Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Toward an Individualized Approach

Nephron ◽  
2021 ◽  
pp. 1-17
Author(s):  
Javier Villacorta ◽  
Laura Martinez-Valenzuela ◽  
Irene Martin-Capon ◽  
Juliana Bordignon-Draibe
Keyword(s):  
Alternative Pathway ◽  
Treatment Options ◽  
Immunosuppressive Treatment ◽  
Standard Of Care ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Organ Damage ◽  
Cumulative Exposure ◽  
Clinical Approach ◽  
Clinical Syndromes ◽  
Individualized Approach

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), characterized by the presence of autoantibodies to neutrophil cytoplasmic antigens, proteinase 3 (PR3), and myeloperoxidase (MPO), typically involves small blood vessels of the respiratory tract and kidneys. It includes distinct clinical syndromes: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA. GPA is commonly associated with PR3-ANCA, while MPA is associated with MPO-ANCA. AAVs have a complex pathogenesis, influenced by genetics and environmental factors. There is evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation and injury, with effector T cells and activation of the alternative pathway of the complement also involved. Advances in immunosuppressive treatment have drastically reduced mortality of AAV in the past decades, opting for a more individualized approach. Careful assessment of ANCA specificity, disease activity, organ damage, and quality of life allows for a tailored immunosuppressive therapy. Contemporary AAV treatment is characterized by regimens that minimize the cumulative exposure to glucocorticoids and cyclophosphamide, and novel approaches including complement blockage and immunosuppressant combinations might be the standard of care in the future. In this review, we examine the pathogenesis, clinical approach, and evidence-based treatment options for the management of AAV patients.

Autoimmune Epilepsy: The Evolving Science of Neural Autoimmunity and Its Impact on Epilepsy Management

2018 ◽  
Vol 38 (03) ◽  
pp. 290-302 ◽  
Author(s):  
Orna O'Toole ◽  
Amy Quek
Keyword(s):  
Patient Outcomes ◽  
Treatment Options ◽  
Immunosuppressive Treatment ◽  
Substantial Reduction ◽  
Risk Scores ◽  
Seizure Freedom ◽  
Clinical Approach ◽  
Treatment Trial ◽  
Autoimmune Epilepsy ◽  
Immune Mediated

AbstractAutoimmune epilepsy is increasingly recognized as a distinct clinical entity, driven in large part by the recent discovery of neural autoantibodies in patients with isolated or predominant epilepsy presentations. Detection of neural autoantibodies in high-risk epilepsy patients supports an immune-mediated cause of seizures and, if applicable, directs the search for an underlying cancer when the paraneoplastic association of the associated antibody is compelling. Early diagnosis of autoimmune epilepsy is crucial, as prompt initiation of immunosuppressive treatment increases the likelihood of achieving either seizure freedom or a substantial reduction in seizure frequency. A practical clinical approach that incorporates risk scores to guide patient selection on the basis of clinical features, neural autoantibodies, and a treatment trial of immunotherapy is suggested. Elucidating an immunological basis of epilepsy provides neurologists with wider treatment options (incorporating immune-suppressive treatment), in addition to standard antiepileptic drugs, which often improves patient outcomes.

scholarly journals Effect of Treatment on Damage and Hospitalization in Elderly Patients with Microscopic Polyangiitis and Granulomatosis with Polyangiitis

2019 ◽  
Vol 47 (4) ◽  
pp. 580-588 ◽  
Author(s):  
Maria Weiner ◽  
Su Mein Goh ◽  
Aladdin J. Mohammad ◽  
Zdenka Hrušková ◽  
Anisha Tanna ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Cause Of Death ◽  
Granulomatosis With Polyangiitis ◽  
Microscopic Polyangiitis ◽  
Immunosuppressive Treatment ◽  
Damage Index ◽  
Positive Association ◽  
Oral Prednisolone ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Organ Damage

Objective.Age is a risk factor for organ damage, adverse events, and mortality in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, the relationship between treatment and damage, hospitalizations, and causes of death in elderly patients is largely unknown.Methods.Consecutive patients from Sweden, the United Kingdom, and the Czech Republic diagnosed between 1997 and 2013 were included. Inclusion criteria were a diagnosis of MPA or GPA and age 75 years or more at diagnosis. Treatment with cyclophosphamide (CYC), rituximab (RTX), and corticosteroids the first 3 months was registered. Outcomes up to 2 years from diagnosis included Vasculitis Damage Index (VDI), hospitalization, and cause of death.Results.Treatment data were available for 167 of 202 patients. At 2 years, 4% had no items of damage. There was a positive association between VDI score at 2 years and Birmingham Vasculitis Activity Score at onset, and a negative association with treatment using CYC or RTX. Intravenous methylprednisolone dose was associated with treatment-related damage. During the first year, 69% of patients were readmitted to hospital. Myeloperoxidase–antineutrophil cytoplasmic antibody positivity and lower creatinine levels decreased the odds of readmission. The most common cause of death was infection, and this was associated with cumulative oral prednisolone dose.Conclusion.Immunosuppressive treatment with CYC or RTX in elderly patients with MPA and GPA was associated with development of less permanent organ damage and was not associated with hospitalization. However, higher doses of corticosteroids during the first 3 months was associated with treatment-related damage and fatal infections.

