Retrospective review of Treponema pallidum PCR and serology results: Are both tests necessary?

There has been a resurgence of syphilis diagnoses in Australia. We investigated whether ourpolymerase chain reaction (PCR) test provides any additional diagnostic information over syphilis serology (chemi-luminescence immunoassay (CMIA),particle agglutination (TPPA) and rapid reagin (RPR) flocculation test). A retrospective audit was conducted of allPCR requests that came through our laboratory from January 2010 to June 2017; data collected included age, gender, site of swab,PCR, syphilis serology and HSV 1 and HSV 2 PCR results. A total of 441PCR tests were performed, with on average three requests forPCR per month in 2011, which increased to 17.2 per month in 2017. There were 323 patients who had bothPCR and syphilis serology performed, with 67% of swabs taken from the genitals.PCR was positive in 61/323 (19%) patients, of which 59/61 (97%) also had positive syphilis serology result (sensitivity 68%, specificity 99%, positive predictive value 97% and negative predictive value 89%). Syphilis serology was positive in 91/323 patients (28%) of which 61 (66%) were alsoPCR positive (sensitivity 97%, specificity 88%, positive predictive value 60% and negative predictive value 99%). The Cohen's Kappa value was 0.74, indicating substantial agreement between the two tests. Our results show most patients with positivePCR results also had positive syphilis serology. Therefore,PCR adds little clinical value over serology for diagnosis of syphilis in certain clinical settings

First reported Australian case of Cladophilophora arxii: features consistent with possible primary pulmonary chromoblastomycosis.

We describe the first case of possible pulmonary chromoblastomycosis in the absence of any identified cutaneous lesions in a relatively immunosuppressed man. The causative organism was Cladophialophora arxii, which is a rare pathogen that has only been described as causing human disease two times previously

A Retrospective Case-Series of Children With Bone and Joint Infection From Northern Australia.

Our clinical workload as infectious diseases pediatricians in northern Australia is dominated by complicated bone and joint infections in indigenous children. We reviewed the clinical presentation, microbiology, management, and outcomes of children presenting to Royal Darwin Hospital with bone and joint infections between 2010 and 2013, and aimed to compare severity and incidence with other populations worldwide.A retrospective audit was performed on children aged 0 to 18 years who were admitted to Royal Darwin Hospital between 1 January 2010 and 31 December 2013 with a bone and joint infection.Seventy-nine patients were identified, of whom 57 (72%) had osteomyelitis ? associated septic arthritis and 22 (28%) had septic arthritis alone. Sixty (76%) were indigenous Australians. The incidence rate of osteomyelitis for indigenous children was 82 per 100,000 children. Staphylococcus aureus was the confirmed pathogen in 43/79 (54%), of which 17/43 (40%) were methicillin resistant. Median length of stay was 17 days (interquartile range: 10-31 days) and median length of IV antibiotics was 15 days (interquartile range: 6-24 days). Fifty-six (71%) required at least 1 surgical procedure. Relapse within 12 months was documented in 12 (15%) patients.We report 3 key findings: osteomyelitis incidence in indigenous children of northern Australia is amongst the highest reported in the world; methicillin-resistant S aureus accounts for 36% of osteomyelitis with a positive microbiological diagnosis; and the severity of disease requires extended antibiotic therapy. Despite this, 15% of the cohort relapsed within 12 months and required readmission

Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation

Acknowledgements: We are grateful to Dr. F. Sanchez-Madrid (Hospital Princesa and CNIC, Madrid, Spain), Dr. D. Cebrian (CNIC, Madrid, Spain), and Dr. A. Valledor (University of Barcelona, Spain) for helpful insights on early versions of the manuscript. We thank Dr. C. Stephan-Otto Attolini (BIST-IRB, Barcelona, Spain) and Dr. J. Rios (IDIBAPS, Hospital Clinic, and Autonomous University of Barcelona, Barcelona, Spain) for their expert guidance on the statistical analyses of the data in the study. We also thank Dr. L. Ribas de Pouplana (BIST-IRB, Barcelona, Spain) for advice on mitochondrial translation experiments. We acknowledge technical assistance by staff in the Flow Cytometry Unit at IDIBAPS, the Molecular Interactions Services Unit at the Biomedical Research Institute of Bellvitge (IDIBELL), and the Transmission Electron Microscopy Unit at the University of Barcelona School of Medicine. We also thank A Téllez (Hospital Clinic, Barcelona, Spain) for his help in collecting samples from septic patients, and Dr. MJ Fernández-Aceñero (Hospital Clinico San Carlos, Madrid, Spain) for help in collecting skin samples from healthy controls, psoriatic patients, and melanoma patients. We are also thankful to Dr. DC Dean (University of Louisville, KY, USA) for his generous gift of an anti-ZEB1 polyclonal antibody. We thank Dr. A. Garcia for the artistic drawing of schematics in the article. IDIBAPS is partly funded by the CERCA Programme of Generalitat de Catalunya. The study was conducted at IDIBAPS’ Centre de Recerca Biomèdica Cellex building, which was partly funded by the Cellex Foundation. The different parts of this study were independently funded by grants to AP from the Leo Foundation (LF-OC-19-000166), the Catalan Agency for Management of University and Research Grants (AGAUR) (2017-SGR-1174 and 2021-SGR-01328), and the Spanish State Research Agency (AEI) of the Ministry of Science and Innovation (MICINN) (PID2020-116338RB-I00) as part of MICINN’s National Scientific and Technical Research and Innovation 2021-2023 Plan, which is co-financed by the European Regional Development Fund (ERDF) of the European Union Commission. AB is a recipient of a PhD scholarship from AGAUR (FI Program, 2021 FI_B 00514).Funder: Government of Catalonia | Agència de Gestió d&apos;Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants)AbstractAcute inflammation can either resolve through immunosuppression or persist, leading to chronic inflammation. These transitions are driven by distinct molecular and metabolic reprogramming of immune cells. The anti-diabetic drug Metformin inhibits acute and chronic inflammation through mechanisms still not fully understood. Here, we report that the anti-inflammatory and reactive-oxygen-species-inhibiting effects of Metformin depend on the expression of the plasticity factor ZEB1 in macrophages. Using mice lacking Zeb1 in their myeloid cells and human patient samples, we show that ZEB1 plays a dual role, being essential in both initiating and resolving inflammation by inducing macrophages to transition into an immunosuppressed state. ZEB1 mediates these diverging effects in inflammation and immunosuppression by modulating mitochondrial content through activation of autophagy and inhibition of mitochondrial protein translation. During the transition from inflammation to immunosuppression, Metformin mimics the metabolic reprogramming of myeloid cells induced by ZEB1. Mechanistically, in immunosuppression, ZEB1 inhibits amino acid uptake, leading to downregulation of mTORC1 signalling and a decrease in mitochondrial translation in macrophages. These results identify ZEB1 as a driver of myeloid cell metabolic plasticity, suggesting that targeting its expression and function could serve as a strategy to modulate dysregulated inflammation and immunosuppression.</jats:p

Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation

Acknowledgements: We are grateful to Dr. F. Sanchez-Madrid (Hospital Princesa and CNIC, Madrid, Spain), Dr. D. Cebrian (CNIC, Madrid, Spain), and Dr. A. Valledor (University of Barcelona, Spain) for helpful insights on early versions of the manuscript. We thank Dr. C. Stephan-Otto Attolini (BIST-IRB, Barcelona, Spain) and Dr. J. Rios (IDIBAPS, Hospital Clinic, and Autonomous University of Barcelona, Barcelona, Spain) for their expert guidance on the statistical analyses of the data in the study. We also thank Dr. L. Ribas de Pouplana (BIST-IRB, Barcelona, Spain) for advice on mitochondrial translation experiments. We acknowledge technical assistance by staff in the Flow Cytometry Unit at IDIBAPS, the Molecular Interactions Services Unit at the Biomedical Research Institute of Bellvitge (IDIBELL), and the Transmission Electron Microscopy Unit at the University of Barcelona School of Medicine. We also thank A Téllez (Hospital Clinic, Barcelona, Spain) for his help in collecting samples from septic patients, and Dr. MJ Fernández-Aceñero (Hospital Clinico San Carlos, Madrid, Spain) for help in collecting skin samples from healthy controls, psoriatic patients, and melanoma patients. We are also thankful to Dr. DC Dean (University of Louisville, KY, USA) for his generous gift of an anti-ZEB1 polyclonal antibody. We thank Dr. A. Garcia for the artistic drawing of schematics in the article. IDIBAPS is partly funded by the CERCA Programme of Generalitat de Catalunya. The study was conducted at IDIBAPS’ Centre de Recerca Biomèdica Cellex building, which was partly funded by the Cellex Foundation. The different parts of this study were independently funded by grants to AP from the Leo Foundation (LF-OC-19-000166), the Catalan Agency for Management of University and Research Grants (AGAUR) (2017-SGR-1174 and 2021-SGR-01328), and the Spanish State Research Agency (AEI) of the Ministry of Science and Innovation (MICINN) (PID2020-116338RB-I00) as part of MICINN’s National Scientific and Technical Research and Innovation 2021-2023 Plan, which is co-financed by the European Regional Development Fund (ERDF) of the European Union Commission. AB is a recipient of a PhD scholarship from AGAUR (FI Program, 2021 FI_B 00514).Funder: Government of Catalonia | Agència de Gestió d&apos;Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants)Acute inflammation can either resolve through immunosuppression or persist, leading to chronic inflammation. These transitions are driven by distinct molecular and metabolic reprogramming of immune cells. The anti-diabetic drug Metformin inhibits acute and chronic inflammation through mechanisms still not fully understood. Here, we report that the anti-inflammatory and reactive-oxygen-species-inhibiting effects of Metformin depend on the expression of the plasticity factor ZEB1 in macrophages. Using mice lacking Zeb1 in their myeloid cells and human patient samples, we show that ZEB1 plays a dual role, being essential in both initiating and resolving inflammation by inducing macrophages to transition into an immunosuppressed state. ZEB1 mediates these diverging effects in inflammation and immunosuppression by modulating mitochondrial content through activation of autophagy and inhibition of mitochondrial protein translation. During the transition from inflammation to immunosuppression, Metformin mimics the metabolic reprogramming of myeloid cells induced by ZEB1. Mechanistically, in immunosuppression, ZEB1 inhibits amino acid uptake, leading to downregulation of mTORC1 signalling and a decrease in mitochondrial translation in macrophages. These results identify ZEB1 as a driver of myeloid cell metabolic plasticity, suggesting that targeting its expression and function could serve as a strategy to modulate dysregulated inflammation and immunosuppression

Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial

© 2015 The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected]. Background. In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal ß-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. Methods. In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. Results. We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P =. 06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. Conclusions. Combining an antistaphylococcal ß-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au)

Visual and Hearing Impairment Are Associated With Delirium in Hospitalized Patients: Results of a Multisite Prevalence Study

Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing&nbsp;and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium