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https://www.readbyqxmd.com/read/29352723/which-hiv-infected-adults-with-high-cd4-t-cell-counts-benefit-most-from-immediate-initiation-of-antiretroviral-therapy-a-post-hoc-subgroup-analysis-of-the-start-trial
#1
Jean-Michel Molina, Birgit Grund, Fred Gordin, Ian Williams, Mauro Schechter, Marcello Losso, Matthew Law, Ernest Ekong, Noluthando Mwelase, Athanasios Skoutelis, Martin J Wiselka, Linos Vandekerckhove, Thomas Benfield, David Munroe, Jens D Lundgren, James D Neaton
BACKGROUND: Immediate initiation of antiretroviral therapy (ART) in asymptomatic adults with CD4 counts higher than 500 cells per μL, as recommended, might not always be possible in resource-limited settings. We aimed to identify subgroups of individuals who would benefit most from immediate treatment. METHODS: The START trial was a randomised controlled trial in asymptomatic, HIV-positive adults previously untreated with ART. Participants with CD4 counts higher than 500 cells per μL were randomly assigned to receive immediate ART or to defer ART until CD4 counts were lower than 350 cells per μL...
January 15, 2018: Lancet HIV
https://www.readbyqxmd.com/read/29352704/treatment-of-adult-chronic-indeterminate-chagas-disease-with-benznidazole-and-three-e1224-dosing-regimens-a-proof-of-concept-randomised-placebo-controlled-trial
#2
Faustino Torrico, Joaquim Gascon, Lourdes Ortiz, Cristina Alonso-Vega, María-Jesús Pinazo, Alejandro Schijman, Igor C Almeida, Fabiana Alves, Nathalie Strub-Wourgaft, Isabela Ribeiro
BACKGROUND: Chagas disease is a major neglected vector-borne disease. In this study, we investigated the safety and efficacy of three oral E1224 (a water-soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult chronic indeterminate Chagas disease. METHOD: In this proof-of-concept, double-blind, randomised phase 2 clinical trial, we recruited adults (18-50 years) with confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in Bolivia...
January 15, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29352703/inotuzumab-ozogamicin-in-combination-with-low-intensity-chemotherapy-for-older-patients-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukaemia-a-single-arm-phase-2-study
#3
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
January 15, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29352633/current-concerns-and-perspectives-on-zika-virus-co-infection-with-arboviruses-and-hiv
#4
REVIEW
Hussin A Rothan, Mehdi R M Bidokhti, Siddappa N Byrareddy
Dissemination of vector-borne viruses, such as Zika virus (ZIKV), in tropical and sub-tropical regions has a complicated impact on the immunopathogenesis of other endemic viruses such as dengue virus (DENV), chikungunya virus (CHIKV) and human immunodeficiency virus (HIV). The consequences of the possible co-infections with these viruses have specifically shown significant impact on the treatment and vaccination strategies. ZIKV is a mosquito-borne flavivirus from African and Asian lineages that causes neurological complications in infected humans...
January 16, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29352469/amoxicillin-current-use-in-swine-medicine
#5
REVIEW
D G S Burch, D Sperling
Amoxicillin has become a major antimicrobial substance in pig medicine for the treatment and control of severe, systemic infections such as Streptococcus suis. The minimum inhibitory concentration 90% (MIC 90) is 0.06 μg amoxicillin/ml, and the proposed epidemiological cut-off value (ECOFF) is 0.5 μg/ml, giving only 0.7% of isolates above the ECOFF or of reduced susceptibility. Clinical breakpoints have not been set for amoxicillin against porcine pathogens yet, hence the use of ECOFFs. It has also been successfully used for bacterial respiratory infections caused by Actinobacillus pleuropneumoniae and Pasteurella multocida...
