Fever lasting 48 hours as a predictive factor of ESBL-producing bacteria in non-critically ill patients with urinary tract infection.

Urinary tract infection (UTI) is the most prevalent urological condition worldwide. Choosing appropriate antibiotics for patients who have fever before receiving a culture result is challenging. This retrospective study enrolled patients 394 patients hospitalized at Gangneung Asan Hospital for UTI from May 2017 to April 2021. Fever at 48 h of hospitalization was the analysis point, as this is when the response to antibiotic therapy manifest, although the results of antibiogram are not available. Multivariate analysis was performed to assess the correlation between ESBL producing bacteria (EPB) and fever at 48 h. Overall, 36.3% of patients had EPB and 27.9% had fever at 48 h. In multivariate analysis, a significant positive association was found between EPB and fever (odds ratio 1.17, 95% CI 1.05-1.30, P = 0.004) Female had negative association with multivariate model (OR 0.83, 95% CI 0.73-0.94, P = 0.004). Diabetes did not demonstrate a significant association with EPB. (OR 1.10, 95% CI 0.99-1.22, P = 0.072). Fever at 48 h is associated with EPB and could be considered a predictive factor for EPB infection in patients with UTI. Antibiotic escalation may be considered in patients with fever at 48 h.

Effectiveness of a healthy lifestyle program based on a mobile serious game for childhood cancer survivors: A quasi-randomized trial.

PURPOSE: This study aimed to develop and evaluate the effectiveness of a healthy lifestyle program based on a mobile serious game (HLP-MSG) to enhance the lifestyles of childhood cancer survivors (CCSs). METHODS: This program proceeded in two stages: development and evaluation, using a non-synchronized design with a quasi-randomized trial. The participants were CCSs aged 6-13 years whose treatment was terminated at least 12 months prior. Data were collected at baseline, and post-intervention, with a follow-up after four weeks using the Child Healthy Lifestyle Profile (CHLP). The experimental (n = 26) and control groups (n = 25) were compared. Data were analyzed using descriptive statistics, chi-squared tests, t-tests, and repeated-measures ANOVA. RESULTS: The HLP-MSG promoted a healthy lifestyle by solving 26 quests, including seven sub-elements (nutrition, exercise, hygiene, interpersonal relationships, stress management, meaning of life, and health responsibility). This study revealed significant differences in the interaction between measurement time and group assignment in the CHLP (p = .006) and physical activity (p = .013), one of the seven sub-dimensions. CONCLUSIONS: A healthy lifestyle program based on a mobile serious game is a feasible health education modality to enhance the physical, psychological, social, and spiritual health of CCSs. IMPLICATIONS TO PRACTICE: The findings add to scientific evidence on a mobile serious game for health education among CCSs. The HLP-MSG provides an evolutionary educational modality that can be delivered non-face-to-face to promote CCSs' continuous healthy behavior maintenance. Moreover, the HLP-MSG is adolescent-friendly and can be utilized as a healthcare tool for parents and children to cooperate.

HER2 overexpression predicts pathological T2 stage and improved survival in de novo muscle-invasive bladder cancer after immediate radical cystectomy: a retrospective cohort study.

INTRODUCTION: Human epidermal growth factor receptor type 2 (HER2) overexpression is a prognostic factor and a therapeutic target for breast cancer; however, anti-HER2 therapies are ineffective in patients with bladder cancer. The authors investigated the effect of HER2 overexpression (HER2 + ) on the prognosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: This retrospective cohort study included patients who underwent initial transurethral resection of bladder tumors between 2005 and 2013 and were registered in the Korea National Health Insurance Database, which provides data on overall survival (OS). Sixty-one patients with clinically nonmetastatic de novo MIBC were included in this study. As a subgroup, 33 patients who underwent immediate radical cystectomy (RC) were analyzed. Univariate and multivariate Cox proportional hazards models were used to identify prognostic factors for survival. A multivariable binary logistic regression model was used to identify the favorable T stage. RESULTS: Among the 61 patients with d-MIBC, 14 were HER2 + and 47 HER2 - . Age less than 70 years [hazard ratio (HR): 0.312, CI: 0.16-0.59, P <0.001] and HER2 + status (HR: 0.40, CI: 0.19-0.85, P =0.02) were favorable prognostic factors for OS after adjusting for clinical variables. In the RC subgroup, HER2 + status was a significant predictive factor for the pT2 stage (HR): 36.8, CI: 4.83-797.41, P <0.01). Age less than 70 years (HR: 0.15, CI: 0.05-0.42, P <0.001) and HER2 + status (HR: 0.11, CI: 0.02-0.54, P =0.01) were favorable prognostic factors for OS after adjusting for RC pathological variables. CONCLUSIONS: HER2 + status could be a marker for an indolent subset of MIBC and could predict favorable survival regardless of RC status. Moreover, HER2 + status not only consistently predicted a favorable T stage after RC, but also predicted better survival than pathological outcomes.

