Vascular Disease in Systemic Lupus Erythematosus

Vascular disease, either as a direct complication of the disease or developing as an accompanying comorbidity impairs significantly the quality of life of patients with SLE and represents the most frequent cause of death in established lupus. This paper aims to give an overview of the prevalence of the different forms of vasculopathy that can be encountered in a lupus patient, describe their pathogenesis, and address their impact on disease severity and outcome

Targeting the B-Cell Pathway in Lupus Nephritis: Current Evidence and Future Perspectives

Nephritis represents a frequent, severe complication of systemic lupus erythematosus. Autoantibodies appear to be fundamental in the pathogenesis of lupus nephritis. Several hypotheses are currently experimentally tested to further elucidate the direct induction of inflammation through interaction of the pathological autoantibodies with intrinsic glomerular components and the triggering of a complement-driven autoinflammatory cascade. B-cells have, in the last decade, emerged as a promising new therapeutic target, as biological treatments successfully attempting B-cell depletion, inhibition of B-cell proliferation and differentiation, or modulation of B-cell function have become bioengineered. Clinical trials have so far proved controversial regarding the efficacy of these new agents. Thus, despite the short and long-term side effects associated with immunosuppressive treatment alternative emerging treatments are still regarded “rescue” regimens in refractory patients. In an effort to accurately evaluate the potential of these therapies in lupus nephritis, several issues have been raised mainly in terms of patient selection criteria and trial duration. This review aims to expand on the proposed pathophysiologic mechanisms implicating the B-cell pathway in the pathogenesis of lupus nephritis and summarize current knowledge obtained from clinical trials introducing these biologics in its treatment. Finally, it will elaborate on potential applications of currently available biologic agents and forthcoming treatment options

Eosinophilic Enteritis with Ascites in a Patient with Overlap Syndrome

Gastrointestinal involvement is frequent in patients with systemic lupus erythematosus (SLE). Eosinophilic gastroenteritis, however, has only rarely been described in rheumatological conditions, despite its reported connection to autoimmune diseases, such as hypereosinophilic syndrome, vasculitides, and systemic mastoidosis. It presents typically with abdominal pain and diarrhea and is only exceptionally associated with ascites. Diagnosis can be problematic, as several other clinical conditions (malignancies, infection/tuberculosis, and inflammatory bowel diseases) have to be ruled out. It is basically a nonsurgical disease, with excellent recovery on conservative treatment. We report the rare case of a young woman with overlap syndrome who presented with abdominal pain and ascites. The diagnosis of eosinophilic enteritis was made based on clinical, radiological, and laboratory criteria. The patient was treated with corticosteroids with excellent response

Baseline Chest Computed Tomography as Standard of Care in High-Risk Hematology Patients

Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases (n = 69; 49%), hematology (n = 68; 48%), and others (n = 41; 29%). BCT was performed in 57% (n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%; IQR 5-15%) and non-BCT centers (7%; IQR 5-10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% (n = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-beta-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation The main risk factors for CRE infections in hospitals with high incidence included previous coloni-zation, urinary catheter and exposure to broad spectrum antibiotics

Αλληλεπιδράσεις του πυρηνικού φακέλου με τη χρωματίνη: Βιοχημικός χαρακτηρισμός παραγόντων που συνδέουν την έσω πυρηνική μεμβράνη με τη χρωματίνη

Morphological studies have established a close association of peripheral heterochromatin with the nuclear envelope, which has been attributed both to nuclear lamin and lamin-asociated proteins. It remains to be determined which of these elements are essential and which play an auxiliary role in nuclear envelope -chromatin interactions. To address this question, we used in vitro reconstituted vesicles assembled from octyl glucoside solubilized nuclear envelopes as a model system. Comparison of the chromosome-binding properties of normal, immunodepleted and chemically extracted vesicles led to the conclusion that the principal chromatin anchorage site at the nuclear envelope is LBR, a ubiquitous integral protein of the inner nuclear membrane. Consistent with this interpretation, purified LBR binds directly to chromatin fragments and decorates the surface of chromosomes in a pattern highly reminiscent of Q-bandingΜορφολογικές μελέτες δείχνουν μια στενή σύνδεση περιφεριακής ετεροχρωματίνης με τον πυρηνικό φάκελλο η οποία αποδιδόταν ως τώρα τόσο στις πυρηνικές λαμίνες όσο και σε διαμεμβρανικές πρωτεϊνες, υποδοχείς των λαμινών. Απομένει να καθοριστεί ποιές πρωτεϊνες είναι όντως απαραίτητες και ποιές παίζουν απλώς βοηθητικό ρόλο στη σύνδεση του πυρηνικού φακέλλου με τη χρωματίνη. Για να απαντήσουμε αυτό το ερώτημα χρησιμοποιήσαμε επανασχηματισμένα κυστίδια παρασκευασμένα από πυρηνικούς φακέλλους, που είχαν διαλυτοποιηθεί με οκτυλγλυκοζίδιο. Σύγριση της ικανότητας σύνδεσης "ακέραιων" κυστιδίων", κυστιδίων από τα οποία είχαν ανοσοαφαιρεθεί συγκεκριμένες πρωτεϊνες και χημικά εκχυλισμένων μεμβρανών οδήγησε στο συμπέρασμα ότι ο πυρηνικός συνδέεται με τη χρωματίνη μέσω του LBR (Lamin B Receptor), μιας διαμεμβρανικής πρωτεϊνης της έσω πυρηνικής μεμβράνης. Απομονωμένος LBR συνδέεται άμεσα με κομμάτια χρωματίνες, τα οποία διακοσμεί κατά τρόπο που θυμίζει ζώνες Q

