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ABSTRACT Isatuximab, a novel anti‐CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa‐Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real‐world efficacy and safety are poorly reported. In this Italian multicenter real‐life observational retrospective study, efficacy and safety of the Isa‐Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1‐year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa‐Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1‐year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa‐Kd as an effective treatment option for RRMM with a manageable safety profile even in real‐life settings. [ABSTRACT FROM AUTHOR]

Aim: We retrospectively evaluated the effect of dabrafenib/trametinib combination in patients with BRAF-mutated non-small-cell lung cancer (NSCLC) treated in a single center from 2017 to 2022. Patients: The response and safety data of 42 patients (27 treated in first-line and 15 as second/subsequent lines) were analyzed. Results: The objective response was 73.8%, with no differences between patients undergoing first- or second-line. A longer, statistically significant median progression-free survival (PFS) was observed in patients receiving the combination in first-line vs those in the second/subsequent lines (19.9 months [95% CI: 19.7–20] vs 13.1 months [95% CI: 8.6–17.6], respectively; p = 0.012). The median overall survival (OS) was 29.9 months (95% CI: 14.1–45.7) for patients treated with the combination in first-line and 22.4 months (95% CI: 14.6–30.2) for those treated in subsequent lines. The combination was well tolerated Conclusion: We confirm the efficacy of dabrafenib/trametinib in BRAF-V600-mutated NSCLC. First-line treatment of dabrafenib and trametinib is effective in non-small-cell lung cancer patients with V600 BRAF mutation. A longer, statistically significant median progression-free survival was found in patients receiving the combination in first-line versus those in the second/subsequent lines. The efficacy is confirmed in real-world setting from a single center. More than 70% of the patients reached a partial response. The combination is safe with dose reduction necessary only in two patients for pyrexia. The treatment is feasible in elder patients. [ABSTRACT FROM AUTHOR]

Background: Dupilumab, a monoclonal antibody targeting IL-4 and IL-13, has demonstrated its efficacy in several clinical trials. However, to date, real-life data remains limited. Objective: The aim of our study was to assess the real-life impact of dupilumab on patients with severe and uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) quality of life. Materials and methods: This was a retrospective, monocentric, observational, real-life study, conducted in accordance with the STROBE guidelines. The following parameters were collected before treatment and at 1, 4, and 12 months: Sino-Nasal Outcome Test-22 (SNOT-22), nasal polyp score (NPS), Sniffin' Sticks-16 (SST-16), visual analog scale (VAS) for loss of smell, nasal congestion score (NCS), gustatory VAS, asthma control, oral corticosteroid usage, surgery rates, and occurrence of side effects. Results: The study included 47 patients. SNOT-22 scores decreased from 52.4 ± 24.3 to 12.7 ± 10.5 at 12 months (p < 0.001). NPS decreased from 6.15 ± 1.71 to 1.57 ± 1.40 at 12 months (p < 0.001). SST-16 scores increased from 1.6 ± 2.83 to 9.1 ± 5.4 at 12 months (p < 0.001). NCS decreased from 2.45 ± 0.72 to 0.38 ± 0.63 at 12 months (p < 0.001). Prior to treatment, 72.3% were using oral corticosteroids, compared to 17.0% at 12 months (p < 0.01). Two patients required additional surgery, and 17% reported completely uncontrolled asthma, compared to 0% at 12 months (p < 0.01). Conclusion: Our real-life results confirm the efficacy of Dupilumab in the treatment of severe and uncontrolled CRSwNP. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy and safety of tildrakizumab for the treatment of plaque psoriasis were demonstrated by randomized clinical studies, but the reappraisal of prolonged experiences in the clinical practice helps to optimize the use of this biologic drug. The aim of this study was to evaluate the long-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the real world. Methods: This is a long-term retrospective observational study in a real-life setting. Overall, 136 adult patients with moderate-to-severe plaque psoriasis and treated with tildrakizumab were included. Results: One hundred percent reduction of Psoriasis Area Severity Index (PASI100) was reached by 21.7% of patients at 4 weeks of therapy and by 51.2% at week 16, and the proportion of patients with this improvement was between 66.9% and 64.5% from 36 weeks to 3 years. The mean PASI of the cohort progressively improved from 12.6 at baseline to 1.8 at week 36 and was stable at 1 year, 2 years and 3 years. We could not confirm a previous observation that patients naïve to biologic had a better response, but we observed that those with a short history of psoriasis had a higher probability of 90% PASI reduction (PASI90) or PASI 100 within 36 weeks, suggesting that early treatment could be useful. Conclusion: This long-term observation in the real life of patients with moderate-to-severe plaque psoriasis receiving tildrakizumab 100 mg showed that PASI100 can be obtained in a high proportion of patients by week 36 and be maintained for up to 3 years. [ABSTRACT FROM AUTHOR]

Abstract Introduction The efficacy and safety of tildrakizumab for the treatment of plaque psoriasis were demonstrated by randomized clinical studies, but the reappraisal of prolonged experiences in the clinical practice helps to optimize the use of this biologic drug. The aim of this study was to evaluate the long-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the real world. Methods This is a long-term retrospective observational study in a real-life setting. Overall, 136 adult patients with moderate-to-severe plaque psoriasis and treated with tildrakizumab were included. Results One hundred percent reduction of Psoriasis Area Severity Index (PASI100) was reached by 21.7% of patients at 4 weeks of therapy and by 51.2% at week 16, and the proportion of patients with this improvement was between 66.9% and 64.5% from 36 weeks to 3 years. The mean PASI of the cohort progressively improved from 12.6 at baseline to 1.8 at week 36 and was stable at 1 year, 2 years and 3 years. We could not confirm a previous observation that patients naïve to biologic had a better response, but we observed that those with a short history of psoriasis had a higher probability of 90% PASI reduction (PASI90) or PASI 100 within 36 weeks, suggesting that early treatment could be useful. Conclusion This long-term observation in the real life of patients with moderate-to-severe plaque psoriasis receiving tildrakizumab 100 mg showed that PASI100 can be obtained in a high proportion of patients by week 36 and be maintained for up to 3 years.

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06–30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24–14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04–1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94–6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71–76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10−19–NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19–269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05–16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22–20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58–91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7–75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9–112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16–73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response. [ABSTRACT FROM AUTHOR]

Objectives: To study real-world effect of switching to Insulin Glargine 300 U/mL (Gla-300) on glucose metrics in people with type 1 diabetes. Methods: This retrospective secondary-use study compared 151 adults who switched to Gla-300 from first-generation long-acting insulins (Switchers) to 281 propensity-score matched controls (Non-switchers) who continued first-generation long-acting insulins. Primary endpoint was difference in time in range (TIR) evolution. A fictive "switching" date was assigned to Non-switchers to facilitate between-group comparisons. Results: In the period before switching, TIR decreased numerically for people in whom Gla-300 was eventually initiated (−0.05%/month [−0.16 to 0.07]), while it increased for matched controls (0.08%/month [0.02 to 0.015]; between-group difference P = 0.047). After Gla-300-initiation, Switchers had similar TIR increase compared to Non-switchers (P = 0.531). Switchers used higher basal dose than before switch (Δ0.012 U/[kg·d] [0.006 to 0.018]; P < 0.0001). Conclusion: In real-life, Gla-300 was typically initiated in people where TIR was decreasing, which was reversed after switch using slightly higher basal insulin dose. ClinicalTrials:ClinicalTrials.gov number NCT05109520. [ABSTRACT FROM AUTHOR]

