Rapid Antibacterial Activity Assessment of Chimeric Lysins.

Various chimeric lysins have been developed as efficacious antibiotics against multidrug-resistant bacteria, but direct comparisons of their antibacterial activities have been difficult due to the preparation of multiple recombinant chimeric lysins. Previously, we reported an Escherichia coli cell-free expression method to better screen chimeric lysins against Staphylococcus aureus, but we still needed to increase the amounts of expressed proteins enough to be able to detect them non-isotopically for quantity comparisons. In this study, we improved the previous cell-free expression system by adding a previously reported artificial T7 terminator and reversing the different nucleotides between the T7 promoter and start codon to those of the T7 phage. The new method increased the expressed amount of chimeric lysins enough for us to detect them using Western blotting. Therefore, the qualitative comparison of activity between different chimeric lysins has become possible via the adjustment of the number of variables between samples without protein purification. We applied this method to select more active chimeric lysins derived from our previously reported chimeric lysin (ALS2). Finally, we compared the antibacterial activities of our selected chimeric lysins with reported chimeric lysins (ClyC and ClyO) and lysostaphin and determined the rank orders of antibacterial activities on different Staphylococcus aureus strains in our experimental conditions.

What are the risk factors for recurrent UTI with repeated ESBL-producing Enterobacteriaceae? A retrospective cohort study.

INTRODUCTION: A previous study has shown that two-thirds of patients with urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae experience recurrence with the same bacteria on subsequent UTI episodes. However, little is known about which patients suffer from UTI due to ESBL-producing Enterobacteriaceae repeatedly. This study aimed to investigate the risk factors for recurrent UTI due to repeated ESBL-producing organism infections. METHODS: This retrospective, single-center, observational cohort study screened all patients with UTI caused by ESBL-producing strains between January 2012 and April 2019. Among the patients who were followed up, patients who experienced UTI recurrence were enrolled and divided into two groups: ESBL recurrence group and non-ESBL recurrence group. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between patient characteristics and the development of recurrent UTI caused by ESBL-producing Enterobacteriaceae. RESULTS: A total of 330 patients were followed up after the diagnosis of UTI caused by ESBL-producing organisms. Among the patients, 115 (34.8%) experienced UTI recurrence, and 71 (61.7%) of them experienced subsequent recurrent UTI due to ESBL-producing organisms. Patient's age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00-1.04; P = 0.046) and recurrent UTI history (HR, 1.69; 95% CI, 1.05-2.72; P = 0.031) were significantly associated with an increased risk of recurrence with ESBL-producing Enterobacteriaceae. CONCLUSION: These findings showed that a history of previous frequent UTI recurrence is the risk factor for recurrence of UTI due to repeated ESBL producing Enterobacteriaceae infections.

The organic anion transporter (OAT) family: a systems biology perspective.

The organic anion transporter (OAT) subfamily, which constitutes roughly half of the SLC22 (solute carrier 22) transporter family, has received a great deal of attention because of its role in handling of common drugs (antibiotics, antivirals, diuretics, nonsteroidal anti-inflammatory drugs), toxins (mercury, aristolochic acid), and nutrients (vitamins, flavonoids). Oats are expressed in many tissues, including kidney, liver, choroid plexus, olfactory mucosa, brain, retina, and placenta. Recent metabolomics and microarray data from Oat1 [Slc22a6, originally identified as NKT (novel kidney transporter)] and Oat3 (Slc22a8) knockouts, as well as systems biology studies, indicate that this pathway plays a central role in the metabolism and handling of gut microbiome metabolites as well as putative uremic toxins of kidney disease. Nuclear receptors and other transcription factors, such as Hnf4α and Hnf1α, appear to regulate the expression of certain Oats in conjunction with phase I and phase II drug metabolizing enzymes. Some Oats have a strong selectivity for particular signaling molecules, including cyclic nucleotides, conjugated sex steroids, odorants, uric acid, and prostaglandins and/or their metabolites. According to the "Remote Sensing and Signaling Hypothesis," which is elaborated in detail here, Oats may function in remote interorgan communication by regulating levels of signaling molecules and key metabolites in tissues and body fluids. Oats may also play a major role in interorganismal communication (via movement of small molecules across the intestine, placental barrier, into breast milk, and volatile odorants into the urine). The role of various Oat isoforms in systems physiology appears quite complex, and their ramifications are discussed in the context of remote sensing and signaling.

Adding non-contrast and delayed phases increases the diagnostic performance of arterial CTA for suspected active lower gastrointestinal bleeding.

OBJECTIVES: When assessing for lower gastrointestinal bleed (LGIB) using CTA, many advocate for acquiring non-contrast and delayed phases in addition to an arterial phase to improve diagnostic performance though the potential benefit of this approach has not been fully characterized. We evaluate diagnostic accuracy among radiologists when using single-phase, biphasic, and triphasic CTA in active LGIB detection. METHOD AND MATERIALS: A random experimental block design was used where 3 blinded radiologists specialty trained in interventional radiology retrospectively interpreted 96 CTA examinations completed between Oct 2012 and Oct 2017 using (1) arterial only, (2) arterial/non-contrast, and (3) arterial/non-contrast/delayed phase configurations. Confirmed positive and negative LGIB studies were matched, balanced, and randomly ordered. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive and negative predictive values, and time to identify the presence/absence of active bleeding were examined using generalized estimating equations (GEE) with sandwich estimation assuming a binary distribution to estimate relative benefit of diagnostic performance between phase configurations. RESULTS: Specificity increased with additional contrast phases (arterial 72.2; arterial/non-contrast 86.1; arterial/non-contrast/delayed 95.1; p < 0.001) without changes in sensitivity (arterial 77.1; arterial/non-contrast 70.2; arterial/non-contrast/delayed 73.1; p = 0.11) or mean time required to identify bleeding per study (s, arterial 34.8; arterial/non-contrast 33.1; arterial/non-contrast/delayed 36.0; p = 0.99). Overall agreement among readers (Kappa) similarly increased (arterial 0.47; arterial/non-contrast 0.65; arterial/non-contrast/delayed 0.79). CONCLUSION: The addition of non-contrast and delayed phases to arterial phase CTA increased specificity and inter-reader agreement for the detection of lower gastrointestinal bleeding without increasing reading times. KEY POINTS: • A triphasic CTA including non-contrast, arterial, and delayed phase has higher specificity for the detection of lower gastrointestinal bleeding than arterial-phase-only protocols. • Inter-reader agreement increases with additional contrast phases relative to single-phase CTA. • Increasing the number of contrast phases did not increase reading times.

Network analysis for estimating standardization trends in genomics using MEDLINE.

BACKGROUND: Biotechnology in genomics, such as sequencing devices and gene quantification software, has proliferated and been applied to clinical settings. However, the lack of standards applicable to it poses practical problems in interoperability and reusability of the technology across various application domains. This study aims to visualize and identify the standard trends in clinical genomics and to suggest areas on which standardization efforts must focus. METHODS: Of 16,538 articles retrieved from PubMed, published from 1975 to 2020, using search keywords "genomics and standard" and "clinical genomic sequence and standard", terms were extracted from the abstracts and titles of 15,855 articles. Our analysis includes (1) network analysis of full phases (2) period analysis with five phases; (3) statistical analysis; (4) content analysis. RESULTS: Our research trend showed an increasing trend from 2003, years marked by the completion of the human genome project (2003). The content analysis showed that keywords related to such concepts as gene types for analysis, and analysis techniques were increased in phase 3 when US-FDA first approved the next-generation sequencer. During 2017-2019, oncology-relevant terms were clustered and contributed to the increasing trend in phase 4 of the content analysis. In the statistical analysis, all the categories showed high regression values (R2 > 0.586) throughout the whole analysis period and phase-based statistical analysis showed significance only in the Genetics terminology category (P = .039*) at phase 4. CONCLUSIONS: Through comprehensive trend analysis from our study, we provided the trend shifts and high-demand items in standardization for clinical genetics.

N-3-oxododecanoyl homoserine lactone exacerbates endothelial cell death by inducing receptor-interacting protein kinase 1-dependent apoptosis.

