Use In Routine Clinical Practice Research Articles

Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases

Metagenomic next-generation sequencing (mNGS) is a transformative approach in the diagnosis of infectious diseases, utilizing unbiased high-throughput sequencing to directly detect and characterize microbial genomes from clinical samples. This review comprehensively outlines the fundamental principles, sequencing workflow, and platforms utilized in mNGS technology. The methodological backbone involves shotgun sequencing of total nucleic acids extracted from diverse sample types, enabling simultaneous detection of bacteria, viruses, fungi, and parasites without prior knowledge of the infectious agent. Key advantages of mNGS include its capability to identify rare, novel, or unculturable pathogens, providing a more comprehensive view of microbial communities compared to traditional culture-based methods. Despite these strengths, challenges such as data analysis complexity, high cost, and the need for optimized sample preparation protocols remain significant hurdles. The application of mNGS across various systemic infections highlights its clinical utility. Case studies discussed in this review illustrate its efficacy in diagnosing respiratory tract infections, bloodstream infections, central nervous system infections, gastrointestinal infections, and others. By rapidly identifying pathogens and their genomic characteristics, mNGS facilitates timely and targeted therapeutic interventions, thereby improving patient outcomes and infection control measures. Looking ahead, the future of mNGS in infectious disease diagnostics appears promising. Advances in bioinformatics tools and sequencing technologies are anticipated to streamline data analysis, enhance sensitivity and specificity, and reduce turnaround times. Integration with clinical decision support systems promises to further optimize mNGS utilization in routine clinical practice. In conclusion, mNGS represents a paradigm shift in the field of infectious disease diagnostics, offering unparalleled insights into microbial diversity and pathogenesis. While challenges persist, ongoing technological advancements hold immense potential to consolidate mNGS as a pivotal tool in the armamentarium of modern medicine, empowering clinicians with precise, rapid, and comprehensive pathogen detection capabilities.

The Post-Stroke Checklist: longitudinal use in routine clinical practice during first year after stroke

BackgroundFew studies describe the use of the Post-Stroke Checklist (PSC) as a tool for longitudinal stroke follow-up in clinical practice. We mapped the prevalence of stroke-related health problems and targeted interventions at 3 and 12 months post-stroke by using the PSC.MethodsPatients with acute stroke discharged home in 2018–2019 at Skåne University Hospital, Sweden, were invited to participate in a comprehensive nurse-led follow-up based on a 14-item PSC 3 and 12 months post-stroke. We measured time consumption, screened for stroke-related health problems, compared the findings, and recorded targeted healthcare interventions. Problems at 12 months were grouped into new, persistent, or none compared to the 3-month evaluation.ResultsOf 200 consecutively included patients, 146 (77%) completed both the 3- and 12-month follow-ups. At 12-month follow-up, 36% of patients reported no stroke-related health problems, 24% reported persistent problems, and 40% reported new problems since the 3-month evaluation. New problems at 12 months were most common within the domains: secondary prevention (23%) and life after stroke (10%). Stroke recurrence rate was 7.5%, 43% had high blood pressure, and few smokers had quit smoking. At 12 months, 53% received at least one new healthcare intervention, compared to 84% at 3 months.ConclusionsStroke-related health problems decreased beyond 3 months but were still present in two-thirds of patients at 1 year. This emphasizes the relevance of continuous structured follow-up using the PCS. However, the follow-up alone was insufficient to adequately achieve treatment targets for secondary prevention, which require intensified focus.Trial registrationClinicalTrials.gov ID NCT04295226, (04/03/2020)

Imprecision and real-time clinical performance of a whole blood high sensitivity point of care troponin i: ready for prime time?