Background: According to recent data, the age of patients could represent an important risk factor for MACE (major cardiovascular events), cancer, and VTE (venous thromboembolism) during treatment with JAK inhibitors in rheumatoid arthritis. We decided to analyze the population involved in the ReLiFiRa study by identifying two groups of patients: 65 years or more and less than 65 years of age, evaluating the efficacy and tolerability of 200 mg of Filgotinib daily. Methods: Of the 120 ReLiFiRa patients, 54 were younger than 65 years old and 66 patients were 65 years old or older. The data of efficacy and tolerability of treatment with FIL 200 mg daily for 6 months were evaluated. Results: After six months of treatment, FIL was effective in both age groups. In both groups, the median values of steroid DAS28, CDAI, ERS, PCR, tender joints, swollen joints, VAS, HAQ, PGA patients, and PGA physicians were reduced with a statistically significant difference comparing these values with the baseline values. The difference in age did not impact the effectiveness of the drug. The lipid profile data also did not demonstrate significant differences between the two age groups; however, the comparison between younger vs. older patients' populations regarding the total cholesterol/HDL ratio and LDL/HDL ratio shows a statistically significant difference: total cholesterol/HDL 3.4 (2.12–3.66) vs. 3.64 (3.36–4.13) p = 0.0004, LDL/HDL 1.9 (0.98–2.25) vs. 2.41 (2.04–2.73) p = 0.0002. There are no differences regarding the atherogenic index (LDL-C/HDL-C) and coronary risk index (TC/HDL-C) compared to baseline. Conclusions: After six months of treatment with FIL, the older population group showed a higher level of LDL and a lower level of HDL compared to younger patients. The atherogenic index and coronary risk index are higher in patients aged ≥ 65 years, but interestingly, there were no differences when comparing the 6-month data to baseline values. This condition highlights the impact of typical risk factors that act independently of treatment with Filgotinib. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. HPV infection and persistency may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. The objective was to prospectively evaluate the results of using a Coriolus-versicolor-based vaginal gel (Papilocare®) on HPV-dependent low-grade cervical lesion repair in a real-life scenario. HPV-positive women _ 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). A 6-month second treatment cycle was prescribed when needed. Repair of the cervical low-grade lesions through cytology and colposcopy, HPV clearance, and level of satisfaction, and tolerability were evaluated. In total, 192 and 201 patients accounted for the total and safety analyses, respectively, and 77.1% repaired cervical lesions at 6 or 12 months (76.0% for high-risk HPV). Additionally, 71.6% achieved HPV clearance throughout the study’s duration (70.6% for high-risk HPV). Satisfaction level was rated 7.9 and 7.5 out of 10 at 6 and 12 months, respectively. Only three mild–moderate product-related adverse events were reported, and all of them were resolved by the end of the study. In our study, we observed higher regression rates of low-grade cervical lesions in women treated with Papilocare® vaginal gel than spontaneous regression rates reported in the literature. [ABSTRACT FROM AUTHOR]

Summary: Background: In prior randomised controlled trials, lung cancer screening using low-dose computed tomography (LDCT) has been shown to reduce lung cancer mortality and overall mortality. Despite these results, organised screening in France remains a challenge.This study assessed the feasibility and efficacy of lung cancer screening within a real-life context in a French administrative territory. Methods: DEP KP80 was a single-arm prospective study. Participants aged between 55 and 74 years, smokers or former smokers of ≥30 pack-years, were recruited. An annual LDCT scan was scheduled and three rounds were performed. Subjects were selected by general practitioners or pulmonologists, who checked the inclusion criteria and prescribed the CT scan. Findings: Between March 2016 and February 2020, 1254 participants were enrolled. Overall, 945 (75.4%) participants underwent baseline LDCT (T0), 376 (42.8%) completed the first round (T1) and 270 (31%) the second (T2) one. Forty-two lung cancers were diagnosed, 30 cancers (71.4%) were stage I or II and 34 cancers (80.9%) were treated surgically. In this study, the overall positive predictive value for a positive screening was 48% (95% CI 37–59) and the negative predictive value 100% (95% CI 100–100). Interpretation: This study demonstrated the feasibility and efficacy of lung cancer screening in a real-life context with most lung cancers diagnosed at an early stage and surgically removed. Our results also highlighted the importance of participation in each round, underlining the fact that optimising organisation is a major goal. Funding: Agence Régionale de Santé de Picardie, La Ligue contre le cancer, le Conseil Départemental de la Somme, and AstraZeneca.

Abstract Introduction Several systemic therapies have been approved for the treatment of severe AD. In particular, Janus kinase inhibitors (JAKi), including abrocitinib, baricitinib, and upadacitinib, recently received approval for the treatment of patients with severe AD after being evaluated in several clinical trials. However, a few concerns have been raised regarding their long-term safety and the management of these drugs in real-world clinical practice. In this article we described the results of a Delphi consensus aimed at describing the knowledge on JAKi and focusing, in particular, on providing clinical recommendations for dermatologists in daily practice regarding the use of these drugs. Methods Twelve Italian dermatologists reviewed the most recent literature regarding the efficacy and safety profiles of JAKi and proposed 24 statements. Results Agreement was reached for statements focusing on three main topics: (1) place in therapy of JAKi in patients with moderate-to-severe AD; (2) effectiveness and safety of JAK inhibitors in different phenotypes; (3) different approaches to the management of patients treated with JAKi in clinical practice. The panel proposed several recommendations regarding all the statements. Conclusion Given the wide use of JAKi in clinical practice, it is crucial to establish a specific follow-up for each patient’s phenotype in order to achieve the best possible clinical outcome and minimize potential adverse events.

Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of interleukin (IL)-23. Despite its effectiveness and safety, which have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 are limited or characterized by a reduced follow-up period. These data are essential to guide clinicians in biologic switching, considering that anti-IL23 and anti-IL17 partially share their therapeutic targets, as well as some patients who may have to interrupt treatment with anti-IL17 for loss of efficacy over time or the development of adverse events (AEs). In this context, we performed a retrospective study with the aim of evaluating the long-term use (2 years) of guselkumab in psoriasis patients who previously failed at least one anti-IL17 in a real-life setting, also focusing attention on psoriasis located in difficult-to-treat areas (the scalp, palms or soles, fingernails, genitals). A total of 61 patients (35 male, 57.4%; mean age 57.6 ± 8.8 years) were enrolled. Of these, 30 (49.2%) patients failed secukinumab, 21 (34.4%) failed ixekizumab, 7 (11.5%) failed brodalumab, and 3 (4.9%) failed both secukinumab and ixekizumab. At the baseline, the mean PASI and BSA were 12.8 ± 8.4 and 24.5 ± 26.6, respectively. During week 16, PASI90 and PASI100 responses were achieved by 60.7% and 37.7% of patients, respectively, which continued to improve up to week 104 (PASI90: 73.8%, PASI100: 59.0%). Clinical improvement in difficult-to-treat areas was detected as well. In particular, a slower improvement for fingernails and the palmoplantar region was reported compared to scalp and genital psoriasis at week 16. However, no differences were found following 28 weeks of therapy. Primary and secondary inefficacy were reported by 1 (1.6%) and 5 (8.2%) patients. As regards safety, no severe AEs were collected. [ABSTRACT FROM AUTHOR]

