Isolated Avulsion Fracture of the Tibial Tuberosity in an Adult Treated with Suture-Bridge Fixation: A Rare Case and Literature Review.

Background and objectives: Isolated tibial tuberosity avulsion fractures are exceptionally uncommon among adults, with limited instances documented in published literature. Here, we describe a case of an isolated tibial tuberosity avulsion fracture in an adult that was treated successfully with the suture bridge repair technique. Patient concerns: A 65-year-old female visited the outpatient department with left knee pain after a slip and fall. Lateral radiographs and sagittal MR images of the left knee revealed the tibial tuberosity avulsion fracture, but the fracture line did not extend into the knee joint space. Surgical intervention was performed on the patient's knee using an anterior midline approach, involving open reduction and internal fixation. The avulsed tendon was grasped and pulled, and an appropriate suture location was identified. Using a suture hook, the suture was guided through the patellar tendon as near to its uppermost point of the fragment as achievable, and tied over tendon. A single suture limb from each anchor was fastened over the tibial tuberosity to the distally positioned foot print anchor, effectively anchoring the tibial tuberosity using the suture bridge technique. The patient started walking on crutches after one week and was able to walk independently with a brace after two weeks from the operation day. After three months, the patient had regained her mobility to the level prior to the injury and exhibited painless active range of motion from 0 to 130 degrees. Hardware positioning and bony union were maintained at the one-year follow-up. Conclusions: In our case, the open suture bridge fixation method for tibial tuberosity avulsion fractures produced satisfactory results. Open suture bridge fixation may be considered for isolated tibial tuberosity avulsion fractures in adults, especially when the avulsion tip is too small for screw fixation.

Is the Surface Anatomy of the Popliteal Crease Related to Lower Extremity Alignment or Knee Osseous Morphology? A Radiographic Study.

Background and objectives: The popliteal crease varies among individuals, and there has been no prior study on this aspect. We assumed that it may be associated with lower extremity alignment and osseous morphology. To demonstrate this, we conducted a radiographic analysis. Materials and Methods: The study was conducted on 121 knees of 63 patients, whose popliteal creases were well distinguished on clinical photographs. PCOA was defined as the angle between the longitudinal axis of the lower leg and the popliteal crease. Through the radiologic examinations performed, the HKA, MPTA, mLDFA, JLCA, MFCA/TEA, and PCA/TEA were measured. Pearson correlation analysis and multiple linear regression analysis were performed on the PCOA and the six radiologic measurements to analyze the relationship. Results: Pearson correlation analysis found HKA had the highest coefficient at 0.568. In multiple linear regression, only HKA was associated, excluding all other measurements. Conclusions: Popliteal crease obliquity is significantly associated with coronal plane lower extremity alignment and exhibits a stronger correlation than with underlying knee osseous morphology. If future research is conducted based on this, popliteal crease could serve as a valuable clue for predicting lower extremity alignment and the risk of osteoarthritis development.

Comparing the Anterior-Based Muscle-Sparing Approach with the Direct Anterior Approach in Hip Arthroplasty: A Systematic Review and Pairwise Meta-Analysis.

Background and Objectives: The anterior-based muscle-sparing (ABMS) approach, which utilizes the interval between the tensor fasciae latae posteriorly, offers several advantages, such as the reduced risk of nerve injury and the freedom to choose various implants. Herein, we aimed to compare the outcome of ABMS to the direct anterior (DA) approach using pairwise meta-analysis techniques. Materials and Methods: A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies published up to 7 June 2023, which compared the ABMS approach with the DA approach for hip arthroplasty. We compared (1) perioperative outcomes (operation time, visual analog scale (VAS) score, total opioid consumption, length of hospital stay (LOS), and the number of patients discharged to their homes); (2) postoperative complications (neuropraxia/nerve injury, dislocation, surgical site infection, intraoperative fracture, and reoperation rate); and (3) implant position (cup inclination, cup anteversion, and stem alignment). Results: Ten studies were eligible for meta-analysis, including 1737 patients who underwent hip arthroplasty with the ABMS approach and 1979 with the DA approach. The pooled analysis showed no differences in all outcome variables, including perioperative outcomes, postoperative complications, and the implant position between the two surgical approaches. Conclusions: In current meta-analysis, the ABMS approach demonstrated comparable results to the conventional DA approach in terms of both clinical and radiologic outcomes as well as postoperative complications. Furthermore, the ABMS approach has the advantage of a broader indication and fewer limitations in terms of the surgical position compared to the DA approach. Therefore, the ABMS approach can be even more beneficial as an option within MSA, surpassing the utility of the DA approach.