Enhancing the Plasma-Resistance Properties of Li2O-Al2O3-SiO2 Glasses for the Semiconductor Etch Process via Alkaline Earth Oxide Incorporation.

To develop plasma-resistant glass materials suitable for semiconductor etching processes, we introduced alkaline earth oxides (ROs) into a Li2O-Al2O3-SiO2 (LAS) glass. Analysis of glass properties with respect to the additives revealed that among the analyzed materials, the LAS material in which Li2O was partially replaced by MgO (MLAS) exhibited the most favorable characteristics, including a low dielectric constant (6.3) and thermal expansion coefficient (2.302 × 10-6/°C). The high performance of MLAS is attributed to the high ionic field strength of Mg2+ ions, which restricts the movement of Li+ ions under the influence of electric fields and thermal vibrations at elevated temperatures. When exposed to CF4/O2/Ar plasma, the etching speed of RO-doped glasses decreased compared with that of quartz and LAS glass, primarily owing to the generation of a high-sublimation-point fluoride layer on the surface. Herein, MLAS demonstrated the slowest etching speed, indicating exceptional plasma resistance. X-ray photoelectron spectroscopy analysis conducted immediately after plasma etching revealed that the oxidation-to-fluorination ratio of Li was the lowest for MLAS. This observation suggests that the presence of Mg2+ ions in the plasma discharge inhibits the migration of Li+ ions toward the surface, thereby contributing to the excellent plasma resistance of MLAS.

Preparation of Remote Plasma Atomic Layer-Deposited HfO2 Thin Films with High Charge Trapping Densities and Their Application in Nonvolatile Memory Devices.

Optimization of equipment structure and process conditions is essential to obtain thin films with the required properties, such as film thickness, trapped charge density, leakage current, and memory characteristics, that ensure reliability of the corresponding device. In this study, we fabricated metal-insulator-semiconductor (MIS) structure capacitors using HfO2 thin films separately deposited by remote plasma (RP) atomic layer deposition (ALD) and direct-plasma (DP) ALD and determined the optimal process temperature by measuring the leakage current and breakdown strength as functions of process temperature. Additionally, we analyzed the effects of the plasma application method on the charge trapping properties of HfO2 thin films and properties of the interface between Si and HfO2. Subsequently, we synthesized charge-trapping memory (CTM) devices utilizing the deposited thin films as charge-trapping layers (CTLs) and evaluated their memory properties. The results indicated excellent memory window characteristics of the RP-HfO2 MIS capacitors compared to those of the DP-HfO2 MIS capacitors. Moreover, the memory characteristics of the RP-HfO2 CTM devices were outstanding as compared to those of the DP-HfO2 CTM devices. In conclusion, the methodology proposed herein can be useful for future implementations of multiple levels of charge-storage nonvolatile memories or synaptic devices that require many states.

Corticosteroid-Antibiotic Interactions in Bacteria that Cause Corneal Infection.

