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Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar. Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome. Results: We present the preliminary data collected in the last 2 months (mos) on 37 pts who received the diagnosis between 2015 and 2020, with a median age of 52.5 years (range 32–78). The median number of trabectedin cycles administered was four (range 2–50) for a median follow up of 5.83 months (range 1–60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6 months (CI95% 2.7–4.6); median overall survival was 34.3 months (CI95% 0–75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33 pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen’s kappa coefficient of concordance was 0.792 (p-value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center. Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results. [ABSTRACT FROM AUTHOR]

Background: The advent of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a challenge. Objective: This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. Methods: We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Results: Our search included 61 pertinent studies conducted between 2019 and 1 March 2024. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, and disability), high responder rates, and optimal safety and tolerability profiles. Conclusions: Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an extraordinary finding in clinical neurology. [ABSTRACT FROM AUTHOR]

Blinatumomab is a bispecific T-cell engager approved for relapsed/refractory and minimal residual disease positive B-cell Acute Lymphoblastic Leukemia. We conducted a retrospective study evaluating the outcome of Blinatumomab. The impact of clinical and treatment-related variables on cumulative incidence of relapse/progression (CIRP), event-free (EFS) and overall survival (OS) was analyzed. From January 2016 to December 2022 50 Ph'- (37) and Ph+ (13) B-ALL patients received Blinatumomab. The median age was 37. Indications to blinatumomab were relapsed/refractory B-ALL in 29 and MRD-positive in 21 patients. Blinatumomab was the 2nd and 3rd line in 40 and in 10 patients, respectively. Twenty patients were treated pre-transplantation, ten were treated for relapse after transplant, twenty were not eligible for transplant. Out of 29 patients treated for relapsed/refractory disease, 16 (55%) achieved complete response and 12 achieved MRD-negativity. Out of 21 patients treated for MRD, 16 (76%) achieved MRD-negativity. At a median follow-up of 46 months the median EFS and OS were 11.5 and 16.2 months. The CIRP was 50%. In univariate analysis age, disease-status (overt vs. minimal disease) at blinatumomab, bridging to transplant after blinatumomab and MRD-response resulted significant for EFS and OS. In multivariate analysis only disease-status and MRD-response retained significance both for EFS and OS. Disease-status and MRD-response resulted significant for EFS and OS also after censoring at HSCT. This retrospective study on B-ALL patients treated with blinatumomab confirms a superior outcome for MRD-responsive over MRD non-responsive patients. Survival depends also on the disease-status prior treatment. [ABSTRACT FROM AUTHOR]

Background: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. Methods: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. Results: Of 212 patients, 108 (mean age 48.9years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9months (SD ± 3.2) and one quadruple therapy (2.1months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. Conclusions: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile. [ABSTRACT FROM AUTHOR]

Matteo Megna,&ast; Angelo Ruggiero,&ast; Nello Tommasino, Claudio Brescia, Fabrizio Martora, Sara Cacciapuoti, Luca Potestio Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy&ast;These authors contributed equally to this workCorrespondence: Luca Potestio, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 – 7462442, Email potestioluca@gmail.comAbstract: Tildrakizumab is a humanised IgG1/k-type monoclonal antibody that targets the p19 protein subunit of IL23. Despite its effectiveness and safety have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 (brodalumab, ixekizumab, bimekizumab and/or secukinumab) are scant. Therefore, further studies on this topic would be beneficial for clinicians in guiding the selection of biologic shifting, considering that anti-IL23, − 12/23, and -IL17 partially share their therapeutic targets. In this context, we performed a 28-week, single-center, real-life, retrospective study, with the aim of assessing the efficacy and safety of tildrakizumab in patients who previously failed anti-IL17, also focusing the attention on psoriasis located in difficult-to-treat areas (scalp, palms or soles, fingernails, genitals). A total of 23 patients (12 male, 52.2%; mean age 52.8 ± 12.4 years) were enrolled. Of these, 11 (47.8%) failed secukinumab, 7 (30.4%) ixekizumab, 3 (13.0%) brodalumab, 1 (4.3%) both secukinumab and ixekizumab and 1 (4.3%) bimekizumab. At baseline, mean PASI and BSA were 12.8 ± 5.9 and 18.7 ± 9.6, respectively. At W16 PASI75 and PASI90 response were achieved by 15 (65.2%), and 9 (39.1%) patients, respectively, whereas 19 (82.6%) and 13 (56.6%) subjects reached these scores at W28. One (4.3%) case of primary inefficacy and 1 (4.3%) case of secondary inefficacy were assessed. Finally, no severe adverse events were collected. Tildrakizumab seems to be a valuable option in selected patients with psoriasis unresponsive to anti-IL17, suggesting that prior exposure to biological therapies seem not directly affect its effectiveness.Keywords: Tildrakizumab, psoriasis, real-life, anti-IL23

We conducted a multicenter, prospective study (EMBRACE) evaluating the real-life effectiveness, safety, and tolerability of eptinezumab (100 mg/300 mg)—a monoclonal antibody targeting the calcitonin-gene-related peptide (anti-CGRP mAb)—in high-frequency episodic migraine (HFEM) or chronic migraine (CM). The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at weeks 9–12 compared to baseline. The secondary endpoints included changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates. The safety analysis involved 44 subjects; the effectiveness analysis included 26 individuals. Eptinezumab was well-tolerated. In CM patients, eptinezumab significantly reduced MHD (−16.1 ± 9.9, p < 0.001), MAI, NRS, HIT-6, MIDAS, and MIBS-4. In HFEM patients, it significantly reduced NRS, HIT-6, MIDAS, and MIBS-4, though reductions in MMD (−3.3 ± 4.5) and MAI were not statistically significant. Overall, ≥50% and ≥75% response rates were 61.5% and 30.8%, respectively (60% and 30% in non-responders to subcutaneous anti-CGRP mAbs). The clinical change was rated as much or very much improved by 61.0% of the patients. Eptinezumab demonstrated high effectiveness, safety, and tolerability in real-life among hard-to-treat migraine patients with multiple treatment failures, including anti-CGRP mAbs. [ABSTRACT FROM AUTHOR]

Control charts are widely used in the manufacturing and service sectors to track, regulate, and enhance process output. A manufacturing industry desires to utilize a control chart that has an effective structure and is sensitive to detect infrequent variations in the process. Generally, control charts are developed with the presumption that the understudy quality variable is normally distributed. In actual application, many processes have skewed distributions. The purpose of this study is to use the moving average (MA) charts to track the dispersion of a log‐normal distribution. The design of the proposals is developed and the performance is assessed by run‐length properties. The cumulative distributions of run‐length under in‐control and out‐of‐control are provided to have a broad view of the performance. The simulation findings show that when the value of the log‐normal dispersion parameter is large, the proposed chart is more sensitive to the changes in the dispersion. Additionally, an industrial application is given to illustrate the suggested charts in this research. [ABSTRACT FROM AUTHOR]

