Clinical research assessment by flow cytometry of biomarkers for infectious stratification in an Emergency Department.

Aim: Management of patients with infections within the Emergency Department (ED) is challenging for practitioners, as the identification of infectious causes remains difficult with current techniques. A new combination of two biomarkers was tested with a new rapid flow cytometry technique. Materials & methods: Subjects from the ED were tested for their CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169) levels and results were compared to their clinical records. Results: Among 139 patients, 29% had confirmed bacterial infections and 5% viral infections. nCD64 and mCD169 respectively showed 88 and 86% sensitivity and 90 and 100% specificity for identifying subjects in bacterial or viral conditions. Conclusion: This point-of-care technique could allow better management of patients in the ED.

Longitudinal assessment of T cell inhibitory receptors in liver transplant recipients and their association with posttransplant infections.

Current immunosuppression regimens in organ transplantation primarily inhibit T cells. However, T cells are also critical in protective immunity, especially in immune-compromised patients. In this study, we examined the association of T cell dysfunction, as marked by expression of T cell exhaustion molecules, and posttransplant infections in a cohort of liver transplant patients. We focused on Programmed Death 1 (PD-1) and T cell Ig- and mucin-domain molecule 3 (Tim-3), which are potent co-inhibitory receptors, and their persistent expression often leads to T cell dysfunction and compromised protective immunity. We found that patients with the highest expression of PD-1 +Tim-3+ T cells in the memory compartment before transplantation had increased incidence of infections after liver transplantation, especially within the first 90 days. Longitudinal analysis in the first year showed a strong association between variability of PD-1 and Tim-3 expression by T cells and infectious episodes in transplant patients. Furthermore, T cells that expressed PD-1 and Tim-3 had a significantly reduced capacity in producing interferon (IFN)-γ in vitro, and this reduced IFN-γ production could be partially reversed by blocking PD-1 and Tim-3. Interestingly, the percentage of Foxp3+ regulatory T cells in liver transplant patients was stable in the study period. We concluded that the functional status of T cells before and after liver transplantation, as shown by PD-1 and Tim-3 expression, may be valuable in prognosis and management of posttransplant infections.

Global analysis of strategies to tackle antimicrobial resistance.

BACKGROUND: Antimicrobial resistance (AMR) is a global public health issue driven by inappropriate use of antimicrobials resulting in decreased efficacy on the background of an extremely limited pipeline for new antibiotics. We sought to analyse the effectiveness of key policies and strategies in tackling AMR globally and identify gaps in these. METHOD: The scope, magnitude, history and drivers of AMR were reviewed using supporting evidence. Our methodology included a literature review and semi-structured survey, whilst the analyses process was guided by an adapted health policy analyses framework. RESULTS: Six key policies of global, UK and Nigerian origin were identified along with supporting literature. Seven respondents from key organisations were identified and interviewed. Their responses were analysed using framework analyses principles. CONCLUSIONS: Antimicrobial resistance is driven by several factors, ranging from poverty to poor implementation of inadequate policies. The UK AMR strategy is the most comprehensive with room for improvement. Nigeria lacks a specific AMR policy, but has other policies which address health system drivers of AMR. Similarly, the UK's surveillance system is extensive with recent findings corresponding to global findings. Nigeria's surveillance system is focused on detecting and tackling epidemics as indicated by its recent success with Ebola, but there is room for improvement and it could be expanded to cover AMR. Global policies do not add much value to the UK strategy and provide little guidance on how low-income countries, for example Nigeria can fill current gaps in surveillance and policies as key drivers are not fully addressed.

Preclinical Assessment of a 68Ga-DOTA-Functionalized Depsipeptide as a Radiodiagnostic Infection Imaging Agent.

The study assessed a radiolabeled depsipeptide conjugate (68Ga-DOTA-TBIA101) for its potential as an imaging agent targeting infection or infection-associated inflammation. 68Ga-labeled DOTA-TBIA101 imaging was performed in (NZR1) healthy rabbits; (NZR2) rabbits bearing muscular sterile inflammation and Staphylococcus aureus (SA) infection; and (NZR3) rabbits infected with Mycobacterium tuberculosis (MTB) combined with a subcutaneous scruff infection of SA in the same animal. All animals were imaged using a PET/CT scanner at 5 and 60 min post injection. Images showed elevated accumulation of 68Ga-DOTA-TBIA101 in the sterile muscular inflammation site (T/NT ratio = 2.6 ± 0.37 (5 min) and 2.8 ± 2.3 (60 min)) and muscles infected with MTB (T/NT ratio = 2.6 ± 0.35 (5 min) and 2.8 ± 0.16 (60 min)). The findings suggest that 68Ga-DOTA-TBIA101-PET/CT may detect MTB-associated inflammation, although more foundational studies need to be performed to rationalize the diagnostic value of this technique.

[What place and what future for the pathology of infectious and tropical diseases in France?]. / Quelle place et quel avenir pour l'anatomo-cyto-pathologie des maladies infectieuses et tropicales en France?

The management of tissues and cellular samples by the pathologists in the infectious and tropical diseases pathology field in 2014 needs a strong knowledge of both morphological and molecular domains which includes the good control: (i) of the taxonomy of infectious and tropical diseases pathology leading to the pathogens identification and (ii) of the ancillary methods which can be used in fixed samples in order to detect or better identify these pathogens. There is a recent paradox in France concerning the frequency of infectious diseases to be diagnosed in pathology laboratories and the progressive loss of pathologist's expertise in this domain. Different reasons could explain this statement including the omnipresence of the tumour lesions to be managed in a pathology laboratory as well as the recent constraints associated with the different biomarkers that are mandatory to be detected by immunohistochemistry and/or by molecular biology. Even if the microbiologists play a pivotal role for identifying the different pathogens as well as for the assessment of their sensitivity to the anti-microbial drugs, a large number of infectious diseases can be diagnosed only on fixed tissue and/or cells by the pathologists. The purpose of this review is to describe the current and future issues of infectious and tropical diseases diagnoses in pathology laboratories, in particular in France.

