MRSA and VRE colonization in solid organ transplantation: a meta-analysis of published studies.

The burden of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) colonization among the increasing number of solid organ transplant patients has not been systematically explored. We searched PubMed and EMBASE for pertinent articles, performed a meta-analysis of prevalence across eligible studies and estimated the risk of ensuing MRSA or VRE infections relative to colonization status. We stratified effects in the pretransplant and posttransplant period. Twenty-three studies were considered eligible. Seventeen out of 23 (74%) referred to liver transplants. Before transplantation, the pooled prevalence estimate for MRSA and VRE was 8.5% (95% confidence interval [CI] 3.2­15.8) and 11.9% (95% CI 6.8­18.2), respectively. MRSA estimate was influenced by small studies and was lower (4.0%; 95% CI 0.4­10.2) across large studies (>200 patients). After transplantation, the prevalence estimates were 9.4% (95% CI 3.0­18.5) for MRSA and 16.2% (95% CI 10.7­22.6) for VRE. Pretransplant as well as posttransplant MRSA colonization significantly increased the risk for MRSA infections (pooled risk ratio [RR] 5.51; 95% CI 2.36­12.90 and RR 10.56; 95% CI 5.58­19.95, respectively). Pretransplant and posttransplant VRE colonization were also associated with significant risk of VRE infection (RR 6.65; 95% CI 2.54­17.41 and RR 7.93; 95% CI 2.36­26.67, respectively). Solid organ transplantation is a high-risk setting for MRSA and VRE colonization, and carrier state is associated with infection. Upgraded focus in prevention and eradication strategies is warranted.

A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.

WHAT IS KNOWN AND OBJECTIVE: The relative effectiveness and safety profile of the treatments with marketing authorization for relapsing multiple sclerosis (MS) are not well known because randomized controlled trials with head-to-head comparisons between these treatments do not exist. Thus, a network of multiple-treatments meta-analysis was performed using four clinical outcomes: 'patients free of relapse', 'patients without disease progression', 'patients without MRI progression' and 'patients with adverse events'. METHODS: Randomized controlled trials (RCTs) on MS were systematically searched in PubMed and Cochrane Central Register of Controlled Trial. The network analysis performed pairwise comparisons between the marketed treatments (Betaferon 250mcg, Avonex 30mcg, Rebif 44mcg, Rebif 22mcg, Aubagio 7 mg, Aubagio 14 mg, Copaxone 20 mg, Tysabri 300 mg, Gilenya 0·5 mg and Novantrone 12 mg/m(2)) using direct and indirect analyses. RESULTS AND DISCUSSION: The analysis included 48 articles, involving 20 455 patients with MS. The direct analysis showed better response for more than one outcome for Gilenya compared with Avonex ('patients free of relapse' and 'patients without MRI progression') and for Betaferon compared with Avonex ('patients without disease progression' and 'patients without MRI progression'). The indirect analysis indicated that Tysabri may have better relative effectiveness compared with the other treatments for two outcomes: 'patients free of relapse' and 'patients without MRI progression'. Regarding 'patients with adverse events', no data were available for all comparisons to make fair inferences. WHAT IS NEW AND CONCLUSION: This was an attempt, for the first time, to compare the efficacy and safety profile of existing approved treatments for relapsing MS. Although some treatments have shown better response, the results of the network analysis should be interpreted with caution because of the lack of RCTs with head-to-head comparisons between treatments.

Lupus nephritis and non-Hodgkin lymphoma simultaneously diagnosed in a patient on methimazole.

