Expert consensus on the diagnosis and treatment of end-stage liver disease complicated by infections.

End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections.

Dexmedetomidine Stereotaxic Injection Alleviates Neuronal Loss Following Bilateral Common Carotid Artery Occlusion via Up-Regulation of BDNF Expression.

BACKGROUND/AIM: Neurogenesis is an important process in the recovery from neurological damage caused by ischemic lesions. Endogenous neurogenesis is insufficient to restore neuronal damage following cerebral ischemia. Dexmedetomidine (DEX) exerts neuroprotective effects against cerebral ischemia and ischemia/reperfusion injury. DEX promotes neurogenesis, including neuronal proliferation and maturation in the hippocampus. In a previous study, we showed that early neurogenesis increased 3 days after bilateral common carotid artery occlusion (BCCAO). In this study, we investigated the effect of DEX on neurogenesis 3 days after BCCAO. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats (7-8 weeks old) were used as a BCCAO model. Right and left common carotid arteries of the rats were occluded using 4-0 silk sutures. Two hours after surgery, an intracranial DEX injection was administered to rats that underwent surgery using a stereotaxic injector. Brains were obtained from control and BCCAO rats 3 days after surgery. Immunohistochemistry was performed on the cortex and dentate gyrus of the hippocampus using a NeuN antibody. Western blot was performed with HIF1α and brain-derived neurotrophic factor (BDNF) antibodies. RESULTS: The number of mature neurons decreased 3 days after BCCAO, but DEX treatment alleviated neural loss in the parietal cortex and hippocampus. Up-regulation of BDNF was also observed after dexmedetomidine treatment. CONCLUSION: Stereotaxic injection of dexmedetomidine alleviates neural loss following BCCAO by up-regulating BDNF expression.

Intraoperative sudden arrhythmias in cervical spine surgery adjacent to the stellate ganglion: A case report.

BACKGROUND: Atrial arrhythmias such as paroxysmal supraventricular tachycardia (PSVT) and atrial flutter (AF) are common in the perioperative setting. They commonly resolve spontaneously. However, occasionally, they may continually progress to fatal arrhythmias or cause complications. Therefore, prompt and appropriate management is important. CASE SUMMARY: A 46-year-old female patient diagnosed with cervical C6-7 radiculopathy characterized by decreased sensation in the right third, fourth and fifth fingers underwent C6-7 anterior cervical disc fusion surgery. Electrocardiography showed PSVT and ventricular tachycardia during C6-7 disc retraction. However, the patient remained stable. Initial treatment with esmolol and lidocaine for ventricular tachycardia was ineffective. Carotid massage and Valsalva maneuver were attempted but PSVT did not resolve. The surgery was paused, and the patient's fraction of inspired oxygen was set to 100%. Adenosine was administered for pharmacological management of PSVT. The arrhythmia temporarily resolved. However, it then transformed into AF. Diltiazem was administered, which briefly decreased blood pressure, which immediately recovered. Surgery resumed while the patient was in normal sinus rhythm. She was discharged safely on postoperative day 6 without complications or abnormalities. Currently, she is living a healthy life without arrhythmia recurrence. CONCLUSION: Ganglia associated with cardiac arrhythmias in the surgical site should be identified during cervical spine surgery.

Transverse myelitis caused by herpes zoster following COVID-19 vaccination: A case report.

BACKGROUND: Transverse myelitis (TM) is characterized by sudden lower extremity progressive weakness and sensory impairment, and most patients have a history of advanced viral infection symptoms. A variety of disorders can cause TM in association with viral or nonviral infection, vascular, neoplasia, collagen vascular, and iatrogenic, such as vaccination. Vaccination has become common through the global implementation against coronavirus disease 2019 (COVID-19) and reported complications like herpes zoster (HZ) activation has increased. CASE SUMMARY: This is a 68-year-old woman who developed multiple pustules and scabs at the T6-T9 dermatome site 1 wk after vaccination with the COVID-19 vaccine (Oxford/AstraZeneca ([ChAdOx1S{recombinant}]). The patient had a paraplegia aggravation 3 wk after HZ symptoms started. Spinal magnetic resonance imaging (MRI) showed transverse myelitis at the T6-T9 Level. Treatment was acyclovir with steroids combined with physical therapy. Her neurological function was slowly restored by Day 17. CONCLUSION: HZ developed after COVID-19 vaccination, which may lead to more severe complications. Therefore, HZ treatment itself should not be delayed. If neurological complications worsen after appropriate management, an immediate diagnostic procedure, such as magnetic resonance imaging and laboratory tests, will start and should treat the neurological complications.

