al. (1990), whereas only one General Alliance factor was identifiable on the between-trainee level. After removing poorly or double-loaded items, a six-item brief version of SWAI (SWAI-Brief) was obtained. Using Sample 2, multilevel confirmatory factor analysis and multilevel bifactor models supported the factor structure found in M-EFA with Sample 1. Empirical evidence also supported the reliability of the SWAI-Brief, as well as its criterion-related concurrent and predictive validity given its significant associations with trainee's counseling self-efficacy at the same week and in the subsequent week. Results suggested that the six-item SWAI-Brief could be a reliable and valid measure for assessing supervisory working alliance in the Chinese cultural context and may be used to continuously track clinical supervision processes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A narrative review of genetic biomarkers in non-small cell lung cancer: an update and future perspectives.

Lung cancer has long been the leading cause of cancer deaths in the United States. Lung cancer has a poor prognosis, and our understanding of who will maximally benefit from different therapies is incomplete. This article discusses genetic biomarkers that may help in this regard. From origin until February 25, 2022, PubMed database was searched for terms "non-small cell lung cancer", "genomics" and "biomarker", with special attention paid to literature published within the past 10 years. Search was language restricted to English. Additional literature was identified through hand searches of the references of retrieved literature. The most robustly described biomarkers for non-small cell lung cancer (NSCLC) are assessment of specific gene mutations. These are currently used in clinical practice for both prediction and prognostication. Abnormal mutation status of STK11/LKB1 and KEAP1-NFE2L2 are associated with poor response to radiotherapy (RT), and STK11/LKB1 is further associated with resistance to PD-L1 immunotherapy. Abnormal TP53 is associated with decreased benefit from cisplatin in squamous cell carcinoma (SCC). In terms of prognostication, RB1 mutations are associated with decreased overall survival (OS) in NSCLC and KEAP1-NFE2L2 mutations are associated with increased local recurrence (LR).Additional work has focused on gene expression levels, as well as analysis of genetic factors and signaling molecules affecting the tumor microenvironment (TME). High levels of Rad51c and NFE2L2 are associated with resistance to chemotherapy, and high Rad51c levels are further associated with resistance to RT. High nuclear expression of β-catenin has additionally been associated with poor RT response. Further, there is increasing evidence that some long non-coding RNAs (lncRNAs) may play a crucial role in regulation of tumor radiosensitivity. Much of this work has had promising early results but will require further validation before routine clinical use. Finally, there is evidence that quantification of some signaling molecules and microRNAs (miRNAs) may have clinical utility in predicting adverse outcomes in RT. An improved understanding of tumor genetics in NSCLC has led to the development of targeted therapies and improved prognostication. As more work is done in this field, more and more genetic biomarkers will become candidates for clinical use. Much work will be required to validate these findings in the clinical setting.

Development of a novel Ultra Performance Liquid Chromatography Tandem-Mass Spectrometry (UPLC-MS/MS) method to measure l-arginine metabolites in plasma

IntroductionArginine metabolism is involved in the regulation of several biological processes. Many liquid chromatography tandem-mass spectrometry methods for the determination of arginine and its metabolites have been developed but they are time consuming and imply long pre-analytical procedures. The purpose of this study was to develop a rapid method for the simultaneous determination of arginine, citrulline, ornithine, symmetric and asymmetric dimethylarginine and monomethylarginine in human plasma. Materials and methodsThe pre-analytical procedure consisted in a simple deproteinization. The chromatographic separation was performed using hydrophilic interaction liquid chromatography. Analytes detection was performed with a triple quadrupole equipped with electrospray ion source operating in positive ion mode. Mass spectrometry experiments were conducted in multiple reaction monitoring mode. Results and conclusionsRecovery ranged from 92.2 to 108.0%. The within-run imprecision and between-run imprecision ranged from 1.5 to 6.8 % and 3.8 to 11.9%, respectively.Carry over and matrix effect did not affect quantitative analysis. Extraction recovery was between 95 and 105 %. Stability after pre-analytical procedure was tested and all the metabolites were stable after 48 h at 4 °C.In conclusion, our novel method allow a rapid and easy determination of arginine and its metabolites both for research and clinical routine use.

Simplified calculation of peritoneal dialysis-associated peritonitis rate: Accuracy of a recently developed estimating equation.

