Hemolytic anemia due to acute cytomegalovirus infection in an immunocompetent adult: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Cytomegalovirus is a common virus responsible for a wide range of clinical manifestations. Hemolysis is a rare but potentially life-threatening complication of cytomegalovirus infection, described mostly in immunocompromised patients, the pathogenesis of which is still unclear.</p> <p>We performed a review of the literature regarding cases of hemolytic anemia during acute cytomegalovirus infection in apparently immunocompetent individuals. We searched for relevant articles in PubMed for the period of 1980 through 2008.</p> <p>Case presentation</p> <p>We describe a case of Coombs-negative hemolytic anemia in a 44-year-old Caucasian immunocompetent man with acute cytomegalovirus infection.</p> <p>Conclusion</p> <p>Clinicians should consider cytomegalovirus infection in the differential diagnosis of hemolytic anemia in immunocompetent adults. Possible therapeutic options include antiviral therapy and steroids, although the best treatment strategy is still controversial.</p

Lessons from in vitro perifusion of pancreatic islets isolated from 80 human pancreases.

We report the average insulin response to acute glucose measured by in vitro perifusion of pancreatic islets isolated from 80 consecutive human organs. Different perifusion parameters were considered [basal release, stimulation index (SI), time to peak, incremental area under the curve Δ-AUCa)], and the correlation among them was determined. SI positively correlated with Δ-AUCa (p < 0.001, r = 0.80) while negatively with time to peak (p < 0.05, r = −0.23). We also evaluated several variables of the isolation procedure that might affect responsiveness to glucose by human islets. Sex and age of pancreas donors, cold ischemia time, duration of the digestion, collagenase concentration, and lot characteristics (collagenase, trypsin, clostripain, and proteases activity), and final islet yield were considered. Multivariate regression analysis showed only an independent association between SI and the concentration of collagenase (p = 0.01)

Fabrication of photothermally active poly(vinyl alcohol) films with gold nanostars for antibacterial applications.

The unique photothermal properties of non-spherical gold nanoparticles under near-infrared (NIR) irradiation find broad application in nanotechnology and nanomedicine. The combination of their plasmonic features with widely used biocompatible poly(vinyl alcohol) (PVA) films can lead to novel hybrid polymeric materials with tunable photothermal properties and a wide range of applications. In this study, thin PVA films containing highly photothermally efficient gold nanostars (GNSs) were fabricated and their properties were studied. The resulting films displayed good mechanical properties and a pronounced photothermal effect under NIR irradiation. The local photothermal effect triggered by NIR irradiation of the PVA-GNS films is highly efficient at killing bacteria, therefore providing an opportunity to develop new types of protective antibacterial films and coatings

Evaluation of BAFF, APRIL and CD40L in ocrelizumab-treated pwMS and infectious risk

