This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA2LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
OBJECTIVE:There has been major controversy regarding the long term risk of death associated with the use of paclitaxel coated devices in the lower limbs. The authors performed a contemporary systematic review and meta-analysis. DATA SOURCES:Data sources included published literature and repositories of regulatory agencies. REVIEW METHODS:All cause mortality was analysed on the intention to treat principle. Because of violation of proportional hazards, reconstructed patient level survival data (R2 = 0.999) were fitted with piecewise Cox models and flexible generalised survival models with natural splines and shared frailty terms. Survival differences were summarised with the non-parametric statistical tests of the difference and the ratio of restricted mean survival time lost (RMTL). RESULTS:Thirty-four randomised studies with 7 486 subjects and 25 465 person years were included, more than twice the size of the latest industry sponsored meta-analysis for regulatory purposes. In the long term, there were 575 deaths amongst 4 231 patients in the paclitaxel arms (13.6% crude risk) vs. 367 deaths amongst 3 255 patients in the control arms (11.3% crude risk), with an average hazard ratio (HR) of 1.18 (95% confidence interval [CI] 1.03 - 1.35; p = .015). The RMTL ratio (non-parametric analogue of HR) was 1.21 times (95% CI 1.07 - 1.38; p = .003) at 5 years. The absolute RMTL difference was 0.08 years (95% CI 0.03 - 0.13; p = .004) at 5 years. The HR significantly varied over time, displaying a dynamic temporal pattern. Soon after treatment, HR progressively increased and became statistically significantly higher before the end of the first year and for most of the second year (HR 1.45, 95% CI 1.11 - 1.89; p = .007), before declining towards unity (neutral) again up to 5 years. There was modest between trial heterogeneity (θ = 0.083; p = .017) and level of certainty by Grading of Recommendations Assessment, Development and Evaluation was moderate. CONCLUSION:There is a significant, dynamic increase in all cause mortality following application of paclitaxel coated devices in the femoropopliteal artery.
The objective of this multicenter, real-world study, designed by the Greek Research Alliance for the Study of headache and Pain (GRASP), was to prospectively evaluate the 6-month effectiveness and safety of eptinezumab 100 mg for migraine prophylaxis in difficult-to-treat patients. A total of 142 participants (81
Importance:Novel blood culture diagnostics provide rapid antimicrobial susceptibility testing (AST) results for bacteria causing bloodstream infections (BSIs) but have unclear clinical impact. Objective:To evaluate clinical outcomes of blood culture testing using a rapid AST method compared with standard AST in patients with BSIs caused by gram-negative bacilli in regions with high prevalence of antimicrobial resistance. Design, Setting, and Participants:Open-label randomized clinical trial that enrolled participants from December 2023 to May 2025 (final follow-up, June 18, 2025) at 7 medical centers in Greece (n = 2), India (n = 1), Israel (n = 3), and Spain (n = 1). Hospitalized patients (adults and children) with BSIs caused by gram-negative bacilli were eligible. Statistical analysis was conducted from August 2025 to January 2026. Intervention:Patients were randomized to undergo blood culture evaluation using rapid, phenotypic AST directly from positive blood cultures plus standard susceptibility testing (n = 413) vs standard susceptibility testing alone (n = 437). Local antimicrobial stewardship teams reviewed all patients and provided treatment recommendations. Main Outcomes and Measures:The primary outcome was a desirability of outcome ranking (DOOR) at day 30, with 3 categories (alive without deleterious events, alive with deleterious events, and death). The difference between rapid and standard testing was summarized as the probability that the DOOR outcomes were more desirable in the rapid testing group. Superiority was concluded if the lower limit of the 95% CI exceeded 50%. Secondary outcomes included 30-day mortality, length of hospitalization, intensive care unit admission, acquisition of hospital-acquired infections, time to effective antibiotic therapy within 3 days, and time to antibiotic escalation or deescalation within 3 days. Results:Of the 899 patients randomized, 850 were included in the primary outcome analysis (median [IQR] age, 72 [21] years; 43% female). The probability that DOOR outcomes were more favorable in the rapid testing group was 48.8% (95% CI, 45.3%-52.4%). Median time to effective antibiotic therapy was not different between the groups in the as-randomized population. Median time to antibiotic escalation or deescalation was faster in the rapid testing group by 14 hours (95% CI, 6-22) in the as-randomized population. There were no differences between the groups in other secondary outcomes. In the prespecified subgroup with carbapenem-resistant infections, median time to effective therapy was 9.5 hours in the rapid testing group vs 28 hours in the standard testing group (difference, -18 hours [95% CI, -42 to 6]). Conclusions and Relevance:Among patients with gram-negative bacilli BSIs, rapid blood culture AST was not superior to standard testing by DOOR. When considered with other efficacy and safety outcomes, these findings may help inform the use of rapid susceptibility testing in clinical practice. Trial Registration:ClinicalTrials.gov Identifier: NCT06174649.
Lung resection for necrotizing pneumonia and lung abscess is often required to treat septic complications from refractory lung infections. All extents of parenchymal resection can be performed either by thoracotomy or thoracoscopic to successfully remove destroyed non-functional parenchyma while preserving viable tissue. Lobectomy is the commonest anatomic procedure while creation of pedicled muscular and pericardial flaps for stump reinforcement or space obliteration is common adjunct. As single lung ventilation is required for anatomic resections, treatment of any contralateral respiratory infection is mandatory. Respiratory support is not a contraindication but ventilated patients and those in ECMO are at higher risk. Early intervention and hemodynamic stabilization are important for improved outcomes.