Differential Expression of Pax6 Following Bilateral Common Carotid Artery Occlusion.

BACKGROUND/AIM: Chronic cerebral hypoperfusion causes neuronal damage involving cognitive impairment and development of dementia. Permanent bilateral common carotid artery occlusion (BCCAO) in rat models is used to study chronic cerebral hypoperfusion. Pax6 is used as an early neurogenesis marker which affects the maturation of neuronal cells. However, the expression of PAX 6 after BCCAO is not well understood. In this study, we investigated the expression of PAX6 in the neurogenic zones after BCCAO to evaluate the effects of Pax6 on chronic hypoperfusion. MATERIALS AND METHODS: Chronic hypoperfusion was induced by BCCAO. Common carotid artery was laid parallel to the vagus nerve and separated from it. Both arteries were occluded using 4-0 silk sutures. Rats who underwent bi-common carotid artery occlusion formed in the BCCAO group, while unoperated rats served as the control group. Brain samples were obtained on days 3 and 14 after BCCAO and subjected to immunohisto-chemistry with NeuN and western blotting for Pax6 and HIF1α. RESULTS: Compared to the control, the expression of Pax6 increased three days after surgery but did not differ on day 14, while that of NeuN showed the opposite trend. The expression of HIF1α increased three days after surgery. CONCLUSION: Bilateral common carotid artery occlusion induced early neurogenesis at three days after BCCAO but this result was not maintained at fourteen days after BCCAO.

EEG Parameter Selection Reflecting the Characteristics of Internet Gaming Disorder While Playing League of Legends.

Game playing is an accessible leisure activity. Recently, the World Health Organization officially included gaming disorder in the ICD-11, and studies using several bio-signals were conducted to quantitatively determine this. However, most EEG studies regarding internet gaming disorder (IGD) were conducted in the resting state, and the outcomes appeared to be too inconsistent to identify a general trend. Therefore, this study aimed to use a series of statistical processes with all the existing EEG parameters until the most effective ones to identify the difference between IGD subjects IGD and healthy subjects was determined. Thirty subjects were grouped into IGD (n = 15) and healthy (n = 15) subjects by using the Young's internet addition test (IAT) and the compulsive internet use scale (CIUS). EEG data for 16 channels were collected while the subjects played League of Legends. For the exhaustive search of parameters, 240 parameters were tested in terms of t-test, factor analysis, Pearson correlation, and finally logistic regression analysis. After a series of statistical processes, the parameters from Alpha, sensory motor rhythm (SMR), and MidBeta ranging from the Fp1, C3, C4, and O1 channels were found to be best indicators of IGD symptoms. The accuracy of diagnosis was computed as 63.5-73.1% before cross-validation. The most interesting finding of the study was the dynamics of EEG relative power in the 10-20 Hz band. This EEG crossing phenomenon between IGD and healthy subjects may explain why previous research showed inconsistent outcomes. The outcome of this study could be the referential guide for further investigation to quantitatively assess IGD symptoms.

Outcome of Intermittent Thoracentesis versus Pigtail Catheter Drainage for Hepatic Hydrothorax.