Recently, we validated a simple method for estimating peritoneal dialysis (PD) peritonitis rate. Despite good agreement between estimates and gold-standard measurements in two large dialysis registries, the International Society of Peritoneal Dialysis (ISPD) was hesitant to recommend adoption of the estimating equation. Their perception is that inaccuracies, as small as they are, might still be detrimental to clinical decision-making. In this study, we apply new analyses to the original validation data sets. We quantify agreement using standards from the International Organization for Standardization (ISO). We also identify a subset of centres with poorest performance of the estimating equation and qualitatively assess the potential for compromised clinical decision-making associated with its use. Inter-assay % coefficient of variation between estimates and measurements was 4.2% in the Australia and New Zealand Dialysis and Transplant Registry and 4.6% in Le Registre de Dialyse Péritonéale de Langue Française, easily meeting ISO requirements. Mandel's h values and Grubb's tests confirmed more outlying estimates compared to the measurements, while Mandel's k values and Cochran's C tests showed that identical precision by the two methods. Misclassification of centres as being above versus below the ISPD standard of 0.4 episodes/patient-year occurred only with rates close to the threshold, affecting approximately 3% of patient-years. In the 26 (out of 268) centres with poorest performance of the estimating equation, examination of the time series of their annual PD peritonitis rate estimates/measurements showed that using estimates would not detrimental to clinical decision-making. In conclusion, the estimating equation is sufficiently accurate for routine clinical use.

One-Piece Zirconia Oral Implants for Single Tooth Replacement: Five-Year Results from a Prospective Cohort Study

The intention of this 5-year prospective cohort investigation was to clinically and radiographically investigate the outcomes of a one-piece zirconia implant system for single tooth replacement. Sixty-five patients received a total of 66 single-tooth implants. All implants immediately received temporary restorations and were finally restored with all-ceramic crowns. Follow-ups were performed at the prosthetic delivery, after 1, 3, and 5 years. Peri-implant and dental soft-tissue parameters were evaluated and patient-reported outcomes recorded. To monitor peri-implant bone remodelling, standardised radiographs were taken at the implant insertion and at the 1-, 3-, and 5-year follow-ups. In the course of 5 years, 14 implants were lost, resulting in a cumulative implant survival rate of 78.2%. The mean marginal bone loss from the implant insertion to the 5-year follow-up amounted to 1.12 mm. Probing depth, clinical attachment level, bleeding, and plaque index increased over time. In 91.5% of the implants, the papilla index showed levels of 1 or 2, respectively. At the end of the study, the patient satisfaction was higher compared to the pre-treatment measurements. Due to the low survival rate after five years and the noticeably high frequency of advanced bone loss observed in this study, the implant has not met the launch criteria, as it would have not been recommended for routine clinical use.

Longitudinal analysis of annual national hemovigilance data to assess pathogen reduced platelet transfusion trends during conversion to routine universal clinical use and 7-day storage.

France converted to universal pathogen reduced (PR; amotosalen/UVA) platelets in 2017 and extended platelet component (PC) shelf-life from 5- to 7-days in 2018and2019. Annual national hemovigilance (HV) reports characterized longitudinal PC utilization and safety over 11 years, including several years prior to PR adoption as the national standard of care. Data were extracted from published annual HV reports. Apheresis and pooled buffy coat [BC] PC use was compared. Transfusion reactions (TRs) were stratified by type, severity, and causality. Trends were assessed for three periods: Baseline (2010-14; ~7% PR), Period 1 ([P1] 2015-17; 8%-21% PR), and Period 2 ([P2] 2018-20; 100% PR). PC use increased by 19.1% between 2010 and 2020. Pooled BC PC production increased from 38.8% to 68.2% of total PCs. Annual changes in PCs issued averaged 2.4% per year at baseline, -0.02% (P1) and 2.8% (P2). The increase in P2 coincided with a reduction in the target platelet dose and extension to 7-day storage. Allergic reactions, alloimmunization, febrile non-hemolytic TRs, immunologic incompatibility, and ineffective transfusions accounted for >90% of TRs. Overall, TR incidence per 100,000 PCs issued declined from 527.9 (2010) to 345.7 (2020). Severe TR rates declined 34.8% between P1-P2. Forty-six transfusion-transmitted bacterial infections (TTBI) were associated with conventional PCs during baseline and P1. No TTBI were associated with amotosalen/UVA PCs. Infections with Hepatitis E (HEV) a non-enveloped virus resistant to PR, were reported in all periods. Longitudinal HV analysis demonstrated stable PC utilization trends with reduced patient risk during conversion to universal 7-day amotosalen/UVA PCs.

