Characteristics and outcomes of patients with do-not-resuscitate and physician orders for life-sustaining treatment in a medical intensive care unit: a retrospective cohort study.

BACKGROUND: In the intensive care unit (ICU), we may encounter patients who have completed a Do-Not-Resuscitate (DNR) or a Physician Orders to Stop Life-Sustaining Treatment (POLST) document. However, the characteristics of ICU patients who choose DNR/POLST are not well understood. METHODS: We retrospectively analyzed the electronic medical records of 577 patients admitted to a medical ICU from October 2019 to November 2020, focusing on the characteristics of patients according to whether they completed DNR/POLST documents. Patients were categorized into DNR/POLST group and no DNR/POLST group according to whether they completed DNR/POLST documents, and logistic regression analysis was used to evaluate factors influencing DNR/POLST document completion. RESULTS: A total of 577 patients were admitted to the ICU. Of these, 211 patients (36.6%) had DNR or POLST records. DNR and/or POLST were completed prior to ICU admission in 48 (22.7%) patients. The DNR/POLST group was older (72.9 ± 13.5 vs. 67.6 ± 13.8 years, p < 0.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (26.1 ± 9.2 vs. 20.3 ± 7.7, p < 0.001) and clinical frailty scale (5.1 ± 1.4 vs. 4.4 ± 1.4, p < 0.001) than the other groups. Solid tumors, hematologic malignancies, and chronic lung disease were the most common comorbidities in the DNR/POLST groups. The DNR/POLST group had higher ICU and in-hospital mortality and more invasive treatments (arterial line, central line, renal replacement therapy, invasive mechanical ventilation) than the other groups. Body mass index, APAHCE II score, hematologic malignancy, DNR/POLST were factors associated with in-hospital mortality. CONCLUSIONS: Among ICU patients, 36.6% had DNR or POLST orders and received more invasive treatments. This is contrary to the common belief that DNR/POLST patients would receive less invasive treatment and underscores the need to better understand and include end-of-life care as an important ongoing aspect of patient care, along with communication with patients and families.

Do the Clinical Characteristics of Lipomas Influence the Incision Length During Minimal Incision Extraction?

BACKGROUND: Minimal incision extraction technique is widely accepted for the surgical removal of lipomas, but no consensus for the incision length has been made yet. OBJECTIVE: To investigate the clinical characteristics of lipomas which affect the minimal incision length during the minimal incision extraction. METHODS: We retrospectively analyzed 50 patients who underwent minimal incision extraction for 55 medium-sized (3-5 cm) or large lipomas (> 5 cm) between March 2020 and May 2022. If the mass is not fully dissected, or adequate visual field for hemostasis was not provided through the initial one-third incision, the incision was extended to the minimal extent. RESULTS: There were 33 males and 17 females with a mean age of 53.5 ± 12.7 years. There was no statistical difference in the minimal % incision length, defined as [(incision length) / (tumor diameter)] x 100, between the medium-sized (n = 31) and large lipomas (n = 24). Lipomas of the long incision group (minimal % incision length ≥66.7%, n = 21) had a higher frequency of head and neck location than lipomas of the short incision group (minimal % incision length <66.7%, n = 34) (odds ratio = 14.5, P < .05). However, no association was found between the tumor diameter or depth and the minimal % incision length. The occurrence of postoperative complications was not associated also (P = .296). CONCLUSION: The minimal % incision length for lipoma removal does not show statistical difference between medium-sized and large lipomas, and is affected by its anatomical location, but not by tumor diameter or depth.

Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. METHODS: This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. RESULTS: The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127loFoxP3+ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4+CD25+CD127loFoxP3+ Treg cells and PD-1+CD4+CD25+CD127loFoxP3+ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). CONCLUSION: Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.

Characteristics and outcomes of patients screened by rapid response team who transferred to the intensive care unit.

