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Job analysis of vaccination health workers at public health centers and sub-centers
Get PDFObjective: To analyze duties, tasks, and task elements of health workers in charge of vaccination at public health centers in South Korea. Design: Descriptive study using a survey. Sample: Health workers in charge of vaccination for more than 1 year at 254 public health centers in South Korea. Of 631 health workers, 401 responded to the questionnaire, and 379 responses were included in the analysis after excluding 22 incomplete responses. Measurements: The Developing A Curriculum (DACUM) workshop was conducted to identify the frequency, importance, and difficulty of duties, tasks, and task elements. Results: Four duties (vaccination promotion, vaccination administration and symptom management, execution of vaccination, and vaccination education), 18 tasks, and 81 task elements were identified. “Execution of vaccination” exhibited the highest determinant coefficient. “Implementing the budget” exhibited the highest determinant coefficient among tasks, and “dealing with an emergency in the case of adverse events” exhibited the highest determinant coefficient among task elements. Conclusions: Duty, task, and task elements with high determinant coefficients have high educational needs. Education demands was higher for administrative work than for direct vaccination. Developing an educational curriculum based on DACUM results could contribute to the professional education of vaccine workers
Downregulation of otulin induces inflammasome activation in neutrophilic asthma
No full textBackground: Neutrophilic asthma (NA) is a severe asthma phenotype associated with steroid resistance and IL-1β overproduction; however, the exact mechanism remains unclear. Moreover, the dysfunction of TNF-α signaling pathway, a regulator of IL-1β production, was associated with the deficiency of ovarian tumor protease deubiquitinase with linear linkage specificity (otulin) in autoimmune patients. Objective: We hypothesized that otulin downregulation in macrophages (Mφ) could trigger Mφ activation via the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathway. Methods: We assessed the expressions of otulin in blood monocyte subsets from NA patients and in alveolar Mφ from NA mice. Additionally, we evaluated the functional consequences of otulin deficiency in bone marrow–derived Mφ. The effects of inhibiting receptor-interacting protein kinase (RIPK)-1 and RIPK-3 on neutrophils and group 3 innate lymphoid cells (ILC3s) were assessed in vitro and in vivo. Results: When comparing nonclassical monocytes, a significant downregulation of otulin in the intracellular components was observed in NA patients compared to healthy controls (P = .005). Moreover, isolated alveolar Mφ from the NA mice exhibited lower otulin expression compared to those from control mice. After otulin knockdown in bone marrow–derived Mφ, we observed spontaneous IL-1β production depending on NLRP3 inflammasome. Moreover, the infiltrated neutrophils and ILC3s were significantly decreased by combined treatment of RIPK-1 and RIPK-3 inhibitors through blocking IL-1β release in NA. Conclusions: IL-1β overproduction caused by a deficiency of otulin, an upstream triggering factor, could be a promising diagnostic and therapeutic target for NA
Clinical Validation of Artificial Intelligence-Powered PD-L1 Tumor Proportion Score Interpretation for Immune Checkpoint Inhibitor Response Prediction in Non-Small Cell Lung Cancer
No full textPURPOSEEvaluation of PD-L1 tumor proportion score (TPS) by pathologists has been very impactful but is limited by factors such as intraobserver/interobserver bias and intratumor heterogeneity. We developed an artificial intelligence (AI)-powered analyzer to assess TPS for the prediction of immune checkpoint inhibitor (ICI) response in advanced non-small cell lung cancer (NSCLC).MATERIALS AND METHODSThe AI analyzer was trained with 393,565 tumor cells annotated by board-certified pathologists for PD-L1 expression in 802 whole-slide images (WSIs) stained by 22C3 pharmDx immunohistochemistry. The clinical performance of the analyzer was validated in an external cohort of 430 WSIs from patients with NSCLC. Three pathologists performed annotations of this external cohort, and their consensus TPS was compared with AI-based TPS.RESULTSIn comparing PD-L1 TPS assessed by AI analyzer and by pathologists, a significant positive correlation was observed (Spearman coefficient = 0.925; P <.001). The concordance of TPS between AI analyzer and pathologists according to TPS ≥50%, 1%-49%, and <1% was 85.7%, 89.3%, and 52.4%, respectively. In median progression-free survival (PFS), AI-based TPS predicted prognosis in the TPS 1%-49% or TPS <1% group better than the pathologist's reading, with the TPS ≥50% group as a reference (hazard ratio [HR], 1.49 [95% CI, 1.19 to 1.86] v HR, 1.36 [95% CI, 1.08 to 1.71] for TPS 1%-49% group, and HR, 2.38 [95% CI, 1.69 to 3.35] v HR, 1.62 [95% CI, 1.23 to 2.13] for TPS <1% group).CONCLUSIONPD-L1 TPS assessed by AI analyzer correlates with that of pathologists, with clinical performance also being comparable when referenced to PFS. The AI model can accurately predict tumor response and PFS of ICI in advanced NSCLC via assessment of PD-L1 TPS
