Acid Sphingomyelinase Inhibitor, Imipramine, Reduces Hippocampal Neuronal Death after Traumatic Brain Injury.

Traumatic brain injury (TBI) broadly degrades the normal function of the brain after a bump, blow, or jolt to the head. TBI leads to the aggravation of pre-existing brain dysfunction and promotes neurotoxic cascades that involve processes such as oxidative stress, loss of dendritic arborization, and zinc accumulation. Acid sphingomyelinase (ASMase) is an enzyme that hydrolyzes sphingomyelin to ceramide in cells. Under normal conditions, ceramide plays an important role in various physiological functions, such as differentiation and apoptosis. However, under pathological conditions, excessive ceramide production is toxic and activates the neuronal-death pathway. Therefore, we hypothesized that the inhibition of ASMase activity by imipramine would reduce ceramide formation and thus prevent TBI-induced neuronal death. To test our hypothesis, an ASMase inhibitor, imipramine (10 mg/kg, i.p.), was administrated to rats immediately after TBI. Based on the results of this study, we confirmed that imipramine significantly reduced ceramide formation, dendritic loss, oxidative stress, and neuronal death in the TBI-imipramine group compared with the TBI-vehicle group. Additionally, we validated that imipramine prevented TBI-induced cognitive dysfunction and the modified neurological severity score. Consequently, we suggest that ASMase inhibition may be a promising therapeutic strategy to reduce hippocampal neuronal death after TBI.

CF3-Substituted Mollugin 2-(4-Morpholinyl)-ethyl ester as a Potential Anti-inflammatory Agent with Improved Aqueous Solubility and Metabolic Stability.

Although mollugin, the main ingredient of the oriental medicinal herb Rubia cordifolia, has considerable anti-inflammatory effects, it has poor aqueous solubility as well as poor metabolic and plasma stability. To overcome these shortfalls, various mollugin derivatives have been synthesized and evaluated for their ability to inhibit U937 monocyte cell adhesion to HT-29 colonic epithelial cells in TNF-α- or IL-6-induced models of colon inflammation. The 2-(4-morpholinyl)-ethyl ester of CF3-substituted mollugin (compound 15c) showed good water solubility, improved metabolic and plasma stability, and greater inhibitory activity than mesalazine in both the TNF-α- and IL-6-induced colonic epithelial cell adhesion assays, suggesting that 15c is a potential anti-inflammatory agent.

Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca2+) and other metal ions, such as zinc (Zn2+) and magnesium (Mg2+), into the cytosol. This Ca2+ influx at the presynaptic terminal triggers the release of Zn2+ and glutamate to the postsynaptic terminal. Zn2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects.

A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure.

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses. We hypothesized that amlexanox, an anti-inflammatory drug and non-selective PDE4 inhibitor, could offer neuroprotection by addressing lysosomal dysfunction and mitigating neuroinflammation, ultimately preventing neuronal death in epileptic conditions. Our research utilized a pilocarpine-induced epilepsy animal model to investigate amlexanox's potential benefits. Administered intraperitoneally at a dose of 100 â€‹mg/kg daily following the onset of a seizure, we monitored its effects on lysosomal function, inflammation, neuronal death, and cognitive performance in the brain. Tissue samples from various brain regions were collected at predetermined intervals for a comprehensive analysis. The study's results were significant. Amlexanox effectively improved lysosomal function, which we attribute to the modulation of zinc's influx into the lysosomes, subsequently enhancing autophagic processes and decreasing the release of inflammatory factors. Notably, this led to the attenuation of neuronal death in the hippocampal region. Additionally, cognitive function, assessed through the modified neurological severity score (mNSS) and the Barnes maze test, showed substantial improvements after treatment with amlexanox. These promising outcomes indicate that amlexanox has potential as a therapeutic agent in the treatment of epilepsy and related brain disorders. Its ability to combat lysosomal dysfunction and neuroinflammation positions it as a potential neuroprotective intervention. While these findings are encouraging, further research and clinical trials are essential to fully explore and validate the therapeutic efficacy of amlexanox in epilepsy management.

