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Mediterranean Journal of Hematology and... 2015Classical Hodgkin lymphoma (cHL) is a relatively rare disease, with approximately 9,200 estimated new cases and 1,200 estimated deaths per year in the United States.... (Review)
Review
Classical Hodgkin lymphoma (cHL) is a relatively rare disease, with approximately 9,200 estimated new cases and 1,200 estimated deaths per year in the United States. First-line chemo-radiotherapy leads to cure rates approaching 80% in patients with advanced-stage disease. However, 25 to 30% of these patients are not cured with chemotherapy alone (i.e., the ABVD regimen) and show either primary refractoriness to chemotherapy, early disease relapse or late disease relapse. Second-line salvage high-dose chemotherapy (HDC) and autologous stem cell transplantation (SCT) have an established role in the management of refractory/relapsed cHL, leading to durable responses in approximately 50% of relapsed patients and a minority of refractory patients. However, due to the poor responses to second-line salvage chemotherapy and dismal long-term disease control of primary refractory and early relapsed patients, their treatment represents an unmet medical need. Allogeneic SCT represents, by far, the only strategy with a curative potential for these patients; however, as discussed in this review, it's role in cHL remains controversial. Despite a general consensus that early relapsed and primary refractory patients represent a clinical challenge requiring effective treatments to achieve long-term disease control, there has been no consensus on the optimal therapy that should be offered to these patients. This review will briefly discuss the clinical results and the main issues regarding autologous SCT as well as the current role of allogeneic SCT.
PubMed: 25745542
DOI: 10.4084/MJHID.2015.015 -
ImmunoTargets and Therapy 2024Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable autoimmune disorder, for which different treatment options are available. Current... (Review)
Review
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable autoimmune disorder, for which different treatment options are available. Current first-line evidence-based therapies for CIDP include intravenous and subcutaneous immunoglobulins, corticosteroids and plasma exchanges. Despite lack of evidence, cyclophosphamide, rituximab and mycophenolate mofetil are commonly used in circumstances of refractoriness and, more debatably, of perceived overdependence on first-line therapies. Rituximab is currently the object of a randomized controlled trial for CIDP. Based on case series, and although rarely considered, haematopoietic autologous stem cell transplants may be effective in refractory disease, with low mortality and high remission rates. A new therapeutic option has appeared with efgartigimod, a neonatal Fc receptor blocker, recently shown to significantly lower relapse rate versus placebo, after withdrawal from previous immunotherapy. Other neonatal Fc receptor blockers, nipocalimab and batoclimab, are under study. The C1 complement-inhibitor SAR445088, acting in the proximal portion of the classical complement system, is currently the subject of a new study in treatment-responsive, refractory and treatment-naïve subjects. Finally, Bruton Tyrosine Kinase inhibitors, which exert anti-B cell effects, may represent another future research avenue. The widening of the therapeutic armamentarium enhances the need for improved evaluation of treatment effects and reliable biomarkers in CIDP.
PubMed: 38435981
DOI: 10.2147/ITT.S388151 -
Journal of Clinical Medicine Oct 2020Belching is a common phenomenon. However, it becomes bothersome if excessive. Impedance-pH monitoring can classify the belching into two types: gastric belching and... (Review)
Review
Belching is a common phenomenon. However, it becomes bothersome if excessive. Impedance-pH monitoring can classify the belching into two types: gastric belching and supragastric belching (SGB). The former is a physiological mechanism to vent swallowed air from the stomach, whereas the latter is a behavioral disorder. Gastroesophageal reflux disease (GERD) is the most relevant condition in both types of belching. Recent findings have raised awareness that excessive SGB possibly sheds light on the pathogenesis of a part of proton pump inhibitor (PPI) refractoriness in GERD. SGB could cause typical reflux symptoms such as heartburn, regurgitation or chest pain in two ways: SGB-induced gastroesophageal reflux or SGB-induced esophageal distension. In PPI-refractory GERD, it is important to detect hidden SGB as a cause of reflux symptoms since SGB requires psychological treatment instead of high dose PPIs or pain modulators. In the case of PPI-refractory GERD with excessive SGB, recent studies imply that the combination of a psychological approach and conventional treatment can improve treatment outcome.
