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.

BACKGROUND: The availability of mechanical thrombectomy (MT) is limited. Thus, there are two paradigms for patients living closer to a primary stroke center (PSC) than a comprehensive stroke center (CSC) capable of MT: \"Mothership\" (direct referral to a CSC) and \"Drip-and-Ship\" (referral to a PSC for imaging and thrombolysis and transfer to a CSC for thrombectomy or monitoring). We aimed to compare the prognosis of patients at three months between the two paradigms in a rural area.
METHODS: From September 2019 to March 2021, we prospectively included patients living closer to a PSC than the one CSC, regardless of the type of stroke or reperfusion treatment. The proportion of patients with a good functional outcome (Rankin≤2) at three months was compared between the two initial orientations for all patients and for subgroups: patients with ischemic stroke and patients treated by MT.
RESULTS: Among the 206 patients included, 103 were admitted directly to the CSC (82.5% had an ischemic stroke and 24.3% a MT) and 103 initially admitted to a PSC and then transferred to the CSC (100% had an ischemic stroke and 52.4% a MT). The proportion of patients with a good outcome was comparable between the two groups (54.5% vs. 43.7%, P=0.22). Among the 79 patients who underwent MT, the prognosis at three months was better in the Mothership group (49.3% vs. 15.3%, P=0.01).
CONCLUSIONS: The functional prognosis is comparable between Mothership and Drip-and-Ship paradigms in our setting, despite a trend towards a better prognosis for the Mothership. As has been shown in urban settings, the mothership paradigm also leads to a better prognosis for patients treated with MT in a rural setting.

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.

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.

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.

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.

BACKGROUND: 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.
CONCLUSIONS: 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.

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.
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).
CONCLUSIONS: Our real-life results confirm the efficacy of Dupilumab in the treatment of severe and uncontrolled CRSwNP.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.