Use In Routine Clinical Practice Research Articles

Value of synthetic MRI quantitative parameters in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate.

Transrectal ultrasonography (TRUS)/magnetic resonance imaging (MRI) fusion-guided biopsy has a high clinical application value. However, this technique has some limitations, which limit its use in routine clinical practice. Therefore, the selection of suitable proatate lesions for this technique is worthy of our attention. Synthetic MRI (SyMRI) is capable of quantifying multiple relaxation parameters, which might have potential value in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate. The aim of our study is to examine the value of SyMRI quantitative parameters in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate. We prospectively selected 148 lesions in 137 patients who underwent prostate biopsy in our hospital. Next, 2-4 needles of TRUS/MRI fusion-guided biopsy combined with 10 needles of system biopsy(SB) were used as the protocol for prostate biopsy. Before biopsy, the MAGiC sequences of the MRI images of the enrolled patients underwent post-processing, and the longitudinal relaxation time (T1), transverse relaxation time (T2), and proton density (PD) were extracted. The biopsy pathology results were used as a gold standard to compare the differences in SyMRI quantitative parameters between benign and malignant prostate lesions in the peripheral and transitional zones. The receiver operating characteristic (ROC) curves were plotted to confirm the optimal SyMRI quantitative parameter for prostate lesion benignancy/malignancy performance, and the cutoff values of these parameters were used for grouping the lesions. The single-needle biopsy prostate cancer (PCa)-positivity rates (number of positive biopsy needles/total biopsy needles) and PCa overall detection rates by TRUS/MRI fusion-guided biopsy and SB were compared in different subgroups. The T1 and T2 values can determine the benignancy/malignancy of prostate transition lesions(p < 0.01), and the T2 value has a greater diagnostic performance (p = 0.0376). The T2 value can determine the benignancy/malignancy of prostate peripheral lesions. The optimal diagnostic cutoff values for T2 were 77 and 81 ms, respectively. The single-needle PCa positivity rate of TRUS/MRI fusion-guided biopsy was higher than SB for any prostate lesions in different subgroups (p < 0.01). However, only in the subgroup of transition zone lesions with T2 ≤ 77 ms, the PCa overall detection rate of TRUS/MRI fusion-guided biopsy was significantly higher than that of SB (p = 0.031). SyMRI-T2 value can provide a theoretical basis for the selection of suitable lesions for TRUS/MRI fusion-guided biopsy.

Attitudes of Neurologists Toward the Use of Biomarkers in the Diagnosis of Early Alzheimer's Disease.

Alzheimer's disease (AD) biomarkers reflect key elements of pathophysiology and improve the diagnostic process. However, their use in routine clinical practice is still limited. We aimed to assess neurologists' barriers and enablers to early AD diagnosis using core AD biomarkers. We conducted an online study in collaboration with the Spanish Society of Neurology. Neurologists answered a survey exploring their attitudes towards AD diagnosis using biomarkers in mild cognitive impairment (MCI) or mild AD dementia. Multivariate logistic regression analyses were conducted to determine the association between neurologists' characteristics and diagnostic attitudes. We included 188 neurologists with a mean age (SD) of 40.6 (11.3) years, 52.7% male. Most participants had access to AD biomarkers, mainly in cerebrospinal fluid (CSF) (89.9%,#x0025;, n = 169). The majority of participants (95.2%,#x0025;, n = 179) considered CSF biomarkers useful for an etiological diagnosis in MCI. However, 85.6% of respondents (n = 161) used them in less than 60% of their MCI patients in routine clinical practice. Facilitating patients and their families to plan for the future was the most frequent enabler for the use of biomarkers. Short consultation time and practicalities associated with the programming of a lumbar puncture were the most common barriers. A younger neurologist age (p = 0.010) and a higher number of patients managed weekly (p = 0.036) were positively associated with the use of biomarkers. Most neurologists had a favorable attitude to the use of biomarkers, especially in MCI patients. Improvements in resources and consultation time may increase their use in routine clinical practice.

Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer's disease.