Background: The SQ tree sublingual immunotherapy (SLIT)‐tablet is authorised for treatment of allergic rhinoconjunctivitis with or without asthma in trees of the birch homologous group in 21 European countries. The primary objective of this study was to explore the safety in real‐life. Methods: In a prospective, non‐interventional post‐authorisation safety study (EUPAS31470), adverse events (AEs) and adverse drug reactions (ADRs) at first administration and follow‐up visits, symptoms, medication use, and pollen food syndrome were recorded by physicians in 6 European countries during the first 4–6 months of treatment. Results: ADRs with the SQ tree SLIT‐tablet were reported in 57.7% of 1069 total patients (median age 36.0 years, 53.7% female) during the entire observation period (severity, mild‐to‐moderate: 70.1%, severe: 4.7%, serious: 0.7%) and in 45.9% after first administration. ADRs were not increased with pollen exposure at first administration. With coadministration of the SQ tree and grass SLIT‐tablet AEs were reported in 73.8% of patients and in 52.8% with the SQ tree SLIT‐tablet alone. Nasal and eye symptoms improved in 86.9% and 80.9% of patients and use of symptomatic medication in 76.0%. PFS with symptoms was reported in 43.0% of patients at baseline and in 4.3% at the individual last visit. Conclusions: The results of this non‐interventional safety study with the SQ tree SLIT‐tablet confirm the safety profile from placebo‐controlled clinical trials and support effectiveness in real‐life according to the published efficacy data. Safety was not impaired by pollen exposure at first administration or co‐administration with other SLIT‐tablets. [ABSTRACT FROM AUTHOR]

Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12–82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0–100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1–49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7–50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area. [ABSTRACT FROM AUTHOR]

Ropeginterferon-alfa2b (ropegIFNα2b) is a long-acting IFN formulation with broad FDA/EMA approval as a therapy of polycythemia vera (PV) with no symptomatic splenomegaly. There is currently lack of information on the real-world patient selection, including the impact of local reimbursement policies, and drug management, particularly: type/timing of screening and follow-up tests; absolute/relative contraindications to therapy; ropegIFNα2b dose and combinations with hydroxyurea. As a sub-analysis of the PV-ARC retrospective study (NCT06134102), we here report our monocenter experience with ropegIFNα2b in the period from January 2021, corresponding to drug availability outside clinical trial, and December 2023. Among the 149 patients with EMA/FDA indication, only 55 (36.9%) met the local reimbursement criteria and 18 (12.1%) received ropegIFNα2b. Thanks to appropriate screening, relative/absolute contraindications to ropegIFNα2b were detected and managed in a multidisciplinary manner. Efficacy and safety of ropegIFNα2b was confirmed, with 3 cases of early molecular response. General use of low ropegIFNα2b dose, with frequent need for hydroxyurea combinations, was noted. This real-world experience suggests a significant impact of local regulations on drug prescription and the need for greater real-world data collection on ropegIFNα2b in PV patients. Also, it describes appropriate multidisciplinary screening and monitoring procedures during ropegIFNα2b therapy. [ABSTRACT FROM AUTHOR]

Poor literature report actual and detailed costs of chimeric antigen receptor (CAR) T-cell pathway in a real-life setting. We retrospectively collect data for all patients with relapsed/refractory aggressive large B-cell lymphoma who underwent leukapheresis between August 2019 and August 2022. All costs and medical resource consumption accountability were calculated on an intention-to-treat (ITT) basis, starting from leukapheresis to the time when the patient (infused or not) exited the CAR T-cell pathway for any reason. Eighty patients were addressed to leukapheresis and 59 were finally infused. After excluding CAR-T product cost, the main driver of higher costs were hospitalizations followed by the examinations/procedures and other drugs, respectively 43.9%, 26.3% and 25.4% of the total. Regarding costs of drugs and medications other than CAR T products, the most expensive items are those referred to AEs, both infective and extra-infective within 30 days from infusion, that account for 63% of the total. Density plot of cost analyses did not show any statistically significant difference with respect to the years of leukapheresis or infusion. To achieve finally 59/80 infused patients the per capita patients without CAR-T products results 74,000 euros. This analysis covers a growing concern on health systems, the burden of expenses related to CAR T-cell therapy, which appears to provide significant clinical benefit despite its high cost, thus making economic evaluations highly relevant. The relevance of this study should be also viewed in light of continuously evolving indications for this therapy. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy of galcanezumab has been demonstrated in randomized controlled trials, but evidence about its use under clinical practice conditions is still limited. This study aimed to describe the characteristics of the patients treated with galcanezumab in routine clinical practice in Spain as well as treatment patterns, persistence, and effectiveness. Methods: A retrospective chart review study was carried out in six hospitals. Information of adults with migraine, who started treatment with galcanezumab between November 2019 and September 2021, was analyzed until end or loss of follow-up. Continuous variables were described as mean (standard deviation, SD) and median (interquartile range, IQR), and categorical variables as frequency and percentages. Persistence to treatment was estimated using Kaplan–Meier analysis. Results: A total of 314 patients were analyzed over median follow-up period of 17.5 months (13.8–20.7), with a mean age of 46.3 (12.6), 85% women, 80.6% chronic migraine, and reporting a mean of monthly migraine days of 16.7 (7.8). Overall, 72.9% had comorbid conditions, with anxiety and depression disorders being the most frequent. More than 60% had received ≥ 6 previous preventive drugs, the most common being antiepileptics, antidepressants, and botulinum toxin (95.2%, 89.8% and 84.1%, respectively). Overall, 60.3% of the patients with other preventive treatments maintained them after galcanezumab initiation. The median time on galcanezumab was 14.6 months (9.4–22.8); 95.7%, 82.0%, 76.2% and 59.8% of patients were persistent to treatment at 3, 6, 9 and 12 months, respectively. Of the patients who discontinued (151: 48.1%), 57.6% were due to lack of effectiveness and 31.1% were due to improvement in migraine. The average reduction of monthly migraine days at 3, 6, 9 and 12 months was 7.9 (7.2), 9.1 (7.5), 8.8 (6.6) and 9.0 (6.9) days, respectively. Conclusions: In real clinical practice, galcanezumab is an effective treatment and has a high persistence in patients with migraine, mostly chronic and with multiple use of previous preventive treatments. [ABSTRACT FROM AUTHOR]

Introduction: Lanadelumab is a first-line long-term prophylaxis (LTP) in hereditary angioedema (HAE). Real-life data on its long-term efficacy and safety are limited. It is unknown whether patients using lanadelumab need short-term prophylaxis (STP). Objectives: To provide 4-year follow-up data for our first 34 patients treating with lanadelumab. Methods: Patients were assessed for their current injection interval, attacks, treatment satisfaction, disease control (AECT), quality of life impairment (AEQoL), events that can induce attacks, and the use of STP since the start of their treatment with lanadelumab. Results: Of 34 patients who started lanadelumab treatment, 32 were still using it after 4 years, with a median injection interval of 33 (range 14-90) days. HAE patients (n=28) reported longer intervals, i.e. 35 (14-90) days, than patients with angioedema due to acquired C1 inhibitor deficiency (n=4, 23 (14-31) days). With their current injection intervals, used for a mean duration of 29 ± 17 months, patients reported a yearly attack rate of 0.3 ± 0.1. More than 70% of patients were attack-free since starting their current injection interval. All patients reported well-controlled disease, i.e. =10 points in the AECT; 21 patients had complete control (16 points). AE-QoL scores improved further compared to our initial report, most prominently in the fears/shame domain (-6 points). Treatment satisfaction was very high. No angioedema occurred after 146 of 147 potentially attack-inducing medical procedures without STP. Conclusions: Our results demonstrate the long-term efficacy and safety of lanadelumab in real-life and question the need for STP in patients who use effective LTP. [ABSTRACT FROM AUTHOR]

Objective: Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders). Methods: In this multicenter (n = 16), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM), with ≥ 3 prior therapeutic failures, treated with any anti-CGRP mAbs for ≥ 48 weeks. We defined responders patients with a ≥ 50% response rate ≤ 12 weeks, late responders those with a ≥ 50% response rate ≤ 24 weeks, and ultra-late responders those achieving a ≥ 50% response only > 24 weeks. Results: A total of 572 migraine patients completed ≥ 48 weeks of anti-CGRP mAbs treatment. Responders accounted for 60.5% (346/572), late responders for 15% (86/572), and ultra-late responders for 15.7% (90/572). Among ultra-late responders, 7.3% (42/572) maintained the ≥ 50% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered persistent ultra-late responders, while 8.4% (48/572) missed the ≥ 50% response rate at ≥ 1 subsequent time interval and were classified as fluctuating ultra-late responders. Fifty patients (8.7%) did not respond at any time interval ≤ 48 weeks. Ultra-late responders differed from responders for higher BMI (p = 0.033), longer duration of medication overuse (p < 0.001), lower NRS (p = 0.017) and HIT-6 scores (p = 0.002), higher frequency of dopaminergic symptoms (p = 0.002), less common unilateral pain—either alone (p = 0.010) or in combination with UAS (p = 0.023), allodynia (p = 0.043), or UAS and allodynia (p = 0.012)—a higher number of comorbidities (p = 0.012), psychiatric comorbidities (p = 0.010) and a higher proportion of patients with ≥ 1 comorbidity (p = 0.020). Conclusion: Two-thirds of patients not responding to anti-CGRP mAbs ≤ 24 weeks do respond later, while non-responders ≤ 48 weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2–3 months of treatment. [ABSTRACT FROM AUTHOR]

IntroductionThe regimen with daratumumab, bortezomib, melphalan, and prednisone (D-VMP) is one of the recommended treatments for newly diagnosed multiple myeloma (NDMM) non-transplant eligible due to the results described in the ALCYONE trial. However, real-life outcomes with this regimen are limited. This study assesses the real-life effectiveness and safety of this regimen.MethodsWe retrospectively analyzed the data on efficacy, safety, and survival parameters of D-VMP regimen in 112 patients with NDMM not eligible for autologous stem-cell transplantation with attention to the effect of age, R2-ISS, high-risk cytogenetic abnormalities (CA), and depth of response.ResultsPatients aged ≥75 years constituted 70% of our cohort. Fifty-two percent had R2-ISS 3-4, and 60% had high-risk CA. Twenty-three percent of patients would have been excluded from the ALCYONE trial. After a median follow-up of 31.4 months, all patients had completed induction, with a median number of cycles of 9 (IQR 6-9). The overall response rate was 95%, and 72% achieved very good partial response (VGPR) or better. The median progression-free survival (PFS) was 41.5 (95% CI, 34.3 to NE), and the median overall survival (OS) was not reached. The most frequent adverse event (AE) was neuropathy (27%), followed by gastrointestinal symptoms (13%) and hematological AE (10%). Age did not negatively impact survival outcomes. Patients with ≥2 high-risk CA or those who achieved

Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar.Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome.Results: We present the preliminary data collected in the last 2 months (mos) on 37 pts who received the diagnosis between 2015 and 2020, with a median age of 52.5 years (range 32–78). The median number of trabectedin cycles administered was four (range 2–50) for a median follow up of 5.83 months (range 1–60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6 months (CI95% 2.7–4.6); median overall survival was 34.3 months (CI95% 0–75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33 pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen’s kappa coefficient of concordance was 0.792 (p-value

Abstract Introduction The efficacy of galcanezumab has been demonstrated in randomized controlled trials, but evidence about its use under clinical practice conditions is still limited. This study aimed to describe the characteristics of the patients treated with galcanezumab in routine clinical practice in Spain as well as treatment patterns, persistence, and effectiveness. Methods A retrospective chart review study was carried out in six hospitals. Information of adults with migraine, who started treatment with galcanezumab between November 2019 and September 2021, was analyzed until end or loss of follow-up. Continuous variables were described as mean (standard deviation, SD) and median (interquartile range, IQR), and categorical variables as frequency and percentages. Persistence to treatment was estimated using Kaplan–Meier analysis. Results A total of 314 patients were analyzed over median follow-up period of 17.5 months (13.8–20.7), with a mean age of 46.3 (12.6), 85% women, 80.6% chronic migraine, and reporting a mean of monthly migraine days of 16.7 (7.8). Overall, 72.9% had comorbid conditions, with anxiety and depression disorders being the most frequent. More than 60% had received ≥ 6 previous preventive drugs, the most common being antiepileptics, antidepressants, and botulinum toxin (95.2%, 89.8% and 84.1%, respectively). Overall, 60.3% of the patients with other preventive treatments maintained them after galcanezumab initiation. The median time on galcanezumab was 14.6 months (9.4–22.8); 95.7%, 82.0%, 76.2% and 59.8% of patients were persistent to treatment at 3, 6, 9 and 12 months, respectively. Of the patients who discontinued (151: 48.1%), 57.6% were due to lack of effectiveness and 31.1% were due to improvement in migraine. The average reduction of monthly migraine days at 3, 6, 9 and 12 months was 7.9 (7.2), 9.1 (7.5), 8.8 (6.6) and 9.0 (6.9) days, respectively. Conclusions In real clinical practice, galcanezumab is an effective treatment and has a high persistence in patients with migraine, mostly chronic and with multiple use of previous preventive treatments.

Luciano Ibba,1,2 Luigi Gargiulo,1,2 Carlo Alberto Vignoli,1,2 Giovanni Fiorillo,1,2 Mario Valenti,1,2 Antonio Costanzo,1,2 Alessandra Narcisi1 1Dermatology Unit, IRCCS Humanitas Research Hospital, Milan, Italy; 2Department of Biomedical Sciences, Humanitas University, Milan, ItalyCorrespondence: Luciano Ibba, Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, 20089, Italy, Email luciano.ibba@humanitas.itAbstract: Upadacitinib is a selective Janus kinase inhibitor approved for the treatment of severe atopic dermatitis (AD). This systematic review aims to summarize the most recent data in terms of effectiveness and safety of upadacitinib in the treatment of severe AD in a real-world setting. The review included a comprehensive search of databases, including PubMed, Google Scholar and Web of Science, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The literature search initially identified 242 studies. Of these, 214 were excluded after reviewing their titles and abstracts. We then conducted a full-text review of 25 studies, of which 17 met our inclusion criteria and were therefore included in our systematic review. The analysis of real-world studies showed high effectiveness of upadacitinib, in terms of both clinical signs and subjective symptoms, in different patient populations, including those resistant to other treatments. No new significant safety concerns have emerged as compared to randomized clinical trials.Keywords: JAKi, real-life, upadacitinib, atopic dermatitis, systematic review

Abstract Background Spinal Muscular Atrophy (SMA) is a rare neuromuscular disorder characterized by progressive degeneration of motor neurons and muscle weakness resulting in premature death or severe motor disability. Over the last decade, SMA has dramatically changed thanks to new advances in care and the emergence of disease-specific treatments. RegistrAME is a self-reported specific disease registry with an accurate curation system. It has collected data on SMA patients in Spain since 2015, gathering demographic, clinical, and patient-reported outcome data, all of which are patient-relevant. RegistrAME is part of the TREAT NMD network. This study aims to describe the advantages and disadvantages of a self–reported SMA registry, as well as the different variables of interest in the health status of RegistrAME patients. Results In total, 295 living patients with a confirmed diagnosis of SMA-5q were included (aged 1 to 77 years; mean 20.28). Half of the patients (50.2%) were ≥ 16 years old; 22.03% were type 1, 48.47% were type 2, 28.82% were type 3, and 0.7% were type 4. All functional statuses (non-sitter, sitter, and walkers) could be observed in each SMA type. Adult patients harbored the least aggressive SMA types, however, they presented the greatest level of disability. Patients with SMA type 1 had scoliosis surgery about five years earlier than patients with SMA type 2. None of the type 1 patients who achieved ambulation were wheelchair-free outdoors. This was also evident in 62.5% of type 2 walker patients and 44% of type 3 walker patients. Of the SMA type 1 patients, 40% had a gastrostomy (of which 84% had two SMN2 copies). One in five children with SMA type 1 (one to seven years of age) were ventilation-free. Conclusions The information provided by RegistrAME in a “real-world” setting allows better management of family expectations, an adequate approach to the disease and patients’ needs, as well as a better understanding of the impact of the disease. It also helps monitor the evolution of care, which will result in the need for updated guidelines.

