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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 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 -
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 -
Pathogens (Basel, Switzerland) Feb 2024A three-year-old, intact female mix-breed dog, weighing 30 kg, was presented due to vomitus and diarrhea. At presentation, the patient had a slightly reduced general...
A three-year-old, intact female mix-breed dog, weighing 30 kg, was presented due to vomitus and diarrhea. At presentation, the patient had a slightly reduced general condition and moderately enlarged mandibular and popliteal lymph nodes. The initial blood work showed severe azotemia and hypoalbuminemia. In the urinalysis, marked proteinuria with a urine protein/creatinine ratio (UPC) of 4.69 was found. Further workup showed a high leishmania antibody titer. The dog was diagnosed with leishmaniosis and glomerulonephritis. Initial treatment consisted of intravenous fluid therapy, allopurinol, miltefosine, amlodipine, clopidogrel, and a diet with a low purine content. Creatinine temporarily decreased but increased again after three days. For further supportive treatment, intermittent hemodialysis in combination with hemoperfusion with the cytosorb adsorber was performed. A total blood volume of 17.7 L was processed within three hours. Thereafter, immunoadsorption (IA) was performed with the COM.TEC and ADAsorb platforms and a LIGASORB adsorber to eliminate circulating immunocomplexes. Treatment time for IA was two hours with a blood flow of 50 mL/min. A total plasma volume of 2.4 L was processed. Over the following days, creatinine declined, and the patient improved significantly. UPC decreased to 1.74 on day 17 after IA. The patient was discharged after two and a half weeks. Two years after the initial event, the patient is still in excellent condition, with creatinine, UPC, and albumin levels in the reference range. Therefore, IA might be an additional therapeutic option for dogs with leishmaniosis-induced glomerulonephritis and subsequent severe azotemia to improve immunocomplex-mediated glomerulonephritis.
PubMed: 38535536
DOI: 10.3390/pathogens13030193 -
Hong Kong Medical Journal = Xianggang... Apr 2024Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [hereafter, SJS/TEN] are uncommon but severe mucocutaneous reactions. Although they have been...
INTRODUCTION
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [hereafter, SJS/TEN] are uncommon but severe mucocutaneous reactions. Although they have been described in many populations worldwide, data from Hong Kong are limited. Here, we explored the epidemiology, disease characteristics, aetiology, morbidity, and mortality of SJS/TEN in Hong Kong.
METHODS
This retrospective cohort study included all hospitalised patients who had been diagnosed with SJS/TEN in Prince of Wales Hospital from 1 January 2004 to 31 December 2020.
RESULTS
There were 125 cases of SJS/TEN during the 17-year study period. The annual incidence was 5.07 cases per million. The mean age at onset was 51.4 years. The mean maximal body surface area of epidermal detachment was 23%. Overall, patients in 32% of cases required burns unit or intensive care unit admission. Half of the cases involved concomitant sepsis, and 23.2% of cases resulted in multiorgan failure or disseminated intravascular coagulation. The mean length of stay was 23.9 days. The cause of SJS/TEN was attributed to a drug in 91.9% of cases, including 84.2% that involved anticonvulsants, allopurinol, antibiotics, or analgesics. In most cases, patients received treatment comprising either best supportive care alone (35.2%) or combined with intravenous immunoglobulin (43.2%). The in-hospital mortality rate was 21.6%. Major causes of death were multiorgan failure and/or fulminant sepsis (81.5%).
CONCLUSION
This study showed that SJS/TEN are uncommon in Hong Kong but can cause substantial morbidity and mortality. Early recognition, prompt withdrawal of offending agents, and multidisciplinary supportive management are essential for improving clinical outcomes.