Effects of Pyruvate Kinase M2 (PKM2) Gene Deletion on Astrocyte-Specific Glycolysis and Global Cerebral Ischemia-Induced Neuronal Death.

Ischemic stroke is caused by insufficient blood flow to the brain. Astrocytes have a role in bidirectionally converting pyruvate, generated via glycolysis, into lactate and then supplying it to neurons through astrocyte-neuron lactate shuttle (ANLS). Pyruvate kinase M2 (PKM2) is an enzyme that dephosphorylates phosphoenolpyruvate to pyruvate during glycolysis in astrocytes. We hypothesized that a reduction in lactate supply in astrocyte PKM2 gene deletion exacerbates neuronal death. Mice harboring a PKM2 gene deletion were established by administering tamoxifen to Aldh1l1-CreERT2; PKM2f/f mice. Upon development of global cerebral ischemia, mice were immediately injected with sodium l-lactate (250 mg/kg, i.p.). To verify our hypothesis, we compared oxidative damage, microtubule disruption, ANLS disruption, and neuronal death between the gene deletion and control subjects. We observed that PKM2 gene deletion increases the degree of neuronal damage and impairment of lactate metabolism in the hippocampal region after GCI. The lactate administration groups showed significantly reduced neuronal death and increases in neuron survival and cognitive function. We found that lactate supply via the ANLS in astrocytes plays a crucial role in maintaining energy metabolism in neurons. Lactate administration may have potential as a therapeutic tool to prevent neuronal damage following ischemic stroke.

[Gastrointestinal Disease in the Population Aged 80 Years and above in Korea during Recent Decades: Multi-center Cross-sectional Study].

Background/Aims: Globally, the population aged 80 years or older is growing faster due to the rising life expectancy. Korea has already entered into an advanced aged society, and a post-aged society is expected in 2025. This study evaluated the patterns of gastrointestinal disease in the population aged 80 years or older during the recent decade in Korea. Method: This study retrospectively reviewed the medical records of patients admitted to the gastrointestinal department of Suwon St. Vincent's hospital, Incheon St. Mary's hospital, and Uijeongbu St. Mary's Hospital - general hospitals of Seoul-Gyeonggi province in Korea. It was a repeated cross-sectional study in 2009 and 2019. Results: The number of admitted patients aged 80 years or older increased from 549 (9.0%) in 2009 to 1,073 (14.4%) in 2019 (p<0.01). As for the in-hospital mortality, there was no significant difference (p=0.25). On the other hand, the combined morbidities increased, and the duration of admission also increased (7.2±7.8 days vs. 8.1±8.2 days, p=0.03). The number of upper gastrointestinal hemorrhage and patients who are bleeding associated with drugs users increased (p<0.01). The proportion of lower gastrointestinal disease decreased (p<0.01) because of the decrease in procedure-related admissions (p<0.01). The number of those with pancreaticobiliary tract disease increased markedly (p<0.01), and the rate of cases that could not perform the procedure decreased (p=0.04). Conclusion: The patterns of gastrointestinal disease in the population aged 80 years or older have changed in the recent decade in Korea. Hence, more preparation for this medical environment is needed.

The trial of application for interpretation on brain computed tomography by emergency medicine residents assisted artificial intelligence algorithm-based solution

Objective@#This study examined the efficacy of artificial intelligence (AI) algorithm-based diagnostic assistant solutions in the interpretation of brain computed tomography (CT) by emergency medicine (EM) residents. @*Methods@#This study included 350 patients who visited a local emergency medical center over 5 months and underwent brain CT scans. EM residents initially interpreted the patients’ scans. A second interpretation was performed using an AI algorithm-based solution. The initial and second interpretations were compared with that of a radiology physician. @*Results@#The first interpretation by EM residents showed agreement in 318 cases (90.9%), while the second, assisted by an AI algorithm-based solution, showed agreement in 308 cases (88.0%). The first interpretation had an accuracy, sensitivity, and specificity of 93.1%, 43.9%, and 99.7%, respectively, and the second had an accuracy, sensitivity, and specificity of 92.0%, 39.0%, and 99.0%, respectively (P<0.001). Most of the discrepancies observed in the first and second interpretations were classified as Grade 1. @*Conclusion@#The interpretations assisted by the AI algorithm-based solution resulted in lower accuracy and higher discrepancy rates than independent interpretations by EM residents. The AI algorithm-based solution provided efficacy in accurate interpretation depending on the cases. Further study will be needed to address the weaknesses of the function and utility of AI.

