Purpose: Alectinib has been approved for anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) at 300 mg twice daily in Japan, lower than global standard of 600 mg twice daily. This study evaluated the clinical relevance of the reduced dose by comparing outcomes between the two doses. Materials and Methods: This study included patients with advanced ALK-positive NSCLC who received alectinib at Samsung Medical Center, Korea. The progression-free survival (PFS), overall survival, cumulative incidence of central nervous system (CNS) progression, and safety profiles were retrospectively reviewed and compared. Results: Among 306 patients, 32 and 274 received alectinib at either 300 or 600 mg twice daily, respectively. The 300 mg group showed a slight but not significant advantage in PFS (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.44 to 1.51; p=0.51) and overall survival (HR, 0.51; 95% CI, 0.20 to 1.21; p=0.13). Superior outcome with 300 mg was remarkable in patients with lower body weight (≤ 60 kg), but diminished in patients with higher body weights. Patients with baseline brain metastasis in the 300 mg group exhibited a slight increase in incidence of CNS failure (HR, 1.76; 95% CI, 0.53 to 5.8; p=0.36). Although the safety profiles were mostly mild, adverse events were more frequent in the 600 mg group, 50% of which requiring dose reduction. Conclusion Alectinib at 300 mg twice daily seems an acceptable dose in East Asians with ALK-positive NSCLC. Notably, our data favor 300 mg twice daily in patients with lower body weight and no baseline brain metastasis, considering the more tolerable safety profiles and the potential to reduce medical costs.

Purpose: The career ladder system is a pivotal strategy for securing excellent nurses. The aim of this study is to understand hospital nurses’ experiences of participating in the career ladder system and to explore the essence of this system. Methods: In February 22 to March 3, 2022, nurses employed at a general hospital in South Korea were selected for this study using snowball and purposive sampling. Data were collected from interviews with three focus groups, the compositions of which are as follows: group 1, 6 participants; group 2, 5 participants; and group 3, 6 participants. All interviews were recorded, transcribed verbatim, and subsequently analyzed using qualitative research methods. Results: The following six categories were derived under the overall theme of “the arduous journey to discovering a nurse’s true name”: (1) rites of passage to becoming the ideal nurse; (2) unexpected challenges in the promotion preparation process; (3) biased criteria for evaluating nursing competencies; (4) unclear changes in roles and perceptions after promotion; (5) self-discovered pride and fulfillment as a nurse; and (6) the unspoken struggles of evaluators. Conclusion The findings suggest that the career ladder system fosters nurses’ professional growth and self-actualization. However, for effective implementation, nurses’ deep understanding and systematic management of the career ladder system are essential. This study offers valuable insights and benchmarks for healthcare institutions aiming to adopt the system.

Purpose: The career ladder system is a pivotal strategy for securing excellent nurses. The aim of this study is to understand hospital nurses’ experiences of participating in the career ladder system and to explore the essence of this system. Methods: In February 22 to March 3, 2022, nurses employed at a general hospital in South Korea were selected for this study using snowball and purposive sampling. Data were collected from interviews with three focus groups, the compositions of which are as follows: group 1, 6 participants; group 2, 5 participants; and group 3, 6 participants. All interviews were recorded, transcribed verbatim, and subsequently analyzed using qualitative research methods. Results: The following six categories were derived under the overall theme of “the arduous journey to discovering a nurse’s true name”: (1) rites of passage to becoming the ideal nurse; (2) unexpected challenges in the promotion preparation process; (3) biased criteria for evaluating nursing competencies; (4) unclear changes in roles and perceptions after promotion; (5) self-discovered pride and fulfillment as a nurse; and (6) the unspoken struggles of evaluators. Conclusion The findings suggest that the career ladder system fosters nurses’ professional growth and self-actualization. However, for effective implementation, nurses’ deep understanding and systematic management of the career ladder system are essential. This study offers valuable insights and benchmarks for healthcare institutions aiming to adopt the system.

Purpose: The career ladder system is a pivotal strategy for securing excellent nurses. The aim of this study is to understand hospital nurses’ experiences of participating in the career ladder system and to explore the essence of this system. Methods: In February 22 to March 3, 2022, nurses employed at a general hospital in South Korea were selected for this study using snowball and purposive sampling. Data were collected from interviews with three focus groups, the compositions of which are as follows: group 1, 6 participants; group 2, 5 participants; and group 3, 6 participants. All interviews were recorded, transcribed verbatim, and subsequently analyzed using qualitative research methods. Results: The following six categories were derived under the overall theme of “the arduous journey to discovering a nurse’s true name”: (1) rites of passage to becoming the ideal nurse; (2) unexpected challenges in the promotion preparation process; (3) biased criteria for evaluating nursing competencies; (4) unclear changes in roles and perceptions after promotion; (5) self-discovered pride and fulfillment as a nurse; and (6) the unspoken struggles of evaluators. Conclusion The findings suggest that the career ladder system fosters nurses’ professional growth and self-actualization. However, for effective implementation, nurses’ deep understanding and systematic management of the career ladder system are essential. This study offers valuable insights and benchmarks for healthcare institutions aiming to adopt the system.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Purpose: Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC. Materials and Methods: Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]). Results: Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9). Conclusion Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.

Purpose: Alectinib and brigatinib are second-generation anaplastic lymphoma receptor tyrosine kinases (ALKs) that are widely used as first-line therapy for treating ALK-positive advanced non–small cell lung cancer (NSCLC). Given the lack of a head-to-head comparison of these drugs as first-line therapies, this retrospective observational study aimed to compare the real-world efficacy and safety of alectinib and brigatinib. Materials and Methods: Patients who received alectinib or brigatinib as the first-line treatment for ALK-positive advanced NSCLC were evaluated for clinical outcomes of objective response rate (ORR), intracranial ORR, time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), and safety profiles. Results: Of 208 patients who received either alectinib or brigatinib as a first-line treatment, 176 received alectinib and 32 received brigatinib. At the data cutoff point, the median follow-up duration was 16.5 months (95% confidence interval [CI], 14.7 to 18.3) in the brigatinib group and 27.5 months (95% CI, 24.6 to 30.4) in the alectinib group. The ORR was 92.5% with alectinib and 93.8% for brigatinib. The intracranial ORR rates were 92.7% (38/41) and 100% (10/10), respectively. The rate of PFS at 12 months was comparable between the alectinib group and the brigatinib groups (84.4% vs. 84.1%, p=0.64), and the median TTNT, PFS, and OS were not reached in either group. Treatment-related adverse events were usually mild, and treatment discontinuation due to adverse events was rare (alectinib 4.5% vs. brigatinib 6.25%). Conclusion Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.