Background: Proteasome inhibitors (PIs) represent one of the most effective classes of therapy for patients with multiple myeloma (MM) and are incorporated in many of the current treatment regimens. The first-generation PI, bortezomib, has shown impressive results in patients with either newly diagnosed or relapsed/refractory MM, but once patients become resistant, treatment is increasingly challenging. Although the existing data show that the second-generation PI, carfilzomib, is highly efficient, there is still limited knowledge regarding the response to carfilzomib-based therapy in bortezomib-resistant patients. The aim of this study was to evaluate carfilzomib treatment performance in bortezomib-sensitive versus -refractory patients, in a real-life eastern European country setting. Methods: We retrospectively evaluated 127 adult patients exposed to bortezomib with relapsed or refractory MM, that subsequently received a carfilzomib-based therapy. We investigated the differences in the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) after carfilzomib-based therapy between the two patient groups. Results: The ORR in the bortezomib-sensitive group was significantly higher than that in the refractory group, leading to a superior PFS in this category of patients. For patients presenting with a high cytogenetic risk, we observed a significant difference in PFS between the bortezomib-sensitive and -refractory group, while standard cytogenetic risk patients presented a similar PFS regardless of the bortezomib sensitivity status. In addition, in patients with ISS (International Staging System) stage I or II, the previous sensitivity to bortezomib correlated with an improved PFS, while for patients with ISS stage III, both groups had a comparable PFS. No significant differences in OS were observed between the two groups. Conclusions: In countries where novel or experimental therapies are not readily available, carfilzomib-based therapy can still be a viable therapy option for patients presenting with bortezomib-refractory status, an ISS stage III, and standard cytogenetic risk. [ABSTRACT FROM AUTHOR]

Introduction: Several systemic therapies have been approved for the treatment of severe AD. In particular, Janus kinase inhibitors (JAKi), including abrocitinib, baricitinib, and upadacitinib, recently received approval for the treatment of patients with severe AD after being evaluated in several clinical trials. However, a few concerns have been raised regarding their long-term safety and the management of these drugs in real-world clinical practice. In this article we described the results of a Delphi consensus aimed at describing the knowledge on JAKi and focusing, in particular, on providing clinical recommendations for dermatologists in daily practice regarding the use of these drugs. Methods: Twelve Italian dermatologists reviewed the most recent literature regarding the efficacy and safety profiles of JAKi and proposed 24 statements. Results: Agreement was reached for statements focusing on three main topics: (1) place in therapy of JAKi in patients with moderate-to-severe AD; (2) effectiveness and safety of JAK inhibitors in different phenotypes; (3) different approaches to the management of patients treated with JAKi in clinical practice. The panel proposed several recommendations regarding all the statements. Conclusion: Given the wide use of JAKi in clinical practice, it is crucial to establish a specific follow-up for each patient's phenotype in order to achieve the best possible clinical outcome and minimize potential adverse events. [ABSTRACT FROM AUTHOR]

Background: Real-world evidence of the efficacy and adverse events of JAK inhibitor treatment (Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib) in rheumatoid arthritis is still limited. Methods: We studied 115 patients from the Rheumatology Unit of S. Giovanni di Dio Hospital affected by D2T-RA, according to the 2010 EULAR criteria. Out of the 115 patients, 17 had been treated with Baricitinib 8 mg/daily, 32 with Filgotinib 200 mg/daily, 21 with Tofacitinib 10 mg/daily, and 45 with Upadacitinib 15 mg/daily. We evaluated the clinical response after 3, 6, and 12 months of treatment and the follow-up from September 2022 to September 2023. All patients were evaluated according to the number of tender joints (NTJs), number of swollen joints (NSJs), visual analog scale (VAS), global assessment (GA), health assessment questionnaire (HAQ), Disease Activity Score (DAS28), and CDAI. Furthermore, laboratory parameters of efficacy and tolerability were evaluated. Results: All treatments demonstrated a statistically significant decrease in the DAS28 and CDAI scores, tender and swollen joint counts, VAS, HAQ, and patient global assessment (PGA) after 3, 6, and 12 months of treatment. All treatments showed similar behavior, and statistically significant decreases in circulating calprotectin, TNFα, and IL-6 were observed for all drugs after 12 months of treatment. In addition, soluble urokinase plasminogen activator receptor (suPAR) values showed significant differences at baseline and after 12 months of treatment for Filgotinib: 4.87 ± 4.53 vs. 3.61 ± 0.9 (0.009) and Upadacitinib: 6.64 ± 7.12 vs. 4.06 ± 3.61 (0.0003), while no statistically significant differences were found for Baricitinib: 3.4 ± 0.1 vs. 3.78 ± 0.1 and Tofacitinib: 3.95 ± 1.77 vs. 2.58 ± 0.1. The TC/HDL-C ratio (atherogenic index) showed significant differences when comparing Baricitinib vs. Filgotinib (0.0012), Filgotinib vs. Tofacitinib (0.0095), and Filgotinib vs. Upadacitinib (0.0001); furthermore, the LDL-C/HDL-C ratio in the Filgotinib group did not change (2.37 ± 0.45 vs. 2.35 ± 2.13 (NS)) after 12 months of treatment. Venous Thrombotic Events (VTEs) and major adverse cardiovascular events (MACEs) accounted for 1% of adverse events after treatment with Baricitinib. Herpes zoster reactivation accounted for 1% of adverse events after treatment with Filgotinib and Tofacitinib, while non-melanoma skin cancer (NMSC) accounted for 1% of adverse events after Upadacitinib treatment. Conclusions: Our real-world data from patients with RA show differences in some laboratory parameters and in the impact of lipid metabolism in JAK inhibitor treatment. [ABSTRACT FROM AUTHOR]

Introduction: This was an observational, retrospective, multicenter study, enrolling elderly patients (>65 years old) treated with ixekizumab with a diagnosis of psoriasis (PsO) and/or psoriatic arthritis (PsA) during the period 2020 to 2023. Objectives: We sought to investigate the efficacy of ixekizumab in elderly patients in the treatment of moderate to severe psoriasis. Methods: We included 73 patients with psoriasis (32.9%), psoriatic arthritis (1.4%) and both of them (PsO-PsA 65.8%), attending the outpatient clinics of seven Italian referral center for psoriasis in Lazio region: Policlinico Umberto I Università Roma La Sapienza, Sant’Andrea Università di Roma La Sapienza, Polo Pontino Università Roma La Sapienza, Fondazione Policlinico Universitario A. Gemelli, Università Campus Biomedico Roma, Istituto Dermopatico dell’Immacolata, and Policlinico Tor Vergata. We collected data related to the characteristics of the patients (age, sex, body mass index) and of the disease (age at onset, duration of psoriasis, previous treatments). The severity of psoriasis was measured with the Psoriasis Area and Severity Index (PASI) score at baseline and after 16, 24, 52, 104 and 156 weeks of treatment. Results: PASI90 was achieved by all the patients in week 16 and remained stable until the end of the study. PASI100 has been achieved by 55.1% of patients at weeks 16 and by 81.3% at week 104. A statistically significant difference has been highlighted between baseline and all the other time points (p