Introduction: Coronavirus diseases-2019 (COVID-19) have been ongoing for more than two years. Despite the scientific research conducted in this process, there is still no widely accepted definitive treatment for the disease. For treating COVID-19, using antiviral agents previously used for the treatment of other RNA-virus infections has been seen as a fast way to a solution, and favipiravir is one of the leading agents. This prospective, multicenter, observational study was designed to investigate the safety of favipiravir in 500 patients treated with favipravir for favipravir. Methods: This study was conducted as a multicenter prospective study. Eight different sites from four cities participated, and 500 patients were included in the study. Follow-up of laboratory parameters, adverse events (AEs), and amelioration of fever, dyspnea, and cough symptoms of the patients was recorded in a case report form. Results: A total of 475 patients from eight centers completed the study. A total of 401 AEs were reported in 206 (51.4%) patients, which were mild-to-moderate in the majority of cases. Serious AEs occurred in 5 patients and death occurred in 4 patients. From the first to the last measurement, serum alanine aminotransferase levels (31.9±27.7 vs. 47.2±49.7 U/L, p37.8 for 6.6% on day 3, 3.2% on day 5, and 0.6% on day 10), dyspnea (for 56.4% on day 5, 62.4% on day 7, and 81.2% on day 10), and cough (46.0% on day 5, 73.0% on day 7, and 87.3% on day 10) were noted in an increasingly higher percentage of patients with continued therapy. Conclusion: The current study provides real-life data of favipiravir, which is a unique option in Turkey for treating COVID-19 patients. The results revealed that favipiravir is a well-tolerated agent with a low side-effect profile. However, it needs to be evaluated with well-designed, dose-compared, randomized controlled studies for the evaluation of efficacy.

Background Methods Results Conclusion Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp.We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real‐life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75–99%) of treated AKs.Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow‐up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded.Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real‐life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult‐to‐treat areas. [ABSTRACT FROM AUTHOR]

To identify small‐to‐moderate shifts (also known as outliers and anomalies) in the process parameters (location and/or dispersion), the classical cumulative sum (CUSUM) and exponential weighted moving average (EWMA) control charts are famous. The traditional CUSUM control chart is less capable to detect out‐of‐control signals of ±$ \pm $1.0 standard deviation shifts. The advanced versions of the traditional CUSUM and EWMA control charts are ACUSUM (adaptive CUSUM) and AEWMA (adaptive EWMA) control charts, respectively. The aforementioned issue of the traditional CUSUM control chart can be addressed through the ACSUUM control chart. It also identifies various sizes of shifts in the process parameters. In order to efficiently identify and remove outliers and anomalies (i.e., shifts) from datasets, the score functions are typically used to establish ACUSUM control charts. The goal of the study is to propose a new ACUSUM control chart based on the Hampel (score) function and it is symbolized as ACUSUMHampel${\mathrm{ACUSU}}{{\mathrm{M}}_{{\mathrm{Hampel}}}}$ control chart. Different sizes of shift in the process location parameter can be distinguished using the ACUSUMHampel${\mathrm{ACUSU}}{{\mathrm{M}}_{{\mathrm{Hampel}}}}$ control chart. The primary novelty is the substitution of a proposed time‐varying parameter for the typical CUSUM control chart's prioritization of the process characteristic by appropriate weights. The proposed ACUSUMHampel${\mathrm{ACUSU}}{{\mathrm{M}}_{{\mathrm{Hampel}}}}$ control chart's run length feature is obtained through the Monte Carlo simulation technique for zero‐state and steady‐states. For evaluating a single shift, performance measures like average run length (ARL), standard deviation of run length (RL), and different percentiles of run length are preferred. However, for evaluating a range of shifts, extra quadratic loss, relative average run length, and performance comparison index are used. Comparison based on performance measures shows the superiority of the proposed ACUSUMHampel${\mathrm{ACUSU}}{{\mathrm{M}}_{{\mathrm{Hampel}}}}$ control chart against the classical CUSUM and EWMA, ACUSUM, AEWMA, mixed EWMA‐CUSUM, and mixed CUSUM‐EWMA control charts. Furthermore, the proposed ACUSUMHampel${\mathrm{ACUSU}}{{\mathrm{M}}_{{\mathrm{Hampel}}}}$ control chart is also implemented with real‐life data which is taken from cost of medical insurance to demonstrate its competency in statistical process control field for quality engineers, practitioners, experts, and researchers. [ABSTRACT FROM AUTHOR]

Introduction: Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE‐MM1. Objectives and Methods: We conducted a retrospective–prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life. Results: At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high‐risk cytogenetic abnormalities [del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp], 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)‐exposed (including both Len‐sensitive and Len‐refractory pts), and 22% were Len‐refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non‐hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1‐2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow‐up of 38 m, median PFS (mPFS) was 16 m and the 1‐year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len‐naïve (NR), age ≥70 (20 m). In pts exposed to Len, non‐refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len‐refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31). Conclusion: IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len‐sensitive, independent of age, and cytogenetic risk. [ABSTRACT FROM AUTHOR]

Background: Spinal Muscular Atrophy (SMA) is a rare neuromuscular disorder characterized by progressive degeneration of motor neurons and muscle weakness resulting in premature death or severe motor disability. Over the last decade, SMA has dramatically changed thanks to new advances in care and the emergence of disease-specific treatments. RegistrAME is a self-reported specific disease registry with an accurate curation system. It has collected data on SMA patients in Spain since 2015, gathering demographic, clinical, and patient-reported outcome data, all of which are patient-relevant. RegistrAME is part of the TREAT NMD network. This study aims to describe the advantages and disadvantages of a self–reported SMA registry, as well as the different variables of interest in the health status of RegistrAME patients. Results: In total, 295 living patients with a confirmed diagnosis of SMA-5q were included (aged 1 to 77 years; mean 20.28). Half of the patients (50.2%) were ≥ 16 years old; 22.03% were type 1, 48.47% were type 2, 28.82% were type 3, and 0.7% were type 4. All functional statuses (non-sitter, sitter, and walkers) could be observed in each SMA type. Adult patients harbored the least aggressive SMA types, however, they presented the greatest level of disability. Patients with SMA type 1 had scoliosis surgery about five years earlier than patients with SMA type 2. None of the type 1 patients who achieved ambulation were wheelchair-free outdoors. This was also evident in 62.5% of type 2 walker patients and 44% of type 3 walker patients. Of the SMA type 1 patients, 40% had a gastrostomy (of which 84% had two SMN2 copies). One in five children with SMA type 1 (one to seven years of age) were ventilation-free. Conclusions: The information provided by RegistrAME in a "real-world" setting allows better management of family expectations, an adequate approach to the disease and patients' needs, as well as a better understanding of the impact of the disease. It also helps monitor the evolution of care, which will result in the need for updated guidelines. [ABSTRACT FROM AUTHOR]

