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Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti‐ vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real‐world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR‐TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first‐line EGFR‐TKI with anti‐VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high‐grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti‐VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR‐TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large‐scale registry‐based cohort studies may be needed to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Patients with influenza-related acute respiratory distress syndrome (ARDS) are critically ill and require mechanical ventilation (MV) support. Prolonged mechanical ventilation (PMV) is often seen in these cases and the optimal management strategy is not established. This study aimed to investigate risk factors for PMV and factors related to weaning failure in these patients. Methods: This retrospective cohort study was conducted by eight medical centers in Taiwan. All patients in the intensive care unit with virology-proven influenza-related ARDS requiring invasive MV from January 1 to March 31, 2016, were included. Demographic data, critical illness data and clinical outcomes were collected and analyzed. PMV is defined as mechanical ventilation use for more than 21 days. Results: There were 263 patients with influenza-related ARDS requiring invasive MV enrolled during the study period. Seventy-eight patients had PMV. The final weaning rate was 68.8% during 60 days of observation. The mortality rate in PMV group was 39.7%. Risk factors for PMV were body mass index (BMI) > 25 (kg/m2) [odds ratio (OR) 2.087; 95% confidence interval (CI) 1.006–4.329], extracorporeal membrane oxygenation (ECMO) use (OR 6.181; 95% CI 2.338–16.336), combined bacterial pneumonia (OR 4.115; 95% CI 2.002–8.456) and neuromuscular blockade use over 48 h (OR 2.8; 95% CI 1.334–5.879). In addition, risk factors for weaning failure in PMV patients were ECMO (OR 5.05; 95% CI 1.75–14.58) use and bacteremia (OR 3.91; 95% CI 1.20–12.69). Conclusions: Patients with influenza-related ARDS and PMV have a high mortality rate. Risk factors for PMV include BMI > 25, ECMO use, combined bacterial pneumonia and neuromuscular blockade use over 48 h. In addition, ECMO use and bacteremia predict unsuccessful weaning in PMV patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastasis is a factor of a poor prognosis in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The standard treatment is systemic therapy combined with intracranial intervention, such as craniotomy or radiotherapy. However, intracranial intervention may result in neurological or cognitive deficiency. We conducted a retrospective study to determine the optimal treatment strategy for EGFR-mutant NSCLC patients with brain metastasis receiving or not receiving intracranial intervention. Intracranial intervention had no statistically significant impact on response rate (RR), progression-free survival (PFS), or overall survival (OS) of patients with EGFR mutations and brain metastasis who received EGFR tyrosine kinase inhibitors (TKIs) as a first-line therapy. Treatment with different EGFR TKIs did not result in significant differences in RR or OS, but PFS differed significantly between the therapies. Afatinib and osimertinib both showed significantly longer PFS than gefitinib in a Cox regression model. The OS of patients with higher graded prognostic assessment (GPA) scores was significantly longer. Physicians should be vigilant about patients who have lower GPA scores at initial diagnosis of NSCLC with brain metastasis. Brain metastasis in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is a factor of poor prognosis. We conducted a retrospective study to determine the optimal treatment strategy for EGFR-mutant NSCLC patients with brain metastasis receiving or not receiving intracranial intervention. A total of 186 patients treated with an EGFR TKI were enrolled in the study, and 79 (42%) received intracranial intervention. Patients who received intracranial intervention and those who did not had a similar treatment response rate (RR), progression-free survival (PFS) (median PFS: 11.0 vs. 10.0 months, p = 0.4842), and overall survival (OS) (median OS: 23.0 vs. 23.2 months, p = 0.2484). Patients treated with gefitinib, erlotinib, afatinib, or osimertinib had a similar RR (63%, 76%, 81%, or 100%, respectively, p = 0.1390), but they had significantly different PFS (median PFS: 7.5, 10.0, 14.8 months, or not reached, respectively, p = 0.0081). In addition, OS tended to be different between different EGFR TKI treatments (median OS of 19.2, 23.7, or 33.0 months for gefitinib, erlotinib, or afatinib treatments, respectively, p = 0.0834). Afatinib and osimertinib both demonstrated significantly longer PFS than gefitinib in a Cox regression model. Graded prognostic assessment (GPA) versions 2017 and 2022 stratified patients with different OS; patients with higher GPA index scores had significantly longer OS (p = 0.0368 and 0.0407 for version 2017 and 2022, respectively). [ABSTRACT FROM AUTHOR]

In this paper, we demonstrate full closed-loop control of electrostatically actuated double-gimbaled MEMS mirrors and use them in an optical cross-connect. We show switching times of less than 10 ms and optical power stability of better than 0.2 dB. The mirrors, made from 10-[micro]m-thick single-crystal silicon and with a radius of 400-450 [micro]m, are able to tilt to 8[degrees] corresponding to 80% of touchdown angle. This is achieved using a nonlinear closed-loop control algorithm, which also results in a maximum actuation voltage of 85 V, and a pointing accuracy of less than 150 [micro]rad. This paper will describe the MEMS mirror and actuator design, modeling, servo design, and measurement results. Index Terms--Electrostatic actuator, microelectromechanical systems (MEMS), nonlinear closed-loop control, optical cross-connects, snap-down, torsional spring.