Topographic Consideration on the Occurrence of Ipsilesional Facial Paresis in Lateral Medullary Infarction.

INTRODUCTION: The purpose of this study was to identify course of the corticobulbar tract and factors associated with the occurrence of facial paresis (FP) in lateral medullary infarction (LMI). METHODS: Patients diagnosed with LMI who were admitted to tertiary hospital were retrospectively investigated and divided into two groups based on the presence of FP. FP was defined as grade 2 or more by the House-Brackmann scale. Differences between the two groups were analyzed with respect to anatomical location of the lesions, demographic data (age, sex), risk factors (diabetes, hypertension, smoking, prior stroke, atrial fibrillation, and other cardiac risk factors for stroke), large vessel involvement on magnetic resonance angiography, other symptoms and signs (sensory symptoms, gait ataxia, limb ataxia, dizziness, Horner syndrome, hoarseness, dysphagia, dysarthria, nystagmus, nausea/vomiting, headache, neck pain, diplopia, and hiccup). RESULTS: Among 44 LMI patients, 15 patients (34%) had FP, and all of them had ipsilesional central-type FP. The FP group tended to involve upper (p < 0.0001) and relative ventral (p = 0.019) part of the lateral medulla. Horizontally large lesion was also related to the presence of FP (p = 0.044). Dysphagia (p = 0.001), dysarthria (p = 0.003), and hiccups (p = 0.034) were more likely to be accompanied by FP. Otherwise, there were no significant differences. CONCLUSION: The results of present study indicate that the corticobulbar fibers innervating the lower face decussate at the upper level of the medulla and ascend through the dorsolateral medulla, where the concentration of the fibers is densest near the nucleus ambiguus.

The origin of sequence type 72 community-associated methicillin-resistant Staphylococcus aureus (MRSA) and fusidic acid (FA) resistant sequence type 5 MRSA: Analysis of FA resistance and spa type in a single center in South Korea.

INTRODUCTION: We investigated the prevalence of fusidic acid (FA) resistance in MSSA and MRSA stratified by sequence (ST) and spa types, and determined the prevalence of FA resistance mechanisms. METHODS: From August 2014 to April 2020, S. aureus blood isolates were collected in Asan Medical Center, Seoul, South Korea. Antimicrobial susceptibility tests were performed using broth microdilution and interpreted according to EUCAST's FA criteria. We performed spa typing for fusA mutation presence and acquired FA resistance determinants (fusB, fusC, and fusD) by PCR. RESULTS: Of the 590 MRSA isolates, 372 were FA resistant, and among 425 MSSA isolates, 136 were resistant. Of the 380 ST5-MRSA isolates, 350 were FA resistant, whereas only 1 of 14 ST5-MSSA isolates was FA resistant. Conversely, of the 163 ST72-MRSA isolates, only 8 were resistant, whereas 37 of 42 ST72-MSSA were resistant. The fusA mutation (80%) was the most common determinant. The one FA resistant ST5-MSSA isolate belonged to the t2460 spa type, the most common spa type (24 of 35 isolates) of FA resistant ST5-MRSA. In addition, t324 and t148, which are minor spa types of ST72-MSSA, were susceptible to FA, in contrast to other ST72-MSSA spa types, and the major spa type of ST72-MRSA (110 of 163 isolates). CONCLUSIONS: FA resistance was common in ST5-MRSA and ST72-MSSA, and rare in ST5-MSSA and ST72-MRSA. Our findings suggest that minor clones of ST5-MSSA isolates, with the fusA mutation and minor clones of ST72-MSSA susceptible to FA, may have evolved to harbor the mecA gene.

Electrochemical Detection of Dopamine Release from Living Neurons Using Graphene Oxide-Incorporated Polypyrrole/Gold Nanocluster Hybrid Nanopattern Arrays.