Background: Local anesthetic (LA) drugs are commonly used in clinical practice to provide effective analgesia, including in dentistry and minor surgical procedures. The perception of a high risk of allergy in daily applications leads to the referral of atopic patients and those with other drug allergies to allergy clinics for the evaluation of allergic reactions to LA. The aim of this study was to determine who should be referred to the allergy clinic for LA allergy testing, assess the frequency of LA allergy in pediatric patients, and identify the negative predictive value of skin tests in diagnosis. Methods: January 2017–July 2023, the clinical and laboratory data, as well as the results of drug allergy tests, of patients referred to our pediatric allergy clinic by dentists and physicians performing minor surgical procedures with suspected LA allergy were retrospectively evaluated. Results: Our study included a total of 153 patients, comprising 84 girls (54.9%) and 69 boys (45.1%), with a mean age of 8.9 (±3.3) years. The most common reason for referral was a history of non‐LA drug allergies (n = 66, 43.2%), followed by asthma (n = 25, 16.3%). Hypersensitivity reactions (HRs) with LA were most commonly associated with articaine (n = 7, 4.8%), followed by lidocaine (n = 6, 4.1%). When intradermal tests were evaluated, 17 patients (11.1%) had a positive test result. The positivity for lidocaine was 70.6% (n = 12), and prilocaine was 29.4% (n = 5). Subcutaneous provocation was administered to 109 patients (71.2%), and one patient exhibited local erythema and swelling with prilocaine. Conclusion: Although LA allergy is a rare occurrence, consultations of this nature are frequently requested from allergy clinics in real life. Considering the negative predictive value of skin tests performed with LA drugs, the reaction rate appears to be low in patients with atopy or other drug allergies. It is crucial for all relevant healthcare professionals to be knowledgeable about the appropriate approach to suspected LA allergies to avoid unnecessary tests. To the best of our knowledge, our study is the most comprehensive work in the literature that evaluates the results of diagnostic tests in children referred with a suspicion of LA allergy. [ABSTRACT FROM AUTHOR]

Few studies have evaluated the effect of bovine lactoferrin (bLf) on reducing respiratory infections in preschool children. This randomized controlled trial evaluated the effect of bLf in preschool children with recurrent respiratory infections. Participants were randomly assigned bLf (n = 25) or control (n = 25). Outcomes included respiratory infection episodes (RIEs), symptom duration, school absence and medication. Fifty children aged 4.2 ± 0.1 years were included. During the active 4-month phase, median number of RIEs was reduced by 50% in the bLf group [1-episode, interquartile range (IQR): 0–2] vs. control (2, IQR: 1–3; p = 0.02). The proportion of participants with >3 RIEs was significantly lower in bLf (n = 1, 4%) vs. control (n = 7, 28%) with 80% lower odds of upper RIEs in the bLf arm (odds ratio: 0.20, 95% CI:0.06–0.74, p = 0.015). The duration of symptoms (3 vs. 6, p = 0.009) and days absent from school (3 vs. 6, p = 0.15) were lower in the active arm. Over the 2-month follow-up, no significant differences were observed between groups for infection episodes, symptom duration or school absence. However, bLf-treated children received significantly less corticosteroids over the entire 6-month study period (32% vs. 60%; p = 0.047). bLf supplementation significantly reduced the frequency and duration of RIEs in children with decreased corticosteroid use. [ABSTRACT FROM AUTHOR]

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation. [ABSTRACT FROM AUTHOR]

Background: The evaluation of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in clinical trials has shown high rates of virological suppression but information about its use in real-life settings is scarce. Objective: To evaluate the effectiveness, safety, durability, and predictive variables of therapeutic failure of BIC/FTC/TAF in a real-life cohort. Methods: This observational, retrospective, multicentered cohort study included treatment-naive (TN) and treatment-experienced (TE) adult patients living with HIV (PLWH) who started treatment with BIC/FTC/TAF from January 1, 2019, to January 31, 2022. Treatment effectiveness (based on intention-to-treat [ITT], modified ITT [mITT], and on-treatment [OT]), tolerability, and safety were evaluated in all patients who started BIC/FTC/TAF antiretroviral therapy. Results: We included a total of 505 PLWH of whom 79 (16.6%) were TN and 426 (83.4%) were TE. Patients were followed up for a median (interquartile range [IQR]) of 19.6 (9.6-27.3) months, and 76% and 56% of PLWH reached month 6 and month 12 of treatment, respectively. Rates of TN PLWH with HIV-RNA <50 copies/mL in the OT, mITT, and ITT groups were 94%, 80%, and 62%, respectively, after 12 months of BIC/FTC/TAF treatment. Rates of TE PLWH with HIV-RNA <50 copies/mL were 91%, 88%, and 75% at month 12. The multivariate analysis revealed that neither age, sex, CD4 cell count <200 cells/μL, or viral load >100 000 copies/mL were associated with therapeutic failure. Conclusion and relevance: Our real-life data showed that BIC/FTC/TAF is effective and safe for use in the treatment of both TN and TE patients in clinical practice. [ABSTRACT FROM AUTHOR]

Background and Objectives: Tirbanibulin 1% ointment is a novel synthetic anti-proliferative agent that inhibits tubulin polymerization. It is approved for treating actinic keratosis (AK) on the face and scalp in adults. It has demonstrated good efficacy, an adequate safety profile and excellent patient adherence in the phase 3 clinical trials, however data about its real-life efficacy and safety are lacking. Here we report the experience of the dermatology unit of the University Hospital of Messina. Materials and Methods: We performed a spontaneous open-label, prospective non-randomized study to assess the effectiveness and safety of tirbanibulin 1% ointment for the treatment of 228 AKs in 38 consecutive patients—28 males (73%) and 10 females (26%)—aged between 52 and 92 years (mean age: 72 ± 8.92 years). Results: Total clearance was recorded in 51% of lesions, while partial clearance was recorded in 73% of lesions. An excellent tolerability profile and high compliance rate were observed, with no treatment discontinuation due to the onset of adverse events. Conclusion: Our real-life experience confirms the effectiveness and safety of tirbanibulin ointment for the treatment of AKs. [ABSTRACT FROM AUTHOR]

Abstract Background The SQ tree sublingual immunotherapy (SLIT)‐tablet is authorised for treatment of allergic rhinoconjunctivitis with or without asthma in trees of the birch homologous group in 21 European countries. The primary objective of this study was to explore the safety in real‐life. Methods In a prospective, non‐interventional post‐authorisation safety study (EUPAS31470), adverse events (AEs) and adverse drug reactions (ADRs) at first administration and follow‐up visits, symptoms, medication use, and pollen food syndrome were recorded by physicians in 6 European countries during the first 4–6 months of treatment. Results ADRs with the SQ tree SLIT‐tablet were reported in 57.7% of 1069 total patients (median age 36.0 years, 53.7% female) during the entire observation period (severity, mild‐to‐moderate: 70.1%, severe: 4.7%, serious: 0.7%) and in 45.9% after first administration. ADRs were not increased with pollen exposure at first administration. With coadministration of the SQ tree and grass SLIT‐tablet AEs were reported in 73.8% of patients and in 52.8% with the SQ tree SLIT‐tablet alone. Nasal and eye symptoms improved in 86.9% and 80.9% of patients and use of symptomatic medication in 76.0%. PFS with symptoms was reported in 43.0% of patients at baseline and in 4.3% at the individual last visit. Conclusions The results of this non‐interventional safety study with the SQ tree SLIT‐tablet confirm the safety profile from placebo‐controlled clinical trials and support effectiveness in real‐life according to the published efficacy data. Safety was not impaired by pollen exposure at first administration or co‐administration with other SLIT‐tablets.

