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  • 1
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    Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support–Free Days in Patients Hospitalized With COVID-19 : A Randomized Clinical Trial
    American Medical Association (AMA) ; 2023
    In:  JAMA Vol. 329, No. 14 ( 2023-04-11), p. 1183-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 14 ( 2023-04-11), p. 1183-
    Abstract: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02735707
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2023.4480
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 2
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    The value of open-source clinical science in pandemic response: lessons from ISARIC
    Elsevier BV ; 2021
    In:  The Lancet Infectious Diseases Vol. 21, No. 12 ( 2021-12), p. 1623-1624
    Details
    In: The Lancet Infectious Diseases, Elsevier BV, Vol. 21, No. 12 ( 2021-12), p. 1623-1624
    Type of Medium: Online Resource
    ISSN: 1473-3099
    URL: Article
    DOI: 10.1016/S1473-3099(21)00565-X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 3
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    Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study
    Springer Science and Business Media LLC ; 2022
    In:  Critical Care Vol. 26, No. 1 ( 2022-09-13)
    Details
    In: Critical Care, Springer Science and Business Media LLC, Vol. 26, No. 1 ( 2022-09-13)
    Abstract: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10] ), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11] ), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18] ). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30] ). Conclusions In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.
    Type of Medium: Online Resource
    ISSN: 1364-8535
    URL: Article
    DOI: 10.1186/s13054-022-04155-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2051256-9
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  • 4
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    15 First-line platinum-based chemotherapy combined with PD-1/PD-L1 inhibitors (ICI) prevents hyperprogression in non-small cell lung cancer (NSCLC) patients by reducing circulating immature neutrophils
    BMJ ; 2021
    In:  Journal for ImmunoTherapy of Cancer Vol. 9, No. Suppl 2 ( 2021-11), p. A16-A17
    Details
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 9, No. Suppl 2 ( 2021-11), p. A16-A17
    Abstract: Hyperprogression (HPD) has been described in ≃14–26% of NSCLC patients upon single-agent ICI 1 and has not been reported upon ICI and platinum-based chemotherapy (PCT) combinations. Both high circulating neutrophils 2 and senescent T-cells 3 correlated with HPD, however the exact neutrophils-T-cells interplay and the role of specific neutrophils subsets in driving HPD is unknown. Methods NSCLC patients treated with 1st line ICI as single-agent or in combination with PCT were assessed for HPD and circulating neutrophils’ phenotype. HPD required 3 assessment (2 before ICI, 1 upon ICI) and was defined as delta tumor growth rate (TGR) (TGR upon ICI – TGR before ICI) 〉 50% and/or TGR ratio (TGR upon ICI/TGR before ICI) ≥2. Circulating low density neutrophils (LDNs) subtypes were assessed by flow cytometry on peripheral blood mononuclear cells (PMBCs). LDNs were defined as CD66b+CD15+ cells among CD11b+ PBMCs. Immature subtypes were defined as CD10- LDNs. T-cells were isolated from healthy donors and cocultured with patients‘ LDNs to characterize the neutrophils-T-cells interplay. LDNs subtypes were isolated from patients and treated in-vitro with cisplatin to assess cell death. Results 46 NSCLC patients were treated with single-agent ICI and 17 with PCT+ICI (table 1). In the ICI single-agent cohort, PD and HPD occurred in 21 (41%) and 4 (9%) patients. Before ICI start, HPD patients had significantly higher median% of circulating immature CD10- LDNs neutrophils [43.5 (min 29.5; max 82.6) vs 10.3 (min 0.1; max 79.4), p=0.01] compared to PD patients (figure 1). In the ICI-PCT cohort no HPD was reported. 5 patients had baseline CD10- LDNs ≥ 43.5% (median% of CD10- LDNs in HPD patients upon single-agent ICI), 2 of them had stable disease and 3 PD upon ICI-PCT. In these 5 patients, CD10- LDNs significantly decreased during ICI-PCT compared to what observed in HPD patients upon single-agent ICI [median variation -43.4 (min -67.6, max -31.6) vs +6.9 (min -33, max +44), p= 0.03] (figure 2). After 7 days of coculture with T-cells, immature CD10- LDNs significantly reduced T-cells survival and promoted a T-cell senescent phenotype (CD28 loss, CD57 gain) impairing T-cells proliferation and increasing IFN-gamma production (figure 3). Cisplatin treatment significantly increased necrotic cell death among CD10- LDNs compared to CD10+ LDNs (figure 4). Abstract 15 Table 1 Patients characteristics in the single-agent ICI and PCT+ICI cohorts Abstract 15 Figure 1 Patterns of response, progression and hyperprogression to single-agent ICI and correlation with mature (CD10+) or immature (CD10-) LDNs’ subtypes Abstract 15 Figure 2 Neutrophils dynamic variation upon treatment (5 patients with high baseline CD10- LDNs and PD/SD to chemo-ICI vs 4 patients with HPD upon single-agent ICI) Abstract 15 Figure 3 Mature (CD10+) and immature (CD10-) LDNs in coculture with T-cells from an healthy donor differently influence CD8 and CD4 T-cells survival, proliferation, IFN-gamma production and expression of a senescent (CD28- CD57+) phenotype. Abstract 15 Figure 4 Cisplatin in-vitro treatment at different concentration (1 uM and 5 uM) increases necrotic (7AAD expression) cell death preferentially of immature (CD10-) rather than mature (CD10+) LDNs Conclusions Higher baseline immature CD10- LDNs impair T-cell survival and promote T-cell senescence being a circulating biomarker of HPD upon single-agent ICI. The addition of PCT prevents HPD by inducing immature neutrophils cell death. References Ferrara R, Mezquita L, Texier M, Lahmar J, Audigier-Valette C, Tessonnier L, et al . Hyperprogressive disease in patients with advanced non-small cell lung cancer treated with pd-1/pd-l1 inhibitors or with single-agent chemotherapy. JAMA Oncol 2018; 4 :1543–52. https://doi.org/10.1001/jamaoncol.2018.3676 Kim Y, Kim CH, Lee HY, Lee S-H, Kim HS, Lee S, et al. Comprehensive clinical and genetic characterization of hyperprogression based on volumetry in advanced non-small cell lung cancer treated with immune checkpoint inhibitor. J Thorac Oncol 2019; 14 :1608–18. https://doi.org/10.1016/j.jtho.2019.05.033 Ferrara R, Naigeon M, Auclin E, Duchemann B, Cassard L, Jouniaux JM, et al . Circulating T-cell immunosenescence in advanced non-small cell lung cancer patients treated with single agent PD-1/PD-L1 inhibitors or platinum-based chemotherapy. Clin Cancer Res 2020. https://doi.org/10.1158/1078-0432.CCR-20-1420. Ethics Approval Patients blood was obtained after signature of informed consent and within an observational prospective study (INT 22_15) approved by local Institutional Ethical Committee.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    URL: Article
    DOI: 10.1136/jitc-2021-SITC2021.015
    Language: English
    Publisher: BMJ
    Publication Date: 2021
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  • 5
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    Neurological manifestations of COVID-19 in adults and children
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 4 ( 2023-04-19), p. 1648-1661
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 4 ( 2023-04-19), p. 1648-1661
    Abstract: Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P & lt; 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac332
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 6
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    Clinical outcomes of NSCLC patients experiencing early immune-related adverse events to PD-1/PD-L1 checkpoint inhibitors leading to treatment discontinuation
    Springer Science and Business Media LLC ; 2022
    In:  Cancer Immunology, Immunotherapy Vol. 71, No. 4 ( 2022-04), p. 865-874
    Details
    In: Cancer Immunology, Immunotherapy, Springer Science and Business Media LLC, Vol. 71, No. 4 ( 2022-04), p. 865-874
    Type of Medium: Online Resource
    ISSN: 0340-7004 , 1432-0851
    URL: Article
    DOI: 10.1007/s00262-021-03045-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1458489-X
    detail.hit.zdb_id: 195342-4
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  • 7
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    Abstract 1669: Immunometabolism of circulating neutrophils in hyperprogressive disease (HPD) upon first-line PD-1/PD-L1 inhibitors (ICI) alone or in combination with platinum-based chemotherapy (PCT) in non-small cell lung cancer (NSCLC) patients (pts)
