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This study aimed to evaluate the permissible joint-line obliquity (JLO) based on radiologic and clinical outcomes with midterm follow-up after medial open-wedge high tibial osteotomy (MOWHTO).Patients who had undergone MOWHTO from March 2014 to May 2016 were retrospectively evaluated. They were divided into 4 groups based on JLO as represented by postoperative medial proximal tibial angle (MPTA). Radiologic parameters including MPTA, joint-line orientation angle (JLOA), joint-line convergence angle (JLCA), posterior tibial slope, weightbearing line ratio (WBLR), and coronal translation were analyzed. Clinical outcomes were evaluated with American Knee Society Score (AKSS), Western Ontario and McMaster University Index, and short-form 36 health survey (SF-36). The changes between preoperation and final follow-up in JLOA and MPTA were defined as ΔJLOA and ΔMPTA.A total of 135 knees were finally included (MPTA ≤90.32° as group I; 90.33° to 92.62° as group II; 92.74° to 95.22° as group III; and ≥95.23° as group IV). The last follow-up MPTA, JLOA, and JLCA values were different between the groups (P.001, P.001, and P = .015, respectively). WBLR and JLOA positively correlated with MPTA; however, WBLR showed an abrupt increase at MPTA96.5°, and the JLOA distribution tended to be greater than the regression line at MPTA96°. Moreover, ΔJLOA was not as large as ΔMPTA. The percentage of patients attaining a minimal clinically important difference was significantly lower in the AKSS-functional score and SF-36 physical component summary in group IV (P = .008 and 0.021, respectively).The JLOA did not change as much as the MPTA, but an MPTA95.2° abruptly increased the JLOA and valgus overcorrection after MOWHTO. Poor clinical outcomes were more evident in excessive MPTA (95.2°) than in mildly undercorrected or properly corrected MPTA (95.2°).III, retrospective cohort study.

Objectives The presence of a fistula between the thoracic aorta and the esophagus is a rare and highly fatal condition. This study aimed to evaluate the outcomes of the surgical treatment of an aortoesophageal fistula (AEF). Methods We retrospectively reviewed patients with AEF who underwent surgery at our institution. Results Between 2007 and 2018, a total of 10 patients who underwent surgery for AEF. The mean age was 63 ± 12 years, and 6 patients were men. Four patients had primary AEFs and 6 patients had secondary AEFs (3 graft replacements and 3 thoracic endovascular aortic repairs). The timing of AEF since graft replacement or thoracic endovascular aortic repairs was 21.6 ± 27 days. We performed aortic replacement with a prosthetic graft (4 patients) or a homograft (5 patients) and extra-anatomical bypass due to a previous aortic graft infection (1 patient). As a treatment of the esophagus, we conducted primary repair in 7 of 10 patients. The median lengths of hospital and intensive care unit stay were 59 days (range, 9-225 days) and 6.3 days (range, 1-87 days), respectively. Seven patients achieved oral feeding after a median 10.3 postoperative days (range, 7-78 postoperative days). Two of the 10 patients died of sepsis at 9 and 74 days postoperatively. Conclusions The strategy for patients with AEF should be individualized. Our surgical strategy for AEF, which includes simultaneous aortic graft replacement and primary repair of esophagus in the same operative field, is feasible and promising.

Background/Aims Improving quality of life has been gaining importance in ulcerative colitis (UC) management. The aim of this study was to investigate changes in health-related quality of life (HRQL) and related factors in patients with moderate-to-severe UC. Methods A multicenter, hospital-based, prospective study was performed using a Moderateto- Severe Ulcerative Colitis Cohort in Korea (the MOSAIK). Changes in HRQL, evaluated using the 12-Item Short Form Health Survey (SF-12) and Inflammatory Bowel Disease Questionnaire (IBDQ), were analyzed at the time of diagnosis and 1 year later. Results In a sample of 276 patients, the mean age was 38.4 years, and the majority of patients were male (59.8%). HRQL tended to increase in both the IBDQ and SF-12 1 year after diagnosis. A higher partial Mayo score was significantly related to poorer HRQL on the IBDQ and SF-12 in a linear mixed model (p

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

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.