Purpose: Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their co-administration has not been well studied to date. A systematic pharmacodynamic/pharmacokinetic study to determine the effects of cotreatment with various antibiotics and corticosteroids was conducted. Methods: Four bacterial strains, seven antibiotics, and four corticosteroids were used in the analyses. Drug interactions were evaluated by considering antibacterial effects with a checkerboard assay and intracellular concentrations in human corneal epithelial cells. Results: The drug combinations that showed the most stable effects against Pseudomonas aeruginosa was levofloxacin-prednisolone. Stable combinations against the three types of Gram-positive bacteria were neomycin-prednisolone, ofloxacin-dexamethasone, ofloxacin-prednisolone, and polymyxin-dexamethasone. The cellular concentrations were changed for the gatifloxacin-fluorometholone, moxifloxacin-fluorometholone, tobramycin-dexamethasone, and tobramycin-prednisolone combinations. Conclusions: Loteprednol and fluorometholone reduced the antibacterial effects of all of the tested antibiotics in this study. Dexamethasone and prednisolone showed various effects in this regard, depending on the co-administered antibiotic. Prior knowledge of specific antibiotic/corticosteroid interactions provides valuable information to clinical practitioners by combining data on the antibacterial and intracellular uptake effects of their co-administration. Translational Relevance: When using antibiotics and corticosteroids, drug combinations can be selected by referring to the results of this study.

Synthesis of Planar-Type ZnO Powder in Non-Nano Scale Dimension and Its Application in Ultraviolet Protection Cosmetics.

ZnO is one of the most widely used inorganic sunscreens, owing to its fine particle size and UV light shielding capability. However, powders at nanosizes can be toxic and cause adverse effects. The development of non-nanosized particles has been slow. The present work investigated synthesis methods of non-nanosized ZnO particles for ultraviolet protection application. By altering the starting material, KOH concentration, and input speed, the ZnO particles can be obtained in different forms, including needle type, planar type, and vertical wall type. Cosmetic samples were made by mixing different ratios of synthesized powders. The physical properties and the UV blockage efficacy of different samples were evaluated using scanning electron microscopy (SEM), X-ray diffraction (XRD), particle size analyzer (PSA), and ultraviolet/visible (UV/Vis) spectrometer. The samples with 1:1 ratio of needle-type ZnO and vertical wall-type ZnO exhibited superior light blocking effect owing to improved dispersibility and prevention of particle agglomeration. The 1:1 mixed sample also complied with the European nanomaterials regulation due to the absence of nanosized particles. With superior UV protection in the UVA and UVB regions, the 1:1 mixed powder showed potential to be used as a main ingredient in UV protection cosmetics.

Characteristics of Hf0.5Zr0.5O2 Thin Films Prepared by Direct and Remote Plasma Atomic Layer Deposition for Application to Ferroelectric Memory.

Hf0.5Zr0.5O2 (HZO) thin film exhibits ferroelectric properties and is presumed to be suitable for use in next-generation memory devices because of its compatibility with the complementary metal-oxide-semiconductor (CMOS) process. This study examined the physical and electrical properties of HZO thin films deposited by two plasma-enhanced atomic layer deposition (PEALD) methods- direct plasma atomic layer deposition (DPALD) and remote plasma atomic layer deposition (RPALD)-and the effects of plasma application on the properties of HZO thin films. The initial conditions for HZO thin film deposition, depending on the RPALD deposition temperature, were established based on previous research on HZO thin films deposited by the DPALD method. The results show that as the measurement temperature increases, the electric properties of DPALD HZO quickly deteriorate; however, the RPALD HZO thin film exhibited excellent fatigue endurance at a measurement temperature of 60 °C or less. HZO thin films deposited by the DPALD and RPALD methods exhibited relatively good remanent polarization and fatigue endurance, respectively. These results confirm the applicability of the HZO thin films deposited by the RPALD method as ferroelectric memory devices.

Development of PZN-PMN-PZT Piezoelectric Ceramics with High d33 and Qm Values.

To achieve good long-term temperature stability in devices used in energy-conversion applications, this study is aimed at developing combined ceramics, referred to as PZN-PMN-PZT, comprising Pb(Zn1/3Nb2/3)O3 (PZN) and Pb(Mn1/3Nb2/3)O3 (PMN), which are typical relaxor ferroelectric materials, and Pb(Zr,Ti)O3 (PZT). The piezoelectric properties were compared based on several parameters according to the change in the composition ratio between relaxor materials, amounts of Sb2O3 dopant, and Zr/Ti ratio in the PZT system. Finally, we established optimal poling conditions to improve the electrical properties of the optimized piezoelectric material, based on the evaluation of ceramic properties according to the applied voltage during the poling process. The optimized composition of the investigated piezoelectric ceramics is represented by 0.14PZN-0.06PMN-0.80PbZr0.49Ti0.51 + 0.3 wt.% CuO + 0.3 wt.% Fe2O3 with 0.1 wt.% Sb2O3 doping, which yielded the superior properties (d33 = 361 pC/N, Qm = 1234, Tc = 306 °C).

