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International Journal of Hematology Jun 2024Guidelines recommend rasburicase for high-risk patients to prevent tumor lysis syndrome (TLS). However, little information is available on the incidence and outcome of...
Guidelines recommend rasburicase for high-risk patients to prevent tumor lysis syndrome (TLS). However, little information is available on the incidence and outcome of TLS in AML patients. We analyzed 145 patients with AML who underwent induction therapy before the approval of rasburicase to evaluate the incidence of TLS and the necessity of rasburicase as prophylaxis. Three patients had already developed clinical TLS (CTLS) at diagnosis of AML, and another three developed CTLS after the initiation of chemotherapy. In patients without TLS at diagnosis of AML, the risk for developing TLS was classified as high in 44 patients, intermediate in 41 and low in 57, according to the current guidelines. Allopurinol alone was administered to prevent hyperuricemia in all patients. All three patients who developed CTLS after diagnosis of AML were at high risk of TLS, and had elevated serum creatinine levels and a WBC count greater than 200,000 per microliter at diagnosis of AML. Allopurinol may be insufficient to prevent TLS in high-risk patients with renal dysfunction at diagnosis of AML, especially those with a high tumor burden and a WBC count of 200,000 or more, which indicates that prophylactic administration of rasburicase should be considered.
Topics: Humans; Tumor Lysis Syndrome; Urate Oxidase; Leukemia, Myeloid, Acute; Male; Female; Middle Aged; Allopurinol; Aged; Adult; Induction Chemotherapy; Aged, 80 and over; Hyperuricemia; Adolescent; Incidence; Young Adult
PubMed: 38575822
DOI: 10.1007/s12185-024-03752-w -
Schweizer Archiv Fur Tierheilkunde Apr 2024This case report describes the long-term success of a subcutaneous ureteral bypass device in a dog for treatment of a ureteral obstruction. The suspected xanthine...
This case report describes the long-term success of a subcutaneous ureteral bypass device in a dog for treatment of a ureteral obstruction. The suspected xanthine urolithiasis was secondary to treatment with allopurinol for leishmaniasis. The dog presented initially with lethargy, anuria and abdominal pain. Mild azotemia was found on biochemical analysis and abdominal ultrasound revealed bilateral ureteral obstruction. A subcutaneous ureteral bypass was subsequently placed using a standard surgical technique. The dog recovered uneventfully and the azotemia resolved within days. Follow-up examinations were performed every trimester for over three years and no complications like obstruction of the bypass tubes, urinary tract infection or azotemia were recognized during this follow-up period. Allopurinol was replaced with domperidone as long-term treatment against Leishmaniasis which resulted in a mild increase of the leishmania serum antibody titer. The subcutaneous ureteral bypass placement was successful and safe in this dog and is a valuable alternative in cases of ureteral obstruction also in dogs.
Topics: Animals; Dogs; Cats; Ureteral Obstruction; Allopurinol; Azotemia; Urolithiasis; Leishmaniasis; Xanthines; Stents; Cat Diseases; Dog Diseases
PubMed: 38572822
DOI: 10.17236/sat00422 -
BMC Medical Imaging Apr 2024To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia.
BACKGROUND
To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia.
METHODS
A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment.
RESULTS
The HUA, AP, and AP + EM group MK and MK values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MK and MK values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MD and FA were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively).
CONCLUSION
DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.
Topics: Rats; Animals; Hyperuricemia; Kidney; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; Fibrosis
PubMed: 38570748
DOI: 10.1186/s12880-024-01259-8 -
Federal Practitioner : For the Health... Oct 2023Hemoglobinopathies are inherited disorders of hemoglobin that alter oxygen binding capacity by affecting the production of a specific subset of globin chains or their...
BACKGROUND
Hemoglobinopathies are inherited disorders of hemoglobin that alter oxygen binding capacity by affecting the production of a specific subset of globin chains or their entire structure. A lesser-known subtype, Syracuse hemoglobinopathy, was first identified in 4 generations of a family in the 1970s. Gout has been reported in several forms of hemoglobinopathy, such as thalassemia and hemoglobin C disorder.
CASE PRESENTATION
A 44-year-old man with a known history of Syracuse hemoglobinopathy, tobacco use disorder, and shoulder osteoarthritis presented with diffuse nodular masses on his joints along with joint pain. His laboratory tests and imaging showed elevated uric acid, urate crystals in his synovial fluid, and bony erosions. These findings were concerning for gout, which was treated with allopurinol, prednisone, and colchicine, resulting in improvement in his symptoms.
CONCLUSIONS
Syracuse hemoglobinopathy, a rare disorder of high oxygen affinity hemoglobin, can present itself with findings of elevated serum uric acid and tophaceous gout. Most patients with hyperuricemia never go on to develop gout. However, having a condition that increases serum levels of uric acid should raise an astute clinician's suspicion when a patient presents with a history of hemoglobinopathy and joint pain.