A robust lyophilized kit for convenient one-step formulation of [68Ga]Ga-DOTA-E−[c(RGDfK)]2 in hospital radiopharmacy for clinical PET imaging

The present article describes the development of robust lyophilized kit for convenient formulation of [68Ga]Ga-DOTA-E−[c(RGDfK)]2 (E = glutamic acid, R = arginine, G = glycine, D = aspartic acid, f = phenylalanine, K = lysine) radiopharmaceutical for clinical use in non-invasive monitoring of malignancies overexpressing integrin αvβ3 receptors. Five batches of the kit were prepared with optimized kit contents, all of which showed high 68Ga-radiolabeling yield (>98%). Pre-clinical evaluation of the [68Ga]Ga-radiotracer in SCID mice bearing FTC133 tumour exhibited significant accumulation in the tumor xenograft. Preliminary human clinical investigation carried out in a 60 year old male patient with metastatic lung cancer revealed high radiotracer uptake in the tumor along with satisfactory target to non-target contrast. The developed kit formulation also showed a long shelf-life of at least 12 months on storage at 0 °C. All these results point towards the promising attributes of the developed kit formulation for convenient preparation of [68Ga]Ga-DOTA-E−[c(RGDfK)]2 for routine clinical use.

The role of vasoactive peptides in skin homeostasis-focus on adiponectin and the kallikrein-kinin system.

Vasoactive peptides often serve a multitude of functions aside from their direct effects on vasodynamics. This article will review the existing literature on two vasoactive peptides and their involvement in skin homeostasis: adiponectin and-as the main representative of the kallikrein-kinin system-bradykinin. Adiponectin is the most abundantly expressed adipokine in the human organism, where it is mainly localized in fat depots including subcutaneous adipose tissue, from where adiponectin can exert paracrine effects. The involvement of adiponectin in skin homeostasis is supported by a number of studies reporting the effects of adiponectin in isolated human keratinocytes, sebocytes, fibroblasts, melanocytes, and immune cells. Regarding skin pathology, the potential involvement of adiponectin in psoriasis, atopic dermatitis, scleroderma, keloid, and melanogenesis is discussed in this article. The kallikrein-kinin system is composed of a variety of enzymes and peptides, most of which have been identified to be expressed in the skin. This also includes the expression of bradykinin receptors on most skin cells. Bradykinin is one of the very few hormones that is targeted by treatment in routine clinical use in dermatology-in this case for the treatment of hereditary angioedema. The potential involvement of bradykinin in wound healing, psoriasis, and melanoma is further discussed in this article. This review concludes with a call for additional preclinical and clinical studies to further explore the therapeutic potential of adiponectin supplementation (for psoriasis, atopic dermatitis, wound healing, scleroderma, and keloid) or pharmacological interference with the kallikrein-kinin system (for wound healing, psoriasis, and melanoma).

Impact and Modification of the New PJI-TNM Classification for Periprosthetic Joint Infections

The comprehensive "PJI-TNM classification" for the description of periprosthetic joint infections (PJI) was introduced in 2020. Its structure is based on the well-known oncological TNM classification to appreciate the complexity, severity, and diversity of PJIs. The main goal of this study is to implement the new PJI-TNM classification into the clinical setting to determine its therapeutic and prognostic value and suggest modifications to further improve the classification for clinical routine use. A retrospective cohort study was conducted at our institution between 2017 and 2020. A total of 80 consecutive patients treated with a two-stage revision for periprosthetic knee joint infection were included. We retrospectively assessed correlations between patients' preoperative PJI-TNM classification and their therapy and outcome and identified several statistically significant correlations for both classifications, the original and our modified version. We have demonstrated that both classifications provide reliable predictions already at the time of diagnosis regarding the invasiveness of surgery (duration of surgery, blood and bone loss during surgery), likelihood of reimplantation, and patient mortality during the first 12 months after diagnosis. Orthopedic surgeons can use the classification system preoperatively as an objective and comprehensive tool for therapeutic decisions and patient information (informed consent). In the future, comparisons between different treatment options for truly similar preoperative baseline situations can be obtained for the first time. Clinicians and researchers should be familiar with the new PJI-TNM classification and start implementing it into their routine practice. Our adjusted and simplified version ("PJI-pTNM") might be a more convenient alternative for the clinical setting.

