A Longitudinal Study of Adult Patients with Staphylococcus aureus Bacteremia over 11 Years in Korea.

BACKGROUND: The temporal changes in the Staphylococcus aureus genotypes causing S. aureus bacteremia (SAB) and the corresponding clinical changes over the last decade in South Korea are rarely investigated. METHODS: A longitudinal study of adult SAB patients was conducted in a large referral hospital in Seoul, South Korea. Adult monomicrobial SAB patients were enrolled between August 2008 and December 2018. Genotyping was performed by multilocus sequence typing (MLST) and staphylococcal protein A (spa) typing. Trends in changes were identified by linear regression analysis. RESULTS: Of 1782 adult SAB patients, the blood isolates of 1,778 (99.8%) and 1,634 (91.7%) were determined to be MLST and spa type, respectively. ST5 (-2.626%/year) and ST239 (-0.354%/year) decreased during the study period (P < 0.001 for both), but ST72 (2.009%/yr)-and ST8 (0.567%/yr) increased (P < 0.001 for both). The most common genotype was changed from ST5 in 2008 (44.9%) to ST72 in 2018 (36.3%). Panton-Valentine leukocidin-positive spa-t008-MRSA (USA300) was found in 28.6%. Central venous catheter (CVC)-related SAB (-2.440%/yr) and persistent SAB (-1.016%/yr) decreased, but mortality and recurrence rates were unchanged. CONCLUSION: Over the last decade, the hospital clones ST5 and ST239 have been replaced by community genotype ST72. This was associated with decreased CVC-related and persistent SAB. Increased USA300 was observed in community and hospital settings. Further research is required to identify the reasons for the ST72 epidemic and predict the impending epidemic of ST8 strains, including USA300.

Beneficial effects on skin health using polysaccharides from red ginseng by-product.

Red Ginseng is well-known functional food in Asia which is produced by steaming and drying fresh ginseng (Panax ginseng). In the production of red ginseng extract, around 65% of the original material is left over as by-product and discarded. Most studies on ginseng are focused on ginsenosides. Many functional substances other than ginsenoside are found in red ginseng, but they have not been studied and are usually discarded. Acidic polysaccharides, which are functional polysaccharides found in the by-product of red ginseng, can be utilized as excellent high-value-added material. In this study, we developed red ginseng by-product polysaccharides (RGBPs) by applying an enzyme-linked high-pressure process (ELHPP). We have demonstrated the antioxidant, anti-aging, and anti-atopic dermatitis efficacy of ELHPP-RGBPs in this study. In acute oral toxicity and skin irritation tests, ELHPP-RGBPs were found to be very low in toxicity. ELHPP-RGBPs inhibited solar ultraviolet-induced matrix metalloproteinase-1 (MMP-1) protein through activator protein-1 (AP-1), a major transcription factor for MMP-1. ELHPP-RGBP attenuated DFE-induced AD-like symptoms as assessed by skin lesion analyses, dermatitis score, and skin thickness. Taken together, these results suggest that ELHPP-RGBP may have potential as a nutraceutical ingredient for skin health. PRACTICAL APPLICATIONS: This paper presents a new method of using ginseng by-product that has not been used and discarded. The use of polysaccharides in ginseng by-product has been shown to prevent skin wrinkles and atopic dermatitis. This is an economical new functional food material.

Selection of an appropriate empiric antibiotic regimen in hematogenous vertebral osteomyelitis.