Abstract Introduction High sensitivity troponin (hs-cTn) measurement is central to rapid diagnostic algorithms in acute coronary syndrome (ACS). Point of care (POC) testing reduces turnaround time when compared to central lab (CL) testing. Currently there is very little data on the performance of POC hs-cTn assays in a clinical environment with non-expert operators. Method In a nested sub-study of a randomised controlled trial (RCT), patients with suspected ACS were randomised to either the ESC 0/1 or 0/3 hour algorithm. They underwent whole blood (WB) sampling for Siemens Atellica VTLi hs-cTnI POC (VTLi POC), CL hs-cTnI and CL hs-cTnT assays. This was for both initial and repeat samples. Assay imprecision of the VTLi POC assay was assessed by 2 runs of 10 tests with whole blood at 9 different troponin levels. 4 devices were used with samples stored at room temperature.Final diagnosis was adjudicated based on all relevant clinical and imaging data together with CL hs-cTnT as the diagnostic biomarker in clinical use (10% coefficient of variation (CV) 3-5 ng/L, 99th percentile 14 ng/L) and using the 4th universal definition of myocardial infarction (MI). Clinical performance was assessed using Receiver Operator Characteristics (ROC) curves. Results 2144 patients consented and had WB VTLi POC, CL hs-cTnI and CL hs-cTnT available. The index adjudicated type 1 MI rate was 6.1%. Assay imprecision of the VTLi POC assay demonstrated a 10% Coefficient of Variation (CV) at 9.8ng/l. This was >50% lower than the 99th centile of 23ng/l (average for males and females) (Figure 1). Clinical performance of the VTLi POC assay was acceptable and equivalent to CL hs-cTnT: Area Under Curve (AUC) 0.92 (0.89-0.96), 0.98 (0.96-0.99) and 0.93 (0.87-0.98) at presentation (Figure 2), 1 and 3 hours respectively. However, clinical performance was inferior to CL hs-cTnI: AUC 0.96 (0.95-0.98) and 0.96 (0.93-0.98) at presentation (p=0.0007) and 3 hours (p<0.0001) respectively. Conclusion The Siemens Altellica VTLi hs-cTnI POC assay has imprecision levels consistent with a high sensitivity troponin assay. It has acceptable clinical performance though inferior to the equivalent CL hs-cTnI. Further validation of this assay, particularly with optimised single sample rule-out, could facilitate its use in routine clinical practice.

Cardiac magnetic resonance in MINOCA patients: a non-tertiary hospital experience

Abstract Background Cardiac magnetic resonance (CMR) is a key tool in the diagnostic process of myocardial infarction with non-obstructive coronary arteries (MINOCA), impacting patient management and prognosis. Its use in non-tertiary hospitals is often constrained mainly by accessibility. Thus, the aim of this study was thoroughly evaluate CMR application in this context to optimize the process. Methods 136 MINOCA patients who were admitted to our hospital between 2016 and January 2024 were analyzed. Each MINOCA patient was reviewed by experts to align with the diagnosis criteria outlined in the 2020 ESC Guidelines and the American Heart Association position paper, which recommended CMR for MINOCA patient’s evaluation. To assess the factors associated with normal-CMR, a logistic regression analysis was performed. In a first step, some factors were detected, showing a trend in the association. In a second step, a backward elimination procedure was used, excluding factors with p>0.1. Results CMR was performed in 65 MINOCA patients (48% of the cohort), with a mean age of 59±15 years old, 35 of them were males (54% of total patients). During the follow-up, there were 4 deaths (6%) and 4 readmissions (6%). Out of the total 65 patients, the CMR diagnosis was myocardial infarction (MI) in 14 (21.5%) and myocarditis in 16 (24.6%), and was normal in 35 (53.9%). Therefore, CMR provided diagnostic information in 46% of the cases. It was noted that a normal CMR was associated with female gender, (OR 2.7, 95% CI 0.96-7.34, p=0.057), hypertension (OR 2.25, 95% CI 0.81-6.22, p=0.11), absence of segmental abnormalities in echocardiography (OR 0.14, 95% CI 0.035-0566, p=0.06) and lower high-sensitivity Troponin T (OR 0.79, 95% CI: 0.66-0.95, p=0.001). In the second step, only segmental abnormalities (OR 0.2, 95%CI 0.04-1.09, p=0.063) and troponin (OR 0.31, 95%CI 0.10-0.99, p=0.048) remained included. Additionally, the Youden Index was determined to obtain the threshold for troponin, resulting a value of 606 nG/mL, area under ROC curve (AUC) = 0.784 (figure). Conclusions - CMR was performed in 48% of the MINOCA patients, reflecting the limitation for its use in routine clinical practice. Furthermore, it was useful in 46% of those patients. - The main factors associated with normal CMR were absence of segmental echocardiography abnormalities and reduced troponin levels. - A troponin cutoff point of 606 ng/mL identified patients with a normal CMR (AUC=0.784).Figure 1.CMR in MINOCA patientsFigure 2.Area under ROC curve = 0.784

Predicting Portal Pressure Gradient in Patients with Decompensated Cirrhosis: A Non-invasive Deep Learning Model.

