The progression of the vertebral body bruise associated with a spinal fracture.

BACKGROUND: Advances in magnetic resonance imaging (MRI) have made it possible to find the vertebral body bruise (VBB), which was not found in computed tomography (CT) after trauma. There has been only one study with adult patients about whether traumatic VBB will cause a collapse of the vertebral body or not. The purpose is to elucidate the progression of VBB in non-osteoporotic adult patients and to identify the possible factors influencing the progression. METHOD: The VBB was defined on MRI as band-like or diffuse zones of high signal intensity on T2-weighted sequences without fracture of the cortex based on CT. The study population with traumatic VBB associated with non-osteoporotic spinal fracture was composed of 15 females and 21 males. The minimal follow-up period was 6 months. The ratio of anterior to posterior heights of the VBB, the ratio of anterior heights of the VBB to the average of those of cranial and caudal adjacent vertebral bodies, the anterior wedge angle of the VBB, and the focal angle around the VBB were compared between the initial and final visits. We evaluated the age of the patients, the C2 plumb line distance, the regional location of VBB, the etiology of VBB, and the treatment methods of the fractures as possible risk factors influencing the progression. RESULTS: There was no difference in the ratios and angles between the initial and final visits. The differences in the ratios and angles between the initial and final visits were not dependent on the possible risk factors. The anterior superior area is the most common in the distribution of VBB. CONCLUSIONS: Unlike compression fractures, the vertebral body with traumatic VBB found in adult patients with non-osteoporotic spinal fractures of AO classification A or B types did not develop collapse. In clinical practice, it is reasonable to diagnose it as a spinal fracture rather than a VBB if the collapse of a possible VBB occurs.

Three-Dimensional Perovskite Nanopixels for Ultrahigh-Resolution Color Displays and Multilevel Anticounterfeiting.

Hybrid perovskites are emerging as a promising, high-performance luminescent material; however, the technological challenges associated with generating high-resolution, free-form perovskite structures remain unresolved, limiting innovation in optoelectronic devices. Here, we report nanoscale three-dimensional (3D) printing of colored perovskite pixels with programmed dimensions, placements, and emission characteristics. Notably, a meniscus comprising femtoliters of ink is used to guide a highly confined, out-of-plane crystallization process, which generates 3D red, green, and blue (RGB) perovskite nanopixels with ultrahigh integration density. We show that the 3D form of these nanopixels enhances their emission brightness without sacrificing their lateral resolution, thereby enabling the fabrication of high-resolution displays with improved brightness. Furthermore, 3D pixels can store and encode additional information into their vertical heights, providing multilevel security against counterfeiting. The proof-of-concept experiments demonstrate the potential of 3D printing to become a platform for the manufacture of smart, high-performance photonic devices without design restrictions.

Chemoradiotherapy after gemcitabine plus erlotinib in patients with locally advanced pancreatic cancer.

PURPOSE: To evaluate the outcomes of chemoradiotherapy (CRT) after neoadjuvant chemotherapy consisting of gemcitabine and erlotinib for unresectable locally advanced pancreatic cancer. METHODS: Between 2010 and 2014, 24 patients with unresectable pancreatic cancer received neoadjuvant gemcitabine/erlotinib followed by CRT. There were 9 men and 15 women, and median age was 61 years (range 48-77). Radiotherapy (RT) was delivered to the tumor and regional lymph nodes with a median dose of 50.4 Gy (range 50.4-56). All patients received concurrent chemotherapy, with 5-fluorouracil (5-FU), capecitabine or gemcitabine and 17 patients received maintenance chemotherapy with gemcitabine plus erlotinib, 5-FU plus leukovorin or capecitabine plus oxaliplatin. The median follow-up period was 17 months (range 7-31). RESULTS: The median overall survival (OS) and post-RT OS (PROS) were 17.8 and 10.7 months, respectively. On multivariate analysis, RT dose (p=0.005) and maintenance chemotherapy (p=0.019) were significant prognostic factors for OS. In addition, RT dose ≥54Gy (p=0.021) and concurrent gemcitabine (p=0.012) were identified as favorable prognostic factors for PROS. Grade 3 hematologic and gastrointestinal toxicities occurred in 3 and 2 patients, respectively. CONCLUSIONS: Intensive treatment with gemcitabine-based CRT, high RT dose, and maintenance chemotherapy may improve survival outcomes in locally advanced pancreatic cancer patients receiving neoadjuvant gemcitabine/erlotinib.