Endothelial dysfunction is associated with the initiation of sepsis-associated organ failure. Bacterial quorum-sensing molecules act as pathogen-associated molecular patterns; however, the effects of quorum-sensing molecules on endothelial cells remain less understood. This study investigated the molecular mechanisms of quorum-sensing molecule-induced cell death and their interaction with lipopolysaccharide (LPS) in human umbilical vein endothelial cells. Endothelial cells were treated with N-3-oxododecanoyl homoserine lactone (3OC12-HSL) and LPS derived from Pseudomonas aeruginosa. Treatment with 3OC12-HSL reduced cell viability in a dose-dependent manner, and cotreatment with 3OC12-HSL and LPS enhanced cell death. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay revealed an increase in apoptotic cell death following 3OC12-HSL treatment; furthermore, cotreatment with 3OC12-HSL and LPS enhanced apoptosis. Western blotting revealed that treatment with 3OC12-HSL activated the receptor-interacting protein kinase 1 (RIPK1) pathway, leading to an increase in the levels of cleaved caspase 8 and 3. In addition, we found that treatment with necrostatin-1, an RIPK1 inhibitor, reduced cell death and ameliorated the activation of the RIPK1-dependent apoptotic pathway in 3OC12-HSL-treated cells. In conclusion, 3OC12-HSL induced endothelial cell apoptosis via the activation of the RIPK1 pathway, independent of LPS toxicity. Inhibition of RIPK1 may act as a therapeutic option for preserving endothelial cell integrity in patients with sepsis by disrupting the mechanism by which quorum-sensing molecules mediate their toxicity.

Considerations in Specialty Selections: What Medical Students Think, Know, and Think They Know about Interventional Radiology.

PURPOSE: To compare the motivation, deterrents, knowledge, exposure, and other specialty considerations of first- to fourth-year medical students interested in interventional radiology (IR) with those who are not. MATERIALS AND METHODS: Matriculants of 5 medical schools varying by region, public/private, class size, and National Institutes of Health research ranking received a 19-question survey with questions about demographics, specialty interests, motivations/deterrents, knowledge, and exposure to IR. RESULTS: A total of 25.8% (611/2370) of students completed the survey, of which 20.5% (125/611) expressed interest in IR, and 25% (47/186), 26% (40/153), 24% (34/143), and 3% (3/117) of first-year, second-year, third-year, and fourth-year medical students, respectively, were seriously considering IR. Those interested in IR were less motivated by direct patient care (mean, 2.8/5; 95% confidence interval [CI], 2.6-3.0) and longitudinal patient care (mean, 1.6/5; 95% CI, 1.4-1.7) (both, P < .01) and more motivated by salary (2.6/5; 95% CI, 2.3-2.9), job market (2.8/5; 95% CI, 2.6-2.9), and procedures (3.1/5; 95% CI, 2.8-3.4) compared with their peers (all P < .05). Those interested in IR were more certain about their IR knowledge (mean range, 1.6-2.0/3.0; 95% CI, 1.3-2.3) than their peers (mean range, 1.9-2.4/3.0; 95% CI, 1.6-2.1, in which 0 = certain, P ≤ .01); however, both groups scored low in actual knowledge (those considering IR: 35.0-73.2% correct; 95% CI, 23.5-81.4; those who were not: 26.6-66.7% correct; 95% CI, 24.3-75.9, P > .05). CONCLUSIONS: Although medical students showed interest in IR, they had a limited understanding of IR. IR educators may increase IR interest and understanding among medical students by clarifying the procedural aspects and longitudinal care present in a comprehensive IR practice.

Safety and efficacy of sucroferric oxyhydroxide in pediatric patients with chronic kidney disease.

BACKGROUND: Pediatric patients with advanced chronic kidney disease (CKD) are often prescribed oral phosphate binders (PBs) for the management of hyperphosphatemia. However, available PBs have limitations, including unfavorable tolerability and safety. METHODS: This phase 3, multicenter, randomized, open-label study investigated safety and efficacy of sucroferric oxyhydroxide (SFOH) in pediatric and adolescent subjects with CKD and hyperphosphatemia. Subjects were randomized to SFOH or calcium acetate (CaAc) for a 10-week dose titration (stage 1), followed by a 24-week safety extension (stage 2). Primary efficacy endpoint was change in serum phosphorus from baseline to the end of stage 1 in the SFOH group. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: Eighty-five subjects (2-18 years) were randomized and treated (SFOH, n = 66; CaAc, n = 19). Serum phosphorus reduction from baseline to the end of stage 1 in the overall SFOH group (least squares [LS] mean ± standard error [SE]) was - 0.488 ± 0.186 mg/dL; p = 0.011 (post hoc analysis). Significant reductions in serum phosphorus were observed in subjects aged ≥ 12 to ≤ 18 years (LS mean ± SE - 0.460 ± 0.195 mg/dL; p = 0.024) and subjects with serum phosphorus above age-related normal ranges at baseline (LS mean ± SE - 0.942 ± 0.246 mg/dL; p = 0.005). Similar proportions of subjects reported ≥ 1 TEAE in the SFOH (75.8%) and CaAc (73.7%) groups. Withdrawal due to TEAEs was more common with CaAc (31.6%) than with SFOH (18.2%). CONCLUSIONS: SFOH effectively managed serum phosphorus in pediatric patients with a low pill burden and a safety profile consistent with that reported in adult patients.

