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Article: A machine learning strategy to mitigate the inappropriateness of procalcitonin request in clinical practice.

Agnello, Luisa / Vidali, Matteo / Ciaccio, Anna Maria / Lo Sasso, Bruna / Iacona, Alessandro / Biundo, Giuseppe / Scazzone, Concetta / Gambino, Caterina Maria / Ciaccio, Marcello

Heliyon

2024 Volume 10, Issue 5, Page(s) e26556

Abstract: Aim: The aim of this study was to develop machine learning (ML) models to mitigate the inappropriate request of Procalcitonin (PCT) in clinical wards.: Material and methods: We built six different ML models based on both demographical data, i.e., sex ...

Abstract	Aim: The aim of this study was to develop machine learning (ML) models to mitigate the inappropriate request of Procalcitonin (PCT) in clinical wards. Material and methods: We built six different ML models based on both demographical data, i.e., sex and age, and laboratory parameters, i.e., cell blood count (CBC) parameters, inclusive of monocyte distribution width (MDW), and C-reactive protein (CRP). The dataset included 1667 PCT measurements of different patients. Based on a PCT cut-off of 0.50 ng/mL, we found 1090 negative (65.4%) and 577 positive (34.6%) results. We performed a 70:15:15 train:validation:test splitting based on the outcome. Results: Random Forest, Support Vector Machine and eXtreme Gradient Boosting showed optimal performances for predicting PCT positivity, with an area under the curve ranging from 0.88 to 0.89. Conclusions: The ML models developed could represent a useful tool to predict PCT positivity, avoiding unusefulness PCT requests. ML models are based on laboratory tests commonly ordered together with PCT but have the great advantage to be easy to measure and low-cost.
Language	English
Publishing date	2024-02-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e26556
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Molecular Biomarkers of Neurodegenerative Disorders: A Practical Guide to Their Appropriate Use and Interpretation in Clinical Practice.

Agnello, Luisa / Gambino, Caterina Maria / Ciaccio, Anna Maria / Masucci, Anna / Vassallo, Roberta / Tamburello, Martina / Scazzone, Concetta / Lo Sasso, Bruna / Ciaccio, Marcello

International journal of molecular sciences

2024 Volume 25, Issue 8

Abstract: Neurodegenerative disorders (NDs) represent a group of different diseases characterized by the progressive degeneration and death of the nervous system's cells. The diagnosis is challenging, especially in the early stages, due to no specific clinical ... ...

Abstract	Neurodegenerative disorders (NDs) represent a group of different diseases characterized by the progressive degeneration and death of the nervous system's cells. The diagnosis is challenging, especially in the early stages, due to no specific clinical signs and symptoms. In this context, laboratory medicine could support clinicians in detecting and differentiating NDs. Indeed, biomarkers could indicate the pathological mechanisms underpinning NDs. The ideal biofluid for detecting the biomarkers of NDs is cerebrospinal fluid (CSF), which has limitations, hampering its widespread use in clinical practice. However, intensive efforts are underway to introduce high-sensitivity analytical methods to detect ND biomarkers in alternative nonivasive biofluid, such as blood or saliva. This study presents an overview of the ND molecular biomarkers currently used in clinical practice. For some diseases, such as Alzheimer's disease or multiple sclerosis, biomarkers are well established and recommended by guidelines. However, for most NDs, intensive research is ongoing to identify reliable and specific biomarkers, and no consensus has yet been achieved.
MeSH term(s)	Humans ; Biomarkers/cerebrospinal fluid ; Neurodegenerative Diseases/diagnosis ; Neurodegenerative Diseases/cerebrospinal fluid ; Neurodegenerative Diseases/metabolism ; Alzheimer Disease/diagnosis ; Alzheimer Disease/cerebrospinal fluid ; Alzheimer Disease/metabolism ; Alzheimer Disease/genetics
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-04-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25084323
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Article ; Online: Prostate Health Index (PHI) as a triage tool for reducing unnecessary magnetic resonance imaging (MRI) in patients at risk of prostate cancer.

Agnello, Luisa / Vidali, Matteo / Salvaggio, Giuseppe / Agnello, Francesco / Lo Sasso, Bruna / Gambino, Caterina Maria / Ciaccio, Marcello

Clinical biochemistry

2024 Volume 127-128, Page(s) 110759

Abstract: Introduction: The aim of this study is to assess the usefulness of the Prostate Health Index (PHI) as a triage tool for selecting patients at risk of prostate cancer (PCa) who should undergo multiparametric Magnetic Resonance Imaging (mpMRI).: ... ...