A Prognostic Index to Identify Patients With Intrahepatic Cholangiocarcinoma Who Could Benefit From Gemcitabine Plus Cisplatin.

Biliary tract cancer is a heterogenous group. Gemcitabine plus cisplatin has been the standard chemotherapy for advanced biliary tract cancer, but there is lack of evidence on treatment in patients with intrahepatic cholangiocarcinoma (IHC). We analyzed 29 patients with only IHC who received gemcitabine plus cisplatin between June 2010 and February 2013. The median age was 63 years (range, 40-78 years), and Eastern Cooperative Oncology Group performance status of all patients was <2. The median progression-free survival and median overall survival (OS) were 4.3 and 7.3 months, respectively. Multivariate analysis showed that platelet count (≤180 × 10 per liter), metastatic site of more than 2, and albumin level (≤3.5 g/dL) were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: zero or 1 (good prognostic group), 2 (intermediate group), or 3 (poor prognostic group). The median OS for good (n = 15), intermediate (n = 10), and poor (n = 4) prognostic group was 10.5, 6.1, and 1.6 months, respectively (P < 0.005). Relatively better prognosis of the good prognosis group comparing to other prognosis groups can be expected from the prognostic model established in this study by analyzing patients with IHC treated with gemcitabine.

Quasicrystal-reinforced Mg alloys.

The formation of the icosahedral phase (I-phase) as a secondary solidification phase in Mg-Zn-Y and Mg-Zn-Al base systems provides useful advantages in designing high performance wrought magnesium alloys. The strengthening in two-phase composites (I-phase + α-Mg) can be explained by dispersion hardening due to the presence of I-phase particles and by the strong bonding property at the I-phase/matrix interface. The presence of an additional secondary solidification phase can further enhance formability and mechanical properties. In Mg-Zn-Y alloys, the co-presence of I and Ca2Mg6Zn3 phases by addition of Ca can significantly enhance formability, while in Mg-Zn-Al alloys, the co-presence of the I-phase and Mg2Sn phase leads to the enhancement of mechanical properties. Dynamic and static recrystallization are significantly accelerated by addition of Ca in Mg-Zn-Y alloy, resulting in much smaller grain size and more random texture. The high strength of Mg-Zn-Al-Sn alloys is attributed to the presence of finely distributed Mg2Sn and I-phase particles embedded in the α-Mg matrix.

Electron-rich hybrid matrix to enhance molybdenum oxide-based anode performance for Lithium-Ion batteries.

Although MoO2-based electrodes have been intensively studied as potential candidate anodes for lithium-ion batteries (LIBs) based on their high theoretical capacity (840 mAh g-1 and 5447 mAh cm-3), common issues such as severe volume variation, electrical conductivity loss, and low ionic conductivity, are prevalent. In this study, we demonstrate enhanced Li-ion kinetics and electrical conductivity of MoO2-based anodes with ternary MoO2-Cu-C composite materials. The MoO2-Cu-C was synthesized via two-step high energy ball milling where Mo and CuO are milled, followed by the secondary milling with C. With the introduction of the Cu-C hybrid matrix in MoO2 nanoparticles via the element transfer method using mechanochemical reactions, the sluggish Li-ion diffusion and unstable cycling behavior were significantly improved. The inactive Cu-C matrix contributes to the increase in electrical and ionic conductivity and mechanical stability of active MoO2 during cycling, as characterized by various electrochemical analyses and ex situ analysis techniques. Hence, the MoO2-Cu-C anode delivered promising cycling performance (674 mAh g-1 (at 0.1 A g-1) and 520 mAh g-1 (at 0.5 A g-1), respectively, after 100 cycles) and high-rate property (73% retention at 5 A g-1 as comparison with the specific capacity at 0.1 A g-1). The MoO2-Cu-C electrode is a propitious next-generation anode for LIBs.