A high portal pressure gradient (PPG) is associated with an increased risk of failure to control esophagogastric variceal hemorrhage and refractory ascites in patients with decompensated cirrhosis. However, direct measurement of PPG is invasive, limiting its routine use in clinical practice. Consequently, there is an urgent need for non-invasive techniques to assess PPG. To develop and validate a deep learning model that predicts PPG values for patients with decompensated cirrhosis and identifies those with high-risk portal hypertension (HRPH), who may benefit from early transjugular intrahepatic portosystemic shunt (TIPS) intervention. Data of 520 decompensated cirrhosis patients who underwent TIPS between June 2014 and December 2022 were retrospectively analyzed. Laboratory and imaging parameters were used to develop an artificial neural network model for predicting PPG, with feature selection via recursive feature elimination for comparison experiments. The best performing model was tested by external validation. After excluding 92 patients, 428 were included in the final analysis. A series of comparison experiments demonstrated that a three-parameter (3P) model, which includes the international normalized ratio, portal vein diameter, and white blood cell count, achieved the highest accuracy of 87.5%. In two distinct external datasets, the model attained accuracy rates of 85.40% and 90.80%, respectively. It also showed notable ability to distinguish HRPH with an AUROC of 0.842 in external validation. The developed 3P model could predict PPG values for decompensated cirrhosis patients and could effectively distinguish HRPH.

Glycopyrrolate Premedication and Procedure-Related Events in Pediatric Upper Endoscopy.

Glycopyrrolate premedication is used for pediatric upper endoscopy procedures, with limited clinical evidence for efficacy. We investigated whether glycopyrrolate use is associated with lower incidence of procedure-related events and serious adverse events (SAEs) using the Pediatric Sedation Research Consortium registry. Pediatric upper endoscopy procedures performed between April 27, 2020 and February 3, 2022 were included (N = 1046). The primary outcome was the incidence of any procedure-related events during induction, maintenance, or recovery, and the secondary outcome was incidence of SAEs. The event rate was 15%, including 30 SAEs (3%). On multivariable analysis, glycopyrrolate was not associated with the overall event rate (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 0.72, 1.61), but was associated with lower odds of SAEs (OR: 0.34; 95% CI: 0.13, 0.91). Although glycopyrrolate was associated with lower odds of SAEs after accounting for patient and procedure characteristics, validation through prospective trials is needed to support its routine use in clinical practice.

Can a Digital Tool Improve the Understanding of Treatment Option for Patients With Head/Neck Cancer and Increase Providers’ Self-perceived Ability to Communicate With Patients?

A digital visual communication tool was recently developed by MyCareGorithm that incorporates explanations of treatments and procedures for cancer patients. This study evaluated if this novel tool can enhance both patient and provider satisfaction. In an IRB approved, prospective, pilot study, patients and caregivers at a single institution receiving head and neck cancer radiation underwent an initial consult using this digital tool and completed a survey of 6 questions to evaluate their understanding of their disease. Providers completed a 7-question survey to rate their satisfaction. Patients and caregivers with 4 or more “Yes” answers and providers with 5 or more “Yes” answers were defined as “Satisfied.” To obtain 90% power to detect that the proportion of “Satisfied” patients (assumed 75%) is greater than 50% with a significance level 5% using a 1-sided Z test, we planned to enroll 30 patients. Thirty patients enrolled and completed all surveys. Most patients were male (66%), White (60%), and spoke English as a primary language (93%). Patients most commonly had oropharyngeal cancer (23%). Overall, 27 of the 30 patients (90%; 1-sided 95% CI, 76.1%) were satisfied (z = 4.38, P < .05), 16 of the 17 caregivers (94%; 1-sided 95% CI, 74.8%) were satisfied, and 100% of providers were satisfied with the digital tool. Most patients (90%) and caregivers (94%) felt that the tool improved their understanding of the disease. One man answered “No” for all 6 questions, commenting that it was only marginally helpful. One woman also answered “No” for all questions, commenting that she did not find it helpful on its own without the provider's explanation. Of the 30 patients, 26 (87%) stayed at our institution to receive treatment. These findings showed high rates of patient, caregiver, and provider satisfaction with their initial consult when incorporating a digital visual tool. Its routine use in clinical practice should be strongly considered.