PubMed: 38567297
DOI: 10.12788/fp.0419 -
Journal of the American Society of... May 2024The SAPPHIRE trial was designed to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with allopurinol in patients with CKD.... (Randomized Controlled Trial)
Randomized Controlled Trial
KEY POINTS
The SAPPHIRE trial was designed to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with allopurinol in patients with CKD. Verinurad 3, 7.5, and 12 mg in combination with allopurinol 300 mg did not reduce albuminuria during 34 weeks treatment compared with allopurinol alone or placebo. Verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared with placebo.
BACKGROUND
Hyperuricemia is associated with elevated risks of cardiovascular and chronic kidney disease (CKD). Since inhibition of urate transporter 1 has been suggested to be potentially nephroprotective, we performed a phase 2b study to assess albuminuria-lowering effects of the urate transporter 1 inhibitor verinurad combined with the xanthine oxidase inhibitor allopurinol in patients with CKD and hyperuricemia.
METHODS
In this randomized placebo and active controlled trial, we enrolled participants with serum urate concentrations ≥6.0 mg/dl, eGFR ≥25 ml/min per 1.73 m, and a urinary albumin-creatinine ratio (UACR) 30–5000 mg/g to one of five treatment arms: placebo, placebo+allopurinol 300 mg/day, verinurad 3 mg+allopurinol 300 mg/day, verinurad 7.5 mg+allopurinol 300 mg/day, or verinurad 12 mg+allopurinol 300 mg/day in a 1:1:1:1:1 ratio. The primary end point was the change in UACR from baseline to 34 weeks. Secondary end points were changes from baseline in UACR at week 60 and changes in serum urate and eGFR at weeks 34 and 60.
RESULTS
Between August 2019 and November 2021, 861 adults with CKD (mean age 65 years, 33.0% female, mean eGFR 48 ml/min per 1.73 m, median UACR 217 mg/g) were enrolled. At 34 weeks, the geometric mean percentage change in UACR from baseline did not differ among treatment groups (16.7%, 95% confidence interval [CI], −0.6 to 37.1 in the 3 mg group, 15.0% [95% CI, −1.85 to 34.6] in the 7.5 mg group, 14.0% [95% CI, −3.4 to 34.4] in the 12 mg group versus 9.9% [95% CI, −6.6 to 29.4] in the allopurinol group, and 37.3% [95% CI, 16.6 to 61.8] in the placebo group). UACR and eGFR change from baseline did not differ among treatment groups after 60 weeks. Verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared with placebo. The proportion of patients with adverse events and serious adverse events was balanced among treatment groups.
CONCLUSIONS
Verinurad in combination with allopurinol did not decrease UACR or eGFR decline, but further reduced serum urate compared with allopurinol alone or placebo.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:
SAPPHIRE Trial registration number, NCT03990363.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Allopurinol; Double-Blind Method; Drug Therapy, Combination; Renal Insufficiency, Chronic
PubMed: 38564654
DOI: 10.1681/ASN.0000000000000326 -
Journal of Rheumatic Diseases Apr 2024While urate-lowering therapy (ULT) is linked to increased cardioprotective benefits on primary prevention of cardiovascular events such myocardial infarction or heart...
OBJECTIVE
While urate-lowering therapy (ULT) is linked to increased cardioprotective benefits on primary prevention of cardiovascular events such myocardial infarction or heart failure, little is known regarding their effects on arrhythmia risk. The purpose of this study was to investigate the relationship between incident arrhythmias and ULT.
METHODS
We searched MEDLINE and Embase from inception to May 2023. Included studies were randomized controlled trials and cohort studies that compared the risk of cardiac arrhythmias among ULT users with non-ULT users.
RESULTS
A total of 12,420 patients from five studies were analyzed, comprising 7,359 subjects in the ULT group and 5,061 subjects in the non-ULT group. Our results showed that ULT users had significant reductions in the risk of arrhythmias (pooled relative risk [RR] 0.82, 95% confidence interval [CI] 0.74~0.92, p<0.001, I2=0.0%) compared to non-ULT users. Subgroup analysis did not show that ULT users had a significant reduced risk of atrial fibrillation (pooled RR 0.76, 95% CI 0.54~1.05, p=0.096 with I2=15.4%) compared to non-ULT users.
CONCLUSION
ULT is associated with lower risk of overall arrhythmias. Further studies are warranted to confirm our findings.
PubMed: 38559794
DOI: 10.4078/jrd.2023.0059 -
Cureus Mar 2024DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome is a rare, life-threatening, hypersensitivity reaction. The prolonged course and non-specific symptoms...
DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome is a rare, life-threatening, hypersensitivity reaction. The prolonged course and non-specific symptoms of the condition make diagnosis challenging. We present a case of DRESS syndrome that was misdiagnosed as urticaria. Investigations revealed deranged liver and kidney functions and abnormal blood count. The presented case emphasizes the need to have a high suspicion for DRESS syndrome in patients who present with jaundice, generalized rash, acute renal failure, and acute liver failure.
PubMed: 38559511
DOI: 10.7759/cureus.55355 -
Inflammopharmacology Jun 2024Gout is a metabolic condition characterized by the accumulation of urate crystals in the synovial joints. These crystal depositions result in joint swelling and...