January 19, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29352435/outcome-of-hip-and-knee-periprosthetic-joint-infections-caused-by-pathogens-resistant-to-biofilm-active-antibiotics-results-from-a-prospective-cohort-study
#6
Doruk Akgün, Carsten Perka, Andrej Trampuz, Nora Renz
BACKGROUND: Periprosthetic joint infections (PJI) caused by pathogens, for which no biofilm-active antibiotics are available, are often referred to as difficult-to-treat (DTT). However, it is unclear whether the outcome of DTT PJI is worse than those of non-DTT PJI. We evaluated the outcome of DTT and non-DTT PJI in a prospective cohort treated with a two-stage exchange according to a standardized algorithm. METHODS: Patients with hip and knee PJI from 2013 to 2015 were prospectively included and followed up for ≥ 2 years...
January 19, 2018: Archives of Orthopaedic and Trauma Surgery
https://www.readbyqxmd.com/read/29352420/diagnosis-and-management-of-hepatitis-c-infection-in-primary-care-settings
#7
Debra Guss, Jagannath Sherigar, Paul Rosen, Smruti R Mohanty
Hepatitis C virus (HCV) infection is a significant health problem worldwide, and is the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation in the United States. The management of HCV has changed significantly over the last 5 years, as treatments have become simpler and more efficacious. Medication efficacy is now greater than 90%, with a high barrier to resistance and few side effects. This review is a collaboration between primary care and hepatology providers to explore all aspects of HCV management: acute versus chronic HCV infection, transmission and testing, and diagnosis and treatment...
January 19, 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29352409/recent-perspectives-on-the-molecular-basis-of-biofilm-formation-by-pseudomonas-aeruginosa-and-approaches-for-treatment-and-biofilm-dispersal
#8
REVIEW
Sinosh Skariyachan, Vaishnavi Sneha Sridhar, Swathi Packirisamy, Supreetha Toplar Kumargowda, Sneha Basavaraj Challapilli
Pseudomonas aeruginosa, a Gram-negative, rod-shaped bacterium causes widespread diseases in humans. This bacterium is frequently related to nosocomial infections such as pneumonia, urinary tract infections (UTIs) and bacteriaemia especially in immunocompromised patients. The current review focuses on the recent perspectives on biofilms formation by these bacteria. Biofilms are communities of microorganisms in which cells stick to each other and often adhere to a surface. These adherent cells are usually embedded within a self-produced matrix of extracellular polymeric substance (EPS)...
January 19, 2018: Folia Microbiologica
https://www.readbyqxmd.com/read/29352387/current-perspectives-on-erythema-multiforme
#9
REVIEW
Marianne Lerch, Carlo Mainetti, Benedetta Terziroli Beretta-Piccoli, Thomas Harr
Recognition and timely adequate treatment of erythema multiforme remain a major challenge. In this review, current diagnostic guidelines, potential pitfalls, and modern/novel treatment options are summarized with the aim to help clinicians with diagnostic and therapeutic decision-making. The diagnosis of erythema multiforme, that has an acute, self-limiting course, is based on its typical clinical picture of targetoid erythematous lesions with predominant acral localization as well as histological findings...
January 19, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29352337/impact-of-hepatitis-b-carrier-status-on-the-outcomes-of-surgical-treatment-of-colorectal-liver-metastases
#10
Kin Pan Au, Kenneth Siu Ho Chok, Albert Chi Yan Chan, Wing Chiu Dai, Tan To Cheung, Chung Mau Lo
BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a lower incidence of colorectal liver metastases. We explored the impact of HBV carrier status on outcomes of surgical treatment of colorectal liver metastases. METHODS: A retrospective analysis was conducted for consecutive patients undergoing liver resection for colorectal liver metastases from 2000 to 2016. HBV carriers were matched with controls by propensity scoring. RESULTS: 304 patients with known HBV carrier status who underwent resection of colorectal liver metastases were studied...
