Publications by authors named "Francesco Bartoli"

104 Publications

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study.

Front Psychiatry 2021 16;12:784366. Epub 2021 Dec 16.

World Health Organization (WHO) Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy.

Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. The STAR Network "Depot Study" was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS ≥ 41). We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions-conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently-showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders.
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http://dx.doi.org/10.3389/fpsyt.2021.784366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716539PMC
December 2021

Assessing vulnerability to psychological distress during the COVID-19 pandemic through the analysis of microblogging content.

Future Gener Comput Syst 2021 Dec 25;125:446-459. Epub 2021 Jun 25.

Department of Informatics, Systems, and Communication (DISCo), University of Milano-Bicocca, Milan, Italy.

In recent years we have witnessed a growing interest in the analysis of social media data under different perspectives, since these online platforms have become the preferred tool for generating and sharing content across different users organized into virtual communities, based on their common interests, needs, and perceptions. In the current study, by considering a collection of social textual contents related to COVID-19 gathered on the Twitter microblogging platform in the period between August and December 2020, we aimed at evaluating the possible effects of some critical factors related to the pandemic on the mental well-being of the population. In particular, we aimed at investigating potential lexicon identifiers of vulnerability to psychological distress in digital social interactions with respect to distinct COVID-related scenarios, which could be "at risk" from a psychological discomfort point of view. Such scenarios have been associated with peculiar topics discussed on Twitter. For this purpose, two approaches based on a "top-down" and a "bottom-up" strategy were adopted. In the top-down approach, three potential scenarios were initially selected by medical experts, and associated with topics extracted from the Twitter dataset in a hybrid unsupervised-supervised way. On the other hand, in the bottom-up approach, three topics were extracted in a totally unsupervised way capitalizing on a Twitter dataset filtered according to the presence of keywords related to vulnerability to psychological distress, and associated with at-risk scenarios. The identification of such scenarios with both approaches made it possible to capture and analyze the potential psychological vulnerability in critical situations.
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http://dx.doi.org/10.1016/j.future.2021.06.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678930PMC
December 2021

Role of Multimodal Imaging in Patients With Suspected Infections After the Bentall Procedure.

Front Cardiovasc Med 2021 1;8:745556. Epub 2021 Dec 1.

Department of Translational Research and New Technology in Medicine and Surgery, Regional Center of Nuclear Medicine, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.

This study aimed to assess the diagnostic performances of multimodal imaging [i.e., white blood cell single-photon emission computed tomography/CT (Tc-HMPAO-WBC SPECT/CT) and 18-fluoride-fluorodeoxyglucose positron emission tomography/CT ([F]FDG PET/CT)] in patients with suspected infection after the Bentall procedure, proposing new specific diagnostic criteria for the diagnosis. Between January 2009 and December 2019, we selected within a cardiovascular infections registry, 76 surgically treated patients (27 women and 49 men, median 66 years, and range 29-83 years). All the patients underwent molecular imaging for a suspected infection after the replacement of the aortic valve and ascending aorta according to the Bentall procedure. We analyzed 98 scans including 49 Tc-WBC and 49 [F]FDG PET/CT. A total of 22 patients with very early/early suspected infection (<3 months after surgery) were imaged with both the techniques. Positive imaging was classified according to the anatomical site of increased uptake: to the aortic valve (AV), to both the AV and AV tube graft (AVTG) or to the TG, to surrounding tissue, and/or to extracardiac sites (embolic events or other sites of concomitant infection). Standard clinical workup included in all the patients having echocardiography/CT, blood culture, and the Duke criteria. Pretest probability and positive/negative likelihood ratio were calculated. Sensitivity and specificity of Tc labeled hexamethylpropylene amine oxime-WBC SPECT/CT (Tc-HMPAO-WBC SPECT/CT) and [F]FDG PET/CT imaging were calculated by using microbiology ( = 35) or clinical follow-up ( = 41) as final diagnosis. Tc-HMPAO-WBC scintigraphy and [F]FDG PET/CT findings were compared with 95% CIs by using the McNemar test to those of echocardiography/CT, blood culture, and the Duke criteria. Sensitivity, specificity, and accuracy of Tc-HMPAO-WBC were 86, 92, and 88%, respectively, with a slightly higher sensitivity for tube graft infection (TGI) as compared to isolated AV and combined AVTG. Overall, sensitivity, specificity, and accuracy of [F]FDG PET/CT were 97, 73, and 90%, respectively. In 22 patients with suspected very early and early postsurgical infections, the two imaging modalities were concordant in 17 cases [10 true positive (TP) and 7 true negative (TN)]. [F]FDG PET/CT presented a higher sensitivity than Tc-HMPAO-WBC scan. Tc-HMPAO-WBC scan correctly classified as negative three false-positive (FP) PET/CT findings. Our findings supported the use of Tc-HMPAO-WBC SPECT/CT and [F]FDG PET/CT in patients with suspicion infection after the Bentall procedure early in the course of the disease onset to confirm the diagnosis and provide a comprehensive assessment of disease burden through the proposed criteria.
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http://dx.doi.org/10.3389/fcvm.2021.745556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671629PMC
December 2021

[F]FMCH PET/CT biomarkers and similarity analysis to refine the definition of oligometastatic prostate cancer.

EJNMMI Res 2021 Nov 27;11(1):119. Epub 2021 Nov 27.

Nuclear Medicine, Department of Translational Research and Advanced Technology in Medicine and Surgery University of Pisa, Pisa University Hospital, Via Roma 67, 56123, Pisa, Italy.

Background: The role of image-derived biomarkers in recurrent oligometastatic Prostate Cancer (PCa) is unexplored. This paper aimed to evaluate [F]FMCH PET/CT radiomic analysis in patients with recurrent PCa after primary radical therapy. Specifically, we tested intra-patient lesions similarity in oligometastatic and plurimetastatic PCa, comparing the two most used definitions of oligometastatic disease.

Methods: PCa patients eligible for [F]FMCH PET/CT presenting biochemical failure after first-line curative treatments were invited to participate in this prospective observational trial. PET/CT images of 92 patients were visually and quantitatively analyzed. Each patient was classified as oligometastatic or plurimetastatic according to the total number of detected lesions (up to 3 and up to 5 or > 3 and > 5, respectively). Univariate and intra-patient lesions' similarity analysis were performed.

