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  1. Article: 3D dynamic cultures of HGSOC organoids to model innovative and standard therapies.

    Cavarzerani, Enrico / Caligiuri, Isabella / Bartoletti, Michele / Canzonieri, Vincenzo / Rizzolio, Flavio

    Frontiers in bioengineering and biotechnology

    2023  Volume 11, Page(s) 1135374

    Abstract: High-grade serous ovarian cancer (HGSOC) needs new technologies for improving cancer diagnosis and therapy. It is a fatal disease with few options for the patients. In this context, dynamic culture systems coupling with patient-derived cancer 3D ... ...

    Abstract High-grade serous ovarian cancer (HGSOC) needs new technologies for improving cancer diagnosis and therapy. It is a fatal disease with few options for the patients. In this context, dynamic culture systems coupling with patient-derived cancer 3D microstructures could offer a new opportunity for exploring novel therapeutic approaches. In this study, we optimized a passive microfluidic platform with 3D cancer organoids, which allows a standardized approach among different patients, a minimum requirement of samples, multiple interrogations of biological events, and a rapid response. The passive flow was optimized to improve the growth of cancer organoids, avoiding the disruption of the extracellular matrix (ECM). Under optimized conditions of the OrganoFlow (tilting angle of 15° and an interval of rocking every 8 min), the cancer organoids grow faster than when they are in static conditions and the number of dead cells is reduced over time. To calculate the
    Language English
    Publishing date 2023-04-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2023.1135374
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  2. Article ; Online: What do clinicians mean by epidemics' preparedness.

    Bartoletti, Michele / Bussini, Linda / Bavaro, Davide Fiore / Cento, Valeria

    Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

    2023  Volume 30, Issue 5, Page(s) 586–591

    Abstract: Background: Infectious disease pandemics and epidemics pose significant global threats, and the risk of emerging infectious diseases has increased because of factors such as international connections, travel, and population density. Despite investments ... ...

    Abstract Background: Infectious disease pandemics and epidemics pose significant global threats, and the risk of emerging infectious diseases has increased because of factors such as international connections, travel, and population density. Despite investments in global health surveillance, much of the world remains unprepared to manage infectious disease threats.
    Objectives: This review article discusses the general considerations and lessons learned from the COVID-19 pandemic in terms of epidemic preparedness.
    Sources: Non-systematic search on PubMed, scientific society websites, and scientific newspapers (performed in April 2023).
    Content: Key factors for preparedness include robust public health infrastructure, adequate allocation of resources, and effective communication between stakeholders. This narrative review emphasizes the need for timely and accurate dissemination of medical knowledge, as well as addressing the challenges of misinformation and infodemics. It also highlights the importance of quick availability of diagnostic tests and vaccines, ensuring equitable access to these technologies. The role of scientific coordination in developing treatment strategies and the safety and mental well-being of healthcare workers are discussed. Lastly, it should be emphasized the need for medical training, multidisciplinary teams, new technologies and artificial intelligence, and the active role of infectious disease physicians in epidemic preparedness efforts.
    Implications: From clinicians' perspective, healthcare authorities play a crucial role in epidemic preparedness even by providing resource management plans, ensuring availability of essential supplies and training, facilitating communication, and improving safe infection management.
    MeSH term(s) Humans ; COVID-19/epidemiology ; COVID-19/prevention & control ; SARS-CoV-2 ; Epidemics/prevention & control ; Health Personnel ; Pandemics/prevention & control ; Public Health ; Global Health
    Language English
    Publishing date 2023-06-15
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1328418-6
    ISSN 1469-0691 ; 1470-9465 ; 1198-743X
    ISSN (online) 1469-0691
    ISSN 1470-9465 ; 1198-743X
    DOI 10.1016/j.cmi.2023.05.030
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  3. Article ; Online: Prevalence of COVID-19-Associated Pulmonary Aspergillosis: Critical Review and Conclusions.

    Egger, Matthias / Bussini, Linda / Hoenigl, Martin / Bartoletti, Michele

    Journal of fungi (Basel, Switzerland)

    2022  Volume 8, Issue 4

    Abstract: First reports of cases and case series of COVID-19-associated pulmonary aspergillosis (CAPA) emerged during the first months of the pandemic. Prevalence rates varied widely due to the fact that CAPA was, and still remains, challenging to diagnose in ... ...