The rapid rise in the application of novel treatment techniques, such as intensity-modulated radiotherapy (IMRT), motivated us to survey the status of Korea's radiation safety management and the shielding designs of facilities employing medical linear accelerators (LINACs). To this end, a questionnaire was used to collect information on LINAC facilities and treatments, workload, shielding design, shielding management, and path of obtaining shielding information. Out of 100 domestic institutions, 52 responded to the survey. Approximately 70% of the institutions utilized IMRT for more than 60% of their cases, and an IMRT factor of 5 was adopted by 75% of these institutions. Over 80% of the institutions accounted for the applied time-averaged dose rate per week and instantaneous dose equivalent rates in their shielding designs. Approximately 45% of the institutions obtained important shielding information via a radiation shielding design company and the NCRP-151 report. Overall, most facilities were shown to follow the standards recommended by the relevant international agencies. However, the requirement to establish standardized shielding design information and clarify ambiguous paths for information acquisition was also highlighted. Therefore, the study's results can be used as a foundation for establishing a safety control system and for creating adequate shielding designs.

Methylglyoxal (MGO), which is produced as a byproduct of glucose metabolism, is the leading to diabetic cardiovascular complications. Salvia miltiorrhiza Bunge (Lamiaceae) has been reported as a potential plant to control diabetes and cardiovascular disease. However, no report exists on the effect of Salvia miltiorrhiza Bunge extract (SME) on MGO-induced glucotoxicity in human umbilical vein endothelial cells (HUVECs).We demonstrated the protective effects of SME (1, 5, and 10 µg/mL) and its components against MGO-induced endothelial dysfunction in HUVECs. Cytotoxicity was evaluated using the several in vitro experiments. Additionally, the protein expression of receptor of advanced glycation end-products (RAGE), mitogen-activated protein kinase (MAPK) pathway and glyoxalase system were measured. Then, the inhibitory effects of SME and its main components on MGO-induced oxidative stress, radical scavenging, formation of MGO-derived advanced glycation end products (AGEs), and MGO-AGEs crosslinking were evaluated.SME (10 µg/mL) strongly prevented expressed levels of RAGE, MGO-induced apoptosis and reduced ROS generation in HUVECs, comparing with 1 mM aminoguanidine. Additionally, SME (5 and 10 µg/mL) reduced the expression of proteins (e.g., p-ERK and p-p38) in the MAPKs pathway and upregulated the glyoxalase system in HUVECs. SME (0.5 - 10 mg/mL), dihydrotanshinone (0.4 mM), and rosmarinic acid (0.4 mM) prevented MGO-AGEs formation and broke the MGO-AGE crosslinking. These results show that S. miltiorrhiza has protective effects against MGO-induced glucotoxicity by regulating the proteins involved in apoptosis, glyoxalase system and antioxidant activity.We expect that S. miltiorrhiza is a potential natural resource for the treatment of MGO-induced vascular endothelial dysfunction.

Background The emergence of carbapenemase-producing Enterobacteriaceae (CPE) represents a major clinical problem. Recently, the occurrence of CPE has increased globally, but epidemiological patterns vary across region. We report the trends in the genotypic distribution and antimicrobial susceptibility of CPE isolated from rectal and clinical samples during a four-year period. Methods Between January 2016 and December 2019, 1,254 nonduplicated CPE isolates were obtained from four university hospitals in Korea. Carbapenemase genotypes were determined by multiplex real-time PCR. Antimicrobial susceptibility was profiled using the Vitek 2 system (bioMerieux, Hazelwood, MO, USA) or MicroScan Walkaway-96 system (Siemens West Sacramento, CA, USA). The proportions of carbapenemase genotypes and nonsusceptibility were analyzed using Pearson's chi-square test. Results Among the 1,254 CPE isolates, 486 (38.8%), 371 (29.6%), 357 (28.5%), 8 (0.6%), 8 (0.6%), and 24 (1.9%) were Klebsiella pneumoniae carbapenemase (KPC), oxacillinase (OXA)-48-like, New Delhi metallo-β-lactamase (NDM), imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), and multiple producers, respectively. The predominant species was K. pneumoniae (72.6%), followed by Escherichia coli (6.5%). More than 90% of the isolates harboring KPC, NDM, and OXA-48-like were nonsusceptible to cephalosporins, aztreonam, and carbapenems. Conclusions The impact of CPE is primarily due to KPC-, NDM-, and OXA-48-like-producing K. pneumoniae isolates. Isolates carrying these carbapenemase are mostly multidrug-resistant. Control strategies based on these genotypic distributions and antimicrobial susceptibilities of CPE isolates are required.