Comparison of the Shoulder External Rotator Strength and Asymmetry Ratio Between Workers With and Without Shoulder Impingement Syndrome.

ABSTRACT: Kim, J-H, Kwon, O-Y, Hwang, U-J, Jung, S-H, Ahn, S-H, and Kim, H-A. Comparison of shoulder external rotator strength and the asymmetry ratio between workers with and without shoulder impingement syndrome. J Strength Cond Res 35(12): 3364-3369, 2021-Shoulder impingement syndrome (SIS) is the most common shoulder problem causing shoulder pain. Several studies have indicated that shoulder external rotator muscles provide dynamic stability to the shoulder joint. However, the relationship of SIS to changes in shoulder external rotator muscle strength remains controversial. The purpose of the study was to compare the shoulder external rotator strength and asymmetry ratio between workers with SIS and the normal group in a side-lying position. Twelve male industrial workers with SIS and the normal group of 12 workers participated in this study. A pulling sensor measured shoulder external rotator muscle strength in a side-lying position with the shoulder at 0° and 90° of flexion. The asymmetry ratio was calculated by a specific formula using the shoulder external rotator muscle strength of the dominant side and the unaffected side. Two-way analysis of variance was used to determine between-group differences in shoulder external rotator muscle strength and the asymmetry ratio among the 2 positions. Subjects with SIS did not exhibit significant differences in shoulder external rotator muscle strength in the side-lying position with the shoulder at 0° and 90° of flexion relative to the normal group. However, subjects with SIS had a significantly increased asymmetry ratio of shoulder external rotation strength in the side-lying position with the shoulder at 90° of flexion compared with the normal group. In conclusion, workers with SIS had an asymmetry of shoulder external rotator strength in side-lying with the shoulder at 90° of flexion.

A Comparison Between Hyaluronic Acid and Polylactic Acid Filler Injections for Temporary Penile Augmentation in Patients with Small Penis Syndrome: A Multicenter, Patient/Evaluator-Blind, Comparative, Randomized Trial.