Comparison of a Fully Automated Platform and an Established ELISA for the Quantification of Neurofilament Light Chain in Patients With Cognitive Decline.

Enzyme-linked immunosorbent assay (ELISA) is the most-used method for neurofilament light chain (NfL) quantification in cerebrospinal fluid (CSF). Recently, fully automated immunoassays for NfL measurement in CSF and blood have allowed high reproducibility among laboratories, making NfLs suitable for routine use in clinical practice. In this study, we compared the Uman Diagnostics NF-light ELISA with the fully automated platform Lumipulse. We enrolled 60 patients with cognitive decline, including Alzheimer disease (AD). CSF NfL levels were measured by a NF-light ELISA kit (UmanDiagnostics), and chemiluminescent enzyme immunoassay (CLEIA) on the Lumipulse G1200 platform (Fujirebio Diagnostics). Serum NfLs levels were measured by CLEIA on the Lumipulse G1200. We found a significant, very strong correlation [Spearman rho = 0.94 (0.90-0.96)] between CLEIA and ELISA in CSF, and a significant moderate correlation between CSF and serum with both analytical methods [CLEIA vs serum CLEIA 0.41 (0.16-0.61); ELISA vs serum CLEIA 0.40 (0.15-0.60)]. It is worth noting that CSF CLEIA measurements were approximately 136.12 times higher than the serum measurements. Our findings show a robust correlation between ELISA Uman Diagnostic and the standardized Lumipulse G1200 platform for CSF NfL measurements.

Systematic Review of Clinical Prediction Models for the Risk of Emergency Caesarean Births.

Globally, caesarean births (CB), including emergency caesareans births (EmCB), are rising. It is estimated that nearly a third of all births will be CB by 2030. Identify and summarise the results from studies developing and validating prognostic multivariable models predicting the risk of EmCBs. Ultimately understanding the accuracy of their development, and whether they are operationalised for use in routine clinical practice. Studies were identified using databases: MEDLINE, CINAHL, Cochrane Central and Scopus with a search strategy tailored to models predicting EmCBs. Prospective studies developing and validating clinical prediction models, with two or more covariates, to predict risk of EmCB. Data were extracted onto a proforma using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). In total, 8083 studies resulted in 56 unique prediction modelling studies and seven validating studies, with a total of 121 different predictors. Frequently occurring predictors included maternal height, maternal age, parity, BMI and gestational age. PROBAST highlighted 33 studies with low overall bias, and these all internally validated their model. Thirteen studies externally validated; only eight of these were graded an overall low risk of bias. Six models offered applications that could be readily used, but only one provided enough time to offer a planned caesarean birth (pCB). These well-refined models have not been recalibrated since development. Only one model, developed in a relatively low-risk population, with data collected a decade ago, remains useful at 36 weeks for arranging a pCB. To improve personalised clinical conversations, there is a pressing need for a model that accurately predicts the timely risk of an EmCB for women across diverse clinical backgrounds. PROSPERO registration number: CRD42023384439.

