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 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 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.

Anosmia, characterized by the loss of smell, is associated not only with dysfunction in the peripheral olfactory system but also with changes in several brain regions involved in olfactory processing. Specifically, the orbitofrontal cortex is recognized for its pivotal role in integrating olfactory information, engaging in bidirectional communication with the primary olfactory regions, including the olfactory cortex, amygdala, and entorhinal cortex. However, little is known about alterations in structural connections among these brain regions in patients with anosmia. In this study, highresolution T1-weighted images were obtained from participants. Utilizing the volumes of key brain regions implicated in olfactory function, we employed a structural covariance approach to investigate brain reorganization patterns in patients with anosmia (n=22) compared to healthy individuals (n=30). Our structural covariance analysis demonstrated diminished connectivity between the amygdala and entorhinal cortex, components of the primary olfactory network, in patients with anosmia compared to healthy individuals (z=-2.22, FDR-corrected p=0.039). Conversely, connectivity between the orbitofrontal cortex—a major region in the extended olfactory network—and amygdala was found to be enhanced in the anosmia group compared to healthy individuals (z=2.32, FDR-corrected p=0.039). However, the structural connections between the orbitofrontal cortex and entorhinal cortex did not differ significantly between the groups (z=0.04, FDR-corrected p=0.968). These findings suggest a potential structural reorganization, particularly of higher-order cortical regions, possibly as a compensatory effort to interpret the limited olfactory information available in individuals with olfactory loss.

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years’ duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups’ gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferronicorrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus (r=0.316, p=0.001) and insular-opercular (r=0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM.

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder. Pain catastrophizing, characterized by magnification, rumination, and helplessness, increases perceived pain intensity and mental distress in CRPS patients. As functional connectivity patterns in CRPS remain largely unknown, we aimed to investigate functional connectivity alterations in CRPS patients and their association with pain catastrophizing using a whole-brain analysis approach. Twenty-one patients with CRPS and 49 healthy controls were included in the study for clinical assessment and resting-state functional magnetic resonance imaging. Between-group differences in whole-brain functional connectivity were examined through a Network-based Statistics analysis. Associations between altered functional connectivity and the extent of pain catastrophizing were also assessed in CRPS patients. Relative to healthy controls, CRPS patients showed higher levels of functional connectivity in the bilateral somatosensory subnetworks (components 1~2), but lower functional connectivity within the prefronto-posterior cingulate (component 3), prefrontal (component 4), prefronto-parietal (component 5), and thalamo-anterior cingulate (component 6) subnetworks (p<0.05, family-wise error corrected). Higher levels of functional connectivity in components 1~2 (β=0.45, p=0.04) and lower levels of functional connectivity in components 3~6 (β=-0.49, p=0.047) were significantly correlated with higher levels of pain catastrophizing in CRPS patients. Higher functional connectivity in the somatosensory subnetworks implicating exaggerated pain perception and lower functional connectivity in the prefronto-parieto-cingulo-thalamic subnetworks indicating impaired cognitive-affective pain processing may underlie pain catastrophizing in CRPS.

Sleep is essential to brain function and mental health. Insomnia and obstructive sleep apnea (OSA) are the two most common sleep disorders, and are major public health concerns. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method of quantifying neurometabolite concentrations. Therefore, 1H-MRS studies on individuals with sleep disorders may enhance our understanding of the pathophysiology of these disorders. In this article, we reviewed 1H-MRS studies in insomnia and OSA that reported changes in neurometabolite concentrations. Previous studies have consistently reported insomnia-related reductions in γ-aminobutyric acid (GABA) levels in the frontal and occipital regions, which suggest that changes in GABA are important to the etiology of insomnia. These results may support the hyperarousal theory that insomnia is associated with increased cognitive and physiological arousal. In addition, the severity of insomnia was associated with low glutamate and glutamine levels. Previous studies of OSA have consistently reported reduced N-acetylaspartate (NAA) levels in the frontal, parietooccipital, and temporal regions. In addition, OSA was associated with increased myo-inositol levels. These results may provide evidence that intermittent hypoxia induced by OSA may result in neuronal damage in the brain, which can be related to neurocognitive dysfunction in patients with OSA. The current review summarizes findings related to neurochemical changes in insomnia and OSA. Future well-designed studies using 1H-MRS have the potential to enhance our understanding of the pathophysiology of sleep disorders including insomnia and OSA.

Immunoreactive dynamics of tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment in breast cancer are not well understood. This study aimed to investigate the spatiotemporal cellular dynamics of TILs in breast cancer models. Breast cancer cells were implanted into the dorsal skinfold chamber of BALB/c nude mice, and T lymphocytes were adoptively transferred. Longitudinal intravital imaging was performed, and the spatiotemporal dynamics of TILs were assessed. In the 4T1 model, TILs progressively exhibited increased motility, and their motility inside the tumor was significantly higher than that outside the tumor. In the MDA-MB-231 model, the motility of TILs progressively decreased after an initial increase. TIL motility in the MDA-MB-231 and MCF-7 models differed significantly, suggesting an association between programmed death-ligand 1 expression levels and TIL motility, which warrants further investigation. Furthermore, intravital imaging of TILs can be a useful method for addressing dynamic interactions between TILs and breast cancer cells.

Sleep is essential to brain function and mental health. Insomnia and obstructive sleep apnea (OSA) are the two most common sleep disorders, and are major public health concerns. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method of quantifying neurometabolite concentrations. Therefore, 1H-MRS studies on individuals with sleep disorders may enhance our understanding of the pathophysiology of these disorders. In this article, we reviewed 1H-MRS studies in insomnia and OSA that reported changes in neurometabolite concentrations. Previous studies have consistently reported insomnia-related reductions in γ-aminobutyric acid (GABA) levels in the frontal and occipital regions, which suggest that changes in GABA are important to the etiology of insomnia. These results may support the hyperarousal theory that insomnia is associated with increased cognitive and physiological arousal. In addition, the severity of insomnia was associated with low glutamate and glutamine levels. Previous studies of OSA have consistently reported reduced N-acetylaspartate (NAA) levels in the frontal, parietooccipital, and temporal regions. In addition, OSA was associated with increased myo-inositol levels. These results may provide evidence that intermittent hypoxia induced by OSA may result in neuronal damage in the brain, which can be related to neurocognitive dysfunction in patients with OSA. The current review summarizes findings related to neurochemical changes in insomnia and OSA. Future well-designed studies using 1H-MRS have the potential to enhance our understanding of the pathophysiology of sleep disorders including insomnia and OSA.

Longitudinal imaging of murine pancreas is technically challenging due to the mechanical softness of the tissue influenced by peristalsis. Here, we report a novel pancreatic imaging window for long-term stabilized cellular-level observation of the islets in the pancreas in vivo. By spatially separating the pancreas from the bowel movement and physiologic respiration with a metal plate integrated in the imaging window, we successfully tracked the pancreatic islets up to three weeks and visualized the dumbbell-shape transformation from the single islet. This window can be a useful tool for long-term cellular-level visualization of the microstructure in the pancreas.