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The recent evidences provided in metastatic hormone sensitive prostate cancer (nmHSPC) and in nonmetastatic castration resistant (nmCRPC) introduced the possibility to adopt Androgen Receptor Signaling inhibitor (ARSi) alone (both settings) or with chemotherapy (in mHSPC). In daily clinical practice there are some opening questions regarding the inclusion of next generation imaging, mainly PSMA-PET, how integrate local treatment as radiotherapy, how to select patients or drugs in a multiple-choice scenario, and how to manage patients with comorbidities and polypharmacy. These issues led the Italian Society for Uro-Oncology (SIUrO) to develop a consensus project involving all of the most important Italian scientific societies engaged in the multidisciplinary and multiprofessional management of the disease. This paper describes the items and statements approved, with the aim to support clinicians in managing metastatic hormone sensitive and nonmetastatic castration resistant prostate cancer patients., Competing Interests: Disclosure Nicolò Borsellino declares grants or contracts from Merck Serono and Pfizer; consulting fees from Bayer and Ipsen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from A.A.A./Novartis, Recordati industria chimica e farmaceutica, Ipsen, Amgen, AstraZeneca and MSD. Sergio Bracarda declares support for attending meetings and/or travel from MSD, Bayer, Pfizer; participation on a Data Safety Monitoring Board or Advisory Board for Bayer, Astellas, Janssen, Ipsen, Novartis, AstraZeneca. Orazio Caffo declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas, Astra Zeneca, Bayer, Janssen, Ipsen, MSD, Pfizer, Recordati; support for attending meetings and/or travel from Janssen, MSD, Ipsen; participation on a Data Safety Monitoring Board or Advisory Board for Astellas, Astra Zeneca, Bayer, MSD, Pfizer. Giuseppe Ferdinando Colloca declares unpaid leadership or fiduciary role in other board, society, committee or advocacy group for Gioger Gruppo italiano oncogeriatria and SIGG società italiana geriatria e gerontologia. Giario Natale Conti declares grants or contracts from Astellas, Janssen, Bayer–Orion, Ipsen, MSD, Recordati, Astrazeneca. Rolando M. D'Angelillo declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas, Janssen, Ipsen, Orion, AstraZeneca, Merck Serono; support for attending meetings and/or travel from Elekta, Tecnologie Avanzate, Tema Sinergie; participation on a Data Safety Monitoring Board or Advisory Board for Astellas, Bayer, Ferring, Janssen, Recordati. Marzia del Re declares consulting fees from Astellas, AstraZeneca, Celgene, Novartis, Pfizer, Bio-Rad, Janssen, Sanofi Aventis, Roche, MSD, Lilly, Ipsen; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, MSD, IPSEN, Janssen, Sanofi-Aventis, Amgen. Stefano Fanti declares grants or contracts from Amgen, Telix; consulting fees from AAA, Amgen, Novartis, Telix, Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AAA, Novartis, Bayer, Telix, Astra Zeneca, Janssen; support for attending meetings and/or travel from AAA, Bayer, Novartis, Telix; participation on a Data Safety Monitoring Board or Advisory Board for AAA, Novartis. Barbara Alicja Jereczek-Fossa declares grants or contracts from ACCURAY, AIRC, IBA, Fondazione IEO-CCM; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ACCURAY, ASTELLAS PHARMA, BAYER, ASTRA ZENECA, IBA, IPSEN, TECNOLOGIE AVANZATE, RECORDATI, NOVARTIS, ELSEVIER, ESO, ESTRO; participation on a Data Safety Monitoring Board or Advisory Board for IPSEN, ASTRA ZENECA, BAYER, SEAGEN, ASTELLAS PHARMA. Alberto Lapini declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from MSDR, ASTRA ZENECA; participation on a Data Safety Monitoring Board or Advisory Board for MEDAC, BAYER. Giovanni Pappagallo declares consulting fees from Astellas, Bayer, Astrazeneca, MSD. Tommaso Prayer Galetti declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Curium; support for attending meetings and/or travel from Ipsen, Recordati. All the other authors do not have any conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Sex may impact clinical outcomes in patients with stroke treated with dual antiplatelet therapy (DAPT). We aimed to investigate the sex differences in the short-term outcomes of DAPT within a real-world population of patients with noncardioembolic mild-to-moderate ischemic stroke or high-risk transient ischemic attack., Methods: We performed a propensity score-matched analysis from a prospective multicentric cohort study (READAPT [Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]) by including patients with noncardioembolic mild-to-moderate stroke (National Institutes of Health Stroke Scale score of 0-10) or high-risk transient ischemic attack (age, blood pressure, clinical features, duration of transient ischemic attack, presence of diabetes [ABCD 2 ] ≥4) who initiated DAPT within 48 hours of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale score ordinal shift, vascular and all-cause mortality, and 24-hour early neurological improvement or deterioration. The safety outcomes included the 90-day risk of moderate-to-severe and any bleeding, symptomatic intracranial hemorrhage, and 24-hour hemorrhagic transformation. Outcomes were compared between sexes using Cox and generalized ordinal logistic regression analyses, along with calculating risk differences and ratios., Results: From 2278 patients in the READAPT study cohort, we included 1643 mild-to-moderate strokes or high-risk transient ischemic attacks treated with DAPT (mean age, 69.8±12.0 years; 34.3% women). We matched 531 women and men. The 90-day risk of new ischemic stroke or other vascular events was significantly lower among women than men (hazard ratio, 0.53 [95% CI, 0.28-0.99]; P =0.039). There were no significant differences in secondary effectiveness outcomes. The 90-day risk of safety outcomes was extremely low and did not differ between women and men (moderate-to-severe bleedings: 0.4% versus 0.8%; P =0.413; symptomatic intracranial hemorrhage: 0.2% versus 0.4%; P =0.563). Subgroup analysis for primary effectiveness outcome showed a lower 90-day risk of new ischemic stroke or other vascular events among women aged <50 years, baseline National Institutes of Health Stroke Scale score of 0 to 5, prestroke modified Rankin Scale score <2, large artery atherosclerosis cause, and no diabetes., Conclusions: Our findings suggest that women with noncardioembolic mild-to-moderate stroke or high-risk transient ischemic attack treated with DAPT may have lower short-term risk of recurrent ischemic events than men. Further research is needed to understand the mechanisms behind potential sex-based differences in outcomes after DAPT use., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05476081., Competing Interests: Dr Piscaglia reports grants from Sanofi Genzyme, Roche Health Solutions, Inc, Novartis Pharma, Biogen, and Merck Company Foundation. Dr Paciaroni reports compensation from Boehringer Ingelheim, PFIZER CANADA INC, Bristol-Myers Squibb; iRhythm Technologies; SANOFI-AVENTIS U.S. LLC, and Daiichi Sankyo Europe GmbH for other services. Dr Zini reports compensation from Bayer Healthcare for other services and Boehringer Ingelheim, Alexion Pharmaceuticals, and CSL Behring for consultant services. Dr Ornello reports grants from Novartis, Pfizer, and Allergan and compensation from Teva Pharmaceutical Industries, Eli Lilly and Company, Novartis, and H. Lundbeck A S for other services; AbbVie and Eli Lilly for data and safety monitoring services; Teva Pharmaceutical Industries for consultant services; and reports and travel support from Teva Pharmaceutical Industries. Dr Sacco reports compensation from Novartis for other services; compensation from Novo Nordisk, Boehringer Ingelheim, Teva Pharmaceutical Industries, Allergan, Novartis, PFIZER CANADA INC, Abbott Canada, H. Lundbeck A S, AstraZeneca, and Eli Lilly and Company for consultant services; and employment by Università degli Studi dell’Aquila. The other authors report no conflicts.

Introduction: Infectious disease treatments are transitioning from a one-size-fits-all approach to a more tailored approach. The increasing adoption of therapeutic drug monitoring (TDM) of antimicrobials is a clear example of this trend. Routine antimicrobial TDM in critically ill patients should be mandatory. Unfortunately, nowadays, only expert centers can provide it. Given the crucial nature of the first hours/days for achieving a favorable clinical outcome, empirical antibiotic therapy with an adequate choice of drug, dose and administration modalities is fundamental., Areas Covered: We outline common scenarios encountered in clinical practice, such as in edematous patients, hypoalbuminemia, patients with liver and renal diseases, patients under renal replacement therapy or extracorporeal membrane oxygenation (ECMO), over or under-weight patients, in old adults and cases of infections caused by relatively high minimum inhibitory concentration (MIC) pathogens. Various clinical situations were analyzed with the help of the available literature (PubMed/MEDLINE/Google Scholar and books written by experts in pharmacology and infectious diseases)., Expert Opinion: In these different scenarios, we reported common examples of optimizing drug utilization to maximize therapeutic outcomes, reduce incorrect prescriptions and limit the emergence of antimicrobial resistance.

