Diabetic Foot Osteomyelitis Undergoing Amputation: Epidemiology and Prognostic Factors for Treatment Failure.

Background: When treating diabetic foot osteomyelitis (DFO), it remains difficult to determine the presence of residual infection and the optimal treatment after bone resection. In this study, we aimed to investigate the clinical characteristics of and prognostic factors in patients with DFO undergoing amputation. Methods: This retrospective study involved 101 patients with DFO who underwent amputation. Data on their demographics, clinical characteristics, tissue culture, and surgery type were collected. Patients were grouped according to primary closure status and clinical outcome postamputation. A good outcome was defined as a successful complete remission, characterized by the maintenance of complete wound healing with no sign of infection at 6 months postamputation. Multivariate logistic regression analysis was performed. Outcomes according to surgery type were also analyzed. Results: Staphylococcus aureus (17%) and Pseudomonas species (14%) were the most prevalent pathogens. Gram-negative bacteria were isolated from 62% of patients. In patients with primary closure, hemodialysis and ankle brachial index (ABI) <0.6 were associated with poor outcomes. In patients with DFO, ABI <0.6 was the only prognostic factor associated with treatment failure. Antimicrobial stewardship allows patients who underwent major amputation to reduce the duration of antibiotic therapy compared to those after minor amputation, although it did not contribute to reducing mortality. Conclusions: Peripheral artery disease and hemodialysis were associated with poor outcomes despite radical resection of the infected bone. Vigilant monitoring after amputation and antimicrobial stewardship implemented based on microbiological epidemiology, prognostic factors, and the type of surgery are important. A multidisciplinary team could assist in these activities to ensure treatment success.

Hierarchical Machine Learning-Based Growth Prediction Model of Panax ginseng Sprouts in a Hydroponic Environment.

Due to an increase in interest towards functional and health-related foods, Panax ginseng sprout has been in the spotlight since it contains a significant amount of saponins which have anti-cancer, -stress, and -diabetic effects. To increase the amount of production as well as decrease the cultivation period, sprouted ginseng is being studied to ascertain its optimal cultivation environment in hydroponics. Although there are studies on functional components, there is a lack of research on early disease prediction along with productivity improvement. In this study, the ginseng sprouts were cultivated in four different hydroponic conditions: control treatment, hydrogen-mineral treatment, Bioblock treatment, and highly concentrated nitrogen treatment. Physical properties were measured, and environmental data were acquired using sensors. Using three algorithms (artificial neural networks, support vector machines, random forest) for germination and rottenness classification, and leaf number and length of stem prediction models, we propose a hierarchical machine learning model that predicts the growth outcome of ginseng sprouts after a week. Based on the results, a regression model predicts the number of leaves and stem length during the growth process. The results of the classifier models showed an F1-score of germination classification of about 99% every week. The rottenness classification model showed an increase from an average of 83.5% to 98.9%. Predicted leaf numbers for week 1 showed an average nRMSE value of 0.27, which decreased by about 33% by week 3. The results for predicting stem length showed a higher performance compared to the regression model for predicting leaf number. These results showed that the proposed hierarchical machine learning algorithm can predict germination and rottenness in ginseng sprout using physical properties.

Late-Onset Granulomatous Pneumocystis jirovecii Pneumonia in A Renal Transplant Recipient: A Clinical Grand Round Conference Case in 2022.

Late-onset Pneumocystis jirovecii pneumonia (PCP) can be developed in solid organ transplant (SOT) patients. Granulomatous P. jirovecii pneumonia (GPCP) can occur in immunocompromised patients, but has rarely been reported in SOT recipients. The diagnosis of GPCP is difficult since the sensitivity of sputum and bronchoalveolar lavage is low and atypical patterns are shown. A 60-year-old man, who had undergone renal transplantation 24 years ago presented with nodular and patchy lung lesions. He was asymptomatic and stable. After empirical treatment with a fluoroquinolone, the condition partially resolved but relapsed 4 months later. The pulmonary nodule was resected, and GPCP was confirmed. The pathogenesis of GPCP remains unclear, but in SOT recipients presenting with an atypical lung pattern, GPCP should be considered. This case was discussed at the Grand Clinical Ground of the Korean Society of Infectious Disease conference on November 3, 2022.

Actinomycosis presenting as an isolated pleural effusion in a patient with an HIV infection: a case report and literature review.

