The Impact of an Antimicrobial Stewardship Program on Days of Therapy in the Pediatric Center: An Interrupted Time-Series Analysis of a 19-Year Study.

BACKGROUND: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. METHODS: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001-2008) and the post-intervention (2009-2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patient-days, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ². RESULTS: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = -16.5; 95% confidence interval [CI], -30.6 to -2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). CONCLUSION: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Prognostic significance of MRI features in patients with solitary large hepatocellular carcinoma following surgical resection.

OBJECTIVE: To assess the prognostic impact of preoperative MRI features on outcomes for single large hepatocellular carcinoma (HCC) (≥ 8 cm) after surgical resection. MATERIAL AND METHODS: This retrospective study included 151 patients (mean age: 59.2 years; 126 men) with a single large HCC who underwent gadoxetic acid-enhanced MRI and surgical resection between 2008 and 2020. Clinical variables, including tumor markers and MRI features (tumor size, tumor margin, and the proportion of hypovascular component on hepatic arterial phase (AP) (≥ 50% vs. < 50% tumor volume) were evaluated. Cox proportional hazards model analyzed overall survival (OS), recurrence-free survival (RFS), and associated factors. RESULTS: Among 151 HCCs, 37.8% and 62.2% HCCs were classified as ≥ 50% and < 50% AP hypovascular groups, respectively. The 5- and 10-year OS and RFS rates in all patients were 62.0%, 52.6% and 41.4%, 38.5%, respectively. Multivariable analysis revealed that ≥ 50% AP hypovascular group (hazard ratio [HR] 1.7, p = 0.048), tumor size (HR 1.1, p = 0.006), and alpha-fetoprotein ≥ 400 ng/mL (HR 2.6, p = 0.001) correlated with poorer OS. ≥ 50% AP hypovascular group (HR 1.9, p = 0.003), tumor size (HR 1.1, p = 0.023), and non-smooth tumor margin (HR 2.1, p = 0.009) were linked to poorer RFS. One-year RFS rates were lower in the ≥ 50% AP hypovascular group than in the < 50% AP hypovascular group (47.4% vs 66.9%, p = 0.019). CONCLUSION: MRI with ≥ 50% AP hypovascular component and larger tumor size were significant factors associated with poorer OS and RFS after resection of single large HCC (≥ 8 cm). These patients require careful multidisciplinary management to determine optimal treatment strategies. CLINICAL RELEVANCE STATEMENT: Preoperative MRI showing a ≥ 50% arterial phase hypovascular component and larger tumor size can predict worse outcomes after resection of single large hepatocellular carcinomas (≥ 8 cm), underscoring the need for tailored, multidisciplinary treatment strategies. KEY POINTS: MRI features offer insights into the postoperative prognosis for large hepatocellular carcinoma. Hypovascular component on arterial phase ≥ 50% and tumor size predicted poorer overall survival and recurrence-free survival. These findings can assist in prioritizing aggressive and multidisciplinary approaches for patients at risk for poor outcomes.

Should we suspect gallbladder cancer if which CT finding is observed in patients with localized gallbladder wall thickening?

PURPOSE: To identify high-risk computed tomography (CT) features for predicting gallbladder (GB) cancer in patients presenting with localized GB wall thickening. METHODS: This retrospective analysis included 120 patients (mean age: 63.9 ± 10.0 years; 51 men) exhibiting localized GB wall thickening on CT scans obtained between January 2008 and May 2017. Two radiologists independently evaluated CT imaging features for predicting GB cancer. The diagnostic performance of significant imaging features and their combinations was evaluated. High-risk CT features ranked by accuracy were delineated for predicting GB cancer. RESULTS: This study included 55 patients with GB cancer and 65 with benign GB conditions. The top-four most accurate CT imaging features for predicting GB cancer were identified: heterogeneously enhancing single layer or strongly enhancing thick inner layer; GB wall thickness > 6.5 mm; hyperenhancement on arterial phase; and absence of intramural small cystic lesions (accuracies of 90.0 %, 88.3 %, 85.0 %, and 85.0 %, respectively). The combination of any three high-risk features exhibited the highest accuracy (94.2 %). The presence of any high-risk feature yielded a sensitivity of 100 %, whereas that of all high-risk features indicated a specificity of 100 %. CONCLUSION: CT imaging features, whether alone or in combination, could effectively and accurately predict GB cancer among patients with localized GB wall thickening. This finding holds significance in guiding decisions regarding further diagnostic tests and treatment planning.

nnU-Net-Based Pancreas Segmentation and Volume Measurement on CT Imaging in Patients with Pancreatic Cancer.