January 19, 2018: World Journal of Surgery
https://www.readbyqxmd.com/read/29352171/a-urine-dependent-human-urothelial-organoid-offers-a-potential-alternative-to-rodent-models-of-infection
#11
Harry Horsley, Dhanuson Dharmasena, James Malone-Lee, Jennifer L Rohn
Murine models describe a defined host/pathogen interaction for urinary tract infection, but human cell studies are scant. Although recent human urothelial organoid models are promising, none demonstrate long-term tolerance to urine, the natural substrate of the tissue and of the uropathogens that live there. We developed a novel human organoid from progenitor cells which demonstrates key structural hallmarks and biomarkers of the urothelium. After three weeks of transwell culture with 100% urine at the apical interface, the organoid stratified into multiple layers...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352135/blocking-zika-virus-vertical-transmission
#12
Pinar Mesci, Angela Macia, Spencer M Moore, Sergey A Shiryaev, Antonella Pinto, Chun-Teng Huang, Leon Tejwani, Isabella R Fernandes, Nicole A Suarez, Matthew J Kolar, Sandro Montefusco, Scott C Rosenberg, Roberto H Herai, Fernanda R Cugola, Fabiele B Russo, Nicholas Sheets, Alan Saghatelian, Sujan Shresta, Jeremiah D Momper, Jair L Siqueira-Neto, Kevin D Corbett, Patricia C B Beltrão-Braga, Alexey V Terskikh, Alysson R Muotri
The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352124/hbv-infection-potentiates-resistance-to-s-phase-arrest-inducing-chemotherapeutics-by-inhibiting-chk2-pathway-in-diffuse-large-b-cell-lymphoma
#13
Xinying Zhao, Xudong Guo, Libo Xing, Wenqin Yue, Haisen Yin, Miaoxia He, Jianmin Wang, Jianmin Yang, Jie Chen
A considerable number of diffuse large B-cell lymphoma (DLBCL) patients are infected with hepatitis B virus (HBV), which is correlated with their poor outcomes. However, the role of HBV infection in DLBCL treatment failure remains poorly understood. Here, our data demonstrated that HBV infection was closely associated with poorer clinical prognosis independent of its hepatic dysfunction in germinal center B-cell type (GCB type) DLBCL patients. Interestingly, we found that DLBCL cells expressing hepatitis B virus X protein (HBX) did not exhibit enhanced cell growth but did show reduced sensitivity to methotrexate (MTX) and cytarabine (Ara-C), which induced S-phase arrest...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352089/cryptic-production-of-trans-3-hydroxyproline-in-echinocandin-b-biosynthesis
#14
Johanna Mattay, Stefanie Houwaart, Wolfgang Hüttel
Echinocandins are antifungal nonribosomal hexapeptides produced by fungi. Two of the amino acids are hydroxy-l-prolines: trans-4-hydroxy-l-proline and, in most echinocandin structures, (trans-2,3)-3-hydroxy-(trans-2,4)-4-methyl-l-proline. In the case of echinocandin biosynthesis by Glarea lozoyensis, both amino acids are found in pneumocandin A0, while in pneumocandin B0 the latter residue is substituted by trans-3- hydroxy-l-proline (3-Hyp). We have recently reported that all three amino acids are generated by the 2-oxoglutarate-dependent proline hydroxylase GloF...
January 19, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29352081/expression-of-the-pseudomonas-aeruginosa-biofilm-antibiotic-resistance-gene-ndvb-requires-the-rpos-stationary-phase-sigma-factor
#15
Clayton W Hall, Aaron J Hinz, Luke B-P Gagnon, Li Zhang, Jean-Paul Nadeau, Sarah Copeland, Bratati Saha, Thien-Fah Mah
Chronic, biofilm-based bacterial infections are exceptionally difficult to eradicate due to the high degree of antibiotic recalcitrance exhibited by cells in biofilm communities. In the opportunistic pathogen Pseudomonas aeruginosa, biofilm recalcitrance is multifactorial and arises in part from the preferential expression of resistance genes in biofilms compared to exponential phase planktonic cells. One such mechanism involves ndvB, which we have previously shown to be expressed specifically in biofilms. In this study, we investigated the regulatory basis of this lifestyle-specific expression by developing an unstable GFP transcriptional reporter to observe the expression pattern of ndvB We found that, in addition to its expression in biofilms, ndvB was also upregulated in planktonic cells as they enter stationary phase...
