Diurnal and day-to-day biological variation of salivary cortisol and cortisone.

OBJECTIVES: There is a growing interest in the relevance of salivary cortisol and cortisone concentrations in stress-related research. To correctly attribute the magnitude of salivary cortisol and cortisone variation as an effect of a stressful event, a coherent understanding of the day-to-day intra-individual and inter-individual variability across the diurnal cycle of the two steroids is required. However, such information is currently lacking. METHODS: This study aimed to overcome these existing limitations by performing an investigation of the biological variation (BV) of salivary cortisol and cortisone within one day and between five days using an LC-MS/MS method. Saliva samples were collected from 20 healthy volunteers immediately after waking up, at 8:00, 12:00, 15:00, 19:00 and 23:00 on each day over five days. All samples were analyzed in duplicate in one run. Nested ANOVA was used to calculate the sums of squares for analytical and biological components of variation. RESULTS: The within-subject BV of salivary cortisol and cortisone (CVI) ranged from a minimum of 29.3 and 19.0 % to a maximum of 56.5 and 49.1 %, respectively, while the between-subject biological variation (CVG) ranged from 29.7 and 29.0 % to 51.6 and 43.6 %. The reference change values (RCVs) ranged from 96 to 245 % for cortisol and from 55 to 194 % for cortisone. A medium index of individuality was observed for both compounds at all time points. CONCLUSIONS: This study provides updated BV estimates and RCVs for different times of day that can be used to assess the magnitude of change in biomarkers in future stress-related research.

Dynamic mirroring: unveiling the role of digital twins, artificial intelligence and synthetic data for personalized medicine in laboratory medicine.

In recent years, the integration of technological advancements and digitalization into healthcare has brought about a remarkable transformation in care delivery and patient management. Among these advancements, the concept of digital twins (DTs) has recently gained attention as a tool with substantial transformative potential in different clinical contexts. DTs are virtual representations of a physical entity (e.g., a patient or an organ) or systems (e.g., hospital wards, including laboratories), continuously updated with real-time data to mirror its real-world counterpart. DTs can be utilized to monitor and customize health care by simulating an individual's health status based on information from wearables, medical devices, diagnostic tests, and electronic health records. In addition, DTs can be used to define personalized treatment plans. In this study, we focused on some possible applications of DTs in laboratory medicine when used with AI and synthetic data obtained by generative AI. The first point discussed how biological variation (BV) application could be tailored to individuals, considering population-derived BV data on laboratory parameters and circadian or ultradian variations. Another application could be enhancing the interpretation of tumor markers in advanced cancer therapy and treatments. Furthermore, DTs applications might derive personalized reference intervals, also considering BV data or they can be used to improve test results interpretation. DT's widespread adoption in healthcare is not imminent, but it is not far off. This technology will likely offer innovative and definitive solutions for dynamically evaluating treatments and more precise diagnoses for personalized medicine.

Evaluation of the Comparability of Wantai Wan200+ Instrument with Routine Laboratory Assays for 21 Different Analytes.

Background: We compared the performance of 21 different assays performed by the Wantai Wan200+ (Wantai BioPharm, Beijing, China) with respect to other methods in use at the University Hospital of Padova (AOPD), Italy. Methods: The plasma (P) or serum (S) of 5027 leftover samples, collected from May to Sept 2023, was either analyzed or frozen at -20 °C. Beckman DXI800 (DXI), Roche Cobas 8000 e801 (RC), Snibe Maglumi 4000 plus (SM), DiaSorin Liaison XL (DL) and Binding Site Optilite (BS) equipment were used at the AOPD. P-procalcitonin (PCT), DXI; P-Troponin I (TnI), DXI; S-CA125, DXI; S-free PSA (f-PSA), DXI; S-total PSA (t-PSA), DXI; S-IL6, SM; P-Troponin T (TnT), RC; P-NT-proBNP, RC; P-Neuron-Specific Enolase (NSE), RC; S-CA15-3, DL; S-CA19-9, DL; S-AFP, DL; and S-CEA, DL were tested in fresh samples. P-Myoglobin (Myo), DXI; P-Cyfra21-1, RC; S-ß2 microglobulin (B2MIC), BS; S-HE4, SM; S-PGI, SM; S-PGII, SM; S-CA72-4, SM; and S-CA50, SM were analyzed in frozen and thawed samples. Bland-Altman (BA), Passing-Bablok (PB) and Cohen's Kappa (CKa) metrics were used as statistics. Results: An excellent comparability profile was found for 11 analytes. For example, the t-PSA CKa was 0.94 (95%CI: 0.90 to 0.98), and the PB slope and intercept were 1.02 (95%CI: 0.99 to 1.03) and 0.02 (95%CI: 0.01 to 0.03), respectively; the BA bias was 2.25 (95%CI: -0.43 to 4.93). Ten tested measurands demonstrated a suboptimal comparability profile. Biological variation in EFLM (EuBIVAS) performance specifications was evaluated to assess the clinical relevance of measured biases. Conclusions: Evaluation of the Wantai Wan200+'s performance suggests that between-method differences did not exceed the calculated bias. Metrological traceability may influence the comparisons obtained for some measurands.

