Background: Alpha-fetoprotein (AFP) and its isoform AFP-L3 are well-established serum biomarkers for hepatocellular carcinoma (HCC), a common malignancy and a leading cause of cancer-related mortality worldwide. Current methods for measuring these biomarkers are primarily lectin-based assays including the liquid-phase binding assay (LiBA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), both of which have limitations in diagnostic sensitivity and clinical utility for samples with low AFP concentrations. We aimed to develop a lectin-independent LC-MS/MS method for quantifying fucosylated AFP proteins (AFP-Fuc%). Methods: We conducted analytical validation, including method comparisons, over 2 months. The analytical sensitivity and diagnostic performance of this method were evaluated using 525 human serum samples—235 from HCC patients and 290 from non-HCC individuals—and compared with those of LiBA, which measured AFP-L3 levels. Results: The LC-MS/MS method demonstrated acceptable within-laboratory imprecision (CVs < 17.1%) without detectable bias, carryover, or matrix effects. Our method exhibited a broader linear dynamic range (spanning five orders of magnitude) and 10-fold higher analytical sensitivity than LiBA. The diagnostic performance of our method was significantly superior to that of LiBA, particularly in patients with low AFP concentrations ( < 7 ng/mL, P < 0.001), with improved accuracy, sensitivity, and precision at a specificity of 96.2%. Conclusions The validated LC-MS/MS method demonstrated robust analytical performance and superior diagnostic accuracy over LiBA for HCC diagnosis while avoiding the inherent limitations of lectin-based assays. Our LC-MS/MS assay shows promise for early HCC detection and may contribute to enhanced patient care.

Background/Aims: Gastroesophageal reflux disease (GERD) after peroral endoscopic myotomy (POEM) is a significant challenge. Disruption of the lower esophageal sphincter during POEM and dysfunction of the crural diaphragm, which contributes to esophagogastric junction pressure, may lead to GERD after POEM. We aim to identify predictors of GERD after POEM and focus on physiological parameters of esophagogastric junction pressure in patients with achalasia before POEM. Methods: We retrospectively analyzed a prospectively collected database of patients who underwent POEM between July 2016 and August 2023. Ninety-two patients with achalasia who underwent high-resolution manometry and endoscopy before and after POEM were included. Results: Forty-nine (53.3%) patients were diagnosed with GERD. Patient demographics, achalasia subtypes, prior treatments, myotomy length, and myotomy orientation were not associated with GERD after POEM. Loss of inspiratory augmentation before POEM was associated with GERD after POEM (P < 0.05). GERD occurred more frequently in patients with a shorter intra-abdominal lower esophageal sphincter length before POEM. Type III esophagogastric junction morphology in the GERD group (37.1%) was more common than that in the non-GERD group (15.8%). Loss of inspiratory augmentation occurred more frequently in patients with type III esophagogastric junction pressure morphology. Conclusion Loss of inspiratory augmentation may predict GERD after POEM.

Background/Aims: Esophageal transit scintigraphy is a non-invasive nuclear medicine imaging modality for people with esophageal transit problems. In particular, changes in esophageal motor function can be evaluated non-invasively before and after the treatment in patients undergoing peroral endoscopic myotomy (POEM) for achalasia. This study compared the changes in several parameters of esophageal transit and manometry in patients with achalasia who underwent POEM. Methods: This study retrospectively analyzed prospectively collected data from POEM participants. We included 38 patients with achalasia who underwent high-resolution manometry and esophageal transit scintigraphy before POEM and after POEM from 2016 to 2023. Results: All patients had clinical treatment successfully (Eckardt score < 3). Lower esophageal sphincter (LES) pressures were significantly reduced after POEM, including basal resting LES pressure and integrated relaxation pressure (P < 0.001).Esophageal emptying, as assessed by the residual fraction of retained radioactivity at 10 seconds after isotope ingestion, improved from 54.3% to 27.3% (P < 0.001). Analysis of the change in time-to-peak on the time-radioactivity curve showed that it shortened significantly in the upper and middle portions of the esophagus (P < 0.05) but not in the lower portion.The Eckardt symptom score significantly correlated with pre-POEM integrated relaxation pressure (P < 0.05). Post-POEM, the symptom score significantly correlated with time-to-peak of the upper portion of the esophagus (P < 0.05). Conclusions Patients with achalasia who received POEM showed improved not only manometric LES parameters but also esophageal transit. Analysis of the radiation curve’s time-to-peak showed that improved retention in the upper portion is an indicator of symptoms improvement in patients who underwent POEM.