Impact of Early Corticosteroids on Preventing Clinical Deterioration in Non-critically Ill Patients Hospitalized with COVID-19: A Multi-hospital Cohort Study.

INTRODUCTION: While guidelines stronglyrecommend dexamethasone in critical COVID-19, the optimal threshold to initiate corticosteroids in non-critically ill patients with COVID-19 remains unclear. Using data from a state-wide COVID-19 registry, we evaluated the effectiveness of early corticosteroids for preventing clinical deterioration among non-critically ill patients hospitalized for COVID-19 and receiving non-invasive oxygen therapy. METHODS: This was a target trial using observational data from patients hospitalized for COVID-19 at 39 hospitals participating in the MI-COVID19 registry between March 16, 2020 and August 24, 2020. We studied the impact of corticosteroids initiated within 2 calendar days of hospitalization ("early steroids") versus no early steroids among non-ICU patients with laboratory-confirmed SARS-CoV2 receiving non-invasive supplemental oxygen therapy. Our primary outcome was a composite of in-hospital mortality, transfer to intensive care, and receipt of invasive mechanical ventilation. We used inverse probability of treatment weighting (IPTW) and propensity score-weighted regression to measure the association of early steroids and outcomes. RESULTS: Among 1002 patients meeting study criteria, 231 (23.1%) received early steroids. After IPTW, to balance potential confounders between the treatment groups, early steroids were not associated with a decrease in the composite outcome (aOR 1.1, 95%CI 0.8-1.6) or in any components of the primary outcome. CONCLUSION: We found no evidence that early corticosteroid therapy prevents clinical deterioration among hospitalized non-critically ill COVID-19 patients receiving non-invasive oxygen therapy. Further studies are needed to determine the optimal threshold for initiating corticosteroids in this population.

Body CT and PET/CT detection of extracranial lymphoma in patients with newly diagnosed central nervous system lymphoma.

BACKGROUND: We aimed to investigate the detection rate of body CT or PET/CT for sites of extracranial disease in patients with a new pathological diagnosis of CNS DLBCL and to identify factors associated with sites of extracranial disease. METHODS: An international multicenter cohort study of consecutive immunocompetent patients with a new diagnosis of CNS DLBCL confirmed by brain biopsy who underwent CT and/or PET/CT to evaluate for sites of extracranial disease between 1998 and 2019. The primary outcome was the detection rate of extracranial lymphoma by CT or PET/CT. Subgroup analyses according to age and EBV status were also performed. Logistic regression analyses were performed to determine factors related to sites of extracranial disease. Detection rates of CT and PET/CT were compared. RESULTS: One thousand and forty-three patients were included. The overall detection rate of CT or PET/CT was 2.6% (27/1043). The treatment approach was adjusted in 74% of these patients. Multivariable analysis demonstrated that age >61 years (OR, 3.10; P = .016) and EBV positivity (OR, 3.78; P = .045) were associated with greater odds of extracranial lymphoma. There was no statistically significant difference in detection rate between CT and PET/CT (P = .802). In patients ≤61 years old, the false-referral rates were significantly higher than the detection rates (P < .001). CONCLUSION: Our results showed increased odds of extracranial lymphoma in patients with older age or EBV-positive lymphoma. Treatment was adjusted in a majority of patients diagnosed with extracranial lymphoma, thereby supporting the current guidelines for the use of contrast-enhanced body CT or PET/CT in patients with newly diagnosed CNS DLBCL.

A combination of second trimester oral metronidazole and no sexual intercourse during second and third trimester may reduce late miscarriage and premature delivery after fertility sparing radical trachelectomy.