Purpose: We aimed to investigate the benefit of a screening tool in selecting head-injured children who can potentially cooperate with computed tomography (CT).Methods: The study population consisted of head-injured children aged 36 months or younger who visited the emergency department (ED) and underwent CT from January 2013 through December 2020. Procedural sedation and analgesia (PSA) using per os chloral hydrate or per rectal thiopental was implemented to children presumed less cooperative for CT as per a clinical screening tool for cooperative candidates for CT (e.g., ability to lie still on bed for 10 seconds without a guardian). According to the PSA and the first attempt success of CT, we compared baseline characteristics, CT findings, clinically important traumatic brain injury, ED length of stay (EDLOS), and ED disposition.Results: Among the 247 children, PSA was used in 102 (41.3%). The PSA group showed a higher proportion of 3-36 months of age (PSA, 96.1% vs. non-PSA, 82.8%; P = 0.001) and longer median EDLOS (PSA, 127.0 [interquartile range, 101.0-172.0] vs. non-PSA, 85.0 minutes [63.0-130.0]; P < 0.001). The number of children undergoing the first attempt success was 213 (86.2%) without a difference in both groups (PSA, 84.3% vs. non-PSA, 87.6%; P = 0.645). In the 213 children, the implementation of PSA was associated with longer median EDLOS (PSA, 121.0 [99.0-156.0] vs. non-PSA, 77.0 minutes [60.0-122.0]; P < 0.001). In the non-PSA group (n = 145), the first attempt failure was associated with the presence of skull fracture (success, 7.1% vs. failure, 27.8%; P = 0.009).Conclusion: This study suggests a potential benefit of the screening tool in selecting cooperative candidates for CT, i.e., those who could forgo PSA using oral chloral hydrate or per rectal thiopental, in young children with head injury.

A 55-year-old woman who had received an implantable left ventricular assist device 3 months earlier presented with dyspnea and a low-flow alarm of the device. Computed tomography and log-file analysis of the device system suggested inflow cannula obstruction. Since the patient had cardiogenic shock due to pump failure, venoarterial extracorporeal membrane oxygenation (ECMO) was initiated. With ECMO, surgical exchange of the pump was considered. However, the obstruction spontaneously resolved without surgical intervention. It turned out that an obstructive thrombus was washed out by rebooting the pump. Moreover, the thrombus was embolized in the patient’s left subclavian artery. The patient underwent heart transplantation 4 months after the pump obstruction accident and continued to do well.

Patient-generated health data (PGHD) can be managed easily by a mobile personal health record (mPHR) and can increase patient engagement. This study investigated the effect of PGHD functions on mPHR usage. We collected usage log data from an mPHR app, My Chart in My Hand (MCMH), for seven years. We analyzed the number of accesses and trends for each menu by age and sex according to the version-up. Generalized estimating equation (GEE) analysis was used to determine the likelihood of continuous app usage according to the menus and version-up. The total number of users of each version were 15,357 and 51,553, respectively. Adult females under 50 years were the most prevalent user group (30.0%). The “My Chart” menu was the most accessed menu, and the total access count increased by ~10 times after the version-up. The “Health Management” menu designed for PGHD showed the largest degree of increase in its likelihood of continuous usage after the version-up (1.245; p < 0.0001) across menus (range: 0.925–1.050). Notably, improvement of PGHD management in adult females over 50 years is needed.