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Resumen: Introducción: La enfermedad pulmonar obstructiva crónica (EPOC) es la tercera causa de muerte a nivel global y en Argentina tiene una prevalencia de 14,5%, pero se desconoce el manejo de los pacientes en la vida real. Los objetivos del trabajo fueron: a) conocer las opiniones de los neumólogos de Argentina que manejan pacientes con EPOC en la práctica diaria. b) Comparar nuestros hallazgos con los especialistas de España y c) considerar nuestros resultados para planificar futuras directrices en el manejo de la EPOC en nuestro país. Material y métodos: Participaron de un consenso Delphi 89 neumólogos de Argentina, expertos en EPOC, quienes respondieron una encuesta con cinco dominios: a) adhesión al tratamiento, b) control de la EPOC, c) rasgos tratables, d) dispositivos de inhalación y e) accesibilidad a los recursos terapéuticos. Resultados: Tras dos rondas, se alcanzó el consenso en 77,6% del total de las afirmaciones y discriminando por dominio los resultados fueron: adhesión al tratamiento: 5/9 (55,5%). Control de la EPOC: 10/14 (71,4%). Rasgos tratables: 6/6 (100%). Dispositivos de inhalación: 10/14 (71,4%) y accesibilidad al tratamiento: 6/6 (100%). En la mayoría de las afirmaciones los resultados fueron similares a los obtenidos por los neumólogos españoles. Conclusiones: Los neumólogos argentinos manejamos a los pacientes con EPOC de manera similar y con mínimas diferencias con nuestros colegas españoles. Se evidenció que, en la práctica diaria, existen factores que impactan negativamente en el acceso a los tratamientos indicados. Nuestro trabajo podría servir como punto de partida para mejorar esta situación. Abstract: Introduction: COPD is the third cause of death globally and in Argentina COPD has a prevalence of 14.5%, but the management of patients in real life is unknown. The objectives of this work were: a) To know the opinions of pulmonologists in Argentina who manage patients with COPD in different aspects of daily practice. b) Compare our findings with specialists from Spain and c) Consider our results to plan future directives in the management of COPD in our country. Material and methods: 89 pulmonologists from Argentina, experts in COPD, participated in a Delphi consensus, who responded to a survey with five domains. a) Adherence to treatment, b) Control of COPD, c) Treatable features, d) Inhalation devices and e) Accessibility to therapeutic resources. Results: After two rounds of questions, total consensus was achieved in 77.6% of the statements and discriminating by domain: Treatment adherence: 5/9 (55.5%). COPD control: 10/14 (71.4%). Treatable traits: 6/6 (100%). Inhalation devices: 10/14 (71.4%) and Accessibility to treatment: 6/6 (100%). In most of the affirmations, the results were similar to those obtained by Spanish pulmonologists. Conclusions: Pulmonologists from Argentina manage COPD patients in a similar way and with minimal differences with our Spanish colleagues. It became evident that, in daily practice, there are factors that negatively impact access to the indicated treatments. Our work could serve as a starting point to improve this situation.

Abstract Background Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA. Methods One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis. Results At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs. At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 ± 13.5 (p

Léa Antoine,1 Eve Puzenat,1 Dragos Popescu,2 Romain Charollais,3 Flora Dresco,3 Anne-Sophie Dupond,2 Dominique Salard,4 Marie-Christine Drobacheff-Thiebaut,1 Anaïs Zanella,1 Anne Ducournau,2 Iréne Gallais-Serezal,1 François Aubin1,5 1Department of Dermatology, University Hospital, Besançon, France; 2Department of Dermatology, Hôpital Nord Franche Comté, Trevenans, France; 3Department of Dermatology, Centre Hospitalier, Vesoul, France; 4Department of Dermatology, Centre Hospitalier, Pontarlier, France; 5Inserm 1098 RIGHT, University of Franche Comté, Besançon, FranceCorrespondence: François Aubin, Centre hospitalier Universitaire, Service de Dermatologie, 3 Bd Fleming, Besançon, 25000, France, Email francois.aubin@univ-fcomte.frPurpose: There are few data on the practical use of dupilumab by the patients and on the patients’ experience with this treatment.Objective: The objective of our study was to describe the experience and perception of dupilumab treatment in patients with atopic dermatitis (AD).Patients and Methods: We conducted a multicenter retrospective observational study including adult patients with moderate to severe AD treated with dupilumab between January 2017 and December 2021. Clinical characteristics were collected and a questionnaire was sent to all patients. It consisted of different parts including the injection method and different numeric rating scales (NRS) evaluating the patient’s satisfaction and the constraints related to the treatment.Results: Eighty-two patients were included and the information was available for 77 patients who responded to the questionnaire. Injection of dupilumab was performed by a nurse in 47% (n=36) of patients and 43% (n=33) were autonomous. Injections were performed by a family member for 7 patients or by the general practitioner (1 patient). A wearing-off of the beneficial effect of dupilumab was reported by 47% of patients leading to shorten the dosing interval. In contrast, dose spacing was reported by 9 patients (11%). After a mean follow-up time of 29.7 ± 10.7 months (median: 27 months), drug survival was 72%. From the patients’ perspective, the mean patient’s satisfaction NRS score was 7.5 ± 1.8, and the constraints related to the treatment were scored at 3.1 ± 2.1 on NRS.Conclusion: Although AD treatments may contribute to the burden of the disease, dupilumab was associated with a lower burden score, likely reflecting both treatment efficacy and easy of use and patient satisfaction.Keywords: atopic dermatitis, dupilumab, real life, experience

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06–30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24–14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04–1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94–6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71–76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10−19–NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19–269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05–16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22–20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58–91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7–75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9–112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16–73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

The metaverse and real life are not in opposition. From the long-term perspective of technology development, nearly all forms of life are shaped by technology. The metaverse, temporarily in juxtaposition with life, is a new form created by hyper-speed technology and will become part of life with the development of technology. The metaverse and real life, the opposition of which results from the dualistic thinking mode, could be viewed holistically. It is necessary to dissolve the “disparity” so as to achieve the consistency of theory and reality. [ABSTRACT FROM AUTHOR]

Background: The outcome of migraine patients retreated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (anti-CGRP) or its receptor (anti-CGRPr) is not completely known. Methods: This multicentric prospective observational cohort study assessed monthly migraine days (MMDs), migraine acute medication intake (MAMI), and HIT-6 at baseline, after 90–112 days (Rev-1), after 84–90 days since Rev-1 (Rev-2) and 30 days after the last injection of anti-CGRP/CGRPr mAbs (Year-end), in the first and the second year after a discontinuation period. Results: We enrolled 226 patients (79.6% with chronic migraine; 55.3% on erenumab and 44.7% on galcanezumab or fremanezumab). MMDs, MAMI, and HIT-6—did not differ at the respective first and second-year evaluations in the entire cohort, and comparing anti-CGRP with anti-CGRPr Abs. MMDs (18.1 ± 7.8 vs. 3.4 ± 7.8), MAMI (26.7 ± 28.3 vs.17.7 ± 17.2), and HIT-6 scores (63.1 ± 5.9 vs. 67.1 ± 10.3) were lower in the second year than in the pre-treatment baseline (consistently, p < 0.0001). Second-year baseline MMDs were lower in patients on anti-CGRP mAbs (p = 0.001) and with lower pre-treatment baseline MMDs (p ≤ 0.001). Conclusion: Anti-CGRP/CGRPr mAbs are effective in the second as in the first year. The use of anti-CGRP or CGRPr mAbs influenced the second-year baseline MMDs, but their effectiveness did not differ during the two treatment years. [ABSTRACT FROM AUTHOR]

[Display omitted] Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. Across 2769 COVID-19–vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination–induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination–induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine–related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated. [ABSTRACT FROM AUTHOR]

Healthcare administrative and pathological anatomy data were used to identify Italian patients with early breast cancer (EBC) with HR+/HER2- status at high risk of recurrence, evaluating drug utilization and other healthcare resource use in clinical practice. This retrospective analysis, based on 9.4 million of Italian National Health Service beneficiaries, included adult patients with hospitalization discharge diagnosis for EBC in 01/2015–12/2020. Those with HR+/HER2- status were selected; among them, patients that underwent removal of lymph nodes (LN) were analyzed. Of 24,137 patients with EBC and HR+/HER2- status, 3619 patients (15%) had documented LN removal. Overall, 4.7% of HR+/HER2- patients and 9.9% of patients with LN removal experienced distant relapse over a median follow-up of 33.2 months (Q1-Q3: 17.0–50.6). Local relapse occurred in approximately 9.1–9.3% of patients in each group. Among the 1,175 patients with LN removal that had available pathological anatomy data, 399 (34.0%) had pathological high-risk characteristics and 13.3% experienced distant relapse. One in ten patients with EBC who underwent LN removal experienced a relapse, highlighting the strong need to prevent early recurrence. [ABSTRACT FROM AUTHOR]