BACKGROUND: Empiric antibiotic therapy for suspected hematogenous vertebral osteomyelitis (HVO) should be initiated immediately in seriously ill patients and may be required in those with negative microbiological results. The aim of this study was to inform the appropriate selection of empiric antibiotic regimens for the treatment of suspected HVO by analyzing antimicrobial susceptibility of isolated bacteria from microbiologically proven HVO. METHOD: We conducted a retrospective chart review of adult patients with microbiologically proven HVO in five tertiary-care hospitals over a 7-year period. The appropriateness of empiric antibiotic regimens was assessed based on the antibiotic susceptibility profiles of isolated bacteria. RESULTS: In total, 358 cases of microbiologically proven HVO were identified. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (33.5%), followed by methicillin-resistant S. aureus (MRSA) (24.9%), Enterobacteriaceae (19.3%), and Streptococcus species (11.7%). Extended spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and anaerobes accounted for only 1.7% and 1.4%, respectively, of the causative pathogens. Overall, 73.5% of isolated pathogens were susceptible to levofloxacin plus rifampicin, 71.2% to levofloxacin plus clindamycin, and 64.5% to amoxicillin-clavulanate plus ciprofloxacin. The susceptibility to these oral combinations was lower in cases of healthcare-associated HVO (52.6%, 49.6%, and 37.6%, respectively) than in cases of community-acquired HVO (85.8%, 84.0%, and 80.4%, respectively). Vancomycin combined with ciprofloxacin, ceftriaxone, ceftazidime, or cefepime was similarly appropriate (susceptibility rates of 93.0%, 94.1%, 95.8%, and 95.8%, respectively). CONCLUSIONS: Based on our susceptibility data, vancomycin combined with a broad-spectrum cephalosporin or fluoroquinolone may be appropriate for empiric treatment of HVO. Fluoroquinolone-based oral combinations may be not appropriate due to frequent resistance to these agents, especially in cases of healthcare-associated HVO.

Infectious Adverse Events Following Acupuncture: Clinical Progress and Microbiological Etiology.

BACKGROUND: We investigated the clinical progress and bacteriological characteristics of infectious adverse events (AEs) following acupuncture and compared patient characteristics between serious and non-serious outcome groups. METHODS: A retrospective observational study was conducted in 1,174 patients with infectious complications associated with acupuncture at the emergency department (ED) in a tertiary hospital in Korea between 2010 and 2014. Serious outcome was defined as development of septic shock, admission to intensive care unit (ICU) or attaining permanent morbidity. RESULTS: Forty-eight patients had certain causality and cellulitis, necrotizing fasciitis and osteomyelitis were common in order. Among them, 9 patients (18.8%) were categorized into serious outcome group, and they showed devastating outcomes such as septic shock (n = 2), ICU admission (n = 4), and permanent sequelae (n = 5). The serious group had delayed admission to the ED after acupuncture (30.0 [4.0-55.0] vs. 3.0 [1.0-10.0] days, P = 0.023). Methicillin-sensitive Staphylococcus aureus was the most frequently identified microorganism. The patients in the serious group required longer treatment duration (139.0 [49.0-183.5] vs. 14.0 [7.0-34.0] days, P < 0.001) as well as more operation with local (44.4% vs. 10.3%, P = 0.031) or general anaesthesia (33.3% vs. 2.6%, P = 0.017). CONCLUSION: The infectious AEs after acupuncture may cause serious outcomes. Patients and primary physicians should be aware of the risk of infectious complications and make efforts to prevent them.

Patient satisfaction after holmium laser enucleation of the prostate (HoLEP): A prospective cohort study.

OBJECTIVE: To investigate patient satisfaction after holmium laser enucleation of the prostate (HoLEP) in a prospective study. SUBJECTS AND METHODS: From May 2012 to December 2014, 397 patients underwent HoLEP by a single surgeon and enrolled in our prospective registry. Baseline data included age, PSA, transrectal ultrasonography, the international prostate symptom score (IPSS), and overactive bladder symptom score (OABSS). Subjective assessment of surgical outcomes was performed at 6 months postoperatively using self-administered questionnaires consisting of 'satisfaction with treatment question' (STQ), 'overall response assessment' (ORA), and 'willingness to undergo surgery question' (WSQ). RESULTS: A total of 331 patients (mean age 69.6±7.0 years) were included in the analysis. Mean total prostate volume was 69.5 (±42.2) ml. Mean preoperative IPSS score was 18.5 (±7.8). The STQ showed that most patients (91.8%) were satisfied after the surgery. Only 11 (3.3%) patients responded with 'dissatisfied', and no patients replied with 'very dissatisfied'. The WSQ showed that 311 (94.0%) patients were willing to undergo the surgery again if they had to reconsider the surgical decision. The ORA showed that all patients (99.4%) experienced an improvement. When compared with satisfied patients, neutral/dissatisfied patients had lower IPSS quality of life scores (2.7 vs. 0.9, p<0.001), higher IPSS voiding symptom scores (7.0 vs. 1.4, p<0.001), and more frequent episodes of urgency urinary incontinence in OABSS (1.0 vs. 0.3, p = 0.017) at 6 months postoperatively. CONCLUSIONS: The overall level of satisfaction after HoLEP was high. The most common reason for dissatisfaction was the occurrence of urgency urinary incontinence after the surgery.