RATIONALE AND OBJECTIVES: To develop and validate a deep learning (DL)-based method for pancreas segmentation on CT and automatic measurement of pancreatic volume in pancreatic cancer. MATERIALS AND METHODS: This retrospective study used 3D nnU-net architecture for fully automated pancreatic segmentation in patients with pancreatic cancer. The study used 851 portal venous phase CT images (499 pancreatic cancer and 352 normal pancreas). This dataset was divided into training (n = 506), internal validation (n = 126), and external test set (n = 219). For the external test set, the pancreas was manually segmented by two abdominal radiologists (R1 and R2) to obtain the ground truth. In addition, the consensus segmentation was obtained using Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm. Segmentation performance was assessed using the Dice similarity coefficient (DSC). Next, the pancreatic volumes determined by automatic segmentation were compared to those determined by manual segmentation by two radiologists. RESULTS: The DL-based model for pancreatic segmentation showed a mean DSC of 0.764 in the internal validation dataset and DSC of 0.807, 0.805, and 0.803 using R1, R2, and STAPLE as references in the external test dataset. The pancreas parenchymal volume measured by automatic and manual segmentations were similar (DL-based model: 65.5 ± 19.3 cm3 and STAPLE: 65.1 ± 21.4 cm3; p = 0.486). The pancreatic parenchymal volume difference between the DL-based model predictions and the manual segmentation by STAPLE was 0.5 cm3, with correlation coefficients of 0.88. CONCLUSION: The DL-based model efficiently generates automatic segmentation of the pancreas and measures the pancreatic volume in patients with pancreatic cancer.

Real-Time Tracheal Ultrasound vs. Capnography for Intubation Confirmation during CPR Wearing a Powered Air-Purifying Respirator in COVID-19 Era.

This study aimed to compare the accuracy of real-time trans-tracheal ultrasound (TTUS) with capnography to confirm intubation in cardiopulmonary resuscitation (CPR) while wearing a powered air-purifying respirator (PAPR). This setting reflects increased caution due to contagious diseases. This single-center, prospective, comparative study enrolled patients requiring CPR while wearing a PAPR who visited the emergency department of a tertiary medical center from December 2020 to August 2022. A physician performed the TTUS in real time and recorded the tube placement assessment. Another healthcare provider attached waveform capnography to the tube and recorded end-tidal carbon dioxide (EtCO2) after five ventilations. The accuracy and agreement of both methods compared with direct laryngoscopic visualization of tube placement, and the time taken by both methods was evaluated. Thirty-three patients with cardiac arrest were analyzed. TTUS confirmed tube placement with 100% accuracy, sensitivity, and specificity, whereas capnography demonstrated 97% accuracy, 96.8% sensitivity, and 100% specificity. The Kappa values for TTUS and capnography compared to direct visualization were 1.0 and 0.7843, respectively. EtCO2 was measured in 45 (37-59) seconds (median (interquartile range)), whereas TTUS required only 12 (8-23) seconds, indicating that TTUS was significantly faster (p < 0.001). No significant correlation was found between the physician's TTUS proficiency and image acquisition time. This study demonstrated that TTUS is more accurate and faster than EtCO2 measurement for confirming endotracheal tube placement during CPR, particularly in the context of PAPR usage in pandemic conditions.

Diffusion-Weighted MR Imaging of the Thymus in Children with Non-Thymic Neoplasms.