A 78 year old white male on methimazole due to Grave's thyroiditis presented with acute renal failure after a short term history of progressive shortness of breath, malaise, myalgias, arthralgias, and bilateral lower limb swelling. The abdomen was remarkable for splenomegaly and lower extremities for erythema nodosum. No peripheral lymphadenopathy was detected. Serum albumin was 1.7 g/dl and very high erythrocyte sedimentation rate. Urine sediment was very active with dysmorphic red blood cells and casts and significant proteinuria (6.6 grams/day). Serum complements were abnormally low and antinuclear and anti-DNA antibodies were positive. Renal histopathology revealed membranoproliferative glomerulonephritis, along with a full house pattern on IFF consistent with lupus nephritis. Bone marrow aspiration revealed a 40% infiltration by a lymphocyte population of small cells consistent with a B cell non-Hodgkin lymphoma. The patient was treated with methylprednisolone, cyclophosphamide and rituximab and acute dialysis. Over the following weeks the patient became dialysis independent and returned to his baseline GFR.

Nutritional risk as predictor for healthcare-associated infection among hospitalized elderly patients in the acute care setting.

BACKGROUND: Poor nutritional status is associated with high rates of healthcare-associated infections (HCAIs) among hospitalized elderly patients. Early recognition of patients at risk for HCAIs is important. The Geriatric Nutritional Risk Index (GNRI) is a screening tool able to predict nutrition-related complications. AIM: To examine the use of GNRI as a predictor of HCAIs in the acute care setting. METHODS: A total of 248 consecutive patients aged >65 years, admitted as emergencies to the medical ward of an acute care hospital, were enrolled. On admission, clinical and laboratory assessment, anthropometric measurements, performance status, and GNRI score estimation were performed. HCAIs were recorded during admission. FINDINGS: On admission, 53.8% of the patients were not at risk, 37.2% at low or medium risk and 8.9% at high risk for nutrition-related complications, as stratified by using the GNRI. During hospitalization 23.7% of the patients developed HCAIs. Patients with HCAIs had higher mortality (P < 0.001) and longer hospital stay (P < 0.001). In multivariate analysis, a performance status >1 [hazard ratio (HR): 2.08; 95% confidence interval (CI): 1.07-4.02; P = 0.03] and diabetes (HR: 2.57; 95% CI: 1.37-4.84; P = 0.003) were associated with increased risk for HCAIs, whereas GNRI score (per unit increase) had a protective effect (HR: 0.97; 95% CI: 0.95-0.99; P = 0.01). Well-nourished patients (GNRI >98) were significantly more likely to remain free from HCAIs during hospitalization (P = 0.003). CONCLUSION: GNRI can accurately stratify hospitalized elderly patients according to risk for developing HCAIs.

Rates of infiltration by macrophages and dendritic cells and expression of interleukin-18 and interleukin-12 in the chronic inflammatory lesions of Sjögren's syndrome: correlation with certain features of immune hyperactivity and factors associated with high risk of lymphoma development.

OBJECTIVE: To evaluate the expression profile of infiltrating macrophages and dendritic cells (DCs) as well as of interleukin-18 (IL-18) and IL-12 in the minor salivary gland (MSG) lesions of patients with Sjögren's syndrome (SS), and to assess the relationship of these factors with disease parameters. METHODS: Macrophages, DCs, T cells, B cells, proIL-18, mature IL-18, and IL-12 were detected by single- and double-labeling immunohistochemistry in MSG specimens from 21 patients with primary SS (13 of 21 tested for IL-12), 7 patients with secondary SS, and 9 disease control patients. Expression profiles were assessed for correlations with various disease parameters, including adverse predictors of lymphoma development. RESULTS: MSGs from patients with SS (but not from disease controls) manifested increased infiltration by macrophages and DCs, strong expression of IL-18 by macrophages (particularly in B cell-rich areas and in germinal center-like structures in primary SS), and expression of IL-12 by mononuclear cell infiltrates. In primary SS, high infiltration by macrophages correlated with SG enlargement (P = 0.01). The DC infiltration rate correlated positively with the macrophage infiltration rate (P = 0.04), occurrence of SG enlargement (P = 0.03), and presence of C4 hypocomplementemia (P = 0.05), and inversely with serum C4 complement levels (P = 0.001). The rate of infiltration by IL-18-expressing cells correlated positively with biopsy focus scores (P < 0.001), larger infiltrates of macrophages (P = 0.01), DCs (P = 0.01), and B cells (P = 0.02), and SG enlargement (P = 0.02), and negatively with serum C4 complement levels (P = 0.02). The rate of infiltration by IL-12-expressing cells correlated inversely with that by IL-18-expressing cells (P = 0.001), biopsy focus scores (P = 0.003), and SG enlargement (P = 0.01), and positively with serum C4 complement levels (P = 0.05). CONCLUSION: In patients with primary SS, infiltration of the SG by macrophages and DCs and expression of IL-18 and IL-12 appear to play active roles in the expansion and organization of infiltrative injuries and have a correlation with certain predictors of lymphoma development.