Effectiveness of Intravenous Non-Opioid Analgesics for Postoperative Pain Management of in Patients Undergoing Hip Surgery: A Systematic Review and Meta-Analysis.

Background and Objectives: Intravenous (IV) non-opioid analgesics (NOAs) have been extensively investigated as a multimodal analgesic strategy for the management of acute pain after hip surgery. This pair-wise meta-analysis examined IV NOA effects following hip surgery. Materials and Methods: A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies investigating the effect of IV NOA for postoperative pain management following hip surgery up to 7 June 2023. We compared in-admission opioid use, postoperative VAS (visual analogue scale) score, hospital stay duration, and opioid-related adverse events between IV NOA and control groups. Results: Seven studies were included with a total of 953 patients who underwent hip surgery. Of these, 478 underwent IV NOA treatment, and 475 did not. The IV NOA groups had lower opioid use within 24-h following hip surgery (SMD, -0.48; 95% CI, -0.66 to -0.30; p < 0.01), lower VAS score (SMD, -0.47; 95% CI, -0.79 to -0.16; p < 0.01), shorter hospital stay (SMD, -0.28; 95% CI, -0.44 to -0.12; p < 0.01), and lower incidence of nausea and vomiting (OR, 0.32; 95% CI, 0.15 to 0.67; p < 0.01) compared with the control groups. Conclusions: This meta-analysis demonstrated that IV NOA administration following hip surgery may have more favorable postoperative outcomes than those in control groups.

Femoral Tunnel Geometry and Graft Inclination Angles in Anterior Cruciate Ligament Reconstruction Using a Flexible Reamer System.

Background and Objectives: The aim of this study is to investigate the femoral tunnel geometry (femoral tunsnel location, femoral graft bending angle, and femoral tunnel length) on three-dimensional (3D) computed tomography (CT) and graft inclination on magnetic resonance imaging (MRI) after anatomic anterior cruciate ligament (ACL) reconstruction using a flexible reamer system. Materials and Methods: A total of 60 patients who underwent anatomical ACL reconstruction (ACLR) using a flexible reamer system were retrospectively reviewed. One day after the ACLR procedure was performed, all patients underwent three-dimensional computed tomography (3D-CT) and magnetic resonance imaging (MRI). The femoral tunnel location, femoral graft bending angle, femoral tunnel length, and graft inclination were assessed. Results: In the 3D-CTs, the femoral tunnel was located at 29.7 ± 4.4% in the posterior to anterior (deep to shallow) direction and at 24.1 ± 5.9% in the proximal to distal (high to low) direction. The mean femoral graft bending angle was 113.9 ± 5.7°, and the mean femoral tunnel length was 35.2 ± 3.1 mm. Posterior wall breakage was observed in five patients (8.3%). In the MRIs, the mean coronal graft inclination was 69.2 ± 4.7°, and the mean sagittal graft inclination was 52.4 ± 4.6°. The results of this study demonstrated that a comparable femoral graft bending angle and longer femoral tunnel length were observed compared with the reported outcomes from previous studies that used the rigid reamer system. Conclusions: ACLR using a flexible reamer system allowed for an anatomic femoral tunnel location and a comparable graft inclination to that of the native ACL. In addition, it achieved a tolerable femoral graft bending angle and femoral tunnel length.

The Effect of Lactobacillus plantarum Extracellular Vesicles from Korean Women in Their 20s on Skin Aging.

