Archive for July 4, 2016

Discordant immune response with antiretroviral therapy in HIV-1: A systematic review of clinical outcomes.

PLoS One 2016 Jun 10; 11:e0156099

Kelly C, Katherine M. Gaskell, Marty Richardson, Nigel Klein, Paul Garner, Peter MacPherson



A discordant immune response (DIR) is a failure to satisfactorily increase CD4 counts on ART despite successful virological control. Literature on the clinical effects of DIR has not been systematically evaluated. We aimed to summarise the risk of mortality, AIDS and serious non-AIDS events associated with DIR with a systematic review.


The protocol is registered with the Centre for Review Dissemination, University of York (registration number CRD42014010821). Included studies investigated the effect of DIR on mortality, AIDS, or serious non-AIDS events in cohort studies or cohorts contained in arms of randomised controlled trials for adults aged 16 years or older. DIR was classified as a suboptimal CD4 count (as defined by the study) despite virological suppression following at least 6 months of ART. We systematically searched PubMed, Embase, and the Cochrane Library to December 2015. Risk of bias was assessed using the Cochrane tool for assessing risk of bias in cohort studies. Two authors applied inclusion criteria and one author extracted data. Risk ratios were calculated for each clinical outcome reported.


Of 20 studies that met the inclusion criteria, 14 different definitions of DIR were used. Risk ratios for mortality in patients with and without DIR ranged between 1.00 (95% CI 0.26 to 3.92) and 4.29 (95% CI 1.96 to 9.38) with the majority of studies reporting a 2 to 3 fold increase in risk.


DIR is associated with a marked increase in mortality in most studies but definitions vary widely. We propose a standardised definition to aid the development of management options for DIR.


July 4, 2016 at 9:43 pm

Fungal periprosthetic joint infection in total knee arthroplasty: a systematic review.

Orthop Rev (Pavia). 2015 Mar 9;7(1):5623.

Jakobs O1, Schoof B1, Klatte TO2, Schmidl S1, Fensky F2, Guenther D3, Frommelt L4, Gehrke T1, Gebauer M5.

Author information

1Department of Orthopedic Surgery, Helios Endo-Klinik Hamburg , Hamburg, Germany.

2Department of Trauma-, Hand- and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf , Hamburg, Germany.

3Department of Trauma, Hannover Medical School , Hamburg, Germany.

4Institute for Clinical Microbiology, Infectiology and Infection Control, Helios Endo-Klinik Hamburg , Hamburg, Germany.

5Department of Orthopedic Surgery, Helios Endo-Klinik Hamburg , Hamburg, Germany ; Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf , Hamburg, Germany.


Fungal periprosthetic joint infection (PJI) is a rare but devastating complication following total knee arthroplasty (TKA). A standardized procedure regarding an accurate treatment of this serious complication of knee arthroplasty is lacking. In this systematic review, we collected data from 36 studies with a total of 45 reported cases of a TKA complicated by a fungal PJI. Subsequently, an analysis focusing on diagnostic, medicaments and surgical procedures in the pre-, intra- and postoperative period was performed. Candida spp. accounts for about 80% (36 out of 45 cases) of fungal PJIs and is therefore the most frequently reported pathogen. A systemic antifungal therapy was administered in all but one patient whereas a local antifungal therapy, e.g. the use of an impregnated spacer, is of inferior relevance. Resection arthroplasty with delayed re-implantation (two-stage revision) was the surgical treatment of choice. However, in 50% of all reported cases the surgical therapy was heterogeneous. The outcome under a combined therapy was moderate with recurrent fungal PJI in 11 patients and subsequent bacterial PJI as a main complication in 5 patients. In summary, this systematic review integrates data from up to date 45 reported cases of a fungal PJI of a TKA. On the basis of the current literature strategies for the treatment of this devastating complication after TKA are discussed.


July 4, 2016 at 9:08 am

How Reliable Is the Alpha-defensin Immunoassay Test for Diagnosing Periprosthetic Joint Infection? A Prospective Study.

