scholarly journals Long-term outcomes and response to treatment in diacylglycerol kinase epsilon nephropathy

2020 ◽  
Vol 97 (6) ◽  
pp. 1260-1274 ◽  
Author(s):  
Vicky Brocklebank ◽  
Gurinder Kumar ◽  
Alexander J. Howie ◽  
Jayanthi Chandar ◽  
David V. Milford ◽  
...  
Keyword(s):  
Diacylglycerol Kinase ◽  
Response To Treatment ◽  
Long Term Outcomes

scholarly journals The Genetic, Environmental, and Immunopathological Complexity of Autoantibody-Negative Rheumatoid Arthritis

2021 ◽  
Vol 22 (22) ◽  
pp. 12386
Author(s):  
Ludovico De Stefano ◽  
Bernardo D’Onofrio ◽  
Antonio Manzo ◽  
Carlomaurizio Montecucco ◽  
Serena Bugatti
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Presentation ◽  
Adaptive Immune System ◽  
Response To Treatment ◽  
Targeted Intervention ◽  
Long Term Outcomes ◽  
Inflammatory Cascade ◽  
Adaptive Immune ◽  
Disease Subtypes

Differences in clinical presentation, response to treatment, and long-term outcomes between autoantibody-positive and -negative rheumatoid arthritis (RA) highlight the need for a better comprehension of the immunopathogenic events underlying the two disease subtypes. Whilst the drivers and perpetuators of autoimmunity in autoantibody-positive RA have started to be disclosed, autoantibody-negative RA remains puzzling, also due its wide phenotypic heterogeneity and its possible misdiagnosis. Genetic susceptibility appears to mostly rely on class I HLA genes and a number of yet unidentified non-HLA loci. On the background of such variable genetic predisposition, multiple exogeneous, endogenous, and stochastic factors, some of which are not shared with autoantibody-positive RA, contribute to the onset of the inflammatory cascade. In a proportion of the patients, the immunopathology of synovitis, at least in the initial stages, appears largely myeloid driven, with abundant production of proinflammatory cytokines and only minor involvement of cells of the adaptive immune system. Better understanding of the complexity of autoantibody-negative RA is still needed in order to open new avenues for targeted intervention and improve clinical outcomes.

Dilated cardiomyopathy caused by truncating titin variants: long-term outcomes, arrhythmias, response to treatment and sex differences

2020 ◽  
pp. jmedgenet-2020-107178
Author(s):  
Christoffer Rasmus Vissing ◽  
Torsten Bloch Rasmussen ◽  
Anne Mette Dybro ◽  
Morten Salling Olesen ◽  
Lisbeth Nørum Pedersen ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Dilated Cardiomyopathy ◽  
Ventricular Arrhythmias ◽  
Left Ventricular ◽  
Response To Treatment ◽  
Composite Outcome ◽  
Long Term Outcomes ◽  
Female Sex ◽  
Negative Predictor

BackgroundTruncating variants in titin (TTNtv) are the most common cause of dilated cardiomyopathy (DCM). We evaluated the genotype-phenotype correlation in TTNtv-DCM, with a special focus on long-term outcomes, arrhythmias, response to treatment and sex-related presentation.MethodsData on patient characteristics and outcomes were collected retrospectively from electronic health records of patients genotyped at two Danish heart transplantation centres.ResultsWe included 115 patients (66% men). At diagnosis of DCM, mean age was 46±13 years and left ventricular ejection fraction (LVEF) was 28%±13%. During a median follow-up of 7.9 years, 26% reached a composite outcome of left ventricular assist device implantation, heart transplantation or death. In 20% an arrhythmia preceded the DCM diagnosis. In total, 43% had atrial fibrillation (AF) and 23% had ventricular arrhythmias. Long-term left ventricular reverse remodelling (LVRR; LVEF increase ≥10% points or normalisation) was achieved in 58% and occurred more frequently in women (72% vs 51%, p=0.042).In multivariable proportional hazards analyses, occurrence of LVRR was a strong independent negative predictor of the composite outcome (HR: 0.05 (95% CI 0.02 to 0.14); p<0.001). Female sex independently predicted lower rates of ventricular arrhythmias (HR: 0.33 (95% CI 0.11 to 0.99); p=0.05), while the location of the TTNtv was not associated with cardiovascular outcomes.ConclusionDCM caused by TTNtv presented in midlife and was associated with a high burden of AF and ventricular arrhythmias, which often preceded DCM diagnosis. Furthermore, LVRR occurred in a high proportion of patients and was a strong negative predictor of the composite outcome. Female sex was positively associated with occurrence of LVRR and longer event-free survival.