Polysaccharides from ginseng leaves inhibit tumor metastasis via macrophage and NK cell activation.

In this study, we purified the polysaccharide fraction (GS-P) from the leaves of Panax ginseng C.A. Meyer and analyzed its monosaccharide composition and antitumor and antimetastatic activity in vitro and in vivo. GS-P is a 10.2kDa pectic polysaccharide consisting of 15 different monosaccharides. GS-P treatment significantly inhibited metastasis in mice, in a dose-dependent manner. GS-P was not cytotoxic to colon 26-M3.1 cells and increased mouse splenocyte proliferation. Secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-12 was enhanced in the peritoneal exudate macrophages (PEMs) of GS-P-treated mice. Moreover, PEMs obtained from GS-P-treated mice showed significantly higher tumoricidal activity against colon 26-M3.1 cells, and splenocytes from GS-P-treated mice significantly enhanced NK cell cytotoxicity against YAC-1 tumor cells. Pretreatment with anti-asialo GM1 (an antibody for NK cell depletion) partly suppressed the inhibitory effects of GS-P on lung metastasis. These data suggest that GS-P exhibits antimetastatic activity by promoting the activation of macrophages and NK cells.

Primary Tumor Characteristics Are Important Prognostic Factors for Sorafenib-Treated Patients with Metastatic Renal Cell Carcinoma: A Retrospective Multicenter Study.

We aimed to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with sorafenib. We investigated 177 patients, including 116 who received sorafenib as first-line therapy, using the Cox regression model. During a median follow-up period of 19.2 months, the PFS and OS were 6.4 and 32.6 months among all patients and 7.4 months and undetermined for first-line sorafenib-treated patients, respectively. Clinical T3-4 stage (hazard ratio [HR] 2.56) and a primary tumor size >7 cm (HR 0.34) were significant prognostic factors for PFS among all patients, as were tumor size >7 cm (HR 0.12), collecting system invasion (HR 5.67), and tumor necrosis (HR 4.11) for OS (p < 0.05). In first-line sorafenib-treated patients, ≥4 metastatic lesions (HR 28.57), clinical T3-4 stage (HR 4.34), collecting system invasion (univariate analysis HR 2.11; multivariate analysis HR 0.07), lymphovascular invasion (HR 13.35), and tumor necrosis (HR 6.69) were significant prognosticators of PFS, as were bone metastasis (HR 5.49) and clinical T3-4 stages (HR 4.1) for OS (p < 0.05). Our study thus identified a number of primary tumor-related characteristics as important prognostic factors in sorafenib-treated mRCC patients.

Pretreatment Prognostic Nutritional Index Is an Independent Predictor of Survival in Patients With Metastatic Renal Cell Carcinoma Treated With Targeted Therapy.

BACKGROUND: In the present study we examined the effect of the Prognostic Nutritional Index (PNI) on the overall survival (OS) and progression-free survival (PFS) of patients with metastatic renal cell carcinoma (RCC) treated with targeted therapy. PATIENTS AND METHODS: The study included 125 patients with metastatic RCC. Pretreatment PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariable and multivariable Cox proportional hazards models were used to assess the correlation between pretreatment PNI and OS and PFS. Harrell concordance index was used to measure discrimination. RESULTS: The median follow-up time was 45.3 months (interquartile range, 23.7-77.3 months). Decreased PNI was significantly associated with older female patients, poor Eastern Cooperative Oncology Group performance status, types of initial drug, and increased Memorial Sloan Kettering Cancer Center (MSKCC) and Heng risk score (P < .05). An increase in the PNI of 1 unit was associated with a 10% decrease in the risk of death from RCC (hazard ratio, 0.90; P < .001). In the multivariable analysis, the PNI was an independent prognostic factor for OS (P < .001). In intermediate-risk patients according to MSKCC and Heng risk criteria, OS was better in the high PNI group than in the low PNI group (P = .0136 and P = .0009, respectively). CONCLUSION: PNI is an independent prognostic factor in patients with metastatic RCC treated with targeted therapy. When used as an adjunct, it increases the prognostic accuracy of established factors and could be a valuable tool for tailoring surveillance, patient counseling, and clinical trial design.

A retrospective study of predictive factors for unexpectedly prolonged or shortened progression-free survival and overall survival among patients with metastatic renal cell carcinoma who received first-line targeted therapy.

BACKGROUND: To identify predictors of prolonged or shortened progression-free survival (PFS) and overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) who received first-line targeted therapies. METHODS: This retrospective study included 146 patients with mRCC who were treated during 2007-2015. These patients were divided into a group with the worst response (WG), an expected group (EG), and a group with the best response (BG), based on their PFS (≤3 monthsnths, 3-18 monthsnths, and >18 monthsnths, respectively) and OS (<1 year, 1-3 years, and >3 years, respectively). To identify significant predictive factors, the BG and WG were compared to the EG using the Memorial Sloan Kettering Cancer Center and Heng risk models. RESULTS: The overall PFS and OS were 9.3 months and 16.4 months, respectively. The median PFS for the WG (41.8 %), EG (45.9 %), and BG (12.3 %) were 2.7 months, 9.3 months, and 56.6 months, respectively, and the median OS for the WG (45.9 %), EG (35.6 %), and BG (18.5 %) were 5.5 months, 21.6 months, and 63.1 months, respectively; these outcomes were significantly different (p < 0.001). Nephrectomy (odds ratio [OR]: 7.15) was a significant predictor of PFS in the BG, and the significant predictors of OS in the BG were MSKCC intermediate risk (OR: 0.12), poor risk (OR: 0.04), and a disease-free interval of <1 year (OR: 0.23) (all, p < 0.05). Anemia (OR: 3.25) was a significant predictor of PFS in the WG, and the significant predictors of OS were age (OR: 1.05), anemia (OR: 4.13), lymphocytopenia (OR: 4.76), disease-free interval of <1 year (OR: 4.8), and synchronous metastasis (OR: 3.52) (all, p < 0.05). CONCLUSION: We identified several significant predictors of unexpectedly good and poor response to first-line targeted therapy among patients with mRCC.

Impact of immune status on the clinical characteristics and treatment outcomes of nocardiosis.

Nocardiosis occurs in both immunocompromised and immunocompetent patients. We aimed to assess how its characteristics differ depending on patients' immune status. Of a total of 54 patients with culture-proven nocardiosis diagnosed over 13 years, 18 (33%) were immunocompetent. Half of immunocompetent patients had chronic lung disease and were not receiving systemic corticosteroid. There were no significant differences in clinical, radiographic, and microbiologic characteristics, and treatment outcomes according to immune status, except that pulmonary cavitation (47% vs. 8%) and coexisting infections (17% vs. 0%) were more frequent in immunocompromised hosts. Nocardia farcinica, the most commonly identified isolates at the species level (51%), was highly susceptible to trimethoprim-sulfamethoxazole (100%) and highly resistant to ceftriaxone (94%). Nocardiosis should be considered in differential diagnosis of pneumonia, brain abscess, or soft tissue infection that does not respond to conventional antibiotic therapy such as ceftriaxone, regardless of whether the patient is immunocompromised or not.

Ultrahigh Pressure Processing Produces Alterations in the Metabolite Profiles of Panax ginseng.