Development of a multi-modal learning-based lymph node metastasis prediction model for lung cancer
No full textPurpose: This study proposed a three-dimensional (3D) multi-modal learning-based model for the automated prediction and classification of lymph node metastasis in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT) images and clinical information. Methods: We utilized clinical information and CT image data from 4239 patients with NSCLC across multiple institutions. Four deep learning algorithm-based multi-modal models were constructed and evaluated for lymph node classification. To further enhance classification performance, a soft-voting ensemble technique was applied to integrate the outcomes of multiple multi-modal models. Results: A comparison of the classification performance revealed that the multi-modal model, which integrated CT images and clinical information, outperformed the single-modal models. Among the four multi-modal models, the Xception model demonstrated the highest classification performance, with an area under the curve (AUC) of 0.756 for the internal test dataset and 0.736 for the external validation dataset. The ensemble model (SEResNet50_DenseNet121_Xception) exhibited even better performance, with an AUC of 0.762 for the internal test dataset and 0.751 for the external validation dataset, surpassing the multi-modal model's performance. Conclusions: Integrating CT images and clinical information improved the performance of the lymph node metastasis prediction models in patients with NSCLC. The proposed 3D multi-modal lymph node prediction model can serve as an auxiliary tool for evaluating lymph node metastasis in patients with non-pretreated NSCLC, aiding in patient screening and treatment planning
A predictive model for lymph node metastasis using tumor location in presumed early-stage endometrioid endometrial cancer patients
Get PDFObjective: The aim of this study was to identify high-and low-risk subgroups of patients with lymph node (LN) metastasis in presumed early-stage endometrioid endometrial cancer (EC) patients. Methods: Clinicopathologic data of presumed early-stage endometrioid EC patients (n=361) treated with lymphadenectomy between March 2000 and July 2022 were analyzed. None of the patient had definite evidence of LN metastasis in a preoperative magnetic resonance imaging (MRI). A received operating characteristic curve analysis was conducted to define the sensitivity and specificity for the combined preoperative risk factors for LN metastasis, which was determined by multivariate analysis. Results: Nineteen patients (5.3%) had LN metastasis. Multivariate analysis identified cervical stromal invasion on MRI (odds ratio [OR]=4.386; 95% confidence interval [CI]=1.020–18.852; p=0.047), cornual location of tumor on MRI (OR=36.208; 95% CI=7.902–165.913; p<0.001), and lower uterine segment/isthmic location of tumor on MRI (OR=8.454; 95% CI=1.567–45.610; p=0.013) as independent prognostic factors associated with LN metastasis. Patients were categorized into low-and high-risk groups according to risk criteria. Significant differences in the rates of LN metastasis were observed between the two groups (0.4% vs. 22.2%, p<0.001). Conclusion: Approximately 95% of presumed early-stage endometrioid EC patients did not have LN metastasis. A model using tumor location was significantly correlated with the risk of LN metastasis. Even in presumed early-stage endometrioid EC patients, therefore, tumor location should be investigated to determine whether to perform LN assessment
Totally laparoscopic versus laparoscopy-assisted distal gastrectomy: the KLASS-07: a randomized controlled trial
Get PDFBACKGROUNDS: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). The authors performed an RCT to confirm if TLDG is different from LADG. METHODS: The KLASS-07 trial is a multi-centre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enroled from 21 cancer care centres in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was quality of life (QoL) for 1 year. This trial is registered at ClinicalTrials.gov (NCT03393182). RESULTS: Four hundred forty-two patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P= 0.006; and 0.5% vs. 4.3%, P= 0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P< 0.05). However, these QoL differences were resolved at 1 year. CONCLUSIONS: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complications but has the advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months
New potential diagnostic markers for verrucous hyperplasia and verrucous carcinoma based on RNA-sequencing data
Get PDFVerrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma (SCC) characterized by its histological presentation as a low-grade tumor with no potential for metastasis, setting it apart from invasive SCC. However, distinguishing VC from its benign counterpart, verrucous hyperplasia (VH), is challenging due to their clinical and morphological similarities. Despite the importance of accurate diagnosis for determining treatment strategies, diagnosis for of VH and VC relied only on lesion recurrence after resection. To address this challenge, we generated RNA profiling data from tissue samples of VH and VC patients to identify novel diagnostic markers. We analyzed differentially expressed (DE) mRNA and long non-coding RNA (lncRNA) in tissue samples from VH and VC patients. Additionally, ChIP-X Enrichment Analysis 3 (ChEA3) was conducted to identify the top five transcription factors potentially regulating the expression of DE mRNAs in VH and VC. Our analysis of mRNA and lncRNA expression profiles in VH and VC provides insights into the underlying molecular characteristics of these diseases and offers potential new diagnostic markers. The identification of specific DE genes and lncRNAs may enable clinicians to more accurately differentiate between VH and VC, leading to better treatment choices