Simple Summary Since B cells have been linked to multiple sclerosis (MS) and its progression as well as T cells, the second-generation anti-CD20 recombinant humanized monoclonal antibody ocrelizumab has been approved for MS treatment. Although ocrelizumab efficiently depletes B cells in peripheral blood, some B cells and CD20 negative plasma cells persist in lymphatic organs, and their survival is regulated by the B-cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system. Moreover, ocrelizumab may result in higher infectious risk. Herein, we investigated plasma BAFF, APRIL and CD40L levels and their relationship with infectious risk in ocrelizumab-treated people with (pw) MS at baseline, at 6 months and at 12 months after starting the treatment, comparing the above-mentioned findings with a control group. At baseline, plasma levels of all three cytokines were higher compared to the control group. In pwMS, the longitudinal assessment showed a significant increase in plasma BAFF levels and a significant reduction in plasma APRIL and CD40L. Moreover, when stratifying pwMS according to the onset of an infectious event during the 12-month follow-up period, significantly higher plasma BAFF levels were found at all time-points in the group with an infectious event than in the group without an infectious event. Hence, BAFF may have a role as a marker of immune dysfunction and infectious risk. Background: The anti-CD20 monoclonal antibody ocrelizumab has been widely employed in the treatment of people with multiple sclerosis (pwMS). However, its B-cell-depleting effect may induce a higher risk of infectious events and alterations in the secretion of B-cell-activating factors, such as BAFF, APRIL and CD40L. Methods: The aim of this study was to investigate plasma BAFF, APRIL and CD40L levels and their relationship with infectious risk in ocrelizumab-treated pwMS at baseline (T0), at 6 months (T6) and at 12 months (T12) after starting the treatment. As a control group, healthy donors (HD) were enrolled too. Results: A total of 38 pwMS and 26 HD were enrolled. At baseline, pwMS showed higher plasma BAFF (p &lt; 0.0001), APRIL (p = 0.0223) and CD40L (p &lt; 0.0001) levels compared to HD. Compared to T0, plasma BAFF levels were significantly increased at both T6 and T12 (p &lt; 0.0001 and p &lt; 0.0001, respectively). Whereas plasma APRIL and CD40L levels were decreased at T12 (p = 0.0003 and p &lt; 0.0001, respectively). When stratifying pwMS according to the development of an infectious event during the 12-month follow-up period in two groups-with (14) and without an infectious event (24)-higher plasma BAFF levels were observed at all time-points; significantly, in the group with an infectious event compared to the group without an infectious event (T0: p &lt; 0.0001, T6: p = 0.0056 and T12: p = 0.0400). Conclusions: BAFF may have a role as a marker of immune dysfunction and of infectious risk

SAT0368 PREGNANCY IN WOMEN WITH SPONDYLOARTHRITIS: WHO ARE THE PATIENTS AT RISK OF DISEASE FLARE?

Background:Patients with Spondyloarthritis (SpA) can experience flares during pregnancy and postpartum even though the available data are limited and not conclusive.Objectives:To assess disease activity and treatment modification during pregnancy and postpartum in patients with SpA and to identify risk factors for disease flare.Methods:Data on SpA pregnancies prospectively-followed in a pregnancy clinic from 2010 to 2019 were retrospectively analysed. Disease activity was assessed during each trimester and postpartum using ASDAS-CRP or DAS28-CRP. Flare was defined as an increase of disease activity leading to treatment modification (introduction or increase ≥5mg/day of prednisone, introduction of cDMARD or bDMARD)1.Results:Data on 50 pregnancies in 46 patients were collected (mean age at conception 33±4.7 years; median disease duration: 60 months (IQR 24-132); 33 psoriatic arthritis, 6 axialSpA, 2 reactive arthritis, 2 IBD-related SpA; 6 undifferentiated SpA, 1 juvenile idiopathic arthritis). Six pregnancies ended in miscarriage, so they weren't considered for the analysis of flares during pregnancy (table 1). Fifteen out of 44 (34%) pregnancies had at least one flare during pregnancy (6, 7 and 4 during 1st, 2ndand 3rdtrimester respectively; 2 pregnancies had multiple flares). A higher rate of flare was observed in pregnancies of patients with axial involvement (p=0.01), on treatment with bDMARDs at preconceptional visit (p=0.03) and who stopped TNFi at positive pregnancy test (p=0.03). Peripheral involvement was associated with a lower rate of flares (p=0.02). Medications resumed during pregnancy were steroids (in 6 pregnancies), cDMARDs (2 sulfasalazine, 1 cyclosporine) and bDMARDs (4 certolizumab, 4 etanercept). During postpartum period flares were recorded in 46% of patients.Table 1.clinical features, medication and disease activity in pregnancies with flare vs without flareCLINICAL FEATURESFLARE (15)NO FLARE (29)pAxial involvement, n (%)11/15 (73)9/29 (31)0.01Peripheral arthritis, n (%)8/15 (53)26/29 (90)0.02Enthesitis, n (%)5/15 (33)14/29 (48)nsDactilitis, n (%)3/15 (20)8/29 (28)nsPsoriasis, n (%)6/15 (40)17/29 (59)nsIBD, n (%)2/15 (13)0nsUveitis, n(%)1/15 (7)3/29 (10)nsHLAB27 +7/11 (64)5/12 (42)nsMEDICATION HISTORYbDMARDs, n (%)11/15 (73)7/29 (24)0.003bDMARDs at preconception visit, n (%)8/15 (53)6/29 (21)0.04bDMARDs stopped at positive pregnancy test, n (%)7/15 (47)4/29 (14)0.03cDMARDs, n (%)12/15 (80)25/29 (86)nsDISEASE ACTIVITYACTIVE DISEASE* preconception visit, n(%)3/14 (21)4/23 (17)nsACTIVE DISEASE 1sttrimester, n(%)6/15 (40)1/29 (3)0.004ACTIVE DISEASE 2ndtrimester, n(%)8/15 (47)2/29 (7)0.001ACTIVE DISEASE 3rdtrimester, n(%)2/15 (13)1/29 (3)ns*DAS28-CRP>3.2 or ASDAS-CRP≥2.1Conclusion:In our cohort of prospectively-followed SpA pregnancies, 34% experienced a flare during pregnancy and 46% during postpartum. Flares occurred especially in those patients who discontinued TNFi early in pregnancy and with axial involvement. When resumed during pregnancy, TNFi was able to control the disease. At preconception counselling, the continuation of TNFi during pregnancy should be considered to ensure a better control of disease.References:[1]Fischer-Betz R et al.Arthritis Rheumatol. 2015; 67.Disclosure of Interests: :None declare

