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⁺CD127^loFoxP3⁺ 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⁺CD127^loFoxP3⁺ Treg cells and PD-1⁺CD4⁺CD25⁺CD127^loFoxP3⁺ 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.

Background: The ratio of oxygen saturation (ROX) index, defined as the ratio of oxygen saturation (SpO₂)/fraction of inspired oxygen (FiO₂) to respiratory rate, can help identify patients with hypoxemic respiratory failure at high risk for intubation following high-flow nasal cannula (HFNC) initiation; however, whether it is effective for predicting intubation in coronavirus disease 2019 (COVID-19) patients receiving HFNC remains unknown. Moreover, the SpO₂/FiO₂ ratio has been assessed as a prognostic marker for acute hypoxemic respiratory failure. This study aimed to determine the utility of the ROX index and the SpO₂/FiO₂ ratio as predictors of failure in COVID-19 patients who received HFNC. Methods: This multicenter study was conducted in seven university-affiliated hospitals in Korea. Data of consecutive hospitalized patients diagnosed with COVID-19 between February 10, 2020 and February 28, 2021 were retrospectively reviewed. We calculated the ROX index and the SpO₂/FiO₂ ratio at 1 h, 4 h, and 12 h after HFNC initiation. The primary outcome was HFNC failure defined as the need for subsequent intubation despite HFNC application. The receiver operating characteristic curve analysis was used to evaluate discrimination of prediction models for HFNC failure. Results: Of 1,565 hospitalized COVID-19 patients, 133 who received HFNC were analyzed. Among them, 63 patients (47.4%) were successfully weaned from HFNC, and 70 (52.6%) were intubated. Among patients with HFNC failure, 32 (45.7%) died. The SpO₂/FiO₂ ratio at 1 h after HFNC initiation was an important predictor of HFNC failure (AUC 0.762 [0.679–0.846]). The AUCs of SpO₂/FiO₂ ratio at 4 h and ROX indices at 1 h and 4 h were 0.733 (0.640–0.826), 0.697 (0.597–0.798), and 0.682 (0.583–0.781), respectively. Multivariable analysis showed that the patients aged ≥70 years are 3.4 times more likely to experience HFNC failure than those aged <70 years (HR 3.367 [1.358–8.349], p = 0.009). The SpO₂/FiO₂ ratio (HR 0.983 [0.972–0.994], p = 0.003) at 1 h was significantly associated with HFNC failure. Conclusions: The SpO₂/FiO₂ ratio following HFNC initiation was an acceptable predictor of HFNC failure. The SpO₂/FiO₂ ratio may be a good prognostic marker for predicting intubation in COVID-9 patients receiving HFNC.

Sepsis is a life-threatening condition that affects individuals of all ages; however, it presents unique challenges in very old patients due to their complex medical histories and potentially compromised immune systems. This study aimed to investigate the influence of underlying conditions and the performance of sepsis bundle protocols in very old patients with sepsis. We conducted a nationwide cohort study of adult patients with sepsis prospectively collected from the Korean Sepsis Alliance Database. Underlying conditions, prognosis, and their association with sepsis bundle compliance in patients with sepsis aged ≥ 80 years were analyzed. Among the 11,981 patients with sepsis, 3,733 (31.2%) were very old patients aged ≥ 80 years. In-hospital survivors (69.8%) were younger, less likely male, with higher BMI, lower Charlson Comorbidity Index, lower Clinical Frailty Scale, and lower Sequential Organ Failure Assessment (SOFA) scores. The in-hospital survivor group had lower lactate measurement but higher fluid therapy and vasopressor usage within the 1-h bundle. Similar trends were seen in the 3-h and 6-h bundles. Furthermore, in-hospital survivors were more likely to receive appropriate empiric antibiotics within 24 h. In-hospital mortality was associated with age, Clinical Frailty Scale, SOFA score, comorbidities, Life sustaining treatment issue, interventions in the ICU and vasopressor use in the 1-h sepsis bundle. Addressing underlying conditions and enhancing sepsis bundle adherence is crucial for better outcomes in very old patients with sepsis. Personalized approaches and increased awareness are essential. Further research should explore interventions to optimize sepsis care in this population.

Purpose: Although increased plasma growth differentiation factor-15 (GDF15) levels have been reported in patients with various cancers, the predictive role of PD-1/PD-L1 inhibitors in advanced cancers remains unknown. This study aimed to investigate GDF15 levels as a predictive marker in advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors and analyze their association with immune cell populations. Methods: This study included 87 patients with advanced NSCLC receiving anti-PD-1/PD-L1 inhibitors between March 2018 and May 2020. Blood samples were obtained immediately before and months after PD-1/PD-L1 inhibitor administration. Results: The objective response rate (ORR) was significantly higher in the low GDF15 than in the high GDF15 group (39.2% vs. 15.3%, P = 0.013). The median progression-free survival (PFS) was significantly longer in the low GDF15 than in the high GDF15 group (13.2 [95% CI 7.6–18.9] vs. 7.2 [95% CI 4.8–9.6] months, P = 0.048). Moreover, plasma GDF15 levels negatively correlated with PD-1⁺/CD8⁺ T cells (r = − 0.399, P = 0.003) and positively with PD-1⁺/Treg cells (r = 0.507, P < 0.001) and PD-1⁺Treg/CD4⁺ T cells (r = 0.439, P < 0.001). The ORR was significantly higher in the group with decreased GDF15 from baseline than in the increased GDF15 group (37.2% vs. 10.0%, P = 0.026). The median PFS was significantly longer in the decreased GDF15 group (14.8 [95% CI 10.4–19.2] vs. 5.9 [95% CI 2.8–9.0] months, P = 0.002). Plasma GDF15 levels were associated with PD-1⁺CD8⁺ T cells and PD-1⁺ Treg cells. Conclusion: Plasma GDF15 could be a potential biomarker for predicting the efficacy and survival benefit of immunotherapy in advanced NSCLC.

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.

Introduction: An increase in age has been observed among patients admitted to the intensive care unit (ICU). Age is a well-known risk factor for ICU readmission and mortality. However, clinical characteristics and risk factors of ICU readmission of elderly patients (≥65 years) have not been studied. Methods: This retrospective single-center cohort study was conducted in a total of 122-bed ICU of a tertiary care hospital in Seoul, Korea. A total of 85,413 patients were enrolled in this hospital between January 1, 2007, and December 31, 2017. The odds ratio of readmission and in-hospital mortality was calculated by logistic regression analysis. Results: Totally, 29,503 patients were included in the study group, of which 2,711 (9.2%) had ICU readmissions. Of the 2,711 readmitted patients, 472 patients were readmitted more than once (readmitted 2 or more times to the ICU, 17.4%). In the readmitted patient group, there were more males, higher sequential organ failure assessment (SOFA) scores, and hospitalized for medical reasons. Length of stay (LOS) in ICU and in-hospital were longer, and 28-day and in-hospital mortality was higher in readmitted patients than in nonreadmitted patients. Risk factors of ICU readmission included the ICU admission due to medical reason, SOFA score, presence of chronic heart disease, diabetes mellitus, chronic kidney disease, transplantation, use of mechanical ventilation, and initial ICU LOS. ICU readmission and age (over 85 years) were independent predictors of in-hospital mortality on multivariable analysis. The delayed ICU readmission group (>72 h) had higher in-hospital mortality than the early readmission group (≤72 h) (20.6 vs. 16.2%, p = 0.005). Conclusions: ICU readmissions occurred in 9.2% of elderly patients and were associated with poor prognosis and higher mortality.