Background: According to the literature, about one third of patients with brain ischemic symptoms lasting <24 h, which are classified as Transient ischemic attacks (TIAs) according to the traditional "time-based" definition, show the presence of acute ischemic lesions at neuroimaging. Recent evidence has shown that the presence of acute ischemic lesions at neuroimaging may impact on the outcome of patients with transient ischemic symptoms treated with dual antiplatelet treatment (DAPT). This uncertainty is even more compelling in recent years as short-term DAPT has become the standard treatment for any non-cardioembolic TIA or minor ischemic stroke., Methods: This is a pre-specified subgroup analysis from a prospective multicenter real-world study (READAPT). The analysis included patients with time-based TIA-that is, those with ischemic symptoms lasting <24 h-who started DAPT. In the whole population, we assessed the presence of acute brain ischemic lesions at neuroimaging and their association with the ABCD 2 score. To assess the impact of acute brain ischemic lesions on 90-day prognosis, we performed a propensity score matching of patients with and without those lesions. We adopted a primary effectiveness outcome which was a composite of new stroke/TIA events and death due to vascular causes at 90 days., Results: We included 517 patients-324 (62.7%) male-with a median (interquartile range-IQR) age of 74 (IQR = 65-81) years; 144 patients (27.9%) had acute brain ischemic lesions at neuroimaging. The proportion of patients with brain ischemic lesions did not vary according to the ABCD 2 score. At follow-up, 4 patients with brain ischemic lesions (2.8%) and 21 patients without lesions (5.6%) reported the primary effectiveness outcome, which was similar between the groups before ( p  = 0.178) and after matching ( p  = 0.518)., Conclusions: In our population, patients with transient ischemic symptoms and acute ischemic lesions at brain magnetic resonance imaging (MRI) had a risk of recurrent ischemic events similar to those without lesions. The risk of recurrent ischemic events was low in both groups., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.Z. reports compensation from Angels Initiative, Boehringer-Ingelheim, and Daiichi Sankyo for consultant services; from Angels Initiative, Boehringer-Ingelheim, and CSL Behring for speaking honoraria or other education services; from Daiichi Sankyo for meeting; from Bayer and Astra Zeneca for participation on a Data Safety, Monitoring Board or Advisory Board; and he is member of ESO guidelines, ISA-AII guidelines, and IRETAS steering committee. R.O. reports grants from Novartis and Allergan; compensation from Teva Pharmaceutical Industries, Eli Lilly and Company, and Novartis for other services; and travel support from Teva Pharmaceutical Industries. S.S. reports compensation from Novartis, NovoNordisk, Allergan, AstraZeneca, Pfizer Canada, Inc., Eli Lilly and Company, Teva Pharmaceutical Industries, H. Lundbeck A/S, and Abbott Canada for consultant services; employment by Università degli Studi dell’Aquila; and compensation from Novartis for other services. MP reports compensation from Daiichi Sankyo Company, Bristol Myers Squibb, Bayer, and Pfizer Canada, Inc., for consultant services. DT reports compensation from Alexion, Astra Zeneca, Medtronic, and Pfizer for consultant services and participation on a Data Safety, Monitoring Board or Advisory Board. The other authors report no conflicts.

Background: Short-term dual antiplatelet treatment (DAPT) is superior to single antiplatelet treatment (SAPT) for secondary prevention in non-cardioembolic minor ischemic stroke and high-risk transient ischemic attack (TIA). As the real-world use of DAPT is broader than in trials, it is important to clarify its benefit/risk profile in a diverse population., Methods: Post hoc analysis of prospectively collected data from the READAPT cohort and three prospective stroke registries including patients with mild-to-moderate (National Institute of Health Stroke Scale (NIHSS) score 0-10) ischemic stroke receiving early DAPT or SAPT. The primary effectiveness outcome was 90-day return to pre-stroke neurological functioning using modified Rankin Scale (mRS) score. Secondary effectiveness outcomes were 90-day mRS shift, new ischemic stroke/TIA, vascular and all-cause death, 24 h early neurological improvement or deterioration. The safety outcome was 90-day intracranial hemorrhage., Results: We matched 1008 patients treated with DAPT and 1008 treated with SAPT. Compared to SAPT, patients treated with DAPT showed higher likelihood of 90-day primary effectiveness outcome (87.5% vs. 84.4%, risk difference 3.1% (95% confidence interval (CI): 0.1%-6.1%); p = 0.047, risk ratio 1.03 (95% CI: 1.01-1.07); p = 0.043) and higher rate of 24-h early neurological improvement (25.3% vs. 15.4%, risk difference 9.9% (95% CI: 6.4%-13.4%); p < 0.001, risk ratio 1.65 (95% CI: 1.37-1.97); p < 0.001). No differences were observed for other study outcomes. Subgroup analysis confirmed benefit of DAPT over SAPT for primary effectiveness outcome in patients with moderate stroke, those treated with intravenous thrombolysis, and those who received antiplatelet loading dose., Conclusion: Our findings suggest that DAPT use might be safe and more effective than SAPT even in the real world and in patients who do not strictly fulfill the criteria of landmark large clinical trials., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AZ reports compensation from Angels Initiative, Boehringer-Ingelheim, Daiichi Sankyo for consultant services; from Angels Initiative, Boehringer-Ingelheim, CSL Behring for speaking honoraria or other education services; from Daiichi Sankyo for meeting; from Bayer, and Astra Zeneca for participation on a Data Safety, Monitoring or Advisory Board; he is member of ESO guidelines, ISA-AII guidelines, and IRETAS steering committee. RO reports grants from Novartis and Allergan; compensation from Teva Pharmaceutical Industries, Eli Lilly and Company, and Novartis for other services; and travel support from Teva Pharmaceutical Industries. SS reports compensation from Novartis, NovoNordisk, Allergan, AstraZeneca, Pfizer Canada, Inc, Eli Lilly and Company, Teva Pharmaceutical Industries, H. Lundbeck A/S, and Abbott Canada for consultant services; compensation from Novartis for other services. MP reports compensation from Daiichi Sankyo Company, Bristol Myers Squibb, Bayer, and Pfizer Canada, Inc., for consultant services. The other authors report no conflicts.

Background : Biofilm-associated infections frequently span multiple body sites and represent a significant clinical challenge, often requiring a multidisciplinary approach involving surgery and antimicrobial therapy. These infections are commonly healthcare-associated and frequently related to internal or external medical devices. The formation of biofilms complicates treatment, as they create environments that are difficult for most antimicrobial agents to penetrate. Fluoroquinolones play a critical role in the eradication of biofilm-related infections. Numerous studies have investigated the synergistic potential of combining fluoroquinolones with other chemical agents to augment their efficacy while minimizing potential toxicity. Comparative research suggests that the antibiofilm activity of fluoroquinolones is superior to that of beta-lactams and glycopeptides. However, their activity remains less effective than that of minocycline and fosfomycin. Noteworthy combinations include fluoroquinolones with fosfomycin and aminoglycosides for enhanced activity against Gram-negative organisms and fluoroquinolones with minocycline and rifampin for more effective treatment of Gram-positive infections. Despite the limitations of fluoroquinolones due to the intrinsic characteristics of this antibiotic, they remain fundamental in this setting thanks to their bioavailability and synergisms with other drugs. Methods : A comprehensive literature search was conducted using online databases (PubMed/MEDLINE/Google Scholar) and books written by experts in microbiology and infectious diseases to identify relevant studies on fluoroquinolones and biofilm. Results : This review critically assesses the role of fluoroquinolones in managing biofilm-associated infections in various clinical settings while also exploring the potential benefits of combination therapy with these antibiotics. Conclusions : The literature predominantly consists of in vitro studies, with limited in vivo investigations. Although real world data are scarce, they are in accordance with fluoroquinolones' effectiveness in managing early biofilm-associated infections. Also, future perspectives of newer treatment options to be placed alongside fluoroquinolones are discussed. This review underscores the role of fluoroquinolones in the setting of biofilm-associated infections, providing a comprehensive guide for physicians regarding the best use of this class of antibiotics while highlighting the existing critical issues.