Background Loss of resistance (LOR) technique is a widely used method to identify the epidural space. However, cases of inadequate epidural anesthesia in cesarean section were frequently reported. Also, the success rate of epidural anesthesia with LOR technique varied depending on the proficiency of the practitioner. The purpose of this study was to assess the efficacy and safety of electrical stimulation to identify epidural spaces in cesarean section for novices or clinicians with recent gap in experience. Methods Pregnant women scheduled for elective cesarean section were randomly allocated to two groups. Groups were classified based on the methods used for identifying the epidural space: the LOR group (group L) and the LOR with epidural electrical stimulation group (group E). Clinicians with less than 10 epidural cesarean section experiences in the recent year performed epidural anesthesia for cesarean section. In the group E, a RegionalStim® conductive catheter was inserted through the Tuohy needle, and the guidewire passing through the catheter was connected to a peripheral nerve stimulator. The intensity of the stimulation was gradually increased from 0.25 mA to 1.5 mA until paresthesia was elicited and radiated. We assessed the success of epidural anesthesia (complete success, partial success or failure). Other clinical parameters including maternal satisfaction, time required for epidural anesthesia, neonatal Apgar scores, pain scores and adverse events were compared between the two groups. Results Except for 6 patients who withdrew consent, 54 patients were enrolled in this study (28 for the group L and 26 for the group E). The demographic data showed no difference between the two groups. There was no adverse event resulted from electrical stimulation. The group E showed higher rate of complete success, sensitivity in finding epidural space and maternal satisfaction compared to the group L (21/26 vs. 15/28, p = 0.034, 0.96 vs. 0.68, p = 0.012 and 4.04 vs. 3.39, p = 0.02, respectively). The other clinical parameters showed no differences between the two groups. Conclusion In addition to the conventional LOR technique, identifying epidural spaces using electrical stimulation led to better outcomes without additional risks for novices as well as clinicians with recent gap in experience. Trial registration This study was retrospectively registered in the ClinicalTrials.gov Registry (NCT03443466) on February 23, 2018.

Ligamentum flavum is one of the structures that could compress the spinal canal. Few studies have reported atrophy of ligamentum flavum after spinal fusion. The purpose of this study was to demonstrate the reduction of ligamentum flavum size after oblique lumbar interbody fusion (OLIF) using magnetic resonance imaging (MRI). Seventeen patients who underwent OLIF without direct decompression were included. The MRI was obtained at the preoperative period, immediate postoperative period, and the follow-up period. Disc height (DH) was measured in plain radiograph. MRI measurements were spinal canal cross-sectional area (SCSA), ligamentum flavum thickness (LFT), ligamentum flavum area (LFA), and foraminal area (FA). Mean age of the patients was 68.5 ± 10.8. Mean times between postoperative MRI and follow-up MRI were 20.2 ± 11.9 months. Mean disc height increased from 7.6 ± 1.6 to 11.6 ± 1.7 mm at an immediate postoperative period but decreased to 10.1 ± 1.6 mm during follow-up (p

Cancer cells predominantly generate energy via glycolysis, even in the presence of oxygen, to support abnormal cell proliferation. Suppression of PDHA1 by PDK1 prevents the conversion of cytoplasmic pyruvate into Acetyl-CoA. Several PDK inhibitors have been identified, but their clinical applications have not been successful for unclear reasons. In this study, endogenous PDHA1 in A549 cells was silenced by the CRISPR/Cas9 system, and PDHA1WT and PDHA13SD were transduced. Since PDHA13SD cannot be phosphorylated by PDKs, it was used to evaluate the specific activity of PDK inhibitors. This study highlights that PDHA1WT and PDHA13SD A549 cells can be used as a cell-based PDK inhibitor-distinction system to examine the relationship between PDH activity and cell death by established PDK inhibitors. Leelamine, huzhangoside A and otobaphenol induced PDH activity-dependent apoptosis, whereas AZD7545, VER-246608 and DCA effectively enhanced PDHA1 activity but little toxic to cancer cells. Furthermore, the activity of phosphomimetic PDHA1 revealed the complexity of its regulation, which requires further in-depth investigation. [BMB Reports 2021; 54(11): 563-568].

Klippel-Trenaunay syndrome (KTS) is a rare complex vascular syndrome with limb hypertrophy. KTS is diagnosed if at least two of the three features of capillary malformation, venous malformation, and soft tissue and/or bone overgrowth are present. Of these, capillary malformation (i.e., port-wine stain) is the most commonly observed feature but may be absent in atypical KTS. We herein report a case of atypical KTS with venous malformation and unilateral soft tissue hypertrophy.