Application of Cartilage Extracellular Matrix to Enhance Therapeutic Efficacy of Methotrexate

BACKGROUND@#Rheumatoid arthritis (RA) is characterized by chronic inflammation and joint damage. Methotrexate (MTX), a commonly used disease-modifying anti-rheumatic drug (DMARD) used in RA treatment. However, the continued use of DMARDs can cause adverse effects and result in limited therapeutic efficacy. Cartilage extracellular matrix (CECM) has anti-inflammatory and anti-vascular effects and promotes stem cell migration, adhesion, and differentiation into cartilage cells. @*METHODS@#CECM was assessed the dsDNA, glycosaminoglycan, collagen contents and FT-IR spectrum of CECM.Furthermore, we determined the effects of CECM and MTX on cytocompatibility in the SW 982 cells and RAW 264.7 cells. The anti-inflammatory effects of CECM and MTX were assessed using macrophage cells. Finally, we examined the in vivo effects of CECM in combination with MTX on anti-inflammation control and cartilage degradation in collageninduced arthritis model. Anti-inflammation control and cartilage degradation were assessed by measuring the serum levels of RA-related cytokines and histology. @*RESULTS@#CECM in combination with MTX had no effect on SW 982, effectively suppressing only RAW 264.7 activity.Moreover, anti-inflammatory effects were enhanced when low-dose MTX was combined with CECM. In a collageninduced arthritis model, low-dose MTX combined with CECM remarkably reduced RA-related and pro-inflammatory cytokine levels in the blood. Additionally, low-dose MTX combined with CECM exerted the best cartilage-preservation effects compared to those observed in the other therapy groups. @*CONCLUSION@#Using CECM as an adjuvant in RA treatment can augment the therapeutic effects of MTX, reduce existing drug adverse effects, and promote joint tissue regeneration.

Optimization of Vinyl Sulfone Derivatives as Potent Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators for Parkinson's Disease Therapy.

We previously developed a novel series of vinyl sulfones as nuclear factor erythroid 2-related factor 2 (Nrf2) activators with therapeutic potential for Parkinson's disease (PD). However, the previously developed lead compound (1) exhibited undesirable druglike properties. Here, we optimized vinyl sulfones by introducing nitrogen heterocycles to improve druglike properties. Among the synthesized compounds, 17e was the most promising drug candidate with good druglike properties. Compound 17e showed superior effects on Nrf2 activation in cell-based assays compared to compound 1 (17e: half-maximal effective concentration (EC50) = 346 nM; 1: EC50 = 530 nM). Compound 17e was further confirmed to induce expression of Nrf2-dependent antioxidant enzymes at both mRNA and protein levels. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD, 17e significantly attenuated loss of tyrosine hydroxylase-immunopositive dopaminergic neurons, suppressed microglial activation, and alleviated PD-associated motor dysfunction. Thus, 17e is a novel Nrf2 activator with excellent druglike properties and represents a potential therapeutic candidate for PD.

