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Article ; Online: Implications of Possible HBV-Driven Regulation of Gene Expression in Stem Cell-like Subpopulation of Huh-7 Hepatocellular Carcinoma Cell Line

Ayse Banu Demir / Domenico Benvenuto / Bilge Karacicek / Yasemin Erac / Silvia Spoto / Silvia Angeletti / Massimo Ciccozzi / Metiner Tosun

Journal of Personalized Medicine, Vol 12, Iss 2065, p

2022 Volume 2065

Abstract: Elevated levels of STIM1, an endoplasmic reticulum Ca 2+ sensor/buffering protein, appear to be correlated with poor cancer prognosis in which microRNAs are also known to play critical roles. The purpose of this study is to investigate possible HBV ... ...

Abstract	Elevated levels of STIM1, an endoplasmic reticulum Ca 2+ sensor/buffering protein, appear to be correlated with poor cancer prognosis in which microRNAs are also known to play critical roles. The purpose of this study is to investigate possible HBV origins of specific microRNAs we identified in a stem cell-like subpopulation of Huh-7 hepatocellular carcinoma (HCC) cell lines with enhanced STIM1 and/or Orai1 expression that mimicked poor cancer prognosis. Computational strategies including phylogenetic analyses were performed on miRNome data we obtained from an EpCAM- and CD133-expressing Huh-7 HCC stem cell-like subpopulation with enhanced STIM1 and/or Orai1 expression originally cultured in the present work. Results revealed two putative regions in the HBV genome based on the apparent clustering pattern of stem loop sequences of microRNAs, including miR3653. Reciprocal analysis of these regions identified critical human genes, of which their transcripts are among the predicted targets of miR3653, which was increased significantly by STIM1 or Orai1 enhancement. Briefly, this study provides phylogenetic evidence for a possible HBV-driven epigenetic remodeling that alters the expression pattern of Ca 2+ homeostasis-associated genes in STIM1 - or Orai1 overexpressing liver cancer stem-like cells for a possible mutual survival outcome. A novel region on HBV-X protein may affect liver carcinogenesis in a genotype-dependent manner. Therefore, detection of the viral genotype would have a clinical impact on prognosis of HBV-induced liver cancers.
Keywords	hepatocellular carcinoma ; HBx ; miR3653 ; epithelial–mesenchymal transition (EMT) ; molecular evolution ; Medicine ; R
Subject code	570
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: An algorithm of good clinical practice to reduce intra-hospital 90-day mortality and need for Intensive Care Unit transfer

Silvia Spoto / Sebastiano Costantino / Marta Fogolari / Emanuele Valeriani / Massimo Ciccozzi / Silvia Angeletti

Italian Journal of Medicine, Vol 14, Iss

a new approach for septic patient management

2020 Volume 1

Abstract: Sepsis accounts for 50% of intra-hospital mortality. Septic shock is diagnosed in 2% of patients with half of these needing for Intensive Care Unit (ICU) transfer. An algorithm was applied for mortality, need for intensive care transfer and length of ... ...

Abstract	Sepsis accounts for 50% of intra-hospital mortality. Septic shock is diagnosed in 2% of patients with half of these needing for Intensive Care Unit (ICU) transfer. An algorithm was applied for mortality, need for intensive care transfer and length of stay decrease. The observational study was performed on 231 consecutive enrolled patients with sepsis or septic shock admitted to the University Campus Bio-Medico of Rome. The algorithm was based on good clinical practice application of antimicrobial stewardship. Data were compared with data from comparable population of National and European surveys. In the study group, the global mortality rate was 26.8% (3.9% was intra-hospital and 23% 90-d mortality), need of ICU transfer was registered in 21.6%, and the median length of stay was 15 days. Globally, intra-hospital and 90-day mortality, were significantly lower than at national level (26.8% vs 63.6%, P<0.0001; 3.9% vs 25%, P<0.0001 and 23% vs 37.5%, P=0.0092). Need for ICU transfer in patients with septic shock was significantly lower than in the English survey (31.9% by vs 80.8% P<0.0001). A significant decrease of intra-hospital, 90-d mortality and need of ICU transfer was achieved.
Keywords	Sepsis ; mortality ; Intensive Care Unit transfer ; algorithm ; antimicrobial stewardship ; Medicine ; R
Subject code	310
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	PAGEPress Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mid-Regional Pro-Adrenomedullin Can Predict Organ Failure and Prognosis in Sepsis?