BACKGROUND: Thoracic actinomycosis is an uncommon, chronic, and progressive infection, especially in patients with HIV. We report a case of thoracic actinomycosis presenting as an isolated pleural effusion in a patient with an HIV infection. CASE PRESENTATION: A 68-year-old patient with progressive dyspnea and fever was admitted. On the right side, an ipsilateral massive pleural effusion was confirmed on the chest radiograph, and an HIV infection was newly diagnosed. A pleural biopsy was performed for the further differential diagnosis of potential opportunistic infections and malignancies. The pathology findings were consistent with actinomycosis. CONCLUSIONS: Active diagnostic approaches such as a pleural biopsy should be considered for indeterminate pleural effusions in immunocompromised patients.

Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM. MATERIAL AND METHODS: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machine-learning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. RESULTS: The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machine-learning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). CONCLUSION: The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea.

IMPORTANCE: There is limited information about the clinical course and viral load in asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVE: To quantitatively describe SARS-CoV-2 molecular viral shedding in asymptomatic and symptomatic patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective evaluation was conducted for a cohort of 303 symptomatic and asymptomatic patients with SARS-CoV-2 infection between March 6 and March 26, 2020. Participants were isolated in a community treatment center in Cheonan, Republic of Korea. MAIN OUTCOMES AND MEASURES: Epidemiologic, demographic, and laboratory data were collected and analyzed. Attending health care personnel carefully identified patients' symptoms during isolation. The decision to release an individual from isolation was based on the results of reverse transcription-polymerase chain reaction (RT-PCR) assay from upper respiratory tract specimens (nasopharynx and oropharynx swab) and lower respiratory tract specimens (sputum) for SARS-CoV-2. This testing was performed on days 8, 9, 15, and 16 of isolation. On days 10, 17, 18, and 19, RT-PCR assays from the upper or lower respiratory tract were performed at physician discretion. Cycle threshold (Ct) values in RT-PCR for SARS-CoV-2 detection were determined in both asymptomatic and symptomatic patients. RESULTS: Of the 303 patients with SARS-CoV-2 infection, the median (interquartile range) age was 25 (22-36) years, and 201 (66.3%) were women. Only 12 (3.9%) patients had comorbidities (10 had hypertension, 1 had cancer, and 1 had asthma). Among the 303 patients with SARS-CoV-2 infection, 193 (63.7%) were symptomatic at the time of isolation. Of the 110 (36.3%) asymptomatic patients, 21 (19.1%) developed symptoms during isolation. The median (interquartile range) interval of time from detection of SARS-CoV-2 to symptom onset in presymptomatic patients was 15 (13-20) days. The proportions of participants with a negative conversion at day 14 and day 21 from diagnosis were 33.7% and 75.2%, respectively, in asymptomatic patients and 29.6% and 69.9%, respectively, in symptomatic patients (including presymptomatic patients). The median (SE) time from diagnosis to the first negative conversion was 17 (1.07) days for asymptomatic patients and 19.5 (0.63) days for symptomatic (including presymptomatic) patients (P = .07). The Ct values for the envelope (env) gene from lower respiratory tract specimens showed that viral loads in asymptomatic patients from diagnosis to discharge tended to decrease more slowly in the time interaction trend than those in symptomatic (including presymptomatic) patients (ß = -0.065 [SE, 0.023]; P = .005). CONCLUSIONS AND RELEVANCE: In this cohort study of symptomatic and asymptomatic patients with SARS-CoV-2 infection who were isolated in a community treatment center in Cheonan, Republic of Korea, the Ct values in asymptomatic patients were similar to those in symptomatic patients. Isolation of asymptomatic patients may be necessary to control the spread of SARS-CoV-2.

Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs.

There are limited data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory specimens after resolution of coronavirus disease 2019 (COVID-19)-associated symptoms/signs. We determined duration of SARS-CoV-2 virus shedding in symptomatic patients after remission of symptoms. We investigated the duration of SARS-CoV-2 RNA detection using real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or sputum or saliva. Six patients were included in the final analysis. The median (range) duration of SARS-CoV-2 viral detection after hospitalization was 34 days (22 to 67). After resolution of symptoms/signs, SARS-CoV-2 RNA was detected for median (range) of 26 days (9 to 48). Among the six patients, one had persistent detection of SARS-CoV-2 RNA until day 67 of hospitalization, which was 30 days after symptom resolution. This case represents the longest duration of SARS-CoV-2 detection, and highlights the need for long-term follow up of COVID-19 patients despite resolution of symptoms to confirm SARS-CoV-2 clearance.

