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Kidney International Jan 2021Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the...
Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the low solubility of cystine at normal urinary pH. We developed clinical practice recommendation for diagnosis, surgical and medical treatment, and follow-up of patients with cystinuria. Elaboration of these clinical practice recommendations spanned from June 2018 to December 2019 with a consensus conference in January 2019. Selected topic areas were chosen by the co-chairs of the conference. Working groups focusing on specific topics were formed. Group members performed systematic literature review using MEDLINE, drafted the statements, and discussed them. They included geneticists, medical biochemists, pediatric and adult nephrologists, pediatric and adult urologists experts in cystinuria, and the Metabolic Nephropathy Joint Working Group of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN members. Overall 20 statements were produced to provide guidance on diagnosis, genetic analysis, imaging techniques, surgical treatment (indication and modalities), conservative treatment (hydration, dietetic, alkalinization, and cystine-binding drugs), follow-up, self-monitoring, complications (renal failure and hypertension), and impact on quality of life. Because of the rarity of the disease and the poor level of evidence in the literature, these statements could not be graded. This clinical practice recommendation provides guidance on all aspects of the management of both adults and children with cystinuria, including diagnosis, surgery, and medical treatment.
Topics: Adult; Child; Consensus; Cystine; Cystinuria; Humans; Kidney; Quality of Life
PubMed: 32918941
DOI: 10.1016/j.kint.2020.06.035 -
Neurological Sciences : Official... Oct 2023Neurological deterioration, soon after anti-copper treatment initiation, is problematic in the management of Wilson's disease (WD) and yet reports in the literature are... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Neurological deterioration, soon after anti-copper treatment initiation, is problematic in the management of Wilson's disease (WD) and yet reports in the literature are limited. The aim of our study was to systematically assess the data according to early neurological deteriorations in WD, its outcome and risk factors.
METHODS
Using PRISMA guidelines, a systematic review of available data on early neurological deteriorations was performed by searching the PubMed database and reference lists. Random effects meta-analytic models summarized cases of neurological deterioration by disease phenotype.
RESULTS
Across the 32 included articles, 217 cases of early neurological deterioration occurred in 1512 WD patients (frequency 14.3%), most commonly in patients with neurological WD (21.8%; 167/763), rarely in hepatic disease (1.3%; 5/377), and with no cases among asymptomatic individuals. Most neurological deterioration occurred in patients treated with d-penicillamine (70.5%; 153/217), trientine (14.2%; 31/217) or zinc salts (6.9%; 15/217); the data did not allow to determine if that reflects how often treatments were chosen as first line therapy or if the risk of deterioration differed with therapy. Symptoms completely resolved in 24.2% of patients (31/128), resolved partially in 27.3% (35/128), did not improve in 39.8% (51/128), with 11 patients lost to follow-up.
CONCLUSIONS
Given its occurrence in up to 21.8% of patients with neurological WD in this meta-analysis of small studies, there is a need for further investigations to distinguish the natural time course of WD from treatment-related early deterioration and to develop a standard definition for treatment-induced effects.
Topics: Humans; Hepatolenticular Degeneration; Penicillamine; Trientine; Copper; Nervous System Diseases
PubMed: 37311952
DOI: 10.1007/s10072-023-06895-6 -
International Immunopharmacology Mar 2021Pemphigus encompasses a rare heterogeneous group of autoimmune blistering diseases characterized by cutaneous and/or mucosal blistering. Multiple factors, such as some...