IntroductionLanadelumab is a first-line long-term prophylaxis (LTP) in hereditary angioedema (HAE). Real-life data on its long-term efficacy and safety are limited. It is unknown whether patients using lanadelumab need short-term prophylaxis (STP).ObjectivesTo provide 4-year follow-up data for our first 34 patients treating with lanadelumab.MethodsPatients were assessed for their current injection interval, attacks, treatment satisfaction, disease control (AECT), quality of life impairment (AE-QoL), events that can induce attacks, and the use of STP since the start of their treatment with lanadelumab.ResultsOf 34 patients who started lanadelumab treatment, 32 were still using it after 4 years, with a median injection interval of 33 (range 14-90) days. HAE patients (n=28) reported longer intervals, i.e. 35 (14-90) days, than patients with angioedema due to acquired C1 inhibitor deficiency (n=4, 23 (14-31) days). With their current injection intervals, used for a mean duration of 29 ± 17 months, patients reported a yearly attack rate of 0.3 ± 0.1. More than 70% of patients were attack-free since starting their current injection interval. All patients reported well-controlled disease, i.e. ≥10 points in the AECT; 21 patients had complete control (16 points). AE-QoL scores improved further compared to our initial report, most prominently in the fears/shame domain (-6 points). Treatment satisfaction was very high. No angioedema occurred after 146 of 147 potentially attack-inducing medical procedures without STP.ConclusionsOur results demonstrate the long-term efficacy and safety of lanadelumab in real-life and question the need for STP in patients who use effective LTP.

Background: Although randomized controlled trials (RCT) are the reference standard of evidence in allergen immunotherapy (AIT), nonrandomized studies (NRS) are needed to confirm their results in more representative populations, particularly for treatment duration and persistence. However, when discrepancies are observed between RCT and NRS, NRS reliability decreases because these discrepant results are generally attributed to the methodologic flaws of NRS. Objective: We compared the benefit of sublingual AIT (SLIT) for allergic rhinoconjunctivitis in NRS versus RCT focusing on a single product/allergen to reduce heterogeneity. Methods: For meta-analysis, house dust mite (HDM) SLIT liquid formulation studies were sourced from computerized (Medline, Web of Science, and LILACS databases, to January 2023) and manual literature searches. Populations, treatments, and outcome data were combined (DerSimonian-Laird method). Noncomparative NRS were compared to RCT’ SLIT arm before and after treatment. Efficacy was determined as the standardized mean difference (SMD) in symptom score (SS) and medication score (MS). Results: Data from 12 NRS (682 patients) and 8 RCT (176 patients) were analyzed. The benefit with index of reactivity (IR)-HDM SLIT liquid formulation was found significant for, first, SS in both NRS (SMD = −1.27; 95% confidence interval [CI], −1.64, −0.90) and RCT (SMD = −0.56; 95% CI, −0.90, −0.21), and second, MS with SMD equal to −1.35 (95% CI, −1.77, −0.93) and −0.46 (95% CI, −0.67, −0.25), respectively. Metaregression showed that symptom improvement was correlated with treatment duration with consistent results in NRS and RCT with 12-month SS data: −0.87 (interquartile range, −1.02, −0.77) and −0.75 (interquartile range, −0.93, −0.41), respectively. Conclusion: This meta-analysis showed comparable clinical benefit of IR-HDM SLIT liquid formulation increasing over time in both NRS and RCT, suggesting that NRS may reliably integrate RCT results and be considered for guidelines.

Background: Bictegravir (BIC), a recently introduced integrase inhibitor, is available in a single tablet regimen with tenofovir alafenamide (TAF) and emtricitabine (FTC) (BIC-STR). This study aimed to describe a real-life experience with BIC-STR. Methods: We retrospectively analyzed the data of people living with HIV (PLWH) on antiretroviral therapy (ART) with BIC-STR followed by the Clinic of Infectious Diseases of Perugia (Perugia, Italy) from September 2019 to February 2023. Results: 270 PLWH were enrolled with a median follow-up time on BIC-STR of 2.2 years (IQR 1.2–2.7). In the overall population, in treatment-experienced (N = 242), in treatment-naïve (N = 28), and in population with age > 60 years old (N = 86), we observed that CD4 cell count improved in absolute number, percentage and CD4/CD8 ratio, under BIC-STR. Patients with viremia < 50 cp/mL increased in all groups. In the overall population, previous ART with TAF and nadir CD4 cell count favored immunological recovery. In the ART-experienced group, time in therapy with BIC-STR was associated with HIV-RNA undetectability. In the older group, previous opportunistic infection and advanced age were associated with lower CD4 count. Conclusions: BIC-STR was demonstrated, in real-life, to be a valid option for a switch, such as initial ART.

Wei Su,1,2 Dong Liu,2 Pingliang Yang,3 Ling Ye1 1Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Department of Pain Management, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610011, People’s Republic of China; 3Department of Anesthesiology, the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of ChinaCorrespondence: Ling Ye, Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85423593, Email zerodq_hx@163.comPurpose: The aim of this study was to analysis of the opioid use of opioid native zoster-related pain (ZRP) patients to evaluate the impact of opioid use on pain control and quality of life improvement based on the clinical database.Patients and Methods: We conducted a retrospective cohort study to identify opioid native patients who were hospitalized in the pain department between May 1, 2020, and May 1, 2021. The primary outcomes were persistent opioid use after discharge, visual analogue scale (VAS) at the admission, VAS remission rate during hospitalization, VAS score and quality of life at follow-up. Then, we assessed patient-level risk factors for persistent opioid use after the discharge.Results: A total of 350 patients met the inclusion criteria. Of those patients, 255 (72.9%) were administered with opioid during hospitalization, and 95 (27.1%) patients were not. Opioid prescription during hospitalization was independently associated with increased odds of persistent use after the discharge (adjusted odds ratio, 20.74; 95% CI, 4.504– 95.474; P < 0.01). In the two groups, the VAS score at admission and the VAS score at follow-up were different. In the group with opioids during hospitalization, the persistent opioid use after discharge was more common (38% vs 2.1%) compared to patients without opioids, and VAS remission rate during hospitalization was less, restrictions on daily life, work or housework, and social activities were more common, and mood, diet and sleep were worse, respectively.Conclusion: Opioids prescription during hospitalization might increase the risk of chronic opioid use in opioid native ZRP patients, and it has limited benefits in pain control and quality of life improvement. Even though PHN was painful and intractable, the use of opioids should also be more cautious, and strict follow-up, management in this population.Keywords: opioids, persistent opioid use after discharge, real-life, zoster-related pain, postherpetic neuralgia

Background: The advent of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a challenge. Objective: This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. Methods: We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Results: Our search included 61 pertinent studies conducted between 2019 and 1 March 2024. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, and disability), high responder rates, and optimal safety and tolerability profiles. Conclusions: Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an extraordinary finding in clinical neurology.