Stem-cell-based therapeutics have shown immense potential in treating various diseases that are currently incurable. In particular, partial recovery of Parkinson's disease, which occurs due to massive loss or abnormal functionality of dopaminergic (DAnergic) neurons, through the engraftment of stem-cell-derived neurons ex vivo is reported. However, precise assessment of the functionality and maturity of DAnergic neurons is still challenging for their enhanced clinical efficacy. Here, a novel conductive cell cultivation platform, a graphene oxide (GO)-incorporated metallic polymer nanopillar array (GOMPON), that can electrochemically detect dopamine (DA) exocytosis from living DAnergic neurons, is reported. In the cell-free configuration, the linear range is 0.5-100 µm, with a limit of detection of 33.4 nm. Owing to its excellent biocompatibility, a model DAnergic neuron (SH-SY5Y cell) can be cultivated and differentiated on the platform while their DA release can be quantitatively measured in a real-time and nondestructive manner. Finally, it is showed that the functionality of the DAnergic neurons derived from stem cells can be precisely assessed via electrochemical detection of their DA exocytosis. The developed GOMPON is highly promising for a wide range of applications, including real-time monitoring of stem cell differentiation into neuronal lineages, evaluating differentiation protocols, and finding practical stem cell therapies.

TAZ/Wnt-ß-catenin/c-MYC axis regulates cystogenesis in polycystic kidney disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease, primarily caused by germline mutation of PKD1 or PKD2, leading to end-stage renal disease. The Hippo signaling pathway regulates organ growth and cell proliferation. Herein, we demonstrate the regulatory mechanism of cystogenesis in ADPKD by transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo signaling effector. TAZ was highly expressed around the renal cyst-lining epithelial cells of Pkd1-deficient mice. Loss of Taz in Pkd1-deficient mice reduced cyst formation. In wild type, TAZ interacted with PKD1, which inactivated ß-catenin. In contrast, in PKD1-deficient cells, TAZ interacted with AXIN1, thus increasing ß-catenin activity. Interaction of TAZ with AXIN1 in PKD1-deficient cells resulted in nuclear accumulation of TAZ together with ß-catenin, which up-regulated c-MYC expression. Our findings suggest that the PKD1-TAZ-Wnt-ß-catenin-c-MYC signaling axis plays a critical role in cystogenesis and might be a potential therapeutic target against ADPKD.

Effectiveness and Adverse Events of Nirmatrelvir/Ritonavir Versus Molnupiravir for COVID-19 in Outpatient Setting: Multicenter Prospective Observational Study.

BACKGROUND: In this study, we aimed to compare the effectiveness and adverse reactions of nirmatrelvir/ritonavir and molnupiravir in high-risk outpatients with coronavirus disease 2019 (COVID-19). METHODS: This multicenter prospective observational study evaluated the rate of hospitalization, death, and adverse events within 28 days of oral antiviral agent prescription (molnupiravir, n = 240; nirmatrelvir/ritonavir, n = 240) to 480 nonhospitalized adult patients with COVID-19 from August 2, 2022 to March 31, 2023. RESULTS: Patients receiving molnupiravir had a higher prevalence of comorbidities (85.8% vs. 70.4%; P < 0.001) and a higher Charlson comorbidity index (2.8 ± 1.4 vs. 2.5 ± 1.5; P = 0.009) than those receiving nirmatrelvir/ritonavir. Three patients required hospitalization (nirmatrelvir/ritonavir group, n = 1 [0.4%]; molnupiravir group, n = 2 [0.8%]; P = 1.000). Nirmatrelvir/ritonavir was associated with a higher risk of adverse events than molnupiravir (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.27-3.03), especially for patients aged 65 years and older (OR, 3.04; 95% CI, 1.71-5.39). The severity of adverse events in both groups was mild to moderate and improved after discontinuation of medication. In the molnupiravir group, age ≥ 65 years (OR, 0.43 95% CI, 0.22-0.86) and appropriate vaccination (OR, 0.37; 95% CI, 0.15-0.91) reduced the occurrence of adverse events. CONCLUSION: The rates of hospitalization and death were low and not significantly different between high-risk patients who received either nirmatrelvir/ritonavir or molnupiravir. Although adverse events were more frequent with nirmatrelvir/ritonavir than with molnupiravir, none were severe. Nirmatrelvir/ritonavir can be safely used to treat COVID-19, while molnupiravir could be considered as an alternative treatment option for high-risk groups.

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.

Control of a nosocomial measles outbreak among previously vaccinated adults in a population with high vaccine coverage: Korea, 2019.