SP3.7 - Patient experiences of using wearable health monitors during cancer treatment: A qualitative study

Abstract Introduction Wearable health monitors (WHM) are being used in healthcare with increasing popularity, and offer a minimally invasive, ambulatory method of 24-hour monitoring. The aim of this study explores the patient experience of using WHMs during cancer treatment, including barriers and enablers of WHM use. Methods A phenomenological qualitative approach was used with single semi-structured interviews conducted in the form of focus groups with individuals enrolled in the EMBRaCE-GM study where WHMs are worn in the perioperative period of at least 6 months during treatment of either colorectal cancer, lung cancer, leukaemia/lymphoma or head &amp; neck cancer. Results We identified 3 major themes of perceived patient benefit, treatment partnerships between patients and healthcare professions and barriers to the adoption. WHMs promoted positive behaviour change, prioritisation of own health and represented a form of “digital advocacy”. Potential barriers were aesthetic, experiential and technological. WHM introduction was time-sensitive, with patients finding their use acceptable at differing stages in their cancer pathway. Patients desired reciprocal interaction with WHMs and were less concerned with data accuracy. Discussion Our study identifies factors influencing a patient’s decision to use WHMs and their importance as a patient-centric interactive component of management. Novel findings include the optimal time to start wearing WHMs and that validity of measurements appears less of a concern for patients (in contrast to clinicians) who use wearable data and trends with their own experiences as part of a sense making exercise. Future work should focus on balancing patient and clinician expectations to provide guidance on the feasibility of WHM use in routine clinical practice.

Prognostic Value of the Lactate/Albumin Ratio for 28-Day Mortality in Pediatric Septic Shock: A Prospective Cohort Study.

Background Septic shock remains a leading cause of mortality in children. The lactate/albumin ratio (LAR) has emerged as a potential prognostic marker for mortality in septic shock, yet most existing research focuses on adults, with limited data available for pediatric populations, particularly in Vietnam. Objectives This study aims to evaluate the prognostic utility of the LAR in predicting 28-day mortality among children aged two months to 15 years with septic shock in Vietnam. Methods We conducted a prospective cohort study involving children diagnosed with septic shock at the largest pediatric intensive care unit (PICU) in the Mekong Delta, Vietnam, from July 2022 to June 2024. Clinical and laboratory parameters, including lactate and albumin levels, were measured at the time of septic shock diagnosis. Patients were followed for 28 days, with outcomes categorized as either survival or mortality. The prognostic performance of LAR was assessed through its discrimination and calibration capabilities. Results The 28-day mortality rate was 63.4%. LAR was significantly higher in non-survivors compared to survivors (p < 0.001). The area under the receiver operating characteristic curve (AUROC) for LAR was 0.91, indicating superior discriminatory power compared to lactate alone and comparable to albumin. Using a Youden index-derived cut-off of 1.84, LAR demonstrated a sensitivity of 84.6% and a specificity of 80%. Kaplan-Meier analysis and log-rank testing revealed significantly lower survival probabilities in children with LAR ≥1.84 (p < 0.05). The Hosmer-Lemeshow test confirmed good calibration of LAR in mortality prediction (p > 0.05). Conclusion The lactate/albumin ratio exhibits excellent discriminatory and calibration properties, making it a valuable tool for predicting 28-day mortality in pediatric septic shock. This ratio should be considered for routine use in clinical practice to improve prognostic assessments in this vulnerable population.

The Role of Inflammation in Depression and Beyond: A Primer for Clinicians.

We evaluate available evidence for the role of inflammation in depression. We reappraise literature involving systemic inflammation, neuroinflammation and neurotransmission and their association with depression. We review the connection between depression, autoimmunity and infectious diseases. We revise anti-inflammatory treatments used in depression. Peripheral inflammatory markers are present in a subset of patients with depression and can alter common neurotransmitters in this population but there is no clear causality between depression and systemic inflammation. Infectious conditions and autoimmune illnesses do not have a clear correlation with depression. Certain medications have positive evidence as adjunctive treatments in depression but studies are heterogenic, hence they are sparsely used in clinical settings. The current evidence does not fully support inflammation, infections or autoimmunity as possible etiologies of depression. The available studies have numerous confounders that obscure the findings. Anti-inflammatory agents may have potential for treatment of depression, but further research is needed to clarify their usefulness in routine clinical practice.