Identification of New Prognostic Markers and Therapeutic Targets for Non-Muscle Invasive Bladder Cancer: HER2 as a Potential Target Antigen.

Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). However, given the current global shortage of BCG, new treatments are needed. We evaluated tumor microenvironment markers as potential BCG alternatives for NMIBC treatment. Programmed death-ligand 1, human epidermal growth factor receptor-2 (HER2), programmed cell death-1 (PD1), CD8, and Ki67 levels were measured in treatment-naïve NMIBC and MIBC patients (pTa, pT1, and pT2 stages). Univariate and multivariate Cox proportional hazard models were used to determine the impact of these markers and other clinicopathological factors on survival, recurrence, and progression. EP263, IM142, PD1, and Ki67 levels were the highest in the T2 stage, followed by the T1 and Ta stages. HER2 and IM263 expressions were higher in the T1 and T2 stages than in the Ta stage. In NMIBC, the significant prognostic factors for recurrence-free survival were adjuvant therapy, tumor grade, and HER2 positivity, whereas those for progression-free survival included age, T-stage, and IM263. Age, T-stage, EP263, PD1, CD8, and Ki67 levels were significant factors associated with overall survival. IM263 and HER2 are potential biomarkers for progression and recurrence, respectively. Therefore, we propose HER2 as a potential target antigen for intravesical therapeutics as a BCG alternative.

Elevated aqueous endothelin-1 concentrations in advanced diabetic retinopathy.

PURPOSE: Endothelin-1 (ET-1) is a potent vasoconstrictor which seems to be involved in the pathogenesis of diabetic retinopathy (DR). However, studies on intraocular ET-1 in DR have been limited. Thus, we investigated aqueous ET-1 levels in patients with DR. METHODS: A total 85 subjects were included in this prospective study. Those were classified into three groups: advanced DR group included those with severe nonproliferative DR or proliferative DR, whereas early DR group included those with mild nonproliferative DR or moderative nonproliferative DR. Those who underwent cataract surgery and had no concomitant ocular disease were included in the control group. Aqueous humor levels of ET-1 were obtained before intravitreal bevacizumab injection (IVB) and after 1 month for the DR patients, and at the time of cataract surgery for the control group. RESULTS: Advanced DR group included 40 eyes (47.1%), whereas early DR group did 19 eyes (22.4%), and control group (26 eyes, 30.5%). Mean aqueous ET-1 level was 10.1±4.1 pg/mL (6.0-21.0 pg/mL) in advanced DR group, 1.9±0.7 pg/mL (0.6-2.8 pg/mL) in early DR group, and 2.1±1.0 pg/mL (0.7-3.9 pg/mL) in control group (P < 0.001). Advanced DR group was further subdivided into severe nonproliferative DR (15 eyes, 12.8%) and proliferative DR (25 eyes, 34.3%). Mean aqueous ET-1 level was 10.1±4.3 pg/mL (6.0-20.1 pg/mL) in patients with severe nonproliferative DR, and 10.0±4.0 pg/mL (6.0-21.0 pg/mL) in those with proliferative DR (P = 0.928) at baseline. Mean ET-1 level at 1 month after intravitreal injection was 2.5±1.0 pg/mL (0.3-4.8 pg/mL) in patients with severe proliferative DR and 2.9±1.7 pg/mL (1.0-7.0 pg/mL) in those with proliferative DR (P = 0.443). Mean aqueous ET-1 level was significantly reduced in both groups (P < 0.001, respectively). CONCLUSION: The mean aqueous ET-1 level was significantly higher in the eyes with advanced DR than those with early DR and the control group. The mean aqueous ET-1 level was significantly reduced after intravitreal injections in the advanced DR group. Based on our results, future studies on the exact role of ET-1 in the pathogenesis of DR and future implication for intervention would be helpful for managing DR.

Design and Preparation of Self-Oscillating Actuators Using Piezoelectric Ceramics with High Coupling Factors and Mechanical Quality Factors.