Purpose: To investigate the diffusion-weighted imaging (DWI) findings and apparent diffusion coefficient (ADC) value of the thymus in children under the age of 13 who have non-thymic neoplasms. Materials and Methods: From January 2021 to April 2023, a single-center retrospective study analyzed consecutive 191 thoracic MRI scans with DWI from 67 children (<13 years) with non-thymic neoplasms. The scans were categorized based on the presence of restricted diffusion on DWI. We analyzed the demographics, laboratory data, and MR findings of the thymus. Statistical differences were assessed using generalized estimating equations. Results: Forty-five percent (86/191) of the scans exhibited restricted diffusion in the thymus: multifocal (n = 65; 76%), focal (n = 19; 22%), and diffuse (n = 2; 2%) patterns. The restricted diffusion group demonstrated higher absolute lymphocyte counts, more prominent thymus sizes, and higher frequency of off-treatment status compared to the unrestricted diffusion group (p>0.05). The mean ADC value across all 191 scans was 1.80 × 10-3 mm2/s. No significant difference was observed in the ADC value related to restricted diffusion patterns, the MRI vendors, or the age at the time of the scan. Conclusions: Restricted diffusion was observed in 45% of the thymus in children with non-thymic neoplasms, with a mean ADC value of 1.80 × 10-3 mm2/s. Recognizing the DWI findings can prevent unnecessary invasive procedures, alleviating concerns for patients and families.

Antithrombotic Therapy Increases the Risk of Bleeding after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Propensity Score-Matched Analysis.

Whether antithrombotic agent (ATA) usage increases the risk of gastric post-endoscopic submucosal dissection (ESD) bleeding remains controversial. The aim of this study was to elucidate the effects of usage, type, and cessation timing of ATA on post-ESD bleeding. A total of 4775 early gastric cancer patients undergoing ESD were analyzed; 1:3 propensity score matching between ATA and non-ATA groups resulted in 318 and 767 matched patients in each group, respectively. Outcomes were compared between the two groups using a generalized estimating equation method. After matching, post-ESD bleeding rates in ATA users and non-users were 9.1% and 4.2%, respectively (p = 0.001). In multivariable analysis, ATA usage was independently associated with an increased risk of post-ESD bleeding (adjusted odds ratio: 2.28, 95% confidence interval: 1.34-3.86). Both the continued or insufficient cessation groups and the sufficient cessation group had an increased incidence of post-ESD bleeding compared to their matched controls (12.5% versus 5.2%, p = 0.048; 8.1% versus 3.9%, p = 0.014). Post-ESD bleeding rates in antiplatelet agent users were significantly higher than those of their matched controls (8.3% versus 4.2%, p = 0.010). ATA usage increased the risk of post-ESD bleeding even after its sufficient cessation. Careful observation after ESD is required regardless of the cessation status of ATA.

Effect of renal insufficiency on the short- and long-term outcomes of endoscopic submucosal dissection for early gastric cancer: Propensity score-matched analysis.

OBJECTIVES: It is unclear whether renal insufficiency (RI) itself is a risk factor for adverse outcomes after gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the safety and efficacy of gastric ESD in patients with and without RI using propensity score-matching analysis. METHODS: In all, 4775 patients with 4775 early gastric cancer lesions undergoing ESD were analyzed. 1:1 propensity score-matching was performed between patients with and without RI using 12 variables. After matching, logistic regression and survival analyses were performed for short- and long-term outcomes of ESD, respectively. RESULTS: The matching yielded 188 pairs of patients with and without RI. In both univariable and multivariable analyses, the presence of RI was not significantly associated with postprocedural bleeding (unadjusted odds ratio 1.81, 95% confidence interval 0.74-4.42; adjusted odds ratio 1.86, 95% confidence interval 0.74-4.65, respectively). When RI patients were subclassified into patients with estimated glomerular filtration rate (eGFR) 30-59 mL/min/1.73 m2 and eGFR <30 mL/min/1.73 m2 , no significant differences in bleeding rates were found compared to their matched controls in both groups. Perforation, en bloc resection, en bloc and R0 resection, and curative resection rates of RI patients were 2.1%, 98.4%, 91.0%, and 78.2%, respectively, which were comparable to those of non-RI patients. During a median follow-up of 119 months, there was no difference in gastric cancer-specific survival between patients with and without RI (P = 0.143). CONCLUSION: The outcomes of ESD were comparable in patients with and without RI. Decreased renal function itself may not be a reason to keep patients with RI from receiving gastric ESD.

Intercomparison study of fragmentation pathways and fragment ion structures for screening of illegal drugs and their novel analogues used to adulterate dietary supplements using liquid chromatography/quadrupole time-of-flight mass spectrometry.

