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The Medical Clinics of North America Jul 2023Nephrotic syndrome (NS) is a key clinical entity for the internist to recognize and understand. A wide range of infectious, metabolic, malignant, and autoimmune... (Review)
Review
Nephrotic syndrome (NS) is a key clinical entity for the internist to recognize and understand. A wide range of infectious, metabolic, malignant, and autoimmune processes drive nephrosis, leading to a syndrome defined by proteinuria, edema, and hypoalbuminemia. NS occurs due to increased permeability to proteins at the level of the glomerulus, which allows for passage of albumin and other proteins into the urine. Proteinuria leads to a cascade of clinical complications characterized by fluid accumulation, kidney inflammation, and dysregulation of coagulation and immunity. In this article, the authors review the clinically important etiologies of NS that should inform an initial clinical evaluation.
Topics: Humans; Nephrotic Syndrome; Proteinuria; Edema
PubMed: 37258010
DOI: 10.1016/j.mcna.2023.03.006 -
Journal of Human Hypertension Oct 2023Patients with hypertensive emergencies, malignant hypertension and acute severe hypertension are managed heterogeneously in clinical practice. Initiating... (Review)
Review
Patients with hypertensive emergencies, malignant hypertension and acute severe hypertension are managed heterogeneously in clinical practice. Initiating anti-hypertensive therapy and setting BP goal in acute settings requires important considerations which differ slightly across various diagnoses and clinical contexts. This position paper by British and Irish Hypertension Society, aims to provide clinicians a framework for diagnosing, evaluating, and managing patients with hypertensive crisis, based on the critical appraisal of available evidence and expert opinion.
Topics: Humans; Antihypertensive Agents; Hypertension; Hypertensive Encephalopathy; Hypertension, Malignant; Emergencies
PubMed: 36418425
DOI: 10.1038/s41371-022-00776-9 -
Lancet (London, England) Jul 2023Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial.
BACKGROUND
Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified interim analysis of luspatercept versus epoetin alfa for the treatment of anaemia due to lower-risk myelodysplastic syndromes in the phase 3 COMMANDS trial.
METHODS
The phase 3, open-label, randomised controlled COMMANDS trial is being conducted at 142 sites in 26 countries. Eligible patients were aged 18 years or older, had a diagnosis of myelodysplastic syndromes of very low risk, low risk, or intermediate risk (per the Revised International Prognostic Scoring System), were ESA-naive, and required red blood cell transfusions (2-6 packed red blood cell units per 8 weeks for ≥8 weeks immediately before randomisation). Integrated response technology was used to randomly assign patients (1:1, block size 4) to luspatercept or epoetin alfa, stratified by baseline red blood cell transfusion burden (<4 units per 8 weeks vs ≥4 units per 8 weeks), endogenous serum erythropoietin concentration (≤200 U/L vs >200 to <500 U/L), and ring sideroblast status (positive vs negative). Luspatercept was administered subcutaneously once every 3 weeks starting at 1·0 mg/kg body weight with possible titration up to 1·75 mg/kg. Epoetin alfa was administered subcutaneously once a week starting at 450 IU/kg body weight with possible titration up to 1050 IU/kg (maximum permitted total dose of 80 000 IU). The primary endpoint was red blood cell transfusion independence for at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), assessed in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. The COMMANDS trial was registered with ClinicalTrials.gov, NCT03682536 (active, not recruiting).