Piezoelectric material properties were optimized to develop materials for an ultrasonic vibrator targeting a high vibration efficiency. Herein, novel materials were developed using a composition represented by 0.08Pb(Ni1/3Nb2/3)O3-0.07Pb(Mn1/3Nb2/3)O3-0.85Pb(Zr0.5Ti0.5)O3 + 0.3 wt.% CuO + 0.3 wt.% Fe2O3 with 0.3 wt.% Sb2O3 doping. A ceramic shape with a thickness of 2 mm was optimized using finite element analysis software, and high values of coupling factors (0.54) and mechanical quality factors (1151) were obtained. This ceramic was used to fabricate a bio-beauty device (frequency = 1 MHz), and the manufactured ultrasonic vibrator indicated that the actuator oscillated with the maximum amplitude at a frequency of 1.06 MHz.

Overweight and obesity as risk factors for biochemical recurrence of prostate cancer after radical prostatectomy.

BACKGROUND: Previous studies have shown a relationship between the occurrence and recurrence of prostate cancer; however, this relationship remains controversial. We investigated the relationship between obesity and biochemical recurrence in patients with prostate cancer. METHODS: Clinicopathological factors were analyzed after dividing the patient population according to the Asian population-specific body mass index (BMI) criteria for "normal" (< 23 kg/m2), "overweight" (23-27.5 kg/m2), and "obese" (≥ 27.5 kg/m2). Among the 389 patients included in this study, 108 were classified as normal, while 227 and 54 patients were classified as overweight and obese, respectively. The relationships between clinicopathological factors and biochemical recurrence were analyzed by univariate and multivariate Cox ≤ proportional hazard models. Biochemical recurrence was defined as two consecutive prostate-specific antigen (PSA) measurements ≥ 0.2 ng/mL. RESULTS: In univariate analysis, the categorical variables of "overweight" and "obese" were significant prognostic factors for biochemical recurrence. In multivariate analysis models including PSA density [hazard ratio (HR) 1.8, p = 0.01], extraprostatic extension (HR 2.0, p < 0.001), Gleason score (HR 1.7, p = 0.01), surgical margin positivity (HR 2.46, p < 0.001), and lymphovascular invasion (HR 2.53, p < 0.001), the categorical variables of "overweight" (HR 1.6, p = 0.03) and "obese" (HR 1.76, p = 0.035) were prognostic factors for biochemical recurrence. CONCLUSION: The obesity status of patients with prostate cancer as "overweight" and "obese" was a risk factor for biochemical recurrence after adjusting for other clinicopathological factors.

Prospective pharmacological methodology for establishing and evaluating anti-cancer drug resistant cell lines.

BACKGROUND: Cell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible. However, the process for establishing anti-cancer drug resistance in cell cultures in vitro and the subsequent method of then evaluating resistance are not clearly established. Traditionally, the IC50 is the most commonly used indicator of resistance evaluation but it cannot represent the effectiveness of anti-cancer drugs in a clinical setting and lacks reliability because it is heavily affected by the cell doubling time. Hence, new indicators that can evaluate anti-cancer drug resistance are needed. METHODS: A novel resistance evaluation methodology was validated in this present study by establishing sunitinib resistance in renal cell carcinoma cells and assessing the cross-resistance of five different anti-cancer drugs. RESULTS: It was confirmed in this present study that the IC50 does not reflect the cell proliferation rates in a way that represents anti-cancer drug resistance. An alternative indicator that can also be clinically meaningful when using in vitro cell line systems is GI100. Additionally, the GR100 allows different cell populations to be calibrated on the same basis when multiple experimental results are compared. CONCLUSION: Since the GR100 has properties that indicate the efficiency of anti-cancer drugs, both the efficacy and GR100 of a particular anti-cancer drug can be used to effectively assess the resistance.

Significant elevation of aqueous endothelin-1 in central retinal vein occlusion.

