Lupus nephritis: clinical presentations and outcomes in the 21st century.
Ontology highlight
ABSTRACT:
SUBMITTER: Gasparotto M
PROVIDER: S-EPMC7751166 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
Lupus nephritis: clinical presentations and outcomes in the 21st century.
Gasparotto Michela M Gatto Mariele M Binda Valentina V Doria Andrea A Moroni Gabriella G
Rheumatology (Oxford, England) 20201201 Suppl5
Lupus nephritis (LN) is a frequent and severe manifestation of SLE. Along the decades, the epidemiology of LN and its clinical presentation have been changing. However, even though retrospective cohort studies report a decreased mortality rate and an improvement in the disease prognosis, the percentage of patients progressing into end stage renal disease (ESRD) keeps steady despite the improvements in therapeutic strategies. Current in-use medications have been available for decades now, yet ove ...[more]
Similar Datasets
Project description:There is no good science in bad models. Cell culture is especially prone to artifacts. A number of novel cell culture technologies have become more broadly available in the 21st century, which allow overcoming limitations of traditional culture and are more physiologically relevant. These include the use of stem-cell derived human cells, cocultures of different cell types, scaffolds and extracellular matrices, perfusion platforms (such as microfluidics), 3D culture, organ-on-chip technologies, tissue architecture, and organ functionality. The physiological relevance of such models is further enhanced by the measurement of biomarkers (e.g., key events of pathways), organ specific functionality, and more comprehensive assessment cell responses by high-content methods. These approaches are still rarely combined to create microphysiological systems. The complexity of the combination of these technologies can generate results closer to the in vivo situation but increases the number of parameters to control, bringing some new challenges. In fact, we do not argue that all cell culture needs to be that sophisticated. The efforts taken are determined by the purpose of our experiments and tests. If only a very specific molecular target to cell response is of interest, a very simple model, which reflects this, might be much more suited to allow standardization and high-throughput. However, the less defined the end point of interest and cellular response are, the better we should approximate organ- or tissue-like culture conditions to make physiological responses more probable. Besides these technologic advances, important progress in the quality assurance and reporting on cell cultures as well as the validation of cellular test systems brings the utility of cell cultures to a new level. The advancement and broader implementation of Good Cell Culture Practice (GCCP) is key here. In toxicology, this is a major prerequisite for meaningful and reliable results, ultimately supporting risk assessment and product development decisions.
| S-EPMC5578455 | biostudies-literature
Project description:ObjectiveWe report a review of outcomes in schizophrenia in the twenty-first century, replicating and extending work undertaken by the late Richard Warner in his seminal book, "Recovery from Schizophrenia: Psychiatry and Political Economy" (1985;2004).MethodWarner's methods were followed as closely as possible. Only observational/naturalistic studies were included. Six scientific databases were searched from 2000 to 2020. 6,640 records were retrieved. 47 met inclusion criteria.ResultsOverall, complete recovery is higher in this study than in Warner's (37.75% cf 20.4%), especially for first episode psychosis (FEP) (57.1% cf 20.7%). Clinical recovery, annualized remission rate (ARR), and employment outcomes were significantly superior for first episode psychosis compared with multiple episode psychosis (MEP). ARR shows a trend toward reduction over time, from 2.2 before the financial crash of 2008 to 1.6 after (t = 1.85 df 40 p = .07). The decline is statistically significant for the MEP group (t = 2.32 df18 p = .03). There were no differences in outcome by region, sample characteristics, outcome measures used, or quality of studies. Heterogeneity of clinical outcome measures across the literature makes evidence synthesis difficult. Weak and inconsistent reporting of functional and employment outcomes mean that findings lack meaning with respect to lived experience.ConclusionFuture research strategies should aim to reduce heterogeneity in clinical outcome measures and to increase the emphasis on capture and reporting of more sophisticated measures of social and functional outcome. Outcome domains should be disaggregated rather than conflated into unitary recovery constructs.