    Abstract First reports of cases and case series of COVID-19-associated pulmonary aspergillosis (CAPA) emerged during the first months of the pandemic. Prevalence rates varied widely due to the fact that CAPA was, and still remains, challenging to diagnose in patients with COVID-19-associated acute respiratory failure (ARF). The clinical picture and radiological findings of CAPA are unspecific and can resemble those of severe COVID-19. Hence, mycological evidence became a key component in establishing a diagnosis. However, blood tests lack sensitivity in early treatable phases of CAPA and once positive, mortality has been shown to exceed 80% despite systemic antifungal therapy. The primarily airway invasive growth in non-neutropenic patients and the late occurrence of angioinvasion in the course of disease may mainly account for these diagnostic obstacles. Testing of bronchoalveolar lavage (BAL) is therefore crucial in the diagnostic process, but was rarely performed during the early phase of the pandemic, which potentially interfered with the accuracy of reported prevalence. Current guidelines recommend treatment of CAPA during its early airway invasive phase, which may result in some overtreatment (i.e., treatment in patients that may not develop angioinvasive infection) and adverse drug events, yet there is no viable alternative approach. Timely treatment of cases needs to be ensured for patients with mycological evidence of CAPA in the lower respiratory tract given the independent contribution of CAPA to devastating mortality rates of around 50% that have been shown in multiple studies. Here, we review the evolution of reported CAPA prevalence and the role of CAPA as an important opportunistic infection affecting COVID-19 patients in intensive care units (ICUs).
    Language English
    Publishing date 2022-04-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2784229-0
    ISSN 2309-608X ; 2309-608X
    ISSN (online) 2309-608X
    ISSN 2309-608X
    DOI 10.3390/jof8040390
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  4. Article: Clinical experience with therapeutic dose of Low-Molecular-Weight Heparin.

    Viale, Pierluigi / Bartoletti, Michele

    Le infezioni in medicina

    2020  Volume 28, Issue suppl 1, Page(s) 118–121

    Abstract: A 71-year old gentleman with history of arterial hypertension treated with valsartan presented on was hospitalized at the Infectious Diseases Unit, University of Bologna (Italy) for severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2) and ... ...

    Abstract A 71-year old gentleman with history of arterial hypertension treated with valsartan presented on was hospitalized at the Infectious Diseases Unit, University of Bologna (Italy) for severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2) and received treatment with hydroxychloroquine 200mg bid (400 mg bid the first day), azithromycin 400 mg qd, thrombotic prophylaxis with enoxaparin 4000 UI qd and Venturi mask oxygen delivering FiO2 of 31%. The case highlights the high frequency of coagulopathy in patients with moderate to severe cases of SARS-CoV-2 associated disease (COVID-19). After one week the patient significantly improved and the daily dose of enoxaparin was reduced and definitively discontinued four days later. The case highlights the high frequency of coagulopathy in patients with moderate to severe cases of SARS-CoV-2 associated disease (COVID-19). Considering the available information we believe that LMWH may represent a promising treatment for COVID-19 but further well-designed trials are needed to address these points.
    MeSH term(s) Aged ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Anticoagulants/pharmacology ; Anticoagulants/therapeutic use ; Antihypertensive Agents/therapeutic use ; Azithromycin/administration & dosage ; Azithromycin/therapeutic use ; Combined Modality Therapy ; Coronavirus Infections/complications ; Coronavirus Infections/diagnostic imaging ; Coronavirus Infections/drug therapy ; Coronavirus Infections/therapy ; Drug Therapy, Combination ; Enoxaparin/pharmacology ; Enoxaparin/therapeutic use ; Humans ; Hydroxychloroquine/administration & dosage ; Hydroxychloroquine/therapeutic use ; Hypertension/complications ; Hypertension/drug therapy ; Male ; Oxygen Inhalation Therapy ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/diagnostic imaging ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/therapy ; Thrombophilia/drug therapy ; Thrombophilia/etiology ; Tomography, X-Ray Computed ; Valsartan/therapeutic use
    Chemical Substances Anti-Inflammatory Agents ; Anticoagulants ; Antihypertensive Agents ; Enoxaparin ; Hydroxychloroquine (4QWG6N8QKH) ; Valsartan (80M03YXJ7I) ; Azithromycin (83905-01-5)
    Keywords covid19
    Language English
    Publishing date 2020-06-05
    Publishing country Italy
    Document type Case Reports ; Journal Article
    ZDB-ID 2041081-5
    ISSN 1124-9390
    ISSN 1124-9390
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    Zs.A 5576: Show issues Location:
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  5. Article ; Online: Copper nitroprusside: An innovative approach for targeted cancer therapy via ROS modulation.

    Asif, Kanwal / Adeel, Muhammad / Mahbubur Rahman, Md / Bartoletti, Michele / Brezar, Simona Kranjc / Cemazar, Maja / Canzonieri, Vincenzo / Rizzolio, Flavio / Caligiuri, Isabella

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2024  Volume 171, Page(s) 116017

    Abstract: The clinical application of nanomaterials for chemodynamic therapy (CDT), which generate multiple reactive oxygen species (ROS), presents significant challenges. These challenges arise due to insufficient levels of endogenous hydrogen peroxide and ... ...

    Abstract The clinical application of nanomaterials for chemodynamic therapy (CDT), which generate multiple reactive oxygen species (ROS), presents significant challenges. These challenges arise due to insufficient levels of endogenous hydrogen peroxide and catalytic ions necessary to initiate Fenton reactions. As a result, sophisticated additional delivery systems are required. In this study, a novel bimetallic copper (II) pentacyanonitrosylferrate (Cu(II)NP, Cu[Fe(CN) 5 NO]) material was developed to address these limitations. This material functions as a multiple ROS generator at tumoral sites by self-inducing hydrogen peroxide and producing peroxynitrite (ONOO
    MeSH term(s) Humans ; Copper ; Hydrogen Peroxide ; Nitroprusside ; Reactive Oxygen Species ; Neoplasms
    Chemical Substances Copper (789U1901C5) ; Hydrogen Peroxide (BBX060AN9V) ; Nitroprusside (169D1260KM) ; Reactive Oxygen Species
    Language English
    Publishing date 2024-01-08
    Publishing country France
    Document type Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2023.116017
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  6. Article: Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis.

    Gatti, Milo / Fornaro, Giacomo / Pasquini, Zeno / Zanoni, Andrea / Bartoletti, Michele / Viale, Pierluigi / Pea, Federico

    Antibiotics (Basel, Switzerland)

    2023  Volume 12, Issue 4

    Abstract: 1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole ... ...

    Abstract (1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole for the management of proven or probable CAPA between January 2021 and December 2022 were included. The concentration/dose ratio (C/D) was used as a surrogate marker of voriconazole total clearance. A receiving operating characteristic (ROC) curve analysis was performed by using C-reactive protein (CRP) or procalcitonin (PCT) values as the test variable and voriconazole C/D ratio > 0.375 (equivalent to a trough concentration [C
    Language English
    Publishing date 2023-04-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics12040764
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  7. Article ; Online: Prevention and management of infectious complications in patients with chronic lymphocytic leukemia (CLL) treated with BTK and BCL-2 inhibitors, focus on current guidelines.

    Mikulska, Malgorzata / Oltolini, Chiara / Zappulo, Emanuela / Bartoletti, Michele / Frustaci, Anna Maria / Visentin, Andrea / Vitale, Candida / Mauro, Francesca R

    Blood reviews

    2024  Volume 65, Page(s) 101180

    Abstract: CLL is associated with an increased risk of infectious complications. Treatment with BTK or BCL-2 inhibitors does not seem to increase significantly the risk of opportunistic infections, but the role of combination therapies including BTK and/or BCL-2 ... ...

    Abstract CLL is associated with an increased risk of infectious complications. Treatment with BTK or BCL-2 inhibitors does not seem to increase significantly the risk of opportunistic infections, but the role of combination therapies including BTK and/or BCL-2 inhibitors remains to be established. Various infectious complications can be successfully prevented with appropriate risk management strategies. In this paper we reviewed the international guidelines on prevention and management of infectious complications in patients with CLL treated with BTK or BCL-2 inhibitors. Universal pharmacological anti-herpes, antibacterial or antifungal prophylaxis is not warranted. Reactivation of HBV should be prevented in HBsAg-positive subjects. For HBsAg-negative/HBcAb-positive patients recommendations differ, but in case of combination treatment should follow those for other, particularly anti-CD20, agent. Immunization should be provided preferably before the onset of treatment. Immunoglobulin therapy has favourable impact on morbidity but not mortality in patients with hypogammaglobulinemia and severe or recurrent infections. Lack of high-quality data and heterogeneity of patients or protocols included in the studies might explain differences among the main guidelines. Better data collection is warranted.
    MeSH term(s) Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/complications ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Hepatitis B Surface Antigens/therapeutic use ; Antineoplastic Agents/therapeutic use ; Immunization ; Proto-Oncogene Proteins c-bcl-2
    Chemical Substances Hepatitis B Surface Antigens ; Antineoplastic Agents ; Proto-Oncogene Proteins c-bcl-2
    Language English
    Publishing date 2024-02-01
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 639015-8
    ISSN 1532-1681 ; 0268-960X
    ISSN (online) 1532-1681
    ISSN 0268-960X
    DOI 10.1016/j.blre.2024.101180
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    Zs.A 2207: Show issues Location:
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  8. Article ; Online: Prevalence of COVID-19-Associated Pulmonary Aspergillosis

