Background/Aims: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge. Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab. Results: The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of antitumor macrophages and activated T-cells, potentially explaining its better response. Conclusions Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

Objectives: The aim of this study was to determine the most effective treatment approach by comparing the impacts of various otolith reduction techniques in patients with apogeotropic lateral semicircular canal benign paroxysmal positional vertigo (LC-BPPV). Methods: We performed a multicenter randomized prospective study from January to December 2015, involving 72 consecutive patients with apogeotropic LC-BPPV. The patients were divided into three treatment groups: therapeutic head-shaking (group A), the Gufoni-Appiani maneuver (group B), and the cupulolith repositioning maneuver (CuRM; group C). Each group underwent evaluation and treatment up to the fourth week. Treatment success was defined as the disappearance of positional vertigo and nystagmus. Results: This study included 72 patients (49 male and 23 female), with a mean (±standard deviation) age of 55.4±13.5 years. The mean duration of vertigo experienced prior to treatment was 3.9±4.4 days. The mean latency and duration of nystagmus were 2.7±3.0 seconds and 47.9±15.8 seconds, respectively. The overall treatment frequency was 2.0±0.9. The number of treatments differed significantly among the three groups (P<0.05). After 4 weeks, the success rates for groups A, B, and C were 90.5%, 92.3%, and 100%, respectively. No significant difference was observed in the success rate across treatment methods and periods (P>0.05). However, CuRM was the only method with a 100% treatment success rate. Conclusion While no clear difference was observed among the three treatments for LC-BPPV, CuRM was found to be superior to the other approaches in the long term.

Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Objective: This study was performed to investigate the associations of life event stress with impulsivity, anxiety, and depressed mood as a function of the presence of a sleep disturbance. Methods: In total, 214 participants (age 38.96±10.53 years; 111 females) completed self-report questionnaires, including the Life Experience Survey (LES), Pittsburgh Sleep Quality Index (PSQI), Barratt’s Impulsivity Scale (BIS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI). The presence of a sleep disturbance was defined as a PSQI score >5. Results: In total, 127 participants presented with a sleep disturbance (age 39.33±10.92 years; 64 females), whereas the remaining 87 did not (age 38.43±9.97 years; 47 females). Negative LES scores were significantly correlated with BIS (r=0.22, p=0.001), BAI (r=0.46, p< 0.001), and BDI (r=0.51, p<0.001) scores, and PSQI scores were significantly correlated with BAI (r=0.49, p<0.001) and BDI (r=0.60, p< 0.001) scores. Moderation analysis revealed statistically significant interactions between negative LES scores and the presence of a sleep disturbance on BIS (p=0.044) and BDI (p=0.014) but not on BAI (p=0.194) scores. Conclusion The findings of the present study suggest that life event stress has varying degrees of influence on mental health, especially impulsivity and depressed mood, depending on the presence or absence of a sleep disturbance.

OBJECTIVES: The objective of this study was to investigate the correlation between insufficient sleep and visuospatial memory in adolescents using a computerized neurocognitive function test. METHODS: A total of 103 high school students (26 males and 77 females; mean age 17.11 ± 8.50 years) without a serious psychiatric problem was recruited. All subjects were requested to complete a self-report questionnaire about weekday total sleep time and weekend total sleep time. The epworth sleepiness scale (ESS) and the beck depression inventory (BDI) were administered to measure daytime sleepiness and symptoms of depression. Seven subsets of the Cambridge Neuropsychological test automated battery were examined to assess visuospatial memory. RESULTS: After controlling for age, sex, ESS, and BDI, longer weekend total sleep time was correlated with poor performance on delayed matching to sample (r = −0.312, p = 0.002) and immediate recall on pattern recognition memory (r = −0.225, p = 0.025). Increased weekend catch-up sleep time was correlated with poor performance of delayed matching to sample (r = −0.236, p = 0.018), immediate recall on pattern recognition memory (r = −0.220, p = 0.029), and delayed recall on pattern recognition memory (r = −0.211, p = 0.036) after controlling for age, sex, ESS, and BDI. CONCLUSION: This study showed that increased weekend catch-up sleep time reflecting insufficient weekday sleep were associated with poor performance in delayed recall tasks of visual memory. This finding suggests that insufficient sleep during adolescence might produce a decline of visuospatial memory.
Adolescent ; Depression ; Female ; Humans ; Male ; Memory ; Memory, Short-Term ; Neuropsychological Tests

This study was done to evaluate the effect of recombinant human bone morphogenic protein-2 (RhBMP-2) on enhancing the quality and quantity of regenerated bone when injected into distracted alveolar bone. Sixteen adult beagle dogs were assigned to either the control or rhBMP-2 group. After distraction was completed, an rhBMP-2 dose of 330μg in 0.33ml was slowly injected into the distracted alveolar crest of the mesial, middle, and distal parts of the alveolar bone in the experimental group. Histological and micro-computed tomography analyses of regenerated bone were done after 2 and 6 weeks of consolidation. After 6 weeks of consolidation, the vertical defect height of regenerated bone was significantly lower in the rhBMP-2 group (2.2 mm) than in the control group (3.4 mm) (P<0.05). Additionally, the width of the regenerated bone was significantly greater in the rhBMP-2 group (4.3 mm) than in the control group (2.8 mm) (P<0.05). The bone density and volume of regenerated bone in the rhBMP-2 group were denser and greater, respectively, than in the control group after 6 weeks of consolidation (P<0.001). Injection of rhBMP-2 into regenerated bone after a distraction osteogenesis procedure significantly increased bone volume in the dentoalveolar distraction site and improved both the width and height of the alveolar ridge and increased the bone density.

BACKGROUND/AIMS: The aim of this study was to analyze the trend of the prevalences of atrophic gastritis (AG) and intestinal metaplasia (IM) from 2011 to 2016~2017 in Korea. And, the risk factors of AG and IM were compared between 2011 and 2016~2017. MATERIALS AND METHODS: A total of 4,023 subjects in 2011 and 2,506 subjects in 2016~2017 were enrolled. AG and IM were diagnosed on the basis of endoscopic findings. Multivariate analysis was performed for risk factors of AG and IM. Seventeen factors were analyzed. RESULTS: The seroprevalence of Helicobacter pylori decreased from 2011 (59.8%; 2,407/4,023) to 2016~2017 (51.6%; 1,293/2,506; P < 0.001). The prevalence of AG decreased from 2011 to 2016~2017 (P=0.018), but that of IM increased (P < 0.001). The risk factors of AG in 2011 were male sex, old age, H. pylori immuoglobulin G (IgG) positivity, family history of gastric cancer (GC), and high-salt diet. For IM in 2011, the risk factors were male sex, old age, H. pylori IgG positivity, and family history of GC. Risk factors of AG in 2016~2017 were old age, H. pylori IgG positivity, and country of residence. For IM in 2016~2017, the risk factors were male sex, old age, family history of GC, high fasting glucose level (≥126 mg/dL), H. pylori IgG positivity, and low income level. CONCLUSIONS: The difference in prevalence trends of AG and IM between 2016~2017 and 2011 could be the result of the different risk factors of AG and IM, such as decreased prevalence of H. pylori infection.
Diet ; Fasting ; Gastritis, Atrophic ; Glucose ; Helicobacter pylori ; Humans ; Immunoglobulin G ; Korea ; Male ; Metaplasia ; Multivariate Analysis ; Prevalence ; Risk Factors ; Seroepidemiologic Studies ; Stomach Neoplasms