FINDINGS
Between Jan 2, 2019 and Aug 31, 2022, 356 patients were randomly assigned to receive luspatercept (178 patients) or epoetin alfa (178 patients), comprising 198 (56%) men and 158 (44%) women (median age 74 years [IQR 69-80]). The interim efficacy analysis was done for 301 patients (147 in the luspatercept group and 154 in the epoetin alfa group) who completed 24 weeks of treatment or discontinued earlier. 86 (59%) of 147 patients in the luspatercept group and 48 (31%) of 154 patients in the epoetin alfa group reached the primary endpoint (common risk difference on response rate 26·6; 95% CI 15·8-37·4; p<0·0001). Median treatment exposure was longer for patients receiving luspatercept (42 weeks [IQR 20-73]) versus epoetin alfa (27 weeks [19-55]). The most frequently reported grade 3 or 4 treatment-emergent adverse events with luspatercept (≥3% patients) were hypertension, anaemia, dyspnoea, neutropenia, thrombocytopenia, pneumonia, COVID-19, myelodysplastic syndromes, and syncope; and with epoetin alfa were anaemia, pneumonia, neutropenia, hypertension, iron overload, COVID-19 pneumonia, and myelodysplastic syndromes. The most common suspected treatment-related adverse events in the luspatercept group (≥3% patients, with the most common event occurring in 5% patients) were fatigue, asthenia, nausea, dyspnoea, hypertension, and headache; and none (≥3% patients) in the epoetin alfa group. One death after diagnosis of acute myeloid leukaemia was considered to be related to luspatercept treatment (44 days on treatment).
INTERPRETATION
In this interim analysis, luspatercept improved the rate at which red blood cell transfusion independence and increased haemoglobin were achieved compared with epoetin alfa in ESA-naive patients with lower-risk myelodysplastic syndromes. Long-term follow-up and additional data will be needed to confirm these results and further refine findings in other subgroups of patients with lower-risk myelodysplastic syndromes, including non-mutated SF3B1 or ring sideroblast-negative subgroups.
FUNDING
Celgene and Acceleron Pharma.
Topics: Male; Humans; Female; Aged; Epoetin Alfa; Hematinics; Erythropoiesis; COVID-19; Anemia; Hypertension; Myelodysplastic Syndromes; Hemoglobins; Neutropenia; Dyspnea; Body Weight
PubMed: 37311468
DOI: 10.1016/S0140-6736(23)00874-7 -
Arthritis & Rheumatology (Hoboken, N.J.) Feb 2024Thrombotic microangiopathy (TMA) refers to a diverse group of diseases that share clinical and histopathologic features. TMA is clinically characterized by... (Review)
Review
Thrombotic microangiopathy (TMA) refers to a diverse group of diseases that share clinical and histopathologic features. TMA is clinically characterized by microangiopathic hemolytic anemia, consumptive thrombocytopenia, and organ injury that stems from endothelial damage and vascular occlusion. There are several disease states with distinct pathophysiological mechanisms that manifest as TMA. These conditions are associated with significant morbidity and mortality and require urgent recognition and treatment. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are traditionally considered to be primary forms of TMA, but TMA more commonly occurs in association with a coexisting condition such as infection, pregnancy, autoimmune disease, or malignant hypertension, among others. Determining the cause of TMA is a diagnostic challenge because of limited availability of disease-specific testing. However, identifying the underlying etiology is imperative as treatment strategies differ. Our understanding of the conditions that cause TMA is evolving. Recent advances have led to improved comprehension of the varying pathogenic mechanisms that drive TMA. Development of targeted therapeutics has resulted in significant improvements in patient outcomes. In this article, we review the pathogenesis and clinical features of the different TMA-causing conditions. We outline a practical approach to diagnosis and management and discuss empiric and disease-specific treatment strategies.
