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Background Myringotomy with tympanostomy tube insertion (MTI) is a superficial surgical procedure used to prevent hearing loss in children with serous otitis media. Intravenous anesthesia, often ketamine, is preferred for this procedure because of its ability to induce sedation without compromising airway reflexes. However, ketamine alone may be insufficient and potentially lead to spontaneous movement during surgery. This study evaluated the effectiveness of midazolam and fentanyl as adjuvants to ketamine in reducing spontaneous movement during MTI and enhancing the quality of recovery. Methods This study involved two groups of 30 patients each: one group received intravenous ketamine (1.5 mg/kg) with an equal volume of normal saline (K group), while the other received a combination of midazolam, fentanyl, and ketamine (0.05 mg/kg, 1 μg/kg, and 1.5 mg/kg, respectively; MFK group). We assessed side effects, intraoperative patient movement, surgeon satisfaction, and emergence agitation scores. Results The MFK group exhibited significantly lower scores for patient movement (p

Continuous fasciculation that occurs without weakness is referred to as benign fasciculation. Although generally considered non-threatening, cases that persist can significantly impact an individual's quality of life. This study presents a case of a male patient in his 30s experiencing unyielding twitching localized to the sole of his left foot for 2 years. His medical history was devoid of any notable neuromuscular diseases. Results from electromyography testing were also normal for all parameters. Attempts with pharmacological intervention did not yield any improvement of his condition. Although a nerve block targeting the left tibial nerve managed to reduce the severity of the twitching, it failed to decrease its frequency or provide a lasting solution. In search of a more effective treatment, botulinum toxin was administered via ultrasound guidance into the flexor hallucis and digitorum longus muscles. This approach resulted in a marked reduction in both the frequency and severity of the twitching, enabling the patient to resume his daily activities and achieve restful sleep without experiencing any adverse effects. Through this case, the efficacy of botulinum toxin injections as a treatment for intractable twitching is underscored, offering valuable insights into potential therapeutic strategies for similar clinical presentations.

Background/Aims The model for end-stage liver disease (MELD) serves as an indicator for short-term mortality among patients diagnosed with liver cirrhosis (LC) and is used to prioritize patients for liver transplantation. In 2021, the updated version of MELD, MELD-3.0, was introduced to improve the accuracy of the mortality prediction of MELD. Therefore, this study aimed to compare the efficacy of MELD 3.0 and MELD-Na in predicting mortality among Korean patients with LC. Methods A retrospective review was conducted using the medical records of patients diagnosed with LC who were admitted to Konkuk University Hospital From 2011 to 2021. The study calculated the predictive values of MELD-Na and MELD-3.0 for 3- and 6-months mortality using the area under the receiver operating curve (AUROC) and compared the results using the DeLong test. Results Of the 3,034 patients enrolled in the study, 339 (11.2%) died within 3 months and 421 (14.4%) died within 6 months. The AUROCs values for predicting 3 months mortality were 0.846 for MELD-Na and 0.851 for MELD-3.0. The corresponding AUROC values for predicting 6 months mortality were 0.843 for MELD-Na and 0.848 for MELD-3.0. MELD-3.0 exhibited better discrimination ability than MELD-Na for both 3 (p = 0.03) and 6 months mortality (p = 0.01). Conclusions Our study found a significant difference between the performance of MELD-3.0 and MELD-Na in Korean patients with LC.

ABSTRACTNicotinamide Adenine Dinucleotide (NAD) is an endogenous substance in redox reactions and regulates various functions in metabolism. NAD and its precursors are known for their anti-ageing and anti-obesity properties and are mainly active in the liver and muscle. Boosting NAD+ through supplementation with the precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), enhances insulin sensitivity and circadian rhythm in the liver, and improves mitochondrial function in the muscle. Recent evidence has revealed that the adipose tissue could be another direct target of NAD supplementation by attenuating inflammation and fat accumulation. Moreover, murine studies with genetically modified models demonstrated that nicotinamide phosphoribosyltransferase (NAMPT), a NAD regulatory enzyme that synthesizes NMN, played a critical role in lipogenesis and lipolysis in an adipocyte-specific manner. The tissue-specific effects of NAD+ metabolic pathways indicate a potential of the NAD precursors to control metabolic stress particularly via focusing on adipose tissue. Therefore, this narrative review raises an importance of NAD metabolism in white adipose tissue (WAT) through a variety of studies using different mouse models.

Background and Objectives: Rectal cancer is considered cured if no recurrence is found during the 5-year follow-up period after treatment. After this period, patients often believe that the cancer is completely eradicated. However, in modern society, where lifespans have become longer, it is important to recognize that metastatic cancer may occur long after the initial treatment has concluded. This highlights the necessity of continued vigilance and the long-term follow-up of cancer survivors. Case report: We present a case of metastatic cancer of the coccyx in an 87-year-old female patient. This patient had undergone successful surgery and treatment for rectal cancer 10 years prior. She was considered cured after the standard 5-year follow-up period as she showed no signs of recurrence. The patient presented with simple coccygeal pain as the main complaint, without any other accompanying symptoms such as weight loss, fever, or changes in bowel habits, typically associated with cancer recurrence. During the clinical evaluation, irregularities in the bone cortex were detected while performing a nerve block using ultrasound. Given these findings, further diagnostic evaluations were performed. Advanced imaging techniques including MRI and CT scans led to a diagnosis of coccygeal metastasis. Conclusions: While the 5-year mark post-treatment is a significant milestone for rectal cancer patients, it does not guarantee the absolute eradication of the disease. Long-term monitoring and a thorough evaluation of new symptoms are essential for the early detection and management of late metastatic recurrences. This approach ensures that patients receive timely and appropriate care, potentially improving outcomes and quality of life.

