Serum Tests Research Articles

A Machine Learning Approach for Enhanced Glucose Prediction in Biosensors

The detection of glucose is crucial for diagnosing diseases such as diabetes and enables timely medical intervention. In this study, a disposable enzymatic screen-printed electrode electrochemical biosensor enhanced with machine learning (ML) for quantifying glucose in serum is presented. The platinum working surface was modified by chemical adsorption with biographene (BGr) and glucose oxidase, and the enzyme was encapsulated in polydopamine (PDP) by electropolymerisation. Electrochemical characterisation and morphological analysis (scanning and transmission electron microscopy) confirmed the modifications. Calibration curves in Cormay serum (CS) and selectivity tests with chronoamperometry were used to evaluate the biosensor’s performance. Non-linear ML regression algorithms for modelling glucose concentration and calibration parameters were tested to find the best-fit model for accurate predictions. The biosensor with BGr and enzyme encapsulation showed excellent performance with a linear range of 0.75–40 mM, a correlation of 0.988, and a detection limit of 0.078 mM. Of the algorithms tested, the decision tree accurately predicted calibration parameters and achieved a coefficient of determination above 0.9 for most metrics. Multilayer perceptron models effectively predicted glucose concentration with a coefficient of determination of 0.828, demonstrating the synergy of biosensor technology and ML for reliable glucose detection.

Perioperative anaphylaxis in Malaysia: A nine-year retrospective study.

Diagnosis of perioperative anaphylaxis (POA) and identification of causative agents remain challenging. This study aimed to describe the estimated incidence, characteristics and causative agents of POA in Malaysia. This is a retrospective review of all cases of suspected POA referred to the only anaesthetic allergy centre in Malaysia from March 2014 to December 2022. One hundred and ninety patients with suspected POA of Grade 2 and above were included. Data on clinical presentation, severity, management, serum tryptase and subsequent allergy workup (including skin and serum testing results) of these patients were extracted from the database. Dynamic tryptase was elevated in half of the cases where tryptase results were available and skin tests were positive in 96% of these cases. Skin testing was positive in 113 patients (60%) overall, and more than 70% of Grades 3 and 4 anaphylaxis cases. Neuromuscular blocking agents (NMBAs) and antibiotics were the most commonly identified causative agents (27.4% and 23% respectively). The commonest NMBAs were rocuronium and atracurium, both commonly cross-reacting with cisatracurium. The overall cross-reactivity rate among NMBAs was 58%. For antibiotics, the commonest causative agents were cefuroxime, ceftriaxone and amoxicillin/clavulanic acid. Using these data, the estimated incidence of Grades 2-4 POA over this period in Malaysia was approximately 1 in 30,000 anaesthetics. However, owing to the voluntary nature of reporting, it is possible that this is an underestimate, particularly in relation to some milder Grade 2 cases which may have gone unrecognised or unreported.

Real-world clinical experience with serum MOG and AQP4 antibody testing by live versus fixed cell-based assay.

To assess the real-world performance of a live (LCBA) versus a fixed (FCBA) cell-based assay for the detection of serum antibodies directed against myelin oligodendrocyte glycoprotein (MOG-IgG) and aquaporin-4 (AQP4-IgG). This was a retrospective study of patients evaluated at a single tertiary academic referral center, with serum testing performed clinically for AQP4-IgG and/or MOG-IgG by FCBA and LCBA on the same day. Additionally, frozen banked sera from the same day for patients tested only by one assay were retrieved and tested by the other assay. FCBA was performed by the Johns Hopkins Immunology Laboratory using Euroimmun kits with detection by indirect immunofluorescence (FCBA-IF), whereas LCBA was performed by the Mayo Clinic Neuroimmunology Laboratory with detection by flow cytometry (LCBA-FACS). Of 594 specimens with paired MOG-IgG testing, 500 were negative by both assays, 33 were positive by both assays, 56 were positive exclusively by LCBA-FACS, and 5 were only positive by FCBA-IF. Overall, MOG-IgG LCBA-FACS exhibited 95.1% sensitivity and 97.7% specificity, whereas MOG-IgG FCBA-IF had 45.7% sensitivity and 99.8% specificity. Of 577 specimens with paired AQP4-IgG testing, 503 were negative by both assays, 51 were positive by both assays, 21 were positive exclusively by LCBA-FACS, and 2 were only positive by FCBA-IF. Overall, AQP4-IgG LCBA-FACS exhibited 97.3% sensitivity and 100% specificity, whereas AQP4-IgG FCBA-IF had 71.6% sensitivity and 100% specificity. LCBA-FACS for both MOG-IgG and AQP4-IgG had markedly better sensitivity than FCBA-IF, with similar specificity. The use of FCBA-IF may result in underrecognition of both MOG antibody-associated disease (MOGAD) and AQP4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD).