Plasma lipids paediatric reference intervals: Indirect estimation using a large 14-year database.

OBJECTIVES: Establishing direct reference intervals (RIs) for paediatric patients is a very challenging endeavour. Indirect RIs can address this problem, using existing clinical laboratory databases from real-world data research. Compared to the traditional direct method, the indirect approach is highly practical, widely applicable, and low-cost. Considering the relevance of dyslipidemia in the paediatric age, to provide better laboratory services to the local paediatric population, we established population-specific lipid RIs via data mining. METHODS: Our laboratory information system was searched for cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) of patients aged less than 18 years, performed from January 2009 until December 2022. RIs were estimated using RefineR algorithm. RESULTS: Values from 215,594 patients were initially collected. After refining data on the basis of specific exclusion criteria that left 17,933 patients, we determined the RIs for each analyte, including corresponding 95% confidence interval (95% CI). Age and sex partitions were required for proper stratification of the heterogenous subpopulations. Age-related variations in TC and TG values were observed mainly in children until 5 years. RIs were defined for children less than 3 years and for those of 3-18 years. In our population, the obtained RIs were comparable with those of the literature, but the upper TG limit in subjects under the age of 3 (2.03 mmol/L with 95% CI: 1.45-2.86) was lower than that previously reported. CONCLUSIONS: Our RIs, necessary for paediatric lipid monitoring, are tailored to the serviced patient population as should be done whenever possible.

Risk of SARS-CoV-2 Reinfection in Children Within the 12 Months Following Mild COVID-19: Insights From a Survey Study.

Understanding the correlation between immune response and protection from COVID-19 will play a pivotal role in predicting the effectiveness of vaccines in children. We studied SARS-CoV-2 reinfection risk in children 12 months post-mild COVID-19. Children under 5 years old exhibited lower reinfection risk than older infected or vaccinated siblings during 12 months postimmunization.

Clinical and Analytical Performance of ELISA Salivary Serologic Assay to Detect SARS-CoV-2 IgG in Children and Adults.

Saliva is a promising matrix with several purposes. Our aim is to verify if salivary anti-SARS-CoV-2 antibody determination is suitable for monitoring immune responses. One hundred eighty-seven subjects were enrolled at University-Hospital Padova: 105 females (56.1%) and 82 males (43.9%), 95 (50.8%) children and 92 (49.2%) adults. Subjects self-collected saliva using Salivette; nineteen subjects collected three different samples within the day. A serum sample was obtained for all individuals. The N/S anti-SARS-CoV-2 salivary IgG (sal-IgG) and serum anti-SARS-CoV-2 S-RBD IgG (ser-IgG) were used for determining anti-SARS-CoV-2 antibodies. The mean (min-max) age was 9.0 (1-18) for children and 42.5 (20-61) for adults. Of 187 samples, 63 were negative for sal-IgG (33.7%), while 7 were negative for ser-IgG (3.7%). Spearman's correlation was 0.56 (p < 0.001). Sal-IgG and ser-IgG levels were correlated with age but not with gender, comorbidities, prolonged therapy, previous SARS-CoV-2 infection, or time from last COVID-19 infection/vaccination. The repeatability ranged from 23.8% (7.4 kAU/L) to 4.0% (3.77 kAU/L). The linearity of the assay was missed in 4/6 samples. No significant intrasubject differences were observed in sal-IgG across samples collected at different time points. Sal-IgG has good agreement with ser-IgG. Noninvasive saliva collection represents an alternative method for antibody measurement, especially in children.