The regulation of the circadian clock plays an important role in influencing physiological conditions. While it is reported that the timing and quantity of energy intake impact circadian regulation, the underlying mechanisms remain unclear. This study investigated the impact of dietary protein intake on peripheral clocks. Firstly, transcriptomic analysis was conducted to investigate molecular targets of low-protein intake. Secondly, mPer2::Luc knock-in mice, fed with either a low-protein, normal, or high-protein diet for 6 weeks, were analyzed for the oscillation of PER2 expression in peripheral tissues and for the expression profiles of circadian and metabolic genes. Lastly, the candidate pathway identified by the in vivo analysis was validated using AML12 cells. As a result, using transcriptomic analysis, we found that the low-protein diet hardly altered the circadian rhythm in the central clock. In animal experiments, expression levels and period lengths of PER2 were different in peripheral tissues depending on dietary protein intake; moreover, mRNA levels of clock-controlled genes and endoplasmic reticulum (ER) stress genes were affected by dietary protein intake. Induction of ER stress in AML12 cells caused an increased amplitude of Clock and Bmal1 and an advanced peak phase of Per2. This result shows that the intake of different dietary protein ratios causes an alteration of the circadian rhythm, especially in the peripheral clock of mice. Dietary protein intake modifies the oscillation of ER stress genes, which may play key roles in the regulation of the circadian clock.

Background/Aims Because hepatitis B virus (HBV) replication has been known to play an important role in cancer recurrence after curative treatment of HBV-related hepatocellular carcinoma (HCC), we examined whether treatment based on nucleos(t)ide analogues (NAs) might decrease the recurrence rate and improve patient survival. Methods The retrospective cohort study enrolled 73 patients with chronic hepatitis B who were treated with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) with curative intent for HCC. Among those, 30 and 43 patients were treated with tenofovir disoproxil fumarate (TDF) and entecavir (ETV), respectively. Results Of the 73 patients, 51 experienced HCC recurrence, and 14 patients were dead during a follow-up of 73±34 months. Multivariate analyses showed that tumor size (hazard ratio [HR], 1.590; 95% confidence-interval [CI], 1.106–2.285; P=0.012) and Child-Pugh class B (vs. class A/non cirrhosis; HR, 5.794; 95% CI, 2.311–14.523; P=0.001) was significantly associated with HCC recurrence, and Child-Pugh class B (HR, 7.357; 95% CI, 2.100–25.777; P=0.002) was an independent unfavorable prognostic factor for survival. During NAs therapy, TDF was superior to ETV for complete viral response at 1 year after the date of combination of TACE and RFA (P=0.016). However, the risks of HCC recurrence and survival were not significantly different between those treated with TDF versus ETV. Conclusions TDF was superior to ETV for achieving complete viral response. However, the recurrence and mortality after TACE and RFA for HBV-related HCC were not significantly different between patients treated with TDF versus ETV.

Background/Aims: The HBsAg levels have been used to monitor the chronic hepatitis B (CHB) treatment response to antiviral therapy. On the other hand, it is unclear if the HBsAg quantification levels at each treatment point differ according to the HBeAg status and drug in CHB patients. This study compared the changes in HBsAg in CHB patients according to the HBeAg status and treatment drugs. Methods: CHB patients with at least 1 year of follow-up treatment with one drug, either entecavir (ETV) or tenofovir (TDF), were enrolled in this study. The mean HBsAg levels were measured annually for up to 6 years. A linear mixed model was used to compare the HBsAg quantification levels during the follow-up period. An independent samples t-test was used to analyze the differences in the HBsAg quantification levels at each treatment time point. Results: Ninety-seven patients were enrolled in this study; 59 among them were HBeAg-positive. Two patients in the TDF group achieved HBsAg seroconversion. The HBsAg level decreased during the follow-up in the ETV and TDF groups. The HBsAg level was lower in the TDF group than the ETV group during the follow-up. On the other hand, subgroup analysis showed that this trend was the same only in the HBeAg-negative patients, not in the HBeAg-positive patients. In the HBeAg-negative patients, HBsAg level in the TDF group was significantly lower than that in the ETV group at 36, 48, and 72 months. The change in HBsAg level from the baseline increased at a decreasing rate during the follow-up in both groups. Furthermore, the change in the HBsAg level in the TDF group was significantly larger than that of the ETV group at 36 months in the HBeAg-negative patients. Conclusions: Although TDF might be more efficient than ETV in reducing the HBsAg level in HBeAg-negative patients in a few years, HBsAg seroconversion occurred very rarely. A further large-scale, long-term study will be needed to confirm the antiviral effects on the HBsAg level.