Post-vaccination campaign evaluation of systemic and mucosal immunity of trivalent oral poliovirus vaccine in Karachi, Pakistan (2020-2021): a cross-sectional study.

The transmission of wild poliovirus (WPV1) and circulating vaccine-derived poliovirus (cVDPV) continues to be a major Public Health Emergency of International Concern. Currently, only Afghanistan and Pakistan remain polio-endemic for WPV1. In response to the co-circulation of VDPV2 with WPV1, the Technical Advisory Group of WHO had recommended two nationwide campaigns of trivalent oral poliovirus vaccine (tOPV) for children aged <5 years in Pakistan in 2020. We assessed the humoral and mucosal immune responses in children who received two doses of tOPV (during vaccination campaigns) in Karachi, Pakistan. A cross-sectional survey was conducted in four peri-urban sites (Cattle Colony, Ibrahim Hyderi, Ali Akber Shah, Rehri Goth) Karachi, Pakistan. Venous blood samples from children aged between 1 month and 5 years were obtained. Children who were acutely ill, requiring hospitalisation, with primary immunodeficiency, or with a chronic medical illness, were excluded from the study. Stool and serum testing was performed at the National Institute of Health, Pakistan. Sera samples were analysed using microneutralization assays to quantify polio antibodies for all three serotypes: type 1, 2, and 3. The stool samples collected at baseline, 7, 14, and 28 days (after each tOPV dose) were tested for the presence of poliovirus. Of 285 eligible children, 225 had received both tOPV doses and provided three analysable blood samples, and 193 children provided seven viable stool samples. The seroconversion rate for type 2 was 72% (44/61, 95% CI: 59.8-81.8) after the first tOPV dose; cumulative seroconversion after two doses was 93.4% (95% CI: 84.3-97.4). Seven days after the first and second tOPV campaigns, 32.7% and 18.6% excreted Sabin (vaccine) poliovirus type 2, respectively. The study demonstrated enhanced mucosal immunity as well as a high type 2 seroconversion rate and antibody seroprevalence after two tOPV campaigns. WHO, Geneva, Switzerland.

The Phenytoin Ataxia Enigma Unveiled “A Case Report’’

Background: Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic drug monitoring (TDM). PTH has been observed to induce a variety of Adverse drug reactions (ADRs) including ataxia, dystonia, nystagmus, dyskinesia, etc. Phenytoin-induced ataxia is an uncommonly observed ADR of Phenytoin whose reports are extremely limited. Case: Herein, we present a case report of a 16-year-old Asian patient with a past history of epilepsy that was admitted to a tertiary care hospital due to the development of ataxia, giddiness, and vomiting when taking Phenytoin in addition to Oxcarbazepine, Clobazam, and Levetiracetam to treat seizures. On admission, Magnetic resonance imaging (MRI) findings revealed bilateral variable cerebrospinal fluid (CSF) lesions in the parieto-occipital region of the periventricular area (periventricular leukomalacia). Additionally, serum Phenytoin levels were observed to be in the toxic range (40 μg/mL) due to which physicians confirmed the ADR to be due to Phenytoin toxicity. Thus, the Phenytoin drug was discontinued in the patient gradually and he was continued on clobazam, oxcarbazepine, and brivaracetam which led to reversal of the ADR in the patient. Conclusion: In this case, ataxia resulted from Phenytoin overdose, as confirmed by MRI and serum tests suggesting that TDM of Phenytoin is essential to prevent ADRs. Given the scarcity of ataxia cases caused by Phenytoin, awareness is lacking within the scientific community. Our aim is to provide insights to promote better monitoring and patient-centered treatment outcomes for epileptic patients.