Treatment of lenalidomide refractory (Len-R) multiple myeloma (MM) patients still represents an unmet clinical need. In the last years, daratumumab-bortezomib-dexamethasone (D-VD) combination was extensively used in this setting, even though only a small fraction of Len-R patients was included in the pivotal trial. This real-life study aimed to evaluate the efficacy and safety of the D-VD regimen in a cohort that exclusively enrolled Len exposed or refractory MM patients. The study cohort included 57 patients affected by relapsed/refractory MM. All patients were previously exposed to Len, with 77.2% being refractory. The overall response rate (ORR) was 79.6% with 43% of cases obtaining at least a very good partial response (VGPR). The D-VD regimen showed a favorable safety profile, with low frequency of grade 3–4 adverse events, except for thrombocytopenia observed in 21.4% of patients. With a median follow-up of 13 months, median progression-free survival (PFS) was 17 months. No significant PFS differences were observed according to age, ISS, LDH levels, type of relapse, and high-risk FISH. Len exposed patients displayed a PFS advantage as compared to Len refractory patients (29 vs 16 months, p = 0.2876). Similarly, patients treated after Len maintenance showed a better outcome as compared to patients who had received a full-dose Len treatment (23 vs 13 months, p = 0.1728). In conclusion, our real-world data on D-VD combination showed remarkable efficacy in Len-R patients, placing this regimen as one of the standards of care to be properly taken into account in this MM setting. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background: Biologics targeting IL‐23 and IL‐17 show efficacy and safety in the treatment of moderate‐to‐severe psoriasis. Objective: To investigate drug survival in patients with psoriasis treated with biologics. Patients and methods: We performed a comparative evaluation of the achievement of PASI 90 and PASI ≤ 3 at 16, 28, and 52 weeks along with a DS (drug survival) analysis with IL‐17 and IL‐23 inhibitors brodalumab, ixekizumab, secukinumab, risankizumab, tildrakizumab, and guselkumab on 1,057 patients. Results: IL‐17 inhibitors showed a faster achievement of PASI 90 and PASI ≤ 3 with significant superiority over IL‐23 inhibitors at week 16 (p < 0.001; 56% vs. 42% and 70% vs. 59%, respectively). A difference was shown in favor of IL‐23 inhibitors regarding DS (p < 0.001), which was 88% at 24 months vs. 75% for IL‐17 inhibitors. In multivariate analysis, IL‐23 inhibitors (HR 0.54 CI 0.37–0.78, p = 0.001), and male sex (HR 0.57 CI 0.42–0.76, p < 0.001) were all associated with a lower probability of drug interruption. Risankizumab (HR 0.42 CI 0.26‐0.69, p = 0.001), guselkumab (HR 0.49 CI 0.24–0.99, p = 0.046), and male sex (HR 0.57 CI 0.43–0.77, p < 0.001) were associated with a lower probability of drug interruption than secukinumab. Conclusions: IL‐23 inhibitors showed the best performance on DS. Overall, the most effective class was IL‐17 inhibitors considering the short‐term effectiveness, but long‐term effectiveness is in favor of anti‐IL‐23. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Hospital Pharmacy / Journal Canadien de la Pharmacie Hospitalière is the property of Canadian Society of Hospital Pharmacists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background The objective of this study was to expand real-life data on cefiderocol efficacy to treat multidrug-resistant Acinetobacter baumannii infections. Methods This was a retrospective monocentric study including patients hospitalized (>24 hours) at Policlinico Tor Vergata, Rome, Italy, between May 1, 2021, and September 1, 2022, treated with cefiderocol (>48 hours). The primary objective was early clinical improvement at 48–72 hours from cefiderocol start; secondary objectives were clinical success (composite outcome of infection resolution and 14-day survival), breakthrough infection, overall 30-day mortality, and cefiderocol-related adverse events. Results Eleven patients were enrolled; 91% males (10/11), with a median age (interquartile range [IQR]) of 69 (59–71) years, 91% had ≥1 comorbidity, and 72.7% (8/11) were hospitalized in internal medicine wards. Six patients with bloodstream infection (54.5%; 4 primary, 2 central line–associated), 2 with pneumonia (18.2%), 2 with urinary tract infections (18.2%), and 1 with intra-abdominal infection (9.1%) were treated. Four patients (36.3%) presented with septic shock at cefiderocol start. Cefiderocol was used as monotherapy in 3/11 patients (27.3%), was combined with colistin in all the other 8 cases, and was used in triple combination with tigecycline in 2 patients. The median duration of treatment (IQR) was 12 (10–14) days. Early clinical improvement was documented in 8/11 patients (72.7%), clinical success in 8/11 patients (72.7%). Overall 30-day mortality was 27.3% (3/11), with death occurring a median (IQR) of 19 (17.5–20.5) days after the start of therapy. No cefiderocol-related adverse events were documented. Conclusions Cefiderocol seems to be a safe and effective option for multidrug-resistant Acinetobacter baumannii infections. [ABSTRACT FROM AUTHOR]

A panel of chronic lymphocytic leukemia (CLL) experts from Tuscany propose a real-life diagnostic and therapeutic approach CLL that considers the role of genomic and somatic prognostic factors in risk stratification and treatment decisions. Safety and efficacy of new agents has been demonstrated now not only in clinical trials but also in many real-world series. The BTK inhibitors, ibrutinib and acalabrutinib, and BH3 mimetic venetoclax are now indicated as first-line therapy and chemoimmunotherapy can be spared to the majority of CLL patients, thus preventing unnecessary hematological and non-hematological toxicity and second primary tumors. For treatment, FISH for 17 p and P53 mutational status are essential. IGHV mutation can be done at diagnosis or before treatment. Echography is the gold standard radiological investigation in CLL, at both diagnosis and response evaluation. Chemotherapy is virtually abandoned. Age, genetic risk, and patient comorbidities have to be carefully evaluated for treatment decision. With the availability of different drugs, there is a need for a uniform and shared approach in daily therapeutic choice. The proposed approach is based on current evidence and guidelines as well as results from clinical trials and daily clinical experience. [ABSTRACT FROM AUTHOR]

Background: Bictegravir (BIC), a recently introduced integrase inhibitor, is available in a single tablet regimen with tenofovir alafenamide (TAF) and emtricitabine (FTC) (BIC-STR). This study aimed to describe a real-life experience with BIC-STR. Methods: We retrospectively analyzed the data of people living with HIV (PLWH) on antiretroviral therapy (ART) with BIC-STR followed by the Clinic of Infectious Diseases of Perugia (Perugia, Italy) from September 2019 to February 2023. Results: 270 PLWH were enrolled with a median follow-up time on BIC-STR of 2.2 years (IQR 1.2–2.7). In the overall population, in treatment-experienced (N = 242), in treatment-naïve (N = 28), and in population with age > 60 years old (N = 86), we observed that CD4 cell count improved in absolute number, percentage and CD4/CD8 ratio, under BIC-STR. Patients with viremia < 50 cp/mL increased in all groups. In the overall population, previous ART with TAF and nadir CD4 cell count favored immunological recovery. In the ART-experienced group, time in therapy with BIC-STR was associated with HIV-RNA undetectability. In the older group, previous opportunistic infection and advanced age were associated with lower CD4 count. Conclusions: BIC-STR was demonstrated, in real-life, to be a valid option for a switch, such as initial ART. [ABSTRACT FROM AUTHOR]

Background & Aims: Subcutaneous vedolizumab formulation has been shown to be as effective and safe as the intravenous one in randomized control trials. Real-life data are limited especially for patients receiving long-term intravenous therapy. This study aimed to evaluate the safety and effectiveness of switching from intravenous to subcutaneous vedolizumab in a large cohort of patients with stable clinical remission. Methods: In this prospective cohort study, we enrolled consecutive patients attending our center between September 2021 and April 2022. The baseline demographic characteristics, 12- and 24-weeks follow-up clinical activity, C-reactive protein levels, and adverse events were recorded. The primary endpoint was to assess combined steroid-free clinical remission plus biochemical remission 24-week after the switch. Results: 93 patients (43 Crohn's disease, 50 ulcerative colitis), switched to subcutaneous vedolizumab after a median duration of intravenous treatment of 36 months [IQR 16-52]. At baseline, 80 patients (86%) had a combined remission. At 24-week, 89.2% (n=74) maintained combined steroid-free clinical remission plus biochemical remission. 25 adverse events were reported, mostly SARS-CoV-2 infections and injection site reactions, with a further four recurrence episodes. Twelve patients (12.9%) discontinued subcutaneous administration and restarted intravenous vedolizumab. Conclusions: Switching from intravenous to subcutaneous vedolizumab can be considered effective and safe for maintaining remission in patients with inflammatory bowel disease. In addition, this might reduce healthcare costs. However, large-scale real-life studies with long-term follow-up are necessary. [ABSTRACT FROM AUTHOR]