Myocardial late gadolinium enhancement using delayed 3D IR-FLASH in the pediatric population: feasibility and diagnostic performance compared to single-shot PSIR-bSSFP

BackgroundThis study compares three-dimensional (3D) high-resolution (HR) late gadolinium enhancement (LGE; 3D HR-LGE) imaging using a respiratory navigated, electrocardiographically-gated inversion recovery gradient echo sequence with conventional LGE imaging using a single-shot phase-sensitive inversion recovery (PSIR) balanced steady-state free precession (bSSFP; PSIR-bSSFP) sequence for routine clinical use in the pediatric population. MethodsPediatric patients (0–18 years) who underwent clinical cardiovascular magnetic resonance (CMR) with both 3D HR-LGE and single-shot PSIR-bSSFP LGE between January 2018 and June 2020 were included. Image quality (0–4) and detection of LGE in the left ventricle (LV) (per 17 segments), in the right ventricle (RV) (per 3 segments), as endocardial fibroelastosis (EFE), at the hinge points, and at the papillary muscles was analyzed by two blinded readers for each sequence. Ratios of the mean signal intensity of LGE to normal myocardium (LGE:Myo) and to LV blood pool (LGE:Blood) were recorded. Data is presented as median (1st–3rd quartiles). Wilcoxon signed rank test and chi-square analyses were used as appropriate. Inter-rater agreement was analyzed using weighted κ-statistics. Results102 patients were included with median age at CMR of 8 (1–13) years-old and 44% of exams performed under general anesthesia. LGE was detected in 55% of cases. 3D HR LGE compared to single-shot PSIR-bSSFP had longer scan time [4:30 (3:35–5:34) vs 1:11 (0:47–1:32) minutes, p < 0.001], higher image quality ratings [3 (3–4) vs 2 (2–3), p < 0.001], higher LGE:Myo [23.7 (16.9–31.2) vs 5.0 (2.9–9.0), p < 0.001], detected more segments of LGE in both the LV [4 (2–8) vs 3 (1–7), p = 0.045] and RV [1 (1–1) vs 1 (0–1), p < 0.001], and also detected more cases of LGE with 13/56 (23%) of patients with LGE only detectable by 3D HR LGE (p < 0.001). 3D HR LGE specifically detected a greater proportion of RV LGE (27/27 vs 17/27, p < 0.001), EFE (11/11 vs 5/11, p = 0.004), and papillary muscle LGE (14/15 vs 4/15, p < 0.001). Inter-rater agreement for the recorded variables ranged from 0.42 to 1.00. Conclusions3D HR LGE achieves greater image quality and detects more LGE than conventional single-shot PSIR-bSSFP LGE imaging, and should be considered an alternative to conventional LGE sequences for routine clinical use in the pediatric population.

Abstract WP162: Primary Results Of Mechanical Thrombectomy For Acute Ischemic Stroke In Clinical Practice: K-net Registry

Background: Endovascular treatment (EVT) for acute large vessel occlusion has been found to be effective in several randomized controlled trials. We conducted a prospective cohort study to evaluate the real-world efficacy of EVT in patients with acute ischemic stroke in a metropolitan area with a high population density and a large number of comprehensive stroke centers. Methods: We analyzed the Kanagawa Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry, a prospective, multicenter observational study of patients treated by EVT and/or intravenous tissue-type plasminogen activator (tPA), in Kanagawa, Japan. Of the 2488 patients enrolled from January 2018 to June 2020, 1764 patients treated with EVT were included. The primary outcome was a good outcome, which was defined as a modified Rankin Scale (mRS) of 0 to 2 at 90 days. Secondary analysis included predicting a good outcome using multivariate logistic regression analysis. Results: The median age was 77 years and the median National Institute of Health Stroke Scale (NIHSS) score was 18. Pretreatment mRS score 0-2 was 87%, and direct transport was 92%. The rate of occlusion in anterior circulation was 90.3%. Successful recanalization was observed in 88.7%. The median time from onset to recanalization was 193 minutes. Good outcomes at 90 days were 43.3% in anterior circulation and 41.9% in posterior circulation. Furthermore, 49.3% of patients with anterior circulation obstruction who had pre-stroke mRS 0-2 had good outcome, which was higher than the HERMES trial. Overall mortality was 12.6%. Significant predictors for a good outcome were: age, male, direct transfer, NIHSS score, Alberta Stroke Program Early Computed Tomography Score, intravenous tPA, and successful recanalization. Conclusions: EVT in routine clinical use in a metropolitan area showed comparable good outcomes and lower mortality compared to previous registries and RCTs, despite the high proportion of patients with older age, pretreatment mRS score of &gt; 2, posterior circulation occlusion, and higher NIHSS. Those results may have been associated with more direct transport and faster onset-to-recanalization times.