Clinical features of thiopurine-induced acute pancreatitis: comparison between patients with and without inflammatory bowel disease

Abstract Background and Aims Patients with inflammatory bowel disease (IBD) are at increased risk of developing acute pancreatitis (AP). Thiopurines (TP) are a well-known cause of AP. The aims of this study were to compare the incidence of AP and TP-induced AP (TIP) between patients with and without IBD under the use of TP and to assess for risk factors of TIP. Methods We examined a retrospective cohort of 664 patients treated with TP from 2016-2021 at our institution. AP was defined as pancreatitis confirmed by symptoms, serum tests, and radiology, and TIP as AP occurring shortly after starting TP and improving after withdrawal. We compared the incidence of AP and TIP between patients with and without IBD and reviewed the clinical features of TIP patients in detail. Results There were 366 IBD patients and 298 without IBD. IBD patients included 249 males (52.4%) with a median age of 39 years. Among them, 211 had ulcerative colitis (UC) and 155 had Crohn's disease (CD). Azathioprine was administered to 560 patients, and 6-mercaptopurine to 104. AP occurred in 13 IBD patients but in none without IBD, with a significantly higher incidence in IBD patients (1.9% vs. 0%, p = 0.009). Seven of 13 patients with AP satisfied the criteria for TIP. Furthermore, five of the seven TIP patients had a prior history of 5-aminosalicylic acid (5-ASA) intolerance. Conclusions TIP may be a condition specific to IBD. IBD patients with 5-ASA intolerance are prone to TIP

P-354. Clinical Utility of Tuberculosis Screening Tests After Tuberculosis Exposure at an Infusion Clinic

Abstract Background Tuberculin skin testing (PPD) and interferon gamma release assays (IGRA) facilitate screening of patients exposed to active tuberculosis (TB), but the clinical utility of TB screening tests in determining management of exposed high-risk patients is not well described. Because the sensitivity of TB screening tests is dependent on patient’s immunocompetency, further studies looking at the correlation between exposure, testing, and risk of progression to active TB in immunocompromised patients are needed. This study aims to describe TB testing and TB transmission among a large cohort of immunocompromised patients after a known TB exposure event. Methods Retrospective case series of patients who were exposed to TB as defined by CDC Guidelines, identified through contact tracing reports during exposure period April-July 2019. Local infection control protocol was to assess exposed patients with an IGRA initially, then place a PPD if IGRA was inconclusive. Results During the exposure period, an employee with direct patient care duties at an oncology infusion clinic developed active TB, exposing 443 patients. Of the 443 exposed patients, 57 either passed away prior to testing or declined testing. Of the 386 patients who underwent screening tests, 351 (91%), 23 (6%), and 12 (3%) were IGRA negative, positive, and indeterminate, respectively. Of the 12 IGRA indeterminate patients, 8 (67%) had a negative PPD, 2 (16%) refused PPD testing and a repeat IGRA turned negative, and 2 (16%) passed away without further testing. Of the 23 IGRA positive patients, latent TB infection (LTBI) treatment was given in 16 (70%) patients with 7 patients either declining therapy or passed away. None of the 443 patients developed active TB after a 5 year follow up. Conclusion The results of this study found no TB transmission occurred during a high-risk exposure event involving immunocompromised patients when protocol driven testing, treatment, and follow-up was completed. Although CDC publications report low sensitivities of IGRAs in immunocompromised patients, given the large number of exposed patients, serum testing was a practical choice for initial exposure testing and this study showed successful interventions when paired IGRA-PPD testing was used to risk stratify high-risk patients for LTBI therapy. Disclosures All Authors: No reported disclosures

P-1195. Incidence and Diagnosis of Neonatal Herpes Simplex Virus (HSV) Following Transition to In-House Serum Testing

Abstract Background Neonatal Herpes simplex virus (HSV) infection is associated with significant morbidity and mortality, and previously estimated to account for 0.2-0.9% of hospitalizations in infants admitted with sepsis nationally. Recently, our institution transitioned the performance of serum HSV PCR testing in-house to expedite evaluation in neonates admitted with concerns for sepsis. This study was conducted to internally review the impact of in-house testing on neonatal HSV diagnosis and incidence.Table 1:Baseline Characteristics, Diagnosis, and Disease Classification in Infants with Positive Diagnostics Methods All infants ≤2 months of age admitted to our institution in the pre-implementation (8/2021-1/2022) or post-implementation (8/2022-5/2023) periods who had at least one HSV PCR obtained were included. Patient demographics and results of HSV testing were collected retrospectively. A complete evaluation was defined as the performance of HSV PCRs from blood, cerebrospinal fluid (CSF), and all surface sites (mouth, both eyes, nasopharynx, and rectum). The diagnosis of neonatal HSV was made by positive diagnostic(s) in conjunction with clinical presentation. Results A total of 335 infants (pre-transition=131, post-transition=204) were included. Demographics were similar overall between time periods. Diagnosis of neonatal HSV was made in 2 (1.5%) infants evaluated in the pre-transition and 17 (8.3%) infants evaluated in the post-transition period. Following transition to in-house performance of serum HSV PCR testing, infants were more likely to have a complete evaluation performed (82% vs. 0%; p=0.012). Both patients in the pre-cohort had isolated HSV-2 disease while 4 (23.5%) patients in the post-cohort had co-infection with HSV-1 and HSV-2 (Table 1). Overall, 5 (29%) patients in in the post-transition period had only a serum HSV PCR positive at diagnosis. Conclusion Incidence of neonatal HSV within our institution was higher than previous national estimates and incidence increased following transition to in-house serum testing, possibly due in part to improved rates of complete evaluation. The nonspecific clinical presentation and frequency for which only a single PCR was positive reinforces the importance of collecting all surface, blood, and CSF PCRs in neonates undergoing a sepsis evaluation. Disclosures All Authors: No reported disclosures