PubMed: 33092195
DOI: 10.3390/jcm9103360 -
British Journal of Haematology Jan 2006Evans syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia (ITP) and autoimmune haemolytic... (Review)
Review
Evans syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) with a positive direct antiglobulin test (DAT) in the absence of known underlying aetiology. This condition generally runs a chronic course and is characterised by frequent exacerbations and remissions. First-line therapy is usually corticosteroids and/or intravenous immunoglobulin, to which most patients respond; however, relapse is frequent. Options for second-line therapy include immunosuppressive drugs, especially ciclosporin or mycophenolate mofetil; vincristine; danazol or a combination of these agents. More recently a small number of patients have been treated with rituximab, which induces remission in the majority although such responses are often sustained for <12 months and the long-term effects in children are unclear. Splenectomy may also be considered although long-term remissions are less frequent than in uncomplicated ITP. For very severe and refractory cases stem cell transplantation (SCT) offers the only chance of long-term cure. The limited data available suggest that allogeneic SCT may be superior to autologous SCT but both carry risks of severe morbidity and of transplant-related mortality. Cure following reduced-intensity conditioning has now been reported and should be considered for younger patients in the context of controlled clinical trials.
Topics: Anemia, Hemolytic, Autoimmune; Autoimmune Diseases; Diagnosis, Differential; Humans; Prognosis; Syndrome; Thrombocytopenia
PubMed: 16398647
DOI: 10.1111/j.1365-2141.2005.05809.x -
Cancers Dec 2023Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma. Approximately 60% of patients are cured with R-CHOP as a frontline treatment, while the... (Review)
Review
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma. Approximately 60% of patients are cured with R-CHOP as a frontline treatment, while the remaining patients experience primary refractory or relapsed disease (R/R). The prognosis for R/R DLBCL patients who are neither eligible for autologous stem-cell transplantations nor CAR-T-cell treatment is poor, representing an important unmet need. Monoclonal antibodies (mAbs) have dramatically improved therapeutic options in anti-cancer strategies, offering new opportunities to overcome chemo-refractoriness in this challenging disease, even in cases of primary non-responder DLBCL. Several novel mAbs, characterized by different mechanisms of action and targets, are now available for R/R DLBCL. Unbound mAbs induce an immune response against cancer cells, triggering different mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), activation of antibody-dependent cell-mediated phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC). Antibody-drug conjugates (ADCs) and radioimmunotherapy (RIT), respectively, deliver a cytotoxic payload or a beta-emitter radionuclide to the targeted cells and nearby bystanders. Bispecific T-cell engagers (BiTes) and immune checkpoint inhibitors (ICIs) redirect and enhance the immune response against tumor cells. Here, we review therapeutic strategies based on monoclonal antibodies for R/R DLBCL.
PubMed: 38201614
DOI: 10.3390/cancers16010187 -
Clinical Reviews in Allergy & Immunology Feb 2015Urgent visits to the clinic and emergency department for acute severe asthma exacerbations are all too frequent. Existing national guidelines do not present consistent... (Review)
Review
Urgent visits to the clinic and emergency department for acute severe asthma exacerbations are all too frequent. Existing national guidelines do not present consistent or specific recommendations for the evaluation and treatment of individual asthma patients in respiratory distress. In this vein, we propose the term "critical asthma syndrome" (CAS) to describe any child or adult who is at high risk for fatal asthma. Acute severe asthma, refractory asthma, status asthmaticus, and near-fatal asthma all describe CAS where physical exhaustion from the overwhelming work of breathing leads to respiratory arrest and death from hypoxia or related complications. The authors of this supplement seek to emphasize the importance of early recognition, prompt and coordinated evaluation, and treatment of CAS in the emergency department, hospital, and intensive care units by experienced healthcare provider teams. CAS is not severe persistent asthma where control of symptoms and prevention of exacerbations are targets of chronic disease management in the outpatient setting. The authors address the distinctions between the two entities throughout the supplement, and elaborate on the considerations important in the care of a critically ill patient, including the common errors to avoid. In addition, gaps in knowledge and clinical experience in regards to critical asthma are highlighted. Knowledge gaps include a lack of understanding of how to recognize CAS, how to coordinate and integrate hospital and outpatient resources, when to further phenotype patients with critical asthma in order to facilitate effective treatment, and how to prevent future acute exacerbations. Lastly, CAS is complicated by the fact that asthma care in diverse healthcare settings is haphazard. We recommend that primary care physicians refer patients promptly to an asthma specialist for consultation to reduce the frequency of acute exacerbations and prevent the development of CAS.