| S-EPMC8213926 | biostudies-literature
Project description:The prognostic significance of histopathologic (sub)classes in the current classification of lupus nephritis (LN) is controversial. We analyzed clinical and histopathologic predictors of renal outcome in LN outside the framework of the classification.Variables (50 histopathologic and ten clinical) were tested in mixed, linear, and Cox regression models for their association with renal flare, ESRD, and eGFR during follow-up (1, 5, and 10 years) in 105 patients with LN who underwent biopsy from 1987 to 2011. The Cockcroft-Gault (normalized to a body surface area of 1.73 m2) and Schwartz formulas were used to calculate eGFR for adults and children, respectively.During median follow-up of 9.9 years (25th-75th percentile, 5.9-13.8), 47 patients experienced a renal flare and 21 progressed to ESRD. Renal flare was predicted by fibrinoid necrosis (hazard ratio [HR], 1.04 per %; 95% confidence interval [95% CI], 1.00 to 1.07) and nonwhite race (HR, 2.23; 95% CI, 1.23 to 4.04). ESRD was predicted by fibrinoid necrosis (HR, 1.08 per %; 95% CI, 1.02 to 1.13), fibrous crescents (HR, 1.09 per %; 95% CI, 1.02 to 1.17), interstitial fibrosis/tubular atrophy (IF/TA) ?25% (HR, 3.89; 95% CI, 1.25 to 12.14), eGFR at baseline (HR, 0.98 per ml/min per 1.73 m2; 95% CI, 0.97 to 1.00), and nonwhite race (HR, 7.16; 95% CI, 2.34 to 21.91). A higher mean eGFR during follow-up was associated with normal glomeruli (+0.2 ml/min per 1.73 m2 per %; 95% CI, 0.1 to 0.4). Like ESRD, a lower eGFR during follow-up was associated with fibrous crescents, IF/TA?25%, and nonwhite race, as well as with cellular/fibrocellular crescents (-0.4 ml/min per 1.73 m2 per %; 95% CI, -0.6 to -0.2) and age (-0.8 ml/min per 1.73 m2 per year; 95% CI, -1.2 to -0.4).The LN classification should include an index of evidence-based prognosticators. Awaiting validation of a formal index, we suggest that at least fibrinoid necrosis, fibrous crescents, and IF/TA warrant explicit independent scoring to assess the risk of progressive renal dysfunction in conjunction with clinical findings.
| S-EPMC5477219 | biostudies-literature
Project description:Systemic lupus erythematosus is a heterogeneous autoimmune disease marked by the presence of pathogenic autoantibodies, immune dysregulation, and chronic inflammation that may lead to increased morbidity and early mortality from end-organ damage. More than half of all systemic lupus erythematosus patients will develop lupus nephritis. Genetic-association studies have identified more than 50 polymorphisms that contribute to lupus nephritis pathogenesis, including genetic variants associated with altered programmed cell death and defective immune clearance of programmed cell death debris. These variants may support the generation of autoantibody-containing immune complexes that contribute to lupus nephritis. Genetic variants associated with lupus nephritis also affect the initial phase of innate immunity and the amplifying, adaptive phase of the immune response. Finally, genetic variants associated with the kidney-specific effector response may influence end-organ damage and the progression to end-stage renal disease and death. This review discusses genetic insights of key pathogenic processes and pathways that may lead to lupus nephritis, as well as the clinical implications of these findings as they apply to recent advances in biologic therapies.
| S-EPMC4653095 | biostudies-literature
Project description:IntroductionIn addition to glomerular lesion, renal vascular lesion is also an important prognostic marker of lupus nephritis (LN). Among patients with various vascular changes, individuals with thrombotic microangiopathy (TMA) present with severe clinical manifestations and have a high mortality. The aim of the present study was to assess the spectrum and impact of TMA on the outcomes of LN. In a prospective observational study of 2.5 years' duration, clinical and renal histopathological data regarding biopsy-proven LN were noted, and evaluation for antiphospholipid syndrome (APS) as a cause of TMA in LN was also carried out.MethodsStudy subjects were followed up actively for 6 months, and various outcomes were noted. Cases were divided into 2 groups as LN with TMA and LN without TMA, and various features were compared between the 2 groups. Outcomes recorded were complete response (CR), partial response (PR), treatment failure, and death.ResultsOf the 197 patients with LN, 50 patients (25.4%) were diagnosed with co-existing renal TMA. Five patients (10%) were found to have concomitant APS. As compared to patients without TMA, those with TMA had significantly higher rates of oliguria (P = 0.035), advanced renal injury, that is, serum creatinine > 3mg/dl (P = 0.002), fibrocellular and fibrous crescents (P = 0.01), and tubular atrophy (P = 0.001). Outcomes included CR in 15 patients (30%), PR in 10 (20%), failure in 19 (38%), and death in 6 (12%). Patients with LN with TMA had higher rates of treatment failure (P = 0.02) compared to the group without TMA.DiscussionThe presence of TMA in patients with LN is associated with adverse clinicopathological presentation and poor outcome.