Abstract	Introduction: The aim of this study is to assess the usefulness of the Prostate Health Index (PHI) as a triage tool for selecting patients at risk of prostate cancer (PCa) who should undergo multiparametric Magnetic Resonance Imaging (mpMRI). Material and methods: We enrolled 204 patients with suspected PCa. For each patient, a blood sample was collected before mpMRI to measure PHI. Findings on mpMRI were assessed according to the Prostate Imaging Reporting & Data System version 2.0 (PI-RADSv2) category scale. Results: According to PI-RADSv2, patients were classified into two groups: PI-RADS < 3 (48 %) and ≥ 3 (52 %). PHI showed the best performance for predicting PI-RADS ≥ 3 [AUC: 0,747 (0,679-0,815), 0,680(0,607-0,754), and 0,613 (0,535-0,690) for PHI, PSA ratio, and total PSA, respectively]. The best PHI cut-off was 30, with a sensitivity of 90%. At the univariate logistic regression, total PSA (p = 0.007), PSA ratio (p = 0.001), [-2]proPSA (p = 0.019) and PHI (p < 0.001) were associated with PI-RADS ≥ 3; however, at the multivariate analysis, only PHI (p < 0.001) was found to be an independent predictor of PI-RADS ≥ 3. Conclusion: PHI could represent a reliable noninvasive tool for selecting patients to undergo mpMRI.
Language	English
Publishing date	2024-04-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	390372-2
ISSN	1873-2933 ; 0009-9120
ISSN (online)	1873-2933
ISSN	0009-9120
DOI	10.1016/j.clinbiochem.2024.110759
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Article: The Role of TAR DNA Binding Protein 43 (TDP-43) as a CandiDate Biomarker of Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

Gambino, Caterina Maria / Ciaccio, Anna Maria / Lo Sasso, Bruna / Giglio, Rosaria Vincenza / Vidali, Matteo / Agnello, Luisa / Ciaccio, Marcello

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 3

Abstract: Background: TAR DNA-binding protein 43 (TDP-43) aggregation in neuronal cells is recognized as a hallmark of amyotrophic lateral sclerosis (ALS). Although the literature strongly supports the pathogenetic role of TDP-43 in ALS pathogenesis, the role of ... ...

Abstract	Background: TAR DNA-binding protein 43 (TDP-43) aggregation in neuronal cells is recognized as a hallmark of amyotrophic lateral sclerosis (ALS). Although the literature strongly supports the pathogenetic role of TDP-43 in ALS pathogenesis, the role of TDP-43 as a biomarker of ALS is controversial. We performed a systematic review and meta-analysis to assess the diagnostic performance of TDP-43 for ALS. Methods: Relevant publications were identified by a systematic literature search on PubMed and Web of Science from their inception to 8 April 2022. Results: Seven studies, including 472 individuals, of whom 254 had ALS according to the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, met the inclusion criteria for our meta-analysis. According to the random-effects model, CSF TDP-43 levels are higher in ALS patients compared with control groups. Conclusions: CSF TDP-43 could represent a biomarker of ALS, but further studies are mandatory before drawing conclusions.
Language	English
Publishing date	2023-01-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13030416
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Article ; Online: Monocyte distribution width (MDW) in sepsis.

Agnello, Luisa / Ciaccio, Anna Maria / Vidali, Matteo / Cortegiani, Andrea / Biundo, Giuseppe / Gambino, Caterina Maria / Scazzone, Concetta / Lo Sasso, Bruna / Ciaccio, Marcello

Clinica chimica acta; international journal of clinical chemistry

2023 Volume 548, Page(s) 117511

Abstract: Sepsis is a life-threatening syndrome due to a dysregulated host response to infection, which can be caused by bacterial, viral, or fungal infection. Thus, it is crucial to know how the different microorganisms influence the levels of a biomarker. In the ...

Abstract	Sepsis is a life-threatening syndrome due to a dysregulated host response to infection, which can be caused by bacterial, viral, or fungal infection. Thus, it is crucial to know how the different microorganisms influence the levels of a biomarker. In the last decade, monocyte distribution width (MDW) has emerged as a promising sepsis biomarker, especially in acute settings, such as the Emergency Department and Intensive Care Unit. In this article, we explore the relationship between MDW and the different pathogens causing infection. Noteworthy, MDW is not a biological molecule, but it is calculated by a mathematical formula based on monocyte characteristics. Monocytes represent the first line defence against microorganisms and undergo activation upon infection, independently from the invading pathogen. According to the knowledge on the biomarker biology and the few literatures evidence, MDW may be considered a biomarker of sepsis, independent of the causative pathogen. However, further investigations are warranted before drawing definite conclusion.
MeSH term(s)	Humans ; Monocytes ; Sepsis ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-08-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	80228-1
ISSN	1873-3492 ; 0009-8981
ISSN (online)	1873-3492
ISSN	0009-8981
DOI	10.1016/j.cca.2023.117511
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Article ; Online: Monocyte distribution width (MDW) kinetic for monitoring sepsis in intensive care unit.

