Hospital General Universitario de Ciudad Real

INTRODUCTION: Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. METHODS: General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. RESULTS: The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. CONCLUSION: Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guideline.

Plant oils have been utilized for a variety of purposes throughout history, with their integration into foods, cosmetics, and pharmaceutical products. They are now being increasingly recognized for their effects on both skin diseases and the restoration of cutaneous homeostasis. This article briefly reviews the available data on biological influences of topical skin applications of some plant oils (olive oil, olive pomace oil, sunflower seed oil, coconut oil, safflower seed oil, argan oil, soybean oil, peanut oil, sesame oil, avocado oil, borage oil, jojoba oil, oat oil, pomegranate seed oil, almond oil, bitter apricot oil, rose hip oil, German chamomile oil, and shea butter). Thus, it focuses on the therapeutic benefits of these plant oils according to their anti-inflammatory and antioxidant effects on the skin, promotion of wound healing and repair of skin barrier.

The graphene family has captured the interest and the imagination of an increasing number of scientists working in different fields, ranging from composites to flexible electronics. In the area of biomedical applications, graphene is especially involved in drug delivery, biosensing and tissue engineering, with strong contributions to the whole nanomedicine area. Besides the interesting results obtained so far and the evident success, there are still many problems to solve, on the way to the manufacturing of biomedical devices, including the lack of standardization in the production of the graphene family members. Control of lateral size, aggregation state (single vs. few layers) and oxidation state (unmodified graphene vs. oxidized graphenes) is essential for the translation of this material into clinical assays. In this Tutorial Review we critically describe the latest developments of the graphene family materials into the biomedical field. We analyze graphene-based devices starting from graphene synthetic strategies, functionalization and processibility protocols up to the final in vitro and in vivo applications. We also address the toxicological impact and the limitations in translating graphene materials into advanced clinical tools. Finally, new trends and guidelines for future developments are presented.

OBJECTIVES: To review the impact of social isolation during COVID-19 pandemic on mental and physical health of older people and the recommendations for patients, caregivers and health professionals. DESIGN: Narrative review. SETTING: Non-institutionalized community-living people. PARTICIPANTS: 20.069 individuals from ten descriptive cross-sectional papers. MEASUREMENTS: Articles since 2019 to 2020 published on Pubmed, Scielo and Google Scholar databases with the following MeSh terms ('COVID-19', 'coronavirus', 'aging', 'older people', 'elderly', 'social isolation' and 'quarantine') in English, Spanish or Portuguese were included. The studies not including people over 60 were excluded. Guidelines, recommendations, and update documents from different international organizations related to mental and physical activity were also analysed. RESULTS: 41 documents have been included in this narrative review, involving a total of 20.069 individuals (58% women), from Asia, Europe and America. 31 articles included recommendations and 10 addressed the impact of social distancing on mental or physical health. The main outcomes reported were anxiety, depression, poor sleep quality and physical inactivity during the isolation period. Cognitive strategies and increasing physical activity levels using apps, online videos, telehealth, are the main international recommendations. CONCLUSION: Mental and physical health in older people are negatively affected during the social distancing for COVID-19. Therefore, a multicomponent program with exercise and psychological strategies are highly recommended for this population during the confinement. Future investigations are necessary in this field.

The objective was to assess the global oral lichen planus prevalence. We searched PubMed, EMBASE, Web of Science, and Scopus for studies published before September 2019. We evaluated the quality of studies and carried out several meta-analyses. The global pooled prevalence was 1.01%, with a marked geographical difference (p < .001). The highest prevalence was reported from Europe (1.43%) and the lowest in India (0.49%), where tobacco-associated keratosis appears to mask oral lichen planus resulting in attenuation of its prevalence. From the age of 40 years, the prevalence increases significantly and progressively (OR = 3.43, 95% CI = 2.48-4.73, p < .001). Studies that define diagnostic criteria report a higher prevalence (1.31% vs. 0.70%, p = .03), although the application of the WHO criteria (year 1978-2007) does not increase the ability to diagnose the disease compared with other criteria (p = .11). The studies performed by oral medicine/oral pathology specialists report significantly higher prevalence (1.80%) than dentists (0.61%) and dermatologists (0.33%; p < .001). In conclusion, we propose that reliable diagnostic criteria should be defined, which should include a set of essential criteria including the presence of white reticular lesions in any location of the oral mucosa. The impact of histopathological confirmation with defined diagnostic criteria must be researched in the future, although its main use should be to determine the presence or absence of epithelial dysplasia. The necessity to improve the knowledge of oral lichen planus among dentists and dermatologists through continuing education is apparent in the results of this meta-analysis.

BACKGROUND: Levels of physical activity and variation in physical activity and sedentary time by place and person in European children and adolescents are largely unknown. The objective of the study was to assess the variations in objectively measured physical activity and sedentary time in children and adolescents across Europe. METHODS: Six databases were systematically searched to identify pan-European and national data sets on physical activity and sedentary time assessed by the same accelerometer in children (2 to 9.9 years) and adolescents (≥10 to 18 years). We harmonized individual-level data by reprocessing hip-worn raw accelerometer data files from 30 different studies conducted between 1997 and 2014, representing 47,497 individuals (2-18 years) from 18 different European countries. RESULTS: Overall, a maximum of 29% (95% CI: 25, 33) of children and 29% (95% CI: 25, 32) of adolescents were categorized as sufficiently physically active. We observed substantial country- and region-specific differences in physical activity and sedentary time, with lower physical activity levels and prevalence estimates in Southern European countries. Boys were more active and less sedentary in all age-categories. The onset of age-related lowering or leveling-off of physical activity and increase in sedentary time seems to become apparent at around 6 to 7 years of age. CONCLUSIONS: Two third of European children and adolescents are not sufficiently active. Our findings suggest substantial gender-, country- and region-specific differences in physical activity. These results should encourage policymakers, governments, and local and national stakeholders to take action to facilitate an increase in the physical activity levels of young people across Europe.