Stronger and durable SARS-CoV-2 immune response to mRNA vaccines in 5-11 years old children with prior COVID-19.

BACKGROUND AND OBJECTIVES: mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is scarce. This study aimed to assess the early and long-term immune response to the mRNA vaccine in children with or without previous SARS-CoV-2 infection. METHODS: In a multicentre prospective observational study, we profiled the immune response to the Pfizer BioNTech (BNT162b2) vaccine in 5-11-year-old children attending the University Pediatric Hospital of Padua and Bambino-Gesù Hospital in Rome (Italy) from December-2021 to February-2023. Blood samples were collected pre-, 1-, and 6-months after vaccination. Neutralizing antibodies (NAbs) and anti-spike-receptor-binding-domain (anti-S-RBD) IgG titers were analyzed through Plaque Reduction Neutralization Test (PRNT) and chemiluminescent immune-enzymatic assay (CLIA), respectively. Immune cell phenotypes were analyzed by flow cytometry. RESULTS: Sixty children (26 [43 %] female, median age = 8 years [IQR = 7-10.7]) were enrolled in the study, including 46 children with a laboratory-confirmed previous COVID-19 (SARS-CoV-2-recovered) and 14 SARS-CoV-2-naïve participants defined as the absence of antigen-specific antibodies before vaccination. SARS-CoV-2-recovered participants recorded higher anti-S-RBD IgG and Wild-type and Omicron BA.2 NAbs titers than SARS-CoV-2-naïve participants at both 1- and 6-months after vaccination. Antibody titers correlated with T (Tregs) and B (Bregs) regulatory cell frequencies in SARS-CoV-2-recovered children. Both SARS-CoV-2-recovered and SARS-CoV-2-naïve participants decreased antibody titers by approximately 100 to 250 % from 1 to 6 months. While children with immunocompromising underlying conditions developed immune responses comparable to those of healthy children, solid organ transplant recipients exhibited lower levels of NAbs and anti-S-RBD IgG titers, as well as reduced frequencies of Tregs and Bregs. CONCLUSIONS: mRNA vaccination triggered a higher production of specific anti-SARS-CoV-2 antibodies along with increased levels of regulatory cells in children with previous SARS-CoV-2 infection up to the following 6 months. These findings provide insights into boosting pre-existing immunity.

Analytical and clinical evaluations of SNIBE Maglumi chemiluminescent immunoassay for the detection of SARS-CoV-2 antigen in salivary samples.

OBJECTIVES: In this study, we describe the analytical and clinical performances of the SNIBE Maglumi SARS-CoV-2 antigen fully-automated chemiluminescent immunoassay (MAG-CLIA) on salivary samples. METHODS: Limit of detection (LOD), linearity and precision were tested for values close to or below the declared LOD. Clinical performance of MAG-CLIA was evaluated on leftover salivary samples from the healthcare workers (HCW) surveillance program, at the University-Hospital of Padova. Salivary samples were analyzed by Lumipulse G SARS-CoV-2 Ag, and in case where the values exceeded 0.41 ng/L, further testing was conducted using TaqPathTM COVID-19 RT-PCR (Applied Biosystems, Thermo Fisher Scientific). RESULTS: The estimated MAG-CLIA LOD was 3 ng/L, with repeatability of 7.5 %. Good linearity was demonstrated by diluting two samples at 52.7 ng/L and 211.4 ng/L. Of the 228 HCW samples, 59/228 (25.9 %) were positive, 169/228 (74.1 %) were negative. MAG-CLIA SARS-CoV-2 sAg median level (and interquartile range [IQR]) was 5.03 ng/L (<0.001-35.8 ng/L) for positive and <0.001 ng/L (<0.001 ng/L) for negative samples. MAG-CLIA AUC was 0.795 (95 % CI: 0.720-0.871). Using the best cut-off, 3.5 ng/L, sensitivity and specificity were 57.1 % (95 % CI: 42.2-71.2 %) and 97.0 % (95 % CI: 93.2-99.0 %), respectively. The agreement with the molecular assay was 88.1 % (Cohen's kappa 0.606 [SE=0.066, p<0.001]). CONCLUSIONS: The analytical performances of MAG-CLIA are satisfactory, also when values below LOD were tested. In saliva samples, although specificity was elevated, clinical performance was not comparable with that on nasopharyngeal swabs (NPS).