We describe a measles outbreak among previously vaccinated healthcare workers (HCWs) and inpatients and the control measures implemented at a tertiary care hospital in 2019. Case-patients were laboratory-confirmed measles with throat swabs tested by quantitative polymerase chain reactions (PCR), during April-May 2019. Medical histories and documented immunization records were obtained. We compared attack rates (ARs) among HCWs by occupational subgroup and age and examined the outbreak-associated costs. The index case was not ascertained. Among 26 measles case-patients (22 HCWs, four inpatients) aged 18-28 years, 25 had previously received measles-mumps-rubella (MMR) vaccine (12/26, 46% (two doses); 13/26, 50% (one dose)), and 16 (62%) had positive results of measles IgG prior to measles diagnosis. ARs were higher among HCWs aged < 30 years (1.88%), especially in the subgroup under 25 years of age (2.22%). Control measures included work restrictions for seronegative HCWs (218/2320, 9.4%) in immunity verification, administration of the MMR vaccine (207 HCWs) or intravenous immunoglobulin (2 HCWs and 11 inpatients), enhanced health surveillance of HCWs, and mandatory assessment of patients with measles-like symptoms at the infectious diseases screening units. The hospital spent 90,417,132 Korean won (US $79,733) in response to the outbreak. Measles outbreaks can occur in healthcare settings despite high population immunity, highlighting the importance of stronger vaccination policies, particularly among young HCWs. Moreover, an effective outbreak response comprising immunization activities and enhanced surveillance of HCWs and patients to rapidly detect measles-like symptoms at a prodromal phase is essential to control nosocomial measles outbreaks.

Emergence and Spread of Cephalosporin-Resistant Neisseria gonorrhoeae with Mosaic penA Alleles, South Korea, 2012-2017.

In South Korea, surveillance of antimicrobial drug resistance in Neisseria gonorrhoeae is extremely limited. We describe the emergence and subsequent national spread of N. gonorrhoeae strains with mosaic penA alleles associated with decreased susceptibility and resistance to extended-spectrum cephalosporins. From 2012 through 2017, the proportion of mosaic penA alleles in gonococcal-positive nucleic acid amplification test (NAAT) specimens across South Korea increased from 1.1% to 23.9%. Gonococcal strains with mosaic penA alleles emerged in the international hubs of Seoul in Gyeonggi Province and Busan in South Gyeongsang Province and subsequently spread across South Korea. Most common was mosaic penA-10.001 (n = 572 isolates; 94.7%), which is associated with cefixime resistance. We also identified mosaic penA-34.001 and penA-60.001, both of which are associated with multidrug-resistant gonococcal strains and spread of cefixime and ceftriaxone resistance. Implementation of molecular resistance prediction from N. gonorrhoeae-positive nucleic acid amplification test specimens is imperative in South Korea and internationally.

Autophagy in FOXD1 stroma-derived cells regulates renal fibrosis through TGF-ß and NLRP3 inflammasome pathway.

Renal fibrosis is the final common pathway of various renal injuries and it leads to chronic kidney disease. Recent studies reported that FOXD1-lineage pericyte plays a critical role in tubulointerstitial fibrosis (TIF). However the regulatory mechanisms remain unclear. Autophagy is a cellular process of degradation of damaged cytoplasmic components that regulates cell death and proliferation. To investigate the role of autophagy in FOXD1-lineage pericytes on renal TIF, we generated the FOXD1-lineage stromal cell-specific Atg7 deletion (Atg7△FOXD1) mice. FOXD1-lineage stromal cell-specific Atg7 deletion enhanced renal TIF through Smad-dependent transforming growth factor (TGF)-ß signaling after unilateral ureteral obstruction (UUO). FOXD1-lineage stromal cell-specific Atg7 deletion increased the accumulation of interstitial myofibroblasts and enhanced the differentiation of pericytes into myofibroblasts after UUO. Peritubular capillary rarefaction was accelerated in Atg7△FOXD1 mice after UUO. Atg7△FOXD1 mice increased the accumulation of SQSTM1/p62-positive aggregates in the obstructed kidney and resulted in increased expression of NLRP3 inflammasome, interleukin (IL) 1-ß and caspase-1 signaling pathway, which enhanced apoptosis of interstitial cells after UUO. In summary, our data showed that autophagy in FOXD1-lineage stromal cells plays a protective role in renal TIF through regulating the Smad4 dependent TGF-ß an NLRP3 inflammasome signaling pathway.