Background/Aims: Tacrolimus has been used as an immunosuppressive agent in organ transplantation. Despite the therapeutic benefits, tacrolimus’s use is limited due to its nephrotoxicity. To reduce tacrolimus nephrotoxicity, effective humanized experimental models may be helpful. Here, we modeled tacrolimus nephrotoxicity using kidney organoids derived from human inducible pluripotent stem cells (iPSCs) in vitro.Methods: Kidney organoids were differentiated from the CMC11 iPSC cell line, re-seeded in 96-well plates, and treated with tacrolimus at doses of 0, 30, or 60 μM for 24 hours. This in vitro model was compared to a mouse model of tacrolimus nephrotoxicity and the associated mechanisms were investigated.Results: The size of the kidney organoids and cell viability decreased in dose-dependent manners after treatment with tacrolimus. The number of tubular cells decreased with a loss of polarity, similar to the effects seen in mouse tacrolimus nephrotoxicity. Ultrastructural analysis showed numerous vacuoles in the proximal tubular cells of the kidney organoids treated with tacrolimus. Tacrolimus treatment induced oxidative stress and mitochondrial dysfunction, and autophagic activity was enhanced in the kidney organoids. Rapamycin, an autophagy inducer, accelerated cell death in the kidney organoid model of tacrolimus nephrotoxicity, which was attenuated by treatment with 3-methyladenine, an autophagy inhibitor. These findings indicate that the augmentation of autophagy by rapamycin treatment accelerated tacrolimus nephrotoxicity.Conclusions: Our data suggest that human kidney organoids are an effective in vitro model of tacrolimus nephrotoxicity and that autophagy plays a critical role in tacrolimus nephrotoxicity.

Flexible displays on a polyimide (PI) substrate are widely regarded as a promising next-generation display technology due to their versatility in various applications. Among other bendable materials used as display panel substrates, PI is especially suitable for flexible displays for its high glass transition temperature and low coefficient of thermal expansion. PI cured under various temperatures (260 °C, 360 °C, and 460 °C) was implemented in metal–insulator–metal (MIM) capacitors, amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFT), and actual display panels to analyze device stability and panel product characteristics. Through electrical analysis of the MIM capacitor, it was confirmed that the charging effect in the PI substrates intensified as the PI curing temperature increased. The threshold voltage shift (ΔVth) of the samples was found to increase with rising curing temperature under negative bias temperature stress (NBTS) due to the charging effect. Our analyses also show that increasing ΔVth exacerbates the image sticking phenomenon observed in display panels. These findings ultimately present a direct correlation between the curing temperature of polyimide substrates and the panel image sticking phenomenon, which could provide an insight into the improvement of future PI-substrate-based displays.

Objectives: Childhood trauma (ChT) is a risk factor for psychosis. Negative lifestyle factors such as rumination, negative schemas, and poor diet and exercise are common in psychosis. The present study aimed to perform a network analysis of interactions between ChT and negative lifestyle in patients and controls.Methods: We used data of patients with early-stage psychosis (n = 500) and healthy controls (n = 202). Networks were constructed using 12 nodes from five scales: the Brief Core Schema Scale (BCSS), Brooding Scale (BS), Dietary Habits Questionnaire, Physical Activity Rating, and Early Trauma Inventory Self Report-Short Form (ETI). Graph metrics were calculated.Results: The nodes with the highest predictability and expected influence in both patients and controls were cognitive (Co) and emotional domains (Em) of the BS and emotional abuse (EMO) of the ETI. The EMO was a mediator in the shortest pathway connecting the ETI and negative lifestyle for both groups. The negative other (NO) and negative self (NS) of the BCSS mediated EMO to other BCSS or BS for patients and controls, respectively.Conclusion: Our findings suggest that rumination and EMO were central symptoms in both groups and that NO and NS played important mediating roles for patients and controls, respectively.Trial Registration: ClinicalTrials.gov identifier: CUH201411002

Primary central nervous system lymphoma is a rare form of extranodal non-Hodgkin lymphoma, and primary T-cell lymphoma of the cauda equina is extremely rare. We describe a case involving a 56-year-old female who presented with low back pain and radiating leg pain for 4 months. MRI of the lumbar spine revealed an elongated, multinodular intradural lesion of approximately 10 cm from the L4 body to the S2 body level with iso-signal intensity on T1-weighted imaging, heterogeneous iso- and high-signal intensity on T2-weighted imaging, and a heterogeneous intense enhancement on gadolinium contrast-enhanced T1-weighted imaging. A peripheral T-cell lymphoma of the cauda equina was diagnosed on the basis of immunohistochemical and T-cell receptor gamma gene rearrangement analysis after intradural biopsy of the mass.