    Matthias Egger / Linda Bussini / Martin Hoenigl / Michele Bartoletti

    Journal of Fungi, Vol 8, Iss 390, p

    Critical Review and Conclusions

    2022  Volume 390

    Abstract: First reports of cases and case series of COVID-19-associated pulmonary aspergillosis (CAPA) emerged during the first months of the pandemic. Prevalence rates varied widely due to the fact that CAPA was, and still remains, challenging to diagnose in ... ...

    Abstract First reports of cases and case series of COVID-19-associated pulmonary aspergillosis (CAPA) emerged during the first months of the pandemic. Prevalence rates varied widely due to the fact that CAPA was, and still remains, challenging to diagnose in patients with COVID-19-associated acute respiratory failure (ARF). The clinical picture and radiological findings of CAPA are unspecific and can resemble those of severe COVID-19. Hence, mycological evidence became a key component in establishing a diagnosis. However, blood tests lack sensitivity in early treatable phases of CAPA and once positive, mortality has been shown to exceed 80% despite systemic antifungal therapy. The primarily airway invasive growth in non-neutropenic patients and the late occurrence of angioinvasion in the course of disease may mainly account for these diagnostic obstacles. Testing of bronchoalveolar lavage (BAL) is therefore crucial in the diagnostic process, but was rarely performed during the early phase of the pandemic, which potentially interfered with the accuracy of reported prevalence. Current guidelines recommend treatment of CAPA during its early airway invasive phase, which may result in some overtreatment (i.e., treatment in patients that may not develop angioinvasive infection) and adverse drug events, yet there is no viable alternative approach. Timely treatment of cases needs to be ensured for patients with mycological evidence of CAPA in the lower respiratory tract given the independent contribution of CAPA to devastating mortality rates of around 50% that have been shown in multiple studies. Here, we review the evolution of reported CAPA prevalence and the role of CAPA as an important opportunistic infection affecting COVID-19 patients in intensive care units (ICUs).
    Keywords invasive aspergillosis ; COVID-19 ; serum ; bronchoalveolar lavage ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
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  9. Article ; Online: Incorporation of anti-PD1 or anti PD-L1 agents to platinum-based chemotherapy for the primary treatment of advanced or recurrent endometrial cancer. A meta-analysis.

    Bartoletti, Michele / Montico, Marcella / Lorusso, Domenica / Mazzeo, Roberta / Oaknin, Ana / Musacchio, Lucia / Scambia, Giovanni / Puglisi, Fabio / Pignata, Sandro

    Cancer treatment reviews

    2024  Volume 125, Page(s) 102701

    Abstract: Importance: Various randomized trials have explored the efficacy of combining immune checkpoint inhibitors (ICIs) with first-line chemotherapy in advanced endometrial cancer. We aimed to summarize available data and clarify the benefit of adding ... ...