The clinical benefit associated with anti-amyloid immunotherapies, a new class of drugs for the treatment of Alzheimer's disease, is predicated on their ability to modify disease course by lowering brain amyloid levels. At the time of writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food and Drug Administration accelerated approval, with further agents of this class in the Alzheimer's disease treatment pipeline. Based on limited published clinical trial data to date, regulators, payors and physicians will need to assess their efficacy, clinical effectiveness and safety, as well as cost and accessibility. We propose that attention to three important questions related to treatment efficacy, clinical effectiveness and safety should guide evidence-based consideration of this important class of drugs. These are: (1) Were trial statistical analyses appropriate and did they convincingly support claims of efficacy? (2) Do reported treatment effects outweigh safety concerns and are they generalizable to a representative clinical population of people with Alzheimer's disease? and (3) Do the data convincingly demonstrate disease course modification, suggesting that increasing clinical benefits beyond the duration of the trials are likely? We suggest specific approaches to interpreting trial results for these drugs and highlight important areas of uncertainty where additional data and a cautious interpretation of existing results is warranted. Safe, effective and accessible treatments for Alzheimer's disease are eagerly awaited by millions of patients and their caregivers worldwide. While amyloid-targeting immunotherapies may be promising disease-modifying Alzheimer's disease treatments, rigorous and unbiased assessment of clinical trial data is critical to regulatory decision-making and subsequently determining their provision and utility in routine clinical practice. Our recommendations provide a framework for evidence-based appraisal of these drugs by regulators, payors, physicians and patients.

The Glasgow Prognostic Score Predicts Survival in Patients with Advanced Non-Small Cell Lung Cancer Harboring Sensitive Epidermal Growth Factor Receptor Mutations Who Are Treated with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors

Introduction: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with sensitive EGFR mutations. The Glasgow prognostic score (GPS) is an inflammation-assessing score based on C-reactive protein and albumin concentrations. Information regarding the association between the GPS and EGFR-TKI treatment effectiveness is limited; hence, we investigated whether the GPS can predict the response of NSCLC to EGFR-TKIs. Methods: We evaluated 340 patients with NSCLC harboring sensitive EGFR mutations who received EGFR-TKI monotherapy between March 2009 and July 2021. The Kaplan-Meier method and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). Results: After a median follow-up of 26.6 months, patients with a GPS of 0, 1, and 2 had PFS of 15.7, 10.0, and 6.3 months, respectively, and OS of 40.1, 25.8, and 14.4 months, respectively; patients with a GPS of 0 had significantly better PFS and OS than those with a GPS of 1 (p = 0.03, p = 0.001, respectively) or 2 (p < 0.001, p < 0.001, respectively). Multivariate analysis identified poor performance status, stage 4 at diagnosis, type of EGFR-TKI (gefitinib/erlotinib vs. afatinib), and GPS = 2 as predictors of a short PFS. Meanwhile, poor performance status, gefitinib/erlotinib administration, and GPS = 2 were predictors of a short OS. Conclusion: The GPS predicted the survival of NSCLC patients harboring sensitive EGFR mutations who were undergoing EGFR-TKI treatment. The GPS might be ideal for routine use in clinical practice, given that it is an easily calculated parameter.

The Gray Zone: LR3, LR-M, and LR-TIV

AbstractThe goal of Liver Imaging Reporting and Data System (LI-RADS) is to standardize the lexicon, imaging techniques, interpretation, and reporting of observations in patients with a potential risk for developing hepatocellular carcinoma (HCC), and, consequently, improve communication between radiologists and physicians. LI-RADS diagnostic algorithms are applied to a population “at risk,” follow a stepwise algorithmic approach which categorize and stratify individual observations as HCC, and also assess the likelihood of non-HCC malignancies and tumor in vein. Risk factors for developing HCC have geographical variations, which significantly impact diagnostic and management strategies; however, these variations are not considered in the LIRADS v2018 version. Further, the diagnostic algorithm includes several major and ancillary features, and, tie-breaking rules, which result in numerous probable combinations by which a plausible observation could be assigned a particular category, inherently increasing its complexity. Heterogeneity of the diagnostic algorithm results in certain imaging pitfalls and poses challenges in the precise characterization of observations, complicating its use in routine clinical practice. This article reviews the gray zones which may be encountered in the evaluation of LR-3, LR-M, and LR-TIV observations during routine clinical imaging with contrast-enhanced computed tomography and magnetic resonance imaging.

Prediction equations to estimate muscle mass using anthropometric data: a systematic review.

Reduced muscle mass is linked to poor outcomes in both inpatients and outpatients, highlighting the importance of muscle mass assessment in clinical practice. However, laboratory methods to assess muscle mass are not yet feasible for routine use in clinical practice because of limited availability and high costs. This work aims to review the literature on muscle mass prediction by anthropometric equations in adults or older people. The following databases were searched for observational studies published until June 2022: MEDLINE, Embase, Scopus, SPORTDiscus, and Web of Science. Of 6437 articles initially identified, 63 met the inclusion criteria for this review. Four independent reviewers, working in pairs, selected and extracted data from those articles. Two studies reported new equations for prediction of skeletal muscle mass: 10 equations for free-fat mass and lean soft tissue, 22 for appendicular lean mass, 7 for upper-body muscle mass, and 7 for lower-body muscle mass. Twenty-one studies validated previously proposed equations. This systematic review shows there are numerous equations in the literature for muscle mass prediction, and most are validated for healthy adults. However, many equations were not always accurate and validated in all groups, especially people with obesity, undernourished people, and older people. Moreover, in some studies, it was unclear if fat-free mass or lean soft tissue had been assessed because of an imprecise description of muscle mass terminology. This systematic review identified several feasible, practical, and low-cost equations for muscle mass prediction, some of which have excellent accuracy in healthy adults, older people, women, and athletes. Malnourished individuals and people with obesity were understudied in the literature, as were older people, for whom there are only equations for appendicular lean mass. PROSPERO registration number CRD42021257200.