Results: [F]FMCH PET/CT identified 370 lesions, anatomically classified as regional lymph nodes and distant metastases. Thirty-eight and 54 patients were designed oligometastatic and plurimetastatic, respectively, using a 3-lesion threshold. The number of oligometastic scaled up to 60 patients (thus 32 plurimetastatic patients) with a 5-lesion threshold. Similarity analysis showed high lesions' heterogeneity. Grouping patients according to the number of metastases, patients with oligometastatic PCa defined with a 5-lesion threshold presented lesions heterogeneity comparable to plurimetastic patients. Lesions within patients having a limited tumor burden as defined by three lesions were characterized by less heterogeneity.

Conclusions: We found a comparable heterogeneity between patients with up to five lesions and plurimetastic patients, while patients with up to three lesions were less heterogeneous than plurimetastatic patients, featuring different cells phenotypes in the two groups. Our results supported the use of a 3-lesion threshold to define oligometastatic PCa.
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http://dx.doi.org/10.1186/s13550-021-00858-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627538PMC
November 2021

Some of us are most at risk: Systematic review and meta-analysis of correlates of depressive symptoms among healthcare workers during the SARS-CoV-2 outbreak.

Neurosci Biobehav Rev 2021 12 13;131:912-922. Epub 2021 Oct 13.

Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy; Division of Psychiatry, University College London, London, UK.

The COVID-19 pandemic has had a severe psychosocial impact on healthcare workers (HCWs). This systematic review and meta-analysis aimed at evaluating the association between individual features and depressive symptoms reported by HCWs during the pandemic. We searched Medline, Embase, and PsycInfo up to 23 June 2020. We included cross-sectional studies testing the association between individual correlates and depressive symptoms in HCWs during the SARS-CoV-2 outbreak. Fourteen studies met inclusion criteria, involving 14,173 HCWs (3,070 with depressive symptoms). Women (OR = 1.50; 95 %CI: 1.28-1.76; I = 40.0 %), individuals with suspected/confirmed COVID-19 (OR = 2.10; 95 %CI: 1.64-2.69; I = 0 %), and those with an infected family member or friend (OR = 1.67; 95 %CI: 1.37-2.04; I = 0%) were more likely to report depressive features, which, instead, were less frequent among doctors (compared with nurses) (OR = 0.80; 95 %CI: 0.66-0.98; I = 48.2 %) and HCWs who felt adequately protected (OR = 0.48; 95 %CI: 0.32-0.72; I = 36.3 %). Our study provided timely evidence on the correlates of depressive symptoms among HCWs during the pandemic. Early screening is crucial to develop tailored health interventions, redesigning the response to COVID-19.
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http://dx.doi.org/10.1016/j.neubiorev.2021.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513395PMC
December 2021

Repurposed drugs as adjunctive treatments for mania and bipolar depression: A meta-review and critical appraisal of meta-analyses of randomized placebo-controlled trials.

J Psychiatr Res 2021 Nov 3;143:230-238. Epub 2021 Sep 3.

Department of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900, Monza, Italy; Division of Psychiatry, University College London, 149 Tottenham Court Rd, Bloomsbury, London, W1T 7BN, United Kingdom.

Several drugs previously tested in clinical trials and approved for different indications have been repurposed for bipolar disorder. We carried out a systematic meta-review of meta-analyses of randomized placebo-controlled trials investigating repurposed drugs as adjunctive treatments for mania and bipolar depression. We performed a critical appraisal using 'A MeaSurement Tool to Assess systematic Reviews' Version 2 (AMSTAR 2). We synthesized results on efficacy, tolerability, and safety, assessing evidence quality according to the 'Grading of Recommendations, Assessment, Development and Evaluations' (GRADE) approach. Our systematic search identified nine eligible studies investigating 12 drugs, four for mania and eight for bipolar depression. The quality of reporting was heterogeneous according to AMSTAR 2. In mania, allopurinol (for symptoms reduction and remission at 4-8 weeks) and tamoxifen (for response and symptoms reduction at 4-6 weeks) showed higher efficacy than placebo, with low and very low quality of evidence, respectively. Concerning bipolar depression, modafinil/armodafinil (for response, remission, and symptoms reduction at 6-8 weeks) and pramipexole (for response and symptoms reduction at 6 weeks) were superior to placebo, despite the low quality of evidence. Results on the efficacy of celecoxib and N-acetylcysteine were of low quality and limited to certain outcomes. Overall, the lack of evidence of high and moderate quality does not allow us to draw firm conclusions on the clinical utility of repurposed drugs as adjunctive treatments for mania and bipolar depression, highlighting the need for additional research.
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http://dx.doi.org/10.1016/j.jpsychires.2021.09.018DOI Listing
November 2021

What to Trust, PSA or [Ga]Ga-PSMA-11: Learn from Experience.

Res Rep Urol 2021 20;13:597-601. Epub 2021 Aug 20.

Regional Center of Nuclear Medicine, Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy.

Brain metastases from prostate cancer typically occur in the more advanced stages of the disease. Clinically, the early diagnosis of visceral disease is crucial, impacting on patient's management and prognosis. Although magnetic resonance imaging (MRI) is the modality of choice for the detection of brain metastases, it is not routinely performed in the surveillance of prostate cancer patients unless neurological manifestations appear. Prostate-specific membrane antigen (PSMA) is a glycoprotein, a membrane-bound metallopeptidase, overexpressed in more than 90% of prostate cancer cells. This molecular target is a suitable tissue biomarker for prostate cancer functional imaging. We present a case of a 73-year gentleman diagnosed with prostate adenocarcinoma and surgically treated (pT3bN1Mx, Gleason Score of 9) in February 2016. Subsequently, he underwent androgen deprivation therapy because of the occurrence of a bone metastasis. Between 2016 and January 2019 PSA levels were maintained under control. Starting from September 2019, it progressively raised up to 0.85 ng/mL with a doubling time of 3.3 months. Therefore, he performed a [Ga]Ga-PSMA-11 PET/CT which showed a focal radiopharmaceutical uptake in the right temporal lobe corresponding to the presence of a rounded cystic lesion on brain MRI. The subsequent excisional biopsy diagnosed a prostate adenocarcinoma metastasis. PSMA expression has been reported in brain parenchyma after ischemic strokes and in some brain tumors including gliomas, meningiomas, and neurofibromas. In our case, the lack of symptoms and the relatively low PSA level raised questions about the nature of the lesion, posing the differential diagnosis between brain metastases and primary brain tumor. Finally, our case shows the capability of [Ga]Ga-PSMA-11 PET/CT to detect metachronous distant brain metastases in a low biochemical recurrent asymptomatic prostate cancer patient, indicating that proper acquisition - from the vertex to thigh - should be always considered, regardless of the PSA level.
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http://dx.doi.org/10.2147/RRU.S316446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384575PMC
August 2021

What to Trust, PSA or [Ga]Ga-PSMA-11: Learn from Experience.

Res Rep Urol 2021 20;13:597-601. Epub 2021 Aug 20.

Regional Center of Nuclear Medicine, Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy.

Brain metastases from prostate cancer typically occur in the more advanced stages of the disease. Clinically, the early diagnosis of visceral disease is crucial, impacting on patient's management and prognosis. Although magnetic resonance imaging (MRI) is the modality of choice for the detection of brain metastases, it is not routinely performed in the surveillance of prostate cancer patients unless neurological manifestations appear. Prostate-specific membrane antigen (PSMA) is a glycoprotein, a membrane-bound metallopeptidase, overexpressed in more than 90% of prostate cancer cells. This molecular target is a suitable tissue biomarker for prostate cancer functional imaging. We present a case of a 73-year gentleman diagnosed with prostate adenocarcinoma and surgically treated (pT3bN1Mx, Gleason Score of 9) in February 2016. Subsequently, he underwent androgen deprivation therapy because of the occurrence of a bone metastasis. Between 2016 and January 2019 PSA levels were maintained under control. Starting from September 2019, it progressively raised up to 0.85 ng/mL with a doubling time of 3.3 months. Therefore, he performed a [Ga]Ga-PSMA-11 PET/CT which showed a focal radiopharmaceutical uptake in the right temporal lobe corresponding to the presence of a rounded cystic lesion on brain MRI. The subsequent excisional biopsy diagnosed a prostate adenocarcinoma metastasis. PSMA expression has been reported in brain parenchyma after ischemic strokes and in some brain tumors including gliomas, meningiomas, and neurofibromas. In our case, the lack of symptoms and the relatively low PSA level raised questions about the nature of the lesion, posing the differential diagnosis between brain metastases and primary brain tumor. Finally, our case shows the capability of [Ga]Ga-PSMA-11 PET/CT to detect metachronous distant brain metastases in a low biochemical recurrent asymptomatic prostate cancer patient, indicating that proper acquisition - from the vertex to thigh - should be always considered, regardless of the PSA level.
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http://dx.doi.org/10.2147/RRU.S316446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384575PMC
August 2021

State of the art of F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation.

Clin Transl Imaging 2021 Jul 10:1-41. Epub 2021 Jul 10.

Regional Center of Nuclear Medicine, Department of Translational Research and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy.

Aim: The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([F]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections.

Methods: In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [F]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020.

Results: Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication.

Conclusions: Currently, [F]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a "common nuclear physicians' language" throughout all the country.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40336-021-00445-w.
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http://dx.doi.org/10.1007/s40336-021-00445-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271312PMC
July 2021

Thyroid hormones in persons with schizophrenia: A systematic review and meta-analysis.

Prog Neuropsychopharmacol Biol Psychiatry 2021 12 15;111:110402. Epub 2021 Jul 15.

Department of Psychiatry, Wroclaw Medical University, Pasteura 10 Street, 50-367 Wroclaw, Poland.

There is accumulating evidence that individuals with schizophrenia show altered levels of thyroid hormones. However, a qualitative and quantitative synthesis of findings in this field has not been performed so far. Therefore, we aimed to perform a systematic review and meta-analysis of studies investigating the levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), total thyroxine (tT4), free triiodothyronine (fT3) and total triiodothyronine (tT3) in multiple-episode schizophrenia (MES) and first-episode psychosis (FEP). Electronic databases were searched from their inception until 30th May 2020 by two independent reviewers. Random-effects meta-analyses and meta-regression analyses were performed. Altogether, 19 studies were included. Persons with FEP had significantly lower TSH levels (5 studies, g = -0.26, 95%CI: -0.47 to -0.06, p = 0.013, I = 21.3%), higher fT4 levels (3 studies, g = 0.58, 95%CI: 0.15-1.01, p = 0.008, I = 64.6%) and lower tT3 levels (2 studies, g = -0.60, 95%CI: -0.82 to -0.37, p < 0.001, I = 0%) compared to controls. Elevated TSH levels were found in persons with MES (13 studies, g = 0.20, 95%CI: 0.02-0.39, p = 0.031, I = 50.0%). Our findings imply that the levels of TSH might be decreased in persons with FEP and increased in those with MES. Other alterations need to be confirmed by additional studies. These findings imply the need to monitor the levels of TSH and thyroid hormones from the onset of psychosis.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110402DOI Listing
December 2021

Artificial intelligence and hybrid imaging: the best match for personalized medicine in oncology.

Eur J Hybrid Imaging 2020 Dec 9;4(1):24. Epub 2020 Dec 9.

Regional Center of Nuclear Medicine, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

Artificial intelligence (AI) refers to a field of computer science aimed to perform tasks typically requiring human intelligence. Currently, AI is recognized in the broader technology radar within the five key technologies which emerge for their wide-ranging applications and impact in communities, companies, business, and value chain framework alike. However, AI in medical imaging is at an early phase of development, and there are still hurdles to take related to reliability, user confidence, and adoption. The present narrative review aimed to provide an overview on AI-based approaches (distributed learning, statistical learning, computer-aided diagnosis and detection systems, fully automated image analysis tool, natural language processing) in oncological hybrid medical imaging with respect to clinical tasks (detection, contouring and segmentation, prediction of histology and tumor stage, prediction of mutational status and molecular therapies targets, prediction of treatment response, and outcome). Particularly, AI-based approaches have been briefly described according to their purpose and, finally lung cancer-being one of the most extensively malignancy studied by hybrid medical imaging-has been used as illustrative scenario. Finally, we discussed clinical challenges and open issues including ethics, validation strategies, effective data-sharing methods, regulatory hurdles, educational resources, and strategy to facilitate the interaction among different stakeholders. Some of the major changes in medical imaging will come from the application of AI to workflow and protocols, eventually resulting in improved patient management and quality of life. Overall, several time-consuming tasks could be automatized. Machine learning algorithms and neural networks will permit sophisticated analysis resulting not only in major improvements in disease characterization through imaging, but also in the integration of multiple-omics data (i.e., derived from pathology, genomic, proteomics, and demographics) for multi-dimensional disease featuring. Nevertheless, to accelerate the transition of the theory to practice a sustainable development plan considering the multi-dimensional interactions between professionals, technology, industry, markets, policy, culture, and civil society directed by a mindset which will allow talents to thrive is necessary.
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http://dx.doi.org/10.1186/s41824-020-00094-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218106PMC
December 2020

Strategies for the Improvement of Metal-Based Chemotherapeutic Treatments.

Biomedicines 2021 May 4;9(5). Epub 2021 May 4.

Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126 Pisa, Italy.

This article provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promising strategies, including (1) drug repurposing, (2) the simple modification of the chemical structures of approved metal-based drugs, (3) testing novel drug combinations, and (4) newly synthesized complexes coupling different anticancer drugs. Accordingly, we aim to suggest and summarize a series of reliable approaches that are exploitable for the development of improved and innovative treatments.
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http://dx.doi.org/10.3390/biomedicines9050504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147839PMC
May 2021

The kynurenine pathway in schizophrenia and other mental disorders: Insight from meta-analyses on the peripheral blood levels of tryptophan and related metabolites.

Schizophr Res 2021 06 17;232:61-62. Epub 2021 May 17.

Department of Medicine and Surgery, University of Milano Bicocca, Italy; Division of Psychiatry, University College London, UK.

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http://dx.doi.org/10.1016/j.schres.2021.04.008DOI Listing
June 2021

Efficacy of Cannabidiol for Δ-9-Tetrahydrocannabinol-Induced Psychotic Symptoms, Schizophrenia, and Cannabis Use Disorders: A Narrative Review.

J Clin Med 2021 Mar 22;10(6). Epub 2021 Mar 22.

Department of Medicine and Surgery, University of Milano Bicocca, via Cadore 48, 20900 Monza, Italy.

Although cannabis' major psychoactive component, Δ-9-tetrahydrocannabinol (THC), has been linked to both earlier onset and poorer outcomes of psychotic disorders, Cannabidiol (CBD) seems to have different pharmacological mechanisms and potential therapeutic properties. However, no clinical study has investigated CBD for the treatment of co-occurring psychotic and cannabis use disorders so far, even though its utility seems grounded in a plausible biological basis. The aim of this work is thus to provide an overview of available clinical studies evaluating the efficacy of CBD for psychotic symptoms induced by THC, schizophrenia, and cannabis use disorders. After searching for relevant studies in PubMed, Cochrane Library, and ClinicalTrials.gov, we included 10 clinical studies. Available evidence suggests that CBD may attenuate both psychotic-like symptoms induced by THC in healthy volunteers and positive symptoms in individuals with schizophrenia. In addition, preliminary data on the efficacy of CBD for cannabis use disorders show mixed findings. Evidence from ongoing clinical studies will provide insight into the possible role of CBD for treating psychotic and cannabis use disorders.
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http://dx.doi.org/10.3390/jcm10061303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005219PMC
March 2021

Comparing Long-Acting Antipsychotic Discontinuation Rates Under Ordinary Clinical Circumstances: A Survival Analysis from an Observational, Pragmatic Study.

CNS Drugs 2021 06 29;35(6):655-665. Epub 2021 Mar 29.

WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation; Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy.

Background: Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses.

Objective: Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors.

Methods: The STAR Network 'Depot Study' was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively.

Results: The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4-44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3-43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4-84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6-40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6-27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742-0.981; p = 0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003-4.634; p = 0.049).

Conclusions: Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation.
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http://dx.doi.org/10.1007/s40263-021-00809-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219561PMC
June 2021

Immune-inflammatory markers and psychosis risk: A systematic review and meta-analysis.

Psychoneuroendocrinology 2021 05 13;127:105200. Epub 2021 Mar 13.

Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA, United States.

Subclinical inflammation has been associated with psychosis; however, it remains unknown whether this phenomenon appears also in the premorbid phase. Therefore, we performed a systematic review and meta-analysis of studies comparing peripheral blood levels of C-reactive protein (CRP) and cytokines between individuals at risk of psychosis and controls. Moreover, we tested the hypothesis that the levels of these markers may be different in high-risk converters versus non-converters. Two independent reviewers searched electronic databases until Dec 16th, 2020. After reviewing publication records, 16 studies (548 high-risk individuals and 559 controls) were included. Random-effects meta-analyses with Hedges' g as the effect size estimate were performed. Individuals at clinical risk of psychosis had significantly higher levels of interleukin-6 (IL-6) compared to controls (g = 0.33, 95%CI: 0.06-0.60, p = 0.018). Heterogeneity was not significant in this subgroup analysis. Changes in the levels of IL-6 in subjects at familial risk of psychosis were not significant (g = 0.04, 95%CI: -0.24 to 0.31, p = 0.798). The use of antidepressants was associated with significantly higher levels of IL-6 in high-risk individuals (Beta = 1.56, 95%CI: 0.60-2.53, p = 0.001). No significant differences in the levels of immune-inflammatory markers were found between high-risk converters and non-converters. Our findings suggest that individuals at clinical risk of psychosis show subclinical inflammation in terms of elevated IL-6 levels. This phenomenon might be related to the use of antidepressants. The present meta-analysis does not support the usefulness of single immune-inflammatory markers in predicting transition to psychosis.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105200DOI Listing
May 2021

Surveilling COVID-19 Emotional Contagion on Twitter by Sentiment Analysis.

Eur Psychiatry 2021 02 3;64(1):e17. Epub 2021 Feb 3.

Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

Background: The fight against the COVID-19 pandemic seems to encompass a social media debate, possibly resulting in emotional contagion and the need for novel surveillance approaches. In the current study, we aimed to examine the flow and content of tweets, exploring the role of COVID-19 key events on the popular Twitter platform.

Methods: Using representative freely available data, we performed a focused, social media-based analysis to capture COVID-19 discussions on Twitter, considering sentiment and longitudinal trends between January 19 and March 3, 2020. Different populations of users were considered. Core discussions were explored measuring tweets' sentiment, by both computing a polarity compound score with 95% Confidence Interval and using a transformer-based model, pretrained on a large corpus of COVID-19-related Tweets. Context-dependent meaning and emotion-specific features were considered.

Results: We gathered 3,308,476 tweets written in English. Since the first World Health Organization report (January 21), negative sentiment proportion of tweets gradually increased as expected, with amplifications following key events. Sentiment scores were increasingly negative among most active users. Tweets content and flow revealed an ongoing scenario in which the global emergency seems difficult to be emotionally managed, as shown by sentiment trajectories.

Conclusions: Integrating social media like Twitter as essential surveillance tools in the management of the pandemic and its waves might actually represent a novel preventive approach to hinder emotional contagion, disseminating reliable information and nurturing trust. There is the need to monitor and sustain healthy behaviors as well as community supports also via social media-based preventive interventions.
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http://dx.doi.org/10.1192/j.eurpsy.2021.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943954PMC
February 2021

Reasons for initiating long-acting antipsychotics in psychiatric practice: findings from the STAR Network Depot Study.

Ther Adv Psychopharmacol 2020 22;10:2045125320978102. Epub 2020 Dec 22.

Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Piazzale L.A. Scuro, 10, Verona, 37134, Italy.

Background: Long acting injectable (LAI) antipsychotics have been claimed to ensure treatment adherence and possibly reduce the daily burden of oral formulations. So far, only surveys investigating the theoretical prescribing attitudes of clinicians have been employed. On this basis, we aimed to investigate reasons for prescribing LAIs in a real-world, unselected sample of patients.

Methods: The STAR Network Depot Study is an observational, multicentre study consecutively enrolling adults initiating a LAI over a 12-months period. Clinical severity was assessed with the Brief Psychiatric Rating Scale, and patient's attitude toward medications with the Drug Attitude Inventory 10 items. Psychiatrists recorded reasons for LAI prescribing for each study participant. Responses were grouped into six non-mutually exclusive categories: aggressiveness, patient engagement, ease of drug taking, side-effects, stigma, adherence.

Results: Of the 451 patients included, two-thirds suffered from chronic psychoses. Improving patient engagement with the outpatient psychiatric service was the most common reason for prescribing LAIs (almost 80% of participants), followed by increasing treatment adherence (57%), decreasing aggressiveness (54%), and improving ease of drug taking (52%). After adjusting for confounders, logistic regression analyses showed that reasons for LAI use were associated with LAI choice (e.g. first-generation LAIs for reducing aggressiveness).

Conclusion: Despite the wide availability of novel LAI formulation and the emphasis on their wider use, our data suggest that the main reasons for LAI use have remained substantially unchanged over the years, focusing mostly on improving patient's engagement. Further, clinicians follow implicit prescribing patterns when choosing LAIs, and this may generate hypotheses for future experimental studies.
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http://dx.doi.org/10.1177/2045125320978102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768845PMC
December 2020

Pre-Discharge Predictors of 1-Year Rehospitalization in Adolescents and Young Adults with Severe Mental Disorders: A Retrospective Cohort Study.

Medicina (Kaunas) 2020 Nov 15;56(11). Epub 2020 Nov 15.

Department of Medicine and Surgery, University of Milano Bicocca, via Cadore 48, 20900 Monza, Italy.

: Readmissions of youths hospitalized for a severe mental disorder are common events and bear a remarkable human, social, and economic burden. The current study aimed at evaluating predictors of 1-year rehospitalization in a sample of adolescents and young adults with severe mental disorders. : Data for ≤25-year-old inpatients with a severe mental disorder and consecutively admitted between 1 January 2016 and 30 June 2019 were collected. Subjects were retrospectively assessed over a follow-up period of one year after the index discharge to track readmissions-i.e., the primary outcome variable. Standard descriptive statistics were used. The association between variables and 1-year rehospitalization was estimated using the univariate Cox proportional hazards regression model. We then carried out a multivariable Cox regression model, also estimating the covariate-adjusted survivor function. Hazard ratios (HRs) with related 95% confidence intervals (95% CIs) were provided. : The final sample included 125 individuals. The multivariable Cox regression model estimated that co-occurring substance use disorders (HR = 2.14; 95% CI: 1.08 to 4.26; = 0.029) and being admitted for a suicide attempt (HR = 2.49; 95% CI: 1.13 to 5.49; = 0.024) were both significant predictors of 1-year rehospitalization. : Our study showed that comorbid substance use disorders and being admitted for a suicide attempt were predictors of early readmission in youths with severe mental disorders. Although their generalizability is limited, our findings could contribute to improve the quality of young patients' mental health care by identifying vulnerable subjects who may benefit from tailored interventions to prevent rehospitalizations.
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http://dx.doi.org/10.3390/medicina56110613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696058PMC
November 2020

Reshaping the Cathodic Catalyst Layer for Anion Exchange Membrane Fuel Cells: From Heterogeneous Catalysis to Homogeneous Catalysis.

Angew Chem Int Ed Engl 2021 Feb 22;60(8):4049-4054. Epub 2020 Dec 22.

College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China.