CD20+ B Cell Depletion in Systemic Autoimmune Diseases: Common Mechanism of Inhibition or Disease-Specific Effect on Humoral Immunity?

Autoimmunity remains a complex physiologic deviation, enabled and perpetuated by a variety of interplayers and pathways. Simplistic approaches, targeting either isolated end-effectors of more centrally placed interactors of these mechanisms, are continuously tried in an effort to comprehend and halt cascades with potential disabling and deleterious effects in the affected individuals. This review focuses on theoretical and clinically proved effects of rituximab-induced CD20+ B cell depletion on different systemic autoimmune diseases and extrapolates on pathogenetic mechanisms that may account for different interindividual or interdisease responses

Pregnancy in Systemic Lupus Erythematosus Patients with Nephritis

Pregnancy in patients with lupus nephritis is a challenging clinical situation. Although not absolutely contraindicated, it is associated with increased risk for foetal and maternal complications, including foetal loss, preterm delivery, intrauterine growth retardation, hypertension, pre-eclampsia, nephritis flare, and, rarely, maternal death. The complication rate is further increased in the presence of antiphospholipid antibodies or the antiphospholipid syndrome. Proliferative classes of nephritis (III and IV) also appear to confer excess risk for complications. Immunosuppressives such as cyclophosphamide and mycophenolate, and antihypertensives such as angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers need to be stopped due to teratogenic effects. Agents like corticosteroids, azathioprine, and probably calcineurin inhibitors are considered compatible with gestation. Lupus activity needs to be assessed and carefully monitored. Thrombotic risk due to antiphospholipid antibodies, thrombotic events, or nephrosis needs to be evaluated and managed accordingly, with the use of aspirin and/or unfractioned or low molecular weight heparin. Differentiating between severe pre-eclampsia and lupus nephritis flare might require a renal biopsy, which might not always be feasible, for example after the 32nd gestational week or in a setting of uncontrolled hypertension or thrombocytopaenia. A 6-month history of quiescent disease on non-teratogenic agents seems to be associated with best chance for favourable outcomes. Pregnancy is optimally managed by a multidisciplinary team of experienced specialists, and close monitoring for disease activity during gestation; additionally, follow-up for maternal flare postpartum is also advised

The Ongoing Epidemic of West Nile Virus in Greece: The Contribution of Biological Vectors and Reservoirs and the Importance of Climate and Socioeconomic Factors Revisited

Emerging infectious diseases have inflicted a significant health and socioeconomic burden upon the global population and governments worldwide. West Nile virus, a zoonotic, mosquito-borne flavivirus, was originally isolated in 1937 from a febrile patient in the West Nile Province of Uganda. It remained confined mainly to Africa, the Middle East, and parts of Europe and Australia until 1999, circulating in an enzootic mosquito-bird transmission cycle. Since the beginning of the 21st century, a new, neurotropic, more virulent strain was isolated from human outbreaks initially occurring in North America and later expanding to South and South-eastern Europe. Since 2010, when the first epidemic was recorded in Greece, annual incidence has fluctuated significantly. A variety of environmental, biological and socioeconomic factors have been globally addressed as potential regulators of the anticipated intensity of the annual incidence rate; circulation within the zoonotic reservoirs, recruitment and adaptation of new potent arthropod vectors, average winter and summer temperatures, precipitation during the early summer months, and socioeconomic factors, such as the emergence and progression of urbanization and the development of densely populated areas in association with insufficient health policy measures. This paper presents a review of the biological and socioenvironmental factors influencing the dynamics of the epidemics of West Nile virus (WNV) cases in Greece, one of the highest-ranked European countries in terms of annual incidence. To date, WNV remains an unpredictable opponent as is also the case with other emerging infectious diseases, forcing the National Health systems to develop response strategies, control the number of infections, and shorten the duration of the epidemics, thus minimizing the impact on human and material resources