Effects of Immunonutrition on Cancer Patients Undergoing Surgery: A Scoping Review.

There is a large body of evidence about immunonutrition formulas; however, there are still doubts about their usefulness in routine clinical practice as compared with standard formulas. In the age of personalized medicine, new studies appear every year regarding several types of patients; therefore, an updated point of view on these formulas is necessary. The Embase database was searched from 2016 to 14 March 2022. Our criteria were articles published in English and Spanish. The evidence quality was evaluated using GRADEpro, and the review was developed according to the PRISMA statement. In this review, a total of 65 unique records were retrieved; however, 36 articles did not meet the inclusion criteria and were thus excluded. In total, 29 articles were included in the final analysis. In the last few years, many meta-analyses have attempted to identify additional existing studies of surgical patients with certain pathologies, mainly oncological patients. Immunonutrition prior to oncological surgery was shown to cause a decrease in inflammatory markers in most of the studies, and the main clinical events that changed were the infectious complications after surgery. The length of stay and mortality data are controversial due to the specific risk factors associated with these events. The use of immunonutrition in patients who have undergone oncological surgery decreases the levels of inflammatory markers and infectious postoperative complications in almost all localizations. However, more studies are needed to assess the use of immunonutrition based on Enhanced Recovery After Surgery (ERAS) protocols.

Abstract P4-07-51: Impact of the Theralink CLIA protein/phosphoprotein assay on treatment selection in routine clinical practice: a prospective observational study in advanced breast cancer

Abstract Background: The Theralink Reverse Phase Protein Array-based (RPPA) CLIA assay is a novel molecular assay developed to assist physicians in therapy selection for patients diagnosed with advanced/recurrent breast cancer. The assay was specifically designed to quantitatively measure protein activation/phosphorylation of 32 FDA-approved and Phase III drug targets and pathway-linked downstream substrates, providing functional information on actionable oncogenic drivers in individual tumors. Given the recent commercialization of the Theralink assay (TLA), knowledge gaps exist regarding its use in routine clinical practice and the impact of the test on clinical decision-making in real world practice. The primary objective of this analysis was to assess how the TLA has been integrated in therapy selection for breast cancer patients with a focus on understanding its target population, the rationale for patient selection by the treating physician, and the utilization of the molecule information generated by the assay as part of the therapeutic decision-making process. Findings from this study will help optimize patient selection and maximize the clinical impact of the test as a tool for advancing precision oncology. Methods: We prospectively collected data from 124 women with advanced breast cancer whose tumors were profiled using the Breast Cancer TLA from February, 2021 to May, 2022. All patients were confirmed as actively managed for advanced/recurrent breast cancer. Eight μm FFPE sections (n=5) from a recently collected tissue biopsy were used to isolate tumor epithelia via Laser Capture Microdissection and to generate RPPA-based molecular profiles. Clinical management and therapy selection information for 68 patients was gathered via surveys completed by treating physicians. Results: Median age of the 124 participants was 53 years (range 26-82) and 111 (89.5%) patients had stage IV disease. The cohort included 66 hormone receptors positive (of which 5 were HER2+), 51 triple negative, and 7 HR-/HER2+ breast cancers. The TLA yielded molecular information for all specimens and profiles were generated on average in 11 days. One or more targets were highly activated (highly actionable) in 91 patients (73.4%) and moderately activated (partially actionable) in 29 patents; only 4 patients had no actionable target (3.2%). Previous treatment information was available for 118 (95.2%) patients. The TLA was requested to assist with the selection of first-line treatment in 36 patients (of which 24 had previously received neoadjuvant treatment), second-line treatment in 35 patients and third- or subsequential-lines of treatment in 47 patients. Clinicians provided feedback on the use of the assay for 68 patients included in the study. The survey revealed that the TLA impacted treatment selection in 50 (73.5%) cases and was used to either expand options beyond standard of care (30 cases), refine/re-prioritize available treatments (11 cases), narrow treatment from a plethora of options (2 cases) or a combination of the three (7 cases). When TLA data were used for treatment selection, physicians defined the assay highly and moderately beneficial for patient management in 15 and 27 cases, respectively. Conclusion: Our study suggests the TLA yields useful information for selecting treatment for breast cancer patients with advanced/recurrent disease. In this prospective analysis, the assay identified actionable targets in more than 90% of patients, which is significantly higher than what has previously been reported for genomic profiling alone. Overall, physicians found the information yielded by the assay useful for selecting treatment. The inclusion of the TLA in oncology may offer important insights for advancing precision medicine for breast cancer patients. Citation Format: Kris Weinberg, Mariaelena Pierobon, Edik Blais, Justin Davis, Joyce O’Shaughnessy, Emanuel F. Petricoin. Impact of the Theralink CLIA protein/phosphoprotein assay on treatment selection in routine clinical practice: a prospective observational study in advanced breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-51.