Background/Aims: The management of hepatic hydrothorax (HH) remains a challenging clinical scenario with suboptimal options. We investigated the effect and safety of pigtail catheter drainage compared to intermittent thoracentesis. Methods: This multicenter, retrospective study included 164 cirrhotic patients with recurrent pleural effusion from March 2012 to June 2017. Patients with neoplasms, cardiopulmonary disease, and infectious conditions were excluded. We compared the clinical outcomes of pigtail catheter drainage versus thoracentesis for variables including complications related to procedures, overall survival, and re-admission rates. Results: A total of 164 patients were divided into pigtail catheter (n = 115) and thoracentesis (n = 49) groups. During the follow-up period of 6.93 months after discharge, 98 patients died (pigtail; n = 47 vs. thoracentesis; n = 51). The overall survival (p = 0.61) and 30-day mortality (p = 0.77) rates were similar between the pigtail catheter and thoracentesis groups. Only MELD scores were associated with overall survival (adjusted HR, 1.08; p < 0.01) in patients with HH. Spontaneous pleurodesis occurred in 59 patients (51.3%) in the pigtail catheter group. Re-admission rates did not differ between the pigtail catheter and thoracentesis groups (13.2% vs 19.6% p = 0.7). A total of five complications occurred, including four total cases of bleeding (one patient in the pigtail catheter group and three in the thoracentesis group) and one case of empyema in the pigtail catheter group. Conclusions: Pigtail catheter drainage is not inferior to that of intermittent thoracentesis for the management of HH, proving it may be an effective and safe clinical option.

Repeated ventricular bigeminy by trigeminocardiac reflex despite atropine administration during superficial upper lip surgery: A case report.

BACKGROUND: The trigeminocardiac reflex (TCR) is usually caused by an increased parasympathetic tone when pressure or traction is applied to the surrounding tissue of the trigeminal nerve. However, the inexperienced anesthesiologists may have challenges on the management of TCR patients. CASE SUMMARY: This is the case of an 18-year-old woman diagnosed with hemangioma of the upper lip. During the operation, about 1 h after surgery started, a constant 1:1 premature ventricular complex was detected, and blood pressure was decreased when approaching the deeper part with more strong traction for exposure of the part. Although the management of arrhythmias, such as lidocaine and atropine, was injected, arrhythmia induced by surgical stimulation could not be eliminated completely. As the traction repeated, bradycardia was also repeated, despite injecting additional atropine. Therefore, the anesthesiologist and the surgeon decided to perform the operation only to the extent that the vascular tissue was selectively removed only at the site without the reflex. CONCLUSION: With TCR, anesthesiologists should perform appropriate monitoring. In addition to proper drug administration, surgeons should be consulted to cope with stopping the surgery and setting the scope of the surgery even if the site is superficial.

Platelet-to-White Blood Cell Ratio: A Feasible Biomarker for Pyogenic Liver Abscess.

The platelet-to-white blood cell ratio (PWR) has been reported to predict the severity of patients with various diseases. However, no previous studies have assessed the use of the PWR as a prognostic marker for pyogenic liver abscesses (PLA). This observational retrospective study was performed between January 2008 and December 2017, including 833 patients with PLA from multiple centers. The enrolled patients, on average, had a PWR of 17.05, and 416 patients had a PWR lower than 17.05. A total of 260 patients (31.2%) with PLA showed complications of metastatic infection, pleural effusion and abscess rupture. A low PWR level was identified as a strong risk factor for metastatic infection and pleural effusion. The low PWR group also had a longer hospital stay. In the multivariate analysis, old age, anemia, albumin and CRP levels and unidentified pathogens were significant factors for low PWR levels. A low PWR, old age, male sex, abscess size, albumin, ALP and unidentified causative pathogens showed significant associations with a hospital stay longer than 28 days. As a result, PLA patients presenting with a low PWR were shown to have more complications and a poor prognosis. Considering its cost-effectiveness, PWR could be a novel biomarker used to predict a prognosis of PLA.

Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is linked to a broad spectrum of diseases, including diabetes, hypertension, atherosclerosis, and even liver carcinoma. The ALD spectrum includes alcoholic fatty liver disease (AFLD), alcoholic hepatitis, and cirrhosis. Most recently, some reports demonstrated that the pathogenesis of ALD is strongly associated with metabolites of human microbiota. AFLD was the onset of disease among ALDs, the initial cause of which is alcohol consumption. Thus, we analyzed the significant metabolites of microbiota against AFLD via the network pharmacology concept. The metabolites from microbiota were retrieved by the gutMGene database; sequentially, AFLD targets were identified by public databases (DisGeNET, OMIM). The final targets were utilized for protein-protein interaction (PPI) networks and signaling pathway analyses. Then, we performed a molecular docking test (MDT) to verify the affinity between metabolite(s) and target(s) utilizing the Autodock 1.5.6 tool. From a holistic viewpoint, we integrated the relationships of microbiota-signaling pathways-targets-metabolites (MSTM) using the R Package. We identified the uppermost six key targets (TLR4, RELA, IL6, PPARG, COX-2, and CYP1A2) against AFLD. The PPI network analysis revealed that TLR4, RELA, IL6, PPARG, and COX-2 had equivalent degrees of value (4); however, CYP1A2 had no associations with the other targets. The bubble chart showed that the PI3K-Akt signaling pathway in nine signaling pathways might be the most significant mechanism with antagonistic functions in the treatment of AFLD. The MDT confirmed that Icaritin is a promising agent to bind stably to RELA (known as NF-Κb). In parallel, Bacterium MRG-PMF-1, the PI3K-Akt signaling pathway, RELA, and Icaritin were the most significant components against AFLD in MSTM networks. In conclusion, we showed that the Icaritin-RELA complex on the PI3K-Akt signaling pathway by bacterial MRG-PMF-1 might have promising therapeutic effects against AFLD, providing crucial evidence for further research.

Platelet-to-White Blood Cell Ratio Is Associated with Adverse Outcomes in Cirrhotic Patients with Acute Deterioration.

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9−15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.

Gut Microbiome in Non-Alcoholic Fatty Liver Disease: From Mechanisms to Therapeutic Role.

Non-alcoholic fatty liver disease (NAFLD) is considered to be a significant health threat globally, and has attracted growing concern in the research field of liver diseases. NAFLD comprises multifarious fatty degenerative disorders in the liver, including simple steatosis, steatohepatitis and fibrosis. The fundamental pathophysiology of NAFLD is complex and multifactor-driven. In addition to viruses, metabolic syndrome and alcohol, evidence has recently indicated that the microbiome is related to the development and progression of NAFLD. In this review, we summarize the possible microbiota-based therapeutic approaches and highlight the importance of establishing the diagnosis of NAFLD through the different spectra of the disease via the gut-liver axis.

A Multicenter Retrospective Study on Clinical Characteristics and Outcome of Pyogenic Liver Abscess Focusing Multidrug-Resistant Organisms.

The emergence of multidrug-resistant organisms (MDROs) is a growing problem worldwide. However, little is known about the incidence, clinical features and outcomes of pyogenic liver abscesses (PLAs) caused by MDROs. A retrospective study of 833 patients with PLA admitted from 2008 to 2017 was performed. MDROs were found in 55 (6.6%) patients, and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae was the most common causative microorganism. To evaluate the clinical features of and risk factors for MDRO-induced PLAs, propensity score matching (PSM) was performed in a 1:3 ratio (55 patients with MDROs and 165 patients without MDROs). After PSM, previous hepatobiliary procedure, preadmission exposure to antibiotics and elevated alkaline phosphatase levels were independent risk factors for MDRO-induced PLA. Sixteen patients (7.3%) died during hospitalization. Admission to intensive care unit (ICU), inadequate initial antibiotic treatment and use of inotropic agents were factors predictive of mortality. Although the presence of MDROs was not associated with in-hospital mortality, inadequate initial antibiotic treatment was prescribed to a large portion of the patients with MDRO-induced PLAs. We conclude that initial empirical antibiotic therapy for PLA should be based on the possibility of infection with MDROs, and close monitoring is necessary for patients with risk factors for in-hospital mortality.

The Gut Microbiota-Derived Immune Response in Chronic Liver Disease.