Understanding the Management and Treatment of Well-Differentiated Pancreatic Neuroendocrine Tumors: A Clinician’s Guide to a Complex Illness

2020 ◽  
Vol 16 (11) ◽  
pp. 720-728
Author(s):  
Daneng Li ◽  
Adam Rock ◽  
Jonathan Kessler ◽  
Richard Ballena ◽  
Shadman Hyder ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Treatment Options ◽  
Arterial Embolization ◽  
Standard Of Care ◽  
Neuroendocrine Cells ◽  
Pancreatic Neuroendocrine Tumors ◽  
Current Standard ◽  
Systemic Treatments ◽  
Individualized Approach ◽  
Diagnostic Modalities

Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms that arise in the neuroendocrine cells of the pancreas. Although their clinical presentations differ depending on cell type, most are indolent, whereas others cause noteworthy hormone-related symptoms. The increasing incidence of PanNETs, attributed to improved diagnostic modalities, demonstrates advances in current standard of care. However, given the heterogeneity of these tumors, treatment decisions can become complex and an individualized approach is often required. Surgical intervention has remained the mainstay for localized tumors, whereas systemic therapies remain viable options for patients with unresectable or metastatic disease. Liver-directed therapies such as radiofrequency ablation and hepatic arterial embolization have also become available adjunct therapies for patients with liver-predominant metastases. Despite the increase in the armamentarium of treatment options for patients with PanNETs, data regarding the ideal sequence of treatment, especially systemic treatments, are currently lacking. Ongoing clinical trials are aimed at addressing this knowledge gap in addition to developing the next generation of novel therapeutics.

Malignant Mesothelioma: Has Anything Changed?

2019 ◽  
Vol 40 (03) ◽  
pp. 347-360 ◽  
Author(s):  
Roger Y. Kim ◽  
Daniel H. Sterman ◽  
Andrew R. Haas
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Multimodal Therapy ◽  
Asbestos Exposure ◽  
Treatment Options ◽  
Standard Of Care ◽  
Turn Of The Century ◽  
Clinical Approach ◽  
Pleural Mesothelioma ◽  
Dismal Prognosis ◽  
Near Future

AbstractMalignant pleural mesothelioma is a rare cancer associated with asbestos exposure and portends a dismal prognosis. Its worldwide incidence has been increasing, and treatment options are currently suboptimal and noncurative. However, since the turn of the century, several encouraging steps have been made toward improving outcomes for mesothelioma patients. An increased understanding of disease pathophysiology has led to more accurate diagnosis and staging, and the establishment of the standard of care first-line pemetrexed/platin doublet chemotherapy regimen in 2003 initially revolutionized treatment. While significant debate remains regarding the preferred approach to surgical and radiation therapy in the context of multimodal therapy, recent breakthroughs in immunotherapy offer hope for another paradigm shift in the near future. This review will summarize the current clinical approach to diagnosis, staging, and treatment of malignant pleural mesothelioma.

scholarly journals Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3708
Author(s):  
Bhaba K. Das ◽  
Aarthi Kannan ◽  
Quy Nguyen ◽  
Jyoti Gogoi ◽  
Haibo Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Aurora Kinase ◽  
Selective Inhibition ◽  
Potential Candidate ◽  
Cycle Arrest

Merkel cell carcinoma (MCC) is an often-lethal skin cancer with increasing incidence and limited treatment options. Although immune checkpoint inhibitors (ICI) have become the standard of care in advanced MCC, 50% of all MCC patients are ineligible for ICIs, and amongst those treated, many patients develop resistance. There is no therapeutic alternative for these patients, highlighting the urgent clinical need for alternative therapeutic strategies. Using patient-derived genetic insights and data generated in our lab, we identified aurora kinase as a promising therapeutic target for MCC. In this study, we examined the efficacy of the recently developed and highly selective AURKA inhibitor, AK-01 (LY3295668), in six patient-derived MCC cell lines and two MCC cell-line-derived xenograft mouse models. We found that AK-01 potently suppresses MCC survival through apoptosis and cell cycle arrest, particularly in MCPyV-negative MCC cells without RB expression. Despite the challenge posed by its short in vivo durability upon discontinuation, the swift and substantial tumor suppression with low toxicity makes AK-01 a strong potential candidate for MCC management, particularly in combination with existing regimens.