Is single fraction the future of stereotactic body radiation therapy (SBRT)? A critical appraisal of the current literature

Stereotactic Body Radiation Therapy (SBRT) is a standard of care for many localizations but the question of the optimal fractionation remains a matter of concern. If single fraction sessions are routinely used for intracranial targets, their utilization for mobile extracranial lesions is a source of debate and apprehension. Single session treatments improve patient comfort, provide a medico-economic benefit, and have proven useful in the context of the SARS-CoV2 pandemic. However, both technical and radiobiological uncertainties remain. Experience from intracranial radiosurgery has shown that the size of the target, its proximity to organs at risk, tumor histology, and the volume of normal tissue irradiated are all determining factors in the choice of fractionation. The literature on the use of single fraction for extracranial sites is still scarce. Only primary and secondary pulmonary tumors have been evaluated in prospective randomized trials, allowing the integration of these fractionation schemes in daily practice, for highly selected cases and in trained teams. The level of evidence for the other organs is mainly based on dose escalation or retrospective trials and calls for caution, with further studies being needed before routine use in clinical practice.

Abstract P6-04-15: AI-based prediction of tertiary lymphoid structures and lymphocyte immune infiltration in breast carcinomas

Abstract Introduction Tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs) in breast carcinomas are prognostic for survival and predictive of certain therapy responses. The presence of TLSs and TILs are identified by manual pathological examination; however, this method often lacks reproducibility, limiting its use in routine clinical practice. Here, we demonstrate that morphological evaluation of whole slide images (WSIs) using an artificial intelligence (AI)-based analytic workflow comprised of convolutional neural network (CNN) deep learning models that accurately and reproducibly characterizes TILs, measured as the lymphocyte immune-infiltrated area (LIIA), and TLSs in the tumor microenvironment (TME) of breast carcinomas. Methods We collected a cohort of 445 TCGA breast cancer H&amp;E WSIs, including clinical and sequencing data, and divided this cohort into luminal invasive lobular carcinoma (ILC) (n = 192), HER2-enriched (n = 110), and basal-like (n = 143) molecular subtypes. After 55 samples were excluded due to artifacts or incomplete clinical annotation, a total of 390 samples were analyzed. A combination of CNN-based deep learning models was used to detect and classify the tumor area, TLSs present in the TME, TLS density (number of TLS per mm2 of tumor), and lymphocyte-rich regions. The LIIA was calculated as the area of the stromal and TIL components of the TME. Validation was performed by manually annotating 10 random WSIs from the dataset. Spatial model predictions of the tumor and TLSs were combined to identify TLS locations. Each model’s predictions were verified by univariate (Kaplan-Meier) and multivariate (Cox regression) survival analyses, and the log-rank test was used to calculate overall survival. Additionally, the relationship between TLSs and LIIAs with CD274 expression (PD-L1) and a high tumor mutational burden (TMB &amp;gt; 10) was analyzed. Statistical analyses included Spearman’s rank correlation and Mann-Whitney tests. Results TLS were detected in 53% (n = 207) of the samples, with a mean density of 26.02 TLS/mm2 (Q3 = 5.53 TLS/mm2). TLS density was higher in basal-like subtype samples compared to luminal and HER2-enriched subtypes. While LIIA and TMB-high samples exhibited a significant relationship (p = 0.00001), no significant association was found between TME and TLS quantities or density. PD-L1 gene expression exhibited weak to moderate correlations with predicted LIIA in basal-like (r = 0.38, p = 0.00001) and HER2-enriched subtypes (r = 0.38, p = 0.0001). The luminal subtype had no significant correlation between PD-L1 expression and predicted LIIA. As a result, LIIA and TLS were characterized as positive prognostic factors for the basal-like subtype. After adjusting for age, stage, and grade, the LIIA and TLS density were found to be significant independent positive prognostic overall survival factors for the basal-like subtype (LIIA HR: 0.02, p = 0.003; TLS-high group HR: 0.09, p = 0.002). For the HER2-enriched subtype, TLS density was also a significant predictor (HR: 0.05, p = 0.035), while LIIA was not a statistically significant prognostic factor (HR: 0.0002, p = 0.08). Associations were not observed between the TLSs and LIIA between the ILC subtypes and survival outcomes. The same result was observed for univariate analyses. Conclusion The developed analytic pipeline accurately identified the presence of LIIA and TLS on H&amp;E slides, demonstrating the potential of CNN for automated characterization of the breast cancer TME. AI-based TLS and LIIA quantification can be a robust tool for pathology processes, offering additional information to help in clinical decision-making. This approach can be used to detect features of immune morphology biomarkers in other cancer types. Citation Format: Vladimir Kushnarev, Daniil Dymov, Nadezhda Lukashevich, Lev Popyvanov, Anna Belozerova, Diana Shamsutdinova, Aida Akaeva, Yury Popov, Svetlana Khorkova, Ivan Valiev, Anastasia Zotova, Jessica H. Brown, Anna Love, Alexander Bagaev, Ekaterina Postovalova, Nathan Fowler. AI-based prediction of tertiary lymphoid structures and lymphocyte immune infiltration in breast carcinomas [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-15.