Agnello, Luisa / Ciaccio, Anna Maria / Del Ben, Fabio / Lo Sasso, Bruna / Biundo, Giuseppe / Giglia, Aurora / Giglio, Rosaria Vincenza / Cortegiani, Andrea / Gambino, Caterina Maria / Ciaccio, Marcello

Diagnosis (Berlin, Germany)

2024

Abstract: Objectives: Monocyte distribution width (MDW) is a measure of monocyte anisocytosis. In this study, we assessed the role of MDW, in comparison to C-reactive protein (CRP), procalcitonin (PCT), and lactate, as a screening and prognostic biomarker of ... ...

Abstract	Objectives: Monocyte distribution width (MDW) is a measure of monocyte anisocytosis. In this study, we assessed the role of MDW, in comparison to C-reactive protein (CRP), procalcitonin (PCT), and lactate, as a screening and prognostic biomarker of sepsis in intensive care unit (ICU) by longitudinally measuring it in the first 5 days of hospital stay. Methods: We considered all consecutive patients admitted to the ICU. At admission, patients were classified as septic or not according to Sepsis-3 criteria. MDW, CRP, PCT, and lactate were measured daily in the first 5 days of hospitalization. ICU mortality was also recorded. Results: We included 193 patients, 62 with sepsis and 131 without sepsis (controls). 58% and 26 % of the patients, with and without sepsis respectively, died during ICU stay. MDW showed the highest accuracy for sepsis detection, superior to CRP, PCT, and lactate (AUC of 0.840, 0.755, 0.708, 0.622, respectively). At admission, no biomarker predicts ICU mortality in patients with sepsis. The kinetic of all biomarkers during the first 5 days of hospitalization was associated with ICU mortality. Noteworthy, above all, the kinetic of MDW showed the best accuracy. Specifically, an increase or decrease in MDW from day 1-4 and 5 was significantly associated with mortality or survival, respectively. Conclusions: MDW is a reliable diagnostic and prognostic sepsis biomarker, better than traditional biomarkers.
Language	English
Publishing date	2024-04-22
Publishing country	Germany
Document type	Journal Article
ISSN	2194-802X
ISSN (online)	2194-802X
DOI	10.1515/dx-2024-0019
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Article ; Online: The Role of TAR DNA Binding Protein 43 (TDP-43) as a CandiDate Biomarker of Amyotrophic Lateral Sclerosis

Caterina Maria Gambino / Anna Maria Ciaccio / Bruna Lo Sasso / Rosaria Vincenza Giglio / Matteo Vidali / Luisa Agnello / Marcello Ciaccio

Diagnostics, Vol 13, Iss 416, p

A Systematic Review and Meta-Analysis

2023 Volume 416

Abstract	Background: TAR DNA-binding protein 43 (TDP-43) aggregation in neuronal cells is recognized as a hallmark of amyotrophic lateral sclerosis (ALS). Although the literature strongly supports the pathogenetic role of TDP-43 in ALS pathogenesis, the role of TDP-43 as a biomarker of ALS is controversial. We performed a systematic review and meta-analysis to assess the diagnostic performance of TDP-43 for ALS. Methods: Relevant publications were identified by a systematic literature search on PubMed and Web of Science from their inception to 8 April 2022. Results: Seven studies, including 472 individuals, of whom 254 had ALS according to the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, met the inclusion criteria for our meta-analysis. According to the random-effects model, CSF TDP-43 levels are higher in ALS patients compared with control groups. Conclusions: CSF TDP-43 could represent a biomarker of ALS, but further studies are mandatory before drawing conclusions.
Keywords	TDP-43 ; biomarker ; ALS ; diagnosis ; Medicine (General) ; R5-920
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Monocyte distribution width (MDW) as a reliable biomarker for urosepsis.

Agnello, Luisa / Ciaccio, Anna Maria / Lo Sasso, Bruna / Vidali, Matteo / Giglio, Rosaria Vincenza / Gambino, Caterina Maria / Bivona, Giulia / Baiamonte, Davide / Pavan, Nicola / Simonato, Alchiede / Ciaccio, Marcello

Clinical chemistry and laboratory medicine

2023 Volume 61, Issue 8, Page(s) e140–e142

MeSH term(s)	Humans ; Monocytes ; Sepsis/diagnosis ; Biomarkers ; Urinary Tract Infections/diagnosis
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-02-03
Publishing country	Germany
Document type	Letter
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2023-0038
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Article ; Online: The role of Killer immunoglobulin-like receptors (KIRs) in the genetic susceptibility to non-celiac wheat sensitivity (NCWS).