Modification of HEART Pathway for Patients With Chest Pain: A Korean Perspective

Background and Objectives@#The History, Electrocardiography, Age, Risk factors, and Troponin (HEART) pathway was developed to identify patients at low risk of a major adverse cardiac event (MACE) among patients presenting with chest pain to the emergency department. @*Methods@#We modified the HEART pathway by replacing the Korean cut-off of 25 kg/m2 with the conventional threshold of 30 kg/m2 in the definition of obesity among risk factors. The primary outcome was a MACE within 30 days, which included acute myocardial infarction, primary coronary intervention, coronary artery bypass grafting, and all-cause death. @*Results@#Of the 1,304 patients prospectively enrolled, MACE occurred in 320 (24.5%). The modified HEART pathway identified 37.3% of patients as low-risk compared with 38.3% using the HEART pathway. Of the 500 patients classified as low-risk with HEART pathway, 8 (1.6%) experienced MACE, and of the 486 low-risk patients with modified HEART pathway, 4 (0.8%) experienced MACE. The modified HEART pathway had a sensitivity of 98.8%, a negative predictive value (NPV) of 99.2%, a specificity of 49.0%, and a positive predictive value (PPV) of 38.6%, compared with the original HEART pathway, with a sensitivity of 97.5%, a NPV of 98.4%, a specificity of 50.0%, and a PPV of 38.8%. @*Conclusions@#When applied to Korean population, modified HEART pathway could identify patients safe for early discharge more accurately by using body mass index cut-off levels suggested for Koreans.

Enantioselective Synthesis of a Novel Thiazoline Core as a Potent Peroxisome Proliferator-Activated Receptor δ Agonist.

The convergent and enantioselective synthesis of a highly potent human peroxisome proliferator-activated receptor delta agonist is presented. More specifically, the thiazoline structure, which constitutes the biosynthetically distinctive core structure of pulicatin (a secondary metabolite of symbiotic bacteria), was synthesized from a commercially available and inexpensive chiral pool of l-threonine.

Depth and combined infection is important predictor of lower extremity amputations in hospitalized diabetic foot ulcer patients.

BACKGROUND/AIMS: As the prevalence of diabetes mellitus and its complications increase rapidly, diabetic foot ulcers (DFUs), which are a major diabetic complication, are expected to increase. For prevention and effective treatment, it is important to understand the clinical course of DFUs. The aim of this study was to investigate the natural course and predictors of amputation in patients with DFUs who required hospitalization. METHODS: A total of 209 patients with type 2 diabetes, aged 30 to 85 years, who visited emergency department or needed hospitalization due to DFUs were consecutively enrolled from May 2012 to January 2016, by retrospective medical record review. The main outcome was lower extremity amputation (LEA). RESULTS: Among 192 patients who completed follow-up, 113 patients (58.9%) required LEAs. Compared to patients without amputation, baseline levels of white blood cell counts and C-reactive protein were higher in patients with amputation. In addition, bone and joint involvement was more frequently observed in patients with amputation. Multivariable regression analysis revealed that combined infection (odds ratio [OR], 11.39; 95% confidence interval [CI], 2.55 to 50.93; p = 0.001) and bone or joint involvement (OR, 3.74; 95% CI, 1.10 to 12.70; p = 0.035) were significantly associated with an increased risk of LEA. CONCLUSION: The depth of the wound and combined infection of DFU, rather than the extent of the wound, were significant prognostic factors of LEAs in patients with type 2 diabetes.

Association between initial fibrinogen levels and adverse outcomes in emergency department patients with primary postpartum hemorrhage

Objective@#This study evaluates the association between the initial fibrinogen levels and adverse outcomes in emergency department (ED) patients with primary postpartum hemorrhage (PPH). @*Methods@#This retrospective observational study was performed between January 2004 and December 2021 in the ED of a university-affiliated tertiary referral center. Primary PPH patients with fibrinogen level assessments in the ED were included. Patients were classified into two groups: the adverse outcome group-defined as patients receiving massive transfusion (transfusion of ≥10 units of packed red blood cells within the initial 24 hours), uterine artery embolization or emergency hysterectomy, intensive care unit admission, and in-hospital mortality-and the non-adverse outcome group. @*Results@#Of the 481 patients included in the study, 276 (57.4%) had adverse outcomes. The median fibrinogen level in patients with adverse outcomes was lower than in patients without adverse outcomes-149.5 mg/dL (range, 66.8-228.8) vs. 288.0 mg/dL (range, 215.0-349.0), respectively; P<0.001. The area under the receiver operating characteristic curve of the initial fibrinogen level for adverse outcomes was 0.811 (95% confidence interval, 0.773-0.849; P<0.001). The occurrence of adverse outcomes increased with decreasing fibrinogen levels (P<0.001). When the cutoff value of the initial fibrinogen level was 400 mg/dL, the sensitivity and negative predictive values for predicting adverse outcomes were 98.6% and 84.6%, respectively. When the cutoff value of the initial fibrinogen level was 100 mg/dL, the specificity and positive predictive values were 96.6% and 92.8%, respectively. @*Conclusion@#The initial fibrinogen levels on ED admission are associated with adverse outcomes.