Extracellular vesicles, which are highly conserved in most cells, contain biologically active substances. The vesicles and substances interact with cells and impact physiological mechanisms. The skin is the most external organ and is in direct contact with the external environment. Photoaging and skin damage are caused by extrinsic factors. The formation of wrinkles is a major indicator of skin aging and is caused by a decrease in collagen and hyaluronic acid. MMP-1 expression is also increased. Due to accruing damage, skin aging reduces the ability of the skin barrier, thereby lowering the skin's ability to contain water and increasing the amount of water loss. L. plantarum suppresses various harmful bacteria by secreting an antimicrobial substance. L. plantarum is also found in the skin, and research on the interactions between the bacteria and the skin is in progress. Although several studies have investigated L. plantarum, there are only a limited number of studies on extracellular vesicles (EV) derived from L. plantarum, especially in relation to skin aging. Herein, we isolated EVs that were secreted from L. plantarum of women in their 20s (LpEVs). We then investigated the effect of LpEVs on skin aging in CCD986sk. We showed that LpEVs modulated the mRNA expression of ECM related genes in vitro. Furthermore, LpEVs suppressed wrinkle formation and pigmentation in clinical trials. These results demonstrated that LpEVs have a great effect on skin aging by regulating ECM related genes. In addition, our study offers important evidence on the depigmentation effect of LpEVs.

Population pharmacokinetics of piperacillin/tazobactam in critically ill Korean patients and the effects of extracorporeal membrane oxygenation.

OBJECTIVES: To explore extracorporeal membrane oxygenation (ECMO)-related alterations of the pharmacokinetics (PK) of piperacillin/tazobactam and determine an optimal dosage regimen for critically ill adult patients. METHODS: Population PK models for piperacillin/tazobactam were developed using a non-linear mixed effect modelling approach. The percentage of time within 24 h for which the free concentration exceeded the MIC at a steady-state (50%fT>MIC, 100%fT>MIC, and 100%fT>4×MIC) for various combinations of dosage regimens and renal function were explored using Monte-Carlo simulation. RESULTS: A total of 226 plasma samples from 38 patients were used to develop a population PK model. Piperacillin/tazobactam PK was best described by two-compartment models, in which estimated glomerular filtration rate (eGFR), calculated using CKD-EPI equation based on cystatin C level, was a significant covariate for total clearance of each piperacillin and tazobactam. ECMO use decreased the central volume of distribution of both piperacillin and tazobactam in critically ill patients. Patients with Escherichia coli or Klebsiella pneumoniae infection, but not those with Pseudomonas aeruginosa infection, exhibited a PK/pharmacodynamic target attainment >90% when the target is 50%fT>MIC, as a result of applying the currently recommended dosage regimen. Prolonged or continuous infusion of 16 g/day was required when the treatment goal was 100%fT>MIC or 100%fT>4×MIC, and patients had an eGFR of 130-170 mL/min/1.73 m2. CONCLUSIONS: ECMO use decreases piperacillin/tazobactam exposure. Prolonged or continuous infusion can achieve the treatment target in critically ill patients, particularly when MIC is above 8 mg/L or when patients have an eGFR of 130-170 mL/min/1.73 m2.

Soluble CCR2 gene therapy controls joint inflammation, cartilage damage, and the progression of osteoarthritis by targeting MCP-1 in a monosodium iodoacetate (MIA)-induced OA rat model.