Spontaneous remission is a well known characteristic of idiopathic membranous nephropathy, but contemporary studies describing predictors of remission and long-term outcomes are lacking. We conducted a retrospective, multicenter cohort study of 328 patients with nephrotic syndrome resulting from idiopathic membranous nephropathy that initially received conservative therapy. Spontaneous remission occurred in 104 (32%) patients: proteinuria progressively declined after diagnosis until remission of disease at 14.7 +/- 11.4 months. Although spontaneous remission was more frequent with lower levels of baseline proteinuria, it also frequently occurred in patients with massive proteinuria: 26% among those with baseline proteinuria 8 to 12 g/24 h and 22% among those with proteinuria >12 g/24 h. Baseline serum creatinine and proteinuria, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, and a >50% decline of proteinuria from baseline during the first year of follow-up were significant independent predictors for spontaneous remission. Only six patients (5.7%) experienced a relapse of nephrotic syndrome. The incidence of death and ESRD were significantly lower among patients with spontaneous remission. In conclusion, spontaneous remission is common among patients with nephrotic syndrome resulting from membranous nephropathy and carries a favorable long-term outcome with a low incidence of relapse. A decrease in proteinuria >50% from baseline during the first year predicts spontaneous remission.

PURPOSE: Germline mutations in DNA damage repair (DDR) genes are identified in a significant proportion of patients with metastatic prostate cancer, but the clinical implications of these genes remain unclear. This prospective multicenter cohort study evaluated the prevalence and effect of germline DDR (gDDR) mutations on metastatic castration-resistance prostate cancer (mCRPC) outcomes. PATIENTS AND METHODS: Unselected patients were enrolled at diagnosis of mCRPC and were screened for gDDR mutations in 107 genes. The primary aim was to assess the impact of ATM/BRCA1/BRCA2/ PALB2 germline mutations on cause-specific survival (CSS) from diagnosis of mCRPC. Secondary aims included the association of gDDR subgroups with response outcomes for mCRPC treatments. Combined progression-free survival from the first systemic therapy (PFS) until progression on the second systemic therapy (PFS2) was also explored. RESULTS: We identified 68 carriers (16.2%) of 419 eligible patients, including 14 with BRCA2, eight with ATM, four with BRCA1, and none with PALB2 mutations. The study did not reach its primary end point, because the difference in CSS between ATM/BRCA1/BRCA2/PALB2 carriers and noncarriers was not statistically significant (23.3 v 33.2 months; P = .264). CSS was halved in germline BRCA2 (g BRCA2) carriers (17.4 v 33.2 months; P = .027), and g BRCA2 mutations were identified as an independent prognostic factor for CCS (hazard ratio [HR], 2.11; P = .033). Significant interactions between g BRCA2 status and treatment type (androgen signaling inhibitor v taxane therapy) were observed (CSS adjusted P = .014; PFS2 adjusted P = .005). CSS (24.0 v 17.0 months) and PFS2 (18.9 v 8.6 months) were greater in g BRCA2 carriers treated in first line with abiraterone or enzalutamide compared with taxanes. Clinical outcomes did not differ by treatment type in noncarriers. CONCLUSION: g BRCA2 mutations have a deleterious impact on mCRPC outcomes that may be affected by the first line of treatment used. Determination of g BRCA2 status may be of assistance for the selection of the initial treatment in mCRPC. Nonetheless, confirmatory studies are required before these results can support a change in clinical practice.

OBJECTIVE: A systematic review was conducted to analyze the tolerability of several oral iron supplements based on data obtained in available publications and to report the incidence of adverse effects (AEs) for each supplement both overall and gastrointestinal. METHODS: Electronic databases - Medline, the Cochrane Library, and Embase were searched for studies published up to January 2009. Clinical or observational studies reporting data on the tolerability of oral iron supplements were included. Results were described statistically and a quasi-binomial logistic regression model was developed to evaluate and compare the tolerability of the supplements studied. RESULTS: For this review 111 studies were included, with data on 10,695 patients. Ferrous sulfate with mucoproteose had the lowest incidence of AEs (4.1% for overall AEs, 3.7% for gastrointestinal AEs [GAEs]) and was used as the reference supplement in the regression model. Incidence rates of overall AEs for the other supplements were 7.3% for iron protein succinylate [GAEs: 7%; OR for AE compared to the reference supplement, 1.96], 23.5% for ferrous glycine sulfate [GAEs: 18.5%; OR: 5.90], 30.9% for ferrous gluconate [GAEs: 29.9%; OR: 11.06], 32.3% for ferrous sulfate without mucoproteose [GAEs: 30.2%; OR: 11.21], and 47.0% for ferrous fumarate [GAEs: 43.4%; OR: 19.87]. The differences in incidence of AEs between extended-release ferrous sulfate with mucoproteose and all other supplements except iron protein succinylate were statistically significant at p < 0.001. These findings are subject to some limitations as the designs and methodologies of the studies included show heterogeneity among them that has partially been counteracted by the large sample size provided by the substantial number of trials, which is considered a strength in tolerability studies. CONCLUSION: Extended-release ferrous sulfate with mucoproteose appears to be the best tolerated of the different oral iron supplements evaluated.