The use of fibrinolysis inhibitors in cardiac surgery with cardiopulmonary bypass (literature review)

In cardiac surgery with cardiopulmonary bypass (CPB) is a common complication. The incidence of this complication in cardiac surgery patients is estimated at about 10%. For this reason, the introduction of a patient blood management (PBM) in cardiac surgery is extremely relevant. Antifibrinolytic therapy is a key pharmacological tool of a multimodal PBM in cardiac surgery with CPB. The use of antifibrinolytics (tranexamic acid (TXA) and epsilon aminocaproic acid (EACA)) is standard practice in complex cardiac surgery with CPB. However, there is currently ongoing discussion regarding the search for the optimal dose of EACA and TXA to achieve an effective concentration in blood plasma in order to inhibit fibrinolysis with the minimization of adverse events. The use of aprotinin has a number of potential advantages, but its use in routine clinical practice is significantly limited. This review presents modern approaches to antifibrinolytic therapy, examines the mechanisms of action of the main drugs, highlights the side effects associated with the use of antifibrinolytic agents.

German Society of Neurology guidelines for the diagnosis and treatment of cognitive impairment and affective disorders in people with Parkinson's disease: new spotlights on diagnostic procedures and non-pharmacological interventions.

Cognitive impairment and dementia as well as affective disorders are common and debilitating syndromes that develop in people with Parkinson's disease (PwPD). The authors summarized recommendations for the 2023 updated German guidelines on "Parkinson's disease" from the German Neurological Society (DGN), focusing on the diagnosis and treatment of these disorders. The recommendations were based on literature reviews, other relevant guidelines, and expert opinions. Measurements to assess cognitive and affective states were reviewed for psychometric properties, use in routine clinical practice, and availability in German. To improve mild cognitive impairment, cognitive trainingand physical aerobic training are recommended. To treat Parkinson's disease (PD)-related dementia, cognitive stimulation (as anon-pharmacologicalintervention) and acetylcholinesterase inhibitors (AChEIs, i.e., rivastigmine) are recommended. Cognitive behavioral therapy is recommended to treat depression, anxiety, and fear of progression. Physical interventions are recommended to treat depression, fatigue, and apathy. Optimized dopaminergic treatment is the first-line pharmacological strategy recommended to manage depression, apathy, anhedonia, fatigue, and mood swings. Major depression can be additionally treated using venlafaxine or desipramine, while moderate depression can be treated pharmacologically according to its clinical phenotype (psychomotor retardation or agitation) and comorbidities (e.g., sleep disturbances, pain). Venlafaxine and nortriptyline can be used to treat anhedonia, while citalopram can be used for anxiety. In addition to the updated pharmacological treatment options, new insights into recommendations for standardized diagnostics and non-pharmacological interventions were provided for the German health care system. However, more studies are needed to explore the full potential of non-pharmacological interventions to treat and prevent cognitive impairment and affective disorders.

Interobserver and intraobserver agreement in PET/CT with [18F]DCFPyL according to TNM molecular and PSMA-RADS 2.0 criteria

PurposeThe aim of this study was to determine the agreement between three observers with different levels of experience using the PSMA-RADS 2.0 criteria and the miTNM system for the interpretation of PET-PSMA with [18F]DCFPyL in males with prostate cancer. Materials and MethodsPET-PSMA images from 114 prostate cancer patients were blindly reported twice by three different observers at intervals of 8 weeks. The evaluations were performed according to the molecular imaging TNM (miTNM) and PSMA-RADS 2.0 criteria. We used Fleiss’ Kappa to analyse inter and intraobserver agreements. ResultsModerate overall agreement was obtained in the assessment of the PET-PSMA results (Fleiss'k = 0.53; 95% CI 0.45−0.62; p < 0.001), with significant agreement in the miT, miN and miM reports. There was a substantial level of agreement in the reporting of prostatic disease and lymphatic involvement (Fleiss'k = 0.66 and 0.65), being lower than that observed in the reporting of metastatic disease (Fleiss'k = 0.86), especially in the M0 group (Fleiss'k = 0.99). Upon re-evaluation of the images, observer 1 had moderate overall agreement for miT (Fleiss'k = 0.51) and substantial agreement for miN and miM (Fleiss'k 0.75 and 0.63, respectively). ConclusionsThe use of a structured scoring system such as PSMA-RADS 2.0, as well as the miTNM classification system in the interpretation of PET-PSMA images in prostate cancer patients, provides a highly reproducible report format. High levels of interobserver and intraobserver agreement are found, especially when ruling out disease, which supports its use in routine clinical practice.