To improve the poor survival rate of lung cancer patients, we investigated the role of HDGF‐related protein 3 (HRP‐3) as a potential biomarker for lung cancer. The expression of endogenous HRP‐3 in human lung cancer tissues and xenograft tumor models is indicative of its clinical relevance in lung cancer. Additionally, we demonstrated that HRP‐3 directly binds to the E2F1 promoter on chromatin. Interestingly, HRP‐3 depletion in A549 cells impedes the binding of HRP‐3 to the E2F1 promoter; this in turn hampers the interaction between Histone H3/H4 and HDAC1/2 on the E2F1 promoter, while concomitantly inducing Histone H3/H4 acetylation around the E2F1 promoter. The enhanced Histone H3/H4 acetylation on the E2F1 promoter through HRP‐3 depletion increases the transcription level of E2F1. Furthermore, the increased E2F1 transcription levels lead to the enhanced transcription of Cyclin E, known as the E2F1‐responsive gene, thus inducing S‐phase accumulation. Therefore, our study provides evidence for the utility of HRP‐3 as a biomarker for the prognosis and treatment of lung cancer. Furthermore, we delineated the capacity of HRP‐3 to regulate the E2F1 transcription level via histone deacetylation., HRP‐3 depletion–mediated S‐phase accumulation augments E2F1 transcription. HRP‐3 depletion induces H3/H4 acetylation and obstructs HRP‐3 binding to the E2F1 promoter. The reduction of HDAC 1/2 recruitment in the E2F1 promoter by HRP‐3 depletion increases H3/H4 acetylation in the E2F1 promoter.

The physiological conditions of small animals are an essential component to be considered when acquiring images for pre-clinical studies, and they play a vital role in the overall results of a study. However, several previous studies did not consider these conditions. In this study, a new animal cradle that can be modified and adjusted to suit multiple imaging modalities such as positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI) was developed. Unlike previous cradles where only one mouse can be imaged at a time, a total of four mice can be imaged simultaneously using this new cradle. Additionally, fusion images with high-throughput multiple-mouse imaging (MMI) of PET/MRI and PET/CT images can be acquired using this newly developed cradle. The dynamic brain images were also acquired simultaneously by applying PET dynamic imaging technology to high-throughput MMI methods. The results of this study suggest that the newly developed small animal cradle can be widely used in pre-clinical studies.

Background: Statin-associated muscle symptoms are one of the side effects that physicians should consider when prescribing statins. In this study, creatine kinase (CK) levels were measured following statin prescription, and various factors affecting the CK levels were determined using machine learning.Methods: Changes in the CK were observed every 3 months for a 12-month period in patients who received statins for the first time at Seoul St. Mary's Hospital. For each visit, we developed four basic models based on changes in the CK levels. Extreme gradient boosting, a scalable end-to-end tree boosting algorithm, which employs a decision-tree-based ensemble machine learning algorithm, was used for the prediction of changes in the CK.Results: A total of 23,860 patients were included. Among them, 19 patients (0.08%) had increased CK levels of 2,000 IU·L−1 or more 3 months after statin prescription, and 65 patients (0.27%) exhibited CK levels of over 2,000 IU·L−1 at least once during the 12-month study period. The area under the receiver operator characteristic of each model for each visit was 0.709–0.769, and the accuracy was 0.700–0.803. In each of the models, the variables that had the strongest influence on changes in the CK were sex and previous CK value.Conclusions: Through machine learning, factors influencing changes in the CK were identified. These results will provide the basis for future research, through which the optimal parameters of the CK prediction model can be found and the model can be used in clinical applications.