OBJECTIVE: To investigate the validity, reproducibility, and responsiveness of a simplified power Doppler ultrasound (PDUS) assessment of joint inflammation compared with a comprehensive 44-joint PDUS assessment in patients with rheumatoid arthritis (RA) who started therapy with a biologic agent. METHODS: A total of 160 patients with active RA who started a biologic agent were prospectively recruited in 18 Spanish centers. The patients underwent clinical and laboratory assessment and blinded PDUS examination at baseline and 6 months. A PDUS examination of 128 synovial sites in 44 joints was performed. US synovitis and PD signal were semiquantitatively graded from 1 to 3 in all synovial sites. US count and index for synovitis and PD signal were obtained. PDUS intraobserver and interobserver reliability were evaluated. A process of data reduction based on the frequency of involvement of synovial sites by both synovitis and PD signal was conducted. Construct and discriminant validity of a simplified PDUS assessment was investigated. RESULTS: A PDUS simplified assessment including 24 synovial sites from 12 joints detected 100% of patients with synovitis and 91% of patients with PD signal. There was a highly significant correlation between the 44-joint count and index for synovitis and PD signal and the 12-joint count and index for synovitis and PD signal at baseline and 6 months (r = 0.84-0.90, P < 0.0005). The smallest detectable difference was lower than the mean change in simplified PDUS variables. CONCLUSION: A 12-joint PDUS assessment of RA joint inflammation may be a valid, feasible method for multicenter monitoring of therapeutic response to biologic agents.

OBJECTIVE: To assess the effects of the prescription formulation of glucosamine sulfate (1,500 mg administered once daily) on the symptoms of knee osteoarthritis (OA) during a 6-month treatment course. METHODS: Three hundred eighteen patients were enrolled in this randomized, placebo-controlled, double-blind trial in which acetaminophen, the currently preferred medication for symptomatic treatment of OA, was used as a side comparator. Patients were randomly assigned to receive oral glucosamine sulfate 1,500 mg once daily (n = 106), acetaminophen 3 gm/day (n = 108), or placebo (n = 104). The primary efficacy outcome measure was the change in the Lequesne index after 6 months. Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and response according to the Osteoarthritis Research Society International criteria. These outcome measures were assessed using an intent-to-treat analysis. RESULTS: At baseline, the study patients had moderately severe OA symptoms (mean Lequesne index approximately 11 points). Glucosamine sulfate was more effective than placebo in improving the Lequesne score, with a final decrease of 3.1 points, versus 1.9 with placebo (difference between glucosamine sulfate and placebo -1.2 [95% confidence interval -2.3, -0.8]) (P = 0.032). The 2.7-point decrease with acetaminophen was not significantly different from that with placebo (difference -0.8 [95% confidence interval -1.9, 0.3]) (P = 0.18). Similar results were observed for the WOMAC. There were more responders to glucosamine sulfate (39.6%) and acetaminophen (33.3%) than to placebo (21.2%) (P = 0.004 and P = 0.047, respectively, versus placebo). Safety was good, and was comparable among groups. CONCLUSION: The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms. Although acetaminophen also had a higher responder rate compared with placebo, it failed to show significant effects on the algofunctional indexes.

AIM: This study evaluated the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and within a subset of Stage 3 chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] ≥ 30 and <50 ml/min/1.73 m(2)). METHODS: In this 52-week, randomized, double-blind, placebo-controlled study, patients (N = 269; mean eGFR, 39.4 ml/min/1.73 m(2)) received canagliflozin 100 or 300 mg and placebo once daily. Efficacy endpoints included changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and systolic blood pressure (BP); adverse events (AEs) were also recorded. RESULTS: At week 52, canagliflozin 100 and 300 mg reduced HbA1c compared with placebo (-0.19, -0.33 and 0.07%, respectively); placebo-subtracted differences (95% confidence interval) were -0.27% (-0.53, 0.001) and -0.41% (-0.68, -0.14). Canagliflozin also lowered FPG, body weight and BP versus placebo. Overall AE incidence was 85.6, 80.9, and 86.7% with canagliflozin 100 and 300 mg and placebo, respectively. Osmotic diuresis-related AEs were more common with both canagliflozin doses, and incidences of urinary tract infections and volume depletion-related AEs were higher with canagliflozin 300 mg versus placebo. Decreases in eGFR (-2.1, -4.0 and -1.6 ml/min/1.73 m(2)) were seen with canagliflozin 100 and 300 mg compared with placebo. Canagliflozin 100 and 300 mg provided median percent reductions in urine albumin to creatinine ratio versus placebo (-16.4, -28.0 and 19.7%). CONCLUSIONS: Canagliflozin improved glycaemic control and was generally well tolerated in patients with T2DM and within a subset of Stage 3 CKD over 52 weeks.

One hundred ten patients with multiple myeloma (MM) failing to achieve at least near-complete remission (nCR) after a first autologous stem cell transplantation (ASCT) were scheduled to receive a second ASCT (85 patients) or a reduced-intensity-conditioning allograft (allo-RIC; 25 patients), depending on the human leukocyte antigen (HLA)-identical sibling donor availability. There was a higher increase in complete remission (CR) rate (40% vs 11%, P = .001) and a trend toward a longer progression-free survival (PFS; median, 31 months vs not reached, P = .08) in favor of allo-RIC. In contrast, it was associated with a trend toward a higher transplantation-related mortality (16% vs 5%, P = .07), a 66% chance of chronic graft-versus-host disease and no statistical difference in event-free survival and overall survival. Although the PFS plateau observed with allo-RIC is very encouraging, this procedure is associated with high morbidity and mortality, and therefore it should still be considered investigational and restricted to well-designed prospective clinical trials. This trial is registered at ClinicalTrials.gov ID number NCT00560053.

Abstract Background Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. Methods STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. Results The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. Conclusion STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies.

