Endoplasmic reticulum (ER) stress plays a crucial role in liver diseases, affecting various types of hepatic cells. While studies have focused on the link between ER stress and hepatocytes as well as hepatic stellate cells (HSCs), the precise involvement of hepatic macrophages in ER stress-induced liver injury remains poorly understood. Here, we examined the effects of ER stress on hepatic macrophages and their role in liver injury. Acute ER stress led to the accumulation and activation of hepatic macrophages, which preceded hepatocyte apoptosis. Notably, macrophage depletion mitigated liver injury induced by ER stress, underscoring their detrimental role. Mechanistic studies revealed that ER stress stimulates macrophages predominantly via the PERK signaling pathway, regardless of its canonical substrate ATF4. hnRNPA1 has been identified as a crucial mediator of PERK-driven macrophage activation, as the overexpression of hnRNPA1 effectively reduced ER stress and suppressed pro-inflammatory activation. We observed that hnRNPA1 interacts with mRNAs that encode UPR-related proteins, indicating its role in the regulation of ER stress response in macrophages. These findings illuminate the cell type-specific responses to ER stress and the significance of hepatic macrophages in ER stress-induced liver injury. Collectively, the PERK-hnRNPA1 axis has been discovered as a molecular mechanism for macrophage activation, presenting prospective therapeutic targets for inflammatory hepatic diseases such as acute liver injury.

Hyponatremia overcorrection can result in irreversible neurologic impairment such as osmotic demyelination syndrome. Few prospective studies have identified patients undergoing hypertonic saline treatment with a high risk of hyponatremia overcorrection. Methods: We conducted a post hoc analysis of a multicenter, prospective randomized controlled study, the SALSA trial, in 178 patients aged above 18 years with symptomatic hyponatremia (mean age, 73.1 years; mean serum sodium level, 118.2 mEq/L). Overcorrection was defined as an increase in serum sodium levels by >12 or 18 mEq/L within 24 or 48 hours, respectively. Results: Among the 178 patients, 37 experienced hyponatremia overcorrection (20.8%), which was independently associated with initial serum sodium level (≤110, 110–115, 115–120, and 120–125 mEq/L with 7, 4, 2, and 0 points, respectively), chronic alcoholism (7 points), severe symptoms of hyponatremia (3 points), and initial potassium level (<3.0 mEq/L, 3 points). The NASK (hypoNatremia, Alcoholism, Severe symptoms, and hypoKalemia) score was derived from four risk factors for hyponatremia overcorrection and was significantly associated with overcorrection (odds ratio, 1.41; 95% confidence interval, 1.24–1.61; p < 0.01) with good discrimination (area under the receiver-operating characteristic [AUROC] curve, 0.76; 95% CI, 0.66–0.85; p < 0.01). The AUROC curve of the NASK score was statistically better compared with those of each risk factor. Conclusion: In treating patients with symptomatic hyponatremia, individuals with high hyponatremia overcorrection risks were predictable using a novel risk score summarizing baseline information.

Methods: This is a post hoc analysis of a prospective, controlled, randomized, unblinded study with 78 Korean hemodialysis patients receiving intravenous (n = 40) or subcutaneous (n = 38) erythropoietin therapy. We evaluated hemoglobin variability by calculating the frequency of hemoglobin measurements outside the target range during all visits. The high-frequency group was defined by those with hemoglobin variability over the median value (25%) while the low-frequency group was defined by those with hemoglobin variability of <25%. Results: In this analysis, 37 patients (51.1%) were men, and the mean age was 50.6 ± 12.5 years. Twenty-five patients (35.2%) had diabetes mellitus. The frequency of the value being outside the target hemoglobin range was higher in the subcutaneous group compared to the intravenous group (0.36 ± 0.19 vs. 0.27 ± 0.12/visit, p = 0.03). The low-frequency group required significantly lower erythropoietin doses compared to the high-frequency group. In the adjusted Cox analysis, the parameter high-frequency group was a significant independent risk factor for cardiovascular events (hazard ratio, 3.53; 95% confidence interval, 1.15–10.83; p = 0.03). Conclusion The risk of missing the target hemoglobin range increased with subcutaneous administration compared with intravenous erythropoietin administration in hemodialysis patients. An increased frequency of the value being outside the target hemoglobin range was also associated with an increased risk of cardiovascular events.

Objectives: . Vertebrobasilar dolichoectasia (VBD), an elongation and distension of vertebrobasilar artery, may present with cranial nerve symptoms due to nerve root compression. The objectives of this study are to summarize vestibulocochlear manifestations in subjects with VBD through a case series and to discuss the needs of thorough oto-neurotologic evaluation in VBD subjects before selecting treatment modalities. Methods: . Four VBD subjects with vestibulocochlear manifestations were reviewed retrospectively. VBD was confirmed by either brain or internal auditory canal magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Patient information, medical history, MRI/MRA findings, and audiometry or vestibular function tests were reviewed according to patient’s specific symptom. Results: . Of the four subjects, three presented with ipsilesional sensorineural hearing loss (SNHL), three with paroxysmal recurrent vertigo, and two with typewriter tinnitus. The MRI/MRA of the four subjects revealed unilateral VBD with neurovascular compression of cisternal segment or the brainstem causing displacement, angulation, or deformity of the cranial nerve VII or VIII that corresponded to the symptoms. Conclusion . Vestibulocochlear symptoms such as SNHL, recurrent paroxysmal vertigo, or typewriter tinnitus can be precipitated from a neurovascular compression of the vestibulocochlear nerve by VBD. Because proper medical or surgical treatments may stop the disease progression or improve audio-vestibular symptoms in subjects with VBD, a high index of suspicion and meticulous radiologic evaluation are needed when vestibulocochlear symptoms are not otherwise explainable, and if VBD is confirmed to cause audiovestibular manifestation, a thorough oto-neurotologic evaluation should be performed before initial treatment.

Methods: A nationwide database (2012–2016) acquired from the Korean Health Insurance Review and Assessment Service was analyzed. International disease categories in the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes, medical procedure codes, and examination codes were used to identify and sort OVCF patients aged >50 years. Results: There were 644,500 OVCF cases from 2012 to 2016. OVCF was most common in patients in their seventies (45%) and the number of patients increased from 117,361 in 2012 to 139,889 in 2016 (p <0.001). During 2012–2016, 8.9% of patients visited the emergency department; of those, 54.3% were hospitalized and 35% underwent magnetic resonance imaging. In OVCF treatment, bone cement augmentation rates increased from 23.4% in 2012 to 25.2% in 2016 (p <0.001), while conservative treatment rates slightly decreased from 76.5% in 2012 to 74.7% in 2016 (p <0.001). The total health insurance cost was $193,210,353.55 in 2012 and $281,968,877.65 in 2016. Conclusions The 5-year incidence of OVCF per 100,000 persons was 852.24 cases, and 45% of OVCF in South Korea occurred in patients in their seventies. The bone cement augmentation rate and total cost of OVCF are continuously increasing.

Purpose: Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. Materials and Methods: To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. Results: Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. Conclusion We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

BACKGROUND/AIMS: Hepatitis A virus (HAV) is a self-limiting infectious disease, but 1% of subjects develop fulminant hepatitis. The prevalence of the anti-HAV immunoglobulin G (IgG) antibody in hemodialysis subjects in Korea remains unknown. The purpose of this study was to describe and compare the seropositive rate of anti-HAV antibody among hemodialysis subjects in two hospitals according to age group. METHODS: A total of 170 hemodialysis subjects were evaluated for the seropositive rate of the anti-HAV IgG antibody and its titer. RESULTS: Of the 170 maintenance hemodialysis subjects in two hospitals (Kangnam 92 vs. Chuncheon 78), 79 (46.5%) were male. The mean age was 53.2 years old, and 94.1% of the subjects were over 40 years old. The median vintage of hemodialysis was 29.0 months. Anti-HAV antibody was found in 163 subjects (95.9%), with no significant difference between the two areas (Kangnam 97.8% [n = 90] vs. Chuncheon 93.6% [n = 73]). Subjects younger than 40 years old showed a seropositive rate of 50%, while the seropositive rate increased with age for subjects aged 40 or older (p for trend < 0.001). Seropositive subjects from Kangnam showed a higher anti-HAV antibody titer than those from Chuncheon (median: Kangnam 14.2 vs. Chuncheon 11.7). Only age influenced seropositivity. The only factor that influenced the antibody level was the location of hospital (p < 0.001). CONCLUSIONS The seropositive rate of the anti-HAV antibody in hemodialysis subjects was 95%, which is similar to findings in the general population. Active immunization against hepatitis A is strongly recommended for hemodialysis subjects under 40 years of age after anti-HAV testing.

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.

A paraffinoma is a type of inflammatory lipogranuloma that develops after the injection of an artificial mineral oil, such as paraffin or silicon, into the foreskin or the subcutaneous tissue of the penis for the purpose of penis enlargement, cosmetics, or prosthesis. The authors experienced a case of macro-paraffinoma associated with sexual dysfunction, voiding dysfunction, and pain caused by a buried glans penis after a paraffin injection for penis enlargement that had been performed 35 years previously. Herein, this case is presented with a literature review.
Foreskin ; Granuloma* ; Male ; Mineral Oil ; Oils ; Paraffin* ; Penis ; Prostheses and Implants ; Silicon ; Subcutaneous Tissue

BACKGROUND: We evaluated the efficacy of capsicum plaster, applied to the Chinese acupuncture point (acupoint) Pericardium 6 (P6), in reducing postoperative nausea and vomiting (PONV) in patients who underwent endoscopic sinus surgery (ESS). METHODS: One hundred and fifty patients scheduled for ESS were randomly placed in one of 3 groups. Each group had 50 patients. Inactive tape was affixed at both P6 acupoints and both shoulders in the control (placebo) group. Capsicum plaster was affixed at both P6 acupoints and inactive tape was affixed at both shoulders in the capsicum plaster (P6) group. Capsicum plaster was affixed at both shoulders and inactive tape at both P6 acupoints in the sham group. Plasters and tapes were affixed before the induction and removed 8 hours after surgery. RESULTS: The incidence of PONV and requirement for antiemetics were significantly lower in the P6 group than in the control and sham groups during the 24 hours after surgery. At postoperative 0-24 hour, nausea was 42% in the control group, 2% in the P6 group, and 38% in the sham group. Postoperative vomiting was 28%, 0% and 26%, respectively, and the use of antiemetics was 34%, 0% and 32%, respectively. CONCLUSIONS: Stimulation of the P6 acupoint with capsicum plaster is effective for preventing PONV at postoperative 0-24 hour in patients undergoing ESS.
Acupuncture Points* ; Antiemetics ; Asian Continental Ancestry Group ; Capsaicin ; Capsicum* ; Humans ; Incidence ; Nausea ; Pericardium ; Postoperative Nausea and Vomiting* ; Shoulder