Impact of health care-associated community-onset cellulitis in Korea: a multicenter study.

We conducted a multicenter study to determine the clinical and microbiological characteristics of health care-associated (HCA) cellulitis in Korea. We retrospectively reviewed the medical records of patients who had been diagnosed with community-onset cellulitis. Of the 2208 cellulitis patients, 232 (10.5%) had HCA cellulitis, 1243 (56.3%) patients were hospitalized, and 15 (0.7%) died in hospital. Compared with community-acquired (CA) cellulitis, patients with HCA cellulitis were older and more frequently presented with comorbidity and septic shock. A total of 355 microorganisms were isolated from 314 patients (14.2%). Staphylococcus aureus (134 isolates) was the most common organism, followed by Streptococcus spp. (86 isolates) and Gram-negative fermenters (58 isolates). Methicillin-resistant S. aureus (MRSA) accounted for 29.1% (39/134) of S. aureus infections. None of the Gram-negative fermenters were resistant to carbapenem. The antibiotic susceptibility pattern of isolated microorganisms was not different between HCA and CA cellulitis. In patients with HCA cellulitis, S. aureus (11.2% [26/232] vs. 5.5% [108/1976], p = 0.001), including MRSA (4.3% [10/232] vs. 1.5% [29/1976], p = 0.003) and Gram-negative fermenters (6.0% [14/232] vs. 2.3% [44/1976], p = 0.002), were more common causative organisms than in CA-cellulitis patients. Age ≥ 65 years, septic shock, and HCA infection were statistically significant factors associated with in-hospital mortality.

Long-term clinical outcomes in patients with untreated non-culprit intermediate coronary lesion and evaluation of predictors by using virtual histology-intravascular ultrasound; a prospective cohort study.

BACKGROUND: It is uncertain whether the coronary lesion with intermediate stenosis is more likely to cause cardiovascular events than a normal or minimal lesion. We conducted a single-center, prospective cohort study to identify long-term clinical outcomes of patients with untreated non-culprit intermediate lesion and evaluate its predictor of cardiovascular events by using virtual histology-intravascular ultrasound (VH-IVUS). METHODS: Subjects with non-culprit intermediate lesion underwent VH-IVUS were prospectively registered after percutaneous coronary intervention at the culprit lesion. Intermediate lesion was defined as 30 to 70% stenosis in coronary angiography and primary outcome was an occurrence of major adverse cardiovascular events (MACE) defined as all-cause death, intermediate lesion revascularization (InLR), minimal lesion revascularization (MnLR, unplanned revascularization elsewhere in the target vessel or in other coronary arteries which looked normal or minimal stenosis), cerebrovascular events, or non-fatal myocardial infarction (MI). The mean follow-up period was 4.2 years. RESULTS: Total 25 MACE, approximately 7% incidence annually, were identified during a follow-up period in 86 patients with 89 intermediate lesions. InLR (n = 13) was a most common event followed by MnLR (n = 6), non-fatal MI (n = 4), all-cause death (n = 3), and cerebrovascular events (n = 1). Diameter stenosis (OR 1.07, 95% CI 1.01-1.12, p = 0.015), plaque burden (PB, OR 1.07, 95% CI 1.00-1.15, p = 0.040), fibrofatty area (FFA, OR 1.61, 95% CI 1.10-2.38, p = 0.016), PB ≥ 70% (OR 3.93, 95% CI 1.28-12.07, p = 0.018), and area stenosis ≥ 50% (OR 2.94, 95% CI 1.01-8.56, p = 0.042) showed significant relationships with an occurrence of MACE. In multivariable Cox-proportional hazard analysis, FFA in intermediate lesion was an only independent predictor of MACE (HR 1.36, 95% CI 1.05-1.77, p = 0.019). CONCLUSIONS: Untreated intermediate lesions had a significantly higher chance for requiring revascularization compared with a normal or minimal lesion. And also, a large FFA in intermediate lesion was a significant predictor of cardiovascular events and which finding was mainly driven by coronary-related events, in particularly intermediate lesion progression.

Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease.

Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular epithelia form fluid-filled cysts. A major barrier to understanding PKD is the absence of human cellular models that accurately and efficiently recapitulate cystogenesis. Previously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidney organoids. Here we show that systematic substitution of physical components can dramatically increase or decrease cyst formation, unveiling a critical role for microenvironment in PKD. Removal of adherent cues increases cystogenesis 10-fold, producing cysts phenotypically resembling PKD that expand massively to 1-centimetre diameters. Removal of stroma enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression and collagen compaction. Cyclic adenosine monophosphate (cAMP), when added, induces cysts in both PKD organoids and controls. These biomaterials establish a highly efficient model of PKD cystogenesis that directly implicates the microenvironment at the earliest stages of the disease.

Gene-Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development.

A critical event during kidney organogenesis is the differentiation of podocytes, specialized epithelial cells that filter blood plasma to form urine. Podocytes derived from human pluripotent stem cells (hPSC-podocytes) have recently been generated in nephron-like kidney organoids, but the developmental stage of these cells and their capacity to reveal disease mechanisms remains unclear. Here, we show that hPSC-podocytes phenocopy mammalian podocytes at the capillary loop stage (CLS), recapitulating key features of ultrastructure, gene expression, and mutant phenotype. hPSC-podocytes in vitro progressively establish junction-rich basal membranes (nephrin+ podocin+ ZO-1+ ) and microvillus-rich apical membranes (podocalyxin+ ), similar to CLS podocytes in vivo. Ultrastructural, biophysical, and transcriptomic analysis of podocalyxin-knockout hPSCs and derived podocytes, generated using CRISPR/Cas9, reveals defects in the assembly of microvilli and lateral spaces between developing podocytes, resulting in failed junctional migration. These defects are phenocopied in CLS glomeruli of podocalyxin-deficient mice, which cannot produce urine, thereby demonstrating that podocalyxin has a conserved and essential role in mammalian podocyte maturation. Defining the maturity of hPSC-podocytes and their capacity to reveal and recapitulate pathophysiological mechanisms establishes a powerful framework for studying human kidney disease and regeneration. Stem Cells 2017;35:2366-2378.

Effect of cerebral embolus size on the timing of cardiac surgery for infective endocarditis in patients with neurological complications.

The optimal timing of cardiac surgery remains unclear for patients with neurological complications of infective endocarditis (IE). However, neuroimaging findings may allow more refined clinical decision-making. We analyzed clinical and advanced neuroimaging data for 135 patients with IE who had preoperatively diagnosed ischemic cerebral complications (86 patients) or hemorrhagic complications (49 patients), between January 1997 and May 2013. The effect of early surgery (within 3 and 7 days of ischemic and hemorrhagic complications respectively) on in-hospital mortality and 1-year adverse outcomes (mortality, relapse, or new embolic events) was estimated. Small cerebral emboli (≤2 cm) led to early surgery (cases with ischemic complications: 57% vs 26%, p = 0.04; cases with hemorrhagic complications: 56% vs 13%, p = 0.02). Early surgery was not significantly associated with increased rates of in-hospital mortality and 1-year adverse outcomes among patients with ischemic complications (14% vs 9%, odds ratio [OR] 1.67, 95% confidence interval [CI] 0.44-6.38, p = 0.52; 17% vs 14%, OR 1.27, 95% CI 0.39-4.14, p = 0.7 respectively). Only 1 patient (4%) with hemorrhagic complications experienced in-hospital mortality in the early surgery group, and early surgery was not significantly associated with 1-year adverse outcomes (21% vs 12%, OR 1.93, 95% CI 0.41-9.16, p = 0.46). The risks of in-hospital mortality and 1-year adverse outcome were not increased, even if cardiac surgery had been carried out earlier than previously described. Our findings suggest that early surgery, when indicated, may be performed for patients with IE and neurological complications, especially if the cerebral embolus has a diameter of ≤2 cm.

Assessment of the accuracy and stability of frameless gamma knife radiosurgery.