Ultrahigh pressure (UHP) treatments are non-thermal processing methods that have customarily been employed to enhance the quality and productivity of plant consumables. We aimed to evaluate the effects of UHP treatments on ginseng samples (white ginseng: WG; UHP-treated WG: UWG; red ginseng: RG; UHP-treated RG: URG; ginseng berries: GB; and UHP-treated GB: UGB) using metabolite profiling based on ultrahigh performance liquid chromatography-linear trap quadrupole-ion trap-tandem mass spectrometry (UHPLC-LTQ-IT-MS/MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Multivariate data analyses revealed a clear demarcation among the GB and UGB samples, and the phenotypic evaluations correlated the highest antioxidant activities and the total phenolic and flavonoid compositions with the UGB samples. Overall, eight amino acids, seven organic acids, seven sugars and sugar derivatives, two fatty acids, three notoginsenosides, three malonylginsenosides, and three ginsenosides, were identified as significantly discriminant metabolites between the GB and UGB samples, with relatively higher proportions in the latter. Ideally, these metabolites can be used as quality biomarkers for the assessment of ginseng products and our results indicate that UHP treatment likely led to an elevation in the proportions of total extractable metabolites in ginseng samples.

In Vitro and In Vivo Tumor Targeted Photothermal Cancer Therapy Using Functionalized Graphene Nanoparticles.

Despite the tremendous progress that photothermal therapy (PTT) has recently achieved, it still has a long way to go to gain the effective targeted photothermal ablation of tumor cells. Driven by this need, we describe a new class of targeted photothermal therapeutic agents for cancer cells with pH responsive bioimaging using near-infrared dye (NIR) IR825, conjugated poly(ethylene glycol)-g-poly(dimethylaminoethyl methacrylate) (PEG-g-PDMA, PgP), and hyaluronic acid (HA) anchored reduced graphene oxide (rGO) hybrid nanoparticles. The obtained rGO nanoparticles (PgP/HA-rGO) showed pH-dependent fluorescence emission and excellent near-infrared (NIR) irradiation of cancer cells targeted in vitro to provide cytotoxicity. Using intravenously administered PTT agents, the time-dependent in vivo tumor target accumulation was exactly defined, presenting eminent photothermal conversion at 4 and 8 h post-injection, which was demonstrated from the ex vivo biodistribution of tumors. These tumor environment responsive hybrid nanoparticles generated photothermal heat, which caused dominant suppression of tumor growth. The histopathological studies obtained by H&E staining demonstrated complete healing from malignant tumor. In an area of limited successes in cancer therapy, our translation will pave the road to design stimulus environment responsive targeted PTT agents for the safe eradication of devastating cancer.

Efficacy and Safety of Sorafenib Therapy on Metastatic Renal Cell Carcinoma in Korean Patients: Results from a Retrospective Multicenter Study.

OBJECTIVE: To evaluate the efficacy and safety of sorafenib for Korean patients with metastatic renal cell carcinoma (mRCC). METHODS: A total of 177 mRCC patients using sorafenib as first- (N = 116), second- (N = 43), and third-line (N = 18) therapies were enrolled from 11 Korean centers between 2006 and 2012. The patient characteristics, therapy duration, tumor response, disease control rate, and tolerability were assessed at baseline and at routine follow-ups, and the progression-free survival (PFS) and overall survival (OS) times and rates were analyzed. RESULTS: Among all patients, 18 (10.2%) stopped sorafenib treatment for a median of 1.7 weeks, including 15 (8.5%) who discontinued the drug, while 40 (22.6%) and 12 (6.8%) patients required dose reductions and drug interruptions, respectively. Severe adverse events (AEs) or poor compliance was observed in 64 (36.2%) patients, with 118 (7.4%) ≥grade 3 AEs. During the treatment, one myocardial infarction was observed. The number of ≥grade 3 AEs in the first-line sorafenib group was 71 (6.8% of the total 1048 AEs). During a median follow-up of 17.2 months, the radiologically confirmed best objective response rate, disease control rate, median PFS, and median OS were 22.0%, 53.0%, 6.4 months (95% confidence interval [CI], 5.2-8.9), and 32.6 months (95% CI, 27.3-63.8) for the total 177 sorafenib-treated patients, respectively, and 23.2%, 56.0%, 7.4 months (95% CI, 5.5-10.5), and not reached yet (95% CI, 1.0-31.1) for the first-line sorafenib group, respectively. CONCLUSIONS: Sorafenib produced tolerable safety, with a ≥grade 3 AE rate of 7.4% and an acceptable disease control rate (53.0%) in Korean mRCC patients.