Silvia Spoto / Stefania Basili / Roberto Cangemi / Giorgio D’Avanzo / Domenica Marika Lupoi / Giulio Francesco Romiti / Josepmaria Argemi / José Ramón Yuste / Felipe Lucena / Luciana Locorriere / Francesco Masini / Giulia Testorio / Rodolfo Calarco / Marta Fogolari / Maria Francesconi / Giulia Battifoglia / Sebastiano Costantino / Silvia Angeletti

International Journal of Molecular Sciences, Vol 24, Iss 24, p

2023 Volume 17429

Abstract: Sepsis causes immune dysregulation and endotheliitis, with an increase in mid-regional pro-adrenomedullin (MR-proADM). The aim of the study is to determine an MR-proADM value that, in addition to clinical diagnosis, can identify patients with localized ... ...

Abstract	Sepsis causes immune dysregulation and endotheliitis, with an increase in mid-regional pro-adrenomedullin (MR-proADM). The aim of the study is to determine an MR-proADM value that, in addition to clinical diagnosis, can identify patients with localized infection or those with sepsis/septic shock, with specific organ damage or with the need for intensive care unit (ICU) transfer and prognosis. The secondary aim is to correlate the MR-proADM value with the length of stay (LOS). In total, 301 subjects with sepsis (124/301 with septic shock) and 126 with localized infection were retrospectively included. In sepsis, MR-proADM ≥ 3.39 ng/mL identified acute kidney injury (AKI); ≥2.99 ng/mL acute respiratory distress syndrome (ARDS); ≥2.28 ng/mL acute heart failure (AHF); ≥2.55 ng/mL Glascow Coma Scale (GCS) < 15; ≥3.38 multi-organ involvement; ≥3.33 need for ICU transfer; ≥2.0 Sequential Organ Failure Assessment (SOFA) score ≥ 2; and ≥3.15 ng/mL non-survivors. The multivariate analysis showed that MR-proADM ≥ 2 ng/mL correlates with AKI, anemia and SOFA score ≥ 2, and MR-proADM ≥ 3 ng/mL correlates with AKI, GCS < 15 and SOFA score ≥ 2. A correlation between mortality and AKI, GCS < 15, ICU transfer and cathecolamine administration was found. In localized infection, MR-proADM at admission ≥ 1.44 ng/mL identified patients with AKI; ≥1.0 ng/mL with AHF; and ≥1.44 ng/mL with anemia and SOFA score ≥ 2. In the multivariate analysis, MR-proADM ≥ 1.44 ng/mL correlated with AKI, anemia, SOFA score ≥ 2 and AHF. MR-proADM is a marker of oxidative stress due to an infection, reflecting severity proportionally to organ damage.
Keywords	sepsis ; septic shock ; organ failure ; mid-regional pro-adrenomedullin (MR-proADM) ; acute kidney injury (AKI) ; acute respiratory distress syndrome (ARDS) ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nosography of systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome in internal medicine patients

Silvia Spoto / Emanuele Valeriani / Sebastiano Costantino

Italian Journal of Medicine, Vol 9, Iss 3, Pp 243-

2015 Volume 251

Abstract: Sepsis is defined by the presence of at least two systemic inflammatory response syndrome criteria associated with an infection microbiologically or clinically evidenced. In Italy sepsis is responsible for 80,000 hospital admissions per year and, in the ... ...

Abstract	Sepsis is defined by the presence of at least two systemic inflammatory response syndrome criteria associated with an infection microbiologically or clinically evidenced. In Italy sepsis is responsible for 80,000 hospital admissions per year and, in the last decades, severe sepsis and septic shock cases are increasing, in correlation with the increased prevalence of multi-drugresistant microbial strains. The predominant etiologic agents are Gram-positive and Gram-negative bacteria, but sepsis caused by fungi is increasing. The host response with both inflammatory and anti-inflammatory processes is responsible for organic failures, which complicate the syndrome, and for the susceptibility to secondary infections. The impairment of one or more organs or systems may be the onset clinical presentation. The organ dysfunctions complicating sepsis involve mainly cardiorespiratory system, kidneys, hemostatis and central nervous system. Fever or hypothermia, tachycardia, tachypnea, leukocytosis or leukopenia, elevated blood levels of lactate and procalcitonin, hypotension are diagnostically sensitive findings for sepsis. Definitive diagnosis requires isolation of the pathogen from blood sample or from the focus of infection. Therapeutic success against sepsis depends on the appropriate use of antibiotics, on the treatment of hemodynamic and respiratory disorder and on general supportive care. In some cases the use of activated protein C is to take in consideration.
Keywords	Sepsis ; severe sepsis ; septic shock ; systemic inflammatory response syndrome ; multiple organ dysfunction syndrome ; Medicine ; R
Subject code	610
Language	English
Publishing date	2015-09-01T00:00:00Z
Publisher	PAGEPress Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Different Biliary Microbial Flora Influence Type of Complications after Pancreaticoduodenectomy