RATIONALE: As public interest in health and immunity has increased in recent years, so has the demand for dietary supplements. However, supplements adulterated with illegal drugs and their novel analogues are being sold even as the pharmacological efficacies of these drugs are being advertised. Since the use of these illegal compounds can have serious side effects, they pose a risk to public health. Hence, in this study, we propose a strategy for proactively testing drugs and novel analogues that may be added to dietary supplements illegally. METHODS: The optimal conditions for liquid chromatography/quadrupole time-of-flight mass spectrometry were explored to determine the fragmentation patterns for 60 compounds. The optimal conditions were established by comparing the areas and heights of the precursor ion peaks at a fragmentor voltage of 125 or 175 V. Furthermore, the optimized spectra were acquired using collision energies of 1 to 50 eV. The energy value was selected based on the condition that the mass error of the precursor ions is 10 ppm or lower. RESULTS: The fragmentation pathway of each product ion and its chemical structure were predicted and determined. In addition, the obtained structural information was used to screen 18 seized samples. Based on the precursor ions and the corresponding fragmentation patterns, the unknown compounds present in the samples were identified as desulfonylchlorosildenafil and propoxyphenylthiohydroxy homosildenafil. CONCLUSIONS: We obtained mass spectrometry-based information for various compounds by predicting the fragmentation pathways and chemical structures of their fragment ions. Subsequently, based on the obtained structural information, we tested several seized samples and were able to detect two novel analogues in four of the samples. Therefore, the proposed approach is suitable for quickly and accurately identifying the unknown compounds detected in real-world samples.

Application of LC-MS/MS and UHPLC-Q-Orbitrap methods for determining 54 steroids in illegal dietary supplements and other sample types.

RATIONALE: With the development of the Internet and social network services, the public access to or use of illegal products has been increased via on/offline black markets. Steroids refer to the compounds yielding strong treatment effects on some diseases or muscle building, and are classified as the pharmaceutical compounds that are prohibited for personal use without a prescription. The prohibition is made for their potential risk to cause serious adverse effects along with their efficacies. METHODS: To monitor the distribution of illicit products containing steroids, a simple and reliable analytical method was established and validated, allowing rapid and simultaneous determination of 54 steroids in them. During the screening, LC-Q-Orbitrap/MS was performed first followed by quantitative analysis using LC-MS/MS. For the accurate and reliable analysis, the samples were extracted using QuEChERS to reduce the matrix effect. RESULTS: After the screening of 617 illegal samples advertised as being effective in alleviating various diseases or improving athletic performance with the established LC-Q-Orbitrap/MS method, the validated LC-MS/MS method was used to perform the quantitative analysis of the detected steroids. Of these, 142 samples were adulterated with steroids, and several samples with two or more steroids were detected. Due to the lack of previous studies on the toxicity of these illicit products, the side effects of consuming them are unpredictable and could be harmful. CONCLUSIONS: The development of LC-Q-Orbitrap/MS method accompanied by LC-MS/MS could be successfully applied to the inspection of illegal steroid products for public health, enabling the rapid and accurate detection of analytes and incorporation of non-analyte components.

Detection of 94 PDE-5is and Their Analogs Including N-Desmethylthiosildenafil in Various Formulations of Dietary Supplements and Food Samples Using HPLC and LC-Q-TOF/MS.

Consumption of foods and dietary supplements (DS) adulterated with unprescribed or non-permitted phosphodiesterase-5 inhibitors (PDE-5i) and their analogs can cause serious risk to human health. This study aims to analyze 93 PDE-5i and their analogs present in adulterated foods and DS using an established and validated method involving high-performance liquid chromatography (HPLC). The method was validated in solid and liquid samples, resulting in a limit of detection and quantitation of 0.03-0.5 and 0.08-1.6 µg/mL, respectively. Using the validated method, a total of 404 samples were screened. It was found that 32% of 404 samples were illegally adulterated with PDE-5i and their analogs; moreover, 16.9% of the adulterated samples were found to contain more than three compounds. HPLC-quadrupole-time-of-flight (TOF)/mass spectrometry (MS) analysis was conducted on all the samples to confirm the detected compounds accurately based on fragmentation ion patterns. In addition, sildenafil and tadalafil were detected from the capsule shells of DS unusually. Subsequently, the detected compounds were identified and quantified using HPLC at concentrations ranging from 0.007 to 370.0 mg/g. NMR analysis was carried out to confirm the accurate chemical structure of a compound found during the TOF/MS analysis, which did not match with the 93 reference standards.; it was identified to be N-desmethylthiosildenafil. In this study, various PDE-5i compounds and their analogs were detected from low to high concentrations in a sample. Therefore, the study sheds light on the misuse of PDE-5i and their analogs in consumable products, which pose a severe threat to public health.