Efficacy and safety of holmium laser enucleation of the prostate for extremely large prostatic adenoma in patients with benign prostatic hyperplasia.

PURPOSE: To evaluate the efficacy and safety of holmium laser enucleation of the prostate (HoLEP) for extremely large prostates. MATERIALS AND METHODS: Patients undergoing HoLEP between July 2008 and December 2013 from the Seoul National University Hospital Benign Prostatic Hyperplasia Database Registry were retrospectively analyzed. The patients were divided into three groups according to their total prostate volume (TPV): group A (TPV<100 mL), group B (100 mL≤TPV<200 mL), and group C (TPV≥200 mL); the clinical data of the three groups were compared. All patients were followed up 2 weeks, 3 months, and 6 months after surgery. RESULTS: A total of 502 patients (group A, 426; group B, 70; group C, 6) with a mean age of 69.0 (standard deviation, ±7.3) years were included in our analysis. The mean prostate volume and prostate-specific antigen level were 68.7±36.9 mL and 4.15±4.24 ng/mL, respectively. The enucleation and morcellation times were longer in group C (p<0.001), and the enucleation efficacy was higher in this group (p<0.001, R(2)=0.399). Moreover, the mean postoperative catheterization and hospitalization periods were significantly longer in group C (p=0.004 and p=0.011, respectively). However, there were no significant differences between the groups in any other postoperative events, including recatheterization, reoperation, urinary tract infection, clot retention, and bladder neck contracture (p range, 0.516-0.913). One patient in group C experienced recurrence of the urethral stricture. CONCLUSIONS: HoLEP in patients with an extremely large prostate can be performed efficiently and safely.

Fluorescent carbon nanoparticles derived from natural materials of mango fruit for bio-imaging probes.

Water soluble fluorescent carbon nanoparticles (FCP) obtained from a single natural source, mango fruit, were developed as unique materials for non-toxic bio-imaging with different colors and particle sizes. The prepared FCPs showed blue (FCP-B), green (FCP-G) and yellow (FCP-Y) fluorescence, derived by the controlled carbonization method. The FCPs demonstrated hydrodynamic diameters of 5-15 nm, holding great promise for clinical applications. The biocompatible FCPs demonstrated great potential in biological fields through the results of in vitro imaging and in vivo biodistribution. Using intravenously administered FCPs with different colored particles, we precisely defined the clearance and biodistribution, showing rapid and efficient urinary excretion for safe elimination from the body. These findings therefore suggest the promising possibility of using natural sources for producing fluorescent materials.

Factors affecting de novo urinary retention after Holmium laser enucleation of the prostate.