To monitor adherence to diets and to design and evaluate nutritional interventions, it is essential to obtain objective knowledge about eating behavior. In most research, measures of eating behavior are based on self-reporting, such as 24-h recalls, food records (food diaries) and food frequency questionnaires. Self-reporting is prone to inaccuracies due to inaccurate and subjective recall and other biases. Recording behavior using nonobtrusive technology in daily life would overcome this. Here, we provide an up-to-date systematic overview encompassing all (close-to) publicly or commercially available technologies to automatically record eating behavior in real-life settings. A total of 1328 studies were screened and, after applying defined inclusion and exclusion criteria, 122 studies were included for in-depth evaluation. Technologies in these studies were categorized by what type of eating behavior they measure and which type of sensor technology they use. In general, we found that relatively simple sensors are often used. Depending on the purpose, these are mainly motion sensors, microphones, weight sensors and photo cameras. While several of these technologies are commercially available, there is still a lack of publicly available algorithms that are needed to process and interpret the resulting data. We argue that future work should focus on developing robust algorithms and validating these technologies in real-life settings. Combining technologies (e.g., prompting individuals for self-reports at sensed, opportune moments) is a promising route toward ecologically valid studies of eating behavior. [ABSTRACT FROM AUTHOR]

Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients. A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF. We enrolled 166 patients with a median follow-up of 24 (IQR 8–36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment (p = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded. Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment. [ABSTRACT FROM AUTHOR]

Devant l'augmentation du nombre de cas de COVID-19, l'Établissement Public de Santé (EPS) de Ville-Évrard a mis en place des mesures strictes pour minimiser les risques d'infection et pour assurer la continuité des soins. Dans ce contexte, il nous a paru pertinent de s'intéresser au vécu de la crise sanitaire par nos patients hospitalisés lors de la première vague. Notre équipe a élaboré un questionnaire semi-structuré, composé de 8 items, permettant au patient de s'exprimer librement sur leur vécu de la crise sanitaire, de la prise en charge durant cette crise et du confinement. Nous avons recueilli les témoignages de 12 patients en réponse aux différents items du questionnaire concernant leur vécu en abordant les différents aspects de la crise sanitaire, parmi ceux qui ont été touchés par la COVID-19 et ceux qui ne l'ont pas contractée. Les réponses apportées par les patients aux différents items du questionnaire ont permis d'évoquer leur vécu de la crise sanitaire et du confinement. Nos patients ont fait preuve d'une bonne conscience de la complexité de la situation tout en se montrant coopérant à leur prise en charge et en respectant les nouvelles mesures mises en place. Ce travail nous a permis de constater que le retentissement de la crise lors de la première vague a été globalement bien vécu par nos patients avec une prise de conscience satisfaisante des risques encourus. Since the beginning of the health crisis, health care personnel have been confronted with an influx of patients with COVID-19. Given the complexity of the situation, the reorganization of care was done on an emergency basis to ensure careful management to limit the spread of the disease among health care personnel and patients. As patients suffering from psychiatric disorders were not spared, the Ville-Évrard Public Health Establishment set up a strategy to deal with this crisis by setting up a COVID+ unit specialized in the care of patients suffering from mental disorders and infected by the Coronavirus. Patients diagnosed as positive by PCR test were transferred to this unit so that they could benefit from a global management. The aim of our work was to focus on psychiatric patients (whether they were carriers of the COVID-19 virus or not) on their experiences during the health crisis in the first wave from March to June 2020, during the first containment. We have developed a semi-structured questionnaire composed of 8 questions, allowing to explore different aspects of the experience of the health crisis. We interviewed 12 patients (six patients affected by COVID-19 and six unaffected patients) with different mental disorders. The patients expressed themselves freely and their answers to the questions were presented question by question and separated according to the two groups. The first question was intended only for patients in the first cluster infected with the Coronavirus and the second question for patients with a family member infected with the virus. For the first question, two patients among the six infected with the Coronavirus, expressed anxiety. For the second question, two patients in the Covid+ group had a family member who had contracted the virus. One patient felt guilty, and one patient was anxious. In the Covid− group, one patient whose spouse had contracted the virus was very worried. For the third question, in the Covid+ group, four of the six patients were compliant with containment, two patients were not. In the Covid− group, four patients experienced containment between home and the hospital, and two patients experienced the entire containment at home. Regarding the fourth question, all patients (in both groups) acknowledged that the health crisis had a significant impact on their lifestyle. In response to the fifth question, all patients in the Covid+ group talked about their stay in the COVID+ unit and its setting. For patients in the Covid− group, the answers were varied mentioning simple means of distraction. For the sixth question, all patients (in both groups) were globally satisfied with their care. Concerning the seventh question, all patients in the Covid+ group thought they had been sufficiently careful without expressing any fear about the risk of contamination. In the Covid− group, the answers were centered on the fear of contracting the virus in the hospital. The responses to the eighth and final question were marked by a glimmer of hope. In the light of this work, the repercussions of this crisis, during the first wave, were generally well experienced by our patients, in the psychiatric environment, with a good awareness of the stakes and the risks incurred but also with a glimmer of hope for a resolution of the situation soon. Finally, most of the psychiatric patients in this sample behaved as respectful citizens during this first wave of confinement. [ABSTRACT FROM AUTHOR]

L'expérience extraordinaire (ExE), comme son nom l'indique, est une expérience qui sort de l'ordinaire et ne correspond pas au modèle de la réalité connue en termes de qualités et de processus. Le défi des chercheurs en ce domaine repose sur la question : l'ExE est-elle un symptôme psychopathologique qu'il faut soigner ou une expansion de conscience qu'il faut accompagner et encourager ? Plusieurs études se sont intéressées à mieux définir l'un ou l'autre de ces phénomènes ou à créer des échelles pour les distinguer. Dans la recherche présente, l'objectif repose sur une mise en parallèle de toutes les expériences extraordinaires afin d'investiguer et de rassembler les aspects communs qui la caractérisent. Cette première étape permet d'accroître les connaissances à ce sujet dans le but de créer à moyen terme un instrument de screening qui aidera les intervenants en psychiatrie à adapter le suivi pour ces personnes au vécu si particulier. Vingt-sept participants concernés par cette thématique ont raconté leur récit à trois chercheurs juges qui ont analysé leur contenu de manière qualitative afin d'en déduire des caractéristiques communes. Vingt-trois catégories similaires en termes de contenu thématique ont émergé. Cinq étapes importantes sont apparues qui aident à appréhender l'ExE comme un processus dynamique avec un début, un passage, un milieu, un retour et une fin qui mène à des conséquences psychologiques et personnelles positives. L'analyse qualitative de toutes les expériences extraordinaires confondues a permis de faire émerger 23 aspects communs qui se dessinent le long d'un processus temporel dynamique. Les résultats tendent à montrer que ce type de vécu amène à des changements positifs chez les personnes concernées plutôt qu'à des symptômes psychopathologiques. An extraordinary experience (ExE), as the name suggests, is an experience that is out of the ordinary and which does not fit the model of known reality in terms of qualities and processes. The challenge for researchers in this field is to determine whether an ExE is a psychopathological symptom that must be treated or an expansion of consciousness that should be supported and encouraged. Several studies have focused on better defining one or the other of these phenomena or on creating scales of measurement to distinguish them. In the present study, the objective is to establish a correlation between all the extraordinary experiences in order to investigate and identify the common aspects that characterize them. This first step will make it possible to improve our knowledge of this subject in order to create, in the medium term, a screening instrument that will help psychiatric practitioners to adapt the follow-up of those individuals who have had particular experiences. Twenty-seven participants concerned by this theme shared their stories with three researchers who qualitatively analyzed their content in order to identify common characteristics. Twenty-three similar categories in terms of thematic content emerged. Five important steps were identified that help to understand ExE as a dynamic process with a beginning, a passage, a middle, a return, and an end phase that results in positive psychological and personal consequences. The qualitative analysis of all combined extraordinary experiences has made it possible to identify 23 common aspects that reveal themselves along a dynamic temporal process. The results tend to show that this type of experience leads to positive changes in those concerned rather than in psychopathological symptoms. [ABSTRACT FROM AUTHOR]