Self-assembled monolayers of copper sulfide nanoparticles on glass as antibacterial coatings

We developed an easy and reproducible synthetic method to graft a monolayer of copper sulfide nanoparticles (CuS NP) on glass and exploited their particular antibacterial features. Samples were fully characterized showing a good stability, a neat photo-thermal effect when irradiated in the Near InfraRed (NIR) region (in the so called \u201cbiological window\u201d), and the ability to release controlled quantities of copper in water. The desired antibacterial activity is thus based on two different mechanisms: (i) slow and sustained copper release from CuS NP-glass samples, (ii) local temperature increase caused by a photo-thermal effect under NIR laser irradiation of CuS NP\u2013glass samples. This behavior allows promising in vivo applications to be foreseen, ensuring a \u201cstatic\u201d antibacterial protection tailored to fight bacterial adhesion in the critical timescale of possible infection and biofilm formation. This can be reinforced, when needed, by a photo-thermal action switchable on demand by an NIR light

Modular approach for bimodal antibacterial surfaces combining photo-switchable activity and sustained biocidal release

Photo-responsive antibacterial surfaces combining both on-demand photo-switchable activity and sustained biocidal release were prepared using sequential chemical grafting of nano-objects with different geometries and functions. The multi-layered coating developed incorporates a monolayer of near-infrared active silica-coated gold nanostars (GNS) decorated by silver nanoparticles (AgNP). This modular approach also enables us to unravel static and photo-activated contributions to the overall antibacterial performance of the surfaces, demonstrating a remarkable synergy between these two mechanisms. Complementary microbiological and imaging evaluations on both planktonic and surface-attached bacteria provided new insights on these distinct but cooperative effects

Silencing Nfix rescues muscular dystrophy by delaying muscle regeneration

Muscular dystrophies are severe disorders due to mutations in structural genes, and are characterized by skeletal muscle wasting, compromised patient mobility, and respiratory functions. Although previous works suggested enhancing regeneration and muscle mass as therapeutic strategies, these led to no long-term benefits in humans. Mice lacking the transcription factor Nfix have delayed regeneration and a shift toward an oxidative fiber type. Here, we show that ablating or silencing the transcription factor Nfix ameliorates pathology in several forms of muscular dystrophy. Silencing Nfix in postnatal dystrophic mice, when the first signs of the disease already occurred, rescues the pathology and, conversely, Nfix overexpression in dystrophic muscles increases regeneration and markedly exacerbates the pathology. We therefore offer a proof of principle for a novel therapeutic approach for muscular dystrophies based on delaying muscle regeneration