INTRODUCTION: There are only a few studies on the clinical utility of filler injections for penile augmentation (PA) in patients with small penis syndrome (SPS), which is a type of anxiety or body dysmorphic disorder, not a true micropenis. AIM: To compare the clinical outcomes of hyaluronic acid (HA) with polylactic acid (PLA) filler injection for temporary PA in patients with SPS. METHODS: Our prospective, patient/evaluator-blind, comparative, randomized, non-inferiority trial consisted of a single filler injection and a 24-week post-injection period. Seventy-four men with SPS were included between November 2017 and February 2018. Patients were divided into those injected with HA (n = 39) and those injected with PLA filler (n = 35). MAIN OUTCOME MEASURE: The psychological effects of PA, based on the Beliefs about Penis Size Scale, penile girth, and satisfaction, were assessed at baseline and at 4, 12, and 24 weeks post-injection. RESULTS: At 24 weeks, the mean penile girth increases were 2.1 ± 1.0 cm (P < .001) in the HA group and 1.6 ± 0.9 cm (P < .001) in the PLA group, with a mean difference of 0.5 ± 0.2 cm between groups (P = .031). In both groups, satisfaction levels significantly increased at 24 weeks, with 1.8 ± 1.7 and 1.6 ± 1.4 mean increases in the visual analog scale for penile appearance satisfaction in the HA and PLA groups, respectively (each P < .001), and 1.0 ± 1.1 and 0.7 ± 1.2 mean increases in the visual analog scale for sexual life satisfaction in the HA and PLA groups, respectively (each P < .001), with no significant differences between groups (P = .950 and P = .287). The mean Beliefs about Penis Size Scale scores significantly decreased at 24 weeks, with 7.8 ± 8.3 and 5.3 ± 7.2 mean decreases in the HA and PLA groups, respectively (each P < .001), and no significant difference between the groups (P = .920). There were no serious adverse events, but filler injection-related adverse events in the HA and the PLA groups were reported in 2 cases (5.13%) and 5 cases (14.29%), respectively (P = .245). CLINICAL IMPLICATIONS: Our study provides an overview of clinical course after HA and PLA filler injections for PA and suggests that filler injections can be considered an alternative approach in patients with SPS. STRENGTHS & LIMITATIONS: Our study is the first to assess the psychological symptoms in patients with SPS who received the filler injection for PA; however, the follow-up duration was insufficient to prove the long-term outcomes of fillers. CONCLUSION: Without serious adverse events, HA and PLA filler injections for PA significantly resulted in not only an augmentative effect but also improvement of psychological distress, and the clinical utility was comparable between the fillers. Yang DY, Jeong HC, Ahn ST, et al. A Comparison Between Hyaluronic Acid and Polylactic Acid Filler Injections for Temporary Penile Augmentation in Patients with Small Penis Syndrome: A Multicenter, Patient/Evaluator-Blind, Comparative, Randomized Trial. J Sex Med 2020;17:133-141.

Machine Learning Offers Exciting Potential for Predicting Postprocedural Outcomes: A Framework for Developing Random Forest Models in IR.

PURPOSE: To demonstrate that random forest models trained on a large national sample can accurately predict relevant outcomes and may ultimately contribute to future clinical decision support tools in IR. MATERIALS AND METHODS: Patient data from years 2012-2014 of the National Inpatient Sample were used to develop random forest machine learning models to predict iatrogenic pneumothorax after computed tomography-guided transthoracic biopsy (TTB), in-hospital mortality after transjugular intrahepatic portosystemic shunt (TIPS), and length of stay > 3 days after uterine artery embolization (UAE). Model performance was evaluated with area under the receiver operating characteristic curve (AUROC) and maximum F1 score. The threshold for AUROC significance was set at 0.75. RESULTS: AUROC was 0.913 for the TTB model, 0.788 for the TIPS model, and 0.879 for the UAE model. Maximum F1 score was 0.532 for the TTB model, 0.357 for the TIPS model, and 0.700 for the UAE model. The TTB model had the highest AUROC, while the UAE model had the highest F1 score. All models met the criteria for AUROC significance. CONCLUSIONS: This study demonstrates that machine learning models may suitably predict a variety of different clinically relevant outcomes, including procedure-specific complications, mortality, and length of stay. Performance of these models will improve as more high-quality IR data become available.

N-[2-(4-Acetyl-1-Piperazinyl)Phenyl]-2-(3-Methylphenoxy)Acetamide (NAPMA) Inhibits Osteoclast Differentiation and Protects against Ovariectomy-Induced Osteoporosis.

Osteoclasts are large, multinucleated cells responsible for bone resorption and are induced in response to the regulatory activity of receptor activator of nuclear factor-kappa B ligand (RANKL). Excessive osteoclast activity causes pathological bone loss and destruction. Many studies have investigated molecules that specifically inhibit osteoclast activity by blocking RANKL signaling or bone resorption. In recent years, we screened compounds from commercial libraries to identify molecules capable of inhibiting RANKL-induced osteoclast differentiation. Consequently, we reported some compounds that are effective at attenuating osteoclast activity. In this study, we found that N-[2-(4-acetyl-1-piperazinyl)phenyl]-2-(3-methylphenoxy)acetamide (NAPMA) significantly inhibited the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells from bone marrow-derived macrophages in a dose-dependent manner, without cytotoxic effects. NAPMA downregulated the expression of osteoclast-specific markers, such as c-Fos, NFATc1, DC-STAMP, cathepsin K, and MMP-9, at the transcript and protein levels. Accordingly, bone resorption and actin ring formation were decreased in response to NAPMA treatment. Furthermore, we demonstrated the protective effect of NAPMA against ovariectomy-induced bone loss using micro-CT and histological analysis. Collectively, the results showed that NAPMA inhibited osteoclast differentiation and attenuated bone resorption. It is thus a potential drug candidate for the treatment of osteoporosis and other bone diseases associated with excessive bone resorption.