The efficacy mepolizumab in severe asthmatic patients is proven in the literature. Primarily to study the effect of mepolizumab on exacerbations, steroid dependence, and the continuation of efficacy in the long term. Secondarily to evaluate the effect of the drug on nasal polyps. Analyzing data from SANI (Severe Asthma Network Italy) clinics, we observed severe asthmatic patients treated with mepolizumab 100 mg/4 weeks, for a period of 3 years. 157 patients were observed. Exacerbations were reduced from the first year (−84.6%) and progressively to 90 and 95% in the second and third ones. Steroid-dependent patients decreased from 54% to 21% and subsequently to 11% in the second year and 6% in the third year. Patients with concomitant nasal polyps, assessed by SNOT-22, showed a 49% reduction in value from baseline to the third year. The study demonstrated the long-term efficacy of mepolizumab in a real-life setting. [ABSTRACT FROM AUTHOR]

Background: Vismodegib is approved for advanced cases of basal cell carcinomas not amenable to surgery or radiotherapy. Large studies on the use of vismodegib in clinical practice are scarce. Objectives: The main objective of the study was to analyse the evolution and therapeutic management of relapses and lack of response in patients who had received vismodegib for locally advanced and/or multiple basal cell carcinomas in a real-life multicentre setting. Methods: This nationwide retrospective study collected data on patients treated with vismodegib in 15 specialized centres. We included patients who first received vismodegib until intolerable toxicity, maximum response, or progressive disease. Exploratory research variables referred to patient and tumour characteristics, vismodegib effectiveness and safety, relapse rate and management, and mortality. A multivariable logistic regression model was used to identify predictors of complete clinical response. Results: 133 patients with advanced BCC were included in the registry. The objective response rate (ORR) was 77.5% and nearly half of the patients (45.9%) achieved complete remission. Long-term information and detailed information of subsequent treatments after a regime of vismodegib was available for 115 patients. Only 34% of the patients in this group were subsequently treated with other therapies or vismodegib rechallenge. Sixty-nine percent of the patients who had shown a complete remission with vismodegib remained free of recurrence while 30.7% relapsed. Almost half of the patients who received additional therapies after the first course of vismodegib achieved complete tumour remission. Three and 2 out of 9 patients who were rechallenged with vismodegib achieved complete and partial responses, respectively, with an ORR of 55.5%. Conclusion: Our study confirms efficacy of vismodegib in routine clinical practice. The risk of recurrence after achieving complete response with vismodegib was lower than previous reports. Rechallenge with vismodegib is feasible and most patients responded to re-treatment. [ABSTRACT FROM AUTHOR]

This study investigates how 7th-grade students engaged in mathematics education in outdoor learning environments and how these experiences influenced their perception of mathematics. The research employed a qualitative approach with a case study design and involved 21 students in the 7th-grade middle school. Structured interview forms, student diaries, and unstructured observation notes were used as data collection tools. The data collected was analyzed using content analysis, resulting in the identification of themes and codes. The study examined the students' expectations for the activities to be carried out in outdoor learning environments. They expressed the highest positive expectations about learning problem-solving techniques and study methods for mathematics. Additionally, the students expressed a desire to learn mathematics enjoyably, overcome their prejudices against mathematics, and understand its logic. Before the research, the students knew that mathematics is used in real-life situations, primarily in calculations and transactions. However, after the study, it was observed that students not only had their expectations met but also gained awareness of the more diverse applications of mathematics in real-life contexts. Additionally, a positive change was observed in their attitudes toward mathematics, and they gained the awareness that mathematics goes beyond being just a subject learned in school and has many real-life applications. Consequently, it was concluded that outdoor learning environments can contribute to mathematics education and positively influence students' perception of mathematics. These findings provide an important perspective for evaluating different learning environments and experiences in mathematics education. [ABSTRACT FROM AUTHOR]

This study aims to investigate students' mathematical connection ability in solving the problem of mathematical and correlation between indicators of mathematical connection ability. This research is correlation research. The sample of the study is 35 girls’ students in the 9th grade in a middle school in Kerman province (south-east of Iran). Data collection is done by giving a test on mathematical connection skills. The variables in this study are indicators of mathematical connection ability, namely the connection between mathematical concepts, connections between mathematics and other sciences, and connections between mathematics and everyday life. Spearman's correlation coefficient was used to analyze the data after calculating the score and percentage of test answers. The findings showed that qualification of students in the indicator of the connection between mathematical concepts was good enough (69%), in the indicator of the connection between mathematics and other sciences was also good enough (66%), and the indicator of the connection between mathematics and everyday life was not enough (42%). Also, the results of Spearman's correlation coefficient showed that there is a significant relationship between both indicators of mathematical connection ability. Therefore, the connection between mathematics and everyday life of Students must be improved.

Abstract Background Around 50% of gastric cancers are diagnosed at an advanced stage. Several chemotherapy regimens are now internationally validated. Few data are available on the routine daily management of advanced gastric or gastroesophageal junction cancers. We aimed to describe chemotherapy practices, tolerance, and efficacy overall survival (OS) and Progression free survival (PFS) in a prospective French cohort. Methods Patients starting palliative chemotherapy were prospectively enrolled in 49 French centres. The primary objective was to report and describe patients' characteristics and treatment strategies. Secondary objectives were OS, PFS, objective response rate, adverse events rate, performance status deterioration during the chemotherapy. Results A total of 182 patients were included; 179 were analysed. Most patients received platinium‐based chemotherapy as the first treatment and FOLFIRI as second; 62.0% of patients received a second line, and 32.4% a third line. More than two thirds of Her2‐positive patients were first treated with trastuzumab. The FOLFIRI regimen was the most frequently used second‐line therapy. Median OS was 13.3 months, similar whatever the chemotherapy or combinations used in the first line. One‐ and 2‐year OS increased with the number of chemotherapy lines received, from respectively 24.7% and 5.7% (1 line), to 46.9% and 12.4% (2 lines) and 88.1% and 29.9% (3 or more lines) (p

Abstract Background Information is lacking from real‐life studies evaluating the efficacy of tildrakizumab in moderate‐to‐severe psoriasis. Materials and Methods We retrospectively analysed a database of 30 patients with moderate‐to‐severe psoriasis (PsO) that were treated with tildrakizumab (100 mg, s.c.) and followed for 36 weeks. Clinical efficacy (disease severity and treatment response) was evaluated by the Psoriasis Area and Severity Index (PASI) at baseline and after 4, 12, 24, and 36 weeks. The quality of life (QoL) of PsO patients was measured using the Dermatology Life Quality Index (DLQI). Results A PASI score of