Background and Purpose: Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs., Methods: READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD 2 score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment., Results: We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding., Conclusions: In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AZ reports compensation from Angels Initiative, Boehringer-Ingelheim, Daiichi Sankyo, CSL Behring, Bayer, and Astra Zeneca; and he is member of ESO guidelines, ISA-AII guidelines, and IRETAS steering committee. RO reports compensations from Novartis and Allergan, Teva Pharmaceutical Industries, Eli Lilly and Company, SS reports compensations from Novartis, NovoNordisk, Allergan, AstraZeneca, Pfizer Canada, Inc, Eli Lilly and Company, Teva Pharmaceutical Industries, H. Lundbeck A/S, and Abbott Canada; employment by Università degli Studi dell’Aquila. MPa reports compensation from Daiichi Sankyo Company, Bristol Myers Squibb, Bayer, and Pfizer Canada, Inc. DT reports compensation from Alexion, AstraZeneca, Medtronic, and Pfizer. The other authors report no conflicts.

Objectives: To retrospectively investigate whether a case-by-case combination of the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS) with the Likert score improves the diagnostic performance of mpMRI for clinically significant prostate cancer (csPCa), especially by reducing false-positives., Methods: One hundred men received mpMRI between January 2020 and April 2021, followed by prostate biopsy. Reader 1 (R1) and reader 2 (R2) (experience of > 3000 and < 200 mpMRI readings) independently reviewed mpMRIs with the PI-RADS version 2.1. After unveiling clinical information, they were free to add (or not) a Likert score to upgrade or downgrade or reinforce the level of suspicion of the PI-RADS category attributed to the index lesion or, rather, identify a new index lesion. We calculated sensitivity, specificity, and predictive values of R1/R2 in detecting csPCa when biopsying PI-RADS ≥ 3 index-lesions (strategy 1) versus PI-RADS ≥ 3 or Likert ≥ 3 index-lesions (strategy 2), with decision curve analysis to assess the net benefit. In strategy 2, the Likert score was considered dominant in determining biopsy decisions., Results: csPCa prevalence was 38%. R1/R2 used combined PI-RADS and Likert categorization in 28%/18% of examinations relying mainly on clinical features such as prostate specific antigen level and digital rectal examination than imaging findings. The specificity/positive predictive values were 66.1/63.1% for R1 (95%CI 52.9-77.6/54.5-70.9) and 50.0/51.6% (95%CI 37.0-63.0/35.5-72.4%) for R2 in the case of PI-RADS-based readings, and 74.2/69.2% for R1 (95%CI 61.5-84.5/59.4-77.5%) and 56.6/54.2% (95%CI 43.3-69.0/37.1-76.6%) for R2 in the case of combined PI-RADS/Likert readings. Sensitivity/negative predictive values were unaffected. Strategy 2 achieved greater net benefit as a trigger of biopsy for R1 only., Conclusion: Case-by-case combination of the PI-RADS version 2.1 with Likert score translated into a mild but measurable impact in reducing the false-positives of PI-RADS categorization, though greater net benefit in reducing unnecessary biopsies was found in the experienced reader only., (© 2024. The Author(s).)

Clostridium perfingens bloodstream infections (BSIs) can be associated with high mortality rates. We performed a subanalysis of all C. perfringens BSIs enrolled during a multicentric retrospective observational study (ITANAEROBY). Data were collected from January 2016 to December 2020. C. perfringens BSIs were 134 (134/1960, 6.8 %). The highest resistance rate was observed for clindamycin (26/120, 21.6 %), penicillin (11/71, 15.4 %) and metronidazole (14/131, 10.7 %). In conclusion, C. perfringens reduced susceptibility phenotype to first-line therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In the past decade, there has been considerable progress in the treatment of adults with newly diagnosed B-cell acute lymphoblastic leukaemia. This evolution is the product of a more profound understanding of acute lymphoblastic leukaemia biology, innovations in measurable residual disease quantification that led to precise disease-risk stratification, adoption of contemporary paediatric-inspired regimens, inclusion of tyrosine kinase inhibitors in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia, and the introduction of immunotherapy in the frontline setting. Nevertheless, outcomes of acute lymphoblastic leukaemia in adults are inferior compared with those of children, with excessive rates of treatment failure, and therapy-related morbidity and mortality. Simultaneously, transplant consolidation has continued to be used frequently for high-risk adults with acute lymphoblastic leukaemia in first complete remission. Considering the rapid pace of evolution in acute lymphoblastic leukaemia management, novel trial designs are warranted to accelerate advancements and streamline approaches. Here, we summarise progress in the treatment of adults with newly diagnosed acute lymphoblastic leukaemia, which adds to previously published guidelines by focusing specifically on first-line decisions for B-cell acute lymphoblastic leukaemia and how to best personalise treatment. This Viewpoint also includes experiences with regimens and testing approaches currently available not only in Europe, but also on multiple continents with different practices and resources., Competing Interests: Declaration of interests IA reports research support from AbbVie and MacroGenics and being on advisory boards for Gilead/Kite, Amgen, Jazz, Syndax, Wugen, Takeda, and Pfizer. GJR is a consultant for Agios, Amgen, Amphivena, Astex, Celator, Celgene, Clovis Oncology, CTI BioPharma, Genoptix, Immune Pharmaceuticals, Janssen Pharmaceuticals, Juno, MedImmune, MEI Pharma, Onconova, Pfizer, Roche, and Sunesis; receives research funding from AbbVie, BMS, Teva, and Karyopharm; is an advisory board member or consultant for Novartis, AbbVie, BeiGene, BerGenBio, Arcellx, Jazz Pharmaceuticals, Syros, BMS, Genentech, ImmunoGen, AstraZeneca, Kura, Ryvu, Magenta, and Qihan Zentalis; and has provided research support to Janssen. RB reports participation in meetings and advisory boards (including fees, travel, and accommodations) for Amgen and Incyte. NB reports honorarium from Amgen, Celgene, Jazz Pharmaceuticals, and Pfizer; and has a consulting or advisory role for Amgen, Novartis, Pfizer, and Servier. DJD is a consultant for Amgen, Autolus, Agios, Blueprint, Forty-Seven, Gilead, Incyte, Jazz, Novartis, Pfizer, Servier, and Takeda; has received research funding from AbbVie, Glycomimetics, Novartis, and Blueprint Pharmaceuticals; is on a data safety monitoring board for Daiichi Sankyo and FibroGen; and is a member of Mt Sinai Myeloproliferative Neoplasms Research Consortium. SF reports research support from Amgen and Pfizer; speaker's honorarium from Amgen, Pfizer, Astellas, Jazz, Gilead/Kite, and Novartis; advisory board membership for Amgen, Pfizer, Astellas, Jazz, and Gilead/Kite. NG reports honoraria from Amgen, Pfizer, Kite/Gilead, Jazz Pharmaceuticals, Incyte, Autolus, Clinigen Group, and Servier; research funding from Amgen, Pfizer, Novartis, Servier, Jazz Pharmaceuticals), Incyte, and Clinigen Group. ACL reports consulting or advisory role for Amgen, Pfizer, Sanofi, Kite, and Takeda; research funding from Astellas Pharma, Pharmacyclics, Kite/Gilead, Kadmon, Amgen, Autolus, Talaris; and travel, accommodations, and expenses from Amgen. SML reports honoraria from Astellas, Daiichi Sankyo, Novartis, Marker Therapeutics, AbbVie, Amgen, Bristol-Myers Squibb, Pluristem, Syros, and Agios; and research funding from BioSight (previous funding from Onconova, Celgene, Hoffman LaRoche, and Kura [travel included]). TM reports travel grants from Amgen, Jazz, Pfizer, Bayer, Kyowa Kirin, Celgene/BMS, Kite/Gilead, Janssen, and Takeda; honoraria for advisory board meetings from Kite/Gilead, Amgen, Novartis, Pfizer, Celgene/BMS, Daiichi Sankyo, Atara, Roche, and Janssen; honoraria for lectures from Kite/Gilead, Takeda, Janssen, Roche, Servier, Novartis, Celgene/BMS, Pfizer, and Incyte; and research funding from Janssen, AstraZeneca, and Novartis. JP reports consulting fees from AffyImmune Therapeutics, Amgen, Autolus, Be Biopharma, BeiGene, Bright Pharmaceutical Services, Curocell, Kite, Medpace, Minerva Biotechnologies, Pfizer, Servier, Sobi, Synthekine, and Takeda; honoraria from OncLive, Physician Education Resource, and MJH Life Sciences; serves on scientific advisory board of Allogene Therapeutics and Artiva Biotherapeutics; received institutional research funding from Autolus, Genentech, Fate Therapeutics, Incyte, Servier, and Takeda. ACS reports honoraria from Celgene, Amgen, Pfizer, Novartis, and Jazz Pharmaceuticals; and research funding from Celgene, Amgen, Agios, and Pfizer. BS reports honoraria from Pharmacyclics/Janssen, Spectrum/Acrotech, BeiGene, Gilead Sciences; consulting or advisory role for Adaptive Biotechnologies, Bristol Myers Squibb/Celgene, Novartis, Pfizer, Amgen, Precision Biosciences, Kite, Jazz Pharmaceuticals, Century Therapeutics, Deciphera, Autolus, Lilly, Pepromene; research funding from Incyte, Jazz Pharmaceuticals, Kite/Gilead, and Servier; and travel, accommodations, and expenses from Celgene, Novartis, Pfizer, Janssen, Seattle Genetics, AstraZeneca, Stemline Therapeutics, and Kite. EJ reports research grants and consultancy fees from AbbVie, Adaptive Biotechnologies, Amgen, Ascentage, Autolus, Bristol Myers Squibb, Hikma, Genentech, Jazz, Kite, Novartis, Pfizer, and Takeda., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn's disease (CD). Only limited real-life data on the long-term outcomes of CD patients treated with UST are available. This study assessed UST's long-term effectiveness and safety in a large population-based cohort of moderate to severe CD patients. Methods: This was a multicenter, retrospective, observational cohort study that included both naïve and biologic-experienced patients treated with UST who achieved clinical remission or clinical response after at least one year of treatment. Clinical activity was scored according to the Harvey-Bradshaw Index (HBI). The primary endpoints were the maintenance or achievement of clinical remission after a further 12-month period of treatment, defined as an HBI of ≤5, and safety. Other endpoints included steroid-free remission, mucosal healing (MH), steroid discontinuation, and the need for treatment optimization during the follow-up. Results: Out of 562 CD patients, after an overall 24-month follow-up, clinical remission was present in 450 (80.0%) patients, and at 12 months, clinical remission was observed in 417/437 (95.4%) patients; 33/125 (26.4%) showed clinical response at 12 months ( p = 0.000). A total of 38/103 (36.9%) patients achieved MH. Only 2.1% (12/562), 3% (17/562), and 1.1% (6/562) of patients required surgery, optimization, and re-induction, respectively. Adverse events occurred in eight patients (1.42%). According to a multivariate analysis, the only predictor of long-term remission was the presence of remission at the 12-month follow-up ( p = 0.000). Conclusions : Long-term treatment with UST presents good efficacy and safety profiles in CD patients, especially for patients who achieve remission after one year.