Background/Aims Chronic hepatitis C (CHC) treatment has dramatically improved since direct-acting antiviral (DAA) therapy was introduced. However, the use of DAA therapy in CHC patients with hepatocellular carcinoma (HCC) remains controversial. We investigated the DAA treatment response in CHC patients with HCC. Methods We retrospectively analyzed CHC patients treated with DAA from 2016 to 2018. Patients were divided into two groups based on their HCC-history before DAA therapy. Baseline characteristics, sustained virologic response at 12 weeks (SVR 12), and HCC recurrence after DAA therapy were evaluated. We also used propensity score matching (PSM) in a 2:1 ratio to reduce confounding variables. Results A total of 192 patients were enrolled; 78.1% were treatment-naïve, and 34.9% had liver cirrhosis (LC). Among these patients, 168 did not have HCC, and 24 had HCC. The HCC group was older (57.0 years vs. 72.0 years, p < 0.001), had a higher incidence of LC (26.2% vs. 95.8%, p < 0.001), fibrosis-4 index (2.6 vs. 9.2, p < 0.001), liver stiffness measurement (7.0 kPa vs. 17.4 kPa, p = 0.012), and α-fetoprotein (4.4 ng/mL vs. 8.2 ng/mL, p ≤ 0.001). The SVR 12 rate was 97.0% in the non- HCC group and 91.7% in the HCC group (p = 0.213). HCC recurrence was observed in 14 patients (58.3%) in the HCC group. Conclusions DAA treatment efficacy in CHC patients with or those without HCC were not significantly different, and HCC recurrence was relatively common.

Background/Aims Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy, arising from the peripheral intrahepatic bile duct epithelium. Hepatitis B virus (HBV) or hepatitis C virus (HCV) may be involved in the development of ICC. We explored the prognostic value of hepatitis virus infection, as well as other prognostic factors affecting survival in patients with ICC. Methods A retrospective chart review was performed for patients diagnosed with ICC between August 2005 and December 2018 at Konkuk University Medical Center. We identified a total of 131 patients with ICC. Overall survival rates of patients with and without hepatitis were determined. Univariate and multivariate analyses were used to estimate factors influencing survival outcomes. Results A total of 17.6% (23/131) of patients were positive for HBV or HCV. Hepatitis B positive ICC patients were significantly younger with higher albumin and higher α-fetoprotein than those without hepatitis viral infections. The median survival of hepatitis-positive and hepatitis-negative groups was 280 and 213 days, respectively. Survival rates were not significantly different between the two groups (p = 0.279). Multivariate analyses indicated that lower serum carbohydrate antigen 19-9 (CA 19-9) (p < 0.001), lower T stage (p = 0.042), the absence of lymph-node metastasis (p = 0.043), and receiving curative surgery (p = 0.033) were independent predictors of better outcomes. Conclusions While hepatitis influenced a number of clinical features in ICC patients, it did not affect survival rate. Prognostic factors influencing survival outcomes with ICC were CA 19-9 level, T stage, the presence of lymph node metastasis, and curative surgery.

Background/Aims: A switch to systemic therapy, such as sorafenib, should be considered for hepatocellular carcinoma (HCC) patients refractory to transarterial chemoembolization (TACE). On the other hand, treatment changes are difficult if the liver function worsens to Child-Pugh B or C. Therefore, predicting the risk factors for non-responsiveness to TACE and deteriorating liver function may be helpful. Methods: Newly diagnosed Child-Pugh A HCC patients who underwent TACE from January 2012 to June 2018 were included. After 1 year, this study evaluated whether there was a treatment response to TACE and whether the Child-Pugh class had worsened. Results: Among 121 patients, 65 were refractory and 56 responded to TACE. In multivariable logistic regression analysis, the tumor size, tumor number, and albumin at the time of the diagnosis of HCC were significant prognostic factors for the treatment response to TACE. Among 65 patients who presented TACE-refractoriness, 27 showed liver function deterioration from Child-Pugh class A to class B or C after TACE. In multivariable logistic regression analysis, bilirubin at the diagnosis of HCC was a significant prognostic factor for liver function deterioration. A predictive algorithm based on the regression equations revealed a sensitivity, specificity, positive predictive value, and negative predictive value of 74.1%, 74.5%, 45.5%, and 90.9%, respectively, for TACE-refractoriness and liver function deterioration. Conclusions: The prognostic model incorporating the tumor size, tumor number, albumin, and bilirubin at the diagnosis of HCC may help identify patients who show a poor response to TACE and aggravation of liver function after TACE, who may benefit from early switching into systemic therapy before liver function aggravation.

Background : /Aims: Surgical resection or ablation is recommended for the treatment of early hepatocellular carcinoma (HCC), whereas transarterial chemoembolization (TACE) is frequently used in early HCC ineligible for curative resection. We evaluated the clinical effects and safety of radiofrequency ablation (RFA) shortly after TACE in patients with Barcelona clinic liver cancer (BCLC) stage A HCC. Methods : : Sixty-seven BCLC stage A HCC patients who failed to achieve complete response to TACE as either a first line treatment and who subsequently received RFA at the Konkuk University Medical Center from January 2005 to December 2017 were included. Evaluation indices included treatment response, overall survival rate, recurrence-free survival, prognostic factors, and procedure-related complications. Results : : Median follow-up was 46.9 months. Fifty-four (80.6%) patients were of Child-Pugh class A, and 13 (19.4%) were of class B. Modified UICC stages were I in 10 (14.9%), II in 46 (68.7%), and III in 11 (16.4%) patients. In the 67 study subjects, cumulative recurrence-free survival rates were 86.8%, 55.9% and 29.7% at 1, 3, and 5 years, respectively, and overall survival rates were 100%, 93.4%, and 83.5% at 1, 3, and 5 years, respectively. Tumor size significantly predicted recurrence. No treatment-related death occurred. Conclusion : s: Combination of RFA was an efficient and safe treatment for BCLC stage A HCC patients that failed to achieve complete response to initial TACE. We suggest TACE plus RFA be considered as a curative option for early HCC patients ineligible for curative resection of RFA.

Background The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. Methods Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. Results Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. Conclusions The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.