Pemphigus encompasses a rare heterogeneous group of autoimmune blistering diseases characterized by cutaneous and/or mucosal blistering. Multiple factors, such as some specific types of drugs, have been found to be involved in the induction of pemphigus. Here, we have designed a systematic review by searching PubMed/Medline and Embase databases to find the drugs, involved in pemphigus induction and exacerbation (updated on 19 August 2019). From 1856 initially found articles, 134 studies (198 patients; 170 patients in the drug-induced patients and 28 in exacerbation group) have been included. Regarding drug-induced cases, the mean age was 57.19 ± 16.9-year-old (ranged 8-105), and patients had developed pemphigus within a mean of 154.27 days. Pemphigus vulgaris (38.9%), pemphigus foliaceus (33.5%), and paraneoplastic pemphigus (3.6%) were the most common subtypes. Furthermore, penicillamine (33.1%), captopril (7.7%), and bucillamine (6.5%) were the most reported drugs related to pemphigus induction; penicillamine was associated with the most persistent disease. Regardless of disease subtype, cutaneous, mucocutaneous, and mucosal involvements were reported in 68.6%, 30.1%, and 1.3% of patients, respectively. In total, the IgG deposition in the pathological studies, being positive for autoreactive antibodies in the serum against desmoglein 3 (Dsg3), and desmoglein 1 (Dsg1), were reported in 93%, 34.9%, and 72.7% of reported patients, respectively. Regarding the management of such patients, in 75% of healed cases, treatment (mainly transient systemic and topical corticosteroids and/or azathioprine) was needed besides stopping the probable pemphigus-inducing culprit drug, while drug cessation was enough to control the disease in 25%. As the outcomes, the lesions in 129 of 147 (87.8%) patients had been healed, while in 18 (12.2%), no healing was reported; fifteen out of 18 had died. In conclusion, some specific groups of treatments can induce pemphigus, including penicillamine, captopril, and bucillamine; despite the similar clinical and pathological manifestations to classical pemphigus, most of the cases are less severe and have a better prognosis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Antirheumatic Agents; Captopril; Cysteine; Drug-Related Side Effects and Adverse Reactions; Humans; Pemphigus; Penicillamine
PubMed: 33418246
DOI: 10.1016/j.intimp.2020.107299 -
JAMA Dermatology Feb 2024While several medications are known to induce dermatomyositis (DM), most existing studies are case reports or small case series from a single institution. There is also...
IMPORTANCE
While several medications are known to induce dermatomyositis (DM), most existing studies are case reports or small case series from a single institution. There is also limited information on DM induced by immune checkpoint inhibitors, which are increasingly used in oncologic therapy.
OBJECTIVE
To characterize causes and clinical presentation of drug-induced DM based on the current literature.
EVIDENCE REVIEW
A systematic review was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, from inception to August 22, 2022. Articles meeting preestablished inclusion criteria (written in English and classified as original articles, case reports, literature reviews, and observation letters) were selected and data abstracted. Articles that met the scope of the review were also added from reference lists. When possible, study results were quantitatively combined.
FINDINGS
In 134 studies (114 from the literature search and 20 additional studies pulled from reference lists) describing 165 cases, 88 patients (53.3%) were female, and the median (IQR) age was 61 (49-69) years. Among the cases of drug-induced DM, the most common associated medications were hydroxyurea (50 [30.3%]), immune checkpoint inhibitors (27 [16.4%]), statins (22 [13.3%]), penicillamine (10 [6.1%]), and tumor necrosis factor inhibitors (10 [6.1%]). Histopathologic testing, when undertaken, helped establish the diagnosis. There was a median (IQR) of 60 (21-288) days between drug initiation and drug-induced DM onset. History of cancer was reported in 85 cases (51.6%).
CONCLUSIONS AND RELEVANCE
In this systematic review, drug-induced DM was associated with multiple types of medications, including chemotherapies and immunotherapies. It is essential that dermatologists promptly recognize and diagnose drug-induced DM so that they can guide management to minimize interruption of therapy when possible.
Topics: Humans; Female; Middle Aged; Aged; Male; Dermatomyositis; Immune Checkpoint Inhibitors; Neoplasms; Hydroxyurea
PubMed: 38198130
DOI: 10.1001/jamadermatol.2023.5418 -
Clinical Neurology and Neurosurgery Aug 2023A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically... (Review)
Review
BACKGROUND
A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically reviewed clinical outcomes in glioma patients treated with one or more nutritional adjunct and/or an antimetabolite drug.
METHODOLOGY
A systematic review of the literature following PRISMA guidelines was performed using Pubmed from inception till February 2023. In total, 22 manuscripts on nutrition representing 828 patients were included in the review. Statistical analyses were performed to compare the outcomes of various adjuncts.
RESULTS
The median overall survival (OS) increased for newly diagnosed (21 months) and recurrent cases (10 months) when compared to historical data. For newly diagnosed cases, a ketogenic diet had the highest median OS of all the adjuncts (42.6 months) while in recurrent cases, a low copper diet coupled with 1 g penicillamine had the highest median OS (18.5 months). However, no statistically significant difference was observed in OS or progression-free survival (PFS) of newly diagnosed or recurrent gliomas.
CONCLUSION
While nutritional adjuncts may offer a therapeutic benefit in the treatment of glioma, more human subject research is needed to derive meaningful conclusions.