Background: Glycated hemoglobin (HbA1c), which reflects the patient's blood sugar level, can only be measured in a hospital setting. Therefore, we developed a model predicting HbA1c using personal information and self-monitoring of blood glucose (SMBG) data solely obtained by a patient.Methods: Leave-one-out cross-validation (LOOCV) was performed at two university hospitals. After measuring the baseline HbA1c level before SMBG (Pre_HbA1c), the SMBG was recorded over a 3-month period. Based on these data, an HbA1c prediction model was developed, and the actual HbA1c value was measured after 3 months. The HbA1c values of the prediction model and actual HbA1c values were compared. Personal information was used in addition to SMBG data to develop the HbA1c predictive model.Results: Thirty model training sessions and evaluations were conducted using LOOCV. The average mean absolute error of the 30 models was 0.659 (range, 0.005–2.654). Pre_HbA1c had the greatest influence on HbA1c prediction after 3 months, followed by post-breakfast blood glucose level, oral hypoglycemic agent use, fasting glucose level, height, and weight, while insulin use had a limited effect on HbA1c values.Conclusions: The patient's SMBG data and personal information strongly influenced the HbA1c predictive model. In the future, it will be necessary to develop sophisticated predictive models using large samples for stable SMBG in patients.

Abeliophyllum distichum Nakai is a deciduous shrub that belongs to Oleaceae Abeliophyllum and grows only in Korea. In this study, the antioxidative activity, cytotoxicity, anti-aging activity, and levels of acteoside and isoacteoside were compared between non-fermented and fermented (using Lactobacillus plantarum and Lactobacillus brevis) extracts of A. distichum Nakai. The cytotoxicity of these extracts, along with their ability to inhibit elastase activity and Matrix metalloproteinase-1 (MMP-1) expression, and their ability to promote type I procollagen synthesis were investigated in human dermal fibroblasts cells. These tests revealed that the fermented extract possessed higher antioxidant and anti-aging activities compared with the non-fermented extract. The levels of acteoside and isoacteoside were about 1.25 and 1.05 times higher in the fermented extract than in the non-fermented extract. It was speculated that they were converted from acteoside glucosides and isoacteoside glucosides via bioconversion by the fermentation strains. Together, these findings indicate that extracts of A. distichum Nakai show good potential as antioxidative and anti-aging cosmetic materials. Key words: Abeliophyllum distichum Nakai, Lactobacillus plantarum, Lactobacillus brevis, fermentation, antioxidative activity, anti-aging activity.

Objectives: This case study examined the effectiveness of Korean medical treatment for pediatric Crohn’s disease.Methods: A 15-year-old female Korean patient with Crohn’s disease received acupuncture, electroacupuncture, herbal medicine, moxibustion, and aromatherapy treatment for 1 month in a hospital.Results: Decreases in the Pediatric Crohn’s Disease Activity Index score (from 22.5 to 7.5) and the size of two abscesses (from 39.97 mm to 33.36 mm, and from 28.14 mm to 18.71 mm) according to an abdominal CT were observed following treatment. Nausea and vomiting disappeared, stool condition improved, and weight increased (from 30 kg to 33 kg) following treatment. Nausea and vomiting disappeared, stool condition improved, and weight increased (from 30 kg to 33 kg) following treatment.Conclusion: It would be worth examining the long-term effectiveness of Korean medical treatment for pediatric Crohn’s disease.

BACKGROUND AND PURPOSE There is a scarcity of information regarding the role of prothrombin kringle-2 (pKr-2), which can be generated by active thrombin, in hippocampal neurodegeneration and Alzheimer's disease (AD). EXPERIMENTAL APPROACH To assess the role of pKr-2 in association with the neurotoxic symptoms of AD, we determined pKr-2 protein levels in post-mortem hippocampal tissues of patients with AD and the hippocampi of five familial AD (5XFAD) mice compared with those of age-matched controls and wild-type (WT) mice, respectively. In addition, we investigated whether the hippocampal neurodegeneration and object memory impairments shown in 5XFAD mice were mediated by changes to pKr-2 up-regulation. KEY RESULTS Our results demonstrated that pKr-2 was up-regulated in the hippocampi of patients with AD and 5XFAD mice, but was not associated with amyloid-β aggregation in 5XFAD mice. The up-regulation of pKr-2 expression was inhibited by preservation of the blood-brain barrier (BBB) via addition of caffeine to their water supply or by treatment with rivaroxaban, an inhibitor of factor Xa that is associated with thrombin production. Moreover, the prevention of up-regulation of pKr-2 expression reduced neurotoxic symptoms, such as hippocampal neurodegeneration and object recognition decline due to neurotoxic inflammatory responses in 5XFAD mice. CONCLUSION AND IMPLICATIONS We identified a novel pathological mechanism of AD mediated by abnormal accumulation of pKr-2, which functions as an important pathogenic factor in the adult brain via blood brain barrier (BBB) breakdown. Thus, pKr-2 represents a novel target for AD therapeutic strategies and those for related conditions.