P-1292. Impact of Discontinuation of Serum Antibody Test Reagents on the Diagnosis of Amebiasis in Japan (2013-2022)

Abstract Background Amebiasis, a notifiable infectious disease in Japan, had shown an increasing trend in reported cases until 2017 when the insurance-covered serum antibody testing reagent was discontinued. This change raised concerns about the subsequent decline in reported cases. Our study aimed to investigate the impact of discontinuing serum antibody test reagent production on amebiasis diagnosis trends. Methods We retrospectively analyzed amebiasis cases from January 2013 to December 2022 using the National Center for Epidemiology of Infectious Diseases system. We employed Poisson analysis to assess weekly amebiasis case trends before and after the discontinuation period, which we divided into pre discontinuation (2013-2017), discontinuation (2018-2019), and COVID-19 pandemic (2020-2022) phases. Results A total of 8,907 cases of amebiasis were reported during the study period. The average weekly number of cases was 20.4 in 2014-2017, 16.4 in 2018-2019, and 10.7 in 2020-2022. After adjusting for the effects of the COVID-19 pandemic, the frequency of diagnosis decreased during the discontinuation period (prevalence rate ratio = 0.76; 95% CI, 0.66-0.86; P &amp;lt; 0.01), especially for extraintestinal amebiasis (prevalence rate ratio = 0.35; 95% CI, 0.22-0.57; P &amp;lt; 0.01) compared with intraintestinal amebiasis (prevalence rate ratio = 0.81; 95% CI, 0.71-0.93; P &amp;lt; 0.01). Conclusion After adjusting for the effects of the COVID-19 pandemic, the number of reported amebiasis cases per week significantly decreased after discontinuation of the serum antibody test reagent, even during the COVID-19 pandemic phase in Japan. To ensure accurate diagnosis, the availability of antibody reagents for serum testing, covered by insurance, should be encouraged. Disclosures Satoshi Ohno, M.D. Ph.D., Otsuka Pharmaceutical Factory: Advisor/Consultant

Nanoencapsulated Optical Fiber-Based PEC Microelectrode: Highly Sensitive and Specific Detection of NT-proBNP and Its Implantable Performance.

Microelectrodes offer exceptional sensitivity, rapid response, and versatility, making them ideal for real-time detection and monitoring applications. Photoelectrochemical (PEC) sensors have shown great value in many fields due to their high sensitivity, fast response, and ease of operation. Nevertheless, conventional PEC sensing relies on cumbersome external light sources and bulky electrodes, hindering its miniaturization and implantation, thereby limiting its application in real-time disease monitoring. To overcome these limitations, we developed a nanoencapsulated optical fiber (OF)-based PEC microelectrode. The microelectrode features TiO2/CdS nanocrystals and bis (2,2'-bipyridine) (10-methylphenanthroline [3,2-a:2'3'-c] pyridine ruthenium(II) dichloride ([Ru(bpy)2dppz]2+) @dsDNA/Au@epigallocatechin gallate nanoparticle (EGCG NP) layers. And its application for the detection of N-terminal pro-brain natriuretic peptide (NT-proBNP) as a biomarker of cardiovascular diseases was explored. An extensive linear range of 1-5000 pg mL-1 combined with a low detection limit of 0.36 pg mL-1 was achieved. This range covers not only the recommended threshold for excluding cardiovascular diseases in the clinical diagnosis of individuals across all age groups but also the prognostic target value. The sensor exhibited excellent selectivity and stability and notable labeling recovery capability in serum tests. Critically, the sensor successfully discriminated the alterations in NT-proBNP secretion levels within human smooth muscle cells, comparing pre- and poststimulation by platelet-derived growth factor-BB. Even more significantly, the skin puncture experiment conducted in mice demonstrated the remarkable implantability and biological compatibility of the OF-PEC microelectrode. This addresses critical challenges commonly faced by microelectrodes when used as implanted devices, such as minimizing invasive trauma, mitigating inflammation, and preventing biofouling, thereby firmly establishing their suitability for the development of advanced implantable sensing devices. Therefore, the present OF microelectrode PEC biosensor is not only cost-effective, easy to operate, and miniaturized but also holds significant potential for enabling more precise, more minimally invasive, and continuous monitoring of biological markers without causing inflammation. This capability is crucial for early disease detection, tracking disease progression, and facilitating personalized treatment strategies, which expands the practical application of PEC sensors.