Alessandro Coppola / Vincenzo La Vaccara / Tommaso Farolfi / Michele Fiore / Chiara Cascone / Sara Ramella / Silvia Spoto / Massimo Ciccozzi / Silvia Angeletti / Roberto Coppola / Damiano Caputo

Journal of Clinical Medicine, Vol 10, Iss 2180, p

A Single Center Retrospective Analysis

2021 Volume 2180

Abstract: Background: Bacterobilia is associated with postoperative morbidity after pancreaticoduodenectomy (PD), mostly due to infectious complications. The aim of this study was to investigate the prevalence of bacteria species isolated from intraoperative ... ...

Abstract	Background: Bacterobilia is associated with postoperative morbidity after pancreaticoduodenectomy (PD), mostly due to infectious complications. The aim of this study was to investigate the prevalence of bacteria species isolated from intraoperative biliary cultures, and related complications after PD. Methods: An ANOVA test was used to assess the prevalence of isolated bacterial species and postoperative complications. The odds ratio was computed to evaluate the association between biliary cultures and each complication, Endoscopic Retrograde CholangioPancreatography (ERCP) and each complication, ERCP and biliary cultures, Delayed Gastric Emptying (DGE) and Postoperative Pancreatic Fistula (POPF). Results: Positive biliary cultures were found in 162/244 (66%) PDs. Different prevalences of polymicrobial biliary culture were detected in patients with postoperative complications. In SSIs, a significant prevalence of biliary culture positive for E. coli , Klebsiella pneumoniæ and Enterococcus fæcalis ( p < 0.001) was detected. Prevalences of polymicrobial biliary cultures with Escherichia coli , Klebsiella pneumoniæ , Enterococcus fæcalis and Enterococcus fæcium were significantly associated with POPF ( p < 0.001). Biliary culture positive for Escherichia coli , Enterococcus fæcalis and Enterococcus fæcium showed a higher prevalence of intra-abdominal collection and DGE ( p < 0.001). Notably, Escherichia coli was significantly associated with DGE as a unique complication (OR = 2.94 (1.30–6.70); p < 0.01). Conclusions: Specific prevalences of polymicrobial bacterobilia are associated with major complications, while monomicrobial Escherichia coli bacterobilia is associated with DGE as a unique complication after PD.
Keywords	bacterobilia ; pancreaticoduodenectomy ; E. coli ; pancreatic fistula ; DGE ; ERCP ; Medicine ; R
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Diagnostic Accuracy and Prognostic Value of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Septic Patients outside the Intensive Care Unit

Silvia Spoto / Domenica Marika Lupoi / Emanuele Valeriani / Marta Fogolari / Luciana Locorriere / Giuseppina Beretta Anguissola / Giulia Battifoglia / Damiano Caputo / Alessandro Coppola / Sebastiano Costantino / Massimo Ciccozzi / Silvia Angeletti

Medicina, Vol 57, Iss 811, p

2021 Volume 811

Abstract: Background and Objectives : The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of ... ...

Abstract	Background and Objectives : The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of sepsis outside the intensive care unit. Materials and methods : In this retrospective study, 251 patients with sepsis and 126 patients with infection other than sepsis were enrolled. NLR and PLR were calculated as the ratio between absolute values of neutrophils, lymphocytes, and platelets by complete blood counts performed on whole blood by Sysmex XE-9000 (Dasit, Italy) following the manufacturer’s instruction. Results : The best NLR value in diagnosis of sepsis was 7.97 with sensibility, specificity, AUC, PPV, and NPV of 64.26%, 80.16%, 0.74 ( p < 0.001), 86.49%, and 53.18%, respectively. The diagnostic role of NLR significantly increases when PLR, C-reactive protein (PCR), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) values, as well as systemic inflammatory re-sponse syndrome (SIRS), sequential organ failure assessment (SOFA), and quick-sequential organ failure assessment (qSOFA) scores, were added to the model. The best value of NLR in predicting 90-day mortality was 9.05 with sensibility, specificity, AUC, PPV, and NPV of 69.57%, 61.44%, 0.66 ( p < 0.0001), 28.9%, and 89.9%, respectively. Sensibility, specificity, AUC, PPV, and NPV of NLR increase if PLR, PCR, PCT, MR-proADM, SIRS, qSOFA, and SOFA scores are added to NLR. Conclusions : NLR and PLR represent a widely useful and cheap tool in diagnosis and in predict-ing 90-day mortality in patients with sepsis.
Keywords	neutrophil-to-lymphocyte ; platelet-to-lymphocyte ; C-reactive protein ; procalcitonin ; MRproAdrenomedullin ; systemic inflammatory response syndrome ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Management and recommendations for the prevention of contrast-induced acute kidney injury