BACKGROUND: The utilization of a rapid response team (RRT) has influenced the clinical outcomes of patients in the general ward. However, the characteristics of RRT-screened patients who are transferred to the intensive care unit (ICU) are unknown. Therefore, the present study aimed to evaluate these factors. METHODS: We conducted a retrospective study using patient data from a tertiary medical center in Republic of Korea between January 2016 and December 2017. Multivariate logistic regression analyses were performed to assess the factors associated with the risk of in-hospital mortality. RESULTS: A total of 1,096 patients were included: 389 patients were transferred to the ICU, and 707 patients stayed in the ward. Patients in the ICU group were more likely to be admitted for medical reasons, hepatobiliary disease, and high heart rate. More interventions were performed, hospital stays were longer, and the 28-day and in-hospital mortality rates were higher in the ICU group than in the ward group. Multivariate logistic regression analyses showed that risk factors affecting ICU admission were higher Sequential Organ Failure Assessment (SOFA) score, National Early Warning Score (NEWS), platelet count, and lactate level. ICU transfer was not associated with in-hospital mortality. CONCLUSIONS: Among RRT-screened patients, those with higher SOFA score, NEWS, and lactate level were more likely to be transferred to the ICU. Therefore, these patients should be closely monitored and considered for ICU transfer.

Suppression of Mig-6 overcomes the acquired EGFR-TKI resistance of lung adenocarcinoma.

BACKGROUND: The resistance of lung cancer to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the unconquered frontiers in chemotherapy. Mitogen-inducible gene 6 (Mig-6) is known to inhibit the kinase activity of epidermal growth factor receptor (EGFR). Similarly, numerous studies of mouse models suggested tumor suppressive function of Mig-6 in lung cancer. On the contrary, the results of clinical investigations revealed that lung cancer patients with elevated expression of Mig-6 are associated with a poor prognosis. More recent work showed that unlike wild type (WT) EGFR, mutant EGFR phosphorylates Mig-6 and phosphorylated Mig-6 negatively regulates the degradation of EGFR mutants in lung adenocarcinoma. Here, we tried to untangle the controversies surrounding Mig-6 function as a protagonist or an antagonist of EGFR-TKI resistant lung cancer. METHODS: We compared the expression and phosphorylation status of Mig-6 in the EGFR-TKI resistant lung adenocarcinoma (PC9/GR cells) to EGFR-TKI sensitive lung adenocarcinoma (PC9 cells). We investigated the function of Mig-6 by either depletion or overexpression of Mig-6 in those cells and evaluated the efficacy of combining of Mig-6 knock-down and EGFR-TKI treatment in PC9/GR. The correlation between Mig-6 expressions and the prognoses of lung adenocarcinoma was examined by The Cancer Genome Atlas (TCGA) data and clinical samples. RESULTS: Our results indicated that the expression of Mig-6 was significantly increased in PC9/GR cells compared to that of PC9 cells. The significant portion of Mig-6 existed as a phosphorylated form in PC9 and PC9/GR cells. Moreover, overexpression of Mig-6 significantly increased the cell proliferation, invasion and epithelial mesenchymal transition (EMT) in PC9 cells. Combination of Mig-6 knock-down and EGFR-TKI treatment significantly overcame the EGFR-TKI resistance of PC9/GR cells. In addition, our analyses of clinical samples confirmed that high Mig-6 expressions positively correlate with a poor prognosis and EGFR-TKI resistance in lung adenocarcinoma. CONCLUSION: Our findings reinforce scientific notion of Mig-6 as an oncoprotein in the context of EGFR-TKI resistant lung adenocarcinoma. We propose that targeting Mig-6 may be a promising strategy to overcome the EGFR-TKI resistance in lung cancer.

Efficacy of Vinorelbine Monotherapy as Third- or Further-Line Therapy in Patients with Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: The survival rate of patients with lung cancer has increased significantly over the years, but there has been no further progress in third- or fourth-line therapy. We investigated the efficacy and tolerability of monotherapy with weekly vinorelbine, a semi-synthetic vinca alkaloid, in advanced non-small-cell lung cancer (NSCLC) patients who had previously been treated several times. METHODS: In all, 159 NSCLC patients who received vinorelbine monotherapy as third- or further-line therapy between January 2008 and July 2017 were included in this study. Patients received vinorelbine intravenously at a dose of 25-30 mg/m2/week. RESULTS: Their mean age was 62.4 years. The histologic types of tumor were adenocarcinoma (50.9%), squamous cell carcinoma (42.8%), and others (6.2%). The overall response rate was 19.5% (31/159). The median progression-free survival (PFS) was 3.0 months (95% confidence interval [CI] 2.5-3.5 months), and the median overall survival (OS) after vinorelbine use was 7.6 months (95% CI 6.2-9.0 months). Vinorelbine therapy showed significantly higher efficacy in patients with adenocarcinoma, and these patients had a longer PFS than patients with other types of cancer. Patients who received vinorelbine as fifth- or further-line treatment had a higher response rate and longer PFS and OS than those who received vinorelbine as third- or fourth-line treatment. CONCLUSIONS: Weekly vinorelbine monotherapy may be a feasible therapeutic option for patients with heavily treated, advanced NSCLC, particularly lung adenocarcinoma.