OBJECTIVES: Women with a previous trachelectomy have an increased risk of premature delivery and second trimester miscarriage. In this study we aim to evaluate factors and regimes possibly affecting the risk for prematurity following fertility sparing robotic radical trachelectomy (RRT) in cervical cancer. METHODS: A retrospective study of the reproductive outcome following RRT with a cervical cerclage performed at one of four academic centers between 2007 and 2019. Factors possibly related to premature delivery, such as postoperative non-pregnant cervical length, previous vaginal deliveries, preservation of the uterine arteries, and the use of a second trimester oral metronidazole/no sexual intercourse regime, were assessed. RESULTS: 109 women remained for analyses after excluding recurrences before pregnancy (n = 8), secondary hysterectomy (n = 2), and women with less than six months follow up (n = 10). 74 pregnancies occurred in 52/71 women attempting to conceive, 56 of which developed past the first trimester. Two of 22 women (9%) who were prescribed an oral metronidazole regime (400 mg × 2 from gestational week 15 + 0 to 21 + 6 and abstaining from sexual intercourse for the duration of the pregnancy) had a premature delivery, compared with 13/31 (42%) where the regime was not applied (p = 0.009). The association remained after regression analyses including possible contributing factors as of above, none of which associated with prematurity at regression analyses (p = 0.001). CONCLUSIONS: The observed four-fold reduction in premature delivery indicates that an oral metronidazole/no sexual intercourse regime may reduce second trimester miscarriage and premature deliveries following an RRT. No association was observed for other investigated factors.

Three-Year Follow-up of 2-Dose Versus 3-Dose HPV Vaccine.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) antibody responses to the 9-valent human papillomavirus (9vHPV) vaccine among girls and boys (aged 9-14 years) receiving 2-dose regimens (months 0, 6 or 0, 12) were noninferior to a 3-dose regimen (months 0, 2, 6) in young women (aged 16-26 years) 4 weeks after last vaccination in an international, randomized, open-label trial (NCT01984697). We assessed response durability through month 36. METHODS: Girls received 2 (months 0 and 6 [0, 6]: n = 301; months 0 and 12 [0, 12]: n = 151) or 3 doses (months 0,2, and 6 [0, 2, 6]: n = 301); boys received 2 doses ([0, 6]: n = 301; [0, 12]: n = 150); and young women received 3 doses ([0, 2, 6]: n = 314) of 9vHPV vaccine. Anti-HPV geometric mean titers (GMTs) were assessed by competitive Luminex immunoassay (cLIA) and immunoglobulin G-Luminex immunoassay (IgG-LIA) through month 36. RESULTS: Anti-HPV GMTs were highest 1 month after the last 9vHPV vaccine regimen dose, decreased sharply during the subsequent 12 months, and then decreased more slowly. GMTs 2 to 2.5 years after the last regimen dose in girls and boys given 2 doses were generally similar to or greater than GMTs in young women given 3 doses. Across HPV types, most boys and girls who received 2 doses (cLIA: 81%-100%; IgG-LIA: 91%-100%) and young women who received 3 doses (cLIA: 78%-98%; IgG-LIA: 91%-100%) remained seropositive 2 to 2.5 years after the last regimen dose. CONCLUSIONS: Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose.

Quantitative live cell imaging reveals influenza virus manipulation of Rab11A transport through reduced dynein association.

Assembly of infectious influenza A viruses (IAV) is a complex process involving transport from the nucleus to the plasma membrane. Rab11A-containing recycling endosomes have been identified as a platform for intracellular transport of viral RNA (vRNA). Here, using high spatiotemporal resolution light-sheet microscopy (~1.4 volumes/second, 330 nm isotropic resolution), we quantify Rab11A and vRNA movement in live cells during IAV infection and report that IAV infection decreases speed and increases arrest of Rab11A. Unexpectedly, infection with respiratory syncytial virus alters Rab11A motion in a manner opposite to IAV, suggesting that Rab11A is a common host component that is differentially manipulated by respiratory RNA viruses. Using two-color imaging we demonstrate co-transport of Rab11A and IAV vRNA in infected cells and provide direct evidence that vRNA-associated Rab11A have altered transport. The mechanism of altered Rab11A movement is likely related to a decrease in dynein motors bound to Rab11A vesicles during IAV infection.