Application of liquid chromatography-high resolution mass spectrometry and liquid chromatography-tandem mass spectrometry methods to 45 weight loss compounds in health functional food, food, and illegal drug.

In order to effectively and quickly monitor such illegal food and drugs, simultaneous screening and quantitative analysis for multiple compounds are needed. In this study, we established a method of identifying fragmentation ions of 45 compounds for weight loss using liquid chromatography and high-resolution mass spectrometry and developed a quantitation method through liquid chromatography and tandem mass spectrometry. Note that, 656 samples selected as health functional food, food, and illegal drug were applied. The detection rate of banned weight loss compounds in health functional food, food, and illegal drug was showed as 19.2, 27.3, 40.7%, respectively. Among them, sibutramine, sennoside A and B, ephedrine were most frequently detected in 237 samples that contained weight loss compounds. The detection range about sibutramine was 0.03-159.3 mg/g, sennoside was 0.1-97.6 mg/g, and ephedrine was 0.1-587.7 mg/g in the detected 237 samples. In addition, the unknown compounds not included in our simultaneous analysis method in some samples were identified as furosemide and chlorpheniramine. High selectivity of high resolution mass spectrometry combined with these fragmentation pathways and tandem mass spectrometry methods can be successfully applied to screening and identifying 45 weight loss compounds for continuous blocking and supervision of illegally distributed health functional food, food, and illegal drug.

Dietary Diversity during Early Infancy Increases Microbial Diversity and Prevents Egg Allergy in High-Risk Infants.

We aimed to investigate associations of dietary diversity (DD) with gut microbial diversity and the development of hen's egg allergy (HEA) in infants. We enrolled 68 infants in a high-risk group and 32 infants in a control group based on a family history of allergic diseases. All infants were followed from birth until 12 months of age. We collected infant feeding data, and DD was defined using 3 measures: the World Health Organization definition of minimum DD, food group diversity, and food allergen diversity. Gut microbiome profiles and expression of cytokines were evaluated by bacterial 16S rRNA sequencing and real-time reverse transcriptase-polymerase chain reaction. High DD scores at 3 and 4 months were associated with a lower risk of developing HEA in the high-risk group, but not in the control group. In the high-risk group, high DD scores at 3, 4, and 5 months of age were associated with an increase in Chao1 index at 6 months. We found that the gene expression of IL-4, IL-5, IL-6, and IL-8 were higher among infants who had lower DD scores compared to those who had higher DD scores in high-risk infants. Additionally, high-risk infants with a higher FAD score at 5 months of age showed a reduced gene expression of IL-13. Increasing DD within 6 months of life may increase gut microbial diversity, and thus reduce the development of HEA in infants with a family history of allergic diseases.

Development of a method for simultaneous screening of four natural-derived steroids and their analogues used as dietary supplements via liquid chromatography-quadrupole-time of flight mass spectrometry and liquid chromatography-tandem mass spectrometry.

Natural-derived steroids and their analogues are present in various plants and insects. To minimize the chance of missing a positive doping test and avoiding potentially serious health problems, adequate screening methods are necessary for the detection of a wide range of natural-derived steroids and their analogues in dietary supplements. In this study, an accurate and simple liquid-chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine and quantify the natural-derived steroids and their analogues according to the International Conference on Harmonization of technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. The validation results indicating excellent extraction efficiency and low matrix effects show that the LC-MS/MS method is reliable for the detection of natural-derived steroids and their analogues. In addition, we established the ion fragmentation of turkesterone and ion fragmentation of four natural-derived steroids and their analogues. The validated method was applied to 60 dietary supplements purchased online and in person from international vendors in 2020. Ecdysterone and 5α-hydroxylaxogenin were detected respectively in 3 and 14 of 60 dietary supplements. Especially, a high amount of 5α-hydroxylaxogenin, an FDA-unapproved ingredient, was detected in two of dietary supplements (44.4 and 32.3 mg/g). This component should be controlled since it may cause unexpected side effects if administered excessively. Thus, this method will be helpful for the continuous control and supervision of unlicensed dietary supplements containing natural-derived steroids and their analogues.

Application of predicted fragmentation pathways and fragment ion structures for detecting steroids and selective androgen receptor modulators in dietary supplements using liquid chromatography-quadrupole time-of-flight mass spectrometry.