Topics: Adult; Ambulatory Care; Animals; Asthma; Child; Critical Illness; Disease Progression; Emergency Medical Services; Humans; Respiratory Insufficiency; Syndrome
PubMed: 24213844
DOI: 10.1007/s12016-013-8395-6 -
Canadian Journal of Gastroenterology =... Jul 2013Autoimmune hepatitis may have cholestatic features that are outside the classical phenotype and that resemble findings in other immune-mediated liver diseases. These... (Review)
Review
BACKGROUND
Autoimmune hepatitis may have cholestatic features that are outside the classical phenotype and that resemble findings in other immune-mediated liver diseases. These cholestatic phenotypes have been designated 'overlap syndromes'.
OBJECTIVES
To recognize the overlap syndromes in adults and manage them appropriately.
METHODS
The MEDLINE database was reviewed for published experiences from 1984 to 2013.
RESULTS
Patients with autoimmune hepatitis may exhibit features of primary biliary cirrhosis (7% to 13%), primary sclerosing cholangitis (6% to 11%) or a cholestatic syndrome without other diagnostic features (5% to 11%). These mixed phenotypes may represent classical autoimmune hepatitis with atypical features, transition states in the evolution of classical cholestatic syndromes, concurrent separate diseases or pathogenically distinct disorders. The 'Paris criteria' have been endorsed for the diagnosis of the overlap syndrome with primary biliary cirrhosis, and treatment with conventional immunosuppressive therapy alone or in combination with low-dose ursodeoxycholic acid can be guided by the serum alkaline phosphatase level. The overlap syndrome with primary sclerosing cholangitis or with cholestasis without diagnostic features is commonly treated with immunosuppressive therapy and ursodeoxycholic acid. Responses are variable and commonly incomplete (20% to 100% improvement) depending on the degree of cholestasis.
DISCUSSION
The overlap syndromes are clinical descriptions rather than pathological entities, and the dominant component of the disease determines its designation and therapy. Cholestatic findings in autoimmune hepatitis influence the response to immunosuppressive therapy.
CONCLUSION
The overlap syndromes must be considered in patients with autoimmune hepatitis and cholestatic findings, concurrent inflammatory bowel disease or steroid-refractory disease.
Topics: Adult; Alkaline Phosphatase; Cholangitis, Sclerosing; Cholestasis; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver Cirrhosis, Biliary; Syndrome; Treatment Outcome; Ursodeoxycholic Acid
PubMed: 23862175
DOI: 10.1155/2013/198070 -
Biomolecules Oct 2021The human gut microbiota consists of bacteria, archaea, fungi, and viruses. It is a dynamic ecosystem shaped by several factors that play an essential role in both... (Review)
Review
The human gut microbiota consists of bacteria, archaea, fungi, and viruses. It is a dynamic ecosystem shaped by several factors that play an essential role in both healthy and diseased states of humans. A disturbance of the gut microbiota, also termed "dysbiosis", is associated with increased host susceptibility to a range of diseases. Because of splanchnic ischemia, exposure to antibiotics, and/or the underlying disease, critically ill patients loose 90% of the commensal organisms in their gut within hours after the insult. This is followed by a rapid overgrowth of potentially pathogenic and pro-inflammatory bacteria that alter metabolic, immune, and even neurocognitive functions and that turn the gut into the driver of systemic inflammation and multiorgan failure. Indeed, restoring healthy microbiota by means of fecal microbiota transplantation (FMT) in the critically ill is an attractive and plausible concept in intensive care. Nonetheless, available data from controlled studies are limited to probiotics and FMT for severe infection or severe inflammatory bowel disease. Case series and observational trials have generated hypotheses that FMT might be feasible and safe in immunocompromised patients, refractory sepsis, or severe antibiotic-associated diarrhea in ICU. There is a burning need to test these hypotheses in randomized controlled trials powered for the determination of patient-centered outcomes.