A real-world data analysis of Clinical Global Impression-Severity (CGI-S) as a transdiagnostic predictor of psychiatric hospitalisation

IntroductionPreventing psychiatric admissions holds benefits for patients as well as healthcare systems. The Clinical Global Impression-Severity (CGI-S) scale is a 7-point measurement of symptom severity, independent of diagnosis, which has shown capability of predicting risk of hospitalisation in schizophrenia. Due to its routine use in clinical practice and ease of administration, it may have potential as a transdiagnostic predictor of hospitalisation.ObjectivesTo investigate whether early trajectories of CGI-S scores predict risk of hospitalisation over a 6 month-follow-up period.MethodsA retrospective cohort study was conducted, analysing Electronic Health Record (EHR) data from the NeuroBlu Database (Patel et al. BMJ Open 2022;12:e057227). Patients were included if they had a psychiatric diagnosis and at least 5 recorded CGI-S scores within a 2-month period, defined as the ‘index’ period. The relationship between early CGI-S trajectories and risk of hospitalisation was investigated using Cox regression. The analysis was adjusted for age, gender, race, number of years in education, and psychiatric diagnosis. Early CGI-S trajectories were estimated as clinical severity (defined as the mean CGI-S score during the index period) and clinical instability (defined as a generalised Root Mean Squared Subsequent Differences of all CGI-S scores recorded during the index period). The primary outcome was time to psychiatric hospitalisation up to 6 months following the index period. Patients who had been hospitalised before or within the index period were excluded.ResultsA total of 36,914 patients were included (mean [SD] age: 29.7 [17.5] years; 57.3% female). Clinical instability (hazard ratio: 1.09, 95% CI 1.07-1.10, p&lt;0.001) and severity (hazard ratio: 1.11, 95% CI 1.09-1.12, p&lt;0.001) independently predicted risk of hospitalisation. These associations were consistent across all psychiatric diagnoses. Patients in the top 50% of severity and/or instability were at a 45% increased risk of hospitalisation compared to those in the bottom 50% (Figure 1).Image:ConclusionsEarly CGI-S trajectories reflecting clinical severity and instability independently predict risk of hospitalisation across diagnoses. This risk was compounded when instability and severity were present together. These results have translation potential in predicting individuals who are at high risk of hospitalisation and could benefit from preventative strategies to mitigate this risk.Disclosure of InterestE. Palmer Employee of: Holmusk, M. Taquet Consultant of: Holmusk, K. Griffiths Employee of: Holmusk, S. Ker Employee of: Holmusk, C. Liman Employee of: Holmusk, S. N. Wee Employee of: Holmusk, S. Kollins Employee of: Holmusk, R. Patel Grant / Research support from: National Institute of Health Research (NIHR301690); Medical Research Council (MR/S003118/1); Academy of Medical Sciences (SGL015/1020); Janssen, Employee of: Holmusk

Management of Chronic Atrophic Candidiasis (Denture Stomatitis)-A Narrative Review.