Purpose: There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the epidermal growth factor receptor (EGFR) mutation. Materials and Methods: A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue. Results: In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22.0%, 9.8%, and 29.3%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 36.6%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 82.9% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation. Conclusion We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

This study aimed to determine the association between trajectories of obesity status and prediabetes reversion to normoglycemia or progression to diabetes. The study included 14,452 participants from the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort who continuously had prediabetes glycemic status during the index period (2002-2008), definedby their fasting plasma glucose. The exposure of the study was the trajectories of obesity (defined by body mass index ≥ 25 kg/m 2 ) generated using latent class growth analysis. The outcomes were reversion to normoglycemia or progression to diabetes, whichever occurred first during the follow-up period (2009-2016). The association between trajectories and changes in prediabetes status were examined using cause-specific hazard regression by obtaining the hazard ratio (HR) with a 95% CI. We identified three distinct trajectories which were “Stable obese”, “Stable non-obese” and “Obese to non-obese”. After a median follow-up of 2years, 51.99% of participants had their glycemic status back to normoglycemia and 32.17% developed diabetes. Compared with participants in the “Stable obese” group, those in “Stable non-obese” and “Obese to non-obese” groups were more likely to have reversion to normoglycemia (HR with a 95% CI = 1.30 [1.23-1.37] and 1.15 [1.07-1.24], respectively) and lower risk of developingdiabetes (0.78 [0.73-0.84] and 0.90 [0.82-0.98], respectively). The findings suggest that maintaining or achieving a non-obese sta-tus is linked to higher reversion to normoglycemia as well as lower risks of developing diabetes.

Background/Aims: Tracheostomy is a crucial intervention for severe pneumonia patients requiring prolonged mechanical ventilation (MV). However, debate persists regarding the influence of tracheostomy timing and performance on long-term survival outcomes. This study utilized propensity score matching to assess the impact of tracheostomy timing and performance on patient survival outcomes. Methods: A retrospective observational study employing propensity score matching was conducted of respiratory intensive care unit (ICU) patients who underwent prolonged acute MV due to severe pneumonia from 2008 to 2023. The primary outcome was the 90-day cumulative mortality rate, with secondary outcomes including ICU medical resource utilization rates. Results: Out of 1,078 patients, 545 underwent tracheostomy with a median timing of 7 days. The tracheostomy group exhibited lower 90-day cumulative mortality and a higher survival probability (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.43–0.63) than the no-tracheostomy group. The tracheostomy group had higher ICU medical resource utilization rates and medical expenditures. The early tracheostomy group (≤ 7 days) had lower ICU medical resource utilization rates and medical expenditures than the late tracheostomy group (> 7 days). However, there were no significant differences in the 90-day cumulative mortality rate and survival probability based on tracheostomy timing (HR 0.94, 95% CI 0.70–1.28). Conclusions Tracheostomy in patients with severe pneumonia requiring prolonged MV significantly reduced the 90-day mortality rate, and early tracheostomy may offer additional benefits for resource utilization efficiency. These findings underscore the importance of considering tracheostomy timing in optimizing patient outcomes and healthcare resource allocation.

Background/Aims: This study aimed to investigate co-occurrence and clinical characteristics of sexually transmitted infections (STIs) and pelvic inflammatory disease (PID) in women hospitalized for acute pyelonephritis (APN). Methods: This single-center retrospective study reviewed medical records of inpatients with APN from January 2019 to February 2023 and identified records of 142 patients who were referred to a gynecologist to evaluate gynecological diseases including STIs. Results: Of the 142 patients, 47 were tested positive for sexually transmitted pathogens in nucleic acid amplification testing, confirming the presence of STIs. In patients with APN, those with STIs were more likely to have lower abdominal pain or cervical motion tenderness (CMT) on pelvic examination and leukocytosis (> 14.5 × 109/L) than those without STIs. Of the 93 patients who underwent pelvic examination, 34 had CMT with one or more of additional criteria for the clinical diagnosis of PID, such as abnormal vaginal discharge and leukorrhea confirmed by microscopic examination, which could be clinically diagnosed as PID. Conclusions In sexually active women with APN, it is important to evaluate the possibility of STIs and PID, considering several risk factors such as lower abdominal pain, abnormal vaginal discharge, CMT, and leukocytosis.