Topics: Humans; Neoplasm Recurrence, Local; Glioma; Progression-Free Survival; Brain Neoplasms
PubMed: 37390567
DOI: 10.1016/j.clineuro.2023.107853 -
Journal of Nephrology Mar 2024Cystinuria is a rare genetic kidney stone disease, with no cure. Current treatments involve lowering urinary cystine levels and increasing cystine solubility. This... (Review)
Review
BACKGROUND
Cystinuria is a rare genetic kidney stone disease, with no cure. Current treatments involve lowering urinary cystine levels and increasing cystine solubility. This systematic review evaluates the available literature regarding non-surgical interventions for cystinuria.
METHODS
Key electronic databases were searched for studies that described the clinical management of cystinuria with high diuresis, alkalinizing agents and thiol-based drugs that were published between 2000 and 2022. Observational studies were included if they contained clinical investigation with at least one previous or current episode of cystine stones, urine cystine levels > 250 mg/L and patients being managed with urinary dilution, alkalinizing agents or other pharmacological agents. All included studies were assessed for study design, patient characteristics and outcomes. A qualitative and critical analysis was performed whereby study quality was assessed using Methodological Index for Non-Randomized Studies (MINORS). Two authors performed the quality assessment and excluded the studies with a low MINORS score.
RESULTS
Fourteen studies met the review inclusion and quality criteria. Of the fourteen studies, two reported treatment using alkalinizing agents, six reported treatment using thiol-based drugs, and six reported combination treatment using alkalinizing agents and thiol-based drugs. These studies indicated that first-line therapies, including high fluid intake and urinary alkalinization, increased urine volume to > 3 L/day and urinary pH > 7.0, and were associated with reduced urinary cystine levels and cystine stone formation. Second-line therapy with cystine-binding thiol drugs, such as tiopronin and D-penicillamine, reduced urinary cystine levels, cystine crystal volume and increased cystine solubility, resulting in decreased cystine stone formation and stone recurrence rate. Further, combined intervention with alkalinizing agents and thiol-based drugs synergistically reduced stone recurrence.
CONCLUSION
Cystinuria treatment may require a combined approach of high diuresis, alkalinization and pharmacological interventions with regular monitoring of urinary pH, cystine levels, cystine crystal volume and solubility. However, poor adherence to treatment is relatively frequent, hence the pressing urgency for improved therapies and treatments.
Topics: Cystinuria; Humans; Cystine; Sulfhydryl Compounds; Treatment Outcome; Diuresis
PubMed: 37957454
DOI: 10.1007/s40620-023-01795-6 -
European Neurology 2022Increasing evidence has shown that oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD). Oxidative stress impairs muscle function,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Increasing evidence has shown that oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD). Oxidative stress impairs muscle function, reduces regenerative capacity, and leads to atrophy and muscle weakness. The present study aimed to evaluate the effectiveness and safety of antioxidants in treatment of DMD patients.
METHODS
Medline, Embase, EBSCOhost, and Cochrane Library databases were searched using relevant keywords regarding DMD and antioxidants. The risk of bias for all included studies was assessed using the Cochrane risk of bias tool. The effectiveness of antioxidants in improving pulmonary function and muscle strength in DMD patients and their rate of adverse events was evaluated by meta-analysis.
RESULTS
A total of nine eligible studies were identified. Among these, two studies involving 85 patients compared idebenone with placebo. Pooled data showed a significant improvement in pulmonary function after idebenone treatment. Flavonoids- and omega 3-based compounds (FLAVOMEGA) significantly improved muscle strength. Two studies evaluated coenzyme Q10 (CoQ10) and reported clinical improvement in physical activity. The remaining four studies evaluated pentoxifylline, superoxide dismutase, vitamin E combination with penicillamine and penicillamine alone, respectively, and found no significant differences between the intervention and placebo groups, measured by pulmonary function, muscle strength, movement function, or quality of life. Most adverse events were mild, while the rates of dropout and serious adverse events were low with respect to antioxidants.
CONCLUSIONS
Idebenone appeared to be safe and effective in improving pulmonary function in DMD patients, while pentoxifylline, superoxide dismutase, penicillamine, or a combination of vitamin E with penicillamine did not show a significant therapeutic effect. CoQ10 and FLAVOMEGA might be beneficial in improving muscle strength or physical activity in DMD patients. However, additional trials with more participants are warranted in the future.