BACKGROUND: Osteoarthritis (OA) is the most common type of degenerative arthritis and affects the entire joint, causing pain, joint inflammation, and cartilage damage. Various risk factors are implicated in causing OA, and in recent years, a lot of research and interest have been directed toward chronic low-grade inflammation in OA. Monocyte chemoattractant protein-1 (MCP-1; also called CCL2) acts through C-C chemokine receptor type 2 (CCR2) in monocytes and is a chemotactic factor of monocytes that plays an important role in the initiation of inflammation. The targeting of CCL2-CCR2 is being studied as part of various topics including the treatment of OA. METHODS: In this study, we evaluated the potential therapeutic effects the sCCR2 E3 gene may exert on OA. The effects of sCCR2 E3 were investigated in animal experiments consisting of intra-articular injection of sCCR2 E3 in a monosodium iodoacetate (MIA)-induced OA rat model. The effects after intra-articular injection of sCCR2 E3 (fusion protein encoding 20 amino acids of the E3 domain of the CCL2 receptor) in a monosodium iodoacetate-induced OA rat model were compared to those in rats treated with empty vector (mock treatment) and full-length sCCR2. RESULTS: Pain improved with expression of the sCCR2 gene. Improved bone resorption upon sCCR2 E3 gene activation was confirmed via bone analyses using micro-computed tomography. Histologic analyses showed that the sCCR2 E3 gene exerted protective effects against cartilage damage and anti-inflammatory effects on joints and the intestine. CONCLUSIONS: These results show that sCCR2 E3 therapy is effective in reducing pain severity, inhibiting cartilage destruction, and suppressing intestinal damage and inflammation. Thus, sCCR2 E3 may be a potential therapy for OA.

Cartilage Regeneration Using Human Umbilical Cord Blood Derived Mesenchymal Stem Cells: A Systematic Review and Meta-Analysis.

Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures with the expectation of improved regeneration capacity. However, the number of studies using hUCB-MSCs is still insufficient, and long-term follow-up results after use are insufficient, indicating the need for additional data and research. We have attempted to prove the efficacy and safety of hUCB-MSC treatment in a comprehensive analysis by including all subjects with knee articular cartilage defect or osteoarthritis who have undergone cartilage repair surgery using hUCB-MSCs. We conducted a meta-analysis and demonstrated efficacy and safety based on a systematic review. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. For this study, we searched the PubMed, Embase, Web of Science, Scopus, and Cochrane Library literature databases up to June 2022. A total of seven studies were included, and quality assessment was performed for each included study using the Newcastle−Ottawa Quality Assessment Scale. Statistical analysis was performed on the extracted pooled clinical outcome data, and subgroup analyses were completed. Results: A total of 570 patients were included in the analysis. In pooled analysis, the final follow-up International Knee Documentation Committee (IKDC) score showed a significant increase (mean difference (MD), −32.82; 95% confidence interval (CI), −38.32 to −27.32; p < 0.00001) with significant heterogeneity (I2 = 93%, p < 0.00001) compared to the preoperative score. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at final follow-up were significantly decreased (MD, 30.73; 95% CI, 24.10−37.36; p < 0.00001) compared to the preoperative scores, with significant heterogeneity (I2 = 95%, p < 0.00001). The visual analog scale (VAS) score at final follow-up was significantly decreased (MD, 4.81; 95% CI, 3.17−6.46; p < 0.00001) compared to the preoperative score, with significant heterogeneity (I2 = 98%, p < 0.00001). Two studies evaluated the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and confirmed sufficient improvement. In a study analyzing a group treated with bone marrow aspiration concentrate (BMAC), there was no significant difference in clinical outcome or M-MOCART score, and the post-treatment International Cartilage Repair Society (ICRS) grade increased. Conclusion: This analysis demonstrated the safety, efficacy, and quality of repaired cartilage following hUCB-MSC therapy. However, there was no clear difference in the comparison with BMAC. In the future, comparative studies with other stem cell therapies or cartilage repair procedures should be published to support the superior effect of hUCB-MSC therapy to improve treatment of cartilage defect or osteoarthritis.

Prospective Cohort Study of Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Adults on Extracorporeal Membrane Oxygenation.