PURPOSE: To investigate aqueous humor concentrations of endothelin-1 (ET-1) in patients with central retinal vein occlusion (CRVO) compared with patients with branch retinal vein occlusion (BRVO) and a normal control group. METHODS: A total 80 subjects were included in this prospective study, including 15 patients with CRVO, 20 patients with BRVO, and 45 patients who underwent cataract surgery and had no concomitant ocular disease. Aqueous humor levels of ET-1 were obtained before intravitreal bevacizumab injection (IVB) and after 1 month. RESULTS: At baseline, the mean aqueous ET-1 level was 12.7±3.6 pg/mL in the CRVO group, 8.0±2.3 pg/mL in the BRVO group, and 2.0±0.9 pg/mL in the control group (P<0.001). After IVB, the mean aqueous level of ET-1 was 3.4±1.9 pg/mL (0.5-6.9 pg/mL) in the CRVO group and 1.8±1.0 pg/mL (0.3-3.2 pg/mL) in the BRVO group (P = 0.008). The mean aqueous ET-1 level was significantly reduced in both the patients with CRVO and those with BRVO (P<0.001). CONCLUSION: The mean aqueous humor ET-1 level was significant higher in the patients with CRVO than those with BRVO and in the control group. After IVB, the mean level was significantly reduced in both the patients with CRVO and those with BRVO.

High SLC2A1 expression associated with suppressing CD8 T cells and B cells promoted cancer survival in gastric cancer.

High expression of glucose transporter family members, which augment glucose uptake and glycolytic flux, has been shown to play a pivotal role in the proliferation and survival of tumor cells, contributing to the energy supply, biosynthesis and homeostasis of cancer cells. Among the many members, solute carrier family 2 member 1 (SLC2A1) encodes a glucose transporter, GLUT1, that is critical in the metabolism of glucose, which is an energy source for cell growth that contributes to cancer progression and development. The aim of this study was to analyze the survival and genetic changes/immune profiles in patients with gastric cancer with high SLC2A1 expression and to provide treatment for improving prognosis. This study investigated the clinicopathologic parameters, the proportion of immune cells and gene sets affecting SLC2A1 expression in 279 and 415 patients with gastric cancer from the Eulji Hospital cohort and The Cancer Genome Atlas, respectively. We assessed the response to conventional chemotherapy drugs, including fluorouracil, a compound of fluoropyrimidine S-1, oxaliplatin, and all-trans-retinoic acid (ATRA), in gastric cancer cell lines with high SLC2A1 expression. High SLC2A1 expression was associated with poor prognosis, cancer cell proliferation, decreased immune cells, including CD8 T cells and B cells, and a low prognostic nutrition index, representing body nutrition-related status. In pathway network analysis, SLC2A1 was indirectly linked to the retinoic signaling pathway and negatively regulated immune cells/receptors. In the drug response analysis, the drug ATRA inhibited gastric cancer cell lines with high SLC2A1 expression. Treatment involving the use of SLC2A1 could contribute to better clinical management/research for patients with gastric cancer.

Preparation and Characterization of Planar-Type ZnO Powder with High Aspect Ratio for Application in Ultraviolet- and Heat-Shield Cosmetics.

In this study, a [0001]-plane planar-type ZnO ceramic powder material with a high aspect ratio ranging from 20:1-50:1 is synthesized using the electrolyte collected from zinc air battery power generation. This high aspect ratio may be due to the Zn(OH)2-4 anion dissolved in the electrolyte. The obtained planar-type ZnO exhibits excellent formulation stability and applicability, even when formulated as a cosmetic with a single inorganic ingredient. Compared to commercial ZnO or TiO2 powders, relatively better protection against infrared and ultraviolet (UV) radiation is realized due to its asymmetric characteristics, with a width of approximately 1 µm and thickness of tens of nm. The synthesized planar-type ZnO is mixed with nanosized ZnO or TiO2 commercial powders and formulated into various combinations to achieve a high UV protection rate and heat-blocking effect. In particular, the addition of planar-type ZnO to nanosized TiO2 powders increases the heat-blocking effect, and improves the applicability and formulation stability of the cosmetic formulation, despite the decrease in turbidity. Among all the ceramic powder combinations examined in this study, the best UV protection rate and heat-blocking effect are obtained when the synthesized planar-type ZnO is mixed with microsized and nanosized TiO2.

Impact of Sampling Period on Population Pharmacokinetic Analysis of Antibiotics: Why do You Take Blood Samples Following the Fourth Dose?

