Purpose: While MRI-based tumor regression grade (mrTRG) has shown promise in evaluating pathologic response to concurrent chemoradiotherapy (CCRT) in rectal cancer, its ability to predict pathologic complete response remains limited.This study aimed to enhance mrTRG’s diagnostic performance in predicting ypT0–1N0 status, a key factor in considering non-radical management after CCRT for locally advanced rectal cancer (LARC). Methods: This retrospective study included 430 patients with LARC who underwent radical resection following CCRT at a single referral hospital between April 2018 and September 2024. Multivariable logistic regression was used to identify predictive factors associated with achieving ypT0–1N0 status. The diagnostic performances of mrTRG1–2 alone and in combination with other factors were assessed by comparing sensitivity, specificity, positive-predictive value (PPV), negative-predictive value, and area under the curve (AUC). Results: Ninety-three patients (21.6%) achieved ypT0–1N0. In the multivariable analysis, fungating type, cT1–2, and mrTRG1–2 were independent predictors for ypT0–1N0. Integrating mrTRG with gross tumor type yielded the highest AUC of 0.689 among the combined models. For predicting ypT0–1N0, the combination of mrTRG and gross tumor type improved PPV (79.2% vs. 41.5% for mrTRG alone) while also demonstrating enhanced sensitivity compared with ycT0–1N0, the conventional MRI-based predictor (40.9% vs. 22.6%). Conclusion This study demonstrated that combining mrTRG and gross tumor type improved the PPV of mrTRG in predicting ypT0–1N0 after CCRT in LARC. Further studies are warranted to validate the role of gross tumor type in refining predictive systems for selecting candidates for non-radical treatment.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Background: Deep neuromuscular blockade (NMB) optimizes surgical conditions, particularly during laparoscopic procedures. However, its effects on systemic cytokines associated with anesthesia-related complications, including postoperative delirium and cognitive dysfunction, remain unclear. In this review, we quantified the impact of deep NMB on serum cytokine levels. Methods: PubMed, EMBASE, CENTRAL, CINAHL, Scopus, Web of Science, and Google Scholar databases were searched to identify randomized controlled trials (RCTs) evaluating serum cytokine levels in surgical patients under deep or moderate NMB. Results: Eight RCTs, including 661 patients undergoing laparoscopic and orthopedic surgeries, met the inclusion criteria. Immediately postoperatively, meta-analysis suggested a potential reduction in tumor necrosis factor-α (TNF-α, standardized mean difference: −0.46, 95% CI [−0.87 to −0.06], P = 0.03), with no significant differences in interleukin-1β (IL-1β) or interleukin-6 (IL-6) levels. At 24-h and 48-h postoperatively, no significant differences were observed in IL-1β, IL-6, TNF-α, or C-reactive protein levels. Meta-regression analysis indicated that inhalational anesthesia was associated with high IL-1β (estimate = 1.2135, 95% CI [0.5107–1.9162], P < 0.01) and TNF-α levels (estimate = 0.6271, 95% CI [0.0544–1.1997], P = 0.032) immediately postoperatively; however, younger patients exhibited elevated IL-1β levels under moderate NMB at 24-h postoperatively (estimate = 0.0242, 95% CI [0.0065–0.0419], P < 0.01). Conclusions Deep NMB may be associated with reduced TNF-α levels immediately postoperatively. Inhalational anesthesia and younger age may contribute more to higher serum cytokine levels compared with total intravenous anesthesia and older age, respectively, suggesting a potential immunomodulatory effect of deep NMB. Further studies should clarify its clinical relevance.