Emanuele Valeriani / Luciana Locorriere / Giuseppina Beretta Anguissola / Angelo Lauria Pantano / Massimo Ciccozzi / Sebastiano Costantino / Silvia Angeletti / Silvia Spoto

Italian Journal of Medicine, Vol 12, Iss

state of the art in clinical practice

2018 Volume 4

Abstract: Contrast-induced acute kidney injury (CI-AKI) is defined as an acute kidney failure following iodine-based contrast medium administration determining relevant health and socio-sanitary implications. Knowledge of pathophysiology, early diagnosis, and ... ...

Abstract	Contrast-induced acute kidney injury (CI-AKI) is defined as an acute kidney failure following iodine-based contrast medium administration determining relevant health and socio-sanitary implications. Knowledge of pathophysiology, early diagnosis, and prevention in patients at risk are critical points in CI-AKI management. Determination of risk and functional kidney evaluation must precede every iodine-based contrast medium (CM) administration in order to eventually introduce medical prophylaxis. Furthermore, early laboratoristic evaluation after iodine-based CM exposure should be performed for a prompt identification of acute kidney injury. Therefore, clinicians must know and strictly follow valid recommendations to minimize the development of complications.
Keywords	Acute kidney injury ; renal insufficiency ; contrast media ; risk factors ; prevention ; Medicine ; R
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	PAGEPress Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Best diagnostic accuracy of sepsis combining SIRS criteria or qSOFA score with Procalcitonin and Mid-Regional pro-Adrenomedullin outside ICU

Silvia Spoto / Edoardo Nobile / Emanuele Paolo Rafano Carnà / Marta Fogolari / Damiano Caputo / Lucia De Florio / Emanuele Valeriani / Domenico Benvenuto / Sebastiano Costantino / Massimo Ciccozzi / Silvia Angeletti

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 11

Abstract: Abstract Early diagnosis and treatment significantly reduce sepsis mortality. Currently, no gold standard has been yet established to diagnose sepsis outside the ICU. The aim of the study was to evaluate the diagnostic accuracy of sepsis defined by SIRS ... ...

Abstract	Abstract Early diagnosis and treatment significantly reduce sepsis mortality. Currently, no gold standard has been yet established to diagnose sepsis outside the ICU. The aim of the study was to evaluate the diagnostic accuracy of sepsis defined by SIRS Criteria of 1991, Second Consensus Conference Criteria of 2001, modified Second Consensus Conference Criteria of 2001 (obtaining SIRS Criteria and SOFA score), Third Consensus Conference of 2016, in addition to the dosage of Procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM). In this prospective study, 209 consecutive patients with clinical diagnosis of sepsis were enrolled (May 2014–June 2018) outside intensive care unit (ICU) setting. A diagnostic protocol could include SIRS criteria or qSOFA score evaluation, rapid testing of PCT and MR-proADM, and SOFA score calculation for organ failure definition. Using this approach outside the ICU, a rapid diagnostic and prognostic evaluation could be achieved, also in the case of negative SIRS, qSOFA or SOFA scores with high post-test probability to reduce mortality and improve outcomes.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Acute complications and mortality in hospitalized patients with coronavirus disease 2019

Nicola Potere / Emanuele Valeriani / Matteo Candeloro / Marco Tana / Ettore Porreca / Antonio Abbate / Silvia Spoto / Anne W. S. Rutjes / Marcello Di Nisio

Critical Care, Vol 24, Iss 1, Pp 1-

a systematic review and meta-analysis

2020 Volume 12

Abstract: Abstract Background The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in ... ...

Abstract	Abstract Background The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19. Methods MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses. Results A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies). Conclusions Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting. Trial registration PROSPERO registration ID for this study is CRD42020177243 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=177243 ).
Keywords	Adult respiratory distress syndrome ; Coronavirus ; COVID-19 ; Oxygen inhalation therapy ; SARS virus ; Medical emergencies. Critical care. Intensive care. First aid ; RC86-88.9 ; covid19
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 18

Abstract: The mechanisms that restore endothelial barrier integrity following inflammation-induced breaching are incompletely understood. Here the authors show that the CD31 immune receptor contributes to reestablishing vascular integrity via its effects on ... ...

Abstract	The mechanisms that restore endothelial barrier integrity following inflammation-induced breaching are incompletely understood. Here the authors show that the CD31 immune receptor contributes to reestablishing vascular integrity via its effects on endothelial cell metabolism.
Keywords	Science ; Q
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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