scholarly journals Secondary Progressive Multiple Sclerosis: New Insights

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012323
Author(s):  
Bruce Anthony Campbell Cree ◽  
Douglas L Arnold ◽  
Jeremy Chataway ◽  
Tanuja Chitnis ◽  
Robert J. Fox ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Response To Treatment ◽  
Disability Progression ◽  
Long Term Outcomes ◽  
Secondary Progressive ◽  
Relapsing Remitting

In most cases, multiple sclerosis (MS) begins with a relapsing–remitting course followed by insidious disability worsening that is independent from clinically apparent relapses and is termed secondary progressive multiple sclerosis (SMPS). Major differences exist between relapsing–remitting MS (RRMS) and SPMS, especially regarding therapeutic response to treatment. This review provides an overview of the pathology, differentiation, and challenges in the diagnosis and treatment of SPMS. We emphasize the criticality of conversion from a relapsing–remitting to a secondary progressive disease course not only because such conversion is evidence of disability progression, but also because, until recently, treatments that effectively reduced disability progression in relapsing MS were not proven to be effective in SPMS. Clear clinical, imaging, immunological, or pathological criteria marking the transition from RRMS to SPMS have not yet been established. Early identification of SPMS will require tools which, together with the use of appropriate treatments, may result in better long-term outcomes for the population of patients with SPMS.

scholarly journals Rajaie Cardiomyopathy and Myocarditis Registry: Protocol for an Observational Study

2021 ◽  
Author(s):  
Majid Maleki ◽  
Freidoun Noohi ◽  
Parham Sadeghipour ◽  
Mohammad Mehdi Peighambari ◽  
Ahmad Amin ◽  
...  
Keyword(s):  
Natural History ◽  
Clinical Signs ◽  
Response To Treatment ◽  
Cardiac Resynchronization ◽  
Therapeutic Approaches ◽  
Long Term Outcomes ◽  
Prediction Of Mortality ◽  
Number Of Patients

Most of the information on the natural history and management of cardiomyopathies and myocarditis in Iran has been obtained from cohort studies in a small number of patients. The prevalence of patients with cardiomyopathies referred to Rajaei Cardiovascular medical and research centers from all over the country is remarkable. Rajaie Cardiomyopathy and myocarditis Registry (RCMR) study is an observational registry of patients with four subtype of cardiomyopathy include: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM) as well as myocarditis designed to determine clinical characteristics, natural history, current therapeutic approaches, response to treatment and long-term outcomes of patients with cardiomyopathy and myocarditis. Prediction of mortality and response to different treatments in these patients using artificial intelligence is another aim of this Registry. COVID 19 Myocarditis and its sequence as cardiomyopathy seem a new challenge in forthcoming years. At the baseline visit, past medical history, clinical signs/symptoms, risk factors, physical examination and family history of cardiomyopathy, current standards for diagnostic workup and clinical follow-up, and relevant electrocardiogram echocardiography, cardiac magnetic resonance, Holter monitoring, or biomarker analyses will be checked. The outcome and results of various therapeutic approaches currently employed for patients, including implantable cardioverter defibrillator, cardiac resynchronization therapy, septal myomectomy, ablation, cardiac transplantation, and medications, will be assessed. Long-term outcomes, including the benefits and complications of therapeutic interventions, will be collected. A follow-up visit will be scheduled after 12 months for all patients, and survival status, hospitalizations, co-morbidities, medications will be assessed.