BACKGROUND: Allergy diagnosis in patients exposed to multiple pollen species is complex and misdiagnosis is often a cause for unsuccessful specific immunotherapy. OBJECTIVE: We studied the sensitization profile of individual allergens (major, minor and pan-allergens) in pollen-sensitized patients in a region with high exposure to olive pollen by investigating the influence of minor allergens on allergic disease and the association between pan- and minor allergen sensitizations. METHODS: A panel of 13 purified allergens, which included the most relevant allergens in the area, as well as minor olive allergens and pan-allergens, were screened using a high-capacity technology (ADVIA-Centaur) in 891 patients. RESULTS: Olive allergy as measured by specific IgE to Ole e 1 was the leading pollinosis in the area. The minor olive allergens Ole e 7 and Ole e 9 were markers of more severe allergic illness. Profilin sensitization was associated mainly with grass allergy, the second most prevalent pollinosis. Salsola kali pollen allergy was the third most common cause of pollinosis in the area. The prevalence of sensitization to the peach allergen Pru p 3, a nonspecific lipid-transfer protein, was notable. CONCLUSION: Epidemiological analysis by component-resolved diagnosis is a new method, which elucidates the interaction between allergen exposure gradient and patient sensitization. High exposure leads to differential sensitization profiles some of which are associated with more severe allergic conditions. Profilin sensitization, related mainly to grass pollinosis, was a marker of more severe grass pollen sensitization.

Continuous subcutaneous apomorphine infusion (CSAI) is, at present, an alternative option for advanced Parkinson's disease (PD) with motor fluctuations. We studied the evolution of patients with PD and severe motor fluctuations long-term treated with CSAI. We reviewed data from 82 patients with PD (mean age, 67 +/- 11.07; disease duration, 14.39 +/- 5.7 years) and severe motor fluctuations referred to 35 tertiary hospitals in Spain. These patients were long-term treated (for at least 3 months) with CSAI and tolerated the procedure without serious side effects. We compared the baseline data of these 82 patients (before CSAI) with those obtained from the last follow-up visit of each patient. The mean follow-up of CSAI was 19.93 +/- 16.3 months. Mean daily dose of CSAI was 72.00 +/- 21.38 mg run over 14.05 +/- 1.81 hours. We found a statistically significant reduction in off-hours, according to self-scoring diaries (6.64 +/- 3.09 vs. 1.36 +/- 1.42 hours/day, P < 0.0001), total and motor UPDRS scores (P < 0.0001), dyskinesia severity (P < 0.0006), and equivalent dose of antiparkinsonian therapy (1,405 +/- 536.7 vs. 800.1 +/- 472.9 mg of levodopa equivalent units P < 0.0001). CSAI is an effective option for patients with PD and severe fluctuations, poorly controlled by conventional oral drug treatment.