Topics: Antioxidants; Flavonoids; Humans; Muscular Dystrophy, Duchenne; Penicillamine; Pentoxifylline; Quality of Life; Superoxide Dismutase; Vitamin E
PubMed: 35697003
DOI: 10.1159/000525045 -
Frontiers in Pharmacology 2022Pharmacological therapy is currently the main treatment method for patients with Wilson disease (WD). We aimed to evaluate the efficacy and safety of the common...
Pharmacological therapy is currently the main treatment method for patients with Wilson disease (WD). We aimed to evaluate the efficacy and safety of the common treatment regimens in these patients. We conducted a systemic review and meta-analysis by searching multiple databases for studies from inception to October 2021. Outcomes of interest were the improved rate and safety of d-penicillamine and zinc salts treatment in WD patients. Two independent reviewers performed the study selection and data extraction. Sixteen studies were included in this meta-analysis. The pooled improved rate for all included symptomatic WD patients was 78.0% (95% CI: 70.8%-85.2%). In symptomatic hepatic WD patients, there is no difference in the treatment efficiency of d-penicillamine and zinc salts (RR: 0.98, 95% CI: 0.86%-1.12%; = 0.765). In neurological WD patients, the pooled improved rate of those who received d-penicillamine and zinc salts was 56.3% (95% CI: 37.5%-75.1%) and 80.2% (95% CI: 67.2%-93.2%), respectively. The incidence of adverse effects (RR: 2.42, 95% CI: 1.20%-4.88%; = 0.014) and neurological deterioration (RR: 1.96, 95% CI: 1.31%-2.93%; = 0.001) in all symptomatic WD patients treated with d-penicillamine was both higher than that of patients treated with zinc salts. Our analysis suggests that symptomatic WD patients treated with d-penicillamine have higher incidence of adverse effects and neurological deterioration than that of zinc salts. The therapeutic effectiveness of these two regimens does not seem to be significantly different, and these results must be interpreted with caution. : PROSPERO registration, identifier CRD 42021287126.
PubMed: 35370752
DOI: 10.3389/fphar.2022.847436 -
Cureus Jun 2023A systematic review was carried out on a rare dermatological condition affecting papillary dermal tissue fibers of the skin known as elastosis perforans serpiginosa... (Review)
Review
A systematic review was carried out on a rare dermatological condition affecting papillary dermal tissue fibers of the skin known as elastosis perforans serpiginosa (EPS). The aim of this review was to highlight this skin disease, its association with other medical conditions, and its management. The search was conducted by using the keywords "elastosis perforans serpiginosa" and "case reports" in the databases. A total of 10 case reports were analyzed and presented by the parameters like age, gender, chief complaints, and medical history. The most common causes of EPS were drug-induced and occurred along with the Wilson disease. The study concluded that as EPS is an uncommon disease with few instances, there is a need for further research to analyze randomized controlled trials that have been conducted in relation to the condition.
PubMed: 37448439
DOI: 10.7759/cureus.40296 -
Current Urology Reports Aug 2023We wanted to analyse the outcomes of surgical (SWL, URS, PCNL) and medical management of cystine stones in the paediatric population in terms of stone-free status and... (Review)
Review
PURPOSE OF REVIEW
We wanted to analyse the outcomes of surgical (SWL, URS, PCNL) and medical management of cystine stones in the paediatric population in terms of stone-free status and complication rates, based on all the available literature evidence.
RECENT FINDINGS
A systematic review of literature was performed for all studies with paediatric cystine stone management. Twelve studies met the eligibility criteria, of which 4 analysed outcomes of SWL, 2 of URS and 3 of PCNL and 3 focused on the effect of either alkalising agents (potassium citrate, citric acid) or cysteine-binding thiol (CBT) agents (tiopronin, penicillamine). The reported SFR in studies ranged from 50 to 83%, 59 to 100% and 63 to 80.6%, with a complication rate of 2.8-51%, 14-27% and 12.9-15.4% with SWL, URS and PCNL, respectively. Paediatric cystine stones treatment should aim at complete stone clearance, preservation of renal function and prevention of further recurrences. SWL achieves inferior results in case of cystine stones. URS and PCNL are safe and effective procedures in the paediatric population, with a low rate of major complications. Adherence to medical prevention therapies may prolong recurrence-free periods.
Topics: Humans; Child; Kidney Calculi; Cystine; Lithotripsy; Ureteroscopy; Ureteral Calculi; Treatment Outcome
PubMed: 37079195
DOI: 10.1007/s11934-023-01162-9