Background: The outcomes of minor ischemic stroke resulting from small artery occlusion (SAO-MIS) have not yet been characterized after dual antiplatelet treatment (DAPT) has become the standard of care. We provided updated figures on the short-term prognosis of SAO-MIS treated with early short-term DAPT and compared the outcomes of SAO-MIS versus non-SAO-MIS patients., Methods: This is a prespecified sub-analysis from a prospective multicentric real-world study (READAPT, NCT05476081) including patients with minor (NIHSS≤5) non-cardioembolic ischemic stroke treated with DAPT. The primary outcome was a composite of 90-day symptomatic ischemic stroke or major cardiovascular events. Secondary outcomes were the 90-day ordinal distribution of modified Rankin Scale (mRS) scores, 90-day excellent functional outcome (mRS of 0 to 1), and 24-h early neurological deterioration (END). Safety outcomes were 90-day intracerebral hemorrhage, moderate-to-severe and any bleedings. All outcomes were compared between SAO-MIS and non-SAO-MIS patients., Results: We included 678 MIS, of whom 253 (37.3 %) were SAO-related. At 90 days, 3 patients with SAO-MIS had primary outcome (1.2 % [95 % CI 0.2 %-3.5 %]), which were all SAO-related ischemic strokes. For the secondary outcomes, most SAO-MIS patients (n = 191, 75.5 %) had 90-day excellent functional outcome and 12 had 24-h END (4.7 % [95 % CI 2.5 %-8.3 %]). Referring to safety outcomes, 90-day intracerebral hemorrhage occurred only in one patient with SAO-MIS (0.4 % [95 % CI 0.0 %- 2.2 %]). Compared to non-SAO-MIS, the 90-day risk of recurrent vascular events was significantly lower among SAO-MIS (aHR 0.24 [95 % CI 0.08-0.68]; p = 0.007), while there were not significant differences in other secondary outcomes, nor in the risk of safety events., Conclusions: Our findings show overall favorable short-term prognosis after SAO-MIS treated with DAPT. Future studies should investigate factors associated with residual stroke risk and long-term outcomes of SAO-MIS., Competing Interests: Declaration of competing interest Andrea Zini reports compensation from Angels Initiative, Boehringer-Ingelheim, Daiichi Sankyo for consultant services; from Angels Initiative, Boehringer-Ingelheim, CSL Behring for speaking honoraria or other education services; from Daiichi Sankyo for meeting; from Bayer, and Astra Zeneca for participation on a Data Safety, Monitoring Board or Advisory Board; and he is member of ESO guidelines, ISA-AII guidelines, and IRETAS steering committee. Raffaele Ornello reports grants from Novartis and Allergan; compensation from Teva Pharmaceutical Industries, Eli Lilly and Company, and Novartis for other services; and travel support from Teva Pharmaceutical Industries. Simona Sacco reports compensation from Novartis, NovoNordisk, Allergan, AstraZeneca, Pfizer Canada, Inc., Eli Lilly and Company, Teva Pharmaceutical Industries, H. Lundbeck A/S, and Abbott Canada for consultant services; employment by University of L'Aquila; and compensation from Novartis for other services. Maurizio Paciaroni reports compensation from Daiichi Sankyo Company, Bristol Myers Squibb, Bayer, and Pfizer Canada, Inc., for consultant services. Danilo Toni reports compensation from Alexion, Astra Zeneca, Medtronic, and Pfizer for consultant services and participation on a Data Safety, Monitoring Board or Advisory Board. The other authors report no conflicts., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Acanthamoeba keratitis (AK) is a rare sight-threatening infectious disease with no approved pharmacological treatments . Topical polihexanide 0.8 mg/ml (PHMB 0.08%) completed a pivotal clinical trial showing a medical cure rate of 84.9%. The purpose of this study is to evaluate the efficacy and safety of PHMB 0.08%, given as monotherapy, in clinical practice., Methods: consecutive cases of AK were included. Diagnosis was confirmed by in vivo confocal microscopy or PCR. Patients were treated with PHMB 0.08% as part of a name-based compassionate use program. Treatment delivery frequency and termination were as advised in the pivotal clinical trial. Medical cure was defined as clinical evidence of healed epithelium and absence of corneal inflammation lasting 3 months after discontinuing all treatments., Results: twelve eyes of 11 contact lens wearers with AK of variable severity were evaluated. Eleven of 12 (91.7%) eyes achieved a medical cure with no surgery. One eye had a corneal perforation and required emergency therapeutic keratoplasty. The median time of treatment with PHMB 0.08% was 100 days (range 35-222). Seven eyes (58.3%) reached a final visual acuity of 20/50 Snellen or better. Two subject reported worsening of conjunctival hyperaemia during the intensive phase of the treatment. No other adverse drug reactions were observed., Conclusion: topical treatment with PHMB 0.08% monotherapy successfully cured AK in 11 of 12 eyes when used in real-world clinical practice, thereby confirming that results observed in the clinical trial could be obtained in this setting., Competing Interests: Declaration of conflicting interestsThe authors declare that they have no competing interest. Vincenzo Papa is employee of SIFI S.p.A. (manufacturer of PHMB 0.08%).