Bone marrow histological findings in systemic lupus erythematosus with hematologic abnormalities: a clinicopathological study.

BACKGROUND: The histopathologic features characterizing the involvement of the bone marrow (BM) in systemic lupus erythematosus (SLE) have not been systematically analyzed to date. OBJECTIVES: The aim of this study was to assess morphologic and immunohistochemical characteristics of BM involvement in SLE. PATIENTS AND METHODS: Clinical and serological data of 40 SLE patients with unexplained cytopenias were studied. Ten patients with myelodysplasia of refractory anemia (RA) were used as controls. BM aspiration, BM biopsy (BMB), and immunohistochemistry were carried out in patients and controls. BM fibrosis, BM necrosis, stromal edema, and abnormal localization of immature precursors (ALIP) were assessed according to standard criteria. RESULTS: Dyserythropoiesis and megakaryocytic atypias were uniform findings in SLE patients. The disruption of the normal BM architecture was a predominant SLE BM feature affecting cells of all three hemopoietic lineages, with both erythroid and megakaryocytic precursors tending to assume paratrabecular locations and ALIP aggregates being present in 27 cases. In addition, BM was hypocellular in 23 cases. BM necrotic alterations were evident in 90% of the cases. The density of reticulin content was generally increased. Vascular changes including dilatation of sinuses were manifest and were associated with the presence of necrotic alterations (P = 0.008). Hemoglobin levels correlated inversely with the presence of ALIP (P = 0.016). Upon comparing BMB features between SLE and RA controls there were striking similarities. CONCLUSIONS: BMB in patients with SLE and unexplained cytopenias presents a variety of histopathologic findings including BM necrosis, stromal alterations, hypocellularity, dyspoiesis, and distortion of normal BM architecture, characterized primarily by the presence of ALIP aggregates.

Suspects in the tale of lupus-associated thrombocytopenia.

Immunologically mediated thrombocytopenia is a frequent clinical manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies targeting platelet membrane glucoproteins have a central role in peripheral platelet destruction. Autoantibodies against thrombopoietin are also present in about one-third of patients, but their pathogenetic role is obscure. Thirty-eight serum samples from SLE patients were tested for anti-platelet antibodies, anti-thrombopoietin antibodies and levels of circulating thrombopoietin. Bone marrow histology was also assessed. Thirty-nine per cent of sera displayed anti-thrombopoietin antibodies and 29% had circulating anti-platelet antibodies. Anti-thrombopoietin antibodies were associated with lower thrombopoietin concentrations, and lower mean platelet values in long-term follow-up. Anti-platelet antibodies were present in about 40% of thrombocytopenic and non-thrombocytopenic individuals but were absent in patients who had recovered from thrombocytopenia, supporting their pathogenetic role. Both autoantibodies were absent in control sera from patients with rheumatoid arthritis and primary Sjögren's syndrome. Decreased bone marrow cellularity, normal or low number of hypolobulated, pyknotic megakaryocytes and stromal alterations were prominent findings in thrombocytopenic SLE patients, suggesting a defect in megakaryopoiesis. These findings were not evident in specimens from patients with idiopathic thrombocytopenic purpura who had increased megakaryocytes, normal cellularity and absence of stromal alterations. In conclusion, peripheral destruction due to platelet autoantibodies, anti-thrombopoetin antibodies, lower effective circulating thrombopoetin and impaired compensatory response due to bone marrow damage interact in SLE and thrombocytopenia ensues.