Evaluation of the recombinant protein Sh-TSP-2 for the serological diagnosis of imported urogenital schistosomiasis and comparison with commercially available tests.

Different agencies have emphasized the need to evaluate current serological methods for screening patients with suspected urogenital schistosomiasis. However, there is still a lack of evidence regarding the most appropriate methods for this purpose. Here we assessed the diagnostic efficacy of a newly developed serological technique that utilizes the recombinant protein Sh-TSP-2, applied to the urine and serum of migrants suspected of having urogenital schistosomiasis. The sensitivity, specificity, positive and negative predictive values of an in-house enzyme-linked immunosorbent assay (ELISA) using the recombinant protein Sh-TSP-2 were analysed and compared with other commercial serological methods. Due to the limitations of microscopy as a perfect reference method, a latent class analysis (LCA) and composite reference standard (CRS) approach was used to determine the sensitivity and specificity of each test. According to the LCA model, the commercial tests NovaLisa® and immunochromatography test (ICT) immunoglobulin G–immunoglobulin M (IgG–IgM) presented the highest sensitivity (100%), whereas the Sh-TSP-2 serum ELISA test had 79.2%. The Sh-TSP-2 urine and serum ELISA tests had the highest specificities among the serological methods (87.5 and 75%, respectively). CRS modelling showed that the ICT IgG–IgM, NovaLisa® and Sh-TSP-2 serum tests led in sensitivity at 97.1, 88.6 and 71.4%, respectively, with all tests except that the ICT IgG–IgM test having a specificity >90%. Sh-TSP-2 has been validated as a screening tool for patients suspected of having urogenital schistosomiasis. Although commercial serological tests have shown higher sensitivities, Sh-TSP-2 could be valuable for confirming results from tests with lower specificity. Nevertheless, further studies with larger patient cohorts are necessary to fully verify its potential.

Multicenter validation of a galactomannan chemiluminescence immunoassay for the diagnosis of pulmonary aspergillosis on serum of patients with hematological disease.

An accurate diagnosis of invasive aspergillosis (IA) in patients with underlying hematological malignancies relies heavily on galactomannan detection. In this study, we compared the VirCLIA chemiluminescence immunoassay (CLIA) with the frequently used Platelia enzyme-linked immunosorbent assay (ELISA) on serum from hematology patients with suspected IA. Patients were categorized according to EORTC/MSGERC 2020 definitions into proven/probable IA and possible/no IA. The first cohort included 161 patients at four centers, and the VirCLIA manufacturer's cutoff of 0.200 was evaluated. Next, the optimal cutoff was determined using the Youden's index. In a second independent cohort of 189 patients from four centers, this optimal cutoff was evaluated again. In the first cohort, sensitivities and specificities for probable/proven IA were 21.1% and 100.0% for ELISA (1.0 cutoff) and 36.6% and 95.6% (0.5 cutoff), compared to 11.3% and 97.8% for CLIA (0.200 cutoff). In the second cohort, the sensitivities of ELISA and CLIA were comparable (ELISA ≥ 1.0: 33.3%, CLIA ≥ 0.200: 38.1%). The area under the ROC curve was lower for CLIA than for ELISA in the first cohort (65.0% vs 78.7%, P = 0.005) but comparable in the second cohort (79.5% vs 81.3%, P = 0.649). Youden's index identified 0.100 as the optimal CLIA cutoff with sensitivities of 35.2% and 61.9% in cohorts 1 and 2, respectively, at slightly reduced specificities of 85.6% and 90.5%. While the sensitivity of both assays was low to moderate at best, in patients with a high pre-test probability, we suggest 0.100 as the cutoff for the VirCLIA assay.IMPORTANCEThis study demonstrates a comparable performance of the novel chemiluminescence immunoassay (CLIA) and the conventionally used enzyme-linked immunosorbent assay for galactomannan serum testing in hematological patients at high risk for invasive aspergillosis. In patients with a high pre-test probability, a lower CLIA cutoff of 0.100 is preferred.