Gambino, Caterina Maria / Agnello, Luisa / Vidali, Matteo / Lo Sasso, Bruna / Mansueto, Pasquale / Seidita, Aurelio / Giuliano, Alessandra / Scazzone, Concetta / Massa, Davide / Masucci, Anna / Tamburello, Martina / Vassallo, Roberta / Ciaccio, Anna Maria / Candore, Giuseppina / Carroccio, Antonio / Ciaccio, Marcello

Clinical chemistry and laboratory medicine

2024

Abstract: Objectives: Non-celiac wheat sensitivity (NCWS) is an emerging clinical condition characterized by gastrointestinal and extraintestinal symptoms following the ingestion of gluten-containing foods in patients without celiac disease (CD) or wheat allergy. ...

Abstract	Objectives: Non-celiac wheat sensitivity (NCWS) is an emerging clinical condition characterized by gastrointestinal and extraintestinal symptoms following the ingestion of gluten-containing foods in patients without celiac disease (CD) or wheat allergy. Despite the great interest for NCWS, the genetic risk factors still need to be fully clarified. In this study, we first assessed the possible contribution of KIR genes and KIR haplotypes on the genetic predisposition to NCWS. Methods: Fifty patients with NCWS, 50 patients with CD, and 50 healthy controls (HC) were included in this study. Results: We found a statistically different distribution of some Conclusions: Our findings suggest a role of KIR genes in NCWS susceptibility, with
Language	English
Publishing date	2024-04-22
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2024-0034
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Article ; Online: Microglial Activation and Priming in Alzheimer's Disease: State of the Art and Future Perspectives.

Bivona, Giulia / Iemmolo, Matilda / Agnello, Luisa / Lo Sasso, Bruna / Gambino, Caterina Maria / Giglio, Rosaria Vincenza / Scazzone, Concetta / Ghersi, Giulio / Ciaccio, Marcello

International journal of molecular sciences

2023 Volume 24, Issue 1

Abstract: Alzheimer's Disease (AD) is the most common cause of dementia, having a remarkable social and healthcare burden worldwide. Amyloid β (Aβ) and protein Tau aggregates are disease hallmarks and key players in AD pathogenesis. However, it has been ... ...

Abstract	Alzheimer's Disease (AD) is the most common cause of dementia, having a remarkable social and healthcare burden worldwide. Amyloid β (Aβ) and protein Tau aggregates are disease hallmarks and key players in AD pathogenesis. However, it has been hypothesized that microglia can contribute to AD pathophysiology, as well. Microglia are CNS-resident immune cells belonging to the myeloid lineage of the innate arm of immunity. Under physiological conditions, microglia are in constant motion in order to carry on their housekeeping function, and they maintain an anti-inflammatory, quiescent state, with low expression of cytokines and no phagocytic activity. Upon various stimuli (debris, ATP, misfolded proteins, aggregates and pathogens), microglia acquire a phagocytic function and overexpress cytokine gene modules. This process is generally regarded as microglia activation and implies that the production of pro-inflammatory cytokines is counterbalanced by the synthesis and the release of anti-inflammatory molecules. This mechanism avoids excessive inflammatory response and inappropriate microglial activation, which causes tissue damage and brain homeostasis impairment. Once the pathogenic stimulus has been cleared, activated microglia return to the naïve, anti-inflammatory state. Upon repeated stimuli (as in the case of Aβ deposition in the early stage of AD), activated microglia shift toward a less protective, neurotoxic phenotype, known as "primed" microglia. The main characteristic of primed microglia is their lower capability to turn back toward the naïve, anti-inflammatory state, which makes these cells prone to chronic activation and favours chronic inflammation in the brain. Primed microglia have impaired defence capacity against injury and detrimental effects on the brain microenvironment. Additionally, priming has been associated with AD onset and progression and can represent a promising target for AD treatment strategies. Many factors (genetics, environmental factors, baseline inflammatory status of microglia, ageing) generate an aberrantly activated phenotype that undergoes priming easier and earlier than normally activated microglia do. Novel, promising targets for therapeutic strategies for AD have been sought in the field of microglia activation and, importantly, among those factors influencing the baseline status of these cells. The CX3CL1 pathway could be a valuable target treatment approach in AD, although preliminary findings from the studies in this field are controversial. The current review aims to summarize state of the art on the role of microglia dysfunction in AD pathogenesis and proposes biochemical pathways with possible targets for AD treatment.
MeSH term(s)	Humans ; Alzheimer Disease/immunology ; Amyloid beta-Peptides/metabolism ; Anti-Inflammatory Agents/pharmacology ; Cytokines/metabolism ; Microglia/immunology
Chemical Substances	Amyloid beta-Peptides ; Anti-Inflammatory Agents ; Cytokines
Language	English
Publishing date	2023-01-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24010884
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