The aim of this study was to develop a population pharmacokinetics (PK) model for vancomycin and to evaluate its pharmacodynamic target attainment in adults on extracorporeal membrane oxygenation (ECMO). After a single 1,000-mg dose of vancomycin, samples were collected 9 times per patient prospectively. A population PK model was developed using a nonlinear mixed-effect model. The probability of target attainment (PTA) of vancomycin was evaluated for various dosing strategies using Monte Carlo simulation. The ratio of the area under the vancomycin concentration-time curve at steady state over 24 h to the MIC (AUC/MIC ratio) was investigated by applying the vancomycin breakpoint distribution of MICs for methicillin-resistant Staphylococcus aureus A total of 22 adult patients with 194 concentration measurements were included. The population PK was best described by a three-compartment model with a proportional residual error model. Vancomycin clearance and steady-state volume of distribution were 4.01 liters/h (0.0542 liters/h/kg) and 29.6 liters (0.400 liters/kg), respectively. If the treatment target AUC/MIC value was only ≥400, a total daily dose of 3 to 4 g would be optimal (PTA of ≥90%) for patients with normal renal function (estimated glomerular filtration rate [eGFR] = 60 to 120 ml/min/1.73 m2) when the MIC was presumed to be 1 mg/liter. However, AUC/MIC values of 400 to 600 were difficult to attain with any dosing strategy regardless of MIC and eGFR. Thus, it is hard to achieve efficacy and safety targets in patients on ECMO using the population dosing approach with Monte Carlo simulations, and therapeutic drug monitoring should be implemented in these patients.

Multivariate analysis of early surgical management factors affecting posttraumatic penoscrotal avulsion injury: a level I trauma center study.

BACKGROUND: To conduct an accurate evaluation of patients presenting with posttraumatic penoscrotal injuries, and to formulate a treatment algorithm based on this assessment. METHODS: We conducted a retrospective chart review study. Patients with penoscrotal defects admitted to our level I trauma center from 2017 to 2019 were evaluated. The Braden scale score was used for wound evaluation and the Korean patient classification system (KPCS) was used for assessment of severity. Univariate and multivariate analyses were performed for potential risk factors associated with early surgical management. RESULTS: In total, there were 58 male patients, and the average Braden scale score was 12.08 ± 2.54, with the scrotum (36.20%), and the penile shaft (32.76%) being popular sites for injuries. The wounds requiring surgical treatment were 20.68% (n = 12), with local flaps (33.33%) being most commonly used. The significant predictors of advanced wounds which required surgical treatment were old age (p = 0.026, odds ratio [OR] 8.238), orthopedic combined injuries (p = 0.044, OR 1.088), intubation (p = 0.018, OR 9.625), restraint (p = 0.036, OR 0.157) and blood transfusion (p < 0.001, OR 2.462). CONCLUSION: In multiple trauma patients, penoscrotal defects caused by high-speed trauma are an important matter of concern. Specifically, patients with combined skeletal injuries or requiring respiratory care were prone to advanced wounds. We proposed a five-category algorithm to manage such patients, which included severity of the patient's condition, respiration, hemodynamic status, comorbidity, and immobilization. Additionally, inter-departmental cooperation and active intervention by plastic surgeons is needed for the comprehensive treatment of such injuries. Trial registration This study was performed in line with the principles of the Declaration of Helsinki. The study and all its protocols were approved by the institutional review board of Ajou Medical Center (approval no. AJIRB-MED-MDB-17-254). The need for informed consent was waived by the institutional review board of our hospital due to the retrospective design of the study.

Ready-to-Use Micronized Human Acellular Dermal Matrix to Accelerate Wound Healing in Diabetic Foot Ulcers: A Prospective Randomized Pilot Study.