Rising adoption of artificial intelligence in scientific publishing: evaluating the role, risks, and ethical implications in paper drafting and review process.

BACKGROUND: In the rapid evolving landscape of artificial intelligence (AI), scientific publishing is experiencing significant transformations. AI tools, while offering unparalleled efficiencies in paper drafting and peer review, also introduce notable ethical concerns. CONTENT: This study delineates AI's dual role in scientific publishing: as a co-creator in the writing and review of scientific papers and as an ethical challenge. We first explore the potential of AI as an enhancer of efficiency, efficacy, and quality in creating scientific papers. A critical assessment follows, evaluating the risks vs. rewards for researchers, especially those early in their careers, emphasizing the need to maintain a balance between AI's capabilities and fostering independent reasoning and creativity. Subsequently, we delve into the ethical dilemmas of AI's involvement, particularly concerning originality, plagiarism, and preserving the genuine essence of scientific discourse. The evolving dynamics further highlight an overlooked aspect: the inadequate recognition of human reviewers in the academic community. With the increasing volume of scientific literature, tangible metrics and incentives for reviewers are proposed as essential to ensure a balanced academic environment. SUMMARY: AI's incorporation in scientific publishing is promising yet comes with significant ethical and operational challenges. The role of human reviewers is accentuated, ensuring authenticity in an AI-influenced environment. OUTLOOK: As the scientific community treads the path of AI integration, a balanced symbiosis between AI's efficiency and human discernment is pivotal. Emphasizing human expertise, while exploit artificial intelligence responsibly, will determine the trajectory of an ethically sound and efficient AI-augmented future in scientific publishing.

Machine learning-based nonlinear regression-adjusted real-time quality control modeling: a multi-center study.

OBJECTIVES: Patient-based real-time quality control (PBRTQC), a laboratory tool for monitoring the performance of the testing process, has gained increasing attention in recent years. It has been questioned for its generalizability among analytes, instruments, laboratories, and hospitals in real-world settings. Our purpose was to build a machine learning, nonlinear regression-adjusted, patient-based real-time quality control (mNL-PBRTQC) with wide application. METHODS: Using computer simulation, artificial biases were added to patient population data of 10 measurands. An mNL-PBRTQC was created using eight hospital laboratory databases as a training set and validated by three other hospitals' independent patient datasets. Three different Patient-based models were compared on these datasets, the IFCC PBRTQC model, linear regression-adjusted real-time quality control (L-RARTQC), and the mNL-PBRTQC model. RESULTS: Our study showed that in the three independent test data sets, mNL-PBRTQC outperformed the IFCC PBRTQC and L-RARTQC for all measurands and all biases. Using platelets as an example, it was found that for 20 % bias, both positive and negative, the uncertainty of error detection for mNL-PBRTQC was smallest at the median and maximum values. CONCLUSIONS: mNL-PBRTQC is a robust machine learning framework, allowing accurate error detection, especially for analytes that demonstrate instability and for detecting small biases.

Machine learning algorithms in sepsis.

Sepsis remains a significant global health challenge due to its high mortality and morbidity, compounded by the difficulty of early detection given its variable clinical manifestations. The integration of machine learning (ML) into laboratory medicine for timely sepsis identification and outcome forecasting is an emerging field of interest. This comprehensive review assesses the current body of research on ML applications for sepsis within the realm of laboratory diagnostics, detailing both their strengths and shortcomings. An extensive literature search was performed by two independent investigators across PubMed and Scopus databases, employing the keywords "Sepsis," "Machine Learning," and "Laboratory" without publication date limitations, culminating in January 2023. Each selected study was meticulously evaluated for various aspects, including its design, intent (diagnostic or prognostic), clinical environment, demographics, sepsis criteria, data gathering period, and the scope and nature of features, in addition to the ML methodologies and their validation procedures. Out of 135 articles reviewed, 39 fulfilled the criteria for inclusion. Among these, the majority (30 studies) were focused on devising ML algorithms for diagnosis, fewer (8 studies) on prognosis, and one study addressed both aspects. The dissemination of these studies across an array of journals reflects the interdisciplinary engagement in the development of ML algorithms for sepsis. This analysis highlights the promising role of ML in the early diagnosis of sepsis while drawing attention to the need for uniformity in validating models and defining features, crucial steps for ensuring the reliability and practicality of ML in clinical setting.

