Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Intervertebral disc degeneration is associated with diverse spine diseases, including spinal stenosis, facet arthropathy, and disc herniation, which have socio-economic effects. A normal intervertebral disc has consistency and homeostasis, consisting of annulus fibrosus, nucleus pulposus, notochordal cells, nucleus pulposus cells, and an endplate with an immune privilege. On the other hand, when the degenerative process has pathologic causes, the inflammatory reaction could lead to nerve sprouting and vascularization into the tissue. Histopathologically, the pathologic process involves the degradation of the extracellular matrix, apoptosis and necrosis of nucleus pulposus cells, inhibition of chondrogenic differentiation, disruption of endplate chondrogenic cells, and other processes. Various approaches for managing disc degeneration have been reported. Among them, mesenchymal stem cells (MSCs) have been regarded as representative trials. In vitro and animal studies with MSCs have reported some promising outcomes in terms of inflammatory modulation and regeneration, but several limitations have been pointed out, including the issues of graft rejection and survival. Because the paracrine mechanism would be a main therapeutic factor of MSCs, extracellular vesicles (EVs), one of the factors released from MSCs, have been considered a promising source for regenerative medicine. EVs possess nucleic acids, functional proteins, and inflammation-related factors, playing a significant role in the inflammatory reaction and regeneration. The current review article discusses the pathophysiology of disc degeneration, outcomes of conventional MSCs and EVs, and current limitations and future perspectives on EV therapeutics.

Intervertebral disc degeneration is associated with diverse spine diseases, including spinal stenosis, facet arthropathy, and disc herniation, which have socio-economic effects. A normal intervertebral disc has consistency and homeostasis, consisting of annulus fibrosus, nucleus pulposus, notochordal cells, nucleus pulposus cells, and an endplate with an immune privilege. On the other hand, when the degenerative process has pathologic causes, the inflammatory reaction could lead to nerve sprouting and vascularization into the tissue. Histopathologically, the pathologic process involves the degradation of the extracellular matrix, apoptosis and necrosis of nucleus pulposus cells, inhibition of chondrogenic differentiation, disruption of endplate chondrogenic cells, and other processes. Various approaches for managing disc degeneration have been reported. Among them, mesenchymal stem cells (MSCs) have been regarded as representative trials. In vitro and animal studies with MSCs have reported some promising outcomes in terms of inflammatory modulation and regeneration, but several limitations have been pointed out, including the issues of graft rejection and survival. Because the paracrine mechanism would be a main therapeutic factor of MSCs, extracellular vesicles (EVs), one of the factors released from MSCs, have been considered a promising source for regenerative medicine. EVs possess nucleic acids, functional proteins, and inflammation-related factors, playing a significant role in the inflammatory reaction and regeneration. The current review article discusses the pathophysiology of disc degeneration, outcomes of conventional MSCs and EVs, and current limitations and future perspectives on EV therapeutics.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Intervertebral disc degeneration is associated with diverse spine diseases, including spinal stenosis, facet arthropathy, and disc herniation, which have socio-economic effects. A normal intervertebral disc has consistency and homeostasis, consisting of annulus fibrosus, nucleus pulposus, notochordal cells, nucleus pulposus cells, and an endplate with an immune privilege. On the other hand, when the degenerative process has pathologic causes, the inflammatory reaction could lead to nerve sprouting and vascularization into the tissue. Histopathologically, the pathologic process involves the degradation of the extracellular matrix, apoptosis and necrosis of nucleus pulposus cells, inhibition of chondrogenic differentiation, disruption of endplate chondrogenic cells, and other processes. Various approaches for managing disc degeneration have been reported. Among them, mesenchymal stem cells (MSCs) have been regarded as representative trials. In vitro and animal studies with MSCs have reported some promising outcomes in terms of inflammatory modulation and regeneration, but several limitations have been pointed out, including the issues of graft rejection and survival. Because the paracrine mechanism would be a main therapeutic factor of MSCs, extracellular vesicles (EVs), one of the factors released from MSCs, have been considered a promising source for regenerative medicine. EVs possess nucleic acids, functional proteins, and inflammation-related factors, playing a significant role in the inflammatory reaction and regeneration. The current review article discusses the pathophysiology of disc degeneration, outcomes of conventional MSCs and EVs, and current limitations and future perspectives on EV therapeutics.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Arterial pH reflects both metabolic and respiratory distress in cardiac arrest and has prognostic implications. However, it was excluded from the 2024 update of the Utstein out-of-hospital cardiac arrest (OHCA) registry template. We investigated the rationale for including arterial pH into models predicting clinical outcomes. Methods: Data were sourced from the Korean Cardiac Arrest Research Consortium, a nationwide OHCA registry (NCT03222999). Prediction models were constructed using logistic regression, random forest, and eXtreme Gradient Boosting frameworks. Each framework included three model types: pH, low-flow time, and combined models. Then the area under the receiver operating characteristic curve (AUROC) of each predicting model was compared. The primary outcome was 30- day death or neurologically unfavorable status (cerebral performance category ≥3). Results: Among the 15,765 patients analyzed, 92.2% experienced death or unfavorable neurological outcomes. The predicting performance of the models including pH (AUROC, 0.92–0.94) were comparable to the models including low-flow time in all frameworks (0.93–0.94) (all P>0.05). Inclusion of pH into low-flow time models consistently showed higher AUROCs than individual models in all frameworks (AUROC, 0.93–0.95; all P<0.05). Conclusions: The predicting performance of models including arterial pH was comparable to models including low-flow time, and addition of arterial pH into low-flow time models could increase the performance of the models. Key Words: blood pH; hydrogen-ion con

Background: Patients with septic shock frequently require tracheal intubation in the emergency department (ED). However, the criteria for tracheal intubation are subjective, based on physician experience, or require serial evaluations over relatively long intervals to make accurate predictions, which might not be feasible in the ED. We used supervised learning approaches and features routinely available during the initial stages of evaluation and resuscitation to stratify the risks of tracheal intubation within a 24-hour time window. Methods: We retrospectively analyzed the data of patients diagnosed with septic shock based on the SEPSIS-3 criteria across 21 university hospital EDs in the Republic of Korea. A principal component analysis revealed a complex, non-linear decision boundary with respect to the application of tracheal intubation within a 24-hour time window. Stratified five-fold cross validation and a grid search were used with extreme gradient boost. Shapley values were calculated to explain feature importance and preferences. Results: In total, data for 4,762 patients were analyzed; within that population, 1,486 (31%) were intubated within a 24-hour window, and 3,276 (69%) were not. The area under the receiver operating characteristic curve and F1 scores for intubation within a 24-hour window were 0.829 (95% CI, 0.801–0.878) and 0.654 (95% CI, 0.627–0.681), respectively. The Shapley values identified lactate level after initial fluids, suspected lung infection, initial pH, Sequential Organ Failure Assessment score at enrollment, and respiratory rate at enrollment as important features for prediction. Conclusions An extreme gradient boosting machine can moderately discriminate whether intubation is warranted within 24 hours of the recognition of septic shock in the ED.