Immunological testing for female infertility: a modern view on the problem

Introduction. According to various estimates, in Russia 10 to 20 % of people of reproductive age are infertile. Changes in the immune system play a key role in the etiology and treatment of various infertility forms. The active introduction of immunological testing into clinical practice can potentially improve the results of infertility diagnostics and treatment.Aim: to analyze the current literature data on immunological testing in female infertility, as well as to assess its potential role in infertility diagnostics and treatment.Materials and Methods. There was conducted a search for publications in the electronic databases PubMed and eLibrary by using the following keywords and their combinations: "infertility", "immunology", "immune system", "immunological testing", "diagnostics", "treatment". The articles were evaluated in accordance with the PRISMA recommendations. Ultimately, 88 publications were included in the review.Results. Testing for antiphospholipid antibodies (APA) may be useful for women undergoing assisted reproductive technology (ART) therapy, as these antibodies increase the risk of pregnancy complications and thrombotic risks associated with ovarian stimulation, but studies assessing AFA effect on in vitro fertilization (IVF) outcomes have ambiguous results. The presence of antithyroid antibodies (ATA) may be associated with infertility, so their assessment is indeed important to determine treatment tactics. It has been suggested that antinuclear antibodies (ANA) may affect reproductive function by disrupting trophoblast cell development and interfering with RNA transcription, which may lead to lowered reproductive success. Studies have shown that patients with a positive ANA data have a lower incidence of pregnancy and a higher rate of miscarriages after IVF procedure. The human herpes virus type 6 (HHV-6) affects female fertility and is often the cause of spontaneous termination of pregnancy. B-cell lymphoma protein 6 (BCL-6) can serve as an important prognostic biomarker to identify individuals with endometriosis and related reproductive disorders, including idiopathic infertility. Evaluation of endometrial decidualization can be a useful tool to assess readiness for endometrial implantation and provide opportunities for targeted therapeutic interventions. The issue of testing for NK-cells in patients undergoing infertility screening remains controversial due to the difficulties of standardizing testing recommendations.Conclusion. To date, there is a limited number of reliable data on the role of various immunological tests in infertility diagnostics and treatment. With the exception of testing for AFA in patients with RPL, as well as for thyroid-stimulating hormone (TSH) and anti-thyroperoxidase antibodies (TPOAb) in patients undergoing therapy using various types of assisted reproductive technologies, the remaining immunological tests provide scant data to justify their routine use in clinical practice. The major limitations of existing studies are coupled to a small patient sample, as well as heterogeneity of inclusion criteria, patient groups and research methods.

A novel approach to therapeutic drug monitoring of Ciclosporin in pediatric renal transplant recipients using volumetric absorptive microsampling (VAMS) – Teaching old dog new tricks

Background and aimsCiclosporin (CSA) is an immunosuppressive agent that requires therapeutic drug monitoring (TDM). High partitioning in erythrocytes indicates that whole blood (WB) is a suitable matrix for CSA determination. Alternative sampling strategies, such as volumetric absorptive microsampling (VAMS), are novel possibilities for blood collection during TDM for various analytes, including immunosuppressants. This technique is attractive for vulnerable pediatric patients, including home-based self-sampling, remote therapy, and adherence control. Materials and methodsThis study aimed to develop and validate a new method for CSA determination based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) of WB and VAMS samples. Additionally, these methods were applied for CSA determination in clinical samples from pediatric transplant recipients. A strong point of this study is the assessment of an external proficiency testing scheme. ResultsBoth methods were successfully validated within the 1–2000 ng/mL calibration range, with LOD 0.5 and 1 ng/mL for WB and VAMS methods, respectively. All the validation parameters fulfilled the international acceptance criteria for bioanalytical methods. Cross-validation confirmed the interchangeability of the LC-MS/MS method developed in this study. ConclusionThis study developed and validated novel methods for CSA determination in whole blood and VAMS using LC-MS/MS. Clinical validation and proficiency testing confirmed their utility in routine clinical practice.

Donor Conditioning and Organ Pre-Treatment Prior to Kidney Transplantation: Reappraisal of the Available Clinical Evidence.