(1) Background/Objectives: Nail psoriasis (NP) is a chronic and difficult-to-treat disease, which causes significant social stigma and impairs the patients' quality of life. Moreover, nail psoriasis is a true therapeutic challenge for clinicians. The presence of nail psoriasis can be part of a severe form of psoriasis and can have predictive value for the development of psoriatic arthritis. Our real-world-evidence multicenter study aims to evaluate the efficacy of bimekizumab in nail psoriasis. (2) Methods: A retrospective analysis of a multicenter observational study included 834 patients affected by moderate-to-severe psoriasis, in 33 Dermatologic Units in Italy, treated with bimekizumab from December 2022 to September 2023. Clinimetric assessments were based on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Physician's Global Assessment of Fingernail Psoriasis (PGA-F) for the severity of nail psoriasis at 0, 12, 24, and 36 weeks. (3) Results: Psoriatic nail involvement was present in 27.95% of patients. The percentage of patients who achieved a complete clearance of NP in terms of PGA-F 0 was 31.7%, 57%, and 88.5% at week 4, 16, and 36, respectively. PASI 100 was achieved by 32.03% of patients at week 4, by 61.8% at week 16, and by 78.92% of patients at week 36. The mean baseline PASI was 16.24. The mean DLQI values for the entire group of patients at baseline, at week 4, at week 16, and at week 36 were 14.62, 3.02, 0.83, and 0.5, respectively. (4) Conclusions: Therapies that promote the healing of both the skin and nails in a short time can also ensure a lower risk of subsequently developing arthritis which is disabling over time. Bimekizumab proved to be particularly effective to treat NP, with a fast response in terms of complete clearance, with over 88.5% of patients free from NP after 36 weeks. The findings of our real-world study showed that patients with moderate-to-severe PsO and concomitant NP had significantly faster and more substantial improvements in NP up to 36 weeks with respect to previous research findings. Considering the rapid healing of the nail, the dual inhibition of IL17 A and F might have a great value in re-establishing the dysregulation of keratin 17 at the nail level.

VEXAS syndrome is a newly described autoinflammatory entity characterized by somatic mutations in the UBA1 X-linked gene in hematopoietic progenitor cells. Several studies have demonstrated that the presence of vacuoles in progenitor cells from bone marrow aspirates is a hallmark finding for this syndrome. Therefore, this study aimed to characterize leukocytes from VEXAS patients versus patients with ANCA-associated vasculitis (AAV), familial Mediterranean fever (FMF), and healthy donors (HD) to define a specific cytological pattern that can support VEXAS diagnosis. Twelve VEXAS patients were included in the study. Blood samples from FMF (n = 16), AAV (n = 16) and HDs (n = 20) acted as controls. May-Grünwald Giemsa (MGG) staining was used for studying cellular morphology, including cytoplasm, granules, and vacuoles and to perform a cytogenic evaluation of leucocytes. Plasma IL-1β, IL-1α, TNFα, IL-18 and IL-8 were measured using ELISA assay. The cytological analysis from blood smears confirmed the presence of immature neutrophils in VEXAS patients. We found a greater number of vacuoles in VEXAS patients vs. FMF, AAV and HD. Micronuclei (MNi) and cell death rate were higher in VEXAS patients vs. HD. Cell death correlated with IL-1β and IL-8 levels. MNi were positively associated with IL-8 and IL-1β levels, and with the percentage of immature neutrophils and vacuoles. In conclusion, our findings suggested that cytological test may be supportive for VEXAS diagnosis, despite genetical analysis is mandatory for confirming the disease. Finally, we identified several cytological hallmarks that may distinguish the VEXAS "cytotype" not only from HD but also from other inflammatory diseases., Competing Interests: AD received consultancy fees from GSK, Eli Lilly, AstraZeneca, Otsuka. PS received grants from Novartis and Sobi. Authors DC, BP and GP were employed by R&I Genetics srl. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Baggio, Oliviero, Padoan, Iorio, Bixio, Orsolini, Bertoldo, Bernardi, Colavito, Paiero, Pregnolato, Ramonda, Doria, Bindoli and Sfriso.)

Cigarette smoke (CS) is a major risk factor for chronic lung diseases and promotes activation of pattern recognition receptors in the bronchial epithelium. NOD-like receptor family, pyrin domain-containing 3 (NLRP3) is a pattern recognition receptor whose activation leads to caspase-1 cleavage, maturation/release of IL-1β and IL-18, and eventually pyroptosis. Whether the NLRP3 inflammasome participates in CS-induced inflammation in bronchial epithelial cells is still unclear. Herein, we evaluated the involvement of NLRP3 in CS-induced inflammatory responses in human primary bronchial epithelial cells. To this purpose, human primary bronchial epithelial cells were stimulated with CS extracts (CSE) and lytic cell death, caspase activation (-1, -8, -3/7), cytokine release (IL-1β, IL-18, and IL-8), NLRP3, pro-IL-1β/pro-IL-18 mRNA, and protein expression were measured. The impact of inhibitors of NLRP3 (MCC950), caspases, and the effect of the antioxidant N-acetyl cysteine were evaluated. We found that CSE increased pro-IL-1β expression and induced activation of caspase-1 and release of IL-1β and IL-18. These events were independent of NLRP3 and we found that NLRP3 was not expressed. N-acetyl cysteine reverted CSE-induced caspase-1 activation. Overall, our findings support that the bronchial epithelium may play a central role in the release of IL-1 family cytokines independently of NLRP3 in the lungs of smokers., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)

Introduction: Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics., Methods: In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics., Results: Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01-6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05-72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16-0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively., Conclusions: Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches., (© 2024. The Author(s).)

This study investigates the prevalence and patterns of transmitted drug resistance mutations (TDRMs) and HIV-1 subtypes among antiretroviral therapy (ART) naïve individuals in Veneto, Italy, from 2017 to 2024. This research aims to understand the dynamic landscape of TDRMs and HIV-1 genetic diversity to inform treatment strategies effectively. We included all adult ART-naïve people with HIV (PWH) from seven infectious disease units in Veneto, Italy. We collected the genotypic resistance testing conducted to predict drug susceptibility and subtype distribution using the Stanford HIVdb algorithm. We included 762 PWH, showing a slight but statistically significant decline in the B subtype among Italian PWH ( p = 0.045) and an increase in non-B subtypes among foreigners, though it was not statistically significant ( p = 0.333). The most frequent mutations were in Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), especially in non-B subtypes, with a notable rise from 10.7% in 2017-2019 to 15.5% in 2020-2024. Notably, TDRMs were consistently detected, highlighting an ongoing challenge despite the stable prevalence observed over the years. In addition, the data revealed a concerning rise in mutations against newer drug classes, such as integrase inhibitors. Conclusively, the study underscores the necessity of continuous surveillance of HIV subtypes and resistance patterns to adapt ART regimens optimally. Despite the stable levels of drug resistance, the emergence of resistance against newer drugs necessitates ongoing vigilance and possible adjustment in treatment protocols to enhance clinical outcomes and manage HIV drug resistance effectively.

Background: The optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS., Methods and Results: This is a prespecified propensity score-matched analysis from a prospective multicentric real-world study (READAPT [Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]). We included patients with MIS (National Institutes of Health Stroke Scale score at admission ≤5), without prestroke disability (modified Rankin scale [mRS] score ≤2). The primary outcomes were 90-day mRS score of 0 to 2 and ordinal mRS distribution. The secondary outcomes included 90-day risk of stroke and other vascular events and 24-hour early neurological improvement or deterioration (≥2-point National Institutes of Health Stroke Scale score decrease or increase from the baseline, respectively). From 1373 patients with MIS, 240 patients treated with IVT plus DAPT were matched with 427 patients treated with DAPT alone. At 90 days, IVT plus DAPT versus DAPT alone showed similar frequency of mRS 0 to 2 (risk difference, 2.3% [95% CI -2.0% to 6.7%]; P =0.295; risk ratio, 1.03 [95% CI 0.98-1.08]; P =0.312) but more favorable ordinal mRS scores distribution (odds ratio, 0.57 [95% CI 0.41-0.79]; P <0.001). Compared with patients treated with DAPT alone, those combining IVT and DAPT had higher 24-hour early neurological improvement (risk difference, 20.9% [95% CI 13.1%-28.6%]; risk ratio, 1.59 [95% CI 1.34-1.89]; both P <0.001) and lower 90-day risk of stroke and other vascular events (hazard ratio, 0.27 [95% CI 0.08-0.90]; P =0.034). There were no differences in safety outcomes., Conclusions: According to findings from this observational study, patients with MIS may benefit in terms of better functional outcome and lower risk of recurrent events from combining IVT and DAPT versus DAPT alone without safety concerns., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05476081.