Clin Orthop Relat Res. 2016 Jun 24. [Epub ahead of print]

Bonanzinga T1, Zahar A2, Dütsch M1, Lausmann C1, Kendoff D3, Gehrke T1.

Author information

1HELIOS ENDO Klinik, Holstenstrasse 2, 22767, Hamburg, Germany.

2HELIOS ENDO Klinik, Holstenstrasse 2, 22767, Hamburg, Germany.

3HELIOS Klinik Berlin-Buch, Berlin, Germany.



A key issue in the treatment of periprosthetic joint infection (PJI) is the correct diagnosis. The main problem is lack of diagnostic tools able to diagnose a PJI with high accuracy. Alpha-defensin has been proposed as a possible solution, but in the current literature, there is a lack of independent validation.


We performed a prospective study to determine (1) what is the sensitivity, specificity, and positive and the negative predictive values of the alpha-defensin immunoassay test in diagnosing PJI; and (2) which clinical features may be responsible for false-positive and false-negative results?


Preoperative aspiration was performed in all patients presenting with a painful hip/knee arthroplasty, including both primary and revision implants. Metallosis, other inflammatory comorbidities, and previous/concomitant antibiotic therapy were not considered as exclusion criteria. An inadequate amount of synovial fluid for culture was an exclusion criterion. A total of 156 patients (65 knees, 91 hips) were included in this prospective study. At the time of revision, synovial fluid samples were taken to perform the alpha-defensin assay. During surgical débridement of tissue, samples for cultures and histologic evaluation were taken, and samples were cultured until positive or until negative at 14 days. A diagnosis of PJI was confirmed in 29 patients according to the International Consensus Group on PJI.


The sensitivity of the alpha-defensin immunoassay was 97% (95% confidence interval [CI], 92%-99%), the specificity was 97% (95% CI, 92%-99%), the positive predictive value was 88% (95% CI, 81%-92%), and the negative predictive value was 99% (95% CI, 96%-99%). Among four false-positive patients, two had metallosis and one had polyethylene wear. The false-negative case presented with a draining sinus, and intraoperative cultures were also negative.


Alpha-defensin assay appears to be a reliable test, but followup evaluation is needed to estimate longer term performance of the test. The authors believe that alpha-defensin has demonstrated itself to be sufficiently robust that PJI diagnostic criteria now should include this test. Future studies are needed to compare the differences among the diagnostic capability of the available tests, in particular when metallosis is present, because metallosis may predispose the test to a false-positive result.


Level I, diagnostic study.



July 4, 2016 at 9:06 am

Fungal periprosthetic joint infection of the hip: a systematic review.

Orthop Rev (Pavia). 2015 Mar 31;7(1):5748.

Schoof B1, Jakobs O1, Schmidl S1, Klatte TO2, Frommelt L3, Gehrke T1, Gebauer M1.

Author information

1Department of Orthopedic Surgery, HELIOS Endo-Clinic Hamburg , Hamburg, Germany.

2Department of Trauma-, Hand- and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf , Hamburg, Germany.

3Centre of Infections and Microbiology, HELIOS Endo-Clinic , Hamburg, Germany.


Periprosthetic joint infection (PJI) is a severe complication of total joint arthroplasty with an incidence of approximately 1%. Due to the high risk of persisting infection, successful treatment of fungal PJI is challenging. The purpose of this study was to gain insight into the current management of fungal PJI of the hip and, by systematically reviewing the cases published so far, to further improve the medical treatment of this serious complication of total hip arthroplasty. Thus, we conducted a systematic review of the available literature concerning fungal PJI in total hip arthroplasty, including 45 cases of fungal PJI. At the moment a two-stage revision procedure is favorable and there is an ongoing discussion on the therapeutic effect of antifungal drug loaded cement spacers on fungal periprosthetic infections of the hip. Due to the fact that there is rare experience with it, there is urgent need to establish guidelines for the treatment of fungal infections of total hip arthroplasty.


July 4, 2016 at 9:04 am


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