One of the most common oral diseases affecting people wearing dentures is chronic atrophic candidiasis or denture stomatitis (DS). The aim of the paper is to provide an update on the pathogenesis, presentation, and management of DS in general dental practice settings. A comprehensive review of the literature published in the last ten years was undertaken using multiple databases, including PubMed via MEDLINE, EMBASE, and Scopus. The eligible articles were analyzed to identify evidence-based strategies for the management of DS. Despite its multifactorial nature, the leading cause of DS is the development of oral Candida albicans biofilm, which is facilitated by poor oral and denture hygiene, long-term denture wear, ill-fitting dentures, and the porosity of the acrylic resin in the dentures. DS affects between 17 and 75% of the population wearing dentures, with a slight predominance in elderly females. The mucosal denture surfaces and posterior tongue are the common sites of DS, and the affected areas exhibit erythema, the swelling of the palatal mucosa and edema. Oral and denture hygiene protocols, adjusting or re-fabricating poorly adapting dentures, smoking cessation, avoiding nocturnal denture wear, and the administration of topical or systemic antifungals are the mainstay of management. Alternate treatments such as microwave disinfection, phytomedicine, photodynamic therapy, and incorporation of antifungals and nanoparticles into denture resins are being evaluated for the treatment of DS but require further evidence before routine use in clinical practice. In summary, DS is the most common oral inflammatory lesion experienced by denture wearers. Most patients with DS can be managed in general dental practice settings. Effective management by general dental practitioners may be supported by a thorough understanding of the pathogenesis, the recognition of the clinical presentation, and an awareness of contemporary treatment strategies.

Diagnostic accuracy of the 4AT for delirium: A systematic review and meta-analysis.

Despite common, serious, costly, and often fatal conditions affecting up to 50 % of older patients, delirium is often unrecognized and overlooked. We examine the accuracy of the 4AT for detecting older patients with delirium. We performed a systematic search of PubMed, Web of Science, PsycINFO, and EMBASE databases from inception to April 2020 and updated to January 2022. Four independently reviewers extracted study data and assessed the methodological quality using the revised quality assessment of diagnostic accuracy studies tool (QUADAS-2). Pooled estimates of sensitivity and specificity were generated using a bivariate random effects model. All statistical analyses were performed with STATA version 15.1 and Meta-DiSc version 1.4 software. Eleven studies with 2789 participants were included. The pooled sensitivity and specificity were 0.87 (95 % CI: 0.81-0.91) and 0.87 (95 % CI: 0.79-0.92), respectively, and the positive and negative likelihood ratios were 6.66 (95 % CI: 4.12-10.74) and 0.15 (95 % CI: 0.10-0.23), respectively. Deeks' test indicated no significant publication bias (t=0.83, P=0.43). Univariable meta-regression showed that patient selection and flow and timing significantly influenced the pooled sensitivity (P<0.05), settings significantly influenced the pooled specificity (P<0.05). Our meta-analysis demonstrates that 4AT is a sensitive and specific screening tool for delirium in older patients. Its brevity and simplicity support its use in routine clinical practice, particularly in time-poor settings. Clinicians should come to a conclusion based largely on the 4AT findings in conjunction with clinical judgment.

Abstract NS4: Impact Of System-wide Implementation Of Tenecteplase For Ischemic Stroke Thrombolysis On Quality Metrics And Outcomes

Background and Purpose: Tenecteplase (TNK) has recently been demonstrated to be an effective thrombolytic agent in patients with acute ischemic stroke. Our 9-hospital stroke network transitioned to tenecteplase as the standard stroke thrombolytic in April 2022. We assessed the impact of TNK use in routine clinical practice on quality metrics and outcomes. Methods: System Stroke Committee (Vascular Neurology, Emergency Medicine, Pharmacy, Nursing) evaluated the scientific evidence, performed a cost analysis and decided to implement TNK system wide. Proposal was submitted to Pharmacy and Therapeutics (P&amp;T) committee. Education plan for providers, nursing and pharmacy was developed and training provided. A before and after analysis was conducted to compare consecutive patients who received thrombolysis for acute ischemic stroke between Jan 2022 to July 2022 before and after the transition to tenecteplase. Quality metrics of National Institute of Health Stroke Scale (NIHSS) on presentation, door to thrombolysis; door in door out of the regional facility; safety outcome of any hemorrhagic transformation and functional outcome of NIHSS at discharge are compared between patients who received TNK versus tPA. Results: A total of 121 ischemic stroke patients treated with thrombolysis were included: 62 patients received TNK and 59 patients received tPA. NIHSS on presentation was similar between the groups (TNK 8 IQR [2-10] vs. tPA 7 IQR [3-11] p=0.73). Door to thrombolysis was similar (TNK 60.3±40.9 min vs. 60.1±44 min; p=0.98) as was door-in-door out time (TNK 186±68.4 min vs. tPA 145±70 min p=0.09) between the groups. Intracerebral hemorrhage rates were not different (TNK 8% vs. tPA 6% p=0.78). Discharge NIHSS was similar between the groups (TNK 1 IQR [0-5] vs. tPA 1 IQR [0-4]; p=0.85). Conclusion: Tenecteplase implementation as stroke thrombolytic of choice in a large stroke network did not impact performance on quality metrics, safety and outcomes.