Production of genetically modified pigs expressing human insulin and C-peptide as a source of islets for xenotransplantation.

Islet xenotransplantation is a promising treatment for type I diabetes. Numerous studies of islet xenotransplantation have used pig-to-nonhuman primate transplantation models. Some studies reported long-term survival and successful function of porcine islets in diabetic monkeys. Genetic engineering techniques may improve the survival and function of porcine islets. A recent study reported the generation of transgenic pigs expressing human insulin rather than porcine insulin by changing one amino acid at the end of the ß-chain in insulin. However, C-peptide from pigs still existed. In this study, we generated transgenic pigs expressing human proinsulin to express human insulin and C-peptide using fibroblasts from proinsulin knockout pigs as donor cells for somatic cell nuclear transfer. Eleven live piglets were delivered from three surrogates and characterized to confirm the genotype and phenotype of the generated piglets. Genotype analysis of the generated piglets showed that five of the eleven piglets contained the human proinsulin gene. Insulin expression was confirmed in the serum and pancreas in two of the five piglets. C-peptide derived from human proinsulin was also confirmed by liquid chromatography tandem mass spectrometry. Non-fasting blood glucose level was measured to verify the function of the insulin derived from the human proinsulin. Two piglets expressing insulin showed normal glucose levels similar to that in the wild-type control. In conclusion, human insulin- and C-peptide-expressing pigs without porcine insulin and C-peptide were successfully established. These pigs can be used as a source of islets for islet xenotransplantation.

A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification.

Peroxiredoxins (Prdxs) are antioxidant enzymes that catalyse the breakdown of peroxides and regulate redox activity in the cell. Peroxiredoxin 5 (Prdx5) is a unique member of Prdxs, which displays a wider subcellular distribution and substrate specificity and exhibits a different catalytic mechanism when compared to other members of the family. Here, the role of a key metabolic integrator coenzyme A (CoA) in modulating the activity of Prdx5 was investigated. We report for the first time a novel mode of Prdx5 regulation mediated via covalent and reversible attachment of CoA (CoAlation) in cellular response to oxidative and metabolic stress. The site of CoAlation in endogenous Prdx5 was mapped by mass spectrometry to peroxidatic cysteine 48. By employing an in vitro CoAlation assay, we showed that Prdx5 peroxidase activity is inhibited by covalent interaction with CoA in a dithiothreitol-sensitive manner. Collectively, these results reveal that human Prdx5 is a substrate for CoAlation in vitro and in vivo, and provide new insight into metabolic control of redox status in mammalian cells.

Image-Guided Cholecystostomy Tube Placement: Short- and Long-Term Outcomes of Transhepatic Versus Transperitoneal Placement.

OBJECTIVE: Image-guided percutaneous cholecystostomy may be performed by a transhepatic or transperitoneal approach. We compared the short- and long-term outcomes of percutaneous cholecystostomy related to route of catheter placement. MATERIALS AND METHODS: A retrospective observational study of image-guided percutaneous cholecystostomy was performed from 2004 to 2016. A search of the hospital's radiology information service was performed using the keywords "percutaneous cholecystostomy," "gallbladder drain," and "cholecystostomy tube" and the relevant Current Procedural Terminology codes. All search results were reviewed to identify the cohort of 373 patients who underwent initial percutaneous cholecystostomy catheter placement. Imaging was reviewed to determine the method and route of percutaneous cholecystostomy and complications. A chart review was performed to determine clinical outcomes. Differences were examined using a generalized linear model assuming a binary distribution and logit function. RESULTS: Percutaneous cholecystostomy catheter placement was performed using ultrasound guidance alone in 229 patients, ultrasound access with fluoroscopic guidance in 129 patients, CT guidance in 14 patients, and fluoroscopic guidance in one patient. The trocar technique was used for 183 patients, and the Seldinger technique was used for 190 patients. Two hundred eighteen percutaneous cholecystostomy catheters were placed via the transhepatic route, and 153 were placed via the transperitoneal route. The most common catheter sizes used were 8.5 French (n = 234) and 10 French (n = 124). No significant differences were observed between transperitoneal and transhepatic placement with regard to the frequency of pain, clogging, skin infection, bleeding, biloma, cholangitis, leakage, abscess, unplanned catheter removal, or need for replacement (p > 0.05). CONCLUSION: No evidence of a difference in outcomes was observed for transhepatic cholecystostomy tube placement over transperitoneal placement. The route that appears safer and less technically challenging should therefore be chosen.