RATIONALE: Dietary supplements advertised to strengthen muscles have earned fame among athletes. However, several products containing unauthorized compounds are often detected, which can cause a public health risk. Particularly, steroids and selective androgen receptor modulators (SARMs) can cause serious side effects as hormone modulators. In this study, we analyzed 15 steroids and 20 SARMs using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC/QTOFMS) to provide fundamental information about fragmentation pathways and fragment ion structures. METHODS: The optimal conditions of LC/QTOFMS were explored to obtain fragmentation patterns for each compound. The optimal conditions were established by comparing the area and height of the precursor ion peak at 125 or 175 V as a fragmentor energy. Furthermore, the optimized spectra were acquired by applying collision energy ranging from 1 to 50 eV. The energy value was selected under the condition that the mass error of precursor ions was less than 10 ppm. RESULTS: The 35 compounds were classified on the basis of their chemical core structures: arylpropionamide (3 compounds), quinolinone (2), pyrrolidinylbenzonitrile (1), indole (2), tropanol (2), phenylaxadaizole (1), hydantoin (2), phenylthiazole (1), nitrothiophene (1) and steroidal derivative (20). Fragmentation pathways and the chemical structure of each product ion were predicted and identified. Furthermore, the obtained structural information was applied to screen seized samples. As a result, 10 seized samples were confirmed to contain one or more SARMs by comparing each precursor ion and fragmentation pattern. CONCLUSIONS: The application to real samples for accurate screening indicated that the same fragmentation patterns and product ions as one or more SARM standards were detected and identified in the seized samples advertised as muscle building. Therefore, this study can contribute to ensuring the safety of public health through providing fundamental information about the risk of illegal adulteration.

Simultaneous screening of 21 potential adulterants in dietary supplements for the treatment of prostate diseases using ultra-performance liquid chromatography and liquid chromatography-electrospray ionization-tandem mass spectrometry.

Reports of the number of adulteration cases using illegal therapeutic substances in dietary supplements have increased. In recent years, various dietary supplements are being distributed that exaggerate the efficacy of treatment for prostate-related diseases. To develop the preemptive monitoring method, we selected 21 prostate-related therapeutic substances and optimized the simultaneous ultra-performance liquid chromatography and liquid chromatography-electrospray ionization-tandem mass spectrometry and pretreatment procedures for various types of matrices including solid, liquid, and soft capsule samples. The methods were validated by determining the specificity, linearity, limit of detection, limit of quantification, method detection limit, method quantitation limit, precision, accuracy, recovery, stability, and matrix effect. The simultaneous methods were validated according to the international guidelines. In addition, using the validated methods, 81 real samples, which were searched and purchased by focusing on promotional phrases, such as prostate and prostatic hyperplasia, were successfully screened. As a result, sildenafil and tadalafil were detected in one seized capsule sample (5.15 and 14.6 mg/g, respectively). Synthetically, our approach could be useful for the determination of illegal therapeutic substances potentially adulterated in various types of dietary supplements.

Association of the ubiquitin specific peptidase 9X -linked and Afadin expression patterns with sexual maturation in boar testis.

Closely correlated expression patterns between ubiquitin specific peptidase 9X-linked (USP9X) and adherens junction formation factor (Afadin) in mouse testis development suggests that Usp9x regulates the deubiquitination of Af-6 (also known as Afadin, AFDN), and subsequently, the cell adhesion dynamics during gametogenesis. However, this relationship has not yet been tested in other domestic animals. The study was examined the temporal and spatial expression patterns of porcine USP9X and AFDN from the pre-pubertal to adult stages using real time-PCR and immunohistochemistry. Furthermore, we detected the transcripts of USP9X and AFDN in the testis of 1-, 6- and 12-months old boar, respectively. USP9X and AFDN were found to have similar expressions patterns, with basal expression after 1 month followed by a significant up-regulation from 6 months (puberty) onwards. In addition, neither the AFDN or USP9X proteins were detected in spermatogenic cells but they were expressed in the leydig cells and sertoli cells. USP9X was detected around the basal lamina during pre-puberty, and predominantly expressed in the leydig cells at puberty. Finally, in adult testis, USP9X was increased at the sertoli cell-cell interface and the sertoli cell-spermatid interface. In summary, closely correlated expression patterns between USP9X and AFDN in boar testis supports the previous findings in mice. Furthermore, the junction connections between the sertoli cells may be regulated by the ubiquitination process mediated via USP9X.

