Clinical impact of vancomycin-resistant enterococci colonization in nonliver solid organ transplantation and its implications for infection control strategies: A single-center, 10-year retrospective study.

BACKGROUND: Vancomycin-resistant enterococci (VRE) colonization in nonliver solid organ transplantation (SOT) is poorly defined. Infection control management of these patients is influenced by the association of VRE with adverse outcomes in liver transplantation. This study examines the frequency and clinical impact of VRE colonization specifically on nonliver SOT patients and discusses implications for nosocomial VRE control. METHODS: We retrospectively reviewed all nonliver SOT patients at a single transplant center from 2005 to 2015. We determined colonization rates in the peritransplant period and the rate of VRE infections. The association between VRE colonization with 90-day mortality and other clinical outcomes was examined. RESULTS: There were 1786 nonliver SOTs from 2005 to 2015, with 81 (4.6%) colonized with VRE in the peritransplantation period. The colonization prevalence varied by organ type: 45 of 423 lung (10.6%), 12 of 352 heart (3.4%), one of 18 heart-lung (5.6%), 20 of 884 kidney (2.3%), three of 63 kidney-pancreas (4.8%), zero of 11 pancreas, zero of five small bowel, and zero of 11 multivisceral. Peritransplant VRE colonization was not associated with 90-day mortality odds ratio = 2.35 (95% CI = 0.53, 10.29) and adjusted odds ratio = 1.52 (95% CI = 0.34, 6.88). In the multivariable logistic regression, there was no association with mortality at 1 year or 5 years, hospital length of stay, rehospitalization, or days alive out of hospital. There were 14 inpatient VRE infections up to 1 year after transplantation. CONCLUSION: Nonliver SOT patients have lower rates of VRE colonization than liver SOT, and colonization was not associated with increased adverse clinical outcomes. Although infection control strategies for VRE in hospital remain controversial, nonliver SOT should be considered among typical hospitalized patients when designing strategies for prevention.

Psoriasis and Smoking: A Systematic Literature Review and Meta-Analysis With Qualitative Analysis of Effect of Smoking on Psoriasis Severity.

BACKGROUND: Smoking has been associated with psoriasis prevalence and severity. OBJECTIVE: To evaluate prevalence of smoking in patients with psoriasis and to examine the relationship between smoking and psoriasis severity. METHODS: MEDLINE, EMBASE, and Cochrane databases (1960-2012) and conference proceedings (2010-2012) were systematically searched using keywords relevant to psoriasis and smoking. Controlled studies addressing psoriasis and smoking status were included. A meta-analysis for the relative risk of smoking in psoriasis patients was performed. RESULTS: Meta-analysis identified a significant association between smoking and psoriasis with a relative risk of 1.88 (95% CI, 1.66-2.13) for smoking in patients with psoriasis versus patients without psoriasis. Eight articles of 11 with data on smoking and psoriasis severity suggested that severity increases with smoking status. CONCLUSIONS: This literature review is in favor of a positive association between the prevalence of smoking and psoriasis as well as an association between smoking and severity of psoriasis.

The Value of Macrolide-Based Regimens for Community-Acquired Pneumonia.

Macrolide antimicrobials are commonly prescribed, specifically for the treatment of respiratory tract infections. Although still effective, the development of widespread macrolide resistance has limited their use. Aside from their antimicrobial effects, macrolides are also known to possess immune-modulatory properties which may confer a survival benefit in both acute and chronic inflammatory states. This review discusses the efficacy, potential mechanisms, and adverse effects of macrolide therapy specifically in community-acquired pneumonia in outpatients, hospitalized ward patients, and those requiring intensive care unit admission. Challenges for ongoing research in this field are discussed and treatment recommendations offered.

Evidence-based Recommendations for the Management of Comorbidities in Rheumatoid Arthritis, Psoriasis, and Psoriatic Arthritis: Expert Opinion of the Canadian Dermatology-Rheumatology Comorbidity Initiative.