MX/MWCNTs composite material aids new strategy for HBV-DNA electrochemical biosensor: achieving multi-level signal amplification and unlabeled detection

Hepatitis B virus DNA (HBV-DNA) serves as a crucial biomarker for the detection of the hepatitis B virus, with variations in its concentration in blood samples providing vital insights into patient infection and recovery status. We have developed an electrochemical biosensor tailored for HBV-DNA detection, exhibiting high sensitivity, specificity, and a broad detection range. The biosensor utilizes a composite material composed of MXene and multiwalled carbon nanotubes (MX/MWCNTs), prepared through a hand-shaking self-assembly technique, to modify the glassy carbon electrode (GCE) and serve as signal receivers. A meticulously designed padlock probe DNA specifically recognizes HBV-DNA and forms a double-stranded DNA structure, which is subsequently degraded by exonuclease III. The resulting sequence then hybridizes with a PolyT-primer to create template, triggering rolling circle amplification and releasing a substantial amount of pyrophosphate for the initial level of signal amplification. Subsequently, the pyrophosphate induces the release of methylene blue (MB) from MB@ZIF-90 composite, achieving a second level of signal amplification. The released MB is then adsorbed by the MX/MWNCNTs-modified GCE, which possesses cationic dye adsorption capabilities and a large specific surface area, generating a detection signal and completing the third level of amplification. This biosensor offers a detection range spanning from 1.0 pM to 1.0 × 106 pM, with a remarkable detection limit as low as 0.5 pM (3σ/S), and is capable of distinguishing base mismatches. Furthermore, it has demonstrated excellent specificity and recovery performance in serum testing. The performance of this biosensor demonstrates significant potential for clinical application, with the ultimate goal of improving the diagnosis and management of hepatitis B.Graphical

A Comparison of the Dimensional Characteristics and Plasma Parameters of Different Centrifuges Used for the Preparation of Autologous Platelet Concentrates: A Randomized Correlational Study.

The objective of this study was to evaluate autologous platelet-rich fibrin (PRF) membrane weights and measurements after production by different centrifuges. Moreover, the values obtained with blood cellular components were correlated. Twelve systemically healthy participants underwent dental implant surgery associated with PRF membranes as the graft biomaterial at the implant site. Prior to the surgical procedure, the chosen participants underwent blood count and coagulogram tests and presented on the surgical day. Nine tubes containing 10 mL of venous blood were collected from each individual. The tubes were randomly distributed and positioned in three different centrifuges: (C1) the Intra-lock L-PRF Process, (C2) the Kasvi Digital, and (C3) the PRF Montserrat. PRF membrane processing was carried out as described by each manufacturer. After the processing steps, the prepared wet PRFs (initial) were placed in the container (box) designated by the manufacturer for the obtention of PRF membranes. The weights and measurements of the "wet" PRFs (initial) and membranes (final) were obtained using a precision scale and digital caliper in an aseptic environment. The data were compared, and the statistical differences were analyzed using the Friedman test and the Dunn post hoc test; Pearson correlation tests were performed between macroscopic data and data from serum tests; statistical significance was set at 5% (p < 0.05). 108 blood collection tubes were collected. The average harvest time for each tube individually was 21.5 ± 9.9 s. The average time for blood collection (nine tubes) from each of the 12 individuals was 193.1 ± 72.4 s (p = 0.728). The average values were very similar between the centrifuges, both for the measurements and weights of the "plugs" as well as for the linear measurements (p > 0.05). Regarding the wet weights and the linear averages of the PRF membranes, it was observed that the wet PRF weights varied from 0.22 to 0.25 mg and the linear measurements from 24.1 to 26.7 mm, with no statistical differences between centrifuges (p > 0.05). The data presented by centrifuges C1 and C2 were more homogeneous, delivering a value of less than 25% variability compared to the C3 centrifuge, which achieved values greater than 33%. The proposed macroscopic dimensional evaluation found no differences between the autologous platelet concentrates obtained by different centrifuges, and no correlation was found between these PRFs and the patients' blood counts.

Diagnostic performance of noninvasive tests for cytomegalovirus ileocolitis: a systematic review and meta-analysis.

