Can complement activation be the missing link in antiphospholipid syndrome?

APS is an autoimmune disorder with life-threatening complications that, despite therapeutic advantages, remains associated with thrombotic recurrences and treatment failure. The role of complement activation in APS pathogenesis is increasingly recognised, specifically in obstetric APS. However, its exact role in thrombotic APS and on the severity of the disease is not yet fully elucidated. Further mechanistic studies are needed to delineate the role of complement activation in the various APS clinical manifestations with aim to identify novel markers of disease severity, together with clinical trials to evaluate the efficacy of complement inhibition in APS. This could ultimately improve risk stratification in APS, patient tailored targeted therapy with complement inhibition identified as an adjunctive treatment. This article reviews current findings and challenges about complement activation in APS, discusses the potential role of platelet mediated complement activation in this setting and provides an overview on clinical implications and current therapeutics.

Where are we now in biological drugs for myositis?

Idiopathic inflammatory myopathies (IIM) are a rare and heterogeneous group of chronic autoimmune disorders. Up to 40% of IIM patients have long-term sequelae and significant functional disability. Its management can be challenging. New therapies are badly needed. The small number of cases with diverse presentations, and different diagnostic criteria interfere significantly with clinical trial results. Only intravenous immunoglobulin has been internationally approved for IIM patients. Most clinical trials of new biological therapies have failed to meet their primary endpoints in IIM, with only one biological drug recommended for refractory IIM treatment (rituximab), although not approved. We review several new emerging biological drugs including B cell depletion therapies, abatacept, janus-kinase inhibitors, and aldesleukin. Encouragingly, some phase II randomized controlled trials have evaluated the efficacy and safety of new biologics in IIM, demonstrating an improvement in clinical and laboratory measures.

The impact of antiphospholipid antibodies/antiphospholipid syndrome on systemic lupus erythematosus.

aPLs are a major determinant of the increased cardiovascular risk in patients with SLE. They adversely affect clinical manifestations, damage accrual and prognosis. Apart from the antibodies included in the 2006 revised classification criteria for APS, other non-classical aPLs might help in identifying SLE patients at increased risk of thrombotic events. The best studied are IgA anti-ß2-glycoprotein I, anti-domain I ß2-glycoprotein I and aPS-PT. Major organ involvement includes kidney and neuropsychiatric systems. aPL/APS severely impacts pregnancy outcomes. Due to increased thrombotic risk, these patients require aggressive cardiovascular risk factor control. Primary prophylaxis is based on low-dose aspirin in high-risk patients. Warfarin is the gold-standard drug for secondary prophylaxis.

Promising Experimental Treatments for Lupus Nephritis: Key Talking Points and Potential Opportunities.

Lupus nephritis (LN) is a frequent and serious complication of systemic lupus erythematosus (SLE), impairing patients' quality of life and significantly increasing mortality. Despite optimizing the use of conventional immunosuppressants and other biological drugs, its management remains unsatisfactory. This is mainly due to the heterogeneity of SLE, but also to insufficiently effective treatment regimens and clinical trial limitations (strict criteria, low number of patients included, and side effects). Most clinical trials of new biological therapies have failed to meet their primary endpoints in both general SLE and LN, with only two biological drugs (belimumab and anifrolumab) being approved by the Food and Drug Administration (FDA) for the treatment of SLE. Recently, several Phase II randomized controlled trials have evaluated the efficacy and safety of new biologics in LN, and some of them have demonstrated an improvement in clinical and laboratory measures. Multi-target therapies are also being successfully developed and encourage a belief that there will be an improvement in LN outcomes.

Targeted Therapy for SLE-What Works, What Doesn't, What's Next.

For many years, the failure of randomized controlled trials (RCTs) has prevented patients with systemic lupus erythematosus (SLE) from benefiting from biological drugs that have proved to be effective in other rheumatological diseases. Only two biologics are approved for SLE, however they can only be administered to a restricted proportion of patients. Recently, several phase II RCTs have evaluated the efficacy and safety of new biologics in extra-renal SLE and lupus nephritis. Six drug trials have reported encouraging results, with an improvement in multiple clinical and serological outcome measures. The possibility of combining B-cell depletion and anti-BLyS treatment has also been successfully explored.

Evaluation of the Synovial Effects of Biological and Targeted Synthetic DMARDs in Patients with Psoriatic Arthritis: A Systematic Literature Review and Meta-Analysis.

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD -0.85 [95% CI -1.23; -0.47]) and CD68+ macrophages (sublining, sl) (SMD -0.74 [-1.16; -0.32]) in synovial biopsies from patients treated for 4-12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.

Prognostic role of the ascending aorta dilatation in patients with arterial hypertension.

BACKGROUND: Ascending aorta (ASC) dilatation (AAD) is a common finding in arterial hypertension, affecting about 15% of hypertensive patients. AAD is associated with an increase in cardiac and vascular hypertension-related organ damage, but its prognostic role is unknown. The aim of the study was to evaluate the prognostic value of AAD as predictor of cardiovascular events in essential hypertensive patients. METHODS: Recruited patients underwent two-dimensional transthoracic echocardiography from 2007 to 2013 and followed-up for cardiovascular events until November 2018 by phone call and hospital information system check. ASC diameter and AAD were defined using both absolute and scaled definitions. Four hundred and twenty-three hypertensive patients were included in our study. RESULTS: During a median follow-up of 7.4 years (interquartile range 5.6-9.1 years), 52 events were observed. After adjusting for age, sex and BSA, both ASC diameter and AAD definition, according to ARGO-SIIA project, resulted associated with a greater risk of cardiovascular event (both P < 0.010), even after adjusting for major confounders (both P < 0.010). Moreover, we observed that the assessment of ASC improves risk stratification compared with pulse wave velocity alone, and that in absence of AAD, sinus of valsalva dilatation lost any prognostic value (P = 0.262). CONCLUSIONS: ASC diameter and AAD are both associated with a greater risk of cardiovascular events. ASC should be assessed to optimize risk stratification in hypertensive patients and its dilatation may be considered as a surrogate for vascular organ damage.

Atención médica en colangitis aguda / Medical care in acute cholangitis

Es un estudio descriptivo de 57 pacientes con diagnósticode colangitis aguda, operados en el Hospital Salvador entre enero de 1987 y junio de 1989. Se establecen un grupo de colangitis y otro de colangitis complicada,estudiándose las variables de atención médica y los factores asociados a una mayor morbimortalidad y su costo económico. Este se midió según días-camas ocupados, uso de ecografía y de antibióticos en el pre y postoperatorio. Se encontró que la colangitis es más grave por demora en el diagnóstico. Ello lleva a operaciones más largas y más complejas, aumento de días-cama y uso de antibióticos de alto costo por más tiempo, además de mayor morbilidad y mortalidad postoperatorias. Llamó la atención el menor empleo de ecografía en las colangitis complicadas. Se concluye que los factores estudiados repercuten, además del sufrimiento de los pacientes y sus familiares, en un mayor costo de la atención médica. Este costo va, según los valores establecidos por el Servicio, desde $29.355 (103 dólares) con colangitis simple hasta $50.717 (179 dólares) en colangitis complicada, por paciente y sin considerar el gasto en ecografía, exámenes de laboratorio y operación. Estos valores se duplicarían aproximadamente si se incluye el acto quirúrgico. La ecografía tiene poco impacto dado el bajo valor establecido