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 1669-1669
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 1669-1669
    Abstract: Background: HPD has been described in 14-26% of NSCLC pts upon single agent ICI and correlates with poor survival. Currently, HPD occurrence has not been explored upon ICI-PCT and biomarkers of HPD are lacking. Although high circulating neutrophils (Ns) correlated with HPD in NSCLC pts, the role of specific Ns subsets is unknown. Methods: NSCLC pts treated with 1st line ICI as single agent or in combination with PCT were assessed for HPD and circulating Ns' phenotype. Tumor response was evaluated by RECIST 1.1. HPD required 3 assessment (2 before ICI, 1 upon ICI) and was defined as delta tumor growth rate (TGR) (TGR upon ICI - TGR before ICI) & gt;50% and/or TGR ratio (TGR upon ICI/TGR before ICI) ≥2. Circulating low density Ns (LDNs) subtypes were assessed by flow cytometry (FC) on peripheral blood mononuclear cells (PBMCs). LDNs were defined as CD66b+CD15+ cells among CD11b+ PBMCs. Immature subtypes were defined as CD10- LDNs. Fatty acids (FA) (bodipy-palmitate) uptake was assessed by FC. T-cells of healthy donors were isolated and activated in vitro with CD3/CD28 beads in presence or not of pts' Ns to characterize their interplay. Results: Of 63 NSCLC pts, 22% had PD-L1 on tumor cells ≥50%. In the ICI single agent cohort (N=46), PD and HPD occurred in 21 (41%) and 4 (9%) pts, respectively. Before ICI start, HPD pts had significantly higher median percentage (%) of circulating immature CD10- LDNs [43.5 (min 29.5; max 82.6) vs 10.3 (min 0.1; max 79.4), p=0.01] compared to PD pts. In the ICI-PCT cohort (N=17), PD occurred in 4 (23%) pts, no HPD was reported. 5 pts had baseline CD10- LDNs ≥ 43.5% (median % of CD10- LDNs in HPD pts upon single agent ICI), 2 of them had SD and 3 PD upon ICI-PCT. In these 5 pts, CD10- LDNs significantly decreased during ICI-PCT compared to what observed in HPD pts during single agent ICI [median variation -43.4 (min -67.6, max -31.6) vs +6.9 (min -33, max +44), p= 0.03] . CD10- LDNs did not impair T-cells proliferation and IFNγ production, measured after 7 days of coculture but significantly reduced T-cell survival compared to CD10+LDNs. Baseline metabolic profile assessment showed that immature CD10- LDNs had a predominant lipid metabolism with a higher FA uptake [bodipy-palmitate mean florescence intensity (MFI) ± standard deviation (SD): 46754±11562] compared to lymphocytes [bodipy-palmitate MFI ±SD: 11542±405] . Conclusion: Higher baseline immature CD10- LDNs is a circulating biomarker of HPD upon single agent ICI. The addition of PCT prevents HPD reducing the immature Ns subset. The FA metabolism of immature LDNs does not affect T-cells proliferation/activation but reduces T-cells survival, suggesting that these two processes are differently regulated and that immature Ns reduce T-cells life span by metabolic competition. Citation Format: Roberto Ferrara, Elena Jachetti, Giuseppina Calareso, Marta Brambilla, Giuseppe Lo Russo, Claudia Proto, Arsela Prelaj, Diego Signorelli, Giulia Galli, Alessandro De Toma, Mario Occhipinti, Sara Manglaviti, Alice Labianca, Monica Ganzinelli, Sestina Maria Spanò, Giuliano Molino, Antonia Martinetti, Francesca Gabriella Greco, Marta Bini, Teresa Beninato, Filippo de Braud, Mario Paolo Colombo, Marina Chiara Garassino, Sabrina Sangaletti. Immunometabolism of circulating neutrophils in hyperprogressive disease (HPD) upon first-line PD-1/PD-L1 inhibitors (ICI) alone or in combination with platinum-based chemotherapy (PCT) in non-small cell lung cancer (NSCLC) patients (pts) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1669.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-1669
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
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    Abstract 5506: Circulating immature neutrophils early detect hyperprogressive disease upon first-line PD-1/PD-L1 inhibitors in non-small cell lung cancer patients selecting best candidates for platinum-based chemotherapy and PD-1/PD-L1 inhibitors combinations
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 5506-5506
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 5506-5506