Risk Factors for Pressure Ulcer by Electrodes in Long-term Electroencephalography Monitoring

Background@#Although electroencephalography is known as non-invasive, long-term electroencephalography monitoring has a significant risk of pressure ulcers caused by electrodes. We investigated the incidence and risk factors of pressure ulcers in long-term electroencephalography monitoring for more than 24 hours. @*Methods@#All patients who underwent long-term electroencephalography monitoring for more than 24 hours from January 2020 to December 2021 were reviewed. Their medical records were reviewed to evaluate the risk factors for pressure ulcers by electroencephalography electrodes. All patients were divided into the presence (lesion positive) and absence (lesion negative) of pressure ulcers confirmed by a clinician. @*Results@#A total of 541 patients were analyzed in this study. Their mean age was 56.0±21.5, and the average duration of the long-term electroencephalography monitoring was 118.0±68.6 hours. Pressure ulcers were identified in 49 patients (9.1%). The odds ratios of age and recording time were 1.032 (95% confidence interval [CI], 1.008-1.056, p=0.009) and 1.022 (95% CI, 1.015-1.029, p<0.001), respectively. The odds ratio of pressure ulcer was 2.702 (95% CI, 1.461-4.999, p=0.002) in patients with comatose mentality (1 point for eye response of Glasgow coma scale). @*Conclusions@#The pressure ulcers caused by electrodes in long-term electroencephalography monitoring can be preventable with due diligence in clinical settings. Risk factor control to prevent pressure ulcers due to electroencephalography electrodes is needed.

Feasibility of Computerized Visuomotor Integration System for Visual Field Defects and Spatial Neglect in Poststroke Patients

Objective@#To develop a computerized visuomotor integration system for assessment and training of visual perception impairments and evaluate its safety and feasibility in patients with a stroke. Visual field defects and spatial neglect lead to substantial poststroke impairment. Most diagnostic assessments are anchored in traditional methods, and clinical effects of rehabilitation treatments are limited. @*Methods@#The CoTras Vision system included two evaluations and four training modules. The evaluation modules were based on the Albert’s test and Star cancellation test, and training modules were based on visual tracking, central-peripheral integration, and visuomotor perception techniques. Bland–Altman plots for agreement with the traditional paper-and-pencil test were performed, and the modified Intrinsic Motivation Inventory, Patient Satisfaction Questionnaire, and Simulator Sickness Questionnaire were conducted. @*Results@#Ten patients with acute stroke completed the study. Bland–Altman plots revealed good agreements for Albert’s test (mean difference, -0.3±4.5) and Star cancellation test (mean difference, 0.3±0.7). The mean±standard deviation scores of the modified Intrinsic Motivation Inventory, Patient Satisfaction Survey, and Simulator Sickness Questionnaire were 84.7±30.6, 40.5±7.9, and 34.0±34.5 respectively. @*Conclusion@#The CoTras Vision system is feasible and safe in patients with stroke. Most patients had a high degree of motivation to use the system and did not experience severe adverse events. Further studies are needed to confirm its usefulness in stroke patients with visual field defects and hemineglect symptoms. Furthermore, a large, well-designed, randomized controlled trial will be needed to confirm the treatment effect of the CoTras Vision system.

Oncostatin M, a muscle-secreted myokine, recovers high-glucose-induced impairment of Akt phosphorylation by Fos induction in hippocampal neuron cells.

Oncostatin M is a muscle-secreted myokine that has various effects on neuronal function, however, the underlying molecular mechanism has been poorly defined. In this study, we showed that Oncostatin M increased the phosphorylation of Akt and ERK, proteins crucial for neuron cell survival and proliferation. Furthermore, Oncostatin M increased the expression of c-Fos, a protein with significant involvement in neuronal cell proliferation and survival, through both Akt and ERK. Oncostatin M also increased intracellular calcium concentrations that act upstream of Akt and ERK. Treatment with Oncostatin M led to the recovery of high-glucose-induced impairment of Akt phosphorylation. Thus, Oncostatin M can protect neuronal cell damage related to high-glucose conditions, showing potential as a therapeutic agent.