Topics: Humans; Stevens-Johnson Syndrome; Hong Kong; Middle Aged; Retrospective Studies; Male; Female; Adult; Incidence; Aged; Length of Stay; Allopurinol; Anticonvulsants; Sepsis; Multiple Organ Failure
PubMed: 38531617
DOI: 10.12809/hkmj2210131 -
Clinical Medicine Insights. Cardiology 2024The association between hyperuricemia and cardiovascular diseases has been studied for many years. Research has shown a link between high uric acid levels and increased... (Review)
Review
The association between hyperuricemia and cardiovascular diseases has been studied for many years. Research has shown a link between high uric acid levels and increased risk of including coronary artery disease hypertension and other cardiovascular conditions. Urate-lowering therapy, particularly with xanthine oxidase inhibitors like allopurinol, has shown promising results in reducing blood pressure in individuals with hyperuricemia and hypertension. Clinical trials and studies have demonstrated significant reductions in both systolic and diastolic blood pressure with urate-lowering treatment. Urate-lowering treatment has shown a favorable effect on reducing systolic blood pressure and major adverse cardiovascular events in patients with previous cardiovascular disease. In terms of cardiovascular safety, clinical trials have indicated that xanthine oxidase inhibitors such as febuxostat are non-inferior to allopurinol and do not increase the risk of death or serious adverse events. Overall, these findings highlight the importance of managing hyperuricemia and utilizing urate-lowering therapy to mitigate the adverse cardiovascular effects associated with elevated uric acid levels.
PubMed: 38529322
DOI: 10.1177/11795468241239542 -
Cureus Feb 2024The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs)... (Review)
Review
The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs) are antibodies that target cytotoxic thymus (T) lymphocyte antigen-4 (CTLA-4) and its receptor. They function by stimulating T-cell activity against malignancies. Immune-related adverse events (irAEs) are a distinct class of inflammatory side effects that are specific to a given organ. Antineoplastic medications can impact any part of the kidney, leading to the development of proteinuria, hypertension, electrolyte abnormalities, glomerulonephritis, and both acute and chronic interstitial nephritis. We reviewed the scientific literature regarding kidney problems that can arise from chemotherapy and immunotherapy for neoplasms, such as various cancers, melanoma, non-small cell lung cancer, and colorectal cancer. We discussed the pathophysiology, associated risk factors, management, and safety measures for patients experiencing acute renal injury after a new immunotherapy medication treatment. Antineoplastic drugs have the potential to damage the renal tubules, glomeruli, parenchyma, and blood vessels, among other kidney tissues. This can result in a broad spectrum of complications, spanning from a rise in serum creatinine levels without symptoms to the development of acute kidney injury (AKI). The research examined a range of risk factors associated with acute kidney injury (AKI). These factors encompassed age, gender, preexisting medical conditions (such as diabetes, hypertension, and chronic kidney disease), and the medications that patients were taking at the beginning of the study, which included non-steroidal anti-inflammatory drugs, renin-angiotensin system inhibitors, allopurinol, diuretics, corticosteroids, and proton pump inhibitors. The data suggests that patients who were receiving baseline treatment with proton pump inhibitors (PPIs) or corticosteroids had a higher risk of mortality. This study serves as an illustration of the effective management of acute kidney injury and proteinuria linked to novel immunotherapy drugs like pembrolizumab. The approach involved the use of corticosteroids tailored to the patient's condition. Furthermore, it references the recommendations outlined in the Common Terminology Criteria for Adverse Events (CTCAE). Prompt recognition and effective management of these side effects are essential to optimizing outcomes for patients undergoing immunotherapy. Our results were refined and focused by utilizing Medical Subject Headings (MeSH) keywords in our search strategy. The MeSH keywords used were "renal side effects" OR "immunotherapy" OR "cancer treatment." The studies reviewed encompassed a total of 48,529 participants among the 21 studies examined.
PubMed: 38516472
DOI: 10.7759/cureus.54487 -
Trials Mar 2024
Correction: Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome - a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).
PubMed: 38491488
DOI: 10.1186/s13063-024-08031-x -
The Journal of Rheumatology Jun 2024Allopurinol is the most widely used urate-lowering medication worldwide. However, allopurinol failure is frequently observed in clinical practice. In this review, we... (Review)
Review
Allopurinol is the most widely used urate-lowering medication worldwide. However, allopurinol failure is frequently observed in clinical practice. In this review, we provide a framework for assessing allopurinol failure, which includes failure of allopurinol to control serum urate concentrations, failure of allopurinol to control clinical symptoms, and failure of allopurinol due to an adverse drug reaction. Understanding the causes of allopurinol failure underpins the approach required to turn failure into success in gout management.
Topics: Allopurinol; Humans; Gout; Gout Suppressants; Treatment Failure; Uric Acid
PubMed: 38490676
DOI: 10.3899/jrheum.2024-0144