Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Background and Objectives: Obstructive sleep apnea (OSA) has been associated with an increased risk of cancer in various organs. OSA is also linked to chronic inflammation in the biliary tract and pancreas, a well-established risk factor for carcinogenesis in these organs. However, its relationship with biliary tract and pancreatic cancers remains unclear and has been rarely investigated. Therefore, we aimed to evaluate whether OSA serves as an independent risk factor for these malignancies by analyzing a nationwide healthcare claims database in South Korea. Methods: A retrospective cohort study was conducted using the Korean National Health Insurance Service (KNHIS) database. Adults aged ≥20 years who were newly diagnosed with OSA (ICD-10: G47.30) between 2007 and 2014 were identified and propensity score-matched (1:5) with controls based on age, sex, and comorbidities. Individuals with pre-existing cancer diagnoses were excluded. The primary endpoints were the incidence of overall cancer, biliary tract cancer (C23–C24), and pancreatic cancer (C25). Cox proportional hazards regression models were used to calculate hazard ratios (HRs), adjusting for demographic and clinical factors. Results: A total of 1,191,444 individuals were included, comprising 198,574 patients diagnosed with OSA and 992,870 matched controls. OSA was associated with an increased overall cancer incidence (HR, 1.132; 95% confidence interval [CI], 1.097–1.169); however, it was not significantly associated with pancreatic cancer (HR, 0.941; 95% CI, 0.823–1.072) or biliary tract cancer (HR, 0.931; 95% CI, 0.751–1.142). Subgroup analyses stratified by sex and age revealed no statistically significant associations across these groups. Conclusion Our findings do not support OSA as an independent risk factor for biliary tract or pancreatic cancers.

Although many wearable devices are used to assess sleep, their accuracy remains controversial. This study aimed to investigate the accuracy of the Actiwatch, a research-grade device, and the Fitbit, a consumer-grade device, against sleep diaries to assess sleep patterns. Methods: Twenty participants wore Fitbit and Actiwatch for two weeks and tracked their sleep patterns using sleep diaries. Total sleep time (TST), time-in-bed (TIB), sleep efficiency (SE), sleep onset latency (SOL), and wake after sleep onset (WASO) from the two devices and sleep diaries were analyzed using analysis of variance and Bland-Altman analysis. Results: The TIB measured by the sleep log, Fitbit, and Actiwatch were 420.9 minutes, 417.3 minutes, and 567.4 minutes, respectively. Compared to the sleep log, the Fitbit underestimated TST, TIB, and SE, with significant differences observed for TST (p<0.001) and SE (p<0.001), but not for TIB. The Actiwatch overestimated TIB (p<0.001) and TST (p=0.02) and underestimated SE (p<0.001) compared to the sleep log. The difference between the Fitbit and Actiwatch was significant for TST, TIB, and SE (all p<0.001). Conclusions: The Fitbit showed a smaller difference than the Actiwatch when compared with the sleep logs. The Fitbit could be used as a tool to assess sleep patterns in the clinic as well as in daily life.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: and Purpose The Treat Stroke to Target (TST) was a randomized clinical trial involving French and Korean patients demonstrating that a lower low-density lipoprotein cholesterol (LDL-C, <70 mg/dL) target group (LT) experienced fewer cerebro-cardiovascular events than a higher target (90–110 mg/dL) group (HT). However, whether these results can be applied to Asian patients with different ischemic stroke subtypes remains unclear. Methods: Patients from 14 South Korean centers were analyzed separately. Patients with ischemic stroke or transient ischemic attack with evidence of atherosclerosis were randomized into LT and HT groups. The primary endpoint was a composite of ischemic stroke, myocardial infarction, coronary or cerebral revascularization, and cardiovascular death. Results: Among 712 enrolled patients, the mean LDL-C level was 71.0 mg/dL in 357 LT patients and 86.1 mg/dL in 355 HT patients. The primary endpoint occurred in 24 (6.7%) of LT and in 31 (8.7%) of HT group patients (adjusted hazard ratio [HR]=0.78; 95% confidence interval [CI]=0.45–1.33, P=0.353). Cardiovascular events alone occurred significantly less frequently in the LT than in the HT group (HR 0.26, 95% CI 0.09–0.80, P=0.019), whereas there were no significant differences in ischemic stroke events (HR 1.12, 95% CI 0.60–2.10, P=0.712). The benefit of LT was less apparent in patients with small vessel disease and intracranial atherosclerosis than in those with extracranial atherosclerosis. Conclusion In contrast to the French TST, the outcomes in Korean patients were neutral. Although LT was more effective in preventing cardiovascular diseases, it was not so in stroke prevention, probably attributed to the differences in stroke subtypes. Further studies are needed to elucidate the efficacy of statins and appropriate LDL-C targets in Asian patients with stroke.