Ischemic and Inflammatory Ocular Adverse Events Following Different Types of Vaccination for COVID-19 and Their Incidence Analysis

Purpose@#To evaluate the ocular adverse event (OAE) and the incidence rate that can occur after the COVID-19 vaccination. @*Methods@#Patients who visited with an ophthalmologic diagnosis within a month of COVID-19 vaccination were retrospectively analyzed. OAEs were categorized as ischemia and inflammation by their presumed pathogenesis and were compared by types of vaccine: messenger RNA (mRNA) and viral vector vaccine. The crude incidence rate was calculated using data from the Korea Disease Control and Prevention Agency. @*Results@#Twenty-four patients with OAEs after COVID-19 vaccination were reviewed: 10 patients after mRNA and 14 after viral vector vaccine. Retinal vein occlusion (nine patients) and paralytic strabismus (four patients) were the leading diagnoses. Ischemic OAE was likely to occur after viral vector vaccines, while inflammatory OAE was closely related to mRNA vaccine (p = 0.017). The overall incidence rate of OAE was 5.8 cases per million doses: 11.5 per million doses in viral vector vaccine and 3.4 per million doses in mRNA vaccine. @*Conclusions@#OAEs can be observed shortly after the COVID-19 vaccination, and their category was different based on the types of vaccine. The information and incidence of OAE based on the type of vaccine can help monitor patients who were administered the COVID-19 vaccine.

Effectiveness and Tolerability of Combination Pharmacotherapy With Stimulant and Non-Stimulant in Children With Attention Deficit Hyperactivity Disorder

Objectives@#This study aimed to investigate the effectiveness and safety of combining psychostimulants and nonstimulants for patients under treatment for attention deficit hyperactivity disorder (ADHD). @*Methods@#The study included 96 patients aged 6–12 years who were diagnosed with ADHD, among whom 34 received combination pharmacotherapy, 32 received methylphenidate monotherapy, and 30 received atomoxetine monotherapy. Statistical analysis was conducted to compare treatment and adverse effects among groups and to analyze changes before and after combination pharmacotherapy.The difference between combination pharmacotherapy and monotherapy was investigated. Logistic regression analysis was used to identify the predictors of combination pharmacotherapy. @*Results@#No significant differences were observed between the groups in terms of age or pretreatment scores. The most common adverse effect experienced by 32% of patients in the combination pharmacotherapy group was decreased appetite. Clinical global impression-severity score decreased significantly after combination pharmacotherapy. All three groups showed significant clinical global impression-severity score improvements over time, with no significant differences among them. The predictive factors for combination pharmacotherapy included the Child Behavior Checklist total score internalizing subscale. @*Conclusion@#Combination pharmacotherapy with methylphenidate and atomoxetine is a relatively effective and safe option for patients with ADHD who do not respond to monotherapy.

Biomechanical Investigation to Establish Stable Fixation Strategies for Distal Tibial Fractures in Various Situations:Finite Element Analysis Studies

Purpose@#This study examined the structural and mechanical stability as well as the clinical significance of various fixation constructs for distal tibial fractures using finite element analysis. @*Materials and Methods@#Fracture models with 20 mm and 120 mm defects were produced, and implants of an intramedullary nail and anatomical plate model were applied. An axial load of 800 N with 60% distribution in the medial compartment and 40% in the lateral compartment was applied and analyzed using Ansys ® software. @*Results@#In the intramedullary nail model, the maximum von Mises stress occurred at the primary lag screw hole and adjacent medial cortex, while in the plate model, it occurred at the locking holes around the fracture. The maximum shear stress on the bone and metal implant in the fracture model with a 20 mm defect was highest in the plate assembly model, and in the fracture model with a 120 mm defect, it was highest in the two-lag screw assembly model. @*Conclusion@#Based on an analysis of the maximum shear stress distribution, securing the fixation strength of the primary lag screw hole is crucial, and the assembly model of the intramedullary nail with two lag screws and a blocking screw applied was the model that best withstood the optimal load. Securing the locking hole directly above the fracture is believed to provide the maximum fixation strength because the maximum pressure in the plate model is concentrated in the proximal locking hole and the surrounding cortex.