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

scholarly journals Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

2021 ◽  
Vol 13 ◽  
pp. 175883592110311
Author(s):  
Chiun Hsu ◽  
Lorenza Rimassa ◽  
Hui-Chuan Sun ◽  
Arndt Vogel ◽  
Ahmed O. Kaseb
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Healthcare Providers ◽  
Safety Data ◽  
Standard Of Care ◽  
Antiangiogenic Agents ◽  
Efficacy And Safety ◽  
First Line

In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.

scholarly journals Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Drug Development ◽  
Surgical Resection ◽  
Treatment Options ◽  
Standard Of Care ◽  
Time Data ◽  
Current Standard ◽  
Innovative Drug ◽  
Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

scholarly journals How we manage smoldering multiple myeloma

2020 ◽  
Vol 12 (s1) ◽  
Author(s):  
Alessandra Romano ◽  
Claudio Cerchione ◽  
Concetta Conticello ◽  
Giovanni Martinelli ◽  
Francesco Di Raimondo
Keyword(s):  
Plasma Cells ◽  
Organ Damage ◽  
Prognostic Models ◽  
Clinical Approach ◽  
High Efficacy ◽  
Clinical Practices ◽  
Bone Marrow Plasma ◽  
Asymptomatic Stage ◽  
Smoldering Myeloma

Smoldering myeloma (SMM) is an asymptomatic stage characterized by bone marrow plasma cells infiltration between 10-60% in absence of myeloma-defining events and organ damage. Until the revision of criteria of MM to require treatment, two main prognostic models, not overlapping each other, were proposed and used differently in Europe and in US. Novel manageable drugs, like lenalidomide and monoclonal antibodies, with high efficacy and limited toxicity, improvement in imaging and prognostication, challenge physicians to offer early treatment to high-risk SMM. Taking advantage from the debates offered by SOHO Italy, in this review we will update the evidence and consequent clinical practices in US and Europe to offer readers a uniform view of clinical approach at diagnosis, follow-up and supportive care in the SMM setting.

The evolution of the education module for men with metastatic prostate cancer (mPC) in the prostate cancer supportive care (PCSC) program.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 279-279
Author(s):  
Jennifer Marie Rauw ◽  
Sunil Parimi ◽  
Nikita Ivanov ◽  
Jessica Noble ◽  
Eugenia Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Standard Of Care ◽  
Primary Therapy ◽  
Oncology Nurse ◽  
Castration Resistant ◽  
Medical Oncologists ◽  
Hormone Sensitive ◽  
Virtual Platform ◽  
Satisfaction Surveys

279 Background: The PCSC Program was initiated in 2013 at the Vancouver Prostate Centre to provide a comprehensive program for patients and partners with prostate cancer. This program provides educational sessions (ES) and clinical services, including decision-making for primary therapy, sexual health, pelvic floor physiotherapy, hormone therapy, counseling, exercise, and nutrition for patients in BC, Canada. In 2016, the PCSC Program expanded to BC Cancer Victoria and in 2017 to other BC Cancer sites. In 2018, medical oncologists (MDs) in Victoria (JR, SP) developed an Education Module addressing treatment options for men with metastatic hormone sensitive (mHSPC) and metastatic castration resistant (mCRPC) disease. MDs delivered in-person ES in Victoria in 2018 and, in 2019, added a virtual platform (VP) option. From 3-5/2020, the ESs were on hold due to the COVID pandemic and parental leaves. In 6/2020, the ESs resumed only on VP, and the PCSC Oncology Nurse Practitioner (NP), NI, gave the presentations for the MDs on leave. In 10/2020, due to a changing standard of care for mHSPC, the PCSC team consolidated the two ESs into one. We report on the evolution of this Education Module in response to both the changing standard of care and the COVID pandemic. Methods: We prospectively collected attendance and patient characteristic metrics from all ES for men with mPC. We tracked presenter type (MD vs. NP) and prospectively collected anonymous patient satisfaction questionnaires. Results: From 1/2018 to 1/2021, 100 men registered for 27 ES; 81 men, 41 partners, and 2 family members actually attended. 48/75 (64%) men were white, 39/75 (52%) retired, and 56/75 (74.7%) married. 47 men attended 12 mHSPC ES, 13 men attended ten mCRPC ES, and 17 attended four consolidated ES. MDs presented 15 ES, and the NP presented 12 ES. Responses to questions on 70 satisfaction surveys were similar for MD vs. NP presenters. 9 responders to the recently added VP-specific questions said they agreed (4) or strongly agreed (5) that it was beneficial to watch the ES at home on a computer. The Table below shows attendance per site per year. Conclusions: The ESs for men with mPC were well-received. Although there was a VP option before COVID, attendance increased significantly after the lockdown as patients and providers became more familiar with VPs. Satisfaction surveys confirmed that an NP could deliver the ES rather than MD. Consolidation of the mHSPC and mCRPC ES reflected the changing standard of care and resulted in more efficient use of presenter time. Virtual delivery of the sessions provided greater access to those living in distant or remote areas of the province and those in lockdown during the COVID pandemic. [Table: see text]

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