Risk Factors for Delayed Isolation of Patients with Active Pulmonary Tuberculosis in an Acute-care Hospital.

The objective of the current study was to determine the factors associated with delayed isolation of pulmonary tuberculosis (TB). In this retrospective study, data of patients newly diagnosed with pulmonary TB from January 2015 through December 2017 at a referral hospital were reviewed. Delayed recognition of pulmonary TB was defined as failure to initiate airborne isolation within the first 3 days of admission. We analyzed the clinical, microbiological, and radiological factors associated with delayed isolation of pulmonary TB. A total of 134 patients with positive sputum acid-fast bacilli (AFB) cultures were analyzed, of which 44 (33%) were isolated within 3 days after admission. In multivariate logistic regression analysis, older age (p = 0.01), admission to departments other than Infectious Disease or Pulmonology (p = 0.005), and presence of malignancy (p = 0.02) were associated with delayed isolation. Patients with a radiologic diagnosis of active pulmonary TB were likely to be isolated early (p = 0.01). Better awareness of pulmonary TB among attending practitioners in hospital settings is required. Delay in isolation is associated with older age, malignancy, hospitalization to departments other than Infectious Disease or Pulmonology, and non-confident radiologic diagnosis of active pulmonary TB.

Monomicrobial gram-negative necrotizing fasciitis: An uncommon but fatal syndrome.

This study aimed to characterize patients with monomicrobial gram-negative necrotizing fasciitis in three university hospitals in Korea. In this study, of the 115 patients with community-acquired necrotizing fasciitis, 67 (58%) had monomicrobial infections: 31 (27%) in the gram-negative group and 36 (31%) in the gram-positive group. The majority of patients in the gram-negative group were infected with Escherichia coli followed by Klebsiella pneumoniae and Vibrio vulnificus. More patients in the gram-negative group showed liver cirrhosis than those in the gram-positive group (39% vs. 14%, P = 0.02). In a multivariable logistic regression analysis, liver cirrhosis (adjusted odds ratio [aOR], 13.7; 95% confidence interval [CI], 2.9-67.0), treatment with antibiotics without surgery (aOR, 10.2; 95% CI, 2.1-48.3), and lower level of albumin (aOR 4.9; 95% CI, 1.6-14.9) were associated with 30-day mortality. Our findings suggest that gram-negative necrotizing fasciitis is more often associated with liver cirrhosis and has poorer outcomes than gram-positive necrotizing fasciitis.

Therapeutic outcome of spinal implant infections caused by Staphylococcus aureus: A retrospective observational study.

Spinal implant infection is a rare but significant complication of spinal fusion surgery, and the most common pathogen is Staphylococcus aureus. It is difficult to treat due to this pathogen's biofilm-forming ability and antibiotic resistance. We evaluated the therapeutic outcome of treatments for S aureus spinal implant infections. We retrospectively reviewed all patients with S aureus spinal implant infections at 11 tertiary-care hospitals over a 9-year period. Parameters predictive of treatment failure and recurrence were analyzed by Cox regression. Of the 102 patients with infections, 76 (75%) were caused by methicillin-resistant S aureus (MRSA) and 51 (50%) were late-onset infections. In all, 83 (81%) patients were managed by debridement, antibiotics, and implant retention (DAIR) and 19 (19%) had their implants removed. The median duration of all antibiotic therapies was 52 days. During a median follow-up period of 32 months, treatment failure occurred in 37 (36%) cases. The median time to treatment failure was 113 days, being <1 year in 30 (81%) patients. DAIR (adjusted hazard ratio [aHR], 6.27; P = .01) and MRSA infection (aHR, 4.07; P = .009) were independently associated with treatment failure. Rifampin-based combination treatments exhibited independent protective effects on recurrence (aHR, 0.23; P = .02). In conclusion, among patients with S aureus spinal implant infections, MRSA and DAIR were independent risk factors for treatment failure, and these risk factors were present in the majority of patients. In this difficult-to-treat population, the overall treatment failure rate was 36%; rifampin may improve the outcomes of patients with S aureus spinal implant infections.

Retrospective analysis of culture-negative versus culture-positive postoperative spinal infections.