A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab. A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab. Primary membranous nephropathy (PMN) is one of the most common causes of nephrotic syndrome in adults.1Couser W. Primary membranous nephropathy.Clin J Am Soc Nephrol. 2017; 12: 983-997Crossref PubMed Scopus (245) Google Scholar In 70%–80% of cases, the disease is mediated by autoantibodies targeting the phospholipase A2 receptor (PLA2R) expressed in podocytes and in 3%–5% by autoantibodies to thrombospondin type 1 domain–containing 7A (THSD7A).2Beck Jr., L.H. Bonegio R.G. Lambeau G. et al.M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.N Engl J Med. 2009; 361: 11-21Crossref PubMed Scopus (1419) Google Scholar, 3Ronco P. Debiec H. Molecular pathogenesis of membranous nephropathy.Annu Rev Pathol. 2020; 15: 287-313Crossref PubMed Scopus (42) Google Scholar, 4Tomas N.M. Beck Jr., L.H. Meyer-Schwesinger C. et al.Thrombospondin type-1 domain–containing 7A in idiopathic membranous nephropathy.N Engl J Med. 2014; 371: 2277-2287Crossref PubMed Scopus (496) Google Scholar Spontaneous remission occurs in one-third of patients,5Polanco N. Gutiérrez E. Covarsí A. et al.Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy.J Am Soc Nephrol. 2010; 21: 697-704Crossref PubMed Scopus (248) Google Scholar and therefore an observational period of at least 6 months is recommended.6Waldman M. Austin H.A. Treatment of idiopathic membranous nephropathy.J Am Soc Nephrol. 2012; 23: 1617-1630Crossref PubMed Scopus (62) Google Scholar, 7Hofstra J.M. Fervenza F.C. Wetzels J.F.M. Treatment of idiopathic membranous nephropathy.Nat Rev Nephrol. 2013; 9: 443-458Crossref PubMed Scopus (88) Google Scholar, 8Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work GroupKDIGO clinical practice guidelines for glomerulonephritis.Kidney Int Suppl. 2012; 2 (139–27)Google Scholar Conversely, about 50% of cases with persistent nephrotic syndrome eventually progress to end-stage kidney disease, and immunosuppressive therapy is recommended for these patients. Controversy persists about the most effective type of immunosuppressive regimen. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for glomerulonephritis recommended a 6-month cyclic regimen of alternating alkylating agents (usually cyclophosphamide) plus corticosteroids for patients at high risk of progression, since it was the only regimen that was shown to be effective in preventing end-stage kidney disease.8Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work GroupKDIGO clinical practice guidelines for glomerulonephritis.Kidney Int Suppl. 2012; 2 (139–27)Google Scholar, 9Ponticelli C. Zucchelli P. Passerini P. et al.A randomized trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy.N Engl J Med. 1989; 320: 8-13Crossref PubMed Scopus (240) Google Scholar, 10Ponticelli C. Zucchelli P. Passerini P. et al.A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy.Kidney Int. 1995; 48: 1600-1604Abstract Full Text PDF PubMed Scopus (336) Google Scholar, 11Ponticelli C. Altieri P. Scolari F. et al.A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.J Am Soc Nephrol. 1998; 9: 444-450Crossref PubMed Google Scholar, 12Jha V. Ganguli A. Saha T.K. et al.A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy.J Am Soc Nephrol. 2007; 18: 1899-1904Crossref PubMed Scopus (215) Google Scholar However, given the important number of serious adverse events associated with cumulative doses of alkylating agents, treatment alternatives were introduced. Calcineurin inhibitors (both cyclosporine and tacrolimus) have shown efficacy in inducing remission of nephrotic syndrome in about 70% of patients.13Cattran D.C. Appel G.B. Hebert L.A. et al.Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial.Kidney Int. 2001; 59: 1484-1490Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar,14Praga M. Barrio V. Juárez G.F. Luño J. Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial.Kidney Int. 2007; 71: 924-930Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar However, the main limitation of these drugs is the high rate of relapse after discontinuation. An observational study found a reduction in relapse rates when rituximab was administered at the time of tapering off cyclosporine or tacrolimus,15Segarra A. Praga M. Ramos N. et al.Successful treatment of membranous glomerulonephritis with rituximab in calcineurin inhibitor-dependent patients.Clin J Am Soc Nephrol. 2009; 4: 1083-1088Crossref PubMed Scopus (82) Google Scholar and a pilot study reported encouraging results of a combined therapy with cyclosporine plus rituximab in high-risk PMN patients.16Waldman M. Beck Jr., L.H. Braun M. et al.Membranous nephropathy: pilot study of a novel regimen cyclosporine and Int Full Text Full Text PDF PubMed Scopus Google Scholar the efficacy of rituximab monotherapy P. P. A. et in idiopathic membranous nephropathy.J Am Soc Nephrol. 2012; 23: PubMed Scopus Google Scholar A of rituximab was to be effective for of remission in an observational P. P. G. rituximab to to therapy in idiopathic membranous nephropathy.Clin J Am Soc Nephrol. 2007; PubMed Scopus Google Scholar in clinical higher doses were for Debiec H. E. et for membranous nephropathy: a 6-month trial with Am Soc Nephrol. 2017; PubMed Scopus Google Scholar, F.C. Appel G.B. et or cyclosporine in the treatment of membranous nephropathy.N Engl J Med. PubMed Scopus Google Scholar, Debiec H. et rituximab and remission in membranous nephropathy.Clin J Am Soc Nephrol. PubMed Scopus Google Scholar the superior efficacy of rituximab versus cyclosporine in the of study was achieved a of F.C. Appel G.B. et or cyclosporine in the treatment of membranous nephropathy.N Engl J Med. PubMed Scopus Google Scholar The for comparing the 6-month cyclic alternating treatment with corticosteroids and cyclophosphamide with the alternatives was in a J. D.C. et and treatment of a Kidney Disease: Improving Global Outcomes (KDIGO) Int. Full Text Full Text PDF PubMed Scopus Google Scholar We the Treatment with Tacrolimus and and in study to cyclic alternating treatment of corticosteroids and cyclophosphamide with a sequential treatment of tacrolimus and rituximab in the and of nephrotic syndrome remission for 24 months. In the of after remission and the of anti-PLA2R autoantibodies the of the patients were for of were the for were the to in the study and of a of membranous nephropathy The 86 patients who the were assigned to the corticosteroid-cyclophosphamide group or to the tacrolimus-rituximab group in significant groups were at were in and anti-PLA2R was in showed at and patients patients with or anti-PLA2R at and patient was Kidney were months patients PMN and PMN to treatment patients was to the Kidney as of of 6 of 43 patients anti-PLA2R was at of 11 of 43 patients anti-PLA2R was at treatment of of 43 of 43 of of 43 of 43 A2 receptor receptor as or was to the Kidney Anti-PLA2R as In 6 of 43 patients anti-PLA2R was at In 11 of 43 patients anti-PLA2R was at in a A2 receptor receptor as or patients at least 1 month of the assigned patients in the corticosteroid-cyclophosphamide group and 6 in the tacrolimus-rituximab group the The in the corticosteroid-cyclophosphamide group and in the tacrolimus-rituximab the complete assigned to the corticosteroid-cyclophosphamide group a of methylprednisolone of in months and with a cumulative of The cumulative of methylprednisolone was The cumulative of cyclophosphamide was and of tacrolimus in the tacrolimus-rituximab group in patients in group a of rituximab in 2 1 in 1 at months and and 2 doses of tacrolimus month the follow-up period after the of the assigned patients in each group were to a to a of efficacy of the assigned In the corticosteroid-cyclophosphamide group, 2 patients were with rituximab at month 2 patients tacrolimus month and 1 patient cyclosporine month In the tacrolimus-rituximab group, the patients a 6-month cyclic treatment with corticosteroid and cyclophosphamide at month month or month the patients who were to a were to be was complete in of the 86 patients. patients (83.7%) in the corticosteroid-cyclophosphamide group and 25 patients (58.1%) in the tacrolimus-rituximab group a primary outcome of remission at 24 months (relative risk 95% confidence interval 1.08 to The significant in the primary outcome of in the corticosteroid-cyclophosphamide group and of in the tacrolimus-rituximab group 95% to The in the number of patients with complete or partial remission in both groups