Analysis of risk factors between influenza and the occurrence of complicated influenza

Objective@#Influenza is an acute, respiratory viral disease, and may lead to complications such as pneumonia, which presents with significant morbidity and mortality. Previous studies did not have sufficient data regarding the risk factors and complications of the H1N1 flu caused by the influenza A virus subtype H1N1 during the 2009 pandemic in Korea. Therefore, this study was conducted to analyze the characteristics and risk factors of complicated influenza. @*Methods@#Data were collected from influenza patients who visited a local emergency center in Daegu from January 2017 to December 2019. The study population was divided into three groups: influenza, influenza pneumonia, and influenza with a bacterial infection. The patients’ sex, age, influenza type, comorbidities, vital signs, symptoms, laboratory findings, and clinical outcomes were investigated for the risk analysis of complicated influenza. @*Results@#The total number of patients was 574, of which 393 (68.5%) had influenza only, 135 (23.5%) had influenza pneumonia, and 46 (8%) had influenza with a bacterial infection. The odds ratio of complicated influenza was found using multivariate logistic regression analysis; for influenza pneumonia, it was 2.94 for patients aged over 65-years, 3.47 for those with an elevated procalcitonin level, 2.24 for cough, 6.41 for dyspnea, and 3.11 for renal disease. For influenza with bacterial infection, the odds ratio was 2.31 for males, 2.68 for over 80-year-olds, 3.75 for elevated procalcitonin levels, 7.61 for dyspnea, and 3.65 for nursing home residents. @*Conclusion@#The risk factors of complicated influenza were advanced age, elevated procalcitonin level, dyspnea, renal disease, and residing in a nursing home.

Association between Elevated Plasma Homocysteine and Low Skeletal Muscle Mass in Asymptomatic Adults

Background@#Homocysteine has been drawing attention with a closed linkage with skeletal muscle. However, the association of hyperhomocysteinemia with decreased skeletal muscle mass remains unclear. We aimed to investigate the association of hyperhomocysteinemia with low skeletal muscle mass (LMM) in asymptomatic adults. @*Methods@#This was a cross-sectional study of 114,583 community-dwelling adults without cancer, stroke, or cardiovascular diseases who underwent measurements of plasma homocysteine and body composition analysis from 2012 to 2018. Hyperhomocysteinemia was defined as >15 μmol/L. Skeletal muscle mass index (SMI) was calculated based on appendicular muscle mass (kg)/height (m)2. Participants were classified into three groups based on SMI: “normal,” “mildly low,” and “severely low.” @*Results@#The prevalence of hyperhomocysteinemia was the highest in subjects with severely LMM (12.9%), followed by those with mildly LMM (9.8%), and those with normal muscle mass (8.5%) (P for trend <0.001). In a multivariable logistic regression model, hyperhomocysteinemia was significantly associated with having a mildly LMM (odds ratio [OR], 1.305; 95% confidence interval [CI], 1.224 to 1.392) and severely LMM (OR, 1.958; 95% CI, 1.667 to 2.286), respectively. One unit increment of log-transformed homocysteine was associated with 1.360 and 2.169 times higher risk of having mildly LMM and severely LMM, respectively. @*Conclusion@#We demonstrated that elevated homocysteine has an independent association with LMM in asymptomatic adults, supporting that hyperhomocysteinemia itself can be a risk for decline in skeletal musculature.