Topics: Pregnancy; Female; Humans; Thrombotic Microangiopathies; Purpura, Thrombotic Thrombocytopenic; Thrombosis; Anemia, Hemolytic; Hypertension, Malignant
PubMed: 37610060
DOI: 10.1002/art.42681 -
Journal of the American Heart... Jul 2023Background To study the prevalence and types of hypertension-mediated organ damage and the prognosis of patients presenting to the emergency department (ED) with... (Meta-Analysis)
Meta-Analysis
Background To study the prevalence and types of hypertension-mediated organ damage and the prognosis of patients presenting to the emergency department (ED) with hypertensive emergencies. Methods and Results PubMed was queried from inception through November 30, 2021. Studies were included if they reported the prevalence or prognosis of hypertensive emergencies in patients presenting to the ED. Studies reporting data on hypertensive emergencies in other departments were excluded. The extracted data were arcsine transformed and pooled using a random-effects model. Fifteen studies (n=4370 patients) were included. Pooled analysis demonstrates that the prevalence of hypertensive emergencies was 0.5% (95% CI, 0.40%-0.70%) in all patients presenting to ED and 35.9% (95% CI, 26.7%-45.5%) among patients presenting in ED with hypertensive crisis. Ischemic stroke (28.1% [95% CI, 18.7%-38.6%]) was the most prevalent hypertension-mediated organ damage, followed by pulmonary edema/acute heart failure (24.1% [95% CI, 19.0%-29.7%]), hemorrhagic stroke (14.6% [95% CI, 9.9%-20.0%]), acute coronary syndrome (10.8% [95% CI, 7.3%-14.8%]), renal failure (8.0% [95% CI, 2.9%-15.5%]), subarachnoid hemorrhage (6.9% [95% CI, 3.9%-10.7%]), encephalopathy (6.1% [95% CI, 1.9%-12.4%]), and the least prevalent was aortic dissection (1.8% [95% CI, 1.1%-2.8%]). Prevalence of in-hospital mortality among patients with hypertensive emergency was 9.9% (95% CI, 1.4%-24.6%). Conclusions Our findings demonstrate a pattern of hypertension-mediated organ damage primarily affecting the brain and heart, substantial cardiovascular renal morbidity and mortality, as well as subsequent hospitalization in patients with hypertensive emergencies presenting to the ED.
Topics: Humans; Emergencies; Hypertension; Hospitalization; Heart Failure; Subarachnoid Hemorrhage; Emergency Service, Hospital
PubMed: 37421281
DOI: 10.1161/JAHA.122.029355 -
Journal of Thoracic Disease Feb 2024Hepatic hydrothorax (HH) refers to the presence of a pleural effusion that develops in the context of underlying liver cirrhosis and portal hypertension. It carries a... (Review)
Review
Hepatic hydrothorax (HH) refers to the presence of a pleural effusion that develops in the context of underlying liver cirrhosis and portal hypertension. It carries a high risk of morbidity and mortality, with a median survival of 8-12 months. Diagnosis is usually confirmed by pleural aspiration, demonstrating typical features of a transudative effusion in the absence of co-existent cardio-pulmonary or renal pathology. The clinical presentation is quite variable, with some patients remaining relatively asymptomatic in the presence of small or incidental effusions, while others present with frank respiratory failure requiring pleural intervention. The development of spontaneous bacterial empyema (SBEM) is a significant and not infrequent complication, requiring prompt recognition and treatment. While the mainstay of management is focused on optimising fluid balance through dietary salt restriction and diuretic therapy, liver transplantation remains the definitive treatment option. As such, it is crucial to adopt a multi-disciplinary approach-involving pulmonologists, hepatologists, dieticians, and palliative care physicians-in order to optimise care for this often complex group of patients. This review will discuss the basic pathophysiology of HH, its clinical presentation and diagnosis, as well as the approach to management of HH in clinical practice, focussing on both interventional and non-interventional treatment modalities.
PubMed: 38505059
DOI: 10.21037/jtd-23-1649 -
Internal Medicine (Tokyo, Japan) Sep 2023Malignant hypertension triggers incremental renin activity, whereas primary aldosteronism suppresses such activity. We encountered a patient with malignant hypertension...
Malignant hypertension triggers incremental renin activity, whereas primary aldosteronism suppresses such activity. We encountered a patient with malignant hypertension refractory to multiple anti-hypertensive agents. Repeated neurohormonal assessments, instead of a single one, eventually uncovered trends in an incremental aldosterone concentration, ranging from 221 up to 468 pg/mL, with a decline in the renin activity from 2.3 to <0.2 ng/mL/h. Adrenal venous sampling confirmed bilateral aldosterone secretion. Following the diagnosis of bilateral primary aldosteronism, we initiated a mineralocorticoid receptor antagonist, which improved his blood pressure. Repeated neurohormonal assessments are encouraged to correctly diagnose underlying primary aldosteronism with malignant hypertension.
Topics: Humans; Aldosterone; Hypertension, Malignant; Hyperaldosteronism; Renin; Mineralocorticoid Receptor Antagonists; Hypertension
PubMed: 36725041
DOI: 10.2169/internalmedicine.1098-22