| S-EPMC5733673 | biostudies-literature
Project description:BackgroundLupus nephritis is associated with increased risk of end-stage renal disease (ESRD) and all-cause mortality. We evaluated the clinical features and outcomes of patients with early and delayed lupus nephritis.MethodsThe medical records of 171 patients who met the 1997 revised classification criteria for systemic lupus erythematosus (SLE) with pathologic confirmation of lupus nephritis were reviewed. Early lupus nephritis was defined when lupus nephritis was histopathologically confirmed as the first clinical manifestation of SLE, whereas delayed lupus nephritis was defined as lupus nephritis that was identified after the diagnosis of SLE. Clinical and laboratory data, as well as kidney histopathology and medication usage were investigated. Kaplan-Meier and Cox-proportional hazard analysis was performed to compare the outcomes of early and delayed lupus nephritis and evaluate factors associated with ESRD and all-cause mortality.ResultsPatients with early lupus nephritis had higher disease activity (median non-renal SLE disease activity index-2000, 6.0 vs. 4.0; p < 0.001) and more frequent skin rash, oral ulcer and serositis; however, the proportion of patients with higher renal chronicity index was greater in the delayed lupus nephritis group (p = 0.007). Nevertheless, no difference was found regarding ESRD and all-cause mortality between the groups. In Cox-proportional hazard analysis, C-reactive protein level, creatinine level and chronicity index were factors associated with ESRD, while age and haemoglobin level were associated with all-cause mortality.ConclusionsIn conclusion, clinical outcomes of early and delayed lupus nephritis are not significantly different. Rigorous adherence to current treatment recommendations is essential for the treatment of lupus nephritis.
| S-EPMC7341643 | biostudies-literature
Project description:It has been nearly 50 years since the golden age of antibiotic discovery (1945-1975) ended; yet, we still struggle to identify novel drug targets and to deliver new chemical classes of antibiotics to replace those rendered obsolete by drug resistance. Despite herculean efforts utilizing a wide range of antibiotic discovery platform strategies, including genomics, bioinformatics, systems biology and postgenomic approaches, success has been at best incremental. Obviously, finding new classes of antibiotics is really hard, so repeating the old strategies, while expecting different outcomes, seems to boarder on insanity. The key questions dealt with in this review include: (1) If mutation based drug resistance is the major challenge to any new antibiotic, is it possible to find drug targets and new chemical entities that can escape this outcome; (2) Is the number of novel chemical classes of antibacterials limited by the number of broad spectrum drug targets; and (3) If true, then should we focus efforts on subgroups of pathogens like Gram negative or positive bacteria only, anaerobic bacteria or other group where the range of common essential genes is likely greater?. This review also provides some examples of existing drug targets that appear to escape the specter of mutation based drug resistance, and provides examples of some intermediate spectrum strategies as well as modern molecular and genomic approaches likely to improve the odds of delivering 21st century medicines to combat multidrug resistant pathogens.
| S-EPMC7277910 | biostudies-literature
Project description: Not available
| S-EPMC1420684 | biostudies-literature
Project description:Medical education has been under a constant state of revision for the past several years. The overarching theme of the curriculum revisions for medical schools across the USA has been creating better physicians for the 21st century, with the same end result: graduating medical students at the optimal performance level when entering residency. We propose a robust, thorough assessment process that will address the needs of clerkships, residents, students, and, most importantly, medical schools to best measure and improve clinical reasoning skills that are required for the learning outcomes of our future physicians. The Accreditation Council for Graduate Medical Education (ACGME) evaluates and accredits medical school graduates based on competency-based outcomes and the assessment of specialty-specific milestones; however, there is some evidence that medical school graduates do not consistently meet the Level 1 milestones prior to entering/beginning residency, thus starting their internship year underprepared and overwhelmed. Medical schools should take on the responsibility to provide competency-based assessments for their students during the clinical years. These assessments should be geared toward preparing them with the cognitive competencies and skills needed to successfully transition to residency. Then, medical schools can produce students who will ultimately be prepared for transition to their residency programs to provide quality care.
| S-EPMC5491574 | biostudies-other
Project description:ImportanceNew technologies are rapidly reshaping health care. However, their effect on drug development to date generally has been limited.ObjectivesTo evaluate disease modeling and simulation, alternative study design, novel objective measures, virtual research visits, and enhanced participant engagement and to examine their potential effects as methods and tools on clinical trials.Evidence reviewWe conducted a systematic search of relevant terms on PubMed (disease modeling and clinical trials; adaptive design, clinical trials, and neurology; Internet, clinical trials, and neurology; and telemedicine, clinical trials, and neurology), references of previous publications, and our files. The search encompassed articles published from January 1, 2000, through November 30, 2014, and produced 7976 articles, of which 22 were determined to be relevant and are included in this review.FindingsFew of these new methods and technologies have been applied to neurology clinical trials. Clinical outcomes, including cognitive and stroke outcomes, increasingly are captured remotely. Other therapeutic areas have successfully implemented many of these tools and technologies, including web-enabled clinical trials.Conclusions and relevanceIncreased use of new tools and approaches in future clinical trials can enhance the design, improve the assessment, and engage participants in the evaluation of novel therapies for neurologic disorders.
| S-EPMC4708881 | biostudies-literature