The aim of this study was to assess the accuracy and stability of frameless gamma knife radiosurgery (GKRS). The accuracies of the radiation isocenter and patient couch movement were evaluated by film dosimetry with a half-year cycle. Radiation isocenter assessment with a diode detector and cone-beam computed tomography (CBCT) image accuracy tests were performed daily with a vendor-provided tool for one and a half years after installation. CBCT image quality was examined twice a month with a phantom. The accuracy of image coregistration using CBCT images was studied using magnetic resonance (MR) and computed tomography (CT) images of another phantom. The overall positional accuracy was measured in whole procedure tests using film dosimetry with an anthropomorphic phantom. The positional errors of the radiation isocenter at the center and at an extreme position were both less than 0.1 mm. The three-dimensional deviation of the CBCT coordinate system was stable for one and a half years (mean 0.04 ± 0.02 mm). Image coregistration revealed a difference of 0.2 ± 0.1 mm between CT and CBCT images and a deviation of 0.4 ± 0.2 mm between MR and CBCT images. The whole procedure test of the positional accuracy of the mask-based irradiation revealed an accuracy of 0.5 ± 0.6 mm. The radiation isocenter accuracy, patient couch movement accuracy, and Gamma Knife Icon CBCT accuracy were all approximately 0.1 mm and were stable for one and a half years. The coordinate system assigned to MR images through coregistration was more accurate than the system defined by fiducial markers. Possible patient motion during irradiation should be considered when evaluating the overall accuracy of frameless GKRS.

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.

The impact of preload on 3-dimensional deformation parameters: principal strain, twist and torsion.

BACKGROUND: Strain analysis is feasible using three-dimensional (3D) echocardiography. This approach provides various parameters based on speckle tracking analysis from one full-volume image of the left ventricle; however, evidence for its volume independence is still lacking. METHODS: Fifty-eight subjects who were examined by transthoracic echocardiography immediately before and after hemodialysis (HD) were enrolled. Real-time full-volume 3D echocardiographic images were acquired and analyzed using dedicated software. Two-dimensional (2D) longitudinal strain (LS) was also measured for comparison with 3D strain values. RESULTS: Longitudinal (pre-HD: -24.57 ± 2.51, post-HD: -21.42 ± 2.15, P < 0.001); circumferential (pre-HD: -33.35 ± 3.50, post-HD: -30.90 ± 3.22, P < 0.001); and radial strain (pre-HD: 46.47 ± 4.27, post-HD: 42.90 ± 3.61, P < 0.001) values were significantly decreased after HD. The values of 3D principal strain (PS), a unique parameter of 3D images, were affected by acute preload changes (pre-HD: -38.10 ± 3.71, post-HD: -35.33 ± 3.22, P < 0.001). Twist and torsion values were decreased after HD (pre-HD: 17.69 ± 7.80, post-HD: 13.34 ± 6.92, P < 0.001; and pre-HD: 2.04 ± 0.86, post-HD:1.59 ± 0.80, respectively, P < 0.001). The 2D LS values correlated with the 3D LS and PS values. CONCLUSION: Various parameters representing left ventricular mechanics were easily acquired from 3D echocardiographic images; however, like conventional parameters, they were affected by acute preload changes. Therefore, strain values from 3D echocardiography should be interpreted with caution while considering the preload conditions of the patients.

Incidence and Risk Factors of Ocular Infection Caused by Staphylococcus aureus Bacteremia.

Staphylococcus aureusbacteremia (SAB) often leads to ocular infections, including endophthalmitis and chorioretinitis. However, the incidence, risk factors, and outcomes of ocular infections complicated by SAB are largely unknown. We retrospectively analyzed the incidence and risk factors of ocular involvement in a prospective cohort of patients with SAB at a tertiary-care hospital. Ophthalmologists reviewed the fundoscopic findings and classified the ocular infections as endophthalmitis or chorioretinitis. During the 5-year study period, 1,109 patients had SAB, and data for 612 (55%) who underwent ophthalmic examinations within 14 days after SAB onset were analyzed. Of those 612 patients, 56 (9% [95% confidence interval [CI], 7 to 12%]) had ocular involvement, including 15 (2.5%) with endophthalmitis and 41 (6.7%) with chorioretinitis. In a multivariate analysis, infective endocarditis (adjusted odds ratio [aOR], 5.74 [95% CI, 2.25 to 14.64]) and metastatic infection (aOR, 2.38 [95% CI, 1.29 to 4.39]) were independent risk factors for ocular involvement. Of the 47 patients with ocular involvement who could communicate, only 17 (36%) had visual disturbances. Two-thirds of the patients with endophthalmitis (10/15 patients) were treated with intravitreal antibiotics combined with parenteral antibiotics, whereas all of the patients with chorioretinitis were treated only with systemic antibiotics. No patients became blind. Among 42 patients for whom follow-up assessments were available, the ocular lesions improved in 29 (69%) but remained the same in the others. Ocular involvement was independently associated with death within 30 days after SAB onset. Ocular involvement is not uncommon among patients with SAB. Routine ophthalmic examinations should be considered for patients with infective endocarditis or metastatic infections caused by SAB.