Plant-based meat substitutes replacing animal meat can potentially support the transition towards more sustainable diets. To enable the required transition, consumer acceptance of plant-based meat is essential. An important aspect of this is the feeling of satiety or being full after eating. This study determined the satiating capacity of both plant-based meat and animal meat in 60 adults under real-life in-home conditions. Participants consumed four fixed ready-to eat meals for lunch at home once per week. Two types of Indian curry with 'chicken' were investigated as well as two types of pasta Bolognese with 'minced meat'. The two 'chicken' dishes and the two 'minced meat' dishes had the same recipe except for a gram-for-gram swap (125 g each) of either animal meat (chicken breast and minced meat) or plant-based (soy) meat. Results showed no difference in the satiating power of an animal meat dish and a plant-based meat dish when these were eaten as part of a full lunch meal at home. In addition, the meals did not result in energy nor macronutrient compensation during the rest of the day after consuming the meals. This occurred despite the caloric differences of the meals as a result of the real-life conditions (i.e., a lower energy content of the pasta with plant-based meat compared to the other meals). We conclude that meals with plant-based meat can be as satiating as meals with animal meat. [ABSTRACT FROM AUTHOR]

Multiple myeloma is a chronic hematologic malignancy that obstinately tends to relapse. Basic research has made giant strides in better characterizing the molecular mechanisms of the disease. The results have led to the manufacturing of new, revolutionary drugs which have been widely tested in clinical trials. These drugs have been approved and are now part of the therapeutic armamentarium. As a consequence, it is essential to combine what we know from clinical trials with real-world data in order to improve therapeutic strategies. Starting with this premise, our review aims to describe the currently employed regimens in multiple myeloma and compare clinical trials with real-life experiences. We also intend to put a spotlight on promising therapies such as T-cell engagers and chimeric antigen receptor T-cells (CAR-T) which are proving to be effective in changing the course of advanced-stage disease. [ABSTRACT FROM AUTHOR]

Background: To compare 24‐month real‐world outcomes of Vascular Endothelial Growth Factor (VEGF) inhibitors for Polypoidal Choroidal Vasculopathy (PCV) and type 1 Macular Neovascularization (MNV) in a Caucasian population. Methods: Retrospective analysis from a prospectively designed observational database. Data from Italian centres participating in the Fight Retinal Blindness! (FRB!) project were collected. Treatment‐naïve PCV or type 1 MNV commencing treatment after January 2009 were included. The primary outcome was 24‐month visual acuity (VA) change; other outcomes included baseline characteristics, number of anti‐VEGF injections, time to lesion inactivation and proportion of active visits. Results: A total of 322 eyes (114 PCVs) from 291 patients were included. Median [Q1, Q3] VA at baseline was comparable (70 [55, 75.8] vs. 70 [58.8, 75] letters, p = 0.95). Adjusted VA change at 2 years was higher in PCV (mean [95% CI], +1.2 [−1.6, 4.1] vs. −3.6 [−6, −1.2] letters, p = 0.005). PCV received fewer anti‐VEGF injections over the first 24 months of treatment than type 1 MNV (median [Q1, Q3], 8 [5, 10] vs. 9 [7, 12.2] injections, p = 0.001), inactivated earlier (median [Q1, Q3], 235 [184, 308] vs. 252 [169, 343] days, p = 0.04) and was less frequently graded 'active' (62% vs. 68% of visits, p = 0.001). Conclusions: PCV had slightly better VA outcomes over 24 months of treatment than type 1 MNV after receiving less anti‐VEGF injections. These results suggest a possible overlap of the two clinical entities with similar visual prognosis in Caucasians. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy of conventional treatments for alopecia areata (AA) has been extremely variable and disappointing, with a high rate of relapse. Recent clinical trials and real-life studies have demonstrated efficacy and safety of baricitinib (an oral Janus kinase 1 and 2 inhibitor) in alopecia areata. Methods: We retrospectively evaluated the effectiveness and tolerance of baricitinib in alopecia areata in a real-life Belgian monocentric adult cohort. The primary outcome was evaluated by the percentage of patients who achieved a Severity of Alopecia Tool (SALT) score of ≤ 20 at the end of the follow-up. All treatment-emergent adverse events were collected. Results: In this 19-patient series, with a median ± interquartile range (IQR) follow-up duration of 13 ± 16.2 months, we demonstrated that: (i) hair regrowth was observed in nearly 90% of patients between 4 and 16 weeks after initiation of baricitinib; (ii) at the end of the follow-up, more than 70% and, in particular, 100% of patients with patchy AA, reached the primary outcome (SALT score ≤ 20); (iii) almost half of the patients, mostly with patchy AA, showed a complete hair regrowth (SALT score = 0), within a median ± IQR treatment time of 8.5 ± 10 months; (iv) baricitinib was discontinued in three patients with total hair regrowth, two of whom relapsed; and (v) no serious adverse events were reported. Conclusion: Baricitinib is effective in treating patients with alopecia areata, particularly for the patchy phenotype, but with a risk of relapse after discontinuation. Safety data are reassuring, with lipid changes being the most frequent adverse event. [ABSTRACT FROM AUTHOR]

Abstract Introduction Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE‐MM1. Objectives and Methods We conducted a retrospective–prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life. Results At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high‐risk cytogenetic abnormalities [del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp], 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)‐exposed (including both Len‐sensitive and Len‐refractory pts), and 22% were Len‐refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non‐hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1‐2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow‐up of 38 m, median PFS (mPFS) was 16 m and the 1‐year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len‐naïve (NR), age ≥70 (20 m). In pts exposed to Len, non‐refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len‐refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31). Conclusion IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len‐sensitive, independent of age, and cytogenetic risk.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce the risk of cardiovascular (CV) complications in patients with type 2 diabetes (T2DM) and atherosclerotic cardiovascular disease (ASCVD) in placebo-controlled CV outcome trials, yet the use of these cardioprotective agents remains rather low in clinical practice. Methods: Analysis of the proportion of T2DM patients treated with GLP-1RAs in retrospective observational studies by comparing patients with versus without established ASCVD. Results: Nine cohorts from seven studies were collected in the international literature between 2019 and 2022. Overall, the percentages of patients treated with GLP-1RAs were low (< 10 %) in most studies, yet a progressive increase was noticed over time. The use of GLP-1RAs in patients with ASCVD was slightly lower in 7 out of 9 cohorts not higher when compared to the use in patients without ASCVD (odds ratio 0.80, 95 % CI 0.79–0.81). Conclusion: Despite a positive trend over the last decade, the real-world use of GLP-1RAs remains limited, especially in patients with established ASCVD. Bridging the gap between clinical evidence of cardioprotective effects of GLP-1RAs and their underuse in clinical practice in T2DM patients at high/very high CV risk should be considered as a key objective for health care providers, especially cardiologists.

AIM: To evaluate the efficacy and tolerability of administering a combined therapy in patients with dry eye syndrome (DES) and associated laryngopharyngeal reflux (LPR). METHODS: The study was retrospective, open, observational, and conducted in a real-life setting. Patients had pathological symptom assessment in dry eye (SANDE) and reflux symptom index (RSI) at baseline. Patients were re-assessed after 1mo and at the end of treatment. The treatment consisted of a three-month course based on the combined therapy: Gastroftal eye drops, one drop three times a day, and Gastroftal tablets, two tablets after lunch and two tablets after dinner. Tear break-up-time (TBUT) test, Schirmer test, RSI, and SANDE questionnaire were evaluated. RESULTS: The study included 253 patients. The mean age was 58±11.19y. TBUT test score and Schirmer's test significantly increased (both P