Brain Derived Neurotrophic Factor Methylation and Long-term Outcomes after Stroke Interacting with Suicidal Ideation

Objective@#This study aimed to evaluate the unexplored relationship between BDNF methylation, long-term outcomes, and its interaction with suicidal ideation (SI), which is closely associated with both BDNF expression and stroke outcomes. @*Methods@#A total of 278 stroke patients were assessed for BDNF methylation status and SI using suicide-related item in the Montgomery–Åsberg Depression Rating Scale at 2 weeks post-stroke. We investigated the incidence of composite cerebro-cardiovascular events (CCVEs) during an 8−14-year period after the initial stroke as long-term stroke outcome.We conducted Cox regression models adjusted for covariates to evaluate the association between BDNF methylation status and CCVEs, as well as its interaction with post-stroke SI at 2 weeks. @*Results@#Higher methylation status of CpG 1, 3, and 5, but not the average value, predicted a greater number of composite CCVEs during 8−14 years following the stroke. The associations between a higher methylation status of CpGs 1, 3, 5, and 8, as well as the average BDNF methylation value, and a greater number of composite CCVEs, were prominent in patients who had post-stroke SI at 2 weeks. Notably, a significant interaction between methylation status and SI on composite CCVEs was observed only for CpG 8. @*Conclusion@#The significant association between BDNF methylation and poor long-term stroke outcomes, particularly amplified in individuals who had post-stroke SI at 2 weeks, suggested that evaluating the biological marker status of BDNF methylation along with assessing SI during the acute phase of stroke can help predict long-term outcomes.

Clinical Significance of Venous Thromboembolism in Patients with Advanced Cholangiocarcinoma

Background/Aims@#Patients with active cancer frequently develop venous thromboembolism (VTE). However, there is little data about VTE in patients with advanced cholangiocarcinoma (CCA). Therefore, we investigated the clinical significance of VTE in patients with advanced CCA. @*Methods@#We analyzed the data of a total of 332 unresectable CCA patients diagnosed between 2010 and 2020 in this retrospective study. We investigated the incidence and risk factors for VTE, and its effect on survival in patients with advanced CCA. @*Results@#During a median follow-up of 11.6 months, 118 patients (35.5%) developed VTE. The cumulative incidence of VTE was 22.4% (95% confidence interval [CI], 0.18 to 0.27) at 3 months and 32.8% (95% CI, 0.27 to 0.38) at 12 months. Major vessel invasion was an independent risk factor for VTE (hazard ratio, 2.88; 95% CI, 1.92 to 4.31; p<0.001). Patients who developed VTE during follow-up had shorter overall survival than patients who did not (11.50 months vs 15.83 months, p=0.005). In multivariable analysis, VTE (hazard ratio, 1.58; 95% CI, 1.23 to 2.02;p<0.001) was associated with poor overall survival. @*Conclusions@#Major vessel invasion is related to the occurrence of VTE in advanced CCA. The development of VTE significantly decreases the overall survival and is an important unfavorable prognostic factor for survival.

Optimal Follow-up of Incidental Pancreatic Cystic Lesions without Worrisome Features: Clinical Outcome after Long-term Follow-up

Background/Aims@#The optimal duration and interval of follow-up for cystic lesions of the pancreas (CLPs) is not well established. This study was performed to investigate the optimal duration and interval of follow-up for CLPs in clinical practice. @*Methods@#Patients with CLPs without worrisome features or high-risk stigmata underwent followup with computed tomography at 6, 12, 18, and 24 months and then every 12 months thereafter. A retrospective analysis of prospectively collected data was performed. @*Results@#A total of 227 patients with CLPs detected from 2000 to 2008 (mean initial diameter, 1.3±0.6 cm) underwent follow-up for a median of 120 months. Twenty-two patients (9.7%) underwent surgery after a median of 47.5 months. Malignancies developed in four patients (1.8%), one within 5 years and three within 10 years. One hundred and fourteen patients (50.2%) were followed up for more than 10 years. No malignancy developed after 10 years of follow-up. During surveillance, 37 patients (16.3%) experienced progression to surgical indication. In patients with CLPs less than 2 cm in diameter, development of surgical indications did not occur within 24 months of follow-up. @*Conclusions@#CLPs should be continuously monitored after 5 years because of the persistent potential for malignant transformation of CLPs. An interval of 24 months for initial follow-up might be enough for CLPs with initial size of less than 2 cm in clinical practice.