Purpose Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.Materials and Methods Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.Results Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.Conclusion Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

Purpose The aim of this study was to examine the rate of expression of estrogen receptor α (ERα) and β1 (ERβ1), progesterone receptor (PR), and rate of overexpression of epidermal growth factor receptor (EGFR) in a relatively large cohort of patients with papillary thyroid carcinoma (PTC). We also aimed to examine whether each receptor influenced clinicopathological characteristics and prognosis of PTC.Materials and Methods We made a microarray of paraffin-embedded PTC surgical tissues from 436 patients. We compared the results of the immunohistochemical staining for each hormone receptor with clinicopathological characteristics.Results The positive expression rate of hormonal receptors was 40.4% for ERα, 83.7% for ERβ1, and 71.3% for PR in patients with PTC. Overexpression of EGFR was shown in 19.3% of patients with PTC. The age was lower (44.6±12.1 years vs. 47.1±12.5 years, p=0.040) and tumor smaller (0.96±0.69 cm vs. 1.13±0.82 cm, p=0.020) in the ERα positive group, which also showed higher PR positivity (80.7% vs. 65.0%, p < 0.001) and overexpression of EGFR (27.3% vs. 13.8%, p < 0.001). However, neither the positivity of hormone receptors nor overexpression of EGFR affected the recurrence of PTC.Conclusion In conclusion, most (94.6%) patients with PTC were found to exhibit positive expression for ERs or PR. We also found that neither the positive expression of hormone receptors nor overexpression of EGFR were associated with the recurrence of PTC.

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

Tailgut cyst, known as retrorectal cystic hamartoma, is a rare congenital lesion derived from the remnants of the embryological tailgut. It is usually located in presacral or retrorectal space. We report the first case of a tailgut cyst presented as an intraperitoneal tumor. In this paper, we present one patient who has undergone surgical excision of tailgut cyst. A 33-year-old woman with no symptoms underwent laparoscopic tumor excision for the definite diagnosis and treatment for a left-sided, cystic, and pelvic mass in computerized tomography (CT). The initial diagnosis was left ovarian benign tumor by radiologic study. Histologic findings revealed a tailgut cyst. After surgery, she was discharged after 3 days without any complications. We report an unusual case of tailgut cyst located in intraperitoneal space. Although it is extremely rare for a tailgut cyst to occur in the intraperitoneal area, physicians may consider tailgut cyst in differential diagnosis of an intraperitoneal cystic mass.

Introduction Enzymatic debridement (ED) is a novel powerful therapy for debridement of severe burns. Standard ED is usually performed within 72 hours after injury following a presoaking phase. Little evidence exists on the effectiveness of ED later than 72 hours after trauma. In this retrospective study, we compared outcomes of burn patients treated within versus later than 72 hours after injury. Patients and Methods 110 patients with severe burns treated with ED between 2016 and 2020 were evaluated. Patients treated later than 72 hours after trauma were identified and matched to a control group treated within 72 hours. Matching criteria included age, area treated with ED, and localization of ED. Exclusion criteria were abbreviated burn severity index (ABSI) > 12 and death within the first 10 days after burn injury. Primary outcomes were time to full epithelialization and number of secondary surgical interventions. Results 16 patients (11 female, 5 male) matched the inclusion criteria and were assigned to the late treatment group. Mean age was 54.0 ± 19.0 years, the = and mean ABSI score 6.3 ± 3.2. 16 matched patients were assigned to the early ED group. Secondary surgical procedures were performed in 62.5 % of cases in both groups with a mean of 1.7 (late treatment) vs. 2.2 (control; p = 0.29) secondary procedures in each group, respectively. No significant difference between groups regarding time to complete epithelialization (28.2 days vs. 27.3 days, p = 0.45) was observed. Infection rate was higher (18.8 % vs. 6.3 %, p = 0.28) in the delayed group. Conclusion Delayed ED is a feasible procedure as part of personalized care in burn surgery. In our retrospective study, we could not identify r safety issues except a slightly higher infection rate. This may however be attributed to delayed initiation of burn treatment itself.