Contemporary Strategies: Incorporating Immunotherapy into Stage 3 Non-small Cell Lung Cancer Treatment.

Stage 3 non-small cell lung cancer (NSCLC) exhibits significant diversity, making it challenging to define an optimal treatment. A collaborative multidisciplinary approach is essential in crafting individualized treatments. Previously, targeted therapies and immunotherapies were commonly used to treat patients with advanced and metastatic lung cancer. Such treatments are now being extended to individuals considered surgery, as well as patients once considered unsuitable for surgery. These changes have increased surgical success and substantially reduced postoperative recurrence. However, the possibility of severe adverse effects from immunotherapy can deter some patients from performing surgery. It is essential to carefully explore the clinical traits and biomarkers of patients who may benefit the most from immunotherapy, and patients for whom immunotherapy should not be prescribed. In summary, it's crucial to effectively integrate the latest immunotherapy in treating stage 3 NSCLC patients, thereby increasing their opportunities for surgical intervention, and ensuring they receive the best possible care.

Diagnostic Value of Transbronchial Lung Cryobiopsy Using an Ultrathin Cryoprobe and Guide Sheath for Peripheral Pulmonary Lesions.

BACKGROUND: The addition of cryobiopsy to conventional biopsy methods improves the diagnostic yield of peripheral pulmonary lesions. Moreover, cryobiopsy with a guide sheath (GS) provides additional diagnostic benefits. Semi-real-time biopsy can be repeatedly performed using conventional biopsy devices and a GS, and subsequent cryobiopsy can be easily performed at the same location. Recently, a disposable 1.1 mm-diameter ultrathin cryoprobe has been developed and can be used with a 1.95 mm GS in a 2.0 mm working channel. In this study, we evaluated the diagnostic performance of transbronchial lung cryobiopsy (TBLC) with the 1.1 mm cryoprobe and a GS in patients with peripheral pulmonary lesions. METHODS: We retrospectively reviewed the medical records of patients who underwent endobronchial ultrasound transbronchial lung biopsy with a guide sheath and TBLC from July 23, 2021 to April 30, 2022 at Chungnam National University Hospital. RESULTS: Of a consecutive series of 229 patients, 199 were included. The diagnostic yields of forceps biopsy and cryobiopsy were 65.3% (130/199) and 84.4% (168/199), respectively, and the total diagnostic yield was 91.5% (182/199) ( P <0.001 vs. forceps biopsy). Multivariate analysis showed that solid lesion morphology [adjusted odds ratio (OR) 3.659, P =0.002] was associated with a significantly greater diagnostic yield of cryobiopsy, whereas a lesion diameter >20 mm ( P =0.026; adjusted OR 3.816) and 'within' orientation ( P =0.004; adjusted OR 6.174) were associated with a significantly greater overall diagnostic yield. CONCLUSION: TBLC using an ultrathin cryoprobe and GS markedly improves the diagnostic yield.

Spontaneous regression of recurrent pulmonary large cell neuroendocrine carcinoma with alteration of PD-L1 expression after surgical resection: A case report.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subtype of non-small cell lung cancer with a poor prognosis. Spontaneous regression, that is, partial or complete disappearance of a malignancy without medical intervention, is extremely rare in LCNEC. Herein, we present a case of spontaneous complete regression in a 71-year-old male patient with recurrent LCNEC after surgical resection. The patient was diagnosed with stage IB LCNEC and underwent surgical resection. At 1-year follow-up, chest computed tomography revealed a recurrent lesion next to the stump site and enlargement of lymph nodes 4R and 7; recurrent LCNEC was confirmed. The patient declined chemoradiation therapy. One year after recurrence, the patient experienced severe multifocal necrotizing pneumonia and was treated with antibiotics, resulting in a gradual decrease in the size of the recurrent lesion. Five years after the initial diagnosis, positron emission tomography/computed tomography revealed no hypermetabolic lesions, indicating the spontaneous complete regression of LCNEC.

Clinical Manifestations and Outcomes of Older Patients with COVID-19: A Comprehensive Review.