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: Maintenance of stable blood pressure (BP) during cerebrovascular bypass surgery is crucial to prevent cerebral ischemia. We compared the effect of remimazolam anesthesia with that of propofol-induced and desflurane-maintained anesthesia on intraoperative hemodynamic stability and the need for vasoactive agents in patients undergoing cerebrovascular bypass surgery. Methods: Sixty-five patients were randomized into remimazolam (n = 31, remimazolam-based intravenous anesthesia) and control groups (n = 34, propofol-induced and desflurane-maintained anesthesia). The primary outcome was the occurrence of intraoperative hypotension. The secondary outcomes included hypotension duration, lowest mean BP (MBP), generalized average real variability (ARV) of MBP, and consumption of phenylephrine, norepinephrine, or remifentanil. Results: Occurrence rate and duration of hypotension were significantly lower in the remimazolam group (38.7% vs. 73.5%, P = 0.005; 0 [0, 10] vs. 7.5 [1.25, 25] min, P = 0.008). Remimazolam also showed better outcomes for lowest MBP (78 [73, 84] vs. 69.5 [66.25, 75.8] mmHg, P < 0.001) and generalized ARV of MBP (1.42 ± 0.49 vs. 1.66 ± 0.52 mmHg/min, P = 0.036). The remimazolam group required less phenylephrine (20 [0, 65] vs. 100 [60, 130] μg, P < 0.001), less norepinephrine (162 [0, 365.5] vs. 1335 [998.5, 1637.5] μg, P < 0.001), and more remifentanil (1750 [1454.5, 2184.5] vs. 531 [431, 746.5] μg, P < 0.001) than the control group. Conclusions Remimazolam anesthesia may provide better hemodynamic stability during cerebrovascular bypass surgery than propofol-induced and desflurane-maintained anesthesia.

The impact of Streptococcus pneumoniae coinfection on coronavirus disease 2019 (COVID-19) prognosis remains uncertain. We conducted a retrospective analysis of patients hospitalized with COVID-19 who underwent a pneumococcal urinary antigen (PUA) test to assess its clinical utility. Results showed that PUA-positive patients required more oxygen support, high-flow nasal cannula, and dexamethasone compared to PUA-negative patients.Furthermore, the significantly higher incidence of a National Early Warning Score ≥5 in the PUA-positive group (P<0.001) suggests that a positive PUA test is associated with a severe disease course. However, no significant difference in mortality was observed between the two groups, and antibiotics were used in almost all patients (96.2%). While the PUA test may help guide antibiotic use in COVID-19 patients, its interpretation should be approached with caution.

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: Maintenance of stable blood pressure (BP) during cerebrovascular bypass surgery is crucial to prevent cerebral ischemia. We compared the effect of remimazolam anesthesia with that of propofol-induced and desflurane-maintained anesthesia on intraoperative hemodynamic stability and the need for vasoactive agents in patients undergoing cerebrovascular bypass surgery. Methods: Sixty-five patients were randomized into remimazolam (n = 31, remimazolam-based intravenous anesthesia) and control groups (n = 34, propofol-induced and desflurane-maintained anesthesia). The primary outcome was the occurrence of intraoperative hypotension. The secondary outcomes included hypotension duration, lowest mean BP (MBP), generalized average real variability (ARV) of MBP, and consumption of phenylephrine, norepinephrine, or remifentanil. Results: Occurrence rate and duration of hypotension were significantly lower in the remimazolam group (38.7% vs. 73.5%, P = 0.005; 0 [0, 10] vs. 7.5 [1.25, 25] min, P = 0.008). Remimazolam also showed better outcomes for lowest MBP (78 [73, 84] vs. 69.5 [66.25, 75.8] mmHg, P < 0.001) and generalized ARV of MBP (1.42 ± 0.49 vs. 1.66 ± 0.52 mmHg/min, P = 0.036). The remimazolam group required less phenylephrine (20 [0, 65] vs. 100 [60, 130] μg, P < 0.001), less norepinephrine (162 [0, 365.5] vs. 1335 [998.5, 1637.5] μg, P < 0.001), and more remifentanil (1750 [1454.5, 2184.5] vs. 531 [431, 746.5] μg, P < 0.001) than the control group. Conclusions Remimazolam anesthesia may provide better hemodynamic stability during cerebrovascular bypass surgery than propofol-induced and desflurane-maintained anesthesia.