Adherence to treatment in intensive care units on the example of pediatric sepsis: a review

INTRODUCTION: Intensive care does not always require only a large amount of resources. An important aspect is the formation of a multidisciplinary team involved in the treatment of patients in critical condition. OBJECTIVE: To demonstrate the need for the staff of intensive care units to use protocols for the diagnosis and treatment of critical conditions on the example of sepsis in children. MATERIALS AND METHODS: The analysis of publications devoted to the study of the impact of the implementation of the clinical recommendations of the Surviving Sepsis Campaign for the treatment of sepsis in children on the outcomes of the disease. The articles were searched in the abstract databases PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science Core Collection and Google Scholar for the period from 2011 to July 2022. Keywords were used: “pediatric sepsis”, “implementation”, “protocolized treatment”, “adherence”. RESULTS: During the search, only thirteen observational studies were found, nine of which were presented retrospectively, which can be attributed to the design flaws of the submitted works. It was revealed that the use of the entire complex of diagnostic and therapeutic measures presented in clinical recommendations and protocols for intensive therapy of sepsis in children can significantly improve the results of treatment, but the commitment of doctors to their use in routine clinical practice remains low and does not exceed 40 %. CONCLUSIONS: The main reason for the lack of commitment to the implementation of recommendations and standards for the treatment of sepsis in children is not only in the presence of organizational obstacles, but also in the absence of reasonable algorithms for its implementation.

P563 Monitoring of vedolizumab drug levels in a treat to target strategy for moderate-severe IBD (MOVE-IBD)

Abstract Background Vedolizumab is an effective drug in moderate-severe ulcerative colitis (UC) and Crohn’s disease (CD). A previous link between drug exposure and clinical response has been suggested in the literature making therapeutic drug monitoring (TDM) for vedolizumab an attractive idea to try and optimize patient outcomes. Recent data from the ENTERPRET induction study in UC presented at Digestive Diseases 2022 suggest no advantage to dose optimizing based on vedolizumab levels. Thus, there is discordance in the literature regarding the clinical relevance of vedolizumab drug levels. We aimed to clarify the utility of proactive TDM of vedolizumab trough levels in our cohort of maintenance vedolizumab patients using objective markers of disease activity in a treat to target strategy. Methods A single-centre retrospective cross sectional cohort study using proactive TDM was performed on 84 patients with moderate to severe IBD on vedolizumab maintenance therapy. All patients were receiving standard vedolizumab dosing of 300 mg every eight weeks. A vedolizumab trough drug level was paired with clinical and objective markers of disease activity. The two endpoints examined were steroid free clinical remission and objective remission. Objective remission targets were individualized for each patient using a treat to target strategy and benchmarked against a baseline abnormal test. Steroid free clinical remission was defined in Crohn’s disease as a Crohn’s disease activity index (CDAI) of &amp;lt; 150 and in ulcerative colitis as a partial MAYO score of &amp;lt; 1 in a patient off steroids. Objective remission was defined as faecal calprotectin &amp;lt; 150 ug/g, normal bowel wall thickness on intestinal ultrasound or magnetic resonance imaging without associated features of inflammation or absence of ulceration on colonoscopy or sigmoidoscopy within 3 months of the vedolizumab level. Results Median trough vedolizumab levels for patients were numerically higher but not statistically different in patients who had achieved steroid free clinical remission (13.3 ug/ml vs 8.89 ug/ml p = 0.544) or objective remission (15.22 ug/ml vs 10.28 ug/ml p = 0.139). See Figures 1. In addition, quartile analysis showed no statistically significant difference between quartiles of vedolizumab levels and clinical or objective remission (p = 0.822). Conclusion Trough serum vedolizumab levels in our real-life cohort of maintenance moderate severe IBD patients were not associated with clinical or objective remission. Caution should be applied to basing treatment decisions off vedolizumab maintenance levels until more data becomes available to support its routine use in clinical practice.

New Biologic Therapies in the Management of Psoriatic Arthritis: An Overview

Psoriatic arthritis is an inflammatory musculoskeletal condition that represents a major cause of physical and psychological disability. This disorder represents a significant diagnostic and management challenge, given that it has different forms of clinical presentation, associated comorbidities, and high rates of therapeutic resistance. Early diagnosis is of crucial importance in impacting the prognosis of the disease. Typical treatment includes the administration of non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and the use of biological medicines. Currently, multiple biological therapies have proven to be advantageous in managing psoriatic arthritis, but they have not been fully approved for use in routine clinical practice. Therefore, in this article, we aim to provide an overview of the role of new biological therapies for the management of psoriatic arthritis.