Purpose: Although dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration., Methods: We conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments., Results: During the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15-96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%)., Conclusion: In conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections., (© 2024. The Author(s).)

Objectives: Advancements in Artificial Intelligence(AI) have made platforms like ChatGPT increasingly relevant in medicine. This study assesses ChatGPT's utility in addressing bacterial infection-related questions and antibiogram-based clinical cases., Methods: This study involved a collaborative effort involving infectious disease (ID) specialists and residents. A group of experts formulated six true/false, six open-ended questions, and six clinical cases with antibiograms for four types of infections (endocarditis, pneumonia, intra-abdominal infections, and bloodstream infection) for a total of 96 questions. The questions were submitted to four senior residents and four specialists in ID and inputted into ChatGPT-4 and a trained version of ChatGPT-4. A total of 720 responses were obtained and reviewed by a blinded panel of experts in antibiotic treatments. They evaluated the responses for accuracy and completeness, the ability to identify correct resistance mechanisms from antibiograms, and the appropriateness of antibiotics prescriptions., Results: No significant difference was noted among the four groups for true/false questions, with approximately 70% correct answers. The trained ChatGPT-4 and ChatGPT-4 offered more accurate and complete answers to the open-ended questions than both the residents and specialists. Regarding the clinical case, we observed a lower accuracy from ChatGPT-4 to recognize the correct resistance mechanism. ChatGPT-4 tended not to prescribe newer antibiotics like cefiderocol or imipenem/cilastatin/relebactam, favoring less recommended options like colistin. Both trained- ChatGPT-4 and ChatGPT-4 recommended longer than necessary treatment periods (p-value = 0.022)., Conclusions: This study highlights ChatGPT's capabilities and limitations in medical decision-making, specifically regarding bacterial infections and antibiogram analysis. While ChatGPT demonstrated proficiency in answering theoretical questions, it did not consistently align with expert decisions in clinical case management. Despite these limitations, the potential of ChatGPT as a supportive tool in ID education and preliminary analysis is evident. However, it should not replace expert consultation, especially in complex clinical decision-making., (© 2024. The Author(s).)

Introduction: Randomized clinical trials (RCTs) represent the mainstay for the approval of new treatments. However, stringent inclusion criteria often cause them to depart from the daily clinical practice. Real-world (RW) evidence have a complementing role, filling the gap between the efficacy of a treatment and its effectiveness. Immune checkpoint inhibitors (ICIs) have changed the treatment scenario for non-small cell lung cancer (NSCLC); immune-related adverse events (irAEs) could become life-threatening events, when not timely managed. We performed a systematic review and meta-analysis on the RW impact of irAEs through the years., Methods: The systematic review focused on irAEs occurred in locally advanced or metastatic NSCLC patients, treated with ICIs in a RW setting. We queried two electronic databases (Embase and Medline) from 1996 to August 2022. We then conducted a meta-analysis dividing the results in two cohorts (2015-2018 and 2019-2021). We described the prevalence of patients with irAEs of any or severe grade (G). Estimates were expressed as proportions up to the second decimal point (effect size, ES). IrAEs of interest were those involving the skin, the liver, the endocrine system or the gastro-intestinal system., Results: Overall, 21 RW studies on 5,439 patients were included in the quantitative and qualitative synthesis. The prevalence of G≥3 irAEs was slightly lower in the 2015-2018 subgroup, while the prevalence of irAEs of any grade was similar for both periods. Overall, we observed a higher ES for gastrointestinal, hepatic and lung irAEs, while a lower ES was reported for skin or endocrine irAEs. Endocrine irAEs were reported in 10 out of 21 studies, with a slight increase in the most recent studies, while cutaneous toxicities were mostly reported in two studies lead within the first time-period. Pulmonary, gastrointestinal, and hepatic toxicities, showed a more heterogeneous distribution of ES over time., Discussion: Our findings showed that the frequency of irAEs remained stable across the two calendar periods examined in our meta-analysis. This finding suggests that RW data might not be able to identify a potential learning curve in detection and management of irAEs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Pasello, Pavan, De Nuzzo, Frega, Ferro, Dal Maso, Bonanno, Guarneri and Girardi.)

Cryptic Aspergillus species are increasingly recognized as pathogens involved in human disease. They are ubiquitarian fungi with high tenacity in their environment and can express various resistance mechanisms, often due to exposure to antifungal agents employed in agriculture and farming. The identification of such species is increasing thanks to molecular techniques, and a better description of this type of pathogen is granted. Nevertheless, the number of species and their importance in the clinical setting still need to be well studied. Furthermore, their cross-sectional involvement in animal disease, plants, and human activities requires a multidisciplinary approach involving experts from various fields. This comprehensive review aims to provide a sharp vision of the cryptic Aspergillus species, from the importance of correct identification to the better management of the infections caused by these pathogens. The review also accentuates the importance of the One Health approach for this kind of microorganism, given the interconnection between environmental exposure and aspergillosis, embracing transversely the multidisciplinary process for managing the cryptic Aspergillus species. The paper advocates the need for improving knowledge in this little-known species, given the burden of economic and health implications related to the diffusion of these bugs.

Background: Enabling, supporting and promoting positive health-related behaviours is critical in addressing the major public health challenges of our time, and the multifaceted nature of behaviours requires an evidence-based approach. This statement seeks to suggest how a much-needed enhanced use of behavioural and cultural science and insights for health could be advanced., Study Design and Methods: and methods: Public health authorities of Europe and Central Asia and international partner organizations in September 2023 met in Copenhagen, Denmark, to discuss the way forward. Drawing on 1) country reporting to WHO, 2) interview study with public health authorities and 3) the meeting deliberations, this meeting statement was developed., Results: The meeting statement presents a joint call for step-change accelerated use of evidence-based approaches for health behaviours. Actionable next steps for public health authorities and international and regional development partners in health are presented., Conclusions: The way forward involves increased resource allocation, integration of behavioural insights into health strategies, advocacy through case and cost-effectiveness examples and capacity building., (© 2024 Published by Elsevier Ltd on behalf of The Royal Society for Public Health.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report the long-term results of the frontline trial with dasatinib and blinatumomab in induction/consolidation (GIMEMA LAL2116, D-ALBA) for adult Philadelphia-positive ALL (Ph+ ALL), which enrolled 63 patients of all ages. At a median follow-up of 53 months, disease-free survival, overall survival, and event-free survival are 75.8%, 80.7%, and 74.6%, respectively. No events have occurred among early molecular responders. A significantly worse outcome was recorded for IKZF1 plus patients. Twenty-nine patients-93.1% being in molecular response (ie, complete molecular response or positive nonquantifiable) after dasatinib/blinatumomab-never received chemotherapy/transplant and continued with a tyrosine kinase inhibitor only; 28 patients remain in long-term complete hematologic response (CHR). An allogeneic transplant was carried out in first CHR mainly in patients with persistent minimal residual disease; 83.3% of patients are in continuous CHR. The transplant-related mortality was 12.5% for patients transplanted in first CHR and 13.7% overall. Nine relapses and six deaths have occurred. ABL1 mutations were found in seven cases. The final analysis of the D-ALBA study shows that a chemotherapy-free induction/consolidation regimen on the basis of a targeted strategy (dasatinib) and immunotherapy (blinatumomab) is effective in inducing durable long-term hematologic and molecular responses in adult Ph+ ALL, paving the way for a new era in the management of these patients.

Tinea capitis is a common disease in children but rare in newborns younger than 1 month of age. Only 29 cases of tinea capitis in newborns have been described in indexed literature from 1990 until now. While antifungal agents can be used topically and systemically, systemic antifungal therapy is generally accepted as the treatment of choice for tinea capitis due to limited penetration of topical agents into the hair follicle. However, there is a lack of data on the use of systemic antifungal agents in newborns, and there are reports of successful treatment of tinea capitis in newborns using only topical therapy. In this paper, we present a case of tinea capitis in a 29-day-old female baby and review the previous 29 reported cases., (© 2023 Wiley Periodicals LLC.)