The consequences of coronavirus disease 2019 (COVID-19) are particularly severe in older adults with a disproportionate number of severe and fatal outcomes. Therefore, this integrative review aimed to provide a comprehensive overview of the clinical characteristics, management approaches, and prognosis of older patients diagnosed with COVID-19. Common clinical presentations in older patients include fever, cough, and dyspnea. Additionally, preexisting comorbidities, especially diabetes and pulmonary and cardiovascular diseases, were frequently observed and associated with adverse outcomes. Management strategies varied, however, early diagnosis, vigilant monitoring, and multidisciplinary care were identified as key factors for enhancing patient outcomes. Nonetheless, the prognosis remains guarded for older patients, with increased rates of hospitalization, mechanical ventilation, and mortality. However, timely therapeutic interventions, especially antiviral and supportive treatments, have demonstrated some efficacy in mitigating the severe consequences in this age group. In conclusion, while older adults remain highly susceptible to severe outcomes from COVID-19, early intervention, rigorous monitoring, and comprehensive care can play a pivotal role in improving their clinical outcomes.

Prediction of lung cancer using novel biomarkers based on microbiome profiling of bronchoalveolar lavage fluid.

There is an unmet need for biomarkers for the diagnosis of lung cancer and decision criteria for lung biopsy. We comparatively investigated the lung microbiomes of patients with lung cancer and benign lung diseases. Patients who underwent bronchoscopy at Chungnam National University Hospital between June 2021 and June 2022 were enrolled. Bronchoalveolar lavage fluid (BALF) was collected from 24 patients each with lung cancer and benign lung diseases. The samples were analyzed using 16S rRNA-based metagenomic sequencing. We found that alpha diversity and the beta diversity distribution (P = 0.001) differed significantly between patients with benign lung diseases and those with lung cancer. Firmicutes was the most abundant phylum in patients with lung cancer (33.39% ± 17.439), whereas Bacteroidota was the most abundant phylum in patients with benign lung disease (31.132% ± 22.505), respectively. In differential abundance analysis, the most differentially abundant microbiota taxon was unclassified_SAR202_clade, belonging to the phylum Chloroflexi. The established prediction model distinguished patients with benign lung disease from those with lung cancer with a high accuracy (micro area under the curve [AUC] = 0.98 and macro AUC = 0.99). The BALF microbiome may be a novel biomarker for the detection of lung cancer.

Immune checkpoint inhibitor score (IChIS) predicts survival benefit of immunotherapy in patients with non-small cell lung cancer.

Background: The use of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer is increasing. Despite ongoing studies to predict the efficacy of ICIs, its use in clinical practice remains difficult. Thus, we aimed to discover a predictive marker by analyzing blood cell characteristics and developing a scoring system for patients treated with ICIs. Methods: This was a prospective multicenter study in patients with advanced non-small cell lung cancer (NSCLC) who received ICIs as second-line treatment from June 2021 to November 2022. Blood cell parameters in routine blood samples were evaluated using an automated hematology analyzer. Immune checkpoint inhibitor score (IChIS) was calculated as the sum of neutrophil count score and immature granulocyte score. Results: A total of 143 patients from 4 institutions were included. The treatment response was as follows: partial response, 8.4%; stable disease, 37.1%; and progressive disease, 44.8%. Median progression-free survival and overall survival after ICI treatment was 3.0 and 8.3 months, respectively. Median progression-free survival in patients with an IChIS of 0 was 4.0 months, which was significantly longer than 1.9 months in patients with an IChIS of 1 and 1.0 month in those with an IChIS of 2 (p = 0.001). The median overall survival in patients with an IChIS of 0 was 10.2 months, which was significantly longer than 6.8 and 1.8 months in patients with an IChIS of 1 and 2, respectively (p < 0.001). Conclusions: Baseline IChIS could be a potential biomarker for predicting survival benefit of immunotherapy in NSCLC.

Cathepsin C regulates tumor progression via the Yes-associated protein signaling pathway in non-small cell lung cancer.