Simple Summary: Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. Although in the case of low-grade lesions the conventional approach is watchful waiting, some infections may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. In this context, Papilocare® is a vaginal gel that combines components with moisturizing, tissue regeneration, and microbiota-balancing properties with ingredients that have positive effects on HPV-dependent cervical lesions and HPV clearance. According to the results obtained in this observational study with real-world data, most participants repaired their cervical lesions and cleared HPV through Papilocare® treatment, with a good treatment tolerability, adherence, and satisfaction rates, regardless of being infected with high-risk HPV, age over 40 years or both of them. Data reported in this study strengthen the role of the vaginal gel Papilocare® as a complementary action to the simple watchful waiting approach in HPV-related low-grade cervical lesions management. Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. HPV infection and persistency may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. The objective was to prospectively evaluate the results of using a Coriolus-versicolor-based vaginal gel (Papilocare®) on HPV-dependent low-grade cervical lesion repair in a real-life scenario. HPV-positive women ≥ 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). A 6-month second treatment cycle was prescribed when needed. Repair of the cervical low-grade lesions through cytology and colposcopy, HPV clearance, and level of satisfaction, and tolerability were evaluated. In total, 192 and 201 patients accounted for the total and safety analyses, respectively, and 77.1% repaired cervical lesions at 6 or 12 months (76.0% for high-risk HPV). Additionally, 71.6% achieved HPV clearance throughout the study's duration (70.6% for high-risk HPV). Satisfaction level was rated 7.9 and 7.5 out of 10 at 6 and 12 months, respectively. Only three mild–moderate product-related adverse events were reported, and all of them were resolved by the end of the study. In our study, we observed higher regression rates of low-grade cervical lesions in women treated with Papilocare® vaginal gel than spontaneous regression rates reported in the literature. [ABSTRACT FROM AUTHOR]

Background: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti‐IgE and anti‐IL5/5R and to compare the effectiveness of both classes of treatment in real life. Methods: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti‐IgE and anti‐IL5/5R. The effectiveness of anti‐IgE and anti‐IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long‐term‐oral corticosteroid (LTOCS) use, asthma‐related emergency room (ER) attendance, and hospital admissions. Results: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti‐IL5/5R group and 38.7% in the anti‐IgE group. Patients treated with anti‐IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti‐IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti‐IL5/5R experienced fewer asthma‐related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). Conclusions: In real life, both anti‐IgE and anti‐IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti‐IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use. [ABSTRACT FROM AUTHOR]

Background: The prevalence of clinical asthma remission with biologics in severe asthma has not been well understood yet. We do not even know whether there might be characteristics that identify subjects prone to remission of the disease. Materials and Methods: Retrospectively, four groups of severe asthmatics already treated with Omalizumab, Mepolizumab, Benralizumab and Dupilumab (302, 55, 95 and 34 patients, respectively) for at least 12 months were considered. The number of individuals with clinical asthma remission was sought in each group. This was considered when patients, after a treatment of at least 1 year with one of the aforesaid biologics, showed the disappearance of asthma symptoms (ACT ≥ 20), zero exacerbations, suspension of oral corticosteroids and a FEV1% ≥ 80%. Baseline characteristics of patients with and without remission were also taken into account. Results: The prevalence of asthma remission after a mean of 37.8 ± 19.2, 13.5 ± 1.7, 15.4 ± 5.5 and 12 ± 0 months of Omalizumab, Mepolizumab, Benralizumab and Dupilumab treatments was 21.8%, 23.6%, 35.8% and 23.5%, respectively. For each biologic, different baseline characteristics, seem to be associated with failure to achieve clinical asthma remission. Older age, higher BMI, a later age of asthma onset, rhinitis/sinusitis/nasal polyposis, comorbidities and a greater asthma severity may be the characteristics of a suboptimal response to biologic treatments. Conclusion: All biologics have the potential to induce disease remission in severe asthmatics. For each biologic, there may be several markers that can identify the patients who will not achieve asthma remission. It would be important to detect them (by carrying out targeted studies) as they would allow us to select the best biologic that may induce clinical asthma remission on a larger number of patients. [ABSTRACT FROM AUTHOR]

Aim: DIAMANTE is a retrospective and prospective, non-interventional, cohort study to describe the effectiveness of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in real clinical practice in Italy. Patients & methods: The study enrolled 246 patients: group 1 included patients treated with a darunavir-based regimen (n = 81); group 2 included patients who received antiretroviral treatment not including darunavir before D/C/F/TAF (n = 43); and group 3 included naive patients (n = 122). Effectiveness was evaluated as the virological response at week 48. Results: The D/C/F/TAF virological response rate was 72.1–78.8% and was obtained despite longer follow-up intervals due to the coronavirus 2019 pandemic. The safety of D/C/F/TAF was good as was the overall patient satisfaction and quality of life. Conclusion: This study confirmed the effectiveness and tolerability of D/C/F/TAF in a real-life setting both in naive and pretreated patients, with and without darunavir. Clinical Trial Registration:NCT03577470 (ClinicalTrials.gov) Darunavir-based antiretroviral therapies have been shown to be effective in providing a long-lasting reduction of HIV-RNA level in the blood up over detection limit and to have a good safety profile in patients infected with HIV. This study shows the effectiveness and safety of the combination of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) given to patients living with HIV. The study, which took place in Italy, included 246 patients infected with HIV. The groups were: Patients that had previously received a darunavir-based treatment; Patients that had received a different antiretroviral treatment (not including darunavir) and; Patients that had never been treated The results of the study confirm that D/C/F/TAF is safe and caused a strong virological response. Italian real-world study confirms efficacy and safety of darunavir-based therapy for HIV patients. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide regimen induces a strong virological response, ensuring long-lasting results. Promising for HIV treatment. #HIVresearch #AntiretroviralTherapy. [ABSTRACT FROM AUTHOR]

Abstract Background Few therapeutic options are approved as second‐line treatment after failure of platinum‐based chemotherapy for patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). Topotecan widespread use remains challenged by the risk of severe toxicities in a pretreated population. Little is known about the efficacy and safety of epirubicin–paclitaxel doublet in second‐line and beyond and especially cerebral outcomes. Methods EpiTax is a retrospective multicenter observational real‐life study. We evaluated the efficacy of epirubicin 90 mg/m2 combined with paclitaxel 175 mg/m2 every 3 weeks in SCLC patients after failure of at least one line of platinum‐based chemotherapy. The primary endpoint was progression‐free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), intracranial control rate (ICR), and safety. Results A total of 29 patients were included. The median of previous systemic therapy lines was 2 (1–4). Eleven patients received the treatment in the second line. Characteristics of patients were a median age of 60 years (45–77), 65.5% of males with 72.4% of PS 0–1. Fifteen patients had a history of brain metastases. Median PFS and OS achieved 11.0 (95% CI, 8.1–16.3) and 23 (95% CI, 14.1–29.6) weeks, respectively. ORR was 34.5% and DCR was 55.2%. ICR was 3/15 (20%). Grade 3–4 adverse events were mainly hematological and concerned 7 patients. No case of febrile neutropenia or toxic death was reported. Conclusion Epirubicin–paclitaxel association highlighted promising efficacy with PFS and OS of 11 and 23 weeks, respectively, ORR of 34.5%, and a tolerable safety profile. This doublet could represent another valuable therapeutic option for ES‐SCLC patients treated in the second line and beyond.