Retrospective analysis.This study aimed to investigate the characteristics, clinical features, and outcomes of culture-negative (CN) and culture-positive (CP) postoperative spinal infections (PSIs).Causative organism cultures and the use of adequate antibiotics are essential for treating postoperative spinal wound infections. However, managing infected surgical sites with negative wound culture results is a common clinical problem. Although the outcomes of microbiologically confirmed PSIs have been well studied, the outcomes and clinical characteristics of CN PSIs have not been previously published.Between January 1995 and December 2014, 69 patients diagnosed with PSIs were enrolled. Enrolled patients were classified into 2 groups: CN (28 patients) and CP (41 patients). Baseline data, clinical manifestations, specific treatments, and treatment outcomes were compared with the groups.The overall rate of CN PSI was 40.6% (28/69). Baseline data and clinical manifestations were similar between the 2 groups. There were no significant differences in the duration of parenteral antibiotic use between the CN and CP groups. Revision surgery was required less often for the CN group (64.3%) than for the CP group (87.8%) (P = .020). Revision surgeries were repeated 0.82 times/case in the CN group and 1.34 times/case in the CP group (P = .014). Treatment outcomes, such as poor radiologic findings, need for additional anterior surgery, extension of fusion to adjacent segment surgery, and total length of hospital stay, were not different between groups.Revision surgery was performed less often for the CN group than for the CP group. From the perspective of revision surgery, CN PSIs have better prognosis than CP PSIs. However, clinical presentations and radiologic prognoses were not different between the two groups. We suggest that CN PSIs may be treated in the same way as CP PSIs.

Prevalence of antibiotic susceptibility and resistance of Escherichia coli in acute uncomplicated cystitis in Korea: Systematic review and meta-analysis.

BACKGROUND: The aim of this study is to determine the prevalence of antibiotic susceptibility and resistance of Escherichia coli Escherichia coli (E coli) in female uncomplicated cystitis in Korea using meta-analysis. METHODS: A cross-search of the literature was performed with MEDLINE for all relevant data published before October 2015 and EMBASE from 1980 to 2015, the Cochrane Library, KoreaMed, RISS, KISS, and DBPia were also searched. Observational or prospective studies that reported the prevalence of antimicrobial susceptibility and resistance of E coli were selected for inclusion. No language or time restrictions were applied. We performed a meta-analysis using a random effects model to quantify the prevalence of antimicrobial susceptibility and resistance of E coli. RESULTS: Ten studies were eligible for the meta-analysis, which together included a total of 2305 women with uncomplicated cystitis. The overall resistance rate to antibiotics was 0.28 (95% confidence interval [CI]: 0.25, 0.32). The pooled resistance rates were 0.08 (95% CI: 0.06, 0.11) for cephalosporin, 0.22 (95% CI: 0.18, 0.25) for fluoroquinolone (FQ), and 0.43 (95% CI: 0.35, 0.51) for trimethoprim/sulfamethoxazole (TMP/SMX). Regression analysis showed that resistance to FQ is increasing (P = 0.014) and resistance to TMP/SMX is decreasing (P = 0.043) by year. The generation of cephalosporin was not a significant moderator of differences in resistance rate. CONCLUSION: The resistance rate of FQ in Korea is over 20% and is gradually increasing. Although the resistance rate of TMP/SMX is over 40%, its tendency is in decreasing state. Antibiotic strategies used for the treatment of uncomplicated cystitis in Korea have to be modified.

RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model.

Systemic siRNA administration to target and treat glioblastoma, one of the most deadly cancers, requires robust and efficient delivery platform without immunogenicity. Here we report newly emerged multivalent naked RNA nanoparticle (RNP) based on pRNA 3-way-junction (3WJ) from bacteriophage phi29 to target glioblastoma cells with folate (FA) ligand and deliver siRNA for gene silencing. Systemically injected FA-pRNA-3WJ RNPs successfully targeted and delivered siRNA into brain tumor cells in mice, and efficiently reduced luciferase reporter gene expression (4-fold lower than control). The FA-pRNA-3WJ RNP also can target human patient-derived glioblastoma stem cells, thought to be responsible for tumor initiation and deadly recurrence, without accumulation in adjacent normal brain cells, nor other major internal organs. This study provides possible application of pRNA-3WJ RNP for specific delivery of therapeutics such as siRNA, microRNA and/or chemotherapeutic drugs into glioblastoma cells without inflicting collateral damage to healthy tissues.

Klebsiella pneumonia-induced prostate abscess: How to work it up?