Impact of Fluoroquinolone Exposure Prior to Tuberculosis Diagnosis on Clinical Outcomes in Immunocompromised Patients.

There have been concerns about an association of fluoroquinolone (FQ) use prior to tuberculosis (TB) diagnosis with adverse outcomes. However, FQ use might prevent clinical deterioration in missed TB patients, especially in those who are immunocompromised, until they receive definitive anti-TB treatment. All adult immunocompromised patients with smear-negative and culture-positive TB at a tertiary care hospital in Korea over a 2-year period were included in this study. Long-term FQ (≥7 days) use was defined as exposure to FQ for at least 7 days prior to TB diagnosis. A total of 194 patients were identified: 33 (17%) in the long-term FQ group and 161 (83%) in the comparator, including a short-term FQ group (n = 23), non-FQ group (n = 78), and a group receiving no antibiotics (n = 60). Patients in the long-term FQ group presented with atypical chest radiologic pattern more frequently than those in the comparator (77% [24/31] versus 46% [63/138]; P = 0.001). The median time from mycobacterial test to positive mycobacterial culture appeared to be longer in the long-term FQ group (8.1 weeks versus 7.7 weeks; P = 0.09), although the difference was not statistically significant. Patients in the long-term FQ group were less likely to receive empirical anti-TB treatment (55% versus 74%; P = 0.03). The median time from mycobacterial test to anti-TB therapy was longer in the long-term FQ group (4.6 weeks versus 2.2 weeks; P < 0.001), but there was no significant difference in FQ resistance (0% versus 3%; P > 0.99) or in the 30-day (6% versus 6%; P > 0.99) or 90-day (12% versus 12%; P > 0.99) mortality rate between the two groups. FQ exposure (≥7 days) prior to TB diagnosis in immunocompromised patients appears not to be associated with adverse outcomes.

Aquaporin 2-labeled cells differentiate to intercalated cells in response to potassium depletion.

The mammalian renal collecting duct consists of principal cells (PCs) and intercalated cells (ICs). Both PCs and ICs are involved in potassium (K(+)) homeostasis, PCs through their role in K(+) secretion and ICs through their ability to facilitate K(+) resorption. We previously hypothesized that PCs may differentiate into ICs upon K(+) depletion. However, no direct evidence has yet been obtained to conclusively demonstrate that PCs differentiate into ICs in response to K(+) depletion. Here, we present direct evidence for the differentiation of PCs into ICs by cell lineage tracing using aquaporin 2 (AQP2)-Cre mice and R26R-EYFP transgenic mice. In control mice, AQP2-EYFP(+) cells exhibited mainly a PC phenotype (AQP2-positive/H(+)-ATPase-negative). Interestingly, some AQP2-EYFP(+) cells exhibited an IC phenotype (H(+)-ATPase-positive/AQP2-negative); these cells accounted for 1.7 %. After K(+) depletion, the proportion of AQP2-EYFP(+) cells with an IC phenotype was increased to 4.1 %. Furthermore, some AQP2-EYFP(+) cells exhibited a "null cell" phenotype (AQP2-negative/H(+)-ATPase-negative) after K(+) depletion. Collectively, our data demonstrate that AQP2-labeled cells can differentiate into ICs, as well as null cells, in response to K(+) depletion. This finding indicates that some of AQP2-labeled cells possess properties of progenitor cells and that they can differentiate into ICs in the adult mouse kidney.