Gout is a metabolic condition characterized by the accumulation of urate crystals in the synovial joints. These crystal depositions result in joint swelling and increased concentration of serum uric acid in blood. The commercially available drugs lower serum uric acid levels and reduce inflammation, but these standard therapies have many side effects. This study aimed to investigate anti-gout and anti-inflammatory properties of curcumin nanoparticles (CNPs). For this purpose, CNPs were prepared by dissolving curcumin into dichloromethane. Then, gout was induced by injecting monosodium urate crystals (MSU) in the ankle joint and in the intra-peritoneal cavity which caused ankle swelling and increased blood uric acid levels. CNPs in different concentrations (5, 10, and 20 ppm) and allopurinol were orally administered. The MSU crystals increased the xanthine oxidase levels both in serum and the liver. Moreover, MSU crystals increased the serum levels of interleukin 1β, interleukin-6, tumor necrosis factor-alpha, liver function tests markers, renal function tests markers, and lipid profiles. However, the administration of CNPs decreased the levels of all these variables. CNPs increased the serum high-density lipoprotein and interleukin-10 levels. Moreover, CNPs also reduced ankle swelling significantly. Hence, the levels of xanthine oxidase, uric acid and ankle swelling were reduced significantly by oral administration of CNPs. Our findings indicate that CNPs through their anti-inflammatory properties significantly alleviate gouty arthritis. Thus, the study concluded that CNPs can be developed as an efficient anti-gout agent with minimal side effects.
Topics: Animals; Curcumin; Uric Acid; Arthritis, Gouty; Mice; Nanoparticles; Anti-Inflammatory Agents; Mice, Inbred BALB C; Male; Xanthine Oxidase; Gout Suppressants; Inflammation
PubMed: 38556563
DOI: 10.1007/s10787-024-01450-x -
Health Technology Assessment... Mar 2024Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol.
OBJECTIVE
To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease.
DESIGN
Prospective, randomised, open-label, blinded endpoint multicentre clinical trial.
SETTING
Four hundred and twenty-four UK primary care practices.
PARTICIPANTS
Aged 60 years and over with ischaemic heart disease but no gout.
INTERVENTIONS
Participants were randomised (1 : 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care.
MAIN OUTCOME MEASURES
The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis.
RESULTS
From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm ( = 2979) or the usual care arm ( = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); = 0.77. The pre-specified health economic analysis plan was to perform a 'within trial' cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval -0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective.
LIMITATIONS
The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis.
CONCLUSIONS
The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout.
FUTURE WORK
The effects of allopurinol on cardiovascular outcomes in patients with ischaemic heart disease and co-existing hyperuricaemia or clinical gout could be explored in future studies.
TRIAL REGISTRATION
This trial is registered as EU Clinical Trials Register (EudraCT 2013-003559-39) and ISRCTN (ISRCTN 32017426).
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in ; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Male; Middle Aged; Aged; Female; Allopurinol; Cost-Benefit Analysis; Acute Coronary Syndrome; Quality of Life; Prospective Studies; Uric Acid; Myocardial Ischemia; Gout; Stroke; Myocardial Infarction
PubMed: 38551218
DOI: 10.3310/ATTM4092 -
Rheumatology International Jul 2024The objective of this study was to analyze and compare the effects of different urate-lowering agents on testicular functions in men with gout in a clinical setting.
OBJECTIVE
The objective of this study was to analyze and compare the effects of different urate-lowering agents on testicular functions in men with gout in a clinical setting.
METHODS
In this prospective cohort study (Clinical Trial Registration Number: NCT04213534), a total of 49 male patients aged 18-45 years with gout were enrolled. They were divided into three groups and received treatment with either allopurinol, febuxostat or benzbromarone for a duration of 3 months. Semen parameters, reproductive hormones and biochemical assessments were evaluated at baseline, month 1, and month 3.
RESULTS
Overall, 40 individuals (81.6%) completed the follow-up visits. In allopurinol group, there were no significant differences in semen parameters from baseline to month 3. Most of sperm parameters in febuxostat group did not show notable changes, except for a decrease in sperm motility at month 3(33.6%, [22.9-54.3] vs 48.4%, [27.4-67.6], p = 0.033). However, the total motile sperm count did not differ significantly after febuxostat treatment. Surprisingly, administration of benzbromarone resulted in improved sperm concentration (37.19 M/mL, [29.6-69.92] vs 58.5 M/mL, [49.8-116.6], p = 0.001). There were no significant changes observed in sperm DNA integrity and reproductive hormones in the three groups from baseline to month 3. The incidence of adverse events did not differ significantly among the three groups as well.
CONCLUSION
This study is the first to demonstrate that urate-lowering agents, allopurinol and febuxostat, do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout, and benzbromarone presents improving sperm concentration. Results provide important preliminary guidance for the development of reproductive health management guidelines for patients RCID with gout.
Topics: Humans; Male; Gout; Adult; Prospective Studies; Gout Suppressants; Middle Aged; Febuxostat; Benzbromarone; Young Adult; Allopurinol; Spermatozoa; Sperm Motility; Semen Analysis; Adolescent; Sperm Count; Uric Acid
PubMed: 38538820
DOI: 10.1007/s00296-024-05572-x