The introduction of monoclonal antibodies (mAbs) directed against the calcitonin gene-related peptide (CGRP), or its receptor (CGRPr), revolutionized migraine management due to their high efficacy and few side effects. Data suggest that the CGRP may even be implicated in circadian rhythm, but studies about the effect of anti-CGRP treatments on sleep are still lacking. The aim of the present study was to assess the effect of erenumab (70 and 140 mg per month), a human mAb directed against CGRPr, on chronotype in chronic migraineurs; secondly, we assessed its efficacy, safety, and the effects on anxiety and depression. Sleep was evaluated using self-administrable questionnaires investigating chronotype, sleep quality, and daytime sleepiness. Migraine diaries and several self-administrable questionnaires regarding headache impact and psychological correlates were evaluated every 3 months during 12 months of treatment. Eighty-eight patients were included; most of them showed a significant reduction in headache frequency and an improvement in psychological symptoms. Moreover, an initial change in chronotype was observed at the three-month assessment from a morning chronotype to an intermediate one; a similar trend remained in the other evaluations, even if it did not reach a statistical significance. Lastly, patients who responded to the treatment showed a progressive sleep efficiency reduction. The present real-life study hypothesized the influence of erenumab on chronotype, representing a link between circadian rhythm, CGRP, and migraine. [ABSTRACT FROM AUTHOR]

Introduction: Carfilzomib, a potent, irreversible, selective proteasome inhibitor has demonstrated consistent results in relapsed/refractory multiple myeloma (RRMM) combined with lenalidomide and dexamethasone (KRd). No prospective studies are yet available that analyzed the efficacy of the KRd combination. Methods: Herein, we report a multicenter prospective observational study on 85 patients who were treated with KRd combination as the second or third line of treatment, according to standard practice. Results: The median age was 61 years; high-risk cytogenetic was found in 26% and renal impairment (estimated glomerular filtration rate (eGFR) <60 ml/min) in 17%. After a median follow-up of 40 months, patients received a median number of 16 cycles of KRd, with a median duration of treatment (DoT) of 18 months (range, 16.1-19.2 months). The overall response rate was 95%, with a high-quality response (=very good partial remission [VGPR]) in 57% of the patients. The median progression-free survival (PFS) was 36 months (range, 29.1-43.2 months). Achievement of at least VGPR and a previous autologous stem cell transplantation (ASCT) were associated with longer PFS. The median overall survival (OS) was not reached (NR); the 5-year OS rate was 73%. Nineteen patients underwent KRd treatment as a bridge to autologous transplantation, obtaining a post-transplant minimal residual disease (MRD) negativity in 65% of cases. The most common adverse events were hematological, followed by infection and cardiovascular events, rarely G3 or higher, with a discontinuation rate for toxicities of 6%. Our data confirmed the feasibility and safety of the KRd regimen in real life. [ABSTRACT FROM AUTHOR]

Background and Aim: In chronic hepatitis B infection, antiviral therapy significantly reduces the incidence of complications. This study aimed to present real-life 12-month effectiveness and safety data for TAF. Materials and Methods: This Pythagoras Retrospective Cohort Study included patients from 14 centers in Turkiye. The study presents 12-month results of 480 patients treated with TAF as initial therapy or after switching from another antiviral drug. Results: The study shows treatment of about 78.1% patients with at least one antiviral agent (90.6% tenofovir disoproxil [TDF]). The rate of undetectable HBV DNA increased in both treatment-experienced and naive patients. In TDF-experienced patients, the rate of alanine transaminase (ALT) normalization increased slightly (1.6%) within 12 months, but the change was not statistically significant (p=0.766). Younger age, low albumin, and high body mass index and cholesterol were identified as risk factors for abnormal ALT after 12 months, but no linear relationship was detected. In TDF-experienced patients, renal and bone function indicators showed significant improvement three months after the transition to TAF and remained stable for 12 months. Conclusion: Real-life data demonstrated effective virological and biochemical responses with TAF therapy. After switching to TAF treatment, gains in kidney and bone functions were achieved in the early period. [ABSTRACT FROM AUTHOR]

Objective: Nationwide reimbursement of intermittently scanned continuous glucose monitoring (isCGM) was introduced in Belgium (2016). This real-world observational study investigates the impact of isCGM over 24 months on adults with type 1 diabetes with impaired or normal awareness of hypoglycemia (IAH or NAH). Methods: We included 1905 people who started first-generation 14-day FreeStyle Libre (without alerts). Sixteen percent had IAH. Primary endpoint was evolution of quality of life (QOL); secondary endpoints were evolution of severe hypoglycemia, work absenteeism, glycated hemoglobin (HbA1c), and sensor-measured outcomes. Results: At baseline, people with IAH (n = 308) had significantly worse QOL than people with NAH (n = 1594). Only people with IAH improved on the hypoglycemia fear survey-worry subscale after 24 months (22.8 [95% confidence interval: 21.4–24.2] at baseline; 20.6 [19.0–22.1] at 24 months, P = 0.002). For both groups, Diabetes Treatment Satisfaction Scale improved over 24 months (IAH: +3.1 [2.1–4.1], P < 0.001; NAH: +2.3 [1.9–2.7], P < 0.001), whereas general QOL, diabetes distress, and HbA1c remained stable. People with IAH showed the strongest decline in work absenteeism and severe hypoglycemia (36.4% having an event 6 months before isCGM initiation; 16.0% having an event during last 6 months of follow-up, P < 0.001), with similar observations for hypoglycemia hospitalization and hypoglycemia coma. Over 24 months, people with IAH spent more time in hypoglycemia, but less time in hyperglycemia than people with NAH. Conclusion: These data show sustained improvement of severe hypoglycemia, work absenteeism, and hypoglycemia fear after isCGM reimbursement, mostly driven by people with IAH. Together with improved treatment satisfaction, irrespective of hypoglycemia awareness level, isCGM without alerts is a valuable tool under long-term real-world conditions. Clinical Trial Registration number: NCT02898714. [ABSTRACT FROM AUTHOR]

Diabetic macular oedema (DMO) is the leading cause of vision loss associated with diabetic eye disease. The exponential increase in the diabetic population and thus, of DMO is an impetus for optimizing the management of DMO. One major challenge in DMO management is the discrepancy between treatment outcomes seen in clinical trials and the real world. Contrary to the homogeneity, better patient motivation and shorter study durations seen in randomised control trials, routine clinical practice is fraught with more diverse populations, undertreatment and variable compliance with long-term therapy. Under both circumstances, this review aims to compare efficacy outcomes and adverse events of DMO therapies within the scope of anti-vascular endothelial growth factor (anti-VEGF) medications, specifically the commonly used ones—bevacizumab, ranibizumab and aflibercept. Impediments and methods to achieve better treatment outcomes in the real world will be addressed to achieve better outcomes. Low- to lower-middle-income countries are faced with even more barriers which range from paucity of data on epidemiology and treatment response to scarce human and financial resources to poorer national level attention and then basic issues like transportation. Additionally, to address the lack of a global consensus in DMO treatment, this review generates and recommends, for clinical and research purposes, an up-to-date consensus algorithm for DMO management universally. Underpinned by results from clinical trials and recent guidelines, this therapeutic flowchart can be utilised in various resource settings including low- and lower-middle-income countries where affordability is a major deterrent to treatment access. [ABSTRACT FROM AUTHOR]

In this study, we compared the failure rates of fosfomycin and nitrofurantoin for uncomplicated urinary tract infections. We used Meuhedet Health Services' large database to collect data on all female patients, older than 18 years, who were prescribed either antibiotic during 2013–2018. Treatment failure was a composite endpoint of hospitalization, emergency-room visit, IV antibiotic treatment, or prescription of a different antibiotic, within seven days of the initial prescription. Reinfection was considered when one of these endpoints appeared 8–30 days following the initial prescription. We found 33,759 eligible patients. Treatment failure was more common in the fosfomycin group than the nitrofurantoin group (8.16% vs. 6.87%, p-value < 0.0001). However, reinfection rates were higher among patients who received nitrofurantoin (9.21% vs. 7.76%, p-value < 0.001). Among patients younger than 40 years, patients treated with nitrofurantoin had more reinfections (8.68% vs. 7.47%, p value = 0.024). Treatment failure rates were mildly higher in patients treated with fosfomycin, despite having less reinfections. We suggest that this effect is related to a shorter duration of treatment (one vs. five days) and encourage clinicians to be more patient before declaring fosfomycin failure and prescribing another antibiotic. [ABSTRACT FROM AUTHOR]