Diagnosis of cytomegalovirus (CMV) ileocolitis traditionally requires colonoscopy with tissue biopsy. Due to potential complications in high-risk patients, there is growing interest in serum and stool tests for diagnosing this condition. We aimed to evaluate the diagnostic accuracy of these noninvasive tests compared to traditional gold standards. Two independent reviewers performed a comprehensive search on MEDLINE and Embase from inception up to October 1, 2023. Prospective and retrospective studies evaluating the performance of serum CMV polymerase chain reaction (PCR), serum CMV antigen (Ag), and stool CMV PCR in diagnosing CMV ileocolitis were included. Tissue histopathology or tissue CMV PCR served as reference standards. Diagnostic performances of each serum and stool test were calculated based on a meta-analysis using random-effects model. A total of 30 studies, comprising 23 studies of serum CMV PCR, 9 of serum CMV Ag, and 7 of stool CMV PCR, were included. The pooled sensitivity, specificity, and area under summary receiver operating characteristic curves were 62% (95% confidence interval [CI], 51%-72%), 90% (95% CI, 79%-96%), and 0.81 for serum CMV PCR, 38% (95% CI, 26%-51%), 94% (95% CI, 70%-99%), and 0.56 for serum CMV Ag, and 53% (95% CI, 35%-70%), 91% (95% CI, 84%-95%), and 0.84 for stool CMV PCR. Serum and stool tests cannot replace colonoscopy for diagnosing CMV ileocolitis due to their low sensitivities but may be useful when colonoscopy is not feasible. Positive results can aid diagnosis, given their high specificities. Serum and/or stool CMV PCR are preferred over CMV Ag.

HETEROPHILE ANTIBODIES – A RARE BUT SIGNIFICANT CAUSE OF FALSE POSITIVE CARDIAC TROPONIN LEVELS

HighlightsPractitioners regularly encounter unexplained (false-positive) causes and mechanisms of increased concentrations of cardiac troponins. One of the most significant and common causes of false increases in cardiac troponin levels are heterophile antibodies. There are no articles in domestic and foreign databases that systematize in detail information about the prevalence, mechanisms of increase and ways to combat this cause of false-positive increase in cardiac troponin concentration, which was the purpose of this manuscript. AnnotationAccording to traditional concepts, cardiospecific troponins (cTnT and cTnI) are the most important laboratory biomarkers with high diagnostic value in myocardial infarction (MI). The development of new generations of methods for determining cTnT and cTnI, also called high- and ultra-sensitive methods, has expanded the diagnostic capabilities of cardiac troponins in relation to other diseases in which myocardial tissue is involved in the pathological process, thereby carrying additional prognostic value. Given the wide scope for use of cTnT and cTnI, which is not limited to the diagnosis of MI, there is an urgent need to carefully identify all factors that can in any significant way affect or distort the result of laboratory testing of blood serum for cTnT and cTnI. Among all known factors affecting the concentration of cTnT and cTnI, heterophile antibodies are the most significant in terms of the degree of change (increase) in serum levels. In this review, we will consider the main causes of the formation of heterophile antibodies, the mechanisms of their influence on the concentration of cTnT and cTnI, as well as methods for detecting and combating heterophile antibodies.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health. Metabolic dysfunction and associated insulin resistance, together with the predilection for ectopic fat deposition in the liver and surrounding tissues, are associated with elevated risk of endothelial dysfunction, systemic inflammatory response, and ectopic fat deposition in the epicardium. This complex pathophysiology can accelerate atherogenic dyslipidemia, atherogenesis, diastolic dysfunction, valvular calcification, and cardiac arrhythmias. Despite the mounting evidence of mechanistic pathways underpinning MASLD and CVD, current recommendations have not clearly focused upon MASLD as a risk factor or target for intervention in CVD. We have brought together a diverse range of international experts committed to promoting cardiovascular-liver-metabolic health and related outcomes across the globe. The overarching goal of this document is to offer a construct for clinicians in the cardiovascular field with regards to (1) diagnosis and screening of MASLD through the use of noninvasive serum and imaging tests; (2) screening for CVD in all individuals with MASLD regardless of established atherosclerotic risk factors; and (3) the approach to management of MASLD with respect to prevention of CVD through lifestyle, as well as pharmacologic and surgical strategies. To achieve this, the modified Delphi method was applied and a series of evidence-based quality standard recommendations have been identified.

Longitudinally persisting KCNA2-autoantibodies in mild amnestic dementia with Alzheimer´s pathology - Report and literature review.