OBJECTIVE: To examine and report clinical outcomes of a ready-to-use micronized dermal matrix for diabetic foot ulcers (DFUs) and compare it to treatment with conventional negative-pressure wound therapy (NPWT) only. METHODS: The researchers randomly allocated 30 DFUs Wagner grade 2 or higher from 30 adult patients into two groups. The control group (n = 15) was treated with conventional NPWT, and the experimental group (n = 15) was treated with micronized dermal matrix and NPWT. The researchers evaluated the following outcomes: granulation tissue formation, proportion of patients with closed or granulated wounds at 42 and 120 days, achievement of complete wound healing in the 6 months of follow-up, and intervals from enrollment to final surgical procedures. RESULTS: All 15 wounds treated with the micronized matrix showed healthy granulation tissue without noticeable complications during follow-up. At 42 days, 46.7% of wounds in the experimental group had closed compared with 28.6% in the conventional NPWT group (P = .007). At 120 days, 86.7% of the experimental group had completely closed wounds, compared with 57.1% in the conventional therapy group (P = .040). During the 6-month follow-up period, 93.3% of the experimental group achieved complete wound healing compared with 85.7% of the conventional therapy group (P = .468). CONCLUSIONS: The healing outcomes for DFUs in the experimental group were superior when micronized matrix treatment was combined with NPWT.

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.

Effect of pharmacokinetic model misspecification on antibiotic probability of target attainment predicted by Monte Carlo simulation
.

OBJECTIVE: The first aim of this study was to compare the predictability of efficacy by Monte Carlo simulation between a true one-compartment model and a true two-compartment model for doripenem. The second aim was to explore how we can identify the usefulness of a one-compartment model when the pharmacokinetic/pharmacodynamic (PK/PD) indices between three misspecified one-compartment models and a true two-compartment model are compared. MATERIALS AND METHODS: The reported two-compartment model parameters of two doripenem studies and a vancomycin study were used to generate 200 virtual concentration-time profiles for each study. Sparse and dense sampling designs were selected to build the one- and two-compartment models, respectively. The probability of target attainment (PTA) for the PK/PD indices were compared between the one- and two-compartment models of the same drug, applying the clinical breakpoint distribution of minimum inhibitory concentrations (MICs). RESULTS: The simulated concentration-time profiles reproduced the original data well. In addition, PTAs were similar between the one- and two-compartment models when infusion time and MIC were the same in the doripenem studies. For vancomycin simulations, the maximum difference was 65.9% between a misspecified one-compartment model and the true two-compartment model. CONCLUSION: When a misspecified one-compartment model was established with sparse sampling data, the PTA was significantly different from that of the two-compartment model. Thus, a useful PK model must be verified through diagnostic plots and visual predictive checks and the range of sampling time should be sufficient to explain the PK of a drug.

A new population pharmacokinetic model for vancomycin in patients with variable renal function: Therapeutic drug monitoring based on extended covariate model using CKD-EPI estimation.

WHAT IS KNOWN AND OBJECTIVE: Although patients may have received vancomycin therapy with therapeutic drug monitoring (TDM), those treated with high-strength and long-term vancomycin therapy might have unstable and time-varying renal function. The methods used to estimate renal function should not be considered interchangeable with pharmacokinetic (PK) modeling and model-based estimation of vancomycin pharmacokinetics. While Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for renal function estimation has been widely integrated into clinical practice, a population PK model including CKD-EPI has not been established. The study was aimed at developing a new population PK model for optimal vancomycin prediction in patients with time-varying and variable renal function to evaluate the interchangeability of estimation methods. METHODS: The most suitable population PK model was explored and evaluated using non-linear mixed-effect modelling for the best fit of vancomycin concentrations from patients who needed to maintain high trough vancomycin concentrations of >10 mg/L or >15 mg/L. Renal function was estimated using the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations. NONMEM 7.4 was used to develop the population PK model. RESULTS: A total of 328 vancomycin concentrations in 99 patients were used to develop the population PK model. Vancomycin pharmacokinetics was best described by a two-compartment model. The CKD-EPI equation for vancomycin clearance was included in the final model among the estimation methods of renal function. A new covariate model, including extended covariate parameters that explain changes in renal function from the population-predicted value and individual dosing time, provided the best explanation for vancomycin pharmacokinetics among the various models tested. WHAT IS NEW AND CONCLUSION: A new extended covariate model for vancomycin using the CKD-EPI method may afford suitable dose adjustment for high-strength and long-term vancomycin therapy that results in unstable renal function.

Serum nitric oxide level correlates with serum brain natriuretic peptide and whole blood viscosity in hemodialysis patients.