Developing tomorrow's antipsychotics: the need for a more personalised approach

2014 ◽  
Vol 20 (1) ◽  
pp. 3-12 ◽  
Author(s):  
Robert Hunter
Keyword(s):  
Risk Factors ◽  
Differential Diagnosis ◽  
Drug Discovery ◽  
Molecular Biology ◽  
Drug Development ◽  
Environmental Risk ◽  
Response To Treatment ◽  
Long Term Outcomes ◽  
Complex Interplay

SummaryThere has been little pharmacological advance in the treatment of schizophrenia since the introduction of chlorpromazine in the 1950s. This may be set to change as recent advances in molecular biology offer the prospect of a better understanding of the pathophysiology of the disorder and allow investigation of the complex interplay of genetic and environmental risk factors. In this review I discuss future approaches to antipsychotic drug development, highlighting the need to better define symptom areas and develop drugs based on an understanding of neurobiological mechanisms. The development of biomarkers has the potential in future to improve differential diagnosis and help predict response to treatment. These developments herald the possibility of a more integrated drug discovery approach and the subsequent provision of more stratified healthcare, and hopefully significant improvements in patient care and improved long-term outcomes.

scholarly journals Acute posterior multifocal placoid pigment epitheliopathy (APMPPE)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilaria Testi ◽  
Sandra Vermeirsch ◽  
Carlos Pavesio
Keyword(s):  
Good Prognosis ◽  
Significant Loss ◽  
Response To Treatment ◽  
Long Term Outcomes ◽  
Comprehensive Overview ◽  
Fundus Imaging ◽  
Inflammatory Eye Disease ◽  
Vision Function

Abstract Background Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a rare inflammatory eye disease, affecting the inner choroid and the outer retina. Recent advances in multimodal imaging have been important in the understanding of the pathophysiology of the disease, allowing a better characterization of the morphology of this condition. Methods Narrative review. Results In this review, a comprehensive overview of clinical features, imaging findings, treatment management, and long-term outcomes of patients with APMPPE will be provided. Conclusions Although APMPPE was originally believed to be a self-limited condition with a good prognosis, the disease can be recurrent and result in significant loss of vision function. Fundus imaging plays an important role in the diagnosis and management of the disease, allowing to evaluate response to treatment and onset of complications.

scholarly journals Diagnostic and therapeutic challenges in the thrombotic thrombocytopenic purpura and hemolytic uremic syndromes

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 604-609 ◽  
Author(s):  
James N. George ◽  
Zayd L. Al-Nouri
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Clinical Features ◽  
Clinical Decision ◽  
Response To Treatment ◽  
Long Term Outcomes ◽  
Thrombocytopenic Purpura ◽  
Long Term Follow Up ◽  
Adamts13 Deficiency

Abstract Evaluation and management of patients with suspected thrombotic thrombocytopenic purpura (TTP) continue to be a critical challenge for hematologists. The diagnostic criteria are not precise, often causing uncertainty about whether it is appropriate to initiate plasma exchange (PEX), the essential treatment for TTP. Initiation of PEX remains a clinical decision; severe ADAMTS13 (< 10% activity) deficiency alone is neither sufficiently sensitive nor specific for the diagnosis of TTP. However, patients who do have severe acquired ADAMTS13 deficiency define the characteristic clinical features of TTP, the response to treatment, and the long-term outcomes. Patients with severe acquired ADAMTS13 deficiency are predominantly young women and the relative frequency of blacks is increased. Patients may present with only microangiopathic hemolytic anemia and thrombocytopenia, neurologic and renal abnormalities are often not present, fever rarely occurs; the complete “pentad” of these clinical features almost never occurs in current practice. Response to PEX is typically rapid but may not be sustained when PEX is stopped. Use of corticosteroids and rituximab has decreased the number of PEX treatments required to achieve a remission and has resulted in fewer PEX-related major complications. Relapse (in approximately 40% of patients) may be the most apparent risk after recovery, but long-term health outcomes are also very important. Minor cognitive abnormalities are common, the frequency of depression is increased, and the frequency of hypertension is increased. Careful long-term follow-up of TTP patients is essential.

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