Therapeutic measures aimed at optimising organ function prior to transplantation-whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal-have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a favourable effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion, in particular, has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy and therapeutic donor hypothermia in the intensive care unit after brain death confirmation, have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to benefits for graft survival, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence from large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.

Validation of the Spanish Childhood Trauma Questionnaire-Short Form in adolescents with suicide attempts.

Child maltreatment is associated with a higher probability of mental disorders and suicidal behavior in adolescence. Therefore, accurate psychometric instruments are essential to assess this. To validate the Spanish version of the Childhood Trauma Questionnaire-Short Form (CTQ-SF) in adolescents with suicide attempts. Multisite cohort study of 208 adolescents with suicide attempts using data from the following scales: Mini International Neuropsychiatric Interview (MINI), Columbia Suicide Severity Rating Scale (C-SSRS), Patient Health Questionnaire (PHQ-9), and CTQ-SF. Statistical analysis: CTQ-SF scores analyzed by descriptive statistics. Internal consistency: McDonald's omega and Cronbach's alpha. Concurrent validity with PHQ-9 and C-SSRS scores: Spearman correlation coefficient. Structural validity: Confirmatory factor analysis. Floor and ceiling effects: Physical abuse and neglect as well as sexual abuse demonstrated high floor effects (50.0, 35.1, and 61.1% of adolescents, respectively). No ceiling effects were found. The CTQ-SF had excellent internal consistency (McDonald's omega = 0.94), as did the majority of its subscales (Cronbach's alpha 0.925-0.831) except for physical neglect (0.624). Its concurrent validity was modest, and the emotional neglect subscale had the lowest Spearman correlation coefficients (0.067-0.244). Confirmatory factor analysis: Compared with alternative factor structures, the original CTQ-SF model (correlated 5-factor) exhibited a better fit [S-B χ 2 = 676.653, p < 0; RMSEA (90% CI = 0.076-0.097) = 0.087; SRMR = 0.078; CFI = 0.980; TLI = 0.978]. The Spanish CTQ-SF is a reliable, valid instrument for assessing traumatic experiences in adolescents at high risk of suicide. It appears appropriate for use in routine clinical practice to monitor maltreatment in this group.

Artificial Intelligence-Based Electrocardiographic Biomarker for Outcome Prediction in Patients With Acute Heart Failure: Prospective Cohort Study.

Although several biomarkers exist for patients with heart failure (HF), their use in routine clinical practice is often constrained by high costs and limited availability. We examined the utility of an artificial intelligence (AI) algorithm that analyzes printed electrocardiograms (ECGs) for outcome prediction in patients with acute HF. We retrospectively analyzed prospectively collected data of patients with acute HF at two tertiary centers in Korea. Baseline ECGs were analyzed using a deep-learning system called Quantitative ECG (QCG), which was trained to detect several urgent clinical conditions, including shock, cardiac arrest, and reduced left ventricular ejection fraction (LVEF). Among the 1254 patients enrolled, in-hospital cardiac death occurred in 53 (4.2%) patients, and the QCG score for critical events (QCG-Critical) was significantly higher in these patients than in survivors (mean 0.57, SD 0.23 vs mean 0.29, SD 0.20; P<.001). The QCG-Critical score was an independent predictor of in-hospital cardiac death after adjustment for age, sex, comorbidities, HF etiology/type, atrial fibrillation, and QRS widening (adjusted odds ratio [OR] 1.68, 95% CI 1.47-1.92 per 0.1 increase; P<.001), and remained a significant predictor after additional adjustments for echocardiographic LVEF and N-terminal prohormone of brain natriuretic peptide level (adjusted OR 1.59, 95% CI 1.36-1.87 per 0.1 increase; P<.001). During long-term follow-up, patients with higher QCG-Critical scores (>0.5) had higher mortality rates than those with low QCG-Critical scores (<0.25) (adjusted hazard ratio 2.69, 95% CI 2.14-3.38; P<.001). Predicting outcomes in patients with acute HF using the QCG-Critical score is feasible, indicating that this AI-based ECG score may be a novel biomarker for these patients. ClinicalTrials.gov NCT01389843; https://clinicaltrials.gov/study/NCT01389843.