Cardiovascular MRI for assessment of infectious and inflammatory conditions of the heart.

OBJECTIVE: This article reviews the role of cardiovascular MRI in the diagnosis and characterization of the spectrum of infectious and inflammatory disorders of the heart. An imaging protocol is described, and typical MRI findings are discussed and illustrated. CONCLUSION: Radiologists should be aware of the spectrum of infectious and inflammatory conditions that can affect the heart and the role of MRI in conjunction with other imaging techniques in their assessment.

The modification of high-dose therapy shortens the duration of neutropaenia by delay of leucocyte nadir.

Infections during neutropaenia contribute still significantly to mortality and morbidity after high-dose therapy and autologous stem cell transplantation. Further acceleration of haemopoietic recovery seems impossible for biological reasons. Another approach to shorten neutropaenia could be to remove drugs from high-dose therapy protocols with strong contribution to immunosuppression and neutropaenia and unproven antineoplastic activity. In this retrospective matched-pair analysis, conventional busulphan/cyclophosphamide (Bu/Cy) high-dose therapy was compared to single-agent busulphan conditioning before autologous stem cell transplantation. This modification led to a significant shorter neutropaenic interval by protraction of cell decrease and to a significant mitigation of neutropaenia. After single-agent busulphan conditioning, leucocytes dropped below 1/nl at median 1.5 days later when compared to the patients from the busulphanBu/Cy control group (P=0.001). In a significant percentage of patients (n=6, 60%) leucocytes did not fall below 0.5 cells/nl at any time. In contrast, all patients from the Bu/Cy control group experienced deep neutropaenia (P=0.004). Thrombocytopaenia and requirement for transfusions of platelets or red cells were not influenced. Antineoplastic activity seemed to be preserved as determined by survival analysis. In conclusion, modification of high-dose regimen with the intention to shorten neutropaenia with preserved antitumour activity could be an approach to reduce infection-related morbidity and mortality and to consider economic necessities.

Allograft bone in spinal fusion for adolescent idiopathic scoliosis.

OBJECTIVE: The purpose of this long-term study was to determine the efficacy of allograft bone for spinal fusion for adolescent idiopathic scoliosis. Prior studies comparing allograft and autograft have been short term. METHODS: This multicenter retrospective study was carried out on 111 patients with 132 total curves fused for adolescent idiopathic scoliosis. Minimum follow-up was 5 years (average 72 months). A variety of segmental instrumentation was used, with most being dual-rod, multiple-hook constructs. RESULTS: Average preoperative curve was 59 degrees with immediate correction to 29 degrees (51%) and final follow-up of 32.24 degrees (45.4%). Average loss of correction was 3.5 degrees (5.9%). There were three pseudarthroses, one infection, and no rod breakage. CONCLUSION: Pseudarthrosis rate of 2.7% and loss of correction of 5.9% are comparable with or better than those in previous reports using autogenous bone graft and either segmental or nonsegmental instrumentation.

Guillain-Barré syndrome: epidemiology, pathophysiology and management.

Guillain-Barré syndrome (GBS) is clinically defined as an acute peripheral neuropathy causing limb weakness that progresses over a time period of days or, at the most, up to 4 weeks. GBS occurs throughout the world with a median annual incidence of 1.3 cases per population of 100 000, with men being more frequently affected than women. GBS is considered to be an autoimmune disease triggered by a preceding bacterial or viral infection. Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus and Mycoplasma pneumoniae are commonly identified antecedent pathogens. In the acute motor axonal neuropathy (AMAN) form of GBS, the infecting organisms probably share homologous epitopes to a component of the peripheral nerves (molecular mimicry) and, therefore, the immune responses cross-react with the nerves causing axonal degeneration; the target molecules in AMAN are likely to be gangliosides GM1, GM1b, GD1a and GalNAc-GD1a expressed on the motor axolemma. In the acute inflammatory demyelinating polyneuropathy (AIDP) form, immune system reactions against target epitopes in Schwann cells or myelin result in demyelination; however, the exact target molecules in the case of AIDP have not yet been identified. AIDP is by far the most common form of GBS in Europe and North America, whereas AMAN occurs more frequently in east Asia (China and Japan). The prognosis of GBS is generally favourable, but it is a serious disease with a mortality of approximately 10% and approximately 20% of patients are left with severe disability. Treatment of GBS is subdivided into: (i) the management of severely paralysed patients with intensive care and ventilatory support; and (ii) specific immunomodulating treatments that shorten the progressive course of GBS, presumably by limiting nerve damage. High-dose intravenous immunoglobulin (IVIg) therapy and plasma exchange aid more rapid resolution of the disease. The predominant mechanisms by which IVIg therapy exerts its action appear to be a combined effect of complement inactivation, neutralisation of idiotypic antibodies, cytokine inhibition and saturation of Fc receptors on macrophages. Corticosteroids alone do not alter the outcome of GBS.

Nailing a key assessment. Learn the significance of certain nail anomalies.

Discover how a patient's fingernails can point out specific health problems.