January 19, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29351986/phase-ii-study-of-oral-jak1-jak2-inhibitor-ruxolitinib-in-advanced-relapsed-refractory-hodgkin-lymphoma
#16
Eric Van den Neste, Marc André, Thomas Gastinne, Aspasia Stamatoullas, Corinne Haioun, Amine Belhabri, Oumedaly Reman, Olivier Casasnovas, Hervé Guesquieres, Gregor Verhoef, Marie-José Claessen, Hélène A Poirel, Marie-Christine Copin, Romain Dubois, Peter Vandenberghe, Ioanna-Andrea Stoian, Anne S Cottereau, Sarah Bailly, Laurent Knoops, Franck Morschhauser
JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351935/an-adult-case-with-shigellosis-associated-encephalopathy
#17
Heleen Joséphine Schuster, Michelle Gompelman, Wim Ang, Albertus Jozef Kooter
A 45-year-old man was presented at the emergency department with altered neurological status and a 1-day history of diarrhoea and fever. The patient's sexual history revealed multiple male partners. As bacterial meningitis or viral encephalitis was suspected, treatment was started accordingly. Cerebrospinal fluid investigations only showed a slight increase of leucocytes, and microbiological studies remained negative. Stool culture revealed Shigella flexneri, after which Shigella-associated encephalopathy was suspected...
January 18, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29351933/vanadium-allergy-following-total-knee-arthroplasty
#18
Fidel Peat, Ross Coomber, Adnan Rana, Alastair Vince
Allergic reactions to metals following joint arthroplasty represent a rare and poorly understood phenomenon. Much is still unknown regarding the natural history of this complication, and how it can best be prevented and managed. We present a case of a 68-year-old woman who underwent a left total knee arthroplasty for treatment of osteoarthritis. After an initial uneventful postoperative course, she developed a troublesome erythematous rash both around the incision site and over her trunk. Blood testing revealed no evidence of infection and clinically her prosthesis was functioning well...
January 18, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29351876/vital-signs-analysis-algorithm-detects-inflammatory-response-in-premature-infants-with-late-onset-sepsis-and-necrotizing-enterocolitis
#19
Leena B Mithal, Ram Yogev, Hannah L Palac, Daniel Kaminsky, Ilan Gur, Karen K Mestan
BACKGROUND: Nonspecific clinical signs and suboptimal diagnostic tests limit accurate identification of late onset sepsis (LOS) and necrotizing enterocolitis (NEC) in premature infants, resulting in significant morbidity and antibiotic overuse. An infant's systemic inflammatory response may be identified earlier than clinical suspicion through analysis of multiple vital signs by a computerized algorithm (RALIS). AIM: To evaluate the revised RALIS algorithm for detection of LOS and NEC in preterm infants...
January 16, 2018: Early Human Development
https://www.readbyqxmd.com/read/29351806/isolated-septic-arthritis-of-hip-joint-a-rare-presentation-of-melioidosis-a-case-report
#20
N P Weerasinghe, H M M Herath, T M U Liyanage
BACKGROUND: Despite, Sri Lanka lies in the melioidosis endemic belt between 5°N and 10°N surrounded by countries known to have endemic melioidosis for many years, comparatively fewer cases of melioidosis infection have been reported in Sri Lanka. Melioidosis has a wide spectrum of clinical presentation, ranging from severe pneumonia to abscess formation in various organs. Isolated septic arthritis, which is a rare but well-recognized manifestation of melioidosis, could be the sole presenting problem in some patients with melioidosis...
January 19, 2018: BMC Research Notes
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