In chronic liver disease, the causative factor is important; however, recently, the intestinal microbiome has been associated with the progression of chronic liver disease and the occurrence of side effects. The immune system is affected by the metabolites of the microbiome, and diet is the primary regulator of the microbiota composition and function in the gut-liver axis. These metabolites can be used as therapeutic material, and postbiotics, in the future, can increase or decrease human immunity by modulating inflammation and immune reactions. Therefore, the excessive intake of nutrients and the lack of nutrition have important effects on immunity and inflammation. Evidence has been published indicating that microbiome-induced chronic inflammation and the consequent immune dysregulation affect the development of chronic liver disease. In this research paper, we discuss the overall trend of microbiome-derived substances related to immunity and the future research directions.

Ensemble effects in Cu/Au ultrasmall nanoparticles control the branching point for C1 selectivity during CO2 electroreduction.

Bimetallic catalysts provide opportunities to overcome scaling laws governing selectivity of CO2 reduction (CO2R). Cu/Au nanoparticles show promise for CO2R, but Au surface segregation on particles with sizes ≥7 nm prevent investigation of surface atom ensembles. Here we employ ultrasmall (2 nm) Cu/Au nanoparticles as catalysts for CO2R. The high surface to volume ratio of ultrasmall particles inhibits formation of a Au shell, enabling the study of ensemble effects in Cu/Au nanoparticles with controllable composition and uniform size and shape. Electrokinetics show a nonmonotonic dependence of C1 selectivity between CO and HCOOH, with the 3Au:1Cu composition showing the highest HCOOH selectivity. Density functional theory identifies Cu2/Au(211) ensembles as unique in their ability to synthesize HCOOH by stabilizing CHOO* while preventing H2 evolution, making C1 product selectivity a sensitive function of Cu/Au surface ensemble distribution, consistent with experimental findings. These results yield important insights into C1 branching pathways and demonstrate how ultrasmall nanoparticles can circumvent traditional scaling laws to improve the selectivity of CO2R.

Identification of Video Game Addiction Using Heart-Rate Variability Parameters.

The purpose of this study is to determine heart rate variability (HRV) parameters that can quantitatively characterize game addiction by using electrocardiograms (ECGs). 23 subjects were classified into two groups prior to the experiment, 11 game-addicted subjects, and 12 non-addicted subjects, using questionnaires (CIUS and IAT). Various HRV parameters were tested to identify the addicted subject. The subjects played the League of Legends game for 30-40 min. The experimenter measured ECG during the game at various window sizes and specific events. Moreover, correlation and factor analyses were used to find the most effective parameters. A logistic regression equation was formed to calculate the accuracy in diagnosing addicted and non-addicted subjects. The most accurate set of parameters was found to be pNNI20, RMSSD, and LF in the 30 s after the "being killed" event. The logistic regression analysis provided an accuracy of 69.3% to 70.3%. AUC values in this study ranged from 0.654 to 0.677. This study can be noted as an exploratory step in the quantification of game addiction based on the stress response that could be used as an objective diagnostic method in the future.

Reduced Levels of Drp1 Protect against Development of Retinal Vascular Lesions in Diabetic Retinopathy.

High glucose (HG)-induced Drp1 overexpression contributes to mitochondrial dysfunction and promotes apoptosis in retinal endothelial cells. However, it is unknown whether inhibiting Drp1 overexpression protects against the development of retinal vascular cell loss in diabetes. To investigate whether reduced Drp1 level is protective against diabetes-induced retinal vascular lesions, four groups of mice: wild type (WT) control mice, streptozotocin (STZ)-induced diabetic mice, Drp1+/- mice, and STZ-induced diabetic Drp1+/- mice were examined after 16 weeks of diabetes. Western Blot analysis indicated a significant increase in Drp1 expression in the diabetic retinas compared to those of WT mice; retinas of diabetic Drp1+/- mice showed reduced Drp1 level compared to those of diabetic mice. A significant increase in the number of acellular capillaries (AC) and pericyte loss (PL) was observed in the retinas of diabetic mice compared to those of the WT control mice. Importantly, a significant decrease in the number of AC and PL was observed in retinas of diabetic Drp1+/- mice compared to those of diabetic mice concomitant with increased expression of pro-apoptotic genes, Bax, cleaved PARP, and increased cleaved caspase-3 activity. Preventing diabetes-induced Drp1 overexpression may have protective effects against the development of vascular lesions, characteristic of diabetic retinopathy.

Opa1 Deficiency Promotes Development of Retinal Vascular Lesions in Diabetic Retinopathy.

This study investigates whether reduced optic atrophy 1 (Opa1) level promotes apoptosis and retinal vascular lesions associated with diabetic retinopathy (DR). Four groups of mice: wild type (WT) control mice, streptozotocin (STZ)-induced diabetic mice, Opa1+/- mice, and diabetic Opa1+/- mice were used in this study. 16 weeks after diabetes onset, retinas were assessed for Opa1 and Bax levels by Western blot analysis, and retinal networks were examined for acellular capillaries (AC) and pericyte loss (PL). Apoptotic cells were detected in retinal capillaries using TUNEL assay, and caspase-3 activity was assessed using fluorometric analysis. Opa1 expression was significantly downregulated in retinas of diabetic and Opa1+/- mice compared with those of WT mice. Inducing diabetes further decreased Opa1 expression in retinas of Opa1+/- mice. Increased cytochrome c release concomitant with increased level of pro-apoptotic Bax and elevated caspase-3 activity were observed in retinas of diabetic and Opa1+/- mice; the number of TUNEL-positive cells and AC/PL was also significantly increased. An additional decrease in the Opa1 level in retinas of diabetic Opa1+/- mice exacerbated the development of apoptotic cells and AC/PL compared with those of diabetic mice. Diabetes-induced Opa1 downregulation contributes, at least in part, to the development of retinal vascular lesions characteristic of DR.

Tunable tunnel barriers in a semiconductor via ionization of individual atoms.

We report scanning tunneling microscopy (STM) studies of individual adatoms deposited on an InSb(110) surface. The adatoms can be reproducibly dropped off from the STM tip by voltage pulses, and impact tunneling into the surface by up to ∼100×. The spatial extent and magnitude of the tunneling effect are widely tunable by imaging conditions such as bias voltage, set current and photoillumination. We attribute the effect to occupation of a (+/0) charge transition level, and switching of the associated adatom-induced band bending. The effect in STM topographic images is well reproduced by transport modeling of filling and emptying rates as a function of the tip position. STM atomic contrast and tunneling spectra are in good agreement with density functional theory calculations for In adatoms. The adatom ionization effect can extend to distances greater than 50 nm away, which we attribute to the low concentration and low binding energy of the residual donors in the undoped InSb crystal. These studies demonstrate how individual atoms can be used to sensitively control current flow in nanoscale devices.

Metal artifact reduction method based on a constrained beam-hardening estimator for polychromatic x-ray CT.

Beam hardening in x-ray computed tomography (CT) is inevitable because of the polychromatic x-ray spectrum and energy-dependent attenuation coefficients of materials, leading to the underestimation of artifacts arising from projection data, especially on metal regions. State-of-the-art research on beam-hardening artifacts is based on a numerical method that recursively performs CT reconstruction, which leads to a heavy computational burden. To address this computational issue, we propose a constrained beam-hardening estimator that provides an efficient numerical solution via a linear combination of two images reconstructed only once during the entire process. The proposed estimator reflects the geometry of metal objects and physical characteristics of beam hardening during the transmission of polychromatic x-rays through a material. Most of the associated parameters are numerically obtained from an initial uncorrected CT image and forward projection transformation without additional optimization procedures. Only the unknown parameter related to beam-hardening artifacts is fine-tuned by linear optimization, which is performed only in the reconstruction image domain. The proposed approach was systematically assessed using numerical simulations and phantom data for qualitative and quantitative comparisons. Compared with existing sinogram inpainting-based and model-based approaches, the proposed scheme in conjunction with the constrained beam-hardening estimator not only provided improved image quality in areas surrounding the metal but also achieved fast beam-hardening correction owing to the analytical reconstruction structure. This work may have significant implications in improving dose calculation accuracy or target volume delineation for treatment planning in radiotherapy.