High prevalence of BRAF V600E mutations in Korean patients with ameloblastoma: Clinicopathological significance and correlation with epithelial-mesenchymal transition.

BACKGROUND: BRAF V600E mutations are activating mutations that have recently been detected in ameloblastoma. However, their prevalence has not been reported in East Asian patients with ameloblastoma and their clinicopathological significance remains unclear. In this study, we examined the prevalence and clinicopathological significance of BRAF V600E mutations in Korean patients with ameloblastoma. In addition, we investigated the relationship between BRAF V600E mutations and epithelial-mesenchymal transition, which has not been studied in ameloblastoma. METHODS: Thirty ameloblastoma tissue samples were collected, and DNA isolation, polymerase chain reaction, and Sanger sequencing were performed to detect BRAF V600E mutations. Immunohistochemistry was carried out using antibodies against two epithelial-mesenchymal transition-inducing transcription factors, Twist and Snail. Associations of BRAF V600E mutations with clinicopathological factors and expression of Twist and Snail were statistically analyzed. RESULTS: We found a high frequency (90.0%) of BRAF V600E mutations, and mutation status was not associated with clinicopathological factors including age, tumor location, and recurrence. Positive expression of Twist and Snail was observed in 33.3% and 56.7% of cases, respectively, and associated with recurrence (P = 0.020 and 0.010, respectively). There was no correlation between BRAF V600E mutation status and expression of Twist and Snail (P = 1.000, for both). CONCLUSIONS: A higher prevalence of BRAF V600E mutations was identified in Korean patients with ameloblastoma compared with previous studies, which indicates that BRAF-targeted therapies can be widely used for refractory ameloblastomas. Furthermore, our findings suggest that BRAF V600E mutations and epithelial-mesenchymal transition may act independently in the development of ameloblastoma.

Does urinary tract infection caused by extended-spectrum ß-lactamase-producing Escherichia coli show same antibiotic resistance when it recurs?

This study was performed to evaluate what percentage of urinary tract infections (UTIs) caused by extended spectrum ß-lactamase (ESBL)-producing strains recurs with ESBL-producing strains during follow up and to assess the risk factors for recurrence with ESBL-producing Escherichia coli strains on subsequent first recurrence episode. We enrolled female patients with UTIs caused by ESBL-producing E. coli between May 2012 and December 2015, who were longitudinally followed up for at least 24 months. Among the 206 patients with ESBL positive UTI, 180 completed the study. 60 (60/180, 33.3%) of patient with first episode of UTI caused by ESBL-producing E. coli experienced recurrent UTIs during follow up. Of 60 patients, 43 (43/60, 71.7%) recurred with ESBL-producing E. coli on the first UTI recurrence episode. On multivariate analysis, the time to recurrence and history of cephalosporin usage in the last 6 months were identified as risk factors for recurrence with ESBL-producing E. coli per se (odds ratio [OR] = 0.9, 95% confidence interval [CI] 0.8-1.0, p = 0.030 and OR = 27.0, 95% CI 2.4-299.8, p = 0.007, respectively). These findings show that high proportion of patient with UTI caused by ESBL-producing E. coli recurs with ESBL-producing E. coli on subsequent recurrence episode. While result of antibiotic susceptibility cannot be identified on the visit day empirical treatment should be referred to the antecedent antibiotic resistance profile in patients whose previous UTIs were due to ESBL-producing strains.

Spontaneous perirenal hemorrhage (Wunderlich syndrome): An analysis of 28 cases.