Topics: Critical Illness; Diarrhea; Dysbiosis; Fecal Microbiota Transplantation; Feces; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases
PubMed: 34680092
DOI: 10.3390/biom11101459 -
European Thyroid Journal Jan 2022Amiodarone-induced thyrotoxicosis (AIT) can sometimes lead to life-threatening complications, especially in patients with congenital heart disease (CHD). We report the...
INTRODUCTION
Amiodarone-induced thyrotoxicosis (AIT) can sometimes lead to life-threatening complications, especially in patients with congenital heart disease (CHD). We report the case of a patient with refractory AIT that was successfully treated with thyroid arterial embolization (TAE).
CASE REPORT
A 34-year-old man with complex cyanotic CHD complicated with heart failure (HF), pulmonary hypertension, and supraventricular tachyarrhythmias, was treated with amiodarone since 2013. In March 2019, he presented worsening of his cardiac condition and symptoms of thyrotoxicosis that were confirmed by laboratory assessment. Thiamazole 30 mg/day and prednisolone 40 mg/day were prescribed, but the patient experienced worsening of his cardiac condition with several hospital admissions in the next 5 months, albeit increasing dosages of thionamide and glucocorticoid and introduction of cholestyramine and lithium. Thyroidectomy was excluded due to the severity of thyrotoxicosis, and plasmapheresis was contraindicated due to the cardiac condition. TAE of the four thyroid arteries was then performed with no immediate complications. Progressive clinical and analytical improvement ensued with gradual reduction and suspension of medication with the patient returning to euthyroid state and his usual cardiac condition previous to the AIT.
CONCLUSION
For patients with medication refractoriness and whose condition precludes thyroidectomy, embolization of thyroid arteries may be an effective and safe option.
ESTABLISHED FACTS
Amiodarone-induced thyrotoxicosis (AIT) can be refractory to a combination therapy of thionamides and glucocorticoids. Restoration of euthyroidism is of paramount importance in heart failure (HF) patients. Emergency thyroidectomy for AIT unresponsive to medical therapy is recommended in patients with severe underlying cardiac disease or deteriorating cardiac function.
NOVEL INSIGHTS
Thyroid arterial embolization (TAE) appeared as a salvage therapy in this patient. To the best of our knowledge, few case reports in the literature have described the embolization of the four thyroid arteries in AIT context. Endovascular embolization techniques are a valuable therapeutic option and can be considered in cases where standard forms of treatment are ineffective or involve unacceptable risks.
PubMed: 34981740
DOI: 10.1530/ETJ-21-0007 -
Hematology. American Society of... Dec 2016T-cell-engaging immunotherapies are exciting new approaches to treat patients with acute lymphoblastic leukemia (ALL). These unique agents, which include blinatumomab, a... (Review)
Review
T-cell-engaging immunotherapies are exciting new approaches to treat patients with acute lymphoblastic leukemia (ALL). These unique agents, which include blinatumomab, a CD3/CD19 bispecific antibody, and chimeric antigen receptor (CAR) modified T cells targeted to CD19 have shown unprecedented remission rates in the relapsed, refractory ALL setting. Cytokine release syndrome (CRS), resulting from the high magnitude of immune activation by these therapies, is the most significant treatment-related toxicity. CRS manifests with fever and malaise and can progress to life-threatening capillary leak with hypoxia and hypotension. The clinical signs of CRS correlate with T-cell activation and high levels of cytokines, including interleukin 6 (IL-6). Tocilizumab, an anti-IL-6 receptor antagonist, is usually effective in the management of severe CRS induced by CAR T cells and has been adopted by most clinical trial programs. With blinatumomab administration, the goal has been to prevent CRS with corticosteroid premedication, disease cytoreduction, and dose adjustments. Collaborative efforts are underway to harmonize the definition and grading system of CRS to allow for better interpretation of toxicities across trials and allow for informed management algorithms.
Topics: Algorithms; Antibodies, Bispecific; Antibodies, Monoclonal, Humanized; Humans; Interleukin-6; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Syndrome
PubMed: 27913530
DOI: 10.1182/asheducation-2016.1.567