Craniofacial hyperhidrosis causes sweating of the face and scalp due to excessive action of the sweat glands and manifests when patients become tense/nervous or develop an elevated body temperature. If noninvasive treatments are ineffective, invasive treatments such as a sympathetic block and resection are considered. A 32-year-old woman with no specific medical history was referred for uncontrolled craniofacial hyperhidrosis that included excessive sweating and hot flushing. Physical examination showed profuse sweating, and infrared thermography showed higher temperature in the neck and face than in the trunk. The patient underwent several stellate ganglion blocks, and her symptoms improved; however, the treatment effect was temporary. Botulinum toxin was then injected into the stellate ganglion. At the time of this writing, her sweating had been reduced for about 6 months and she was continuing to undergo follow-up. Craniofacial hyperhidrosis is a clinical condition in which patients experience excessive sweating of their faces and heads. It is less common than palmar and plantar hyperhidrosis. Botulinum toxin injection into the stellate ganglion is simple and safe and produces longer-lasting effects than other treatments, such as endoscopic sympathectomy and a single nerve block.

Background /Aims: Direct-acting antiviral (DAA) therapy has been shown to achieve a high rate of sustained virologic response (SVR) and favorable outcomes in chronic hepatitis C (CHC) patients. We investigated the virologic response and its clinical impact in CHC patients. Methods : CHC patients with compensated liver function treated with DAAs between 2016 and 2017 were included for retrospective analysis. We analyzed baseline characteristics and virologic and biochemical responses at on-treatment 4 weeks, end of treatment, and post-treatment 12 weeks. Fibrosis was measured as liver stiffness measurement by transient elastography (FibroScan). Adverse events were monitored during the treatment period. Results : A total of 135 patients (61.5% with genotype [GT] 1b and 38.5% with GT 2a) were enrolled 47.4% were male, 79.3% were treatment naive, and 30.4% had cirrhosis. SVR 12 was observed in 97.6% (81/83) in the GT 1b and 98.1% (51/52) in the GT 2a; treatment with daclatasvir+asunaprevir was the most commonly used in GT 1b (55/83), and sofosbuvir+ribavirin was the most commonly used in GT 2a (49/52). The median change of liver stiffness measurement at two time points using the signed rank test was -3.2 kPa in patients who underwent transient elastography before treatment and at SVR 12 (n=25). The most common adverse events were anemia, dyspepsia, and insomnia. One GT 2a patient treated with sofosbuvir+ribavirin stopped the treatment at 8 weeks due to symptomatic bradyarrhythmia; however, he recovered spontaneously and achieved SVR 12. Conclusion s: DAA treatment of chronic hepatitis C genotype 1b and 2a resulted in a high rate of sustained virologic response and improvement of liver fibrosis score.

Since both anesthesia and sleep depress consciousness, bidirectional relationship between them has been further studied. Earlier findings have shown that they share electroencephalographic features and brain regions that are activated in both state of unconsciousness. Despite these similarities, medication-induced sedation provokes different outcome from natural sleep. Enlisting commonly used analgesic drugs, such as benzodiazepines, intravenous agents, benzodiazepine antagonists, opioids, and other adjuvants, the study is comprised of assorted case studies that are clinically applicable or comparable. Acknowledging potential of analgesic drugs on sleep disorders including sleep deprivation, narcolepsy, circadian rhythm disorder, periodic limb movement disorder, and obstructive sleep apnea, the study underscores the clinical importance of studying both fields, sleep and anesthesia. In conclusion, the aim of this review is explaining the consequences of analgesic agents or sedatives on sleep and sleep disorders.

Background/AimsDirect sequencing is the gold standard for the detection of drug-resistance mutations in hepatitis B virus (HBV); however, this procedure is time-consuming, labor-intensive, and difficult to adapt to high-throughput screening. In this study, we aimed to develop a dendron-modified DNA microarray for the detection of genotypic resistance mutations and evaluate its efficiency.Methods : The specificity, sensitivity, and selectivity of dendron-modified slides for the detection of representative drug-resistance mutations were evaluated and compared to those of conventional slides. The diagnostic accuracy was validated using sera obtained from 13 patients who developed viral breakthrough during lamivudine, adefovir, or entecavir therapy and compared with the accuracy of restriction fragment mass polymorphism and direct sequencing data.Results : The dendron-modified slides significantly outperformed the conventional microarray slides and were able to detect HBV DNA at a very low level (1 copy/μL). Notably, HBV mutants could be detected in the chronic hepatitis B patient sera without virus purification. The validation of our data revealed that this technique is fully compatible with sequencing data of drug-resistant HBV.Conclusion : sWe developed a novel diagnostic technique for the simultaneous detection of several drug-resistance mutations using a dendron-modified DNA microarray. This technique can be directly applied to sera from chronic hepatitis B patients who show resistance to several nucleos(t)ide analogues.

Background/Aims Little is known about the effect of early flares on response during first-line tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB). The aim of this study was to investigate the incidence and outcome of early alanine aminotransferase (ALT) flare in treatment-naive patients with CHB during long-term TDF monotherapy. Methods One hundred eighty-one treatment-naive CHB patients were treated with a 300-mg once-daily dose of TDF for more than 12 weeks. Virological markers of hepatitis B virus (HBV) and biochemical data were measured at baseline and every 4-12 weeks during the therapy. The proportion of patients with undetectable HBV DNA level (< 100 copies/mL) was noted. Results The median age was 48.3 years and 122 patients (67.4%) were men. Hepatitis B envelope antigen (HBeAg) was positive in 101 patients (55.8%). No patient had cirrhosis. The median follow-up duration was 45 weeks (12-155 weeks). ALT flare (>5 × upper limit of the normal range) occurred in seven patients (3%) without viral breakthrough within the first 8 weeks after the start of TDF monotherapy. Among them, six patients were HBeAg-positive and one patient was HBeAg-negative. All cases of early ALT flares resolved within 4 weeks and virologic response was observed in all patients without interruption or discontinuation of treatment. Conclusions Continuous TDF monotherapy was effective and safe in treatment-naive patients with CHB who experienced early ALT flares followed by a decrease in HBV DNA level.

Background/Aims: Spontaneous bacterial peritonitis (SBP) is one of critical complications in liver cirrhosis patients with ascites. We aimed to review clinical course of SBP patients in a 10-year period from single center. Methods: This study enrolled SBP patients between 2005 and 2015. Their medical records were reviewed. The laboratory findings of serum and ascites were examined, and characteristics of isolated microorganisms in ascites were analyzed. Results: Total 51 patients were enrolled. Male patients were predominant (64.7%), and mean age was 59.20 years. The most common etiology of cirrhosis was alcohol (41.2%), followed by hepatitis B (39.2%). Microorganism was isolated from the ascites in 31 patients (60.78%). The proportions of Gram negative and Gram positive were 80.64% and 19.36%. The proportions of Escherichia coli, Klebsiella, and Streptococcus species were 29.41%, 19.61% and 11.76%. Among Escherichia colis, 4 cases were ESBL positive (7.84%). The most commonly used first-line antibiotic was cefotaxime (80.40%). Prophylactic antibiotics treatment was performed only in 8 patients, and SBP was recurred in 7 patients (13.72%). When comparing the SBP recurrence group and the non-recurrence group, there were no significant differences in laboratory findings of serum and ascitic fluid. Conclusions: SBP is still a critical complication in cirrhosis patients with ascites, and the clinical features of SBP have not been altered much compared with those in 1990’s. The effective treatment of SBP is still very important for a better prognosis of cirrhosis patients.

A median nerve injury in the forearm may lead to devastating sequelae if left untreated. Even with appropriate treatments involving microsurgical techniques and postoperative care, patients may still experience lasting neuropathic pain that significantly reduces their quality of life. Pulsed radiofrequency (PRF) is widely performed to alleviate such neuropathic pain caused by trauma. A 47-year-old man visited our pain clinic with allodynia, hyperalgesia, paresthesia, skin color changes, and atrophy in the right forearm. In the orthopedic department, the patient was treated by neurectomy of the median nerve to manage the intractable pain. However, the effect was unsatisfactory. The fourth median nerve block performed in our pain clinic after neurectomy produced good results, and ultrasound-guided PRF of the median nerve was performed. The patient showed 80% relief of symptoms within 5 hours after the procedure. The visual analog scale score for the forearm decreased from 8/10 to 1/10. This case suggests that ultrasound-guided PRF can be a therapeutic option for the management of refractory neuropathic pain after neurectomy in patients with a median nerve injury.

Background/Aims: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. Methods: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. Results: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. Conclusions: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.

Portal biliopathy is defined as abnormalities in the extra- and intrahepatic ducts and gallbladder of patients with portal hypertension. This condition is associated with extrahepatic venous obstruction and dilatation of the venous plexus of the common bile duct, resulting in mural irregularities and compression of the biliary tree. Most patients with portal biliopathy remain asymptomatic, but approximately 10% of them advance to symptomatic abdominal pain, jaundice, and fever. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography are currently used as diagnostic tools because they are noninvasive and can be used to assess the regularity, length, and degree of bile duct narrowing. Management of portal biliopathy is aimed at biliary decompression and reducing the portal pressure. Portal biliopathy has rarely been reported in Korea. We present a symptomatic case of portal biliopathy that was complicated by cholangitis and successfully treated with biliary endoscopic procedures.

Background/Aims: Tumor recurrence after curative therapy is common for patients with hepatocellular carcinoma (HCC). As fibrosis and chronic inflammation contribute to the progression of HCC, we aimed to identify the predictive value of inflammatory and fibrosis markers for HCC recurrence after curative therapy using radiofrequency ablation (RFA). Materials and Methods: We retrospectively reviewed the records of patients with HCC treated with RFA between October 2005 and September 2013. The median duration of follow-up was 40 months (4-95 months). Inflammatory and fibrosis markers and demographic and clinical data were analyzed by Cox proportional hazards model using univariate and multivariate analyses and longitudinal analysis. Results: A total of 98 patients were included for analysis. There were 54 cases of HCC recurrence (55.1%). The aspartate aminotransferase-to-platelet ratio index (APRI; 2.3 ± 1.8 vs. 1.3 ± 1.4, P = 0.018) was significantly higher in the recurrence group than in the recurrence-free group. In multivariate analysis, APRI (hazard ratio, 2.64; confidence interval, 1.488-4.714; P = 0.001) was an independent risk factor for tumor recurrence. In particular, patients with APRI >1.38 showed a higher recurrence rate than patients with APRI ≤1.38 (P < 0.001). Longitudinal analysis showed persistently higher APRI values when assessed 12 months after RFA in patients who developed recurrence during follow-up than those who remained recurrence-free. Conclusions: These findings show that a high APRI value is associated with HCC recurrence after RFA. Therefore, APRI could play an important role in predicting HCC recurrence after RFA.

Objective This study was performed to determine the effect of the remifentanil dose on the onset time of rocuronium with electromyography. Methods This retrospective comparative study included 75 patients undergoing general anesthesia for elective surgery. Patients received lidocaine (40 mg) and propofol (2 mg/kg) followed by rocuronium (0.6 mg/kg) with either saline infusion (Group S), remifentanil at 0.5 µg/kg/minute (Group R 0.5), or remifentanil at 1.0 µg/kg/minute (Group R 1.0). Neuromuscular block was monitored by train-of-four (TOF) electromyography, and the times taken to reach TOF 0 and TOF ratio (TOFR) 25% were recorded. Results The times taken to reach TOF 0 and TOFR 25% were significantly higher in Groups R 0.5 and R 1.0 than in Group S. The time taken to reach TOF 0 was 130.0 ± 6.4 s in Group S, 142.6 ± 6.0 s in Group R 0.5, and 183.0 ± 11.6 s in Group R 1.0. The time taken to reach TOFR 25% was also higher in Groups R 0.5 and R 1.0 than in Group S. Conclusions As the remifentanil dose increases, the intubation time required to reach TOF 0 also increases. Remifentanil has an effect on the onset of rocuronium.

Background/Aims: This study aimed to evaluate the antiviral response and safety of tenofovir (TDF) versus entecavir (ETV) in treatment-naïve CHB patients. Patients and Methods: We performed a retrospective cohort study of treatment-naive CHB patients who were treated with TDF or ETV. We analyzed virologic, biochemical, and serologic responses at 3, 6, and 12 months. Results: A total of 107 patients (TDF group = 49, ETV group = 58) were included. Baseline characteristics were similar between the two groups. The estimated proportion of complete virologic response (CVR) in the TDF or ETV group was 44.9% versus 39.7% at 6 months and 89.6% versus 83.2% at 12 months, respectively (P = 0.991). Viral breakthrough was not observed in both groups. One patient in the TDF group and two patients in the ETV group experienced HBeAg loss, respectively (P = 0.657). High HBV DNA level at baseline was a significant negative predictor of virologic response by Cox regression analysis (P = 0.007). The safety profile was similar between the two groups. There was no case with serious adverse event. Conclusions: Both TDF and ETV were effective in achieving CVR and had a favorable safety profile in treatment-naïve CHB patients. High viral load at baseline was a negative predictive factor of CVR.

Reversible focal lesions on the splenium of the corpus callosum (SCC) have been reported in patients with mild encephalitis/encephalopathy caused by various infectious agents, such as influenza, mumps, adenovirus, Varicella zoster, Escherichia coli, Legionella pneumophila, and Staphylococcus aureus. We report a case of a reversible SCC lesion causing reversible encephalopathy in nonfulminant hepatitis A. A 30-year-old healthy male with dysarthria and fever was admitted to our hospital. After admission his mental status became confused, and so we performed electroencephalography (EEG) and magnetic resonance imaging (MRI) of the brain, which revealed an intensified signal on diffusion-weighted imaging (DWI) at the SCC. His mental status improved 5 days after admission, and the SCC lesion had completely disappeared 15 days after admission.

Radio-frequency ablation (RFA) is a curative treatment for hepatocellular carcinoma (HCC). Percutaneous RFA has been shown to be beneficial for patients with small renal cell carcinoma (RCC) lacking indications for resection. We experienced the case of a 53-year-old male who had conditions that suggested HCC, RCC, and alcoholic liver cirrhosis. Abdominal contrast-enhanced computed tomography (CT) and magnetic resonance image showed liver cirrhosis with 2.8 cm ill-defined mass in segment 2 of the liver and 1.9 cm hypervascular mass in the left kidney. These findings were compatible with the double primary cancers of HCC and RCC. Transarterial chemoembolization (TACE) was performed to treat the HCC. After the TACE, a focal lipiodol uptake defect was noticed on a follow up CT images and loco-regional treatment was recommended. Therefore, we performed RFAs to treat HCC and RCC. There was no evidence of recurrence in the follow up image after 1 month.

Background/AimsQuantitation of hepatitis B surface antigen (HBsAg) is an increasingly popular method to determine the treatment response in chronic hepatitis B (CHB) patients. The clinical value of HBsAg level measurement during rescue therapy for lamivudine (LMV)-resistant CHB patients have not been evaluated to date. Therefore, this study investigated the correlation between HBsAg level and treatment response in LMV-resistant CHB patients treated with adefovir (ADV) add-on therapy.MethodsLMV-resistant CHB patients treated with LMV-ADV combination therapy for over 2 years were included. HBsAg levels were measured at 6 month intervals until 1 year, and annually thereafter. Treatment response was assessed by determining the virological response (VR, undetectable HBV DNA levels) during treatment.ResultsFifty patients were included, of which 40 showed a VR. HBsAg levels were not different significantly at baseline (4.0 vs. 3.6 Log10 IU/mL, P=0.072). However, the HBsAg level decreased after 6 months of treatment in patients with a VR and became different significantly between the groups thereafter (3.9 vs. 3.3 at 6 months, P=0.002; 3.8 vs. 3.2 at 1 year, P=0.004; 3.9 vs. 3.2 at 2 years, P=0.008; 3.7 vs. 3.1 at 3 years, P =0.020).ConclusionsThe HBsAg level at 6 months after treatment can help predict treatment response.

Background/AimsA revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal.MethodsThe medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis.ResultsSix hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD.ConclusionsBoth AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.