Impact of pre-analytical sample handling factors on plasma biomarkers of Alzheimer's disease.

An unmet need exists for reliable plasma biomarkers of amyloid pathology, in the clinical laboratory setting, to streamline diagnosis of Alzheimer's disease (AD). For routine clinical use, a biomarker must provide robust and reliable results under pre-analytical sample handling conditions. We investigated the impact of different pre-analytical sample handling procedures on the levels of seven plasma biomarkers in development for potential routine use in AD. Using (1) fresh (never frozen) and (2) previously frozen plasma, we evaluated the effects of (A) storage time and temperature, (B) freeze/thaw (F/T) cycles, (C) anticoagulants, (D) tube transfer, and (E) plastic tube types. Blood samples were prospectively collected from patients with cognitive impairment undergoing investigation in a memory clinic. β-amyloid 1-40 (Aβ40), β-amyloid 1-42 (Aβ42), apolipoprotein E4, glial fibrillary acidic protein, neurofilament light chain, phosphorylated-tau (phospho-tau) 181, and phospho-tau-217 were measured using Elecsys® plasma prototype immunoassays. Recovery signals for each plasma biomarker and sample handling parameter were calculated. For all plasma biomarkers measured, pre-analytical effects were comparable between fresh (never frozen) and previously frozen samples. All plasma biomarkers tested were stable for ≤24 h at 4°C when stored as whole blood and ethylenediaminetetraacetic acid (EDTA) plasma. Recovery signals were acceptable for up to five tube transfers, or two F/T cycles, and in both polypropylene and low-density polyethylene tubes. For all plasma biomarkers except Aβ42 and Aβ40, analyte levels were largely comparable between EDTA, lithium heparin, and sodium citrate tubes. Aβ42 and Aβ40 were most sensitive to pre-analytical handling, and the effects could only be partially compensated by the Aβ42/Aβ40 ratio. We provide recommendations for an optimal sample handling protocol for analysis of plasma biomarkers for amyloid pathology AD, to improve the reproducibility of future studies on plasma biomarkers assays and for potential use in routine clinical practice.

Radiomics in Cardiac Computed Tomography.

In recent years, there has been an increasing recognition of coronary computed tomographic angiography (CCTA) and gated non-contrast cardiac CT in the workup of coronary artery disease in patients with low and intermediate pretest probability, through the readjustment guidelines by medical societies. However, in routine clinical practice, these CT data sets are usually evaluated dominantly regarding relevant coronary artery stenosis and calcification. The implementation of radiomics analysis, which provides visually elusive quantitative information from digital images, has the potential to open a new era for cardiac CT that goes far beyond mere stenosis or calcification grade estimation. This review offers an overview of the results obtained from radiomics analyses in cardiac CT, including the evaluation of coronary plaques, pericoronary adipose tissue, and the myocardium itself. It also highlights the advantages and disadvantages of use in routine clinical practice.

ASSESSMENT OF THE EFFICIENCY OF ANALGETIC ACTION OF LAPAROSCOPICALLY ASSISTED TAP BLOCK AS A COMPONENT OF PERIOPERATIVE MULTIMODAL ANALGESIA PLAN IN OBESE PATIENTS UNDERGOING METABOLIC SURGERY.

The aim: To assess the effectiveness and feasibility of laparoscopically assisted TAP block utilization in the system of multimodal analgesia by comparing the severity of pain and associated postoperative recovery indicators in obese patients after laparoscopic sleeve gastrectomy. Materials and methods: The retrospective study included 39 patients, who underwent metabolic surgery from 2013-2022. All patients were divided into 2 groups depending on the chosen perioperative analgesia protocol. Group 1 included 19 patients who prior to skin incision a local infiltration of the trocar puncture areas of the abdominal wall. Group 2 included 20 patients, whom in addition to the above-described anaesthesia procedure after completion of the main stage of surgery, a laparoscopically assisted bilateral subcostal TAP block was additionally performed. Results: The need to use opioid analgesics in the rescue analgesia mode arose in 17.6% (3/17) of patients of the first group, and 5% (1/20) of patients in the second group Average duration of postoperative hospitalization in group 1 was 7.2±1.1 days, and in group 2 it was 6.2±1.4 days (P <0.05). Conclusions: Subcostal TAP block in obese patients is a safe and effective method of regional anaesthesia. Further study of this option of regional anaesthesia is required in order to be able to form clearer recommendations for its routine use in clinical practice.