Evaluation of a new molecular test for the detection of SARS-CoV-2 nucleic acid in salivary samples.

Background: Molecular testing is considered the gold standard for the detection of SARS-CoV-2. This study aimed to compare the performance of the P742H SARS-CoV-2 Nucleic Acid Multiplex Detection Kit in salivary samples, with respect to the 732HF Novel Coronavirus (2019-nCoV) Nucleic Acid Detection Kit and the TaqPath COVID-19 CEIVD RT-PCR Kit, used at University-Hospital of Padova, Italy. Methods: One hundred twenty-four salivary samples selfcollected by healthcare workers (HCW) during the screening program at University-Hospital of Padova, Italy, from Oct to Nov 2022, were included in the study. RNA extraction was performed by Viral DNA and RNA Extraction Kit (Technogenetics, Lodi, Italy) and amplification by P742H and 732HF (Technogenetics, Lodi, Italy). RNA was extracted using MagNa Pure 96 DNA and Viral NA Small Volume Kit (Roche, Switzerland) for TaqPath analysis (Thermo Fisher Scientific, USA).

The Safety of a High-Flow Nasal Cannula in Neuromuscular Disease Patients with Acute Respiratory Failure: A Retrospective Case-Series Study.

(1) Background: Although Non-Invasive Ventilation (NIV) is effective in preventing mortality and endotracheal intubation in patients with Acute Respiratory Failure (ARF) linked to a neuromuscular disorder, its efficacy can be affected by patient intolerance. A High-Flow Nasal Cannula (HFNC) appears to have a significant advantage over NIV as far as patient tolerance is concerned. The aim of the study was to investigate HFNC's safety profile in a group of consecutive Neuromuscular Disease (NMD) patients intolerant to NIV who were admitted to an Intermediate Respiratory Care Unit (IRCU) for ARF. (2) Methods: The clinical course of nine NMD patients intolerant to NIV and switched to HFNC was reported. HFNC was provided during daytime hours and NIV during the night-time to the NIV-intolerant patients. HFNC was utilized 24 h a day in those patients who were intolerant of even nocturnal NIV. (3) Results: HFNC was simple to use and it was well tolerated by all of the patients. Three out of nine patients experienced treatment failure, consisting of the need for ETI and/or death during their IRCU stay. The remaining 6 had a favorable outcome. Treatment failure was linked to the utilization of HFNC 24 h a day. (4) Conclusion: HFNC during the daytime hours, together with nocturnal NIV, seems to be a safe therapeutic approach for NMD patients with ARF. A round-the-clock use of HFNC tends to be linked to a high likelihood of failure.

Plasma Bile Acid Profiling and Modulation of Secreted Mucin 5AC in Cholangiocarcinoma.

Studies investigating the potential role of circulating bile acids (BAs) as diagnostic biomarkers for cholangiocarcinoma (CCA) are sparse and existing data do not adjust for confounding variables. Furthermore, the mechanism by which BAs affect the expression of the oncogenic mucin 5AC (MUC5AC) has never been investigated. We performed a case-control study to characterise the profile of circulating BAs in patients with CCA (n = 68) and benign biliary disease (BBD, n = 48) with a validated liquid chromatography-tandem mass spectrometry technique. Odd ratios (OR) for CCA associations were calculated with multivariable logistic regression models based on a directed acyclic graph structure learning algorithm. The most promising BAs were then tested in an in vitro study to investigate their interplay in modulating MUC5AC expression. The total concentration of BAs was markedly higher in patients with CCA compared with BBD controls and accompanied by a shift in BAs profile toward a higher proportion of primary conjugated BAs (OR = 1.50, CI: 1.14 to 1.96, p = 0.003), especially taurochenodeoxycholic acid (TCDCA, OR = 42.29, CI: 3.54 to 504.63, p = 0.003) after multiple adjustments. Western blot analysis of secreted MUC5AC in human primary cholangiocytes treated with primary conjugated BAs or with TCDCA alone allowed us to identify a novel 230 kDa isoform, possibly representing a post-translationally modified MUC5AC specie.