To date, many population pharmacokinetic models of antibiotics have been developed using blood sampling data after the fourth or fifth dose, which represents steady-state levels. However, if a model developed using blood sampled after the first dose is equivalent to that using blood sampled after the fourth dose, it would be advantageous to utilize the former. The aim of this study was to investigate the effect of blood sampling after the first and/or fourth drug administration on the accuracy and precision of parameter estimates. A previously reported robust, two-compartment model of vancomycin was used for simulation to evaluate the performances of the parameter estimates. The parameter estimation performances were assessed using relative bias and relative root mean square error. Performance was investigated in 72 scenarios consisting of a combination of two blood sampling periods (the first and fourth dose), two total clearances, three infusion times, and four sample sizes. The population pharmacokinetic models from data collected at the first dose and those collected at the fourth dose produced parameter estimates that were similar in accuracy and precision. This study will contribute to increasing the efficiency and simplicity of antibiotic pharmacokinetic studies.

Genotypic and Phenotypic Resistance to Clarithromycin in Helicobacter pylori Strains.

BACKGROUND: The increasing prevalence of antimicrobial resistance, together with the lack of novel treatment options, negatively affects successful eradication of Helicobacter pylori. The aim of this study was to investigate genetic mutations in the 23S rRNA genes, which is associated with clarithromycin resistance, and to determine the clinical impact of genotype on phenotypic antimicrobial resistance. METHODS: A total of 46 H. pylori strains were obtained from 13 patients, before and after unsuccessful eradication with clarithromycin-based triple therapy. The phenotypic resistance of each H. pylori strain was determined by minimum inhibitory concentration against clarithromycin using the serial two-fold agar dilution method. The genomic sequences of 23S rRNA genes were identified through next-generation sequencing, and nucleotide variants were determined based on comparison with genome sequences of the reference strain H. pylori 26695. RESULTS: Clarithromycin resistance was found in 9 of 13 subjects before treatment and all subjects after unsuccessful eradication. Whole-genome sequencing of the 23S rRNA genes detected 42 mutations on 40 nonidentical loci, including 2147A>G (formerly 2143A>G) and 2146A>G (formerly 2142A>G). All strains with clarithromycin-resistant phenotype had either 2147A>G or 2146A>G mutation. When comparing genotype and phenotype for clarithromycin resistance, there was a significant association between 2147A>G mutation and clarithromycin-resistant phenotype. CONCLUSIONS: All clarithromycin-resistant strains had either 2146A>G or 2147A>G mutation, suggesting that tests targeting these two mutations may be enough for the prediction of clarithromycin resistance in this population.

Nephrotoxicity of amikacin in noncritically ill patients
.

AIMS: Several studies have reported that critically ill patients who require amikacin for the treatment of severe infection require therapeutic drug monitoring (TDM) to prevent acute kidney injury. Moreover, studies so far have mainly focused on patients with critical illnesses; therefore, the probability of occurrence of nephrotoxicity in noncritically ill patients is less known and tends to be overestimated. Recently, with the emergence of multidrug resistant bacteria, the need for aminoglycosides has resurfaced. Therefore, the aim of this study was to investigate the nephrotoxicity and tolerability of amikacin in noncritically ill patients. MATERIALS AND METHODS: This was a retrospective study that included 224 patients who were administered amikacin. Relevant data on patients' clinical course of disease, comorbidities, and clinical laboratory measurements were statistically analyzed. Nephrotoxicity was defined as a serum creatinine level increase by ≥ 0.3 mg/dL or ≥ 50% after therapy initiation. RESULTS: The mean (SD) daily amikacin dose was 13.04 (4.21) mg/kg. The mean (SD) duration of treatment was 12.09 (12.89) days. The incidence rate (95% CI) of amikacin-induced nephrotoxicity was 1.076/person-year (0.46 - 2.12) for the total person-time (3.44 years). In the risk analysis, no risk factor associated with nephrotoxicity could be found. However, an increasing trend of AKI risk was observed in patients with low baseline estimated glomerular filtration rate. CONCLUSION: In noncritically ill patients, the incidence of amikacin-induced nephrotoxicity was lower than that reported in previous studies. The initial monitoring for kidney function in clinical laboratories may be useful, and therapeutic drug monitoring (TDM) may not be necessary in patients with normal kidney function.