Association Between Cytokeratin 19-Specific IgG and Neutrophil Activation in Asthma
Get PDFPurpose: Patients with non-eosinophilic asthma (NEA) are less responsive to anti-inflammatory drugs and suffer from frequent asthma exacerbations. The pathogenic mechanism of NEA is not fully understood; however, the roles of monocytes and autoimmune mechanisms targeting airway epithelial cell (AEC) antigens have been proposed. Methods: The effects of monocyte extracellular traps (MoETs) on cytokeratin 19 (CK19) production in AECs, as well as the impact of CK19-specific immunoglobulin (Ig) G on neutrophil and monocyte activation, were investigated both in vivo and in vitro. Sixty asthmatic patients and 15 healthy controls (HCs) were enrolled, and the levels of serum immune complexes containing CK19-specific IgG and neutrophil extracellular trap (NET)-specific IgG were measured using enzyme-linked immunoassay. Results: MoETs induced CK19 and CK19-specific IgG production. Furthermore, the levels of serum CK19-specific IgG were significantly higher in the NEA group than in the eosinophilic asthma group. Among patients with NEA, asthmatics with high levels of CK19-specific IgG had higher levels of myeloperoxidase and NET-specific IgG than those with low levels of CK19-specific IgG (P = 0.020 and P = 0.017; respectively). Moreover, the immune complexes from asthmatics with high CK19-specific IgG enhanced NET formation and reactive oxygen species production (neutrophil activation), which were suppressed by N-acetylcysteine and anti-CD16 antibody treatment. Conclusions: These findings suggest that circulating CK19 and CK19-specific IgG may contribute to NET formation, leading to airway inflammation and steroid resistance in NEA
A phase 3 study (PATHWAY) of palbociclib plus tamoxifen in patients with HR-positive/HER2-negative advanced breast cancer
Get PDFPalbociclib combined with endocrine therapy is approved for treating patients with hormone-receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer; however, data on palbociclib combined with tamoxifen are limited. We investigated the efficacy and safety of palbociclib–tamoxifen in patients with HR+/HER2− advanced breast cancer. This double-blind phase 3 study included 184 women who were randomly assigned 1:1 to receive palbociclib–tamoxifen or placebo–tamoxifen. Pre/perimenopausal women also received goserelin. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Median PFS was 24.4 months (95% confidence interval [CI], 13.1–32.4) with palbociclib–tamoxifen and 11.1 months (95% CI, 7.4–14.6) with placebo–tamoxifen (hazard ratio [HR], 0.60; 95% CI, 0.43–0.85; P = 0.002). Palbociclib–tamoxifen improved PFS in patients who were treated with first-line or second-line endocrine therapy and pre-, peri-, and postmenopausal patients. Though OS data are still immature (median not reached in both groups), an overall risk reduction of 27% (HR, 0.73; 95% CI, 0.44–1.21) with palbociclib–tamoxifen was observed at the time of PFS analysis. The most common grade 3/4 adverse event with palbociclib–tamoxifen was neutropenia (89.0% [none were febrile] versus 1.1% with placebo–tamoxifen). There were no deaths owing to adverse events in either group. Among patients with HR+/HER2− advanced breast cancer, palbociclib–tamoxifen resulted in significantly longer PFS than tamoxifen alone. Early OS data showed a trend favoring palbociclib–tamoxifen. Trial registration: ClinicalTrials.gov number, NCT03423199. Study registration date: February 06, 2018
GRADE guidance 39: using GRADE-ADOLOPMENT to adopt, adapt or create contextualized recommendations from source guidelines and evidence syntheses
No full textBackground and Objective: The Grading of Recommendations, Assessment, Development and Evaluations (GRADE)-ADOLOPMENT methodology has been widely used to adopt, adapt, or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. The objective of this guidance is to refine the operationalization for applying GRADE-ADOLOPMENT. Methods: Through iterative discussions, online meetings, and email communications, the GRADE-ADOLOPMENT project group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE working group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people), and twice in September 2023 (approximately 60 and 90 people) for approval. Results: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by doing the following: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing evidence-to-decision (EtDs), when available or developing new EtDs, if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others. Conclusion: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over 6 years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources