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Background : Endotension is one of the detrimental complications after endovascular aneurysm repair (EVAR) and surgical management has been considered as standard of care. However, there is a paucity of data regarding the findings and outcomes of such surgical intervention. The aim of this study was to investigate intraoperative findings and outcomes of surgical treatment for endotension after EVAR. Methods : Between January 2005 and October 2018, of the 708 patients who underwent EVAR for aneurysm aortic aneurysm; 12 patients (mean age of 76.1; range 66–88) who underwent open repair for endotension were retrospectively analyzed. The anatomical characteristics of the aorta and surgical findings were reviewed. The rates of early and late procedural complications, and overall mortality were evaluated. Results : The median interval between the EVAR and surgical conversion was 45.9 months (range 17.1–46.9). Three of the twelve patients underwent emergency surgery due to aneurysm rupture. The median aneurysm sac size, the proximal neck diameter, and the proximal neck length before EVAR were 64 mm, 23.5 mm, and 30.5 mm, respectively, that changed before open repair to 93.5 mm (p = .02), 25 mm (p = .011), and 23 mm (p = .003), respectively. In four of the twelve patients, radiographically undetected endoleak was identified during surgery to be Type Ia, Ib, II, and III, respectively. The rates of early and late procedural complications, and overall mortality were 8.3%, 8.3% and 8.3%, respectively. Conclusions : Patients with endotension have a risk of delayed endoleak and aneurysm rupture; secondary intervention should be performed in such cases to prevent fatal complications. Surgical treatment appears to be a curative treatment for endotension with favorable outcomes. In addition, the possibility of an undetected endoleak should be considered as a potential cause of endotension.

Thromboelastography (TEG) is diagnostic modality that analyzes real-time blood coagulation parameters. Clinically, TEG primarily allows for directed blood component resuscitation among patients with acute blood loss and coagulopathy. The utilization of TEG has been widely adopted in among other surgical specialties; however, its use in vascular surgery is less prominent. We aimed to provide an up-to-date review of TEG utilization in vascular and endovascular surgery.Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a literature review with the Medical Subject Headings (MeSH) terms "TEG and arterial events", "TEG and vascular surgery", "TEG and vascular", "TEG and endovascular surgery", "TEG and endovascular", "TEG and peripheral artery disease", "TEG and prediction of arterial events", "TEG and prediction of complications ", "TEG and prediction of thrombosis", "TEG and prediction of amputation", and "TEG and amputation" was performed in Cochrane and PubMed databases to identify all peer-reviewed studies of TEG utilization in vascular surgery, written between 2000 and 2021 in the English language. The free-text and MeSH subheadings search terms included diagnosis, complications, physiopathology, surgery, mortality, and therapy to further restrict the articles. Studies were excluded if they were not in humans or pertaining to vascular or endovascular surgery. Additionally, case reports and studies with limited information regarding TEG utilization were excluded. Each study was independently reviewed by two researchers to assess for eligibility.Of the 262 studies identified through the MeSH strategy, 15 studies met inclusion criteria and were reviewed and summarized. Literature on TEG utilization in vascular surgery spanned cerebrovascular disease (n = 3), peripheral arterial disease (n = 3), arteriovenous malformations (n = 1), venous thromboembolic events (n = 7), and perioperative bleeding and transfusion (n = 1). In cerebrovascular disease, TEG may predict the presence and stability of carotid plaques, analyze platelet function before carotid stenting, and compare efficacy of antiplatelet therapy after stent deployment. In peripheral arterial disease, TEG has been used to predict disease severity and analyze the impact of contrast on coagulation parameters. In venous disease, TEG may predict hypercoagulability and thromboembolic events among various patient populations. Finally, TEG can be utilized in the postoperative setting to predict hemorrhage and transfusion requirements.This systematic review provides an up-to-date summarization of TEG utilization in multiple facets of vascular and endovascular surgery.

Summary Objective Although cartilage degeneration and invasion of the subchondral bone plate in entheseal lesion has been considered to consequently lead bony ankylosis in ankylosing spondylitis (AS), no evident mechanisms are known. Design To identify histopathological and physiological changes in enthesitis-related ankylosis in AS, we performed molecular characterization of transcription factors and surface markers, and transcriptome analysis with human tissues. Entheseal tissue containing subchondral bone was obtained from the facet joints of 9 patients with AS and 10 disease controls, and assessed by using differential staining techniques. Enthesis cells were isolated, characterized, stimulated with TNF and/or IL-17A, and analysed by cell-based experimental tools. Results We found diffusely distributed granular tissue and cartilage in the subchondral bone in AS. Co-expression of SOX9, a specific transcription factor in cartilage, and matrix metalloproteinase 13 (MMP13) was found in the granular tissues within the subchondral bone from AS patients. Intriguingly, SOX9 expression was significantly higher in AS enthesis cells than controls and correlated with TNFR1 and IL-17RA expressions, which is important for high reactivity to TNF and IL-17A cytokines. Co-stimulation by TNF and IL-17A resulted in accelerated mineralization/calcification features, and increased OCN expression in AS enthesis cells. Furthermore, SOX9 overexpression in enthesis leads to promoting mineralization feature by TNF and IL-17A stimuli. Finally, OCN expression is elevated in the destructive enthesis of advanced AS. Conclusion These findings provide insight into the links between inflammation and the mineralization of entheseal tissue as the initiation of spinal ankylosis, emphasizing the importance of SOX9+ enthesis cells.

Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Background and Aims Endoscopic ultrasound-guided through-the-needle biopsy (EUS-TTNB) using microbiopsy forceps is performed for the accurate diagnosis of pancreatic cystic lesions (PCLs). However, there are no standardized protocols for this procedure, and the amount of data on its efficacy is limited. Here, we evaluated the feasibility, efficacy, and safety of EUS-TTNB in categorizing the types of PCLs, and identified the factors associated with diagnostic failure. Methods The prospectively collected and maintained EUS-TTNB database at Asan Medical Center was reviewed to identify patients with PCL who underwent EUS-TTNB between January 2019 and January 2021. The primary outcomes were technical success, diagnostic yield, and adverse events. Factors contributing to diagnostic failure, and the discrepancies in the diagnosis made by conventional modalities (ie, EUS-morphology, cross-sectional imaging, and cystic fluid analysis) were also evaluated. Results A total of 45 patients were analyzed. EUS-TTNB was successfully performed in all patients (technical success = 100%). Histologic diagnosis of PCL was made in 37 patients (diagnostic yield = 82%). When comparing EUS-TTNB with presumptive diagnosis, EUS-TTNB changed the diagnosis in 10 patients in terms of the categorization of the types of PCLs. The diagnostic yield was significantly higher in those who had 4 or more visible biopsy specimens per session (93%) than in those with less than 4 visible biopsy specimens per session (67%; P = .045). During follow-up, 3 (7%) patients experienced adverse events (2 acute pancreatitis, 1 intracystic bleeding), and no life-threatening adverse event occurred. Conclusions EUS-TTNB showed high technical feasibility, diagnostic yield, and good safety profile. EUS-TTNB may improve the categorization of the types of PCLs. Studies with standardized procedure protocols are needed to reduce the diagnostic failure for the types of PCLs.

Background/Aims: Helicobacter pylori (H. pylori) seroconversion may occur during screening for gastric cancer. Our study aimed to assess the number of seroconverted subjects with H. pylori and their results in follow-up tests.Methods: Data were consecutively collected on subjects who were H. pylori-seronegative and presented for gastric cancer screening. Subjects who were followed up using the same serology test and pepsinogen (PG) assays on the day of endoscopy were included in the study.Results: During the follow-up of 57.7±21.4 months, 61 (15.0%) of 407 seronegative subjects showed seroconversion. H. pylori infection was detected in six (9.8%) of 61 seroconverted subjects. A diffuse red fundal appearance, with a significant increase in the Kyoto classification scores for gastritis, was observed in the infected subjects (p

Purpose This study aimed to evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC).Materials and Methods A total of 133 patients with histologically confirmed HPC were included from eight institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 patients (64%). The prognostic effects of sex, age, performance, World Health Organization (WHO) grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses.Results The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p < 0.001) and PFS (p < 0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001), or STR (p < 0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003).Conclusion This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.

Background Seroprevalence studies of coronavirus disease 2019 (COVID-19) cases, including asymptomatic and past infections, are important to estimate the scale of the disease outbreak and to establish quarantine measures. We evaluated the clinical performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays available in Korea for use in seroprevalence studies. Methods The sensitivity, specificity, cross-reactivity, and interference of five SARS-CoV-2 antibody assays were evaluated using the following: 398 serum samples from confirmed COVID-19 patients, 510 negative control samples from before 2018 (pre-pandemic), 163 serum samples from patients with SARS, Middle East respiratory syndrome (MERS), and other viral infections, and five samples for the interference study. Results The sensitivities of the five assays ranged from 92.2% to 98%, and their specificities, including cross-reactivity and interference, ranged from 97.5% to 100%. The agreement rates were excellent (kappa >0.9). Adjustment of the cutoff values could be considered through ROC curve analysis. The positive predictive values of the individual assays varied from 3.5% to 100% at a 0.1% prevalence but were as high as ≥95% when two assays were combined. Conclusions The prevalence of COVID-19 in Korea is considered to be exceptionally low at present; thus, we recommend using a combination of two or more SARS-CoV-2 antibody assays rather than a single assay. These results could help select SARS-CoV-2 antibody assays for COVID-19 seroprevalence studies in Korea.

Objective : To investigate the clinical efficacy and safety of the controlled distraction-compression technique using an expandable titanium cage (ETC) in posttraumatic kyphosis (PTK).Methods : We retrospectively studied and collected data on 20 patients with PTK. From January 2014 to December 2017, the controlled distraction-compression technique using ETC was consecutively performed in 20 patients with PTK of the thoracolumbar zone (range, 36–82 years). Among them, nine were males and 11 were females and the mean age was 61.5 years. The patients were followed regularly at 1, 3, 6, and 12 months, and the last follow-up was more than 2 years after surgery.Results : The mean follow-up period was 27.3±7.3 months (range, 14–48). The average operation time was 286.8±33.1 minutes (range, 225–365). The preoperative regional kyphotic angle (RKA) ranged from 35.6° to 70.6° with an average of 47.5°±8.1°. The immediate postoperative mean RKA was 5.9°±3.8° (86.2% correction rate, p=0.000), and at the last follow-up more than 2 years later, the mean RKA was 9.2°±4.9° (80.2% correction rate, p=0.000). The preoperative mean thoracolumbar kyphosis was 49.1°±9.2° and was corrected to an average of 8.8°±5.3° immediately after surgery (p=0.000). At the last follow-up, a correction of 11.9°±6.3° was obtained (p=0.000). The preoperative mean back visual analog scale (VAS) score was 7.9±0.8 and at the last follow-up, the VAS score was improved to a mean of 2.3±1.0 with a 70.9% correction rate (p=0.000). The preoperative mean Oswestry disability index (ODI) score was 32.3±6.9 (64.6%) and the last follow-up ODI score was improved to a mean of 6.85±2.9 (3.7%) with a 78.8% correction rate (p=0.000). The overall complication was 15%, with two of distal junctional fractures and one of proximal junctional kyphosis and screw loosening. However, there were no complications directly related to the operation.Conclusion : Posterior vertebral column resection through the controlled distraction-compression technique using ETC showed safe and good results in terms of complications, and clinical and radiologic outcomes in PTK. However, to further evaluate the efficacy of this surgical procedure, more patients need long-term follow-up and there is a need to apply it to other diseases.

Background Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) can be used for the differential diagnosis of pancreatic lesions by evaluating microvascular circulation and patterns of contrast enhancement. However, routine use of CEH-EUS is limited by its high cost, the lack of contrast agent availability and the absence of expertise with this technique. Directional eFLOW (D-eFLOW) (Aloka Co., Ltd., Tokyo, Japan) was introduced as a new high-definition modality that detects blood flow in microvessels. Because it uses built-in functions, it entails no additional cost and reduces time for examination. The present study compared the usefulness of D-eFLOW and CEH-EUS for differential diagnosis of pancreatic and peripancreatic lesions. Methods This retrospective study analyzed 130 patients who underwent EUS and D-eFLOW examinations from January 2016 to March 2020 to evaluate pancreatic and peripancreatic masses. Results All 130 patients underwent D-eFLOW and CEH-EUS examinations. Histological diagnoses were confirmed in 130 patients by EUS-FNA and/or surgery. D-eFLOW and CEH-EUS showed good correlation in evaluating the vascularity of pancreatic and peripancreatic tumors (Fisher's exact test, p Conclusions In evaluating the characteristics of tumorous lesions, vascularity detected by D-eFLOW showed good correlation with enhancement patterns of CEH-EUS. D-eFLOW can be considered a good alternative to CEH-EUS in diagnosing pancreatic and peripancreatic masses.

TFEB, a key regulator of lysosomal biogenesis and autophagy, is induced not only by nutritional deficiency but also by organelle stress. Here, we find that Tfeb and its downstream genes are upregulated together with lipofuscin accumulation in adipose tissue macrophages (ATMs) of obese mice or humans, suggestive of obesity-associated lysosomal dysfunction/stress in ATMs. Macrophage-specific TFEB-overexpressing mice display complete abrogation of diet-induced obesity, adipose tissue inflammation and insulin resistance, which is independent of autophagy, but dependent on TFEB-induced GDF15 expression. Palmitic acid induces Gdf15 expression through lysosomal Ca2+-mediated TFEB nuclear translocation in response to lysosomal stress. In contrast, mice fed a high-fat diet with macrophage-specific Tfeb deletion show aggravated adipose tissue inflammation and insulin resistance, accompanied by reduced GDF15 level. Finally, we observe activation of TFEB–GDF15 in ATMs of obese humans as a consequence of lysosomal stress. These findings highlight the importance of the TFEB–GDF15 axis as a lysosomal stress response in obesity or metabolic syndrome and as a promising therapeutic target for treatment of these conditions. Kim et al. reveal that TFEB expression is protective in the setting of diet-induced obesity by activating the expression of GDF15 in adipose tissue macrophages in mice and humans.

Aims Fibrosis-4 index (FIB-4) and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) are the two most widely used non-invasive tools for screening of advanced fibrosis in subjects with NAFLD. Since metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed as a new category of fatty liver disease, we aimed to compare the diagnostic performance of FIB-4 and NFS in subjects with MAFLD and in various subgroups. Methods This study was designed as cross-sectional study. Data from 6,775 subjects who underwent magnetic resonance elastography (MRE) and abdominal ultrasonography at the same time during a health check-up at 13 various health check-up centers were retrospectively reviewed. Advanced fibrosis was defined as an MRE value of ≥3.6 kPa. Results The area under the receiver operating characteristic curves (AUROCs) of FIB-4 and NFS for diagnosing advanced fibrosis were similar in subjects with MAFLD. However, the AUROC of NFS was lower than that of FIB-4 in the diabetic subgroup of MAFLD (0.809 in FIB-4 vs. 0.717 in NFS, P = 0.002). The performances of both FIB-4 and NFS were poor in the subgroup of MAFLD with significant alcohol intake. Conclusions The overall diagnostic performance of FIB-4 and NFS for diagnosing advanced fibrosis did not differ among subjects with MAFLD. However, the performance of NFS was lower in the diabetes subgroup of MAFLD. The diagnostic performance of FIB-4 was better for fibrosis in various subgroups of MAFLD. This article is protected by copyright. All rights reserved.

Background:During high tibial osteotomy (HTO), the superficial medial collateral ligament (sMCL) is cut or released at any degree to expose the osteotomy site and achieve the targeted alignment correction according to the surgeon’s preference. However, it is still unclear whether transection of sMCL increases valgus laxity.Purpose:We aimed to assess the outcomes and safety of sMCL transection, especially focusing on iatrogenic valgus instability.Study Design:Case series; Level of evidence, 4.Methods:Seventy-two patients (89 knees) who underwent medial open wedge HTO (MOWHTO) with transection of the sMCL between October 2013 and September 2018 were retrospectively investigated. Clinical evaluations, including the International Knee Documentation Committee (IKDC) score, Knee injury and Osteoarthritis Outcome Score (KOOS), and Tegner and Lysholm scores, were performed preoperatively and at 2 years postoperatively. The radiographic parameters hip-knee-ankle (HKA) angle, joint line convergence angle on standing radiographs (standing JLCA), and weightbearing line (WBL) ratio were assessed preoperatively and at 3 months, 6 months, 1 year, and 2 years postoperatively. To evaluate valgus laxity, we assessed the valgus JLCA and medial joint opening (MJO) at the aforementioned time points using valgus stress radiographs.Results:All clinical results at the 2-year follow-up were significantly improved compared with those obtained at the preoperative assessment ( P < .001). The postoperative HKA angle significantly differed from the preoperative one, and no significant valgus progression was observed during follow-up (preoperative, 8.5°± 2.7°; 3 months, –3.5°± 2.0°; 6 months, –3.2°± 2.3°; 1 year, –3.1°± 2.3°; 2 years, –2.9°± 2.5°; P < .001) The mean WBL ratio was 62.5% ± 9.0% at 2 years postoperatively. The postoperative valgus JLCA at all follow-up points did not significantly change compared with the preoperative valgus JLCA (preoperative, –0.1°± 2.1°; 3 months, –0.2°± 2.4°; 6 months, –0.1°± 2.5°; 1 year, 0.1°± 2.5°; 2 years, 0.2°± 2.2°) The postoperative MJO at all follow-up points did not significantly change compared with the preoperative MJO (preoperative, 7.1 ± 1.7 mm; 3 months, 7.0 ± 1.7 mm; 6 months, 6.9 ± 1.9 mm; 1 year, 6.7 ± 1.8 mm; 2 years, 6.8 ± 1.8 mm).Conclusion:Transection of the sMCL during MOWHTO does not increase valgus laxity and could yield desirable clinical and radiographic results.

We developed a novel therapeutic radioligand, [177Lu]1h, with an albumin binding motif and evaluated it in a prostate-specific membrane antigen (PSMA)-expressing tumor xenograft mouse model. Fourteen PSMA target candidates were synthesized, and binding affinity was evaluated with an in vitro competitive binding assay. First, four compound candidates were selected depending on binding affinity results. Next, we selected four compounds ([68Ga]1e, [68Ga]1g, [68Ga]1h, and [68Ga]1k) were screened for tumor targeting efficiency by micro–positron emission tomography/computed tomography (micro-PET/CT) imaging. Finally, [177Lu]1h compound was evaluated the tumor targeting efficiency and therapeutic efficiency by micro–single-photon emission computed tomography/computed tomography (micro-SPECT/CT), biodistribution, and radiotherapy studies. Estimated human effective dose was calculated by biodistribution data. Compound 1h showed a high binding affinity (Ki value = 4.08 ± 0.08 nmol/L), and [177Lu]1h showed extended blood circulation (1 hour = 10.32 ± 0.31, 6 hours = 2.68 ± 1.07%ID/g) compared to [177Lu]PSMA-617 (1 h = 0.17 ± 0.10%ID/g). [177Lu]1h was excreted via the renal pathway and showed high tumor uptake (24.43 ± 3.36%ID/g) after 1 hour, which increased over 72 hours (72 hours = 51.39 ± 9.26%ID/g). Mice treated with 4 and 6 MBq of [177Lu]1h showed a median survival rate of >61 days. In particular, all mice treated with 6 MBq of [177Lu]1h survived for the entire monitoring period. The estimated human effective dose of [177Lu]1h was 0.07 ± 0.01 and 0.03 ± 0.00 mSv/MBq in total body and kidney, respectively. The current study indicates that [177Lu]1h has the potential for further investigation of metastatic castration-resistant prostate cancer (mCRPC) therapy in clinical trials.

Various perivascular drug delivery techniques have been demonstrated for localized post-treatment of intimal hyperplasia: a vascular inflammatory response caused by endothelial damages. Although most perivascular devices have focused on controlling the delivery duration of anti-proliferation drug, the confined and unidirectional delivery of the drug to the target tissue has become increasingly important. In addition, careful attention should also be paid to the luminal stability and the adequate exchange of vascular protein or cell between the blood vessel and extravascular tissue to avoid any side effect from the long-term application of any perivascular device. Here, a highly flexible and porous silk fibroin microneedle wrap (Silk MN wrap) is proposed to directly inject antiproliferative drug to the anastomosis sites while ensuring sufficient vascular exchanges. Drug-embedded silk MNs were transfer-molded on a highly flexible and porous silk wrap. The enhanced cell compatibility, molecular permeability, and flexibility of silk MN wrap guaranteed the structural integrity of blood vessels. Silk wrap successfully supported the silk MNs and induced multiple MN penetration to the target tissue. Over 28 days, silk MN wrap significantly inhibited intimal hyperplasia with a 62.1% reduction in neointimal formation.

Background We evaluated feasibility, safety, and total resource use of subcutaneous immunoglobulin (SCIG) in a pilot study of patients who underwent allogeneic hematopoietic cell transplant (HCT) over a 6-month period. Methods A total of 20 eligible patients were treated with SCIG at 0.1 g/kg/week for up to 6 months. Patients were matched to 20 concurrent intravenous immunoglobulin (IVIG) controls. Clinical outcomes measured included adverse reactions, healthcare resource use, patient satisfaction, and quality of life (QOL). (ClinicalTrials.gov Identifier: NCT03401268.) Results Groups were comparable in terms of age, weight, sex, transplant indication, donor type, and conditioning intensity. All 20 IVIG patients completed 6 consecutive months of therapy compared with 13/20 (65%) SCIG patients. There were no adverse reactions in IVIG patients, compared with six (30%) SCIG patients. All adverse reactions in SCIG patients were grade I, transient, and required no medical intervention. Median overall cost per patient was lower with SCIG than with IVIG ($9,756 vs. $13,780, p = .046). Among patients who completed 6 months of SCIG, median preference and satisfaction scores were 100%. Over the 6-month period, QOL scores remained stable in SCIG patients. Conclusions In a subgroup of patients, SCIG was associated with high patient satisfaction and a reduction in total healthcare costs compared with IVIG in a cohort of HCT patients.

BACKGROUND Drain fluid amylase is commonly used as a predictor of pancreatic fistula after pancreaticoduodenectomy (PD). This study aimed to determine the ideal cut-off value of drain fluid amylase on postoperative day 1 (DFA1) for predicting pancreatic fistula after pancreaticogastrostomy (PG). METHODS Prospective data of 272 consecutive patients undergoing PG between 2010 and 2020 was collected and analysed to determine the postoperative pancreatic fistula (POPF) risk factors. RESULTS The incidence of POPF was 143 cases (52.6%). The median DFA1 in patients with POPF was significantly higher than that of patients with NO-POPF (5483 versus 311, P

This study evaluated the prognostic value of leukocyte, lymphocyte, and neutrophil counts in anal cancer patients undergoing concurrent chemoradiotherapy (CCRT). Multi-institutional retrospective data review included 148 non-metastatic anal cancer patients treated with definitive CCRT with 5-fluorouracil plus mitomycin C between the year 2001 and 2019. The median radiation dose to the primary tumor was 54 Gy with a median pelvic dose of 45 Gy. Median follow-up duration was 56 months, and complete blood cell counts were analyzed from baseline to 1 year after the completion of radiotherapy. Although most patients showed a normal number of blood cells before treatment, 6.1% and 4.1% of patients showed leukocytosis (> 10,000/μl) and neutrophilia (> 7500/μl), respectively. After the initiation of treatment, seven patients (4.7%) displayed grade 4 lymphopenia (

BACKGROUND & AIMS Atezolizumab plus bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial. Further evaluation is necessary to investigate the safety and efficacy of Ate/Bev in real settings. METHODS This was a multicentre retrospective analysis. Between May 2020 and February 2021, 138 patients received Ate/Bev as first-line treatment for advanced HCC from 11 institutions. We excluded patients with Child-Pugh B or C and BCLC D stage, and the remaining 121 patients were included in this analysis. RESULTS According to RECIST 1.1, the objective response and disease control rates were 24.0% and 76.0%. The median follow-up duration was 5.9 months (95% confidence interval [CI], 5.4-6.4), the median progression-free survival (PFS) was 6.5 months (95% CI, 4.1-9.0), and median overall survival (OS) was not reached (95% CI, not available). The most frequent grade 3-4 adverse event was aspartate aminotransferase elevation (10.7%). In the multivariate analyses, AFP increase (P = .037), baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 5 (P = .023), and best response to stable disease or progressive disease (P = .019) were significantly associated with worse PFS. Macrovascular invasion (P = .048) and baseline NLR ≥5 (P

The integrity of the vestibulo-ocular reflex (VOR) remains to be delineated in patients with parkinsonism. We aimed to define the findings of the VOR using head-impulse tests (HITs) and their differential diagnostic value in patients with Parkinson’s disease (PD) and multiple system atrophy (MSA). From December 2019 to January 2021, 30 patients with PD and 23 patients with MSA (17 with cerebellar-type MSA and 6 with parkinsonian-type MSA) had a video-oculographic recording of HITs at two university hospitals in South Korea. Reversed (p = 0.034) and perverted (p = 0.015) catch-up saccades were more frequently observed in MSA than in PD during HITs. The gain difference between the ACs and the PCs were larger in MSA than in PD (p = 0.031), and positively correlated with the disease duration in patients with MSA (Spearman’s coefficient = 0.512, p = 0.012). Multivariate logistic regression analysis showed that reversed (p = 0.044) and perverted (p = 0.039) catch-up saccades were more frequently associated with MSA than with PD during HITs. In conclusion, HITs aid in differentiation of MSA from PD, and may serve as a surrogate marker for the clinical decline.

BACKGROUND AND AIM Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. METHODS This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. RESULTS A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P

We report the response process of the Laboratory Analysis Task Force (LATF) for Unknown Disease Outbreaks (UDOs) at the Korea Disease Control and Prevention Agency (KDCA) during January 2020 to coronavirus disease 2019 (COVID-19), which developed as a UDO in Korea. The advanced preparedness offered by the laboratory diagnostic algorithm for UDOs related to respiratory syndromes was critical for the rapid identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enabled us to establish and expand the diagnostic capacity for COVID-19 on a national scale in a timely manner.

Summary Background The prognosis of patients with advanced biliary tract cancer who have progressed on gemcitabine plus cisplatin is dismal. We aimed to investigate the efficacy and safety of second-line liposomal irinotecan plus fluorouracil and leucovorin in patients with metastatic biliary tract cancer that has progressed on gemcitabine plus cisplatin. Methods This multicentre, open-label, randomised, phase 2b (NIFTY) study was done at five academic institutions in South Korea and included patients aged 19 years or older with histologically or cytologically confirmed metastatic biliary tract cancer that had progressed on first-line gemcitabine plus cisplatin and an Eastern Cooperative Oncology Group performance status of 0 or 1. By use of an interactive web-based response system integrated with an electronic data capture system, patients were randomly assigned (1:1) using permuted blocks (block size 4) to receive either intravenous liposomal irinotecan (70 mg/m2 for 90 min) plus intravenous leucovorin (400 mg/m2 for 30 min) and intravenous fluorouracil (2400 mg/m2 for 46 h) every 2 weeks or leucovorin and fluorouracil only every 2 weeks, and were stratified by primary tumour site, previous surgery with curative intent, and participating centre. Study treatment was continued until the patient had disease progression or unacceptable toxicities, or withdrew consent. The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival. The primary endpoint and safety were assessed in the full analysis set and the safety analysis set, respectively, both of which comprised all randomly assigned patients who received at least one dose of the study treatment. This trial is registered with ClinicalTrials.gov , NCT03524508 , and enrolment is complete. Findings Between Sept 5, 2018, and Feb 18, 2020, 193 patients were screened for eligibility, of whom 174 (88 in the liposomal irinotecan plus fluorouracil and leucovorin group and 86 in the fluorouracil plus leucovorin group) were enrolled and included in the full analysis and safety analysis sets. At a median follow-up of 11·8 months (IQR 7·7–18·7), the median BICR-assessed progression-free survival was significantly longer in the liposomal irinotecan plus fluorouracil and leucovorin group (7·1 months, 95% CI 3·6–8·8) than in the fluorouracil and leucovorin group (1·4 months, 1·2–1·5; hazard ratio 0·56, 95% CI 0·39–0·81; p=0·0019). The most common grade 3–4 adverse events were neutropenia (21 [24%] of 88 in the liposomal irinotecan plus fluorouracil and leucovorin group vs one [1%] of 86 in the fluorouracil and leucovorin group) and fatigue or asthenia (11 [13%] vs three [3%]). Serious adverse events occurred in 37 (42%) patients receiving liposomal irinotecan plus fluorouracil and leucovorin and 21 (24%) patients receiving fluorouracil and leucovorin. There were no treatment-related deaths. Interpretation Adding liposomal irinotecan to fluorouracil and leucovorin significantly improved BICR-assessed progression-free survival in patients with advanced biliary tract cancer. Liposomal irinotecan plus fluorouracil and leucovorin could be considered a standard-of-care second-line therapy for advanced biliary tract cancer. Funding Servier and HK inno.N Translation For the Korean translation of the abstract see Supplementary Materials section.

Please see the Editorial Comment by Douglas S. Katz discussing this article. BACKGROUND. Adoption of low-dose CT for the diagnosis of appendicitis has been slow in children and in adults, partly be...

Objective: Circulating progenitor cells possess immune modulatory properties and might mitigate inflammation that is characteristic of patients with coronary artery disease. We hypothesized that patients with fewer circulating progenitor cells (CPCs) will have higher inflammatory markers and worse outcomes. Approach and Results: Patients with stable coronary artery disease were enrolled in a prospective study enumerating CPCs as CD (cluster of differentiation)-34–expressing mononuclear cells (CD34+) and inflammation as levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein) levels. Patients were followed for 5 years for the end points of death and myocardial infarction with repeat inflammatory biomarkers measured after a median of 2 years. In the entire cohort of 392 patients, IL-6 and high-sensitivity CRP levels remained unchanged (0.3±2.4 pg/mL and 0.1±1.0 mg/L; P =0.45) after 2 years. CPC counts (log-transformed) were inversely correlated with the change in IL-6 levels (r, −0.17; P Conclusions: Reduced cardiovascular regenerative capacity is independently associated with progressive inflammation in patients with coronary artery disease that in turn is associated with poor outcomes. Graphic Abstract: A graphic abstract is available for this article.

BACKGROUND Total laparoscopic distal gastrectomy for early gastric cancer has been widely accepted; however, reduced-port laparoscopic distal gastrectomy has not gained the same popularity because of technical difficulties and oncologic safety issues. This study aimed to analyze the oncologic safety and short-term surgical outcomes of patients who underwent reduced-port laparoscopic distal gastrectomy (RpLDG) for gastric cancer. METHODS Consecutive patients who underwent surgical treatment between January 2016 and May 2018 were included in this study. Of the 833 patients enrolled, 158 underwent RpLDG and were propensity-matched with 158 patients who underwent conventional port laparoscopic distal gastrectomy (CpLDG). The groups were compared in terms of short-term outcomes and disease-free and overall survival rates. RESULTS The RpLDG group had shorter operation times (161.8 min vs. 189.0 min, p < 0.00) and shorter postoperative hospital stays (7.6 days vs. 9.1 days, p = 0.04) compared to the CpLDG group. Estimated blood loss was lower in the RpLDG group than in the CpLDG group (52.6 mL vs. 73.7 mL, p < 0.00), while hospital costs incurred by the RpLDG group were lower than those of the CpLDG group (10,033.7 vs. 11,016.8 USD, p < 0.00). No statistical differences were found regarding overall morbidity and occurrence of surgical complications of grade III or higher, as defined by the Clavien-Dindo classification. Furthermore, no significant differences between RpLDG and CpLDG were found in 3-year disease-free (99.4% vs. 98.1%; p = 0.42) and 3-year overall survival rates (98.7% vs. 96.8%; p = 0.25). CONCLUSION Patients who underwent RpLDG had better short-term surgical outcomes than those who underwent CpLDG in terms of operation time, estimated blood loss, duration of hospital stay, and hospital costs. The oncologic safety of RpLDG was satisfactory.

Purpose: To report a case of Exophiala endophthalmitis after cataract surgery, which has not been reported previously in Korea.Case summary: A 70-year-old woman visited the hospital 7 days after cataract surgery in her right eye with unilateral vision impairment. At the time of the visit, visual acuity of the right eye was hand motion, and the fundus was not clearly observed due to numerous inflammatory cells with hypopyon in the anterior chamber. With an initial diagnosis of suspected bacterial endophthalmitis, vitrectomy was performed immediately with intravitreal injection of antibiotics and steroid. On day 14 after vitrectomy, inflammation in the anterior chamber and vitreous opacity worsened, and complete vitrectomy, including of the vitreous base, and removal of the intraocular lens and capsule was performed. Exophiala was detected in the biopsy specimen on day 6 after the second surgery, and the patient was discharged with a prescription for voriconazole eye drops. On day 23 after the second surgery, the best-corrected visual acuity in the right eye had improved to 1.0, and there was no evidence of endophthalmitis recurrence and no observed additional abnormal findings of the fundus until 6 months after second surgery.Conclusions: In a case of fungal endophthalmitis that occurred after cataract surgery, good results were obtained by vitrectomy involving complete removal of the peripheral vitreous body, including the intraocular lens and lens capsule, which was the basis for growth of the fungus in the early stage of endophthalmitis.

Background Retroperitoneal neurogenic tumors are extremely rare pathological entities; therefore, few clinical features and natural courses, especially originating from the pancreatic/peripancreatic regions, have been reported. This study aimed to investigate the clinicopathological features of pancreatic and peripancreatic neurogenic tumors and assess the diagnostic value of computed tomography (CT) and endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). Methods Between 2006 and 2018, patients who were diagnosed with neurogenic tumors were included. In total, 90 histologically confirmed cases of neurogenic tumors located in the pancreatic/peripancreatic regions were selected for analysis. Results The mean age was 49.2 ± 13.1 years. There were no differences in sex distribution of the tumors. Schwannomas (44.4%) and paragangliomas (41.1%) were the most common neurogenic tumors. The sensitivity of CT was 62.2% in 90 cases. EUS-FNB was performed in 30 cases and the sensitivity of it was 83.3%. The diagnosis of neurogenic tumors with EUS-FNB or CT was not significantly associated with tumor location and size. Surgical resection was performed in 78 cases. Of the 12 patients who did not undergo surgery, 10 cases were followed-up without any increase in tumor size. Conclusions Through the present study, we verified radiological, pathological, and clinical aspects of the pancreatic/peripancreatic neurogenic tumors which little known before, therefore, this study can serve as the basis for research to present an optimal diagnosis and treatment of neurogenic tumors. In addition, EUS-FNB is useful in the diagnosis of pancreatic/peripancreatic neurogenic tumors with relatively high sensitivity and can help establish therapeutic plans before the surgery.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a multilevel problematic disease. Major septal deviation (SD) can lead to severe nasal congestion, which, in turn, can lead to sleep apnea. Although SD seems to be related to OSA, very few studies have quantitatively examined this relationship. In this study, we investigate this using a 9-year large-scale cohort study. METHODS: The SD group was selected out of 1 million individuals randomly extracted by the National Health Insurance Service. The non-SD group was obtained through propensity score matching considering several variables. The primary end point was OSA diagnosis. RESULTS: The study (SD) group included 11,238 individuals and the non-SD group (control group) included 22,476 persons. The overall hazard ratio for OSA in the SD group was 4.39 (95% confidence interval [CI]: 3.56–5.42). In subgroup analysis, the hazard ratio for OSA of male individuals was 3.77 (95% CI: 2.83–5.03), high economic status was 1.27 (95% CI: 1.05–1.56), metropolitan area was 1.31 (95% CI: 1.07–1.62), young age was 0.79 (95% CI: 0.64–0.98), hypertension was 1.00 (95% CI: 0.37–2.7), and diabetes mellitus was 2.44 (95% CI: 1.15–5.21). In the SD group, the hazard ratio for OSA after septoplasty was 0.71 (95% CI: 0.54–0.94). CONCLUSIONS: From long-term follow-up, the prevalence of OSA was 4.39 times higher in the SD group compared with the control group. This phenomenon was more pronounced with increasing body mass index and decreased significantly after septoplasty. CITATION: Yeom SW, Chung SK, Lee EJ, et al. Association between septal deviation and OSA diagnoses: a nationwide 9-year follow-up cohort study. J Clin Sleep Med. 2021;17(10):2099–2106.

Background The interest in vascular substitutes has recently increased. We evaluated the feasibility of using a homologous parietal peritoneum as a vascular substitute for venous reconstruction during abdominal surgery. Methods The inferior vena cava was replaced with a homologous parietal peritoneum after cross-linking with glutaraldehyde in 36 rabbits. At 7, 14, and 28 days, the patency rate, outer and inner graft diameters, histology, and immunohistochemistry were evaluated. Results Both the 7- and 14-day groups maintained vascular patency. Vascular patency was maintained in 3 rabbits in the 28-day group. The inner diameters of the anastomotic sites were 6.23 ± 0.18, 5.64 ± 0.16, and 2.34 ± 0.21 mm in the 7-day, 14-day, and 28-day groups, respectively. The midpoint inner diameters of the homologous parietal peritoneum grafts were 624 ± 0.46, 5.74 ± 0.26, and 2.14 ± 0.28 mm in each group, respectively. Endothelial cell proliferation on the homologous parietal peritoneum graft surfaces in all groups was based on the histological findings from the first group. Multiple neovascularizations of the homologous parietal peritoneum graft were found in the 14- and 28-day groups, indicating neo-media formation. Acute inflammation appeared to progress to the entire layer of the homologous parietal peritoneum graft without an intraluminal thrombus, but the graft was patent in the 14-day group. In the 28-day group, 6 rabbits showed near-total occlusion and a thrombus formed in the homologous parietal peritoneum graft at the anastomosis site with severe stricture; however, the rabbits were alive and had collateral vessel formation. Conclusion Using homologous parietal peritoneum is feasible for venous reconstruction in abdominal surgery.

Objective As the average life span in modern society continues to increase, much interest is focused on high-risk procedures in elderly patients, including major surgical operations. We investigated the results of endovascular coiling of unruptured intracranial aneurysms (UIA) in patients over 80 years of age. Methods We retrospectively analyzed 39 patients aged over 80 years who underwent coil embolization for UIA between April 2007 and April 2019 at our hospital. Results Complete occlusion on digital subtraction angiography (DSA) immediately after surgery was performed in 44 (84.6%) of 52 cases of cerebral aneurysms. Four patients (7.7%) had residual aneurysmal necks, and four (7.7%) had contrast flow in the aneurysmal sac. Follow-up magnetic resonance angiography (mean: 8.2 months) was performed in 37 aneurysms in 24 patients. There was evidence of blood flow in the neck in seven cases (18.9%) and aneurysm in two cases (5.4%). Follow-up DSA (mean: 20.5 months) was performed in 14 aneurysms in 11 patients, and 11 aneurysms (78.6%) had complete occlusion, 1 aneurysm (7.1%) had an aneurysmal neck, and 2 aneurysms (14.3%) had contrast filling into the aneurysmal sac. Coil embolization procedure-related complications occurred in 3 patients (7.7%). Cerebral infarction occurred in 1 (2.6%), arterial dissection in 1 (2.6%), and hypoesthesia in 1 (2.6%). Conclusions Active treatment of UIA in elderly patients over 80 years of age through endovascular coil embolization can be considered.

Background Oropharyngeal cancer (OPC) exhibits diverse immunological properties; however, their implications for immunotherapy are unknown. Methods We analysed 37 surgically resected and nine recurrent or metastatic anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-treated OPC tumours. OPCs were classified into immune-rich (IR), mesenchymal (MS) and xenobiotic (XB) subtypes based on RNA-sequencing data. Results All IR type tumours were human papillomavirus (HPV) positive, most XB types were HPV negative, and MS types showed mixed HPV status. The IR type showed an enriched T cell exhaustion signature with PD-1+ CD8+ T cells and type I macrophages infiltrating the tumour nest on multiplex immunohistochemistry. The MS type showed an exclusion of CD8+ T cells from the tumour nest and high MS and tumour growth factor-β signatures. The XB type showed scant CD8+ T cell infiltration and focal CD73 expression. The IR type was associated with a favourable response signature during anti-PD-1/PD-L1 therapy and showed a high APOBEC mutation signature, whereas the MS and XB types showed resistance signature upregulation. Among anti-PD-1/PD-L1-treated OPC patients, the IR type showed a favourable clinical response (3/4 patients), whereas the XB type showed early progression (3/3 patients). Conclusion Our analysis classified OPCs into three subtypes with distinct immune microenvironments that are potentially related to the response to anti-PD-1/PD-L1 therapy.

Arterial stiffness is a precursor for the development of hypertension and premature cardiovascular disease (CVD). Physical activity has been associated with lower arterial stiffness among largely White populations, but the types of activity required and whether these findings apply to Black adults remain unknown. We examined whether physical activity levels were associated with arterial stiffness among Black adults in two independent cohorts. In the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity, 378 Black adults (age 52.8 ± 10.3, 39.7% male) without known CVD living in Atlanta, GA were recruited. Arterial stiffness was measured as pulse wave velocity (PWV). Total and domain-specific physical activity were assessed by self-report. Multiple linear regression models were used to investigate differences across physical activity levels after adjusting for age, sex, CVD risk factors, and socioeconomic status. Findings were validated in an independent cohort of Black adults ( n = 55, age 50.4 ± 9.2, 23.6% male). After adjustment for covariates, lower arterial stiffness was associated with higher self-reported levels of sport/exercise (6.92 ± 1.13 vs 7.75 ± 1.14, p < 0.001, highest vs lowest quartile) and home/life activities (7.34 ± 1.24 vs 7.73 ± 1.07, p = 0.04, highest vs lowest quartile), but not work, active living, or the overall physical activity scores. These findings were replicated in the independent cohort where higher levels of sport/exercise remained associated with lower arterial stiffness (6.66 ± 0.57 vs 8.21 ± 0.66, p < 0.001, highest vs lowest quartile). Higher levels of sport/exercise and home/life-related physical activities (in comparison to occupational physical activity) are associated with lower arterial stiffness in Black adults.

Backgrounds/Aims: This study was performed to reveal the usefulness of the trabecular bone score (TBS) in assessing bone strength in patients with ankylosing spondylitis (AS) in comparison with dual-energy X-ray absorptiometry (DXA) methods.Methods: A total of 215 AS patients (75.8% male) were enrolled from a single university hospital in Korea. Demographic and clinical information were assessed. Patients completed X-rays of the cervical and lumbar spine (L-spine), and spinal ankyloses were quantified using the modified Stoke AS Spine Score (mSASSS). Hip, anteroposterior and lateral L-spine bone mineral density (BMD) and TBS were assessed by DXA methods. Clinical characteristics and bone strength measurement results were compared between male and female AS patients. The accuracy of each bone strength evaluation method in predicting Fracture Risk Assessment Tool (FRAX) scores indicating moderate or higher fracture risk was compared by receiver operating characteristic curves in patients aged ≥ 40 years. Correlations between each bone strength measurement method and mSASSS were examined.Results: Male patients showed higher mSASSS and less prevalent peripheral joint involvement compared to female patients (p < 0.05). TBS, hip BMD, and L-spine lateral BMD showed comparably high areas under the curve (AUCs) for predicting FRAX-major osteoporotic fractures (MOF) ≥ 10% (AUC ranged 0.72 to 0.76). TBS negatively correlated with mSASSS in both male and female patients (p < 0.01).Conclusions: TBS could predict the risk of MOF and is not influenced by spinal osteoproliferation in AS patients, even in those with advanced spinal changes.

Iatrogenic vertebral artery injury (VAI) that occurs during cervical spine surgery can cause life-threatening complications, such as arteriovenous fistulas, catastrophic bleeding, neurological impairment, cerebral ischemia, and death. We report a case of dominant VAI during surgery and the treatment of a 60-year-old man diagnosed with a C1-2-3 metastatic spine tumor from urothelial carcinoma. Active bleeding occurred during tumor resection using pituitary forceps, immediately followed by gauze packing and manual compression. Post further resection, we found that the vertebral artery (VA) was completely severed. After temporary clamping on both sides of the damaged VA, an artificial graft anastomosis was performed. After verifying that the flow was intact using Doppler Sonography, Occiput-C1-4-5-6 posterolateral fusion was performed. Angiography was performed immediately after surgery. We found a thrombus occluding the left VA, and performed mechanical thrombectomy and stent insertion. The final angiography showed good VA flow with no emboli. In this case, VA anastomosis and endovascular treatment were performed within a relatively short period of time post VAI, and the patient was able to recover without any neurological deficits.

Autoimmune gastritis is a corpus-dominant type of gastritis with positive serum anti-parietal cell antibodies (APCA) and/or anti-intrinsic factor antibodies. Serum APCA and pepsinogen (PG) assays were performed in subjects with corpus-dominant gastritis detected by endoscopy. Serum APCA was positive in five patients. All these patients were postmenopausal women (four Koreans and one Caucasian from the Russian Federation) with a mean age of 59.0±3.2 years. They displayed low PG I levels ranging from 8.1 to 18.8 ng/mL (mean, 11.4±4.8 ng/mL) and low PG I/II ratios ranging from 0.7 to 2.4 (mean, 1.2±0.7). Three of the patients were being treated for autoimmune thyroiditis. Multiple gastric neuroendocrine tumors were observed in two Helicobacter pylori (H. pylori)-naive patients with high serum gastrin levels exceeding 700 pg/mL and serum chromogranin A levels exceeding 1,000 ng/mL. In the remaining three patients, intestinal metaplasia was observed in the biopsied specimens from the antrum, suggesting a history of H. pylori infection. Our findings indicate the value of positive serum APCA findings, low serum PG I levels, and low serum PG I/II ratios in confirming autoimmune gastritis in patients showing corpus-dominant atrophy, regardless of their H. pylori infection status.

DA-9601 is an extract obtained from Artemisia asiatica, which has been reported to have anti-inflammatory effects on gastrointestinal lesions; however, its possible anti-inflammatory effects on the small intestine have not been studied yet. Therefore, in this study, we investigated the protective effects of DA-9601 against the ACF-induced small intestinal inflammation. Inflammation of the small intestine was confirmed by histological studies and the changes in the CD4+ T cell fraction induced by the inflammation-related cytokines, and the inflammatory reactions were analyzed. Multifocal discrete small necrotic ulcers with intervening normal mucosa were frequently observed after treatment with ACF. The expression of IL-6 , IL-17, and TNF-α genes was increased in the ACF group; however, it was found to have been significantly decreased in the DA-9601 treated group. In addition, DA-9601 significantly decreased the levels of proinflammatory mediators such as IL-1β, GMCSF, IFN-γ, and TNF-α; the anti-inflammatory cytokine IL-10, on the other hand, was observed to have increased. It is known that inflammatory mediators related to T cell imbalance and dysfunction continuously activate the inflammatory response, causing chronic tissue damage. The fractions of IFN-γ+ Th1 cells, IL-4+ Th2 cells, IL-9+ Th9 cells, IL-17+ Th17 cells, and Foxp3+ Treg cells were significantly decreased upon DA-9601 treatment. These data suggest that the inflammatory response induced by ACF is reduced by DA-9601 via lowering of the expression of genes encoding the inflammatory cytokines and the concentration of inflammatory mediators. Furthermore, DA-9601 inhibited the acute inflammatory response mediated by T cells, resulting in an improvement in ACF-induced enteritis.

Objective Many epidemiological studies have observed the association of air pollutant exposure with the onset, progression, and mortality of stroke. The aim of this study was to investigate the associations of air pollutants, including SO2, NO2, O3, CO, and PM10, with stroke according to exposure duration. Methods Data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2015 were obtained. The 21,240 patients who were admitted for or died due to stroke were 1:4 matched for age, sex, income, and region of residence with 84,960 control participants. The meteorological factors of mean, highest, and lowest temperatures; relative humidity; ambient atmospheric pressure; and air pollutant concentrations (SO2, NO2, O3, CO, and PM10) were analyzed to determine their associations with stroke. The odds ratios for stroke after exposure to each meteorological factor and air pollutant at 7 and 30 days were calculated in the stroke and control groups. Subgroup analyses were conducted according to age, sex, income, and region of residence. Results The odds ratio associated with seven days of exposure to CO was 1.16 (95% CI = 1.04–1.31) in stroke patients. For 30 days of exposure, the odds ratio associated with CO was 1.16 (95% CI = 1.02–1.32) in stroke patients. Seven and 30 days of NO2 exposure were inversely associated with stroke. The odds ratio associated with seven days of exposure to O3 was 1.16 (95% CI = 1.01–1.32) in ischemic stroke patients. Both ischemic and hemorrhagic stroke had negative associations with 7 and 30 days of NO2 exposure. Conclusion Both short- and long-term exposure to CO were related to stroke.

The coronavirus disease 2019 (COVID-19) pandemic has reduced the ability to prevent or control chronic disease due to the concerns about safety in accessing health care. Inflammatory bowel disease (IBD) is a chronic condition requiring long- term sustained treatment, which is difficult in the current panedemic situation. The Korean Association for the Study of Intestinal Diseases (KASID) has developed an expert consensus statement on the clinical practice management of adult inflammatory bowel disease during the COVID-19 pandemic. This expert consensus statement is based on guidelines and clinical reports from several countries around the world. It provides recommendations to deal with the risk of COVID-19 and medication use in IBD patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and emphasizes the importance of right treatment approach to avoid worsening of the disease condition in IBD patients.

The value of squamous-cell carcinoma antigen (SCC-Ag) as a tumor marker for cervical cancer is controversial because it is not elevated (> 2 ng/mL) in a quarter of patients at diagnosis. Two hundred ninety one IB-IVA cervical squamous cell-carcinoma patients who underwent definitive chemoradiotherapy (CRT) were included in four tertiary institutions. Serum conversion pattern between pre- and post-treatment SCC-Ag levels was categorized into the following three arms: (1) Consistent Seronegative arm (both ≤ 2 ng/mL); (2) Negative Conversion arm (from > 2 ng/mL to ≤ 2 ng/mL); and (3) Consistent Seropositive arm (both > 2 ng/mL). Median follow-up time was 40.3 months. For Consistent Seronegative (N = 67), Negative Conversion (N = 165), and Consistent Seropositive (N = 59) arms, the 3-year recurrence-free survival (RFS) rates were 79.4%, 62.0%, and 48.4% (P

Objective A shorter door-to-puncture time is an independent predictor of good clinical outcomes in patients with acute ischemic stroke (AIS) who undergo mechanical thrombectomy (MT). We recently initiated a protocol for direct care from neurointerventionalists (NIs) in the emergency department (ED) rather than from non-NI neurologists for patients with AIS. Our aim was to investigate whether NIs, as the first point-of-care physicians for stroke in the ED, could shorten door-to-puncture time compared to non-NI neurologists. Methods From January 2020 to December 2020, 50 patients with AIS underwent MT at our hospital. Patients were divided into 2 groups based on the type of physician who provided initial care for stroke in the ED: (a) NI group (n = 20) and (b) non-NI group (n = 30). The door-to-puncture time was retrospectively analyzed. Results The NI group had a significantly shorter door-to-puncture time than the non-NI group (135.2 ± 50.0 minutes vs. 167.2 ± 54.3 minutes, P = 0.040). A door-to-puncture time of ≤120 minutes was more frequently achieved in the NI group than in the non-NI group (55.0% vs. 23.3%, P = 0.022). Multivariable logistic regression analysis revealed that a door-to-puncture time of ≤120 minutes was independently associated with the NI group (adjusted odds ratio 4.098, 95% confidence interval 1.085–15.479, P = 0.037). Conclusions Our study showed that NIs, as the first point-of-care stroke physicians in the ED, were associated with shorter door-to-puncture times. We suggest that NIs should be at the forefront of care for patients with AIS in the acute setting by performing triage and deciding on and performing MT.

Tantalizing connections between type 2 diabetes and degenerative lumbar spine disorders have become increasingly evident. However, the association of type 2 diabetes with degenerative lumbar spine disorders remains unclear. We sought to clarify the association between type 2 diabetes and lumbar spine disorders using nationwide data in Korea. Furthermore, we explored the association of diabetes with the prevalence of spinal procedures. The data in this study was obtained from Korean health claim database. Between 2016 and 2019, totals of 479,680 diabetes and 479,680 age- and sex-matched control subjects were enrolled. Patients with diabetes had more likely to have degenerative lumbar spine disorders and spinal procedures than controls. Using multivariate-adjusted analysis, patients with diabetes were at increased risk of being concomitantly affected by lumbar disc disorder [adjusted odds ratio 1.11 (95% confidence interval 1.10–1.12)], lumbar spondylotic radiculopathy [1.12 (1.11–1.13)], spondylolisthesis [1.05 (1.02–1.08)] and spinal stenosis [1.16 (1.15–1.18)], compared to controls. Furthermore, diabetic patients had an increased risk of undergoing lumbar spinal injection [1.13 (1.12–1.14)], laminectomy [1.19 (1.15–1.23)], and fusion surgery [1.35 (1.29–1.42)]. We demonstrated that type 2 diabetes was significantly associated with lumbar spine disorders and frequent spinal procedures. Our results suggest diabetes as a predisposing factor for lumbar spine disorders.

Background: Acute kidney injury (AKI) is a major complication after cardiac surgery and significantly affects postoperative mortality and morbidity. This study was conducted to evaluate the association between target pump flow to achieve adequate oxygen delivery (DO2) and postoperative renal function after aortic valve replacement.Methods: From January 2017 to May 2020, 281 patients (male:female, 160:121; mean age, 68±11 years) who underwent aortic valve replacement were retrospectively reviewed. Target pump flow was calculated based on DO2 level of 280 mL/min/m2. The primary endpoint was postoperative renal dysfunction, defined as the ratio of postoperative peak creatinine level to preoperative value. The ratio of the lowest actual pump flow to the ideal target pump flow, other hemodynamic variables related with cardiopulmonary bypass, intraoperative transfusion, and preoperative characteristics were analyzed to identify factors associated with the primary endpoint using a multivariable linear regression model.Results: Preoperative and peak postoperative creatinine levels were 0.94±0.33 mg/dl and 1.15±0.56 mg/dl, respectively (ratio, 1.22±0.33). The ideal target pump flow was 4.70±0.59 L/min, whereas the lowest actual pump flow was 3.77±0.47 L/min (ratio, 0.81±0.13). The multivariable model showed that the ratio of the lowest pump flow to target pump flow (β±standard error, –0.405±0.162, P=0.013), as well as sex, stroke history, emergency operation, and transfusion of red blood cells were associated with the primary endpoint.Conclusions: Low actual nadir pump flow compared to the ideal target pump flow based on DO2 is associated with the risk of AKI after aortic valve replacement.

Purpose: Few studies have demonstrated the clinical significance of pretreatment serum albumin and globulin in prostate cancer (PCa). This study evaluated the association between the pretreatment albumin to globulin ratio (AGR) and clinicopathologic characteristics of nonmetastatic PCa in a large multicenter setting in Korea. Materials and Methods: This study involved 742 patients with nonmetastatic PCa who underwent radical prostatectomy (RP) in seven institutions between January 2011 and December 2012. The AGR was calculated as follows: albumin/(total protein−albumin). Patients were divided into low and high AGR groups by a cutoff value from a receiver operating characteristic curve analysis. Results: The best cutoff for the AGR was set at 1.53. The area under the curve of the AGR was 0.624 (95% confidence interval, 0.557–0.671; p

Sebaceous carcinoma is a malignant neoplasm that usually arises in the sebaceous glands of the eyelids. Its pathogenesis is unknown; however, irradiation history, immunosuppression, and use of diuretics are known risk factors. The mainstay of treatment for sebaceous carcinoma of the eyelid is wide surgical resection with a safety margin of 5 to 6 mm, which often results in full-thickness defects. The reconstruction of a full-thickness defect of the eyelid should be approached using a three-lamella method: a mucosal component replacing the conjunctiva, a cartilage component for the tarsal plate, and a flap or skin graft for the skin of the eyelid. In this case, a fullthickness defect of the upper eyelid was reconstructed after tumor removal using a combination of a nasal septum chondromucosal composite graft and a forehead transposition flap, also known as a “Fricke flap.” The flap was designed to include a line of the eyebrow on the lower margin of the flap to replace the eyelash removed during tumor excision. The wound healed completely, without any early or late complications, and the outcome was satisfactory.

BACKGROUND AND AIMS Biliary tract cancer (BTC) exhibits diverse molecular characteristics. However, reliable biomarkers that predict therapeutic responses are yet to be discovered. We aimed to identify the molecular features of treatment responses to chemotherapy and immunotherapy in BTCs. APPROACH AND RESULTS We enrolled 121 advanced BTC patients (68 cholangiocarcinomas [33 intrahepatic, 35 extrahepatic], 41 gallbladder cancers, and 12 Ampulla of Vater cancers) whose specimens were analyzed by clinical sequencing platforms. All patients received first-line palliative chemotherapy; 48 patients underwent programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy after failed chemotherapy. Molecular and histopathological characterization was performed using targeted sequencing and immunohistochemical staining to investigate treatment response-associated biomarkers. Genomic analysis revealed a broad spectrum of mutational profiles according to anatomical location. Favorable responses to chemotherapy were observed in the small-duct type compared with the large-duct type intrahepatic cholangiocarcinoma, with frequent mutations in BRCA1-associated protein-1/isocitrate dehydrogenase 1/2 and KRAS proto-oncogene, GTPase/SMAD family member 4 genes, respectively. The molecular features were further analyzed in BTCs, and transforming growth factor beta and DNA damage response pathway-altered tumors exhibited poor and favorable chemotherapy responses, respectively. In PD-1/PD-L1 blockade-treated patients, KRAS alteration and chromosomal instability tumors were associated with resistance to immunotherapy. The majority of patients (95.0%) with these resistance factors show no clinical benefit to PD-1/PD-L1 blockade and low tumor mutational burdens. Low tumor-infiltrating lymphocyte (TIL) density in tumors with these resistance factors indicated immune-suppressive tumor microenvironments, whereas high intratumoral TIL density was associated with a favorable immunotherapy response. CONCLUSIONS This study proposes predictive molecular features of chemotherapy and immunotherapy responses in advanced BTCs using clinical sequencing platforms. Our result provides an intuitive framework to guide the treatment of advanced BTCs benefiting from therapeutic agents based on the tumors' molecular features.

Allogeneic hematopoeitic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF). We evaluate the impact of various factors on survival outcomes post-transplant in MF. Data of 89 consecutive MF patients (primary 47%) who underwent allo-HCT between 2005 and 2018 was evaluated. Fifty-four percent patients had received JAK1/2 inhibitors (JAKi) pre-HCT. The median CD34 count was 7.1x106 cells/kg. Graft failure was seen in 10% of the patients. Grade 3-4 acute GVHD (aGVHD) and moderate/severe chronic graft versus host disease (cGVHD) occurred in 24% and 40% patients, respectively. Two-year overall survival (OS) and relapse free survival (RFS) were 51% and 43%, respectively. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 2 years were 11% and 46%, respectively. Higher CD34 cell dose (≤5 × 106 cells/kg vs 5-9 or ≥9 × 106 cells/kg) and lower pre-HCT ferritin (