Clinical features of COVID-19 in Italian outpatient children and adolescents during Parental, Delta, and Omicron waves: a prospective, observational, cohort study.

Introduction: COVID-19 features changed with the Omicron variant of SARS-CoV-2 in adults. This study aims to describe COVID-19 symptoms in children and adolescents during the Parental, Delta, and Omicron eras. Methods: A single-centre, prospective observational study was conducted on individuals aged 0-20 years attending the University Hospital of Padua (Italy) from April 2020 to December 2022. COVID-19 cases were defined by positive SARS-CoV-2 molecular detection and/or serology; patient/family symptoms and virological positivity were considered to determine the infection onset. Variables were summarized and compared using appropriate tests of descriptive statistics. Results: A total of 509 cases [46% female, median age eight years (IQR: 4-12)] were studied. Three-hundred-eighty-seven (76%), 52 (10%), and 70 (14%) subjects experienced COVID-19 during the Parental, Delta, and Omicron waves, respectively. All subjects developed an asymptomatic/mild COVID-19. Overall, the most frequent symptoms were fever (47%) and rhinitis (21%), which showed a significant increasing incidence from the Parental to Omicron waves (p < 0.001). Conversely, diarrhea was most common during the pre-Omicron eras (p = 0.03). Stratifying symptoms according to the age group, fever, rhinitis, and skin rashes were observed more frequently among infants/toddlers; conversely, fatigue was more common in children older than five years. The duration of symptoms was similar across different SARS-CoV-2 variants of concern (VOCs); conversely, the number of symptoms varied according to the age group (p < 0.0001). Discussion: This study showed differences in COVID-19 clinical presentation among infants, children, and adolescents and confirmed Omicron infection is more likely to be associated with upper respiratory symptoms. However, further population-based studies are needed to support these findings. In addition, active surveillance will play a crucial role in assessing the disease severity of future VOCs.

Tixagevimab/Cilgavimab as pre-exposure prophylaxis against SARS-CoV-2 in patients with hematological malignancies.

The approved combination of Tixagevimab/Cilgavimab has been shown to decrease the rate of symptomatic SARS-CoV-2 infection in patients at increased risk of inadequate response to vaccination. However, Tixagevimab/Cilgavimab was tested in a few studies that included patients with hematological malignancies, even if this population has shown an increased risk of unfavorable outcomes following infection (with high rates of hospitalization, intensive care unit admission, and mortality) and poor significant immunization following vaccines. We performed a real-life prospective cohort study to evaluate the rate of SARS-CoV-2 infection following pre-exposure prophylaxis with Tixagevimab/Cilgavimab in anti-spike seronegative patients compared to a cohort of seropositive patients who were observed or received a fourth vaccine dose. We recruited 103 patients with a mean age of 67 years: 35 (34%) received Tixagevimab/Cilgavimab and were followed from March 17, 2022, until November 15, 2022. After a median follow-up of 4.24 months, the 3-month cumulative incidence of infection was 20% versus 12% in the Tixagevimab/Cilgavimab and observation/vaccine groups respectively (HR 1.57; 95% CI: 0.65-3.56; p = 0.34). In this study, we report our experience with Tixagevimab/Cilgavimab and a tailored approach to SARS-CoV-2 infection prevention in patients with hematological malignancies during the SARS-CoV-2 omicron surge.

Autoinflammatory Diseases and COVID-19 Vaccination: Analysis of SARS-CoV-2 Anti-S-RBD IgG Levels in a Cohort of Patients Receiving IL-1 Inhibitors.