Thrombocytopaenia in lupus as a marker of adverse outcome--seeking Ariadne's thread.

OBJECTIVE: To assess the role of thrombocytopaenia as an independent predictor of outcome in patients with systemic lupus erythematosus (SLE). METHODS: This was a single-centre, retrospective, matched case-control study (1:2). Fifty consecutive Greek SLE patients were selected at random who had developed thrombocytopaenia during the disease course (cases) were compared with 100 SLE patients with no history of thrombocytopaenia, and matched for age, sex and disease duration (controls). Overall damage was assessed at the end of follow-up, using Systemic Lupus International Collaborating Clinics index. Total number of irreversible organ-damage events for both groups were recorded. Rates for specific outcomes and incidence-rate ratios (IRRs) for damage were estimated. Multivariate analysis estimating influential clinical and immunological factors for outcome, including thrombocytopaenia, was performed. RESULTS: After 583 person-years of follow-up for cases and 1155 for controls, we found that thrombocytopaenic individuals have a higher risk for damage (IRR 1.96, 1.52-2.53) compared with their matched controls and this effect persists throughout the course of their disease. They also have a predilection to certain types of damage involving heart and kidneys. Among other significant factors associated with damage in multivariate analysis (disease activity, serositis, anti-cardiolipin antibodies, central nervous system involvement), thrombocytopaenia appears as the most influential. CONCLUSION: Thrombocytopaenia is a quantitive and qualitative marker of impending damage in SLE patients.

Anaemia in systemic lupus erythematosus: from pathophysiology to clinical assessment.

Haematological abnormalities are common in systemic lupus erythematosus. Anaemia is found in about 50% of patients, with anaemia of chronic disease being the most common form. Impaired erythropoietin response and presence of antibodies against erythropoietin may contribute to the pathogenesis of this type of anaemia. Patients with autoimmune haemolytic anaemia usually belong to a distinct category, which is associated with anticardiolipin antibodies, thrombosis, thrombocytopenia, and renal disease, often in the context of secondary antiphospholipid syndrome. Autoantibodies, T lymphocytes, and deregulation of the cytokine network can affect bone marrow erythropoiesis, leading to anaemia.

Lupus thrombocytopenia: clinical implications and prognostic significance.

OBJECTIVES: To clarify clinical manifestations, association with disease activity, and prognostic impact of thrombocytopenia using simple and reliable indices. METHODS: 632 patients were reviewed retrospectively. Fifty patients with thrombocytopenia were included as cases and matched with 100 control patients. Clinical manifestations at first thrombocytopenic episode were recorded. Classification criteria at diagnosis, basic immunological profiles, disease activity (ECLAM), and end organ damage (SLICC) were recorded. RESULTS: 29/50 (58%) had thrombocytopenia at diagnosis of lupus. Haemorrhagic manifestations were associated with the degree of thrombocytopenia (p<0.001). Anticardiolipin antibodies were not related to the degree of thrombocytopenia or the severity of haemorrhagic manifestations. Megakaryocytes were normal or increased in 26/28 (93%) bone marrow specimens, indicating peripheral platelet destruction. Patients with high disease activity were more thrombocytopenic than controls (OR = 2.61, 95% CI 1.13 to 5.96, p = 0.009). Patients with low C3 or CH50 were more likely to be thrombocytopenic (OR = 2.36, 95% CI 1.05 to 5.26, p = 0.029). Median SLICC for lupus patients with thrombocytopenia was 2 (range 0-11) compared with 1 (range 0-12) for controls (p<0.001). No deaths occurred during thrombocytopenic episodes. CONCLUSIONS: Thrombocytopenia is not directly associated with end organ damage and mortality, but defines a subgroup of patients with higher morbidity and is thus a major complication of systemic lupus erythematosus, affecting overall prognosis.