Background/Aims: Tracheostomy is a crucial intervention for severe pneumonia patients requiring prolonged mechanical ventilation (MV). However, debate persists regarding the influence of tracheostomy timing and performance on long-term survival outcomes. This study utilized propensity score matching to assess the impact of tracheostomy timing and performance on patient survival outcomes. Methods: A retrospective observational study employing propensity score matching was conducted of respiratory intensive care unit (ICU) patients who underwent prolonged acute MV due to severe pneumonia from 2008 to 2023. The primary outcome was the 90-day cumulative mortality rate, with secondary outcomes including ICU medical resource utilization rates. Results: Out of 1,078 patients, 545 underwent tracheostomy with a median timing of 7 days. The tracheostomy group exhibited lower 90-day cumulative mortality and a higher survival probability (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.43–0.63) than the no-tracheostomy group. The tracheostomy group had higher ICU medical resource utilization rates and medical expenditures. The early tracheostomy group (≤ 7 days) had lower ICU medical resource utilization rates and medical expenditures than the late tracheostomy group (> 7 days). However, there were no significant differences in the 90-day cumulative mortality rate and survival probability based on tracheostomy timing (HR 0.94, 95% CI 0.70–1.28). Conclusions Tracheostomy in patients with severe pneumonia requiring prolonged MV significantly reduced the 90-day mortality rate, and early tracheostomy may offer additional benefits for resource utilization efficiency. These findings underscore the importance of considering tracheostomy timing in optimizing patient outcomes and healthcare resource allocation.

Background/Aims: This study aimed to investigate co-occurrence and clinical characteristics of sexually transmitted infections (STIs) and pelvic inflammatory disease (PID) in women hospitalized for acute pyelonephritis (APN). Methods: This single-center retrospective study reviewed medical records of inpatients with APN from January 2019 to February 2023 and identified records of 142 patients who were referred to a gynecologist to evaluate gynecological diseases including STIs. Results: Of the 142 patients, 47 were tested positive for sexually transmitted pathogens in nucleic acid amplification testing, confirming the presence of STIs. In patients with APN, those with STIs were more likely to have lower abdominal pain or cervical motion tenderness (CMT) on pelvic examination and leukocytosis (> 14.5 × 109/L) than those without STIs. Of the 93 patients who underwent pelvic examination, 34 had CMT with one or more of additional criteria for the clinical diagnosis of PID, such as abnormal vaginal discharge and leukorrhea confirmed by microscopic examination, which could be clinically diagnosed as PID. Conclusions In sexually active women with APN, it is important to evaluate the possibility of STIs and PID, considering several risk factors such as lower abdominal pain, abnormal vaginal discharge, CMT, and leukocytosis.

Background: With the introduction of disease-modifying treatments for Alzheimer’s disease (AD), less invasive and widely accessible screening tests are urgently needed. We assessed eight blood-based biomarkers in a well-defined cohort of preclinical AD, including participants with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: Amyloid beta (Aβ) oligomerization tendency, Aβ42, Aβ40, Aβ42/Aβ40 ratio, phosphorylated tau (p-tau)181, p-tau217, glial fibrillary acidic protein (GFAP), and neurofilament light (Nf-L) were assessed for distinguishing between SCD and MCI, for correlations, and for predicting Aβ positron emission tomography (PET) positivity. Results: Plasma p-tau181, p-tau217, and GFAP levels were significantly higher in participants with MCI than in those with SCD (P < 0.05) and in Aβ PET-positive versus Aβ PET-negative participants (P < 0.0001), whereas plasma Aβ42 and Aβ42/40 ratio levels were significantly lower in Aβ PET-positive than in Aβ PET-negative participants (P < 0.001). Logistic regression analysis revealed that plasma Aβ42 and p-tau217 levels predicted Aβ PET positivity with an area under the ROC curve (AUC) of 0.930 (95% confidence interval [CI], 0.848–0.976) in the entire cohort, and p-tau217 alone predicted Aβ PET-positivity with an AUC of 0.887 (95% CI, 0.779–0.954) in the MCI subgroup. Conclusions Plasma p-tau217 levels outperform plasma p-tau181 levels in predicting Aβ PET-positivity in participants with preclinical AD. Plasma GFAP levels, along with different ptau isoforms (p-tau181 and p-tau217), effectively differentiate MCI from SCD. The predictive accuracy of blood-based biomarkers for Aβ PET-positivity strongly supports their clinical implementation, particularly with the introduction of disease-modifying therapies.