Spray nozzle for topical anaesthesia during flexible bronchoscopy: a randomised controlled trial.

Background: The effectiveness of using a spray nozzle to deliver lidocaine for superior topical airway anaesthesia during non-sedation flexible bronchoscopy (FB) remains a topic of uncertainty when compared with conventional methods. Methods: Patients referred for FB were randomly assigned to receive topical lidocaine anaesthesia via the bronchoscope's working channel (classical spray (CS) group) or through a washing pipe equipped with a spray nozzle (SN group). The primary outcome was cough rate, defined as the total number of coughs per minute. Secondary outcomes included subjective perceptions of both the patient and operator regarding the FB process. These perceptions were rated on a visual analogue scale, with numerical ratings ranging from 0 to 10. Results: Our study enrolled a total of 126 (61 CS group; 65 SN group) patients. The SN group exhibited a significantly lower median cough rate compared with the CS group (4.5 versus 7.1 counts·min-1; p=0.021). Patients in the SN group also reported less oropharyngeal discomfort (4.5±2.7 versus 5.6±2.9; p=0.039), better tolerance of the procedure (6.8±2.2 versus 5.7±2.7; p=0.011) and a greater willingness to undergo a repeat FB procedure (7.2±2.7 versus 5.8±3.4; p=0.015) compared with those in the CS group. From the operator's perspective, patient discomfort (2.7±1.7 versus 3.4±2.3; p=0.040) and cough scores (2.3±1.5 versus 3.2±2.4; p=0.013) were lower in the SN group compared with the CS group, with less disruption due to coughing observed among those in the SN group (1.6±1.4 versus 2.3±2.3; p=0.029). Conclusions: This study illustrates that employing a spray nozzle for the delivery of lidocaine provides superior topical airway anaesthesia during non-sedation FB compared with the traditional method.

Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients in the context of novel agents. However, current knowledge demonstrates a discrepancy between progression-free survival (PFS) and overall survival (OS) benefit with HDT/ASCT. METHODS: We conducted a systematic review and meta-analysis that included both randomized controlled trials (RCTs) and observational studies evaluating the benefit of upfront HDT/ASCT published during 2012 to 2023. Further sensitivity analysis and meta-regression were also performed. RESULTS: Among the 22 enrolled studies, 7 RCTs and 9 observational studies had a low or moderate risk of bias, while the remaining 6 observational studies had a serious risk of bias. HDT/ASCT revealed advantages in complete response (CR) with an odds ratio (OR) of 1.24 and 95% confidence interval (CI) 1.02 ~ 1.51, PFS with a hazard ratio (HR) of 0.53 (95% CI 0.46 ~ 0.62), and OS with an HR of 0.58 (95% CI 0.50 ~ 0.69). Sensitivity analysis excluding the studies with serious risk of bias and trim-and-fill imputation fundamentally confirmed these findings. Older age, increased percentage of patients with International Staging System (ISS) stage III or high-risk genetic features, decreased proteasome inhibitor (PI) or combined PI/ immunomodulatory drugs (IMiD) utilization, and decreased follow-up duration or percentage of males were significantly related to a greater survival advantage with HDT/ASCT. CONCLUSIONS: Upfront ASCT remains a beneficial treatment for newly diagnosed MM patients in the period of novel agents. Its advantage is especially acute in high-risk MM populations, such as elderly individuals, males, those with ISS stage III or high-risk genetic features, but is attenuated with PI or combined PI/IMiD utilization, contributing to divergent survival outcomes.

Non-small cell lung cancer harbouring non-resistant uncommon EGFR mutations: Mutation patterns, effectiveness of epidermal growth factor receptor-tyrosine kinase inhibitors and prognostic factors.

INTRODUCTION: Non-small cell lung cancer (NSCLC) harbouring EGFR exon 19 deletions or L858R mutation usually respond to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), whereas T790M mutation and exon 20 insertion are frequently resistant to EGFR-TKIs. EGFR mutations other than those above are seldom investigated. METHODS: In this multicentre, retrospective study, we enrolled NSCLC patients with non-resistant uncommon EGFR mutations, which were defined as mutations other than L858R, exon 19 deletions, exon 20 insertions and T790M. The mutation patterns, clinical data and treatment outcomes were analysed. Patients were classified as gefitinib/erlotinib and afatinib groups according to the EGFR-TKIs received as the first-line therapy. RESULTS: A total of 177 patients were identified (177/1983, 8.9%). Sixty-six patients had more than one EGFR mutation, including those coexisting with exon 19 deletion or L858R mutation. In treatment-naïve patients with advanced stages (n = 72), the objective response rate was 35.8% for gefitinib/erlotinib group and 60.6% for afatinib group (p = 0.036). In multivariate analysis, no significant differences were found between gefitinib/erlotinib and afatinib groups in median progression-free survival (PFS) and overall survival (OS). Brain metastasis at diagnosis was associated with a shorter PFS (hazard ratio [HR] = 2.49, 95% confidence interval [CI] = 1.29-4.83) and OS (HR = 3.22, 95% CI = 1.41-7.35). CONCLUSIONS: For patients with NSCLC harbouring non-resistant uncommon EGFR mutations, afatinib use as the first-line therapy may provide a better treatment response but no survival benefit, as compared with gefitinib or erlotinib. Brain metastasis at diagnosis is associated with a poor prognosis.