OBJECTIVE: Comorbidities such as cardiovascular diseases (CVD), cancer, osteoporosis, and depression are often underrecognized in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis (PsO). Recommendations may improve identification and treatment of comorbidities. The Canadian Dermatology-Rheumatology Comorbidity Initiative reviewed the literature to develop practical evidence-based recommendations for management of comorbidities in patients with RA, PsA, and PsO. METHODS: Eight main topics regarding comorbidities in RA, PsA, and PsO were developed. MEDLINE, EMBASE, and the Cochrane Library (1960-12/2012), together with abstracts from major rheumatology and dermatology congresses (2010-2012), were searched for relevant publications. Selected articles were analyzed and metaanalyses performed whenever possible. A meeting including rheumatologists, dermatologists, trainees/fellows, and invited experts was held to develop consensus-based recommendations using a Delphi process with prespecified cutoff agreement. Level of agreement was measured using a 10-point Likert scale (1 = no agreement, 10 = full agreement) and the potential effect of recommendations on daily clinical practice was considered. Grade of recommendation (ranging from A to D) was determined according to the Oxford Centre for Evidence-Based Medicine evidence levels. RESULTS: A total of 17,575 articles were identified, of which 407 were reviewed. Recommendations were synthesized into 19 final recommendations ranging mainly from grade C to D, and relating to a large spectrum of comorbidities observed in clinical practice: CVD, obesity, osteoporosis, depression, infections, and cancer. Level of agreement ranged from 80.9% to 95.8%. CONCLUSION: These practical evidence-based recommendations can guide management of comorbidities in patients with RA, PsA, and PsO and optimize outcomes.

The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis.

The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010-2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.

Meta-analysis of tumor necrosis factor inhibitors and glucocorticoids on bone density in rheumatoid arthritis and ankylosing spondylitis trials.

OBJECTIVE: To examine the impact of antirheumatic drugs on bone mineral density (BMD) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis using a systematic review. METHODS: Electronic databases were systematically searched for randomized controlled trials. Studies were grouped based on disease, treatment, and site of BMD measurement. Change in BMD (ΔBMD) from baseline to end of study was recorded. Standardized mean difference (SMD) of ΔBMD between treatment and controls was standardized for meta-analyses and 95% confidence intervals (95% CIs) were calculated. RESULTS: Treatment effects on BMD were not the primary outcomes of the trials. Thirteen studies were eligible (11 RA, 2 AS, 0 PsA, and 0 psoriasis). For RA, significantly less hand bone loss was seen with tumor necrosis factor inhibitors (TNFi; SMD ΔBMD 0.33 [95% CI 0.13, 0.53], P = 0.001, I(2) = 0%) and glucocorticoids (SMD ΔBMD 0.51 [95% CI 0.20, 0.81], P = 0.001, I(2) = 0%). TNFi had no significant effect on lumbar spine and hip BMD. Glucocorticoids were associated with a negative effect on lumbar spine (SMD ΔBMD -0.30 [95% CI -0.55, -0.04], P = 0.02, I(2) = 52%), but not hip BMD. For AS, a significant increase in BMD was seen with TNFi at the lumbar spine (SMD ΔBMD 0.96 [95% CI 0.64, 1.27], P < 0.001, I(2) = 16%) and hip (SMD ΔBMD 0.38 [95% CI 0.13, 0.62], P = 0.003, I(2) = 0%). Data were insufficient to perform meta-analyses in PsA and psoriasis or for other antirheumatic drugs. CONCLUSION: In RA, TNFi and glucocorticoids appeared to attenuate hand bone loss. TNFi did not impact lumbar spine and hip BMD and glucocorticoids had negative effects on lumbar spine and no effect on hip BMD. In AS, TNFi was associated with improved lumbar spine and hip BMD.

Role of T-type channels in vasomotor function: team player or chameleon?

Low-voltage-activated T-type calcium channels play an important role in regulating cellular excitability and are implicated in conditions, such as epilepsy and neuropathic pain. T-type channels, especially Cav3.1 and Cav3.2, are also expressed in the vasculature, although patch clamp studies of isolated vascular smooth muscle cells have in general failed to demonstrate these low-voltage-activated calcium currents. By contrast, the channels which are blocked by T-type channel antagonists are high-voltage activated but distinguishable from their L-type counterparts by their T-type biophysical properties and small negative shifts in activation and inactivation voltages. These changes in T-channel properties may result from vascular-specific expression of splice variants of Cav3 genes, particularly in exon 25/26 of the III-IV linker region. Recent physiological studies suggest that T-type channels make a small contribution to vascular tone at low intraluminal pressures, although the relevance of this contribution is unclear. By contrast, these channels play a larger role in vascular tone of small arterioles, which would be expected to function at lower intra-vascular pressures. Upregulation of T-type channel function following decrease in nitric oxide bioavailability and increase in oxidative stress, which occurs during cardiovascular disease, suggests that a more important role could be played by these channels in pathophysiological situations. The ability of T-type channels to be rapidly recruited to the plasma membrane, coupled with their subtype-specific localisation in signalling microdomains where they could modulate the function of calcium-dependent ion channels and pathways, provides a mechanism for rapid up- and downregulation of vasoconstriction. Future investigation into the molecules which govern these changes may illuminate novel targets for the treatment of conditions such as therapy-resistant hypertension and vasospasm.