-
Cureus Mar 2020Tumor lysis syndrome (TLS) occurs in rapidly proliferating tumor cells, either spontaneously or after cytotoxic therapy. It has been well-documented in hematological... (Review)
Review
Intricate Interplay of Entwined Metabolic and Inflammatory Life-threatening Processes in Tumor Lysis Syndrome Complicating Prostate Cancer: A Systematic Review with a Single Institution Experience.
Tumor lysis syndrome (TLS) occurs in rapidly proliferating tumor cells, either spontaneously or after cytotoxic therapy. It has been well-documented in hematological diseases but is extremely rare in solid neoplasms, particularly in prostate cancer (PRCA). In the presence of risk factors, it can cause metabolic disturbances and be potentially fatal. We searched PubMed, Medline, ScienceDirect, and Scopus for "tumor lysis syndrome" and "prostate cancer" and conducted a systematic review with a pooled analysis for the published literature and cases from our institution. Twenty-two TLS cases were identified (18 published in the literature and four cases from our institution). The patients' median age was 68 years (range 16-82), and most cases were prostate adenocarcinoma. The median prostate-specific antigen (PSA) was 374 (range 66.7-10,867). Ten cases (45.5%) had spontaneous TLS (STLS) while 12 cases (54.5%) were treatment-related (TTLS). All patients had elevated lactate dehydrogenase (LDH) with other biochemical variables, and all underwent aggressive supportive therapy. Eleven patients underwent hemodialysis, 12 patients received rasburicase, while three patients received allopurinol. The mortality rate was 75% among 12 cases of TTLS, and it was 30% of the 10 cases with STLS. Among patients with PRCA, both TTLS and STLS linked to very high mortality. Early identification of TLS would substantially attain improved survival outcomes. Hence, physicians should consider TLS as a differential diagnosis when evaluating AKI and electrolyte abnormalities, particularly in patients with metastatic PRCA and high disease burden, even before the initiation of cytotoxic therapy.
PubMed: 32226700
DOI: 10.7759/cureus.7395 -
Journal of the European Academy of... Oct 2020Cutaneous leishmaniasis (CL) is one of the major neglected disease worldwide. Although many drugs have been used, the pentavalent antimonials (PA) remain as the... (Meta-Analysis)
Meta-Analysis Review
Cutaneous leishmaniasis (CL) is one of the major neglected disease worldwide. Although many drugs have been used, the pentavalent antimonials (PA) remain as the first-line choice despite their toxicity and limited efficacy. The combination of two drugs has risen as a potential alternative to increase the cure rate while lowering the side-effects caused by pentavalent antimonials (PA). The objective of this study was to critically review and appraise the potential synergism of the adjuvant therapies of PA with other drugs/interventions previously used in the literature. We carried out a search of literature from PubMed, MEDLINE, Embase, Cochrane and clinicaltrials.gov. Articles that described a two-arm or three-arm design in which one of the arms consisted in a combination of a drug/intervention with intralesional or systemic PA were selected. The primary outcome was proportion of complete clearance of the lesions defined as complete re-epithelization and/or negative direct smear. Our literature search identified 554 references. Thirty-one records with a total sample size of 2668 participants met the eligibility criteria. The studies investigated the association of PA with the following: cryotherapy (five studies), allopurinol, imiquimod, pentoxifylline (four studies each), trichloroacetic acid 50% (three studies) and other additional interventions (eleven studies). Overall, the combined therapy of PA with a supplementary intervention was superior to PA monotherapy (RR: 1.23 95% CI: 1.11-1.35, I = 64%). In association with PA, the comparator-specific stratified analysis showed that cryotherapy (RR: 1.50 95% CI: 1.25-1.81, I = 57%) and allopurinol (RR: 1.70 95% CI: 1.37-2.12, I = 28%) were superior to PA in monotherapy. On the contrary, the combined therapy with imiquimod (RR: 1.08 95% CI: 0.88-1.32, I = 40%) and pentoxifylline (RR: 1.14 95% CI: 0.94-1.40, I = 41%) revealed a non-significant result. The application of TCA along with PA did not show significant differences in the clearance rate, although it was close to it (RR: 1.31 95% CI: 0.99-1.73, I = 84%). The present work represents an attempt to find new and reliable treatment modalities to enhance the efficacy based on the adjuvant therapy of pre-existing drugs/interventions with PA. According to our results, the combination of allopurinol-PA is the most effective adjuvant therapy. The application of cryotherapy and TCA stand as useful and encouraging supplementary interventions. The combination of imiquimod-PA and pentoxifylline adds no additional benefit. The results of this work may be helpful in devising and modifying the current guidelines for CL which face major remaining evidence gaps. Triple therapies consisting in cryotherapy-PA-TCA or allopurinol-PA-cryotherapy or allopurinol-PA-TCA can represent promising treatments yet to be confirmed in future trials.
Topics: Combined Modality Therapy; Cryotherapy; Humans; Imiquimod; Leishmaniasis, Cutaneous; Photochemotherapy
PubMed: 32118322
DOI: 10.1111/jdv.16333 -
Chinese Medical Journal Apr 2020Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs.