Background/AimsA close relationship has been established between nonalcoholic fatty liver disease (NAFLD) and an elevated risk of coronary heart disease (CHD), but little is known about the association between alcoholic fatty liver disease (AFLD) and CHD risk. The aim of this study was to determine whether AFLD is associated with elevated CHD risk.MethodsWe retrospectively enrolled 10,710 subjects out of 11,469 individuals who visited the Konkuk University Health Care Center for a routine health checkup in 2010. AFLD was diagnosed made when the usual amount of alcohol consumption exceeded 210 g/week in males and 140 g/week in females for the previous 2 years and when hepatic steatosis was detected by liver ultrasonography. The 10-year risk for CHD was estimated using the Framingham Risk Score.ResultsHepatic steatosis was diagnosed in 4,142 of the 10,710 individuals (38.7%); the remainder (i.e., n=6,568) became the control group. The 4,142 individuals with hepatic steatosis were divided into two groups: NAFLD (n=2,953) and AFLD (n=1,189). The risk of CHD was higher in AFLD (6.72±0.12) than in the control group (5.50±0.04, P

Background/AimsThe modification of the Model for End-Stage Liver Disease (MELD) scoring system (Refit MELD) and the modification of MELD-Na (Refit MELDNa), which optimized the MELD coefficients, were published in 2011. We aimed to validate the superiority of the Refit MELDNa over the Refit MELD for the prediction of 3-month mortality in Korean patients with cirrhosis and ascites.MethodsWe reviewed the medical records of patients admitted with hepatic cirrhosis and ascites to the Konkuk University Hospital between January 2006 and December 2011. The Refit MELD and Refit MELDNa were compared using the predictive value of the 3-month mortality, as assessed by the Child-Pugh score.ResultsIn total, 530 patients were enrolled, 87 of whom died within 3 months. Alcohol was the most common etiology of their cirrhosis (n=271, 51.1%), and the most common cause of death was variceal bleeding (n=20, 23%). The areas under the receiver operating curve (AUROCs) for the Child-Pugh, Refit MELD, and Refit MELDNa scores were 0.754, 0.791, and 0.764 respectively; the corresponding values when the analysis was performed only in patients with persistent ascites (n=115) were 0.725, 0.804, and 0.796, respectively. The significant difference found among the Child-Pugh, Refit MELD, and Refit MELDNa scores was between the Child-Pugh score and Refit MELD in patients with persistent ascites (P=0.039).ConclusionsRefit MELD and Refit MELDNa exhibited good predictability for 3-month mortality in patients with cirrhosis and ascites. However, Refit MELDNa was not found to be a better predictor than Refit MELD, despite the known relationship between hyponatremia and mortality in cirrhotic patients with ascites.

Doubanjiang, a Chinese traditional fermented red pepper paste, is eaten worldwide for its unique flavor. The objective of this study was to evaluate the aroma quality of doubanjiang using solvent-assisted flavor evaporation (SAFE) and headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). A total of 165 volatile compounds, belonging to 13 chemical classes, were identified. Esters and hydrocarbons were the predominant groups. Thirteen aroma-active compounds were detected by AEDA of SAFE and HS-SPME, and their odor activity values (OAVs) were calculated by dividing their concentration by their odor threshold in water. Among them, ethyl isovalerate, β-damascenone, 3-isobutyl-2-methoxypyrazine (IBMP), and sotolone had the highest OAVs (>1000). In addition, sotolone, methional, β-damascenone, 3-isobutyl-2-methoxypyrazine, ethyl isovalerate, phenylethyl alcohol and linalool had high flavor dilution (FD) factors. Sotolone, β-damascenone and 3-isobutyl-2-methoxypyrazine were identified for the first time in doubanjiang and played significant roles in its aroma quality.

Background/AimsQuantification of the hepatitis B surface antigen (HBsAg) is increasingly used to determine the treatment response in patients with chronic hepatitis B (CHB). However, there are limited data about the clinical implications of Quantification of HBsAg long-term nucleoside analogue treatment for CHB. We investigated the clinical correlation between HBsAg level and clinical course in patients with CHB who are treated long-term with nucleoside analogues.MethodsPatients with CHB who started lamivudine or entecavir monotherapy before June 2007 were enrolled. HBsAg was quantified at baseline, at 6 months, and at 1, 2, 3, 4, and 5 years of treatment. We compared data between the groups according to the presence or absence of a virological response (VR) and resistance.ResultsForty-eight patients were analyzed. There was no definite reduction in HBsAg level during the early period of treatment; differences in HBsAg levels between baseline and each time point were significant only at 5 years (P=0.028). In a subgroup analysis, this difference was significant only in non-resistant patients at 5 years (P=0.041).ConclusionsThere was no definite decrease in the HBsAg level during the early period of nucleoside analogue treatment, with long-term treatment being required to observe a significant reduction.

Background/AimsLamivudine (LAM) plus adefovir (ADV) combination therapy has been accepted as one of the best treatments for LAM-resistant chronic hepatitis B (CHB). The aim of this study was to determine the efficacy of this combination therapy in hepatocellular carcinoma (HCC) patients.MethodsThe medical records of CHB patients who developed LAM resistance and were treated with LAM plus ADV combination therapy for more than 6 months were reviewed. Their virological response (VR; undetectable HBV DNA) and biochemical response (BR; alanine aminotransferase normalization) were evaluated, and the findings of HCC and non-HCC patients were compared.ResultsThe data from 104 patients (19 with HCC and 85 without HCC) were analyzed. The VR rates did not differ significantly between the HCC and non-HCC groups: 33.3% vs. 55.6% at 12 months (P=0.119), 58.3% vs. 67.2% at 24 months (P=0.742), 50% vs. 69.8% at 36 months (P=0.280), and 66.7% vs. 71.0% at 48 months (P=1.000). The BR rates also did not differ significantly between the groups: 55.6% vs. 84.0% at 12 months (P=0.021), 58.3% vs. 83.8% at 24 months (P=0.057), 70.0% vs. 77.8% at 36 months (P=0.687), and 66.7% vs. 80.6% at 48 months (P=0.591).ConclusionsThe efficacy of LAM plus ADV combination therapy is comparable in HCC and non-HCC patients.