Purpose: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment., Design: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895)., Participants: One hundred thirty-five patients treated at 6 European centers., Methods: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes., Main Outcome Measures: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates., Results: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred., Conclusions: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: There is little information regarding the hepatitis B virus (HBV), vaccination status, and hepatitis B exposure in Italian women's jails. We aimed to describe the HBV exposure and HBs antibody (anti-HBs) protection levels in female prisoners., Material and Methods: A retrospective multicentric study was performed in Italian prisons from 2021 to 2023. Univariate and multivariate analyses were conducted to identify risk factors for HBc antibody (anti-HBc) seropositivity and non-protective anti-HBs titer., Results: We included 156 patients. The median age was 41.0 (IQR 34.0-48.0). Of the studied subjects, 31 (19.9%) had anti-HBc positive titer. Two women were HBsAg positive. In the multivariate analysis, older age [OR 1.06 (CI 1.01-1.11), p = 0.011], North-Eastern European [OR 11.67 (3.29-41.30), p < 0.001] and African origin [OR 6.92 (CI 1.51-31.60), p = 0.013], and drug use [OR 6.55 (CI 1.96-21.9), p = 0.002] were risk factors for HBV exposure. Thirty-seven (32%) women had no history of HBV vaccination. Forty-four (38%) had an anti-HBs non-protective titer. In the multivariate analysis, North-Eastern European origin [OR 4.55 (CI 1.19-17.50), p = 0.027] was associated with unprotective anti-HBs titer., Conclusion: Our results show both the low prevalence of HBV and protection in female prisoners. Age, North-Eastern European and African origin, and drug use have a role in exposure risk to HBV.

Background: Patients with acute venous thromboembolism (VTE) need anticoagulation (AC) therapy for at least 3/6 months (primary treatment); after that period, they should receive a decision on the duration of therapy., Methods: This study examined the complications occurring during two years of follow-up (FU) in patients with a first VTE who were recruited in 20 clinical centers and had discontinued or prolonged AC. They were included in the START2-POST-VTE prospective observational study., Results: A total of 720 patients (53.5% males) who, after the completion of primary treatment, had received the decision to continue ( n = 281, 39%; 76.1% with a DOAC) or discontinue ( n = 439, 61%) AC were followed up for 2 years (total FU = 1318 years). The decision to prolong or suspend AC was made in similar proportions in patients with unprovoked or provoked index events. Courses of sulodexide treatment or Aspirin (100 mg daily) were prescribed to 20.3% and 4.5%, respectively, of the patients who discontinued AC. The bleeding rate was significantly higher in patients who extended AC (1.6% pt/y) than in those who stopped AC (0.1% pt/y; p = 0.001) and was higher in patients using standard-dose DOACs (3.1% pt/y) than in those using reduced-dose DOACs (0.4% pt/y). The recurrent VTE rates were similar between the two groups (2.2% pt/y during AC vs. 3% pt/y off AC)., Conclusion: Physicians' decisions about AC duration were independent of the unprovoked/provoked nature of the index event. The bleeding rate was higher in patients who continued AC using standard-dose DOACs. Surprisingly, the rate of thrombotic recurrence was not different between those who continued or discontinued AC. Randomized studies comparing different procedures to decide on the duration of AC after a first VTE are needed.

Background: Recent clinical trials demonstrated longer survival in extended small cell lung cancer (SCLC) patients treated with immunotherapy in addition to chemotherapy. However, the magnitude of benefit is modest and the impact in real-world setting has to be fully established., Methods: We collected clinical data and radiological imaging of patients affected by extended or relapsing SCLC and consecutively treated according to clinical practice between 2016 and 2023. As primary end-point, we compared pre-defined outcome indicators before and after the introduction of chemo-immunotherapy (May 2020): 6-month and 12-month progression free survival (PFS) rate, 12-month and 18-month overall survival (OS). Among those who were treated after May 2020, patients who did not receive immunotherapy according to treating physician's choice were included in the analysis to minimize clinical selection bias., Results: The analysis included 214 patients: 132 (61.7%) were treated in an Academic cancer center and 82 (38.3%) in two community hospitals; 104 were treated before May 2020. Median PFS of the overall study population was 4.8 months (95% confidence interval [95% CI]: 4.4-5.4), median OS was 7.1 months (95% CI: 6.3-7.7). Estimated PFS and OS were significantly longer in patients treated after May 2020 with hazard ratio (HR) for PFS and OS of 0.61 (95% CI: 0.46-0.81, p < 0.001) and 0.70 (95% CI: 0.52-0.93, p = 0.015), respectively. 6-month PFS rate increased from 27% to 40% (p = 0.04) while 12-months PFS raised from 1% to 11% (p = 0.003). 12-month and 18-month OS rate increased from 15% to 28% (p = 0.03) and from 2.1% to 12% (p = 0.009), respectively. After May 2020 the median number of hospitalization days per patient decreased significantly and the incidence of severe AEs was similar. Among patients treated with chemo-immunotherapy, the onset of immune-related AEs was associated with improved PFS and OS (HR 0.55, 95% CI: 0.35-0.89, p = 0.012 and HR 0.47, 95%CI 0.28-0.77, p = 0.002, respectively)., Conclusions: The real-world analysis shows a meaningful improvement of outcome indicators after the introduction of chemo-immunotherapy, with reduction of the duration of hospitalization, thus supporting the use of chemo-immunotherapy and the need for further biomarker research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bonanno, Calvetti, Dal Maso, Pavan, Bao, De Nuzzo, Frega, Sartori, Ferro, Pasello, Morandi, Aprile and Guarneri.)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified 10 areas of interest based on published evidence and personal experience: (1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); (2) tailoring surgery to HS characteristics; (3) wide local excision; (4) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Gout is a chronic joint disease caused by the deposition of monosodium urate crystals into and around the articular tissues. In the last two years, new insights regarding diagnosis, genetic involvement, pathogenesis, comorbidities, and clinical data, have allowed the identification of new strategies to improve the control of the disease and its flares. In keeping, the discover of new mechanisms concerning crystal-induced inflammation have suggested new ways for the management not only of gout, but also other systemic diseases, mainly including renal and cardiovascular disorders. In this context it is very representative the case of colchicine which, given the surprising results obtained both in laboratory and clinical experiments, has recently received by FDA the approval for the prevention of cardiovascular disorders.

Objectives: Attenuation of otoacoustic emissions over time has been reported for many patients with hearing impairment harboring mutations in the OTOF gene. In this study, the time course of changes of distortion product otoacoustic emissions (DPOAEs) has been analyzed in a cohort of patients in the light of tympanometry results., Design: The changes of DPOAEs in 16 patients with OTOF -related hearing impairment were retrospectively analyzed., Results: All but one subject showed DPOAEs bilaterally at the time of diagnosis. Three patients diagnosed as adults still had DPOAEs at ages of 27, 31, and 47 years, respectively. Follow-up was available for 7 children diagnosed at the age of 1 to 3 years, who still showed preservation of DPOAEs at ages of 5 to 16 years. The responses were absent or attenuated in amplitude at some follow-up appointments in association with type B or C tympanograms., Conclusions: DPOAEs are preserved much longer than expected in a cohort of patients with OTOF -related hearing impairment. The previously reported loss of DPOAEs may have been caused in some children by increased middle ear impedance due to otitis media., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Ear & Hearing is published on behalf of the American Auditory Society, by Wolters Kluwer Health, Inc.)

Candida auris has emerged globally as a multidrug-resistant health care-associated fungal pathogen. In the literature, nosocomial outbreaks are reported worldwide. In addition, C. auris diffusion occurs in high-dependency settings with infections typically affecting critically ill patients, resulting in life-threatening disease. We describe the first documented case of C. auris in northeastern Italy and the measures applied to contain the transmission that led to zero collateral infections.

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting., Research Design and Methods: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24., Results: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 ( p  = 0.0004) and 24 ( p  = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission ( p  = 0.002) and clinical >response rates ( p  = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy., Conclusion: This real-world study shows that UST effectively and safely treats patients with UC.