Effects of emergency doctor’s hospitalization authority from internal medicine and utilizing emergency ward on length of stay in emergency department

Objective@#The emergency department (ED) length of stay (LOS) is related to ED overcrowding and emergency practice. This study aimed to investigate the effects of enabling an ED doctor to have the authority to make hospitalization decisions and utilization of the emergency ward on ED LOS. @*Methods@#This retrospective observational study included patients who were admitted through a local emergency medical center. We compared the ED LOS between the periods' March to July 2018 and March to July 2019. In the latter period, ED doctors were authorized to take decisions on patient hospitalizations from the internal medicine department, and the emergency ward was operated under these new conditions. @*Results@#A total of 6,291 patients were included in the study, with 2,934 in 2018 and 3,357 in 2019. In the comparison of ED LOS for internal medicine inpatients by year, there was a significant reduction in the total ED LOS (1,129.0 [491.0-1,618.0] minutes vs. 539.0 [344.0-1,016.25] minutes, P<0.001), LOS before the admission decision (345.0 [198.0-634.0] minutes vs. 280.0 [176.0-442.3] minutes, P<0.001), and LOS after the admission decision (415.0 [147.0-1,089.0] minutes vs. 179.5 [80.0-422.0] minutes, P<0.001). In a subgroup analysis of internal medicine inpatients in 2019, the admission sheets of an ED doctor showed a significant decrease in LOS before the admission decision (268.0 [170.5-424.5] minutes vs. 404.0 [252.0-570.5] minutes, P<0.001). Also, the utilization of the emergency ward showed a significant decrease in LOS after the admission decision (147.0 [75.0-283.0] minutes vs. 187.0 [81.0-460.0] minutes, P<0.001). @*Conclusion@#The delegation of hospitalization decisions to the ED doctor and the subsequent utilization of the emergency ward shorten the ED LOS of internal medicine inpatients.

Lifestyle Modification in the Management of Metabolic Syndrome:Statement From Korean Society of CardioMetabolic Syndrome (KSCMS)

With the recent rapid increase in obesity worldwide, metabolic syndrome (MetS) has gained significant importance. MetS is a cluster of obesity-related cardiovascular risk factors including abdominal obesity, atherogenic dyslipidemia, high blood pressure and impaired glucose tolerance. MetS is highly prevalent and strongly associated with an increased risk of developing diabetes and cardiovascular disease, putting a great burden on human society. Therefore, it is very important to reduce MetS risk, which can improve patients’cardiovascular prognosis. The primary and most effective strategy to control each component of MetS is lifestyle change such as losing body weight, keeping regular exercise, adopting a healthy diet, quitting smoking and alcohol drinking in moderation. Many studies have shown that lifestyle modification has improved all components of MetS, and reduces the incidence of diabetes and cardiovascular disease. Here, the Korean Society of CardioMetabolic Syndrome has summarized specific and practical methods of lifestyle modification in the management of MetS in the healthcare field.

Spontaneous Hepatic Infarction in a Patient with Gallbladder Cancer.

Hepatic infarction is known as a rare disease entity in nontransplant patients. Although a few cases of hepatic infarction have been reported to be linked with invasive procedures, trauma, and hypercoagulability, a case of spontaneous hepatic infarction in a nontransplanted patient has hardly ever been reported. However, many clinical situations of patients with cancer, in particular biliary cancer, can predispose nontransplant patients to hepatic infarction. Besides, the clinical outcome of hepatic infarction in patients with cancer can be worse than in patients with other etiologies. As for treatment, anticoagulation treatment is usually recommended. However, because of its multifactorial etiology and combined complications, treatment of hepatic infarction is difficult and not simple. Herein, we report a case of fatal hepatic infarction that occurred spontaneously during the course of treatment in a patient with gallbladder cancer. Hepatic infarction should be considered as a possible fatal complication in patients during treatment of biliary malignancies.