Gender-Specific Association of Serum Uric Acid and Pulmonary Function: Data from the Korea National Health and Nutrition Examination Survey.

Background and Objectives: Hyperuricemia is associated with several comorbidities. The association between uric acid (UA) and pulmonary function is still a controversial issue. This study evaluated the gender-specific association of serum UA and pulmonary function. Materials and Methods: A total of 3177 (weighted n = 19,770,902) participants aged 40 years or older were selected from the 2016 Korean National Health and Nutrition Examination Survey and included. Results: Female participants with hyperuricemia were older than participants with normouricemia. Body mass index (BMI), mean arterial pressure (MAP), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR) were significantly associated with UA levels in both males and females. Hyperuricemia and increase in UA quartile were significantly associated with decreased forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in females after adjustment for age, income, region, education, marital status, alcohol consumption, smoking, BMI, MAP, HbA1c, and eGFR. There was no significant association between UA levels and lung function in males. After additional adjustment for respiratory disease including pulmonary tuberculosis, asthma, and lung cancer, the association between hyperuricemia and decreased FEV1 and FVC in females was revealed. Conclusions: Hyperuricemia was associated with decreased FVE1 and FVC in the female general population.

Combined transarterial chemoembolization and radiofrequency ablation for subphrenic versus nonsubphrenic hepatocellular carcinoma: a propensity score matched study.

PURPOSE: To compare therapeutic outcomes of combined transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) treatment for small hepatocellular carcinoma (HCC) in subphrenic versus nonsubphrenic locations by propensity score matching. METHODS: This retrospective study included 293 patients with single HCC (≤ 3 cm) ineligible for ultrasound-guided RFA who received iodized oil TACE and subsequent RFA between June 2010 and January 2017. The patients were divided into two groups according to the tumor location: subphrenic (n = 99) and nonsubphrenic (n = 194). Subphrenic HCC was defined as a tumor abutting the diaphragm. Local tumor progression (LTP) and overall survival (OS) rates were compared by propensity score matching. Procedure-related complications were also assessed. RESULTS: Matching yielded 93 matched pairs of patients. In the matched cohorts, cumulative 1-, 3-, and 5-year LTP rates were 5.4%, 12.1%, and 12.1% in the subphrenic group and 1.1%, 7.5%, and 8.6% in the nonsubphrenic group, respectively, with no significant differences (p = 0.278). Corresponding OS rates were 100%, 80.2%, and 71.3% in the subphrenic group and 97.9%, 88.1%, and 75.6% in the nonsubphrenic group, respectively, with no significant differences (p = 0.308). The subphrenic location was not a significant risk factor for LTP and OS in multivariate analysis. There were no significant differences in complication rates between the two groups (p > 0.05). CONCLUSION: The therapeutic outcomes of combined TACE and RFA for small subphrenic HCC were similar to those for nonsubphrenic HCC. The combination therapy seems to be an effective and safe method in treating small subphrenic HCC.

Screening sexual performance enhancing compounds and their analogues in counterfeit and illicit erectile dysfunction drugs by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry.

The growth of the counterfeit and illicit drugs market is attributable in part to phosphodiesterase type-5 inhibitor (PDE-5is) medications for erectile dysfunction (ED). PDE-5is and their analogues are being increasingly supplied as counterfeit and illicit drugs marketed to enhance sexual performance. Herein, we screened and confirmed a total of 181 such counterfeit and illicit drugs used to date to enhance sexual performance by high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Out of 181 samples, PDE-5is and their analogues were detected in 156 samples, with 49.4% containing two or more components in a single sample. Sildenafil, tadalafil, and miscellaneous group were detected a rates of 64.1%, 34.4%, and 1.5% times and concentrations of 0.04-496 mg/g, 0.02-147 mg/g, and 0.54-16.4 mg/g, respectively with multiple compound groups also detected in single samples. Overdosing on these drugs can lead to adverse effects, the toxicities of combined administrations have not been researched, and administering multiple components in a single sample can be fatal. We recommend that counterfeit and illicit drugs for enhancing sexual performance be continuously controlled and supervised for the protection of public health, and more studies into toxicity and side effects are required.