Purpose: The objective of this study is to validate Descemet membrane endothelial keratoplasty (DMEK) Rapid device for preloading DMEK grafts with endothelium outward., Methods: In this multicenter retrospective clinical study, DMEK tissues (n = 27) were peeled and preloaded (8.25 mm) in a DMEK Rapid device. The device was loaded in a container prefilled with the storage solution and shipped from a single center in Italy to 4 different centers located in Italy and the United Kingdom. Preloaded tissues were delivered by injecting the graft in the anterior chamber. Patients were monitored at days 1 and 15 and at months 1, 3, and 6, as well as at the last follow-up (9-12 months) postoperatively. Main outcome measures included rebubbling rate and graft failure, corrected distance visual acuity, endothelial cell loss (ECL), and central corneal thickness at all time points. A one-way analysis of variance test comparing day 1 with all later time points was followed with significance at P < 0.05., Results: The average recorded surgical time was 6 to 25 minutes with no immediate surgical complications. Rebubbling was observed in 7 of 26 cases with one graft failure within 15 days postoperatively. The mean corrected distance visual acuity at day 1 was 0.64 ± 0.49 logMAR, which improved to 0.18 ± 0.43 logMAR at the last follow-up. Endothelial cell density values showed a significant decrease at the last follow-up (1827 ± 565 cells/mm 2 ) ( P < 0.001) compared with the preoperative value (2503 ± 128 cells/mm 2 ), with an average endothelial cell loss of 27%. Central corneal thickness significantly dropped from 694 ± 157 μm at day 1 to 502 ± 42 μm at the last follow-up ( P < 0.001)., Conclusions: DMEK Rapid device is quick, easy, and efficient for preloading and shipping DMEK grafts internationally in endothelium-outward orientation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Women represent less than 5% of the incarcerated population in Italy, with very limited data on HCV infection. Higher HCV seroprevalence and active infection rates have been described among incarcerated females in available studies. Our aim is to compare the prevalence and cascade of care of HCV between male and female populations in Italian penitentiaries., Methods: We conducted a multicentre, retrospective study comparing HCV seroprevalence, active infections, treatment, and SVR rates between female (Group A) and male (Group B) populations in Italian prison settings., Results: No significant differences were found between the two groups regarding PWIDs ( p = 0.16), nor in people living with HIV ( p = 0.35) or HBV co-infection ( p = 0.36). HCV seroprevalence was higher in Group A ( p = 0.002). There was no statistically significant difference between the two groups regarding active infections ( p = 0.41). Both groups showed a low level of fibrosis, and the dominant genotype was 3a. Almost all patients underwent antiviral treatment. All treated patients achieved SVR12., Conclusions: Our findings illuminate the importance of recognizing and addressing gender differences in HCV seroprevalence within penitentiary settings. Moving forward, addressing the unique needs of incarcerated females and optimizing HCV care for all incarcerated individuals are essential steps in the pursuit of achieving HCV micro-elimination goals.

Competing Interests: Conflicts of interest None declared for the authors with the exception of Ketty Peris who has served on advisory board, received honoraria for lectures and/or research grants for AbbVie, Almirall, Lilly, Galderma, Leo Pharma, Pierre Fabre, Novartis, Sanofi, Sun Pharma, Janssen; Andrea Chiricozzi who served as advisory board member and consultant and has received fees and speaker's honoraria or has participated in clinical trials for AbbVie, Almirall, Leo Pharma, Lilly, Janssen, Novartis, Pfizer, and Sanofi Genzyme; Maria Concetta Fargnoli has served on advisory boards, received honoraria for lectures and research grants from AMGEN, Almirall, Abbvie, BMS, Galderma, Kyowa Kyrin, Leo Pharma, Pierre Fabre, UCB, Lilly, Pfizer, Janssen, MSD, Novartis, Sanofi-Regeneron, Sunpharma; Maria Esposito who served as advisory board member, speaker and consultant and has participated in clinical trials for AbbVie, Almirall, Leo Pharma, Eli Lilly, Janssen, Novartis, and Sanofi Genzyme, UCB; Cataldo Patruno who served as advisory board member and consultant and has received fees and speaker's honoraria or has participated in clinical trials for AbbVie, Amgen, Eli Lilly, Leo Pharma Novartis, Pfizer, Pierre Fabre, Sanofi.

Background: The clinical value of tumor infiltrating lymphocytes (TILs) in hormone receptor-positive (HR+)/HER2- breast cancer (BC) may be unearthed by focusing on more biologically aggressive tumors. Here we deepen and describe the correlation between RS and TILs, proposing an immuno-genomic model for HR+ /HER2- BC., Methods: We enrolled T1-T3, N0-N1 BC patients with available RS® and TILs in the context of four multicenter, prospective studies. RS® and TILs were considered as continuous and categorical variables. RS® was categorized into: 0-10 (low risk), 11-25 (intermediate risk) and 26-100 (high risk); TILs were categorized into: low TILs (0-10%), intermediate TILs (11-59%) and high TILs (60-100%)., Results: 811 patients were included. RS distribution was (n = 810): low risk 22.0%, intermediate risk 61.2%, high risk 16.8%. TIL distribution was (n = 455): low TILs 84.6%, intermediate TILs 13.6% and high TILs 1.8%. A significant, weak positive, linear correlation was found between continuous TILs and RS (Pearson coefficient=0.223, p < 0.001). When considering RS and TILs categories, tumors with intermediate/high TIL levels significantly enriched the high RS subgroup (p = 0.006). This was confirmed both within Luminal A and Luminal B cohorts. Among high-RS patients, 16.7% of Luminal A and 26.7% of Luminal B tumors had intermediate/high TILs., Conclusions: We observed that RS® and TILs capture only slightly overlapping information on the biology of HR+ /HER2- tumor microenvironment. We demonstrated the feasibility of combining RS and TILs into a composite immuno-genomic model, which may serve the purpose of guiding and focalizing patient selection in the further development of immunotherapy strategies for Luminal-like disease., Competing Interests: Declaration of Competing Interest FM: reports personal fees from Roche, Novartis, Gilead, Seagen, Pfizer, outside the submitted work. MVD: reports personal fees from EliLilly, Exact Sciences, Novartis, Pfizer, Seagen, Gilead, MSD, AstraZeneca, Daiichi Sankyo, and Roche outside of the submitted work. TG: reports personal fees from Gilead, Roche, outside the submitted work. MG: Consulting/Advisor: Roche, AstraZeneca, Lilly, Daichii Sankyo, Novartis, Pfizer, Seagen, MSD, Eisai; Honoraria: Novartis, Pfizer, Lilly, AstraZeneca, Daichii Sankyo; Research funding to the Institution: AstraZeneca; Travel, accommodation, expenses: Lilly, Pfizer, AstraZeneca. MM: personal fees from Accord, Gentili, Novartis, Lilly. EB: received speakers’ and travels’ fee from MSD, Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis and Roche. AZ: reports personal fees and non-financial support from Novartis, Astra-Zeneca, Eli-Lilly, Pfizer, Daiichi Sankyo, MSD, Roche, Seagen, Exact Sciences, Gilead, all disclosures are outside the submitted work. VG: reports personal fees for advisory board membership for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, Pierre Fabre; personal fees as an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK, Novartis, Roche and Zentiva; personal fees for expert testimony for Eli Lilly. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium renowned for its resilience and adaptability across diverse environments, including clinical settings, where it emerges as a formidable pathogen. Notorious for causing nosocomial infections, P. aeruginosa presents a significant challenge due to its intrinsic and acquired resistance mechanisms. This comprehensive review aims to delve into the intricate resistance mechanisms employed by P. aeruginosa and to discern how these mechanisms can be inferred by analyzing sensitivity patterns displayed in antibiograms, emphasizing the complexities encountered in clinical management. Traditional monotherapies are increasingly overshadowed by the emergence of multidrug-resistant strains, necessitating a paradigm shift towards innovative combination therapies and the exploration of novel antibiotics. The review accentuates the critical role of accurate antibiogram interpretation in guiding judicious antibiotic use, optimizing therapeutic outcomes, and mitigating the propagation of antibiotic resistance. Misinterpretations, it cautions, can inadvertently foster resistance, jeopardizing patient health and amplifying global antibiotic resistance challenges. This paper advocates for enhanced clinician proficiency in interpreting antibiograms, facilitating informed and strategic antibiotic deployment, thereby improving patient prognosis and contributing to global antibiotic stewardship efforts.