Background: Remimazolam is a novel short-acting benzodiazepine. This study compared the effects of remimazolam and propofol on cognitive function in adult patients after surgery or other procedures. Methods: We searched electronic databases, including PubMed, Embase, CENTRAL, Web of Science, and Scopus, for relevant studies. The primary outcome was the proportion of participants who experienced delirium or impaired cognitive function postoperatively. Secondary outcomes included the incidence of hypotension, bradycardia, and postoperative nausea and vomiting. We estimated the odds ratios (OR) and mean differences (MD) with 95% CIs using a random-effects model. Results: In total, 1295 patients from 11 randomized controlled trials were included. The incidence of postoperative delirium was 8.0% in the remimazolam group and 10.4% in the propofol group that was not significantly different (OR: 0.74, 95% CI [0.39–1.42], P = 0.369, I2 = 32%). More favorable cognitive function, as assessed using the Mini-Mental State Examination, was observed in the remimazolam group compared to the propofol group (MD: 1.06, 95% CI [0.32–1.80], P = 0.005, I2 = 89%). Remimazolam lowered the incidence of hypotension (OR: 0.28, 95% CI [0.21–0.37], P = 0.000, I2 = 0%) compared to propofol. Conclusions Remimazolam did not increase the risk of postoperative delirium and maintained cognitive function well, providing hemodynamic stability during surgery compared to propofol.

Background: Remimazolam is a novel short-acting benzodiazepine that has recently been used for general anesthesia. This study compared the safety and efficacy of remimazolam-based total intravenous anesthesia (TIVA) and volatile agent-based anesthesia in adults undergoing general anesthesia. Methods: We searched electronic databases including PubMed, Embase, CENTRAL, and Scopus for relevant studies. The primary outcome was the proportion of patients who experienced hypotension during surgery. Secondary outcomes included incidence of bradycardia, extubation time, duration in the post-anesthesia care unit hospital stay, and incidence of postoperative nausea and/or vomiting (PONV). We estimated the relative risk (RR) and mean difference with 95% CIs using a random-effects model. Results: A total of 969 patients from 12 randomized controlled trials were included. The incidence of hypotension was 14% and 34% in the remimazolam and volatile agent groups, respectively. Remimazolam significantly lowered the incidence of hypotension (RR: 0.43, 95% CI [0.29–0.63], P = 0.0000, I2 = 26%). The remimazolam group had a PONV incidence of 13%, compared to 28% in the volatile agent group, indicating a significant difference (RR: 0.51, 95% CI [0.37–0.72], P = 0.0001, I2 = 15%). No significant differences were observed in the other outcomes. Conclusions Remimazolam-based TIVA demonstrated favorable hemodynamic effects, with a lower incidence of hypotension and similar bradycardia rates, compared to volatile agent-based anesthesia. Furthermore, the reduction in PONV supports the use of remimazolam-based TIVA as a valuable method for general anesthesia.

Background: We hypothesized that intranasal combination of dexmedetomidine (2 μg/kg) and ketamine (3 mg/kg) (IN DEXKET) improves the success rate of sedation in pediatric patients compared with chloral hydrate (CH; 50 mg/kg). Methods: This prospective, two-center, single-blinded, randomized controlled trial involved 136 pediatric patients (aged < 7 years) requiring procedural sedation. The participants were randomized to receive CH or IN DEXKET via a mucosal atomizer device. The primary outcome was the success rate of sedation (Pediatric Sedation State Scale, scores 1–3) within 15 min. The secondary outcomes included sedation failure at 30 min and overall complications of first-attempt sedation. Results: After excluding eight patients, 128 were included (CH = 66, IN DEXKET = 62). IN DEXKET showed a similar sedation success rate (75.8% [47/62] vs. 66.7% [44/66]; P = 0.330) but a lower complication rate (3.2% [2/62] vs. 16.7% [11/66]; P = 0.017) than CH. In the subgroup analysis for patients aged < 1 year, IN DEXKET showed a reduced complication rate than CH (2.6% [1/38] vs. 22.9% [8/35]; P = 0.012). In the subgroup analysis of children aged 1–7 years, IN DEXKET showed a higher sedation success rate within 15 min (79.2% [19/24] vs. 51.6% [16/31]; P = 0.049) and a lower sedation failure after 30 min (0% vs. 29.0% [9/31]; P = 0.003) than CH. Conclusions The intranasal combination of dexmedetomidine (2 μg/kg) and ketamine (3 mg/kg) is a safe and effective alternative to CH (50 mg/kg) for sedation in pediatric patients aged < 7 years.