INTRODUCTON: Klebsiella pneumonia (KP) is related to a metastatic phenomenon from the originally affected primary organ. About 28% of patients with pyogenic liver abscess arising from KP suffer from metastatic complications. This study was done to define the clinical features of KP-induced prostate abscess. METHODS: A total of 14 patients were diagnosed with prostate abscess based on clinical, laboratory examination and abdominopelvic computed tomography (CT) scan from 2007 to 2013. RESULTS: Among these 14 patients, KP was the dominant causative microorganism in 6 patients (42.9%), followed by Esherchia coli in 2, Pseudomonas aeroginosa in 1, methicillin-resistant Staphyolcoccus aureus in 1, and no growth in either the urine or blood culture in 4. Four (66.7%) of the 6 KP induced-prostate abscess had other concurrent abscess sites besides the prostate: liver in 3, kidney in 1, and perianal area with endogenous endophthalmitis that ended in loss of vision in 1 patient. CONCLUSIONS: We report on the clinical features of KP-induced prostate abscess based on a small number of patients, which is the main limitation of our study. We believe that if the causative organism of a prostate abscess was KP, more workup would be needed to rule out the presence of an abscess in other organs, especially in the liver. Abdominopelvic CT scan would be a proper imaging modality.

Optogenetics reveals a role for accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine-induced behavioral sensitization.

Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc) have been proposed to contribute to drug-mediated addictive behaviors. Here we have used an optogenetic approach to examine the role of NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2Rs) in cocaine-induced behavioral sensitization. Adeno-associated viral vectors encoding channelrhodopsin-2 (ChR2) were delivered into the NAc of D2R-Cre transgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2R-MSNs form local inhibitory circuits, because photostimulation of D2R-MSN evoked inhibitory postsynaptic currents (IPSCs) in neighboring MSNs. Photostimulation of NAc D2R-MSN in vivo affected neither the initiation nor the expression of cocaine-induced behavioral sensitization. However, photostimulation during the drug withdrawal period attenuated expression of cocaine-induced behavioral sensitization. These results show that D2R-MSNs of NAc play a key role in withdrawal-induced plasticity and may contribute to relapse after cessation of drug abuse.

Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic reticulum stress, and preferentially kills high-grade glioma cells.

BACKGROUNDS: Piperlongumine, a natural plant product, kills multiple cancer types with little effect on normal cells. Piperlongumine raises intracellular levels of reactive oxygen species (ROS), a phenomenon that may underlie the cancer-cell killing. Although these findings suggest that piperlongumine could be useful for treating cancers, the mechanism by which the drug selectively kills cancer cells remains unknown. METHODS: We treated multiple high-grade glioma (HGG) sphere cultures with piperlongumine and assessed its effects on ROS and cell-growth levels as well as changes in downstream signaling. We also examined the levels of putative piperlongumine targets and their roles in HGG cell growth. RESULTS: Piperlongumine treatment increased ROS levels and preferentially killed HGG cells with little effect in normal brain cells. Piperlongumine reportedly increases ROS levels after interactions with several redox regulators. We found that HGG cells expressed higher levels of the putative piperlongumine targets than did normal neural stem cells (NSCs). Furthermore, piperlongumine treatment in HGG cells, but not in normal NSCs, increased oxidative inactivation of peroxiredoxin 4 (PRDX4), an ROS-reducing enzyme that is overexpressed in HGGs and facilitates proper protein folding in the endoplasmic reticulum (ER). Moreover, piperlongumine exacerbated intracellular ER stress, an effect that was mimicked by suppressing PRDX4 expression. CONCLUSIONS: Our results reveal that the mechanism by which piperlongumine preferentially kills HGG cells involves PRDX4 inactivation, thereby inducing ER stress. Therefore, piperlongumine treatment could be considered as a novel therapeutic option for HGG treatment.

The role of c-Src in integrin (α6ß4) dependent translational control.

BACKGROUND: Integrin α6ß4 contributes to cancer progression by stimulating transcription as well as translation of cancer related genes. Our previous study demonstrated that α6ß4 stimulates translation initiation of survival factors such as VEGF by activating mTOR pathway. However, the immediate early signaling events that link α6ß4 to mTOR activation needs to be defined. RESULTS: In the current studies, we demonstrated that c-Src is an immediate early signaling molecule that acts upstream of α6ß4 dependent mTOR activation and subsequent translation of VEGF in MDA-MB-435/ß4 and MDA-MB-231 cancer cells. m7GTP-Sepharose-binding assay revealed that Src activity is required to form eIF4F complex which is necessary for Cap-dependent translation in α6ß4 expressing human cancer cells. CONCLUSIONS: Overall, our studies suggest that integrin ß4 and c-Src activation is important early signaling events to lead mTOR activation and cap-dependent translation of VEGF.

Cytomegalovirus contributes to glioblastoma in the context of tumor suppressor mutations.

To study the controversial role of cytomegalovirus (CMV) in glioblastoma, we assessed the effects of murine CMV (MCMV) perinatal infection in a GFAP-cre; Nf1(loxP/+); Trp53(-/+) genetic mouse model of glioma (Mut3 mice). Early on after infection, MCMV antigen was predominantly localized in CD45+ lymphocytes in the brain with active viral replication and local areas of inflammation, but, by 7 weeks, there was a generalized loss of MCMV in brain, confirmed by bioluminescent imaging. MCMV-infected Mut3 mice exhibited a shorter survival time from their gliomas than control Mut3 mice perinatally infected with mock or with a different neurotropic virus. Animal survival was also significantly shortened when orthotopic gliomas were implanted in mice perinatally infected with MCMV versus controls. MCMV infection increased phosphorylated STAT3 (p-STAT3) levels in neural stem cells (NSC) harvested from Mut3 mice subventricular zone, and, in vivo, there was increased p-STAT3 in NSCs in MCMV-infected compared with control mice. Of relevance, human CMV (HCMV) also increased p-STAT3 and proliferation of patient-derived glioblastoma neurospheres, whereas a STAT3 inhibitor reversed this effect in vitro and in vivo. These findings thus associate CMV infection to a STAT3-dependent modulatory role in glioma formation/progression in the context of tumor suppressor mutations in mice and possibly in humans.

Risk Factors for Mortality in Patients with Acinetobacter baumannii Bacteremia.

BACKGROUND: Acinetobacter baumannii, an opportunistic nosocomial pathogen that can cause significant morbidity and mortality, has emerged as a worldwide problem. The aim of this study was to evaluate the risk factors for mortality in patients with A. baumannii bacteremia. MATERIALS AND METHODS: We retrospectively evaluated 118 patients who had A. baumannii bacteremia between July 2003 and December 2011. The aim of this study was to identify the 30-day mortality in patients with A. baumannii bacteremia and relevant risk factors. RESULTS: The bacteremia-related 30-day mortality rate was 34.1%. Univariate analysis revealed that the risk factors for mortality included malignancy, longer hospital stay before bacteremia, intensive care unit (ICU) stay at the time of bacteremia, mechanical ventilation, use of a central venous catheter, unknown origin of bacteremia, bacteremia due to pneumonia, antimicrobial resistance to carbapenems, and elevated Acute Physiology and Chronic Health Evaluation II and Pitt bacteremia scores. Multivariate logistic regression analysis revealed that resistance to carbapenems (odds ratio [OR]: 4.01, 95% confidence interval [CI]: 1.51 to 0.68, P = 0.005), need for mechanical ventilation (OR: 3.97, 95% CI: 1.41 to 11.13, P = 0.005), and presence of malignancy (OR: 4.40, 95% CI: 1.60 to 12.08, P = 0.004) were significantly related to mortality risk. CONCLUSIONS: Risk factors such as resistance to carbapenems, mechanical ventilation, and presence of malignancy were found to be associated with high mortality rates in the patients with A. baumannii bacteremia.

Suppression of peroxiredoxin 4 in glioblastoma cells increases apoptosis and reduces tumor growth.

Glioblastoma multiforme (GBM), the most common and aggressive primary brain malignancy, is incurable despite the best combination of current cancer therapies. For the development of more effective therapies, discovery of novel candidate tumor drivers is urgently needed. Here, we report that peroxiredoxin 4 (PRDX4) is a putative tumor driver. PRDX4 levels were highly increased in a majority of human GBMs as well as in a mouse model of GBM. Reducing PRDX4 expression significantly decreased GBM cell growth and radiation resistance in vitro with increased levels of ROS, DNA damage, and apoptosis. In a syngenic orthotopic transplantation model, Prdx4 knockdown limited GBM infiltration and significantly prolonged mouse survival. These data suggest that PRDX4 can be a novel target for GBM therapies in the future.