Background/AimsWhile gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.MethodsThe data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.ResultsThe initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P

Background/AimsThis study evaluated the clinical outcomes of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hemorrhage from gastric varices (GV) in Korean patients with liver cirrhosis (LC).MethodsWe retrospectively analyzed data from 183 LC patients who underwent BRTO for GV bleeding in 6 university-based hospitals between January 2001 and December 2010.ResultsOf the 183 enrolled patients, 49 patients had Child-Pugh (CP) class A LC, 105 had CP class B, and 30 had CP class C at the time of BRTO. BRTO was successfully performed in 177 patients (96.7%). Procedure-related complications (e.g., pulmonary thromboembolism and renal infarction) occurred in eight patients (4.4%). Among 151 patients who underwent follow-up examinations of GV, 79 patients (52.3%) achieved eradication of GV, and 110 patients (72.8%) exhibited marked shrinkage of the treated GV to grade 0 or I. Meanwhile, new-appearance or aggravation of esophageal varices (EV) occurred in 54 out of 136 patients who underwent follow-up endoscopy (41.2%). During the 36.0±29.2 months (mean±SD) of follow-up, 39 patients rebled (hemorrhage from GV in 7, EV in 18, nonvariceal origin in 4, and unknown in 10 patients). The estimated 3-year rebleeding-free rate was 74.8%, and multivariate analysis showed that CP class C was associated with rebleeding (odds ratio, 2.404; 95% confidence-interval, 1.013-5.704; P=0.047).ConclusionsBRTO can be performed safely and effectively for the treatment of GV bleeding. However, aggravation of EV or bleeding from EV is not uncommon after BRTO; thus, periodic endoscopy to follow-up of EV with or without prophylactic treatment might be necessary in LC patients undergoing BRTO.

PurposeTo characterize and pharmacologically influence subconjunctival lymphatics in rabbit and mouse eyes.MethodsRabbits received subconjunctival injections of trypan blue or fixable fluorescent dextrans. Bleb-related outflow pathways were quantified. Immunofluorescence for vessel-specific markers (lymphatics [podoplanin and LYVE-1] and blood vessels [CD31]) were performed in native rabbit conjunctiva and after fixable fluorescent dextran injection. Vascular endothelial cell growth factor-C (VEGFC) was injected subconjunctivally in rabbits. mRNA and protein were assessed for the above markers using RT-PCR and Western blot. Alternatively, mouse studies used Prox1-tdTomato transgenic reporter mice. Subconjunctival injection conditions included: no injection, balanced salt solution (BSS), VEGFC, 5-fluorouracil (5FU) and two concentrations of mitomycin-C (MMC). Two mouse injection protocols (short and long) with different follow-up times and number of injections were performed. Mouse eyes were enucleated, flat mounts created, and subconjunctival branching and length assessed.ResultsRabbit eyes demonstrated clear bleb-related subconjunctival outflow pathways that were distinct from blood vessels and were without nasal/temporal predilection. Immunofluorescence against vessel-specific markers showed lymphatics and blood vessels in rabbit conjunctiva, and these lymphatics overlapped with bleb-related subconjunctival outflow pathways. Subconjunctival VEGFC increased lymphatic (P = 0.004-0.04) but not blood vessel (P = 0.77-0.84) mRNA or protein in rabbits. Prox1-tdTomato transgenic reporter mice demonstrated natively fluorescent lymphatics. Subconjunctival VEGFC increased murine lymphatic branching and length (P ≤ 0.001-0.004) while antimetabolites (P ≤ 0.001-0.043) did the opposite for the long protocol.DiscussionSubconjunctival lymphatics are pharmacologically responsive to both VEGFC and antimetabolites in two animal models studied using different methodologies. These results may be important for bleb-forming glaucoma surgeries or ocular drug delivery.

BackgroundMutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator 1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion.MethodsVarious mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration.ResultsPiezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouting. Finally, we assessed a potential therapeutic value of Piezo1 activation in lymphatic regeneration and found that a Piezo1 agonist, Yoda1, effectively suppressed postsurgical lymphedema development.ConclusionsPiezo1 is an upstream mechanosensor for the lymphatic mechanotransduction pathway and regulates lymphatic growth in response to external physical stimuli. Piezo1 activation presents a novel therapeutic opportunity for preventing postsurgical lymphedema. The Piezo1-regulated lymphangiogenesis mechanism offers a molecular basis for Piezo1-associated lymphatic malformation in humans.

This study critically examines the current state of democracy in higher education in Korea, which is being threatened by neoliberalism, and suggests new tasks to make progress in the democratization of higher education. The prevalence of authoritarian culture in universities makes it difficult to form a democratic structure of reflection and discussion. In addition, the hierarchical system of educational capital derived from neoliberalism has led to exclusion and discrimination in university society. In particular, the employment insecurity system of professors further encourages discrimination among faculty members within the university community. Finally, the competitive financial support system among universities threatens the democratic and autonomous ecosystem of universities by forcing them to obey government policies rather than critique them. Historically, the universities in Korea have been able to expand rapidly, receiving full support from the nation and citizens. During this process, a special position has been guaranteed to the universities. This study argues that the social responsibility of higher education in Korea should be strengthened to advance toward a new democracy. Challenging institutional tasks to be carried out by Korean universities are also suggested.