Cathepsin C (CTSC), also known as dipeptidyl peptidase I, is a cathepsin with lysosomal exocysteine protease activity and a central coordinator for the activation of neutrophil-derived serine proteases in the lysosomes of neutrophils. Although the role of CTSC in various cancers, including liver and breast cancers, has recently been reported, its role in non-small cell lung cancer (NSCLC) is largely unknown. This study aimed to investigate the functional role of CTSC in NSCLC and the molecular mechanisms underlying CTSC involvement in disease progression. CTSC overexpression markedly enhanced the growth, motility, and invasiveness of NSCLC cells in vitro and in vivo. CTSC knockdown using shRNA in NSCLC cells reversed the migratory and invasive behavior of NSCLC cells. CTSC also induced epithelial-mesenchymal transition through the Yes-associated protein signaling pathway. In addition, our analyses of clinical samples confirmed that high CTSC expression was associated with lymph node metastasis and recurrence in lung adenocarcinoma. In conclusion, CTSC plays an important role in the progression of NSCLC. Thus, targeting CTSC may be a promising treatment option for patients with NSCLC.

Clinical Characteristics and Prognosis of Older Patients with Coronavirus Disease 2019 Requiring Mechanical Ventilation.

An older age is associated with severe progression and poor prognosis in coronavirus disease 2019 (COVID-19), and mechanical ventilation is often required. The specific characteristics of older patients undergoing mechanical ventilation and their prognostic factors are largely unknown. We aimed to identify potential prognostic factors in this group to inform treatment decisions. This retrospective cohort study collected data from patients with COVID-19 at 22 medical centers. Univariate and multivariate Cox regression analyses were performed to assess factors that influence mortality. We allocated 434 patients in geriatric (≥80 years) and elderly (65-79 years) groups. The former group scored significantly higher than the elderly group in the clinical frailty scale and sequential organ failure assessment, indicating more severe organ dysfunction. Significantly lower administration rates of tocilizumab and extracorporeal membrane oxygenation and higher intensive care unit (ICU) and in-hospital mortality were noted in the geriatric group. The factors associated with ICU and in-hospital mortality included high creatinine levels, the use of continuous renal replacement therapy, prone positioning, and the administration of life-sustaining treatments. These results highlight significant age-related differences in the management and prognosis of critically ill older patients with COVID-19. Increased mortality rates and organ dysfunction in geriatric patients undergoing mechanical ventilation necessitate age-appropriate treatment strategies to improve their prognoses.

Quantitative Computed Tomography Lung COVID Scores with Laboratory Markers: Utilization to Predict Rapid Progression and Monitor Longitudinal Changes in Patients with Coronavirus 2019 (COVID-19) Pneumonia.

Coronavirus disease 2019 (COVID-19), is an ongoing issue in certain populations, presenting rapidly worsening pneumonia and persistent symptoms. This study aimed to test the predictability of rapid progression using radiographic scores and laboratory markers and present longitudinal changes. This retrospective study included 218 COVID-19 pneumonia patients admitted at the Chungnam National University Hospital. Rapid progression was defined as respiratory failure requiring mechanical ventilation within one week of hospitalization. Quantitative COVID (QCOVID) scores were derived from high-resolution computed tomography (CT) analyses: (1) ground glass opacity (QGGO), (2) mixed diseases (QMD), and (3) consolidation (QCON), and the sum, quantitative total lung diseases (QTLD). Laboratory data, including inflammatory markers, were obtained from electronic medical records. Rapid progression was observed in 9.6% of patients. All QCOVID scores predicted rapid progression, with QMD showing the best predictability (AUC = 0.813). In multivariate analyses, the QMD score and interleukin(IL)-6 level were important predictors for rapid progression (AUC = 0.864). With >2 months follow-up CT, remained lung lesions were observed in 21 subjects, even after several weeks of negative reverse transcription polymerase chain reaction test. AI-driven quantitative CT scores in conjugation with laboratory markers can be useful in predicting the rapid progression and monitoring of COVID-19.

The Matrix Stiffness Coordinates the Cell Proliferation and PD-L1 Expression via YAP in Lung Adenocarcinoma.