    Abstract Importance: Various randomized trials have explored the efficacy of combining immune checkpoint inhibitors (ICIs) with first-line chemotherapy in advanced endometrial cancer. We aimed to summarize available data and clarify the benefit of adding immunotherapy according to the DNA mismatch repair status (deficient, dMMR or proficient, pMMR) and the specific type of agent used (anti-PD1 or anti-PD-L1).
    Objective: To assess whether the addition of ICIs to standard platinum-based chemotherapy enhances progression-free survival (PFS) for patients with advanced endometrial cancer both overall and based on DNA mismatch repair status.
    Data sources: Electronic databases (PubMed, Embase and Cochrane Library) and conference proceedings were searched for first line, randomized and controlled trials integrating ICIs with chemotherapy for the treatment of advanced endometrial cancer published or presented by November 1, 2023.
    Study selection: Five studies, comprising 2456 patients (1308 received ICIs with chemotherapy and 1148 treated with chemotherapy alone) met the selection criteria and were included in the analysis. Experimental arms included pembrolizumab, dostarlimab (anti-PD1) and durvalumab, atezolizumab and avelumab (anti-PD-L1) combined with standard three-weekly carboplatin-paclitaxel chemotherapy backbone. Endometrial carcinosarcoma were included in 3 out of 5 trials.
    Data extraction and synthesis: For comparison of PFS outcomes, extrapolation of hazard ratios (HRs), 95% confidence intervals (CI) and PFS events was performed for each included study in the overall population and according to subgroups. Data analysis was conducted using a random-effects model.
    Results: The addition of ICIs to chemotherapy improved PFS compared to chemotherapy alone in the overall population (pooled HR, 0.63; 95 % CI, 0.52--0.76; P <.001). In the dMMR subgroup the benefit was more pronounced (pooled HR, 0.34; 95 % CI, 0.27--0.44; P <.001) and not affected by drugs used with pooled HRs of 0.39 (95 % CI, 0.28--0.55; P <.001) and 0.34 (95 % CI, 0.27--0.44; P <.001) for PD-L1 and PD1 inhibitors, respectively. For pMMR patients, a statistically significant benefit in terms of PFS was confirmed only when anti-PD1 were used (anti-PD-1: HR 0.64, 95 % CI: 0.46-0.90, P =.010 vs anti-PD-L1: HR 0.87, 95 % CI: 0.73-1.03, P =.104) CONCLUSIONS AND RELEVANCE: This meta-analysis confirmed the advantage in terms of PFS of adding ICIs to standard platinum-based chemotherapy. While dMMR patients benefit from the incorporation of both anti PD-1 or anti PD-L1, this benefit is confined to the association of anti-PD1 agents in pMMR patients. Updated analysis of trials is awaited to clarify the impact of immunotherapy on overall survival.
    MeSH term(s) Humans ; Female ; Immune Checkpoint Inhibitors/therapeutic use ; Neoplasm Recurrence, Local/drug therapy ; Paclitaxel ; Immunotherapy ; Endometrial Neoplasms/drug therapy
    Chemical Substances Immune Checkpoint Inhibitors ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2024-02-27
    Publishing country Netherlands
    Document type Meta-Analysis ; Journal Article ; Review
    ZDB-ID 125102-8
    ISSN 1532-1967 ; 0305-7372
    ISSN (online) 1532-1967
    ISSN 0305-7372
    DOI 10.1016/j.ctrv.2024.102701
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  10. Article ; Online: Carbapenemase-producing Enterobacteriaceae in transplant patients.

    Giannella, Maddalena / Bartoletti, Michele / Conti, Michela / Righi, Elda

    The Journal of antimicrobial chemotherapy

    2021  Volume 76, Issue Suppl 1, Page(s) i27–i39

    Abstract: Carbapenemase-producing Enterobacteriaceae (CPE) are a serious public health concern and represent a major threat to immunocompromised hosts, including solid organ (SOT) and stem cell transplant (HSCT) recipients. Transplant patients are at particular ... ...

    Abstract Carbapenemase-producing Enterobacteriaceae (CPE) are a serious public health concern and represent a major threat to immunocompromised hosts, including solid organ (SOT) and stem cell transplant (HSCT) recipients. Transplant patients are at particular risk of developing CPE colonization and/or infection due to their frequent exposure to prolonged courses of broad-spectrum antibiotics, altered immunocompetence and exposure to invasive procedures and immunosuppressive drugs. Gut colonization with CPE, in particular carbapenem-resistant Klebsiella pneumoniae, may occur before or after SOT in 2%-27% of patients and among 2%-9% of HSCT and has been associated with increased risk of developing CPE infections. In endemic areas, CPE infections occur in up to 18% of SOT, and HSCT patients can account for 5%-18% of all patients with CPE bacteraemia. Mortality rates up to 70% have been associated with CPE infections in both patient populations. The rapid initiation of an active therapy against CPE is advocated in these infections. Therapeutic options, however, are limited by the paucity of novel compounds that are currently available and by potential antibiotic-associated toxicities. Therefore, a multidisciplinary approach involving infection control and antimicrobial stewardship programmes still represents the mainstay for the management of CPE infections among transplant patients. The evidence for the use of prevention strategies such as CPE-targeted perioperative prophylaxis or gut decolonization is still scarce. Large, multicentre trials are required to better define prevention strategies and to guide the management of CPE infections in the transplant setting.
    MeSH term(s) Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins ; Carbapenem-Resistant Enterobacteriaceae ; Enterobacteriaceae Infections/drug therapy ; Enterobacteriaceae Infections/epidemiology ; Humans ; Immunocompromised Host ; Klebsiella pneumoniae ; Transplant Recipients ; beta-Lactamases
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; beta-Lactamases (EC 3.5.2.6)
    Language English
    Publishing date 2021-02-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 191709-2
    ISSN 1460-2091 ; 0305-7453
    ISSN (online) 1460-2091
    ISSN 0305-7453
    DOI 10.1093/jac/dkaa495
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