OBJECTIVE: Patients can experience urinary retention (UR) after Holmium laser enucleation of the prostate (HoLEP) that requires bladder distension during the procedure. The aim of this retrospective study is to identify factors affecting the UR after HoLEP. MATERIALS AND METHODS: 336 patients, which underwent HoLEP for a symptomatic benign prostatic hyperplasia between July 2008 and March 2012, were included in this study. Urethral catheters were routinely removed one or two days after surgery. UR was defined as the need for an indwelling catheter placement following a failure to void after catheter removal. Demographic and clinical parameters were compared between the UR (n = 37) and the non-urinary retention (non-UR; n = 299) groups. RESULTS: The mean age of patients was 68.3 (±6.5) years and the mean operative time was 75.3 (±37.4) min. Thirty seven patients (11.0%) experienced a postoperative UR. UR patients voided catheter free an average of 1.9 (±1.7) days after UR. With regard to the causes of UR, 24 (7.1%) and 13 (3.9%) patients experienced a blood clot-related UR and a non-clot related UR respectively. Using multivariate analysis (p<0.05), we found significant differences between the UR and the non-UR groups with regard to a morcellation efficiency (OR 0.701, 95% CI 0.498-0.988) and a bleeding-related complication, such as, a reoperation for bleeding (OR 0.039, 95% CI 0.004-0.383) or a transfusion (OR 0.144, 95% CI 0.027-0.877). Age, history of diabetes, prostate volume, pre-operative post-void residual, bladder contractility index, learning curve, and operative time were not significantly associated with the UR (p>0.05). CONCLUSIONS: De novo UR after HoLEP was found to be self-limited and it was not related to learning curve, patient age, diabetes, or operative time. Efficient morcellation and careful control of bleeding, which reduces clot formation, decrease the risk of UR after HoLEP.

Efficacy of linezolid-based salvage therapy compared with glycopeptide-based therapy in patients with persistent methicillin-resistant Staphylococcus aureus bacteremia.

OBJECTIVE: We evaluated the efficacy of linezolid-based salvage therapy compared with glycopeptide-based therapy in patients with persistent (≥7 days) methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B). METHODS: All patients with MRSA-B during 2-year period at a tertiary-care hospital were prospectively enrolled. Linezolid-based salvage therapy was classified if patients switched glycopeptides to linezolid with/without carbapenem due to persistent MRSA-B. Covariate adjustment using the propensity score and inverse probability of treatment weighting (IPTW) using the propensity score were performed to control for bias in treatment assignment. RESULTS: Of 377 patients with MRSA-B, 90 with persistent MRSA-B were included. Of these, 38 (42%) were classified as linezolid-based salvage group and the remaining 52 (58%) as glycopeptide-based therapy group. The duration of persistent bacteremia (median 16 days vs. 10 days; P = 0.008) was longer in linezolid-based salvage group than in the comparator. However, the 30-day mortality (11% vs. 25%; P = 0.08) had a trend toward being lower in linezolid-based salvage group than those in the comparator. Logistic regression models with covariate adjustment and IPTW using propensity scores also revealed that linezolid-based salvage showed a trend toward having better outcome than the comparator, although this did not reach any statistically significance (OR 0.31; 95% CI 0.03-2.95 and OR 0.19; 95% CI 0.01-3.39, respectively). CONCLUSIONS: While having worse prognostic factors compared with glycopeptide-based therapy, linezolid-based salvage therapy revealed a trend toward better outcomes than the comparator. Our data suggest that linezolid-based salvage therapy would be considered in patients with persistent MRSA-B despite the use of glycopeptides therapy.

Triptolide inactivates Akt and induces caspase-dependent death in cervical cancer cells via the mitochondrial pathway.

Triptolide, the main active component of the traditional Chinese herbal medicine Tripterygium wilfordii Hook F, has been shown to have potent immunosuppressive and anti-inflammatory properties. Here, we investigated the pro-apoptotic effect of triptolide in human cervical cancer cells and its underlying mechanisms. Exposure of cervical cancer cells to triptolide induced apoptosis, which was accompanied by loss of mitochondrial membrane potential, caspase processing (caspase-8, -9 and -3), and cleavage of the caspase substrate, poly(ADP-ribose) polymerase. The cytotoxic effects of triptolide were significantly inhibited by the caspase inhibitor, z-VAD-fmk. Triptolide-induced apoptosis was associated with a marked reduction in Akt phosphorylation and was exacerbated by LY294002 (phosphatidylinositol-3'-kinase inhibitor). Conversely, it was attenuated by Akt overexpression. Triptolide-induced apoptosis was also associated with downregulation of Mcl-1 and was significantly inhibited by Mcl-1 overexpression. These findings show that triptolide induces caspase-dependent, mitochondria-mediated apoptosis in cervical cancer cells, in part, by negatively regulating Akt and Mcl-1.