The purpose of the study was to evaluate the antibody response after COVID-19 vaccination in patients affected by systemic autoinflammatory diseases (SAID) undertaking IL-1 inhibitors (IL-1i) compared to healthy vaccinated controls (HC). The course of COVID-19 in vaccinated patients on IL-1i was also assessed. The serological response was evaluated in SAID patients using the CLIA MAGLUMI TM 2000 Plus test after the first vaccination cycle and the booster dose. Fifty-four fully vaccinated healthcare workers were enrolled as HCs. GraphPad Prism 8 software was used for statistical analysis. All patients developed an adequate antibody response. No differences were observed between the antibody titers of patients on IL-1i and those not on IL-1i, either after the first vaccination cycle or the booster dose (p = 0.99), and to HC (p = 0.99). With increasing age, a decrease in antibody production was assessed after the second vaccine in SAID (r = 0.67, p = 0.0003). In general, 11.6% of SAID patients had COVID-19 after receiving vaccination. None of them developed severe disease or experienced flares of their autoinflammatory disease. In conclusion, patients receiving IL-1i develop an antibody response comparable to HC. No side effects after vaccination were observed; IL-1i was continued before and after injections to avoid flare-ups.

Inflammation, Autoinflammation and Autoimmunity in Inflammatory Bowel Diseases.

In this review, the role of innate and adaptive immunity in the pathogenesis of inflammatory bowel diseases (IBD) is reported. In IBD, an altered innate immunity is often found, with increased Th17 and decreased Treg cells infiltrating the intestinal mucosa. An associated increase in inflammatory cytokines, such as IL-1 and TNF-α, and a decrease in anti-inflammatory cytokines, such as IL-10, concur in favoring the persistent inflammation of the gut mucosa. Autoinflammation is highlighted with insights in the role of inflammasomes, which activation by exogenous or endogenous triggers might be favored by mutations of NOD and NLRP proteins. Autoimmunity mechanisms also take place in IBD pathogenesis and in this context of a persistent immune stimulation by bacterial antigens and antigens derived from intestinal cells degradation, the adaptive immune response takes place and results in antibodies and autoantibodies production, a frequent finding in these diseases. Inflammation, autoinflammation and autoimmunity concur in altering the mucus layer and enhancing intestinal permeability, which sustains the vicious cycle of further mucosal inflammation.

Artificial intelligence and laboratory data in rheumatic diseases.

Artificial intelligence (AI)-based medical technologies are rapidly evolving into actionable solutions for clinical practice. Machine learning (ML) algorithms can process increasing amounts of laboratory data such as gene expression immunophenotyping data and biomarkers. In recent years, the analysis of ML has become particularly useful for the study of complex chronic diseases, such as rheumatic diseases, heterogenous conditions with multiple triggers. Numerous studies have used ML to classify patients and improve diagnosis, to stratify the risk and determine disease subtypes, as well as to discover biomarkers and gene signatures. This review aims to provide examples of ML models for specific rheumatic diseases using laboratory data and some insights into relevant strengths and limitations. A better understanding and future application of these analytical strategies could facilitate the development of precision medicine for rheumatic patients.

Seasonal variation and disease distribution of cytophagocytic mononuclear cells in synovial fluid: A medical record study.

Cytophagocytic mononuclear (CPM) cells, previously known as Reiter's cells, are macrophages containing apoptotic polymorphonuclear leucocytes. Although they can be found in synovial fluid (SF) from different arthropathies, their role remains unclear. This study was performed to determine the frequency and disease distribution of CPM cells in SF in a large cohort of patients with rheumatic diseases over a 12-year period. We also investigated the seasonal variation in their incidence. This record review study included the reports pertaining to SF analyses performed between January 2010 and December 2021. Data were retrieved from the charts of inpatients and outpatients at Rheumatology and Emergency Departments of Padova. The total number of SF samples containing CPM cells was 189: 69% was from patients with seronegative spondyloarthritis (SpA), thus indicating a strong association between CPM cells and SpA. SF samples containing CPM cells were predominantly inflammatory. Our analyses demonstrated a 6-month cyclical fluctuation in concentrations of CPM cells, with an increase in spring and autumn. The presence of CPM cells in SF might offer diagnostic insight into the definition of SpA. Further studies are warranted to ascertain the link between CPM cells and the apoptotic process, shedding light on the mechanisms leading to their formation.