Clinical Factors Affecting Recovery Periods of Vascular and Idiopathic Acquired Paralytic Strabismus

Purpose@#Clinical factors affecting the recovery period in patients with vascular or idiopathic paralytic strabismus were evaluated. @*Methods@#This study involved a retrospective review of medical records of patients diagnosed with vascular and idiopathic acquired paralytic strabismus. Vascular paralysis was defined in cases of hypertension, diabetes mellitus, or cardiovascular disease. The angle of deviation and limitation of extraocular movement were evaluated at each visit. Recovery was defined as the absence of diplopia and complete resolution of limitation of extraocular movement. Factors affecting recovery success and recovery period were analyzed. @*Results@#We retrospectively reviewed data of 145 patients consisting of 87 with vascular paralytic strabismus (cranial nerve [CN] III: 21, CN IV: 28, CN VI: 38) and 58 with idiopathic paralytic strabismus (CN IV: 20, CN VI: 24, CN III: 14). The recovery rate did not significantly differ between vascular (60.9%) and idiopathic (63.8%) groups (p = 0.15). The recovery period was longer in the vascular group (130.1 ± 145.1 days) than in the idiopathic group (92.6 ± 76.6) (p = 0.02). Age at onset was significantly associated with the recovery period in both vascular and idiopathic groups. In the vascular group, the recovery periods were 107.4 ± 74.8 days in CN III palsy, 97.2 ± 51.9 days in CN IV palsy, and 159.3 ± 194.1 days in CN VI palsy. The recovery period was significantly longer in patients with CN VI palsy (p = 0.03). Hypertension was significantly influencing the recovery period in patients with vascular CN VI palsy (odds ratio = 2.54, p = 0.01). @*Conclusions@#The recovery period was longer in patients with vascular paralytic strabismus than in patients with idiopathic paralytic strabismus. Recovery rates were not significantly different between groups. In patients with vascular CN VI palsy, a history of hypertension was significantly associated with the recovery period.

Clinical Factors Affecting Recovery Periods of Vascular and Idiopathic Acquired Paralytic Strabismus

Purpose@#Clinical factors affecting the recovery period in patients with vascular or idiopathic paralytic strabismus were evaluated. @*Methods@#This study involved a retrospective review of medical records of patients diagnosed with vascular and idiopathic acquired paralytic strabismus. Vascular paralysis was defined in cases of hypertension, diabetes mellitus, or cardiovascular disease. The angle of deviation and limitation of extraocular movement were evaluated at each visit. Recovery was defined as the absence of diplopia and complete resolution of limitation of extraocular movement. Factors affecting recovery success and recovery period were analyzed. @*Results@#We retrospectively reviewed data of 145 patients consisting of 87 with vascular paralytic strabismus (cranial nerve [CN] III: 21, CN IV: 28, CN VI: 38) and 58 with idiopathic paralytic strabismus (CN IV: 20, CN VI: 24, CN III: 14). The recovery rate did not significantly differ between vascular (60.9%) and idiopathic (63.8%) groups (p = 0.15). The recovery period was longer in the vascular group (130.1 ± 145.1 days) than in the idiopathic group (92.6 ± 76.6) (p = 0.02). Age at onset was significantly associated with the recovery period in both vascular and idiopathic groups. In the vascular group, the recovery periods were 107.4 ± 74.8 days in CN III palsy, 97.2 ± 51.9 days in CN IV palsy, and 159.3 ± 194.1 days in CN VI palsy. The recovery period was significantly longer in patients with CN VI palsy (p = 0.03). Hypertension was significantly influencing the recovery period in patients with vascular CN VI palsy (odds ratio = 2.54, p = 0.01). @*Conclusions@#The recovery period was longer in patients with vascular paralytic strabismus than in patients with idiopathic paralytic strabismus. Recovery rates were not significantly different between groups. In patients with vascular CN VI palsy, a history of hypertension was significantly associated with the recovery period.