In anion exchange membrane fuel cells, catalytic reactions occur at a well-defined three-phase interface, wherein conventional heterogeneous catalyst layer structures exacerbate problems, such as low catalyst utilization and limited mass transfer. We developed a structural engineering strategy to immobilize a molecular catalyst tetrakis(4-methoxyphenyl)porphyrin cobalt(II) (TMPPCo) on the side chains of an ionomer (polyfluorene, PF) to obtain a composite material (PF-TMPPCo), thereby achieving a homogeneous catalysis environment inside ion-flow channels, with greatly improved mass transfer and turnover frequency as a result of 100 % utilization of the catalyst molecules. The unique structure of the homogeneous catalysis system comprising interconnected nanoreactors exhibits advantages of low overpotential and high fuel-cell power density. This strategy of reshaping of the catalyst layer structure may serve as a new platform for applications of many molecular catalysts in fuel cells.
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http://dx.doi.org/10.1002/anie.202012547DOI Listing
February 2021

The kynurenine pathway in bipolar disorder: a meta-analysis on the peripheral blood levels of tryptophan and related metabolites.

Mol Psychiatry 2021 Jul 19;26(7):3419-3429. Epub 2020 Oct 19.

Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy.

Growing evidence suggests that a dysregulation of the kynurenine pathway (KP) occurs in bipolar disorder (BD). This systematic review and meta-analysis aimed at assessing the possible differences in peripheral blood levels of KP metabolites between individuals with BD and healthy controls. We searched Medline, Embase, and PsycInfo electronic databases for articles indexed up to February 2020. We included any observational study comparing the peripheral blood levels of at least one KP metabolite between adults with BD and healthy controls. Random-effects meta-analyses were carried out generating pooled standardized mean differences (SMDs). Heterogeneity between studies was estimated using the I index. Meta-regression and sensitivity analyses were conducted. Sixteen studies met inclusion criteria and were included in our study. Meta-analyses showed that individuals with BD have lower peripheral blood levels of tryptophan (SMD = -0.29), kynurenine (SMD = -0.28), kynurenic acid (SMD = -0.30), and xanthurenic acid (SMD = -0.55), along with lower kynurenic acid to kynurenine (SMD = -0.60) and kynurenic acid to quinolinic acid (SMD = -0.37) ratios, than healthy controls. Individuals with a manic episode showed the greatest reductions in tryptophan levels (SMD = -0.51), whereas kynurenic acid levels were more reduced among subjects in a depressive phase (SMD = -0.70). Meta-regression and sensitivity analyses confirmed our results. The findings of the present meta-analysis support the hypothesis of an abnormality of the KP in BD. Considering the partial inconsistency of the findings and the small-to-medium magnitude of the estimated effect sizes, additional research assessing possible mediators or confounders is needed.
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http://dx.doi.org/10.1038/s41380-020-00913-1DOI Listing
July 2021

Tolerability and efficacy of vortioxetine versus SSRIs in elderly with major depression. Study protocol of the VESPA study: a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial.

Trials 2020 Aug 3;21(1):695. Epub 2020 Aug 3.

Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.

Introduction: Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed agents in this condition and, although generally safe, tolerability issues cannot be overlooked. Vortioxetine is an antidepressant with a novel mechanism of action. Based on studies to date, it may have a promising tolerability profile in the elderly, as it does not adversely affect psychomotor or cognitive performance and does not alter cardiovascular and endocrine parameters. The present study aims to assess the tolerability profile of vortioxetine in comparison with the SSRIs considered as a single group in elderly participants with depression. The rate of participants withdrawing from treatment due to adverse events after 6 months of follow up will be the primary outcome.

Methods And Analysis: This is a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial funded by the Italian Medicines Agency (AIFA - Agenzia Italiana del Farmaco). Thirteen Italian Community Psychiatric Services will consecutively enrol elderly participants suffering from an episode of major depression over a period of 12 months. Participants will be assessed at baseline and after 1, 3 and 6 months of follow up. At each time point, the following validated rating scales will be administered: Montgomery-Åsberg Depression Rating Scale (MADRS), Antidepressant Side-Effect Checklist (ASEC), EuroQual 5 Dimensions (EQ-5D), Short Blessed Test (SBT), and Charlson Age-Comorbidity Index (CACI). Outcome assessors and the statistician will be masked to treatment allocation. A total of 358 participants (179 in each group) will be enrolled.

Ethics And Dissemination: This study will fully adhere to the ICH E6 Guideline for Good Clinical Practice. Participants' data will be managed and safeguarded according to the European Data Protection Regulation 2016/679. An external Ethical Advisory Board will help guarantee high ethical standards.

Trial Registration: Clinicaltrials.gov: NCT03779789 , Registered on 19 December 2018. Submitted on 19 December. EudraCT number: 2018-001444-66.

Trial Status: Protocol version 1.5; 09/06/2018. Recruitment started In February 2019 and it is ongoing. It is expected to end approximately on 30 September 2021.
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http://dx.doi.org/10.1186/s13063-020-04460-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397635PMC
August 2020

Clinical correlates of DSM-5 mixed features in bipolar disorder: A meta-analysis.

J Affect Disord 2020 11 16;276:234-240. Epub 2020 Jul 16.

Department of Mental Health, ASST Nord Milano, Italy; Department of Medicine and Surgery, University of Milano Bicocca, Italy; Division of Psychiatry, University College London, UK.

Background: Systematic data on clinical correlates of mixed features in bipolar disorder are not available, so far. We conducted a systematic review and meta-analysis estimating the association between DSM-5 mixed features and candidate characteristics in depressive and manic/hypomanic episodes.

Methods: We included observational studies indexed in the main electronic databases. The association between DSM-5 mixed features and relevant correlates was estimated using odds ratio (OR) and standardized mean difference (SMD) with 95% confidence intervals (CIs), for categorical and continuous variables, respectively. Analyses were based on random effects models.

Results: Eight studies were included, involving 3070 individuals (1495 with a major depressive episode and 1575 with hypo/manic episode). No clinical characteristics were associated with mixed features in subjects with a depressive episode. Among subjects with a manic/hypomanic episode, those with mixed features were more likely to have a history of suicide attempts (OR: 2.37; 95%CI: 1.42 to 3.94; I=39.7%), co-occurring anxiety disorders (OR: 2.67; 95%CI: 1.28 to 5.57; I=0%), and a rapid cycling course (OR=4.23; 95%CI: 1.29 to 13.81; I=0%), with less severe manic symptoms (SMD=-0.40; 95%CI: -0.65 to -0.16; I=0%).

Limitations: (1) the heterogeneity of methods across studies and the inconsistency of findings; (2) the limited amount of data on correlates of DSM-5 mixed features; (3) the possible influence of publication bias.

Conclusions: Findings of this meta-analysis show that mixed features among individuals with a manic/hypomanic episode may identify a special clinical population, characterized not only by depressive symptoms, but also by anxiety, rapid cycling, and suicidality.
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http://dx.doi.org/10.1016/j.jad.2020.07.035DOI Listing
November 2020

Cannabidiol for Mood Disorders: A Call for More Research.

Can J Psychiatry 2021 02 14;66(2):182-183. Epub 2020 May 14.

Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.

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http://dx.doi.org/10.1177/0706743720926798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918874PMC
February 2021

Clinical correlates of paliperidone palmitate and aripiprazole monohydrate prescription for subjects with schizophrenia-spectrum disorders: findings from the STAR Network Depot Study.

Int Clin Psychopharmacol 2020 07;35(4):214-220

Department of Medicine and Surgery, University of Milano Bicocca, Monza.

This study, based on the 'Servizi Territoriali Associati per la Ricerca' (STAR) Network Depot Study nationwide baseline data, explored whether individual symptoms severity and clusters might influence the prescription of paliperidone palmitate 1-month (PP1M) vs. aripiprazole monohydrate. The Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology and relevant symptoms clusters. Drug Attitude Inventory, 10 items, was used to test attitude towards medications. Adherence to treatments was rated according to the Kemp seven-point scale. We assessed for eligibility 451 individuals and, among them, we included 195 subjects (n = 117 who started PPM1 and n = 78 aripiprazole monohydrate). Individuals were comparable in terms of age, gender, treatment years, recent hospitalizations, previous long-acting injectable antipsychotic treatments, additional oral treatments, attitude toward drugs, medication adherence, and alcohol/substance-related comorbidities. Subjects starting PP1M presented higher BPRS overall (P = 0.009), positive (P = 0.015), and negative (P = 0.010) symptom scores compared to subjects starting aripiprazole monohydrate. Results were confirmed by appropriate regression models and propensity score matching analysis. No differences were found comparing the other BPRS subscale scores: affect, resistance, and activation. Clinicians may be more prone to prescribe PPM1, rather than aripiprazole monohydrate, to subjects showing higher overall symptom severity, including positive and negative symptoms. No additional clinical factors influenced prescribing attitudes in our sample.
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http://dx.doi.org/10.1097/YIC.0000000000000317DOI Listing
July 2020

Serum amino acid profile in 51 dogs with immunosuppressant-responsive enteropathy (IRE): a pilot study on clinical aspects and outcomes.

BMC Vet Res 2020 Apr 22;16(1):117. Epub 2020 Apr 22.

Professional Association Endovet Rome, Rome, Italy.

Background: Lower levels of tryptophan (TRP) have been identified in people with inflammatory bowel disease and in dogs with protein-losing enteropathy (PLE). No data on serum amino acids (AAs) but some on plasma in canine immunosuppressant-responsive enteropathy (IRE) are available. The aim of this study is to compare serum AAs between healthy and IRE dogs, considering clinicopathological variables and follow-up.

Results: Twenty-six healthy control dogs (CD) and 51 IRE dogs were included. IRE was diagnosed after the exclusion of extra-intestinal diseases and food and antibiotic responsive enteropathies. The canine chronic enteropathy clinical activity index (CCECAI) was assessed at presentation and during the clinical follow-up. In CD and IRE dogs, 19 different serum AAs were measured. IRE dogs were classified into responders, partial responders and non-responders, based on CCECAI after 1 month, and divided into PLE and non-PLE, based on albumin level. IRE dogs showed lower L-Tyrosine (TYR), L-Phenylalanine (PHE) and TRP (p < 0.001) and higher L-Serine (SER), L-Glutamic acid (GLU), L-Arginine (p < 0.001), L-Threonine (p = 0.013), Proline (p = 0.044), L-Cysteine (p = 0.003), L-Valine (p = 0.018), L-Lysine (p = 0.01) and L-Isoleucine (p = 0.005) than CDs. PLE dogs showed lower L-Histidine (HIS) (p = 0.008), PHE (p = 0.005) and TRP (p = 0.005) than non-PLE dogs. In IRE dogs, median GLU was significantly lower in dogs with BCS 3/9 than BCS 5/9 category (p = 0.036). Total protein was positively correlated with PHE and TRP (both p = 0.031, r = 0.30) and albumin was positively correlated with HIS (p = 0.025, r = 0.31), PHE and TRP (both p = 0.001, r = 0.46). HIS (p = 0.041), PHE (p = 0.047) and TRP (p = 0.044) concentrations were significantly lower in non-responders than in responders and partial responders.

Conclusions: This study may suggest further investigation on serum, HIS, PHE, TRP and TYR as markers of intestinal disease and proposed HIS, PHE and TRP as prognostic marker for response to therapy.
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http://dx.doi.org/10.1186/s12917-020-02334-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178940PMC
April 2020

Chemokine alterations in bipolar disorder: A systematic review and meta-analysis.

Brain Behav Immun 2020 08 9;88:870-877. Epub 2020 Apr 9.

Department of Nervous System Diseases, Wroclaw Medical University, Bartla 5 Street, 51-618 Wroclaw, Poland.