METHODS
We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients' history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model.
RESULTS
Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28-2.33) and CVE (RR = 1.35, 95% CI 1.12-1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20-0.62) and CVE (RR = 0.61, 95% CI 0.44-0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54-0.88) rather than MACE (RR = 0.62, 95% CI 0.29-1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE.
CONCLUSIONS
The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.
Topics: Allopurinol; Cardiovascular Diseases; Febuxostat; Humans; Hyperuricemia; Risk Assessment; Uric Acid
PubMed: 32106120
DOI: 10.1097/CM9.0000000000000682 -
European Journal of Clinical... Jun 2020
Topics: Allopurinol; Gout; Humans; Hyperuricemia
PubMed: 32100073
DOI: 10.1007/s00228-020-02849-5 -
Angiology Apr 2020Several trials have been completed in patients with heart failure (HF) treated with uric acid (UA)-lowering agents with inconsistent results. We aimed to investigate... (Meta-Analysis)
Meta-Analysis
Several trials have been completed in patients with heart failure (HF) treated with uric acid (UA)-lowering agents with inconsistent results. We aimed to investigate whether lowering UA would have an effect on mortality and cardiovascular (CV) events in patients with HF in a systematic review and meta-analysis. The primary outcome measures were all-cause mortality, CV mortality, CV events, and CV hospitalization in patients with HF. We included 11 studies in our final analysis. Overall, allopurinol treatment was associated with a significant increase in the risk for all-cause mortality (hazard ratio [HR]: 1.24, 95% confidence interval [CI]: 1.04-1.49, P = .02). The trial heterogeneity is high (heterogeneity χ = 37.3, I2 = 73%, P < .001). With regard to CV mortality, allopurinol treatment was associated with a 42% increased risk of CV mortality (HR: 1.42, 95% CI: 1.11-1.81, P = .005). There was a trend toward increased CV hospitalization in the same group (HR: 1.21, 95% CI: 0.95-1.53, P = .12). Uric acid-lowering treatments increase all-cause and CV mortality but did not increase CV hospitalization significantly in this study.
Topics: Allopurinol; Enzyme Inhibitors; Febuxostat; Heart Failure; Humans; Oxypurinol; Uric Acid; Xanthine Oxidase
PubMed: 32000517
DOI: 10.1177/0003319719897509 -
Recommendations in clinical practice guidelines on gout: systematic review and consistency analysis.Clinical and Experimental Rheumatology 2020To compare and analyse the recommendations from clinical practice guidelines (CPGs) on gout worldwide, examine the consistency across CPGs, and provide suggestions to...
OBJECTIVES
To compare and analyse the recommendations from clinical practice guidelines (CPGs) on gout worldwide, examine the consistency across CPGs, and provide suggestions to develop and update gout guidelines.
METHODS
We conducted systematic searches in MEDLINE, CBM, GIN, NICE, NGC, WHO, SIGN, DynaMed, UpToDate, and Best Practice databases, from their inception to August 2019 to identify and select CPGs related to gout. We used the search terms "gout", "hyperuricaemia" and "guideline". After two rounds of screening, we included the eligible CPGs of gout according to the pre-defined inclusion and exclusion criteria. Methodological quality of included guidelines was assessed with the AGREE-II instrument. The general characteristics of included guidelines and the recommendations were extracted, and the consistency of recommendations across guidelines was compared and analysed.
RESULTS
A total of 15 gout guidelines including 359 recommendations were retrieved. The main topics covered by the recommendations were diagnosis, pharmacologic treatment of gout flares, pharmacologic urate-lowering therapy (ULT) of chronic gouty arthritis, lifestyle interventions, prophylaxis, and management of asymptomatic hyperuricaemia. The results of AGREE-II appraisal showed that only two guidelines achieved high scores (≥50%) in all six domains. There was substantial discrepancy between the guidelines in recommendations covering the value of computed tomography (CT) and x-rays for diagnosis, the use of corticosteroids as a first-line treatment for flare, the use of colchicine, indications for ULT, the use of febuxostat as first-line ULT, the administration of allopurinol, and the timing of ULT initiation.
CONLUSIONS
A number of countries are devoting themselves to the development of gout guidelines, but the process of updating guidelines is slower than that suggested by the WHO. Methodological quality is not satisfactory in most guidelines, and recommendations between guidelines are not consistent.
Topics: Arthritis, Gouty; Gout; Gout Suppressants; Humans; Hyperuricemia; Uric Acid
PubMed: 31969230
DOI: No ID Found -
European Journal of Internal Medicine Apr 2020While there is consensus on starting urate-lowering therapy (ULT) in cases of symptomatic hyperuricemia, the frequent condition of asymptomatic hyperuricemia (AH)...