The extracellular matrix (ECM) exerts physiological activity, facilitates cell-to-cell communication, promotes cell proliferation and metastasis, and provides mechanical support for tumor cells. The development of solid tumors is often associated with increased stiffness. A stiff ECM promotes mechanotransduction, and the predominant transcription factors implicated in this phenomenon are YAP/TAZ, ß-catenin, and NF-κB. In this study, we aimed to investigate whether YAP is a critical mediator linking matrix stiffness and PD-L1 in lung adenocarcinoma. We confirmed that YAP, PD-L1, and Ki-67, a marker of cell proliferation, increase as the matrix stiffness increases in vitro using the lung adenocarcinoma cell lines PC9 and HCC827 cells. The knockdown of YAP decreased the expression of PD-L1 and Ki-67, and conversely, the overexpression of YAP increased the expression of PD-L1 and K-67 in a stiff-matrix environment (20.0 kPa). Additionally, lung cancer cells were cultured in a 3D environment, which provides a more physiologically relevant setting, and compared to the results obtained from 2D culture. Similar to the findings in 2D culture, it was confirmed that YAP influenced the expression of PD-L1 and K-67 in the 3D culture experiment. Our results suggest that matrix stiffness controls PD-L1 expression via YAP activation, ultimately contributing to cell proliferation.

Neutrophil diversity is associated with T-cell immunity and clinical relevance in patients with thyroid cancer.

Neutrophil heterogeneity is involved in autoimmune diseases, sepsis, and several cancers. However, the link between neutrophil heterogeneity and T-cell immunity in thyroid cancer is incompletely understood. We investigated the circulating neutrophil heterogeneity in 3 undifferentiated thyroid cancer (UTC), 14 differentiated thyroid cancer (DTC) (4 Stage IV, 10 Stage I-II), and healthy controls (n = 10) by transcriptomic data and cytometry. Participants with UTC had a significantly higher proportion of immature high-density neutrophils (HDN) and lower proportion of mature HDN in peripheral blood compared to DTC. The proportion of circulating PD-L1+ immature neutrophils were significantly increased in advanced cancer patients. Unsupervised analysis of transcriptomics data from circulating HDN revealed downregulation of innate immune response and T-cell receptor signaling pathway in cancer patients. Moreover, UTC patients revealed the upregulation of glycolytic process and glutamate receptor signaling pathway. Comparative analysis across tumor types and stages revealed the downregulation of various T-cell-related pathways, such as T-cell receptor signaling pathway and T-cell proliferation in advanced cancer patients. Moreover, the proportions of CD8+ and CD4+ T effector memory CD45RA+ (TEMRA) cells from peripheral blood were significantly decreased in UTC patients compared to DTC patients. Finally, we demonstrated that proportions of tumor-infiltrated neutrophils were increased and related with poor prognosis in advanced thyroid cancer using data from our RNA-seq and TCGA (The Cancer Genome Atlas) data. In conclusion, observed prevalence of circulating immature high-density neutrophils and their immunosuppressive features in undifferentiated thyroid cancers underscore the importance of understanding neutrophil dynamics in the context of tumor progression in thyroid cancer.

Incidence of New-Onset Inflammatory Bowel Disease, Oral and Gastrointestinal Candidiasis, Herpes Zoster, Pulmonary Tuberculosis, and Major Cardiovascular Events in Patients with Moderate-to-Severe Psoriasis Exposed to Biologics.

The multicenter, retrospective cohort study was aimed at examining adverse events in biologic-treated patients with moderate-to-severe psoriasis by using a real-world database. Thus, we analyzed exposure-adjusted incidence rates for new-onset inflammatory bowel disease (IBD), oral and gastrointestinal candidiasis, pulmonary tuberculosis, herpes zoster, and major cardiovascular events (MACEs) in biologic-treated patients with moderate-to-severe psoriasis. Overall, 2085 patients were found to have been exposed to tumor necrosis factor (TNF)-α, interleukin (IL)-12/23, IL-17, and IL-23 inhibitors (n = 463, 540, 635, and 447, respectively). No patient developed new-onset IBD. The incidence rates of oral and gastrointestinal candidiasis were comparable between patients treated with IL-23 and IL-17 inhibitors (5.6 and 5.3 per 1000 PY, respectively). None treated with IL-17 or IL-23 inhibitors reported pulmonary tuberculosis. The incidence rate of herpes zoster was the highest in patients treated with TNF-α inhibitors (17.0 per 1000 PY), followed by IL-17, IL-23, and IL-12/23 inhibitors (13.3, 7.8, and 2.7 per 1000 PY, respectively). MACEs were not reported in patients treated with IL-17 inhibitors but were reported in those treated with TNF-α, IL-23, and IL-12/23 inhibitors (incidence: 5.6, 3.8, and 1.8 per 1000 PY, respectively). The study indicated favorable safety profiles of biologics in Korean patients with moderate-to-severe psoriasis.