INTRODUCTION: This study aimed to analyze the characteristics, etiology, and treatment of a series of patients with spontaneous perirenal hemorrhage (Wunderlich syndrome [WS]). METHODS: We retrospectively reviewed the records of 26 patients hospitalized for WS in a tertiary urological center between 2011 and 2018. All patients were evaluated for perirenal hemorrhage observed on computed tomography (CT) in the emergency department. Clinical variables (age, underlying diseases, symptoms, shock, and hospitalization period), laboratory test results, and radiological and pathological results were reviewed. RESULTS: The series included 28 events from 26 patients with a mean follow-up period of 20.2 ±â€¯18.0 months. Flank pain was most common symptoms (92%). Twelve patients (46%) had visible renal lesions and associated hematoma and 14 only showed perirenal hematoma. In six patients with shock (systolic blood pressure < 90 mm Hg), 2 underwent emergency angioembolization. Twelve patients (46%) underwent exploration and total nephrectomy. In the final diagnosis, 4 cases of renal cell carcinoma, 3 of angiomyolipoma, 4 of simple renal cyst, 2 of acquired cystic kidney disease, 4 of sarcoma or other malignancy, 4 of chronic pyelonephritis, and 5 of idiopathic WS were observed. Patient age was associated with prediction of renal cell carcinoma in the patients with WS. CONCLUSION: Renal masses are the main cause of WS, and CT is the diagnostic procedure of choice. Old age is a possible risk factor for renal cell carcinoma in etiology of WS. Surgical treatment is preferred in patients diagnosed with renal malignancy and in cases of hemodynamic instability.

Incidence of Prostate Cancer according to Metabolic Health Status: a Nationwide Cohort Study.

BACKGROUND: We assessed the association between metabolic health status and incidence of prostate cancer using the National Health Check-ups (NHC) database of Korea. METHODS: A total of 11,771,252 men who participated in the NHC between 2009 and 2012 and 56,552 men who were newly diagnosed with prostate cancer were analyzed. Normal-weight and obesity were defined as body mass index (BMI) < 25 kg/m2 and ≥ 25 kg/m2, respectively. Metabolic obesity was defined as the presence ≥ 3 components of the metabolic syndrome. Participants were stratified into 4 groups: metabolically healthy, normal-weight; metabolically obese, normal-weight (MONW); metabolically healthy, obese (MHO); and metabolically obese, obese. Multivariate Cox regression analysis was performed to examine the relationship between metabolic health status and incidence of prostate cancer. RESULTS: During a mean 5.4 ± 1.1 years of follow-up, 56,552 patients were registered with a diagnosis of prostate cancer. When analyzed according to metabolic health status classification, the multivariable-adjusted hazard ratio (HR) was 1.143 for the MONW group, 1.097 for the MHO group, showing the HR for the MONW group was higher than that for the MHO group. As the number of metabolic syndrome components increased, HR increased significantly. When stratified based on BMI, metabolically obese patients showed significantly higher HR than metabolically healthy patients in all BMI groups. CONCLUSION: This population-based nationwide study revealed an association between metabolic health status and the incidence of prostate cancer, and the risk increased according to the number of components of the metabolic syndrome.

Generation of insulin-deficient piglets by disrupting INS gene using CRISPR/Cas9 system.

Diabetes mellitus is a chronic disease with accompanying severe complications. Various animal models, mostly rodents due to availability of genetically modified lines, have been used to investigate the pathophysiology of diabetes. Using pigs for diabetic research can be beneficial because of their similarity in size, pathogenesis pathway, physiology, and metabolism with human. However, the use of pigs for diabetes research has been hampered due to only few pig models presenting diabetes symptoms. In this study, we have successfully generated insulin-deficient pigs by generating the indels of the porcine INS gene in somatic cells using CRISPR/Cas9 system followed by somatic cell nuclear transfer. First, somatic cells carrying a modified INS gene were generated using CRISPR/Cas9 system and their genotypes were confirmed by T7E1 assay; targeting efficiency was 40.4% (21/52). After embryo transfer, three live and five stillborn piglets were born. As expected, INS knockout piglets presented high blood glucose levels and glucose was detected in the urine. The level of insulin and c-peptide in the blood serum of INS knockout piglets were constant after feeding and the expression of insulin in the pancreas was absent in those piglets. This study demonstrates effectiveness of CRISPR/Cas9 system in generating novel pig models. We expect that these insulin-deficient pigs can be used in diabetes research to test the efficacy and safety of new drugs and the recipient of islet transplantation to investigate optimal transplantation strategies.