While there is consensus on starting urate-lowering therapy (ULT) in cases of symptomatic hyperuricemia, the frequent condition of asymptomatic hyperuricemia (AH) remains a challenge due to differences in the findings of studies that have addressed the issue. Uric acid has anti-oxidant properties, but high levels predispose to gout and may play a role in metabolic syndrome. We systematically evaluated randomized controlled trials (RCTs) addressing ULT in patients with AH, to assess the current evidence. We found broad heterogeneity among the studies (13 RCTs), in terms of study design and population, making findings challenging to interpret and generalize; hard end-points were not assessed. Allopurinol is often prescribed for AH despite the fact that its use is not backed by conclusive evidence from prospective RCTs, nor is it recommended by the guidelines. Its potential benefits, in terms of absolute risk reduction, must be weighed against its potential for harm since it can trigger severe adverse hypersensitivity reactions, sometimes even fatal. RCTs with hard end-points are needed to assess the risk/benefit of lowering uric acid in subjects with AH, particularly as secondary prevention for cardiovascular risk and in patients with different degrees of renal disease. To date, particularly after the result from the CARES trial, preventive treatment of asymptomatic and non-severe hyperuricemia is not recommended.
Topics: Allopurinol; Gout; Gout Suppressants; Humans; Hyperuricemia; Uric Acid
PubMed: 31952982
DOI: 10.1016/j.ejim.2020.01.001 -
BJU International Apr 2020To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
OBJECTIVE
To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
PATIENTS AND METHODS
We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. The primary outcomes were prostatitis symptoms and adverse events. The secondary outcomes were sexual dysfunction, urinary symptoms, quality of life, anxiety and depression.
RESULTS
We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Most of our comparisons included short-term follow-up information. The median age of the participants was 38 years. Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies. We found low- to very low-quality evidence that α-blockers may reduce prostatitis symptoms based on a reduction in National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) scores of >2 (but <8) with an increased incidence of minor adverse events such as dizziness and hypotension. Moderate- to low-quality evidence indicates that 5α-reductase inhibitors, antibiotics, anti-inflammatories, and phytotherapy probably cause a small decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. Intraprostatic botulinum toxin A (BTA) injection may cause a large reduction in prostatitis symptoms with procedure-related adverse events (haematuria), but pelvic floor muscle BTA injection may not have the same effects (low-quality evidence). Allopurinol may also be ineffective for reducing prostatitis symptoms (low-quality evidence). We assessed a wide range of interventions involving traditional Chinese medicine; low-quality evidence showed they may reduce prostatitis symptoms without an increased incidence in adverse events. Moderate- to high-quality evidence indicates that the following interventions may be ineffective for the reduction of prostatitis symptoms: anticholinergics, Escherichia coli lysate (OM-89), pentosan, and pregabalin. Low- to very low-quality evidence indicates that antidepressants and tanezumab may be ineffective for the reduction of prostatitis symptoms. Low-quality evidence indicates that mepartricin and phosphodiesterase inhibitors may reduce prostatitis symptoms, without an increased incidence in adverse events.
CONCLUSIONS
Based on the findings of low- to very low-quality evidence, this review found that some pharmacological interventions such as α-blockers may reduce prostatitis symptoms with an increased incidence of minor adverse events such as dizziness and hypotension. Other interventions may cause a reduction in prostatitis symptoms without an increased incidence of adverse events while others were found to be ineffective.
Topics: Humans; Male; Prostatitis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31899937
DOI: 10.1111/bju.14988 -
Allergy May 2020Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours...
Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours after drug administration and include life-threatening conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA-B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA-compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim-sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.
Topics: Carbamazepine; Drug Hypersensitivity; Drug Hypersensitivity Syndrome; HLA-B Antigens; Humans; Pharmaceutical Preparations; Stevens-Johnson Syndrome; T-Lymphocytes
PubMed: 31899808
DOI: 10.1111/all.14174 -
Seminars in Arthritis and Rheumatism Jun 2020The management of gout consists of urate-lowering therapy and acute and chronic anti-inflammatory drugs. Allopurinol, a xanthine oxidase inhibitor, is the primary...
The management of gout consists of urate-lowering therapy and acute and chronic anti-inflammatory drugs. Allopurinol, a xanthine oxidase inhibitor, is the primary urate-lowering therapy employed for decades. Recent studies suggest cardiovascular disease and mortality, chronic kidney disease, prostate cancer, and manic symptoms are reduced in patients with gout treated with allopurinol. These findings support that allopurinol contributes to a variety of beneficial effects beyond urate lowering. This manuscript reviews the analgesic and anti-inflammatory properties of allopurinol, which are rarely discussed. Several mechanisms are suggested to confer these benefits including accumulation of adenosine and inhibitory effects of allopurinol on reactive oxygen species, tumor necrosis factor- α, nuclear factor kappa-light-chain-enhancer of activated B cells, and the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. Also, allopurinol blocks the stimulating effects of thioredoxin-interacting protein and interacts directly with the redox-active domain of thioredoxin as a negative regulator, decreasing NLRP3 activation. The importance of allopurinol's analgesic and anti-inflammatory properties requires further study and the implications to patient care better understood.
Topics: Allopurinol; Analgesics; Anti-Inflammatory Agents; Enzyme Inhibitors; Free Radical Scavengers; Gout; Gout Suppressants; Humans; Oxidative Stress; Uric Acid; Xanthine Oxidase
PubMed: 31839209
DOI: 10.1016/j.semarthrit.2019.11.009