Neural autoantibodies are being increasingly detected in conjunction with neurodegenerative dementias such as Alzheimer's disease dementia (AD), yet their significance is not well clarified. In this case report, we report the previously unreported long-lasting persistence of potassium voltage-gated channel subfamily A member 2 (KCNA2) antibodies in biomarker-supported AD. We report on a 77-year-old, male patient evaluated in our outpatient memory clinic of the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen. Neuropsychological test results and autoantibody testing in serum over a period of 4-5 years is provided. Our patient exhibited mild dementia syndrome and was diagnosed with AD on the basis of a prototypical biomarker profile (reduced Aβ42/40 ratio and elevated p-tau181 protein in cerebrospinal fluid). Within a 5-year follow-up with regular visits to our memory clinic, we observed a nearly stable neuropsychological profile of mild, amnestic variant dementia that did not noticeably progress. KCNA2 autoantibodies were also detectable in serum over 4 years with increasing titers over time. Combined anti-dementia therapy with donepezil, multimodal therapy including non-pharmacological cognitive therapy, and immunotherapy with intravenous methylprednisolone was carried out as an individual treatment approach. KCNA2 autoantibody persistence in biomarker-supported AD does not necessarily trigger a poor outcome in the long-term, as cognitive impairment did not progress subsequently. At the same time, mild immunotherapy did not result in less immunoreactivity in conjunction with the detection of KCNA2 autoantibodies. This detection of KCNA2 autoantibodies in AD could provide indices of a potentially benign long-term AD course that should be further evaluated in studies.

Monitoring of Leishmania infantum exposure in the Iberian lynx (Lynx pardinus)

Leishmaniosis, caused by phlebotomine sand fly-borne Leishmania spp., is a multi-host and zoonotic disease in tropical, subtropical and temperate climates, worldwide. Leishmania infantum is the only endemic pathogenic species in Europe, and exposure to this protozoan has previously been reported in a wide range of wild mammals, including felids. However, the information about the exposure of the threatened Iberian lynx (Lynx pardinus) to L. infantum is still very scarce. Consequently, the aims of the present large-scale epidemiological study were: (1) to evaluate the circulation of L. infantum in the free-ranging and captive Iberian lynx populations and (2) to investigate potential risk factors associated with L. infantum exposure during the study period, between 2010 and 2022. A total of 783 Iberian lynxes from captive (n = 296) and free-ranging (n = 487) populations were sampled from different areas of the Iberian Peninsula. Exposure to L. infantum (positive to indirect fluorescent antibody test (IFAT) in serum and/or real-time quantitative PCR (qPCR) in spleen samples) was detected in 80 of the 783 lynxes, so the estimated prevalence (95% confidence limits) was 10.2% (8.1-12.3%). Specifically, anti-Leishmania antibodies were found in 12 of the 469 lynxes (2.6%; 1.1-4.0%) and L. infantum kDNA was detected in 68 of the 333 lynxes (20.4%; 16.1-24.8%) with a Ct range from 26.0 to 38.0 (median: 36.0). One seroconversion and one seroreversion were observed among the 42 Iberian lynxes longitudinally sampled. Phylogenetic analysis revealed high homology (99.9-100%) with other L. infantum sequences obtained from wild rabbits (Oryctolagus cuniculus), Iberian hares (Lepus granatensis) and humans from Spain. The multivariate analysis identified the habitat status (free-ranging) and age (adult and subadult) as risk factors potentially associated with L. infantum exposure in Iberian lynxes. Our results indicate moderate and widespread circulation of this pathogen in the Iberian lynx populations, suggesting its potential role as spillover hosts in Iberian Mediterranean ecosystems. Additional studies are warranted to determine the clinical impact of L. infantum exposure in this threatened species.

Subacute Upper Motor Neuron Dysfunction Possibly Associated with the Anti-GM1 Autoantibody: A Case Report

Anti-GM1 antibodies are associated with Guillain-Barré syndrome (GBS), primarily peripheral neuropathy. However, there are cases of anti-GM1 IgG antibody-positive GBS with upper motor neuron (UMN) signs. We herein report a case of gastrointestinal infection followed by subacute gait disturbance with predominant signs of UMN on a neurological examination. The serum and cerebrospinal fluid tests were positive for anti-GM1 and anti-asialo-GM1 IgG antibodies. An electrophysiological evaluation revealed normal nerve conduction and prolonged central motor conduction times. No MRI abnormalities were observed. The symptoms improved with treatment, which was accompanied by decreased antibody titers. This case highlights the fact that anti-GM1 IgG-associated disorders may present with predominant UMN involvement.