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The New England Journal of Medicine Feb 2017The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell-related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease.
METHODS
In this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell-related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined as crises other than the acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and the acute chest syndrome, and patient-reported outcomes were also assessed.
RESULTS
A total of 198 patients underwent randomization at 60 sites. The median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (indicating a 45.3% lower rate with high-dose crizanlizumab, P=0.01). The median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, P=0.001), as was the median time to the second crisis (10.32 vs. 5.09 months, P=0.02). The median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab, as compared with 2.91 with placebo (indicating a 62.9% lower rate with high-dose crizanlizumab, P=0.02). Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain.
CONCLUSIONS
In patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events. (Funded by Selexys Pharmaceuticals and others; SUSTAIN ClinicalTrials.gov number, NCT01895361 .).
Topics: Adolescent; Adult; Anemia, Sickle Cell; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydroxyurea; Male; Middle Aged; P-Selectin; Pain; Quality of Life; Young Adult
PubMed: 27959701
DOI: 10.1056/NEJMoa1611770 -
The Journal of Clinical Investigation Mar 2017Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. Decompartmentalized hemoglobin, arginase 1,... (Review)
Review
Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and systemic vasculopathy, including pulmonary hypertension, leg ulcers, priapism, chronic kidney disease, and large-artery ischemic stroke. Nitric oxide (NO) is inactivated by cell-free hemoglobin in a dioxygenation reaction that also oxidizes hemoglobin to methemoglobin, a non-oxygen-binding form of hemoglobin that readily loses heme. Circulating hemoglobin and heme represent erythrocytic danger-associated molecular pattern (eDAMP) molecules, which activate the innate immune system and endothelium to an inflammatory, proadhesive state that promotes sickle vaso-occlusion and acute lung injury in murine models of sickle cell disease. Intravascular hemolysis can impair NO bioavailability and cause oxidative stress, altering redox balance and amplifying physiological processes that govern blood flow, hemostasis, inflammation, and angiogenesis. These pathological responses promote regional vasoconstriction and subsequent blood vessel remodeling. Thus, intravascular hemolysis represents an intrinsic mechanism for human vascular disease that manifests clinical complications in sickle cell disease and other chronic hereditary or acquired hemolytic anemias.
Topics: Anemia, Sickle Cell; Hemolysis; Humans; Methemoglobin; Nitric Oxide; Vascular Diseases; Vasomotor System
PubMed: 28248201
DOI: 10.1172/JCI89741 -
Cureus Jan 2022Priapism is defined as an erection that lasts longer than four hours, is unrelated to sexual interest or stimulation, and is unrelieved by orgasm. The ischemic subtype...
Priapism is defined as an erection that lasts longer than four hours, is unrelated to sexual interest or stimulation, and is unrelieved by orgasm. The ischemic subtype is a urologic emergency and is often caused by medication side effects, most notably selective serotonin reuptake inhibitors and trazodone. We present the case of ischemic priapism thought to be caused by the recent initiation of gabapentin.
PubMed: 35174036
DOI: 10.7759/cureus.21241 -
Hematology/oncology Clinics of North... Dec 2022Patients with sickle cell disease and/or (rarely) trait are at increased risk for developing recurrent episodes of priapism, also known as stuttering priapism, and major... (Review)
Review
Patients with sickle cell disease and/or (rarely) trait are at increased risk for developing recurrent episodes of priapism, also known as stuttering priapism, and major ischemic priapism. Treatment of acute ischemic priapism is reactive; whereas ideal management consists of preventative approaches to ultimately promote the best improvement in patient's quality of life. Leg ulcers in patients with sickle cell disease (SCD) are quite common, with ∼20 % of patients with HBSS reporting either having an active or a past ucler. They can be confused with venous ulcers, with lower extremity hyperpigmentation confounding further the diagnosis. Several factors believed to contribute to the development of leg ulcers in patients with SCD are discussed in this article. Sickle cell liver disease (SCLD) occurs because of a wide variety of insults to the liver that happen during the lifetime of these patients. SCLD includes a range of complications of the hepatobiliary system and is increasing in prevalence with the aging adult sickle population. Liver nodular regenerative hyperplasia (NRH) is more common than realized and underappreciated as a diagnosis and requires liver biopsy with reticulin staining. Undiagnosed, the insidious damage from liver NRH can lead to noncirrhotic portal hypertension or cirrhosis.
Topics: Humans; Male; Adult; Priapism; Quality of Life; Liver Diseases; Anemia, Sickle Cell; Leg Ulcer
PubMed: 36400538
DOI: 10.1016/j.hoc.2022.08.001 -
Asian Journal of Andrology 2020The field of prosthetic urology demonstrates the striking impact that simple devices can have on quality of life. Penile prosthesis and artificial urinary sphincter... (Review)
Review
The field of prosthetic urology demonstrates the striking impact that simple devices can have on quality of life. Penile prosthesis and artificial urinary sphincter implantation are the cornerstone procedures on which this specialty focuses. Modern research largely concentrates on decreasing the rates of complication and infection, as the current devices offer superior rates of satisfaction when revision is not necessary. These techniques are also able to salvage sexual function and continence in more difficult patient populations including female-to-male transgender individuals, those with ischemic priapism, and those with erectile dysfunction and incontinence secondary to prostatectomy. This review summarizes modern techniques, outcomes, and complications in the field of prosthetic urology.
Topics: Erectile Dysfunction; Humans; Male; Penile Implantation; Penile Prosthesis; Postoperative Complications; Prostatectomy; Prosthesis Failure; Prosthesis Implantation; Prosthesis-Related Infections; Surgical Wound Infection; Urethra; Urinary Incontinence, Stress; Urinary Retention; Urinary Sphincter, Artificial; Urology
PubMed: 31696834
DOI: 10.4103/aja.aja_108_19 -
Minerva Urologica E Nefrologica = the... Apr 2020Stuttering priapism is a variation of ischemic priapism, generally transient and self-limiting, occurring during sleep and lasting less than 3-4 hours. It may progress... (Review)
Review
INTRODUCTION
Stuttering priapism is a variation of ischemic priapism, generally transient and self-limiting, occurring during sleep and lasting less than 3-4 hours. It may progress to episodes of complete ischemic priapism in approximately one third of cases, necessitating emergent intervention.
EVIDENCE ACQUISITION
This review aims to provide an up-to-date picture of the pathophysiology and management of stuttering priapism. A search using Medline and EMBASE for relevant publications using the terms "priapism", "stuttering", "diagnosis", "treatment", "fibrosis", was performed.
EVIDENCE SYNTHESIS
Stuttering priapism shares its etiologies with ischemic priapism and a large number of diseases or clinical situations have risk association for developing the disorder. The most common causes are sickle cell disease or other hematologic and coagulative dyscrasias especially in children. In the adult population, idiopathic priapism occurring without any discernible cause is considered to be the most common form in adults. The medical management of priapism represents a therapeutic challenge to urologists. Unfortunately, although numerous medical treatment options have been reported, the majority are through small trials or anecdotal reports. Understanding the underlying pathophysiology and understanding the current and emerging future agents and therapeutic options are mandatory in order to provide the best solution for each patient.
CONCLUSIONS
The goal of management of priapism is to achieve detumescence of the persistent erection in order to preserve erectile function. To achieve successful management, urologists should address this emergency clinical condition. In the present article, we review the diagnosis and clinical management of the three types of priapism.
Topics: Adult; Child; Disease Management; Humans; Male; Priapism
PubMed: 30957473
DOI: 10.23736/S0393-2249.19.03323-X