    Abstract: Background: Hyperprogressive disease (HPD) has been described in ≃14-25% of pretreated non-small cell lung cancer (NSCLC) patients upon single-agent (SA) PD-1/PD-L1 inhibitors (ICI) and has not been reported upon platinum-based chemotherapy (PCT) and ICI combinations. So far, no predictive biomarkers are available for HPD early detection. Methods: NSCLC patients treated with 1st line SA-ICI or PCT-ICI were assessed for HPD and circulating neutrophils. HPD was defined as delta tumor growth rate (TGR) & gt;50% and/or TGR ratio ≥2. Circulating low density neutrophils (LDNs) were assessed by flow cytometry on peripheral blood mononuclear cells (PMBCs). LDNs were defined as CD66b+CD15+ cells among CD11b+ PBMCs and immature subtypes as CD10− LDNs. The LDNs predictive role was assessed by penalized model-based tests. Results: 144 NSCLC patients were included: 75 treated with SA-ICI, 69 with PCT-ICI. In the SA-ICI cohort, HPD occurred in 8 (11%) patients, while progressive disease (PD) and response or stable disease (PR/SD) occurred in 33 (44%) and 34 (45%) of patients respectively. Immature circulating CD10− LDNs were significantly higher in baseline blood samples of HPD patients [median (ME): 39.3, interquartile range (IQR): 28.7] compared to PD [ME: 7.4, IQR: 14.9, p & lt;0.01] or PR/SD patients [ME: 3.7, IQR: 12.6, p & lt;0.01]. Circulating CD10− LDNs were associated with HPD [odds ratio (OR): 1.17, 95% CI: 1.06; 1.29] , with a good prediction capability [cross-validated AUC 0.97 (95%CI: 0.94;1.00)]. A 30.5% cut-off value for CD10− LDNs circulating neutrophils was identified by Younden index to discriminate HPD from others. In the PCT-ICI cohort, 14 patients had circulating CD10− LDNs ≥30.5%, being at high risk of HPD. However, no HPD was observed in PCT-ICI cohort and dynamic LDNs evaluation in high HPD risk patients showed 52.3% (IQR: 28.4) median reduction in CD10− LDNs upon PCT-ICI, versus only 8.9% (IQR: 34.6) reduction in HPD patients upon SA-ICI, suggesting that PCT prevents HPD by reducing selectively immature LDNs. Conclusions: Baseline circulating immature neutrophils characterize HPD upon 1st line SA-ICI and a 30.5% cut-off of immature neutrophils could select NSCLC patients to be addressed to PCT-ICI combinations. Citation Format: Roberto Ferrara, Giuseppe Lo Russo, Chiara Maura Ciniselli, Annamaria Piva, Barbara Bassani, Elena Jachetti, Giuseppina Calareso, Valeria Duroni, Settimio Di Gregorio, Claudia Proto, Arsela Prelaj, Alessandro De Toma, Mario Occhipinti, Marta Brambilla, Sara Manglaviti, Laura Mazzeo, Arturo Rinaldi, Teresa Beninato, Monica Ganzinelli, Filippo De Braud, Marina Chiara Garassino, Paolo Verderio, Mario Paolo Colombo, Sabina Sangaletti. Circulating immature neutrophils early detect hyperprogressive disease upon first-line PD-1/PD-L1 inhibitors in non-small cell lung cancer patients selecting best candidates for platinum-based chemotherapy and PD-1/PD-L1 inhibitors combinations. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5506.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-5506
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
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  • 9
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    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study
    Springer Science and Business Media LLC ; 2021
    In:  Infection Vol. 49, No. 5 ( 2021-10), p. 889-905
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    In: Infection, Springer Science and Business Media LLC, Vol. 49, No. 5 ( 2021-10), p. 889-905
    Abstract: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P   〈  0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.
    Type of Medium: Online Resource
    ISSN: 0300-8126 , 1439-0973
    URL: Article
    DOI: 10.1007/s15010-021-01599-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 10
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    Su1536 DUODENOSCOPE-RELATED INFECTIONS: AN ITALIAN PICK IN 2019
    Elsevier BV ; 2020
    In:  Gastrointestinal Endoscopy Vol. 91, No. 6 ( 2020-06), p. AB369-
    Details
    In: Gastrointestinal Endoscopy, Elsevier BV, Vol. 91, No. 6 ( 2020-06), p. AB369-
    Type of Medium: Online Resource
    ISSN: 0016-5107
    URL: Article
    DOI: 10.1016/j.gie.2020.03.2382
    RVK:
    XA 44545
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2006253-9
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