BACKGROUND: Nitric oxide (NO) is tonically synthesized by the vascular endothelium and known as a marker of vasodilatation and blood flow. As NO has a critical role in hemodynamics, NO may be associated with other hemodynamics-related factors including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and whole blood viscosity (WBV). It has been reported that serum NO level increased in patients undergoing hemodialysis. However, there are few reports about the relationship between NO and hemodynamic parameters in hemodialysis patients. OBJECTIVE: We investigated the associations between serum levels of NO and other hemodynamics-related factors such as ANP, BNP and WBV in patients with hemodialysis. METHODS: NO, ANP, and BNP levels before hemodialysis were measured using ELISA method. We measured WBV in pre- and post-dialysis. RESULTS: Mean serum levels of NO, ANP, and BNP were 13.97 ±â€¯10.34 µg/mL, 198.85 ±â€¯61.56 pg/mL, and 1233.32 ±â€¯280.81 pg/mL, respectively in patients with hemodialysis. The mean WBV values at shear rates of 1, 5, and 300 s-1 for pre-dialyses were 168.5 ±â€¯62.5, 76.9 ±â€¯20.6, and 33.3 ±â€¯3.8 mP, respectively. Serum NO level was positively correlated with WBV at shear rates of 1, 5, and 300 s-1 at pre- and post-hemodialysis. There is a correlation between serum nitrite levels and the change of SBV during hemodialysis. Serum nitrite levels correlated with the serum BNP levels. ANP levels have a negative correlation with pre-dialytic WBV. However, BNP levels did not correlate with WBV during hemodialysis. CONCLUSIONS: WBV is linked to an imbalance in serum vasoactive substances in hemodialysis patients and can cause significant hemodynamic disturbance.

Pharmacokinetics of Doripenem in Healthy Koreans and Monte Carlo Simulations to Explore Optimal Dosage Regimens in Patients With Normal and Enhanced Renal Function.

BACKGROUND: Dose adjustment is often required in patients with normal or enhanced renal function. The aim of this study is to investigate the pharmacokinetic (PK) properties of doripenem and explore optimal dosing regimens in patients with normal or enhanced renal function according to various minimum inhibitory concentrations (MICs). METHODS: The authors conducted a clinical trial and analyzed PK samples in 11 healthy Korean subjects applying noncompartmental analysis and a population approach. The population PK parameter estimates were used in Monte Carlo simulations to explore optimal dosing regimens for a probability of target attainment of 90% at 40% fTMIC (free drug concentrations above MIC). RESULTS: The time course of doripenem concentrations was well described by a 2-compartment model. The population typical values of clearance and steady-state volume were 22.9 L/h and 19.1 L, respectively, and were consistent with our noncompartmental analysis results. When the MIC was greater than 1 mcg/mL, at least increasing the dose or prolonging the infusion time was essential in patients with normal or enhanced renal function. CONCLUSIONS: These results suggest that dosage adjustment such as increasing the dose or lengthening the infusion time should be considered in patients with normal or enhanced renal function.

Outcomes of ureteroscopic double-J ureteral stenting for distal ureteral injury after gynecologic surgery.

INTRODUCTION AND HYPOTHESIS: Ureteral injuries are well-known complications of any gynecologic surgery. We evaluated the safety and feasibility of ureteroscopic double-J (DJ) ureteral stenting in patients with distal ureteral injuries after gynecologic surgery. METHODS: Eleven consecutive patients with an iatrogenic ureteral injury in the distal ureter secondary to gynecologic surgery underwent DJ ureteral stenting between March 2008 and January 2016. Ureteral leakage and stricture were appraised using intravenous pyelography. The operative and clinical outcomes were evaluated. RESULTS: The DJ ureteral stent was successfully inserted using ureteroscopy in all patients, none of whom showed major or minor complications during the intraoperative and perioperative follow-up periods. Intravenous pyelography performed every 3 months during the follow-up period verified recovery at the ureteral injury site, without urine leakage. However, five patients experienced ureteral stricture. Balloon dilatation or Holmium laser endoureterotomy was performed successfully in all patients. One patient with recurring ureteral stricture was retreated using Holmium laser endoureterotomy and balloon dilatation; during 12 months of follow-up, there was no recurrence. Overall long-term success rate was 100%, with a mean follow-up of 20.4 months. CONCLUSION: DJ stenting using ureteroscopy diminishes the necessity for invasive surgical procedures and is regarded as one of the available management options for patients with an iatrogenic ureteral injury before considering an invasive operation. However, since ureteral stricture frequently occurs after ureteroscopic procedures, it is essential to select the appropriate patients.

Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections.

We investigated the population pharmacokinetics (PK) of doripenem in Korean patients with acute infections and determined an appropriate dosing regimen using a Monte Carlo simulation for predicting pharmacodynamics (PD). Patients (n = 37) with a creatinine clearance (CLCR) of 20 to 50 ml/min or >50 ml/min who received a 250-mg or 500-mg dose of doripenem over the course of 1 h every 8 h, respectively, were included in this study. Blood samples were taken predosing and 0 h, 0.5 h, and 4 to 6 h after the fourth infusion. A nonlinear mixed-effect modeling tool was used for the PK analysis and pharmacodynamic simulation; doripenem PK were well described by a one-compartment model. The population mean values of the body weight (WT)-normalized clearance (CL/WT) and the body weight-normalized volume of distribution (V/WT) were 0.109 liter/h/kg of body weight (relative standard error, 9.197%) and 0.280 liter/kg (relative standard error, 9.56%), respectively. Doripenem CL was significantly influenced by CLCR The proposed equation to estimate doripenem CL in Korean patients was CL/WT = 0.109 × WT × (CLCR/57)0.688, where CL/WT is in liters per hour per kilogram. CL in Korean patients was expected to be lower than that in Caucasian patients, regardless of renal function. The Monte Carlo simulation showed that 90% attainment of target PK/PD magnitudes could be achieved with the usual dosing regimens when the MIC was ≤1 mg/liter. However, prolonged infusions (4 h) should be considered, especially when patients have augmented renal function and for patients infected with pathogens with a high MIC. Our results provide an individualized doripenem dosing regimen for patients with various renal functions and for patients infected with bacteria with decreased susceptibility.

Comparison of high- and low-dose intra-articular triamcinolone acetonide injection for treatment of primary shoulder stiffness: a prospective randomized trial.

BACKGROUND: Intra-articular corticosteroid injection has a proven effect for shoulder stiffness, yet the optimal dose is still controversial. The purpose of the study was to compare the outcomes of intra-articular triamcinolone acetonide injection at 2 different doses in patients with shoulder stiffness. METHODS: Intra-articular injection of 40 mg (group I, n = 76) or 20 mg (group II, n = 71) of triamcinolone acetonide was performed in patients with shoulder stiffness. The outcome measures including range of motion (ROM), American Shoulder and Elbow Surgeons score, visual analog scale for pain score, and Simple Shoulder Test score were evaluated at 3 weeks, 6 weeks, 12 weeks, 6 months, 12 months, and the last follow-up. Among the patients with controlled diabetes, the levels of blood glucose, fructosamine, and HbA1c were measured to evaluate systemic serologic changes induced by injection. RESULTS: There were significant improvements in ROM and functional scores in both groups at the last follow-up. However, there was no significant difference between the groups in any of the parameters at each time point. None of the diabetic patients in either group had a significant increase in blood glucose, fructosamine, and HbA1c levels compared with levels before injection. However, those in group I showed significantly higher blood glucose levels at 6 weeks after injection compared with those in group II (P = .01). CONCLUSION: Intra-articular injection of triamcinolone is an effective method for improving ROM and clinical function in patients with shoulder stiffness. However, there was no significant difference in regard to different doses. In diabetic patients, a lower dose is recommended as short-term glucose levels may increase with a high dose of corticosteroid.