We aimed to perform a systematic review and meta-analysis of studies examining the levels of chemokines in peripheral blood of patients with bipolar disorder (BD) and healthy controls. Meta-analysis was based on random-effects models with Hedges' g as the effect size estimate. We included 13 eligible studies (1221 BD patients and 663 controls). The following chemokines were analysed: interleukin-8 (IL-8), monocyte-chemoattractant protein-1 (MCP-1), eotaxin-1, eotaxin-2 and interferon-γ-induced protein 10 (IP-10). The levels of IL-8 (N = 8, g = 0.26, 95%CI: 0.11-0.41, p < 0.001), MCP-1 (N = 8, g = 0.40, 95%CI: 0.18-0.63), eotaxin-1 (N = 3, g = 0.55, 95%CI: 0.21-0.89, p = 0.001) and IP-10 (N = 4, g = 0.95, 95%CI: 0.67-1.22, p < 0.001) were significantly higher in BD patients as compared with controls. Subgroup analyses revealed that elevated levels of IL-8 (N = 5, g = 0.75, 95%CI: 0.42-1.07, p < 0.001) and MCP-1 (N = 4, g = 0.57, 95%CI: 0.28-0.86, p < 0.001) appeared only in BD patients during their depressive phase. Illness duration was associated with significantly lower levels of IL-8 in meta-regression analysis. In turn, elevated levels of IP-10 were present during euthymia (N = 2, g = 0.76, 95%CI: 0.43-1.10, p < 0.001) but not depression (N = 2, g = 1.81, 95%CI: -0.16 to 3.77, p = 0.072). The analysis of eotaxin-1 levels was mainly based on studies of euthymic BD patients (N = 3). Our results suggest that chemokine alterations in BD might be related to mood state. Elevated levels of IL-8 and MCP-1 might be specific to depression. Available evidence indicates that increased levels of eotaxin-1 and IP-10 appear in euthymia; however, more studies are needed to address these alterations in other mood states.
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http://dx.doi.org/10.1016/j.bbi.2020.04.013DOI Listing
August 2020

Purinergic Signaling and Related Biomarkers in Depression.

Brain Sci 2020 Mar 12;10(3). Epub 2020 Mar 12.

Department of Medicine and Surgery, University of Milano Bicocca, Via Cadore 48, 20900 Monza, Italy.

It is established that purinergic signaling can shape a wide range of physiological functions, including neurotransmission and neuromodulation. The purinergic system may play a role in the pathophysiology of mood disorders, influencing neurotransmitter systems and hormonal pathways of the hypothalamic-pituitary-adrenal axis. Treatment with mood stabilizers and antidepressants can lead to changes in purinergic signaling. In this overview, we describe the biological background on the possible link between the purinergic system and depression, possibly involving changes in adenosine- and ATP-mediated signaling at P1 and P2 receptors, respectively. Furthermore, evidence on the possible antidepressive effects of non-selective adenosine antagonist caffeine and other purinergic modulators is reviewed. In particular, A2A and P2X7 receptors have been identified as potential targets for depression treatment. Preclinical studies highlight that both selective A2A and P2X7 antagonists may have antidepressant effects and potentiate responses to antidepressant treatments. Consistently, recent studies feature the possible role of the purinergic system peripheral metabolites as possible biomarkers of depression. In particular, variations of serum uric acid, as the end product of purinergic metabolism, have been found in depression. Although several open questions remain, the purinergic system represents a promising research area for insights into the molecular basis of depression.
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http://dx.doi.org/10.3390/brainsci10030160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139781PMC
March 2020

Glial and neuronal markers in bipolar disorder: A meta-analysis testing S100B and NSE peripheral blood levels.

Prog Neuropsychopharmacol Biol Psychiatry 2020 07 17;101:109922. Epub 2020 Mar 17.

Department of Mental Health and Addiction, ASST Nord Milano, Milano, Italy; Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy; Division of Psychiatry, University College London, London, UK.

S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) might be peripheral markers reflecting glia and neuronal abnormalities in subjects with bipolar disorder. We carried out a systematic review and meta-analysis, searching for studies indexed in main electronic databases, to clarify whether S100B and NSE blood levels might be increased in bipolar disorder. Eleven studies met eligibility criteria, with data on S100B levels and/or NSE levels in subjects with bipolar disorder and healthy controls, respectively. Random-effects meta-analysis estimated higher levels of S100B in bipolar disorder (standardized mean difference [SMD] = 0.81; p < .001), with some inconsistency across studies (I = 81.7%). Findings were confirmed by relevant sensitivity analyses. Meta-regression analyses did not estimate any effect for tested covariates. On the other hand, no differences in NSE levels between individuals with bipolar disorder and healthy controls were estimated (SMD = -0.32; p = .374), with high heterogeneity across studies (I = 89.9%). Meta-regression analyses showed that the effect size was influenced by both mean age (p < .001) and illness duration (p = .001) of subjects with bipolar disorders. Our findings support the hypothesis of a possible role of glial abnormalities in the pathophysiology of bipolar disorder.
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http://dx.doi.org/10.1016/j.pnpbp.2020.109922DOI Listing
July 2020

Detecting Binge Drinking and Alcohol-Related Risky Behaviours from Twitter's Users: An Exploratory Content- and Topology-Based Analysis.

Int J Environ Res Public Health 2020 02 26;17(5). Epub 2020 Feb 26.

Department of Informatics, Systems, and Communication. University of Milano-Bicocca, 20126 Milan, Italy.

Binge Drinking (BD) is a common risky behaviour that people hardly report to healthcare professionals, although it is not uncommon to find, instead, personal communications related to alcohol-related behaviors on social media. By following a data-driven approach focusing on User-Generated Content, we aimed to detect potential binge drinkers through the investigation of their language and shared topics. First, we gathered Twitter threads quoting BD and alcohol-related behaviours, by considering unequivocal keywords, identified by experts, from previous evidence on BD. Subsequently, a random sample of the gathered tweets was manually labelled, and two supervised learning classifiers were trained on both linguistic and metadata features, to classify tweets of genuine unique users with respect to media, bot, and commercial accounts. Based on this classification, we observed that approximately 55% of the 1 million alcohol-related collected tweets was automatically identified as belonging to non-genuine users. A third classifier was then trained on a subset of manually labelled tweets among those previously identified as belonging to genuine accounts, to automatically identify potential binge drinkers based only on linguistic features. On average, users classified as binge drinkers were quite similar to the standard genuine Twitter users in our sample. Nonetheless, the analysis of social media contents of genuine users reporting risky behaviours remains a promising source for informed preventive programs.
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http://dx.doi.org/10.3390/ijerph17051510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084454PMC
February 2020
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