was significant at month and was the study outcome of complete or partial remission at to 24 cyclophosphamide risk of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 cyclophosphamide risk of of of of of of of of of of confidence the patients who the the patients who the of trial In both the primary outcome was the composite of complete or partial remission at 24 or 95% in a confidence The the patients who the the patients who the of trial In both the primary outcome was the composite of complete or partial remission at 24 months. or 95% shown in and 26 patients (60%) in the corticosteroid-cyclophosphamide group achieved complete remission at 24 months. In the tacrolimus-rituximab group, 11 patients (26%) achieved complete remission at 24 months 95% 1.34 to remission at to 24 cyclophosphamide risk of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 cyclophosphamide risk of of of of of of of of of of confidence the patients who the the patients who the of trial In both the primary outcome was the composite of complete or partial remission at 24 or 95% in a confidence The the patients who the the patients who the of trial In both the primary outcome was the composite of complete or partial remission at 24 months. or 95% A for a greater efficacy of the corticosteroid-cyclophosphamide treatment was found by of anti-PLA2R and were found in patients of patients were compared who achieved remission and with a significantly higher proportion of and a significantly higher were a at to at 24 months in the corticosteroid-cyclophosphamide group and at to 1 at 24 months in the tacrolimus-rituximab group a at to at 24 months in the corticosteroid-cyclophosphamide group and at to at 24 months in the tacrolimus-rituximab group was a for higher of rate in the corticosteroid-cyclophosphamide group than in the tacrolimus-rituximab group the follow-up 24 the of patients with a of were 1 in the corticosteroid-cyclophosphamide group and in the tacrolimus-rituximab group The of patients with at 24 months were in the corticosteroid-cyclophosphamide group and in the tacrolimus-rituximab group The only patient who end-stage kidney disease was a who assigned to the corticosteroid-cyclophosphamide group. months after treatment was the study of persistent and and to rituximab doses of 1 response was and was months after Anti-PLA2R showed a significant decrease in both groups The of patients who achieved response at and 6 months were significantly higher in the corticosteroid-cyclophosphamide group (77% and 92%, than in the tacrolimus-rituximab group (45% and 70%, patients who achieved response the study remission of nephrotic syndrome at 24 months. response at months and 6 months was associated with remission at 24 months. patients showed a in anti-PLA2R and a significantly proportion of compared with patients who achieved a complete or partial remission of nephrotic syndrome of anti-PLA2R and of response to treatment phospholipase A2 of were compared with the in a phospholipase A2 of were compared with the of the 36 patients in the corticosteroid-cyclophosphamide group, and of the 25 patients in the tacrolimus-rituximab group who achieved partial remission a relapse The in the tacrolimus-rituximab group occurred at month months after tacrolimus discontinuation. of occurred in patients who an response at month 6 and were by a of anti-PLA2R The relapse occurred in a patient in anti-PLA2R at Tacrolimus was in 2 patients and the one was with The relapse in the corticosteroid-cyclophosphamide group occurred at month in an patient who response at month In the relapse was by a of anti-PLA2R and the patient was with patients 6 the corticosteroid-cyclophosphamide group and the tacrolimus-rituximab at least 1 adverse adverse events were of or but were were adverse events and adverse events patient in the corticosteroid-cyclophosphamide group than in the tacrolimus-rituximab group patients in the corticosteroid-cyclophosphamide group and kidney and were common in the tacrolimus-rituximab group. was a significant the of and the of both in the trial and in each treatment group for the group and for the cyclophosphamide group, for the adverse events occurred the months of the trial of but only of the serious adverse events occurred events to treatment for the in number of events adverse adverse adverse events in at least of patients or serious adverse and kidney for patients as for events as for the in number of events groups. in a for patients as for events as were significant in the of serious adverse events groups. The only of serious kidney occurred in the tacrolimus-rituximab group, of the serious occurred in the corticosteroid-cyclophosphamide group. cases of were of was to be to the treatment occurred in the corticosteroid-cyclophosphamide group and at and 11 and 1 in the tacrolimus-rituximab group at 1 Anti-PLA2R was at in the patients with the time of the 2 patients in the corticosteroid-cyclophosphamide group were in clinical The study to the that sequential therapy with tacrolimus and rituximab was superior to cyclic alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in patients with In found that treatment with corticosteroid and cyclophosphamide was effective than sequential treatment with tacrolimus and rituximab in inducing The of was in the corticosteroid-cyclophosphamide group, with a significant in the number of at months. most were complete in the corticosteroid-cyclophosphamide group, most were partial in the tacrolimus-rituximab group. with calcineurin inhibitors and rituximab have that these drugs effective at inducing remission in that the of calcineurin inhibitors in PMN be to in a C. M. et of kidney podocytes is a target of the of cyclosporine Med. PubMed Scopus Google Scholar However, found that tacrolimus induced a decrease in anti-PLA2R in with A. V. et follow-up study of membranous nephropathy with tacrolimus and corticosteroids versus cyclical corticosteroids and Int 2017; Full Text Full Text PDF PubMed Scopus Google Scholar The main limitation of calcineurin inhibitors is the high relapse rate after in of patients. In the F.C. Appel G.B. et or cyclosporine in the treatment of membranous nephropathy.N Engl J Med. PubMed Scopus Google Scholar rituximab at 1 and after and 2 at month 6 the patient complete was compared with cyclosporine given for months. were significant in the number of at months. However, a higher proportion of patients in the cyclosporine group after treatment and the number of patients in remission at 24 months was significantly higher in the rituximab group In the number of at 6 months was in the tacrolimus-rituximab group than in the corticosteroid-cyclophosphamide group. at month 6 the in remission the number of complete after rituximab An important was the number of after tacrolimus discontinuation. This with a observational study that reported a of at the of calcineurin to in PMN patients who to cyclosporine or A. Praga M. Ramos N. et al.Successful treatment of membranous glomerulonephritis with rituximab in calcineurin inhibitor-dependent patients.Clin J Am Soc Nephrol. 2009; 4: 1083-1088Crossref PubMed Scopus (82) Google Scholar The pathogenesis of after tacrolimus in PMN and the rituximab rituximab is effective in the number of nephrotic syndrome in kidney as disease and and M. et for nephrotic syndrome or nephrotic a 2014; Full Text Full Text PDF PubMed Scopus Google P. P. et in or idiopathic nephrotic Am Soc Nephrol. 2014; PubMed Scopus Google Scholar In the the number of for the than number of at 24 months. the response rate of in the tacrolimus-rituximab group was similar to that with in Debiec H. E. et for membranous nephropathy: a 6-month trial with Am Soc Nephrol. 2017; PubMed Scopus Google F.C. Appel G.B. et or cyclosporine in the treatment of membranous nephropathy.N Engl J Med. PubMed Scopus Google Scholar and than that after cyclosporine or tacrolimus the of rituximab D.C. Appel G.B. Hebert L.A. et al.Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial.Kidney Int. 2001; 59: 1484-1490Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar,14Praga M. Barrio V. Juárez G.F. Luño J. Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial.Kidney Int. 2007; 71: 924-930Abstract Full Text Full Text PDF PubMed Scopus (216) Google A. V. et follow-up study of membranous nephropathy with tacrolimus and corticosteroids versus cyclical corticosteroids and Int 2017; Full Text Full Text PDF PubMed Scopus Google Scholar the it be that the tacrolimus-rituximab group in the corticosteroid-cyclophosphamide and were higher anti-PLA2R a higher of and a of in group. these at have the an outcome in the tacrolimus-rituximab group. the of anti-PLA2R autoantibodies as a of the disease in 70%–80% of patients with a cumulative number of have the of of anti-PLA2R to clinical to the and to the of immunosuppressive Jr., L.H. Bonegio R.G. Lambeau G. et al.M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.N Engl J Med. 2009; 361: 11-21Crossref PubMed Scopus (1419) Google M. Wetzels P. The anti-PLA2R in membranous nephropathy: and a after Int. Full Text Full Text PDF PubMed Scopus Google Scholar, Fervenza F.C. A for a to membranous nephropathy.J Am Soc Nephrol. 2017; PubMed Scopus Google Scholar, E. G. A2 receptor autoantibodies and clinical outcome in patients with primary membranous nephropathy.J Am Soc Nephrol. 2014; PubMed Scopus Google Scholar, P. Debiec H. et receptor outcome of membranous nephropathy.J Am Soc Nephrol. PubMed Scopus Google Scholar, A2 receptor and treatment of membranous nephropathy: a J Am Soc Nephrol. 2014; 9: PubMed Scopus Google Scholar We found that both corticosteroid-cyclophosphamide and tacrolimus-rituximab induced a significant reduction in anti-PLA2R response occurred in the corticosteroid-cyclophosphamide group. and in a reduction in than drugs as rituximab or calcineurin and have the of alkylating agents in the most cases of A. et remission in membranous nephropathy: cyclophosphamide versus Int. Full Text Full Text PDF PubMed Scopus Google Scholar, et for membranous nephropathy: a controlled 2013; Full Text Full Text PDF PubMed Scopus Google Scholar, C. and in mediated kidney Rev Nephrol. 15: PubMed Scopus Google Scholar response was by clinical remission in the of the of anti-PLA2R for a treatment of the The rate of adverse was significantly higher patients with were in the number of serious adverse have shown that in PMN by serious J.M. Wetzels risk after cyclophosphamide treatment in idiopathic membranous nephropathy.Clin J Am Soc Nephrol. 2014; 9: PubMed Scopus Google P. A. et of rituximab compared with steroids and cyclophosphamide for idiopathic membranous nephropathy.J Am Soc Nephrol. 2017; PubMed Scopus Google Scholar However, cumulative doses of cyclophosphamide were higher than in have that of doses of the results in M. H. et of idiopathic membranous nephropathy in patients with cyclophosphamide and 2009; PubMed Scopus Google Scholar Anti-PLA2R to treatment in patients in a response is have reported encouraging results with the of of cyclophosphamide as a for cyclophosphamide in patients with the alternating cyclic regimen of corticosteroids and V. A. G. cyclophosphamide and is a and effective treatment for idiopathic membranous nephropathy.Clin Kidney J. 2017; PubMed Scopus Google P. cyclophosphamide and steroids immunological and clinical remission in and primary membranous 23: PubMed Scopus Google Scholar the it be important to the of doses of corticosteroids the of the of treatment with corticosteroids and cyclophosphamide be compared with calcineurin inhibitors and treatment with tacrolimus 6 months or higher and doses of rituximab the remission rates in patients with tacrolimus-rituximab be in The study important was of and outcome The by or of anti-PLA2R and anti-PLA2R were in a number of patients. were about the of rituximab was However, study was a controlled trial that compared the cyclic alternating treatment with corticosteroids and cyclophosphamide versus the alternatives treatment with tacrolimus and with a and follow-up period that to important about the treatment of PMN in clinical In treatment with corticosteroid-cyclophosphamide induced remission of nephrotic syndrome in a significantly greater number of patients than treatment with were in the group. This randomized, controlled trial with a was by the and at in 1 in the A complete of study and is in the of the and study for the trial in the The study was J. G. A. et al.A and open-label controlled randomized trial to the efficacy of sequential treatment with tacrolimus-rituximab versus steroids plus cyclophosphamide in patients with primary membranous nephropathy: the Kidney J. PubMed Scopus Google Scholar A and the of the and the of the the trial at The trial is at patients with PMN were patients were for an observational period of at least 6 months. were a decrease of the observational and the observational patients the of with receptor for at least 2 months and controlled for at least with in of or the In the of a was were causes of membranous nephropathy or disease, treatment with another or or to drugs treatment with corticosteroids months immunosuppressive months or to or with a risk for the patient and or Full as as and in We a in for with an to with corticosteroid-cyclophosphamide or tacrolimus-rituximab. The were assigned as each the In the corticosteroid-cyclophosphamide group, patients methylprednisolone at months and at and to months and patients cyclophosphamide for and for In the tacrolimus-rituximab group, patients tacrolimus to target of for 6 months. patients rituximab and tacrolimus was by with complete at the of month Tacrolimus was in of kidney with patients 1 and groups with a the treatment were to in of of and patients with a relapse of nephrotic syndrome were as The primary outcome was complete or partial remission at 24 months. the rate of complete and partial remission at and 24 relapse of nephrotic syndrome at and 24 response at to 24 and the of patients of of and with kidney at 24 and adverse were the proportion of patients with adverse events the study and cumulative of each study Complete remission was as a reduction of to a plus kidney partial remission as a reduction of and a plus response was as a reduction of Relapses were as a of and at least the in or in patients with partial or complete were to be for anti-PLA2R when were as with a C. C. et of a for the of autoantibodies phospholipase A2 receptor in primary membranous nephropathy.Clin 2013; PubMed Scopus Google Scholar response was by a of anti-PLA2R was with the Kidney the results of hypothesized a remission rate of at 2 for the corticosteroid-cyclophosphamide group and for the tacrolimus-rituximab group. We to a of Primary outcome remission at 24 was by and the with 95% and compared with or for complete or partial remission at and months were for the of of the primary outcome were to the to of and and were with the of with the 2 groups in were with or as were with or as as and months and 24 were with the of The and as and as with and anti-PLA2R were as and to time to nephrotic syndrome were with the of and patients who of the study the primary outcome were the a was as an of the time and the in The was as when the of the of the time was associated with were with the of a The of was reported as the with 95% A of the is in were by for treatment groups and and Work in study was by the and and and in of the of the for the of a for in with for of and and and We the trial at and the patients who in the and the and in the and to the of the the of the and the F. A A and and and the the be groups with an the for with The calcineurin therapy in membranous trial that in primary membranous nephropathy treatment with tacrolimus plus rituximab be superior to a regimen of alternating cyclophosphamide and This was the were achieved in and of these were complete these results with of the compared rituximab with cyclosporine in an the of calcineurin for PDF progress in membranous Treatment with Tacrolimus and and in PMN the of a corticosteroid-cyclophosphamide regimen However, of these to the In patients nephrotic syndrome with rate a at risk of disease progression. PDF The and for We about the of a treatment of membranous but that the Treatment with Tacrolimus and and in PMN for results the efficacy of cyclic alternating treatment with corticosteroids and cyclophosphamide of at 24 most of the 6-month alternating is by in inducing and clinical remission (77% and at months) be the of and of corticosteroids and PDF phospholipase A2 receptor rituximab treatment in membranous the Treatment with Tacrolimus and versus and in Primary et have shown that a sequential is effective to the to membranous events were in the have shown that and higher immunological remission rate than rituximab and that rituximab is and to PDF The et for and for the results in of patients with membranous nephropathy with an A2 rituximab We that the of A2 receptor a and treatment of membranous PDF

Advances in new technologies for complete slide digitization in pathology have allowed the appearance of a wide spectrum of technologic solutions for whole-slide scanning, which have been classified into motorized microscopes and scanners. This article describes technical aspects of 31 different digital microscopy systems. The most relevant characteristics of the scanning devices are described, including the cameras used, the speed of digitization, and the image quality. Other aspects, such as the file format, the compression techniques, and the solutions for visualization of digital slides, (including diagnosis-aided tools) are also considered. Most of the systems evaluated allow a high-resolution digitization of the whole slide within about 1 hour using a x40 objective. The image quality of the current virtual microscopy systems is suitable for clinical, educational, and research purposes. The efficient use of digital microscopy by means of image analysis systems can offer important benefits to pathology departments.

From organosuperbases capable of base-catalyzing organic reactions, through versatile 'ligand-sets' for use in coordination chemistry, to fundamental entities in medicinal chemistry, guanidines are amongst the most interesting, attractive, valuable, and versatile organic molecules. Since the discovery of these compounds, synthetic chemists have developed new methodologies that are mainly based on multi-step and stoichiometric reactions. Despite the fact that these methodologies are still being used by the interested scientific and industrial communities, drawbacks such as the poor availability of precursors, low yields, and use and production of undesirable substances highlight the need for safe, simple and efficient syntheses of these entities. This review focuses on the metal-mediated catalytic addition of amines to carbodiimides as an atom-economical alternative to the classical synthesis.

El acceso vascular para hemodiálisis es esencial para el enfermo renal tanto por su morbimortalidad asociada como por su repercusión en la calidad de vida. El proceso que va desde la creación y mantenimiento del acceso vascular hasta el tratamiento de sus complicaciones constituye un reto para la toma de decisiones debido a la complejidad de la patología existente y a la diversidad de especialidades involucradas. Con el fin de conseguir un abordaje consensuado, el Grupo Español Multidisciplinar del Acceso Vascular (GEMAV), que incluye expertos de las cinco sociedades científicas implicadas (nefrología [S.E.N.], cirugía vascular [SEACV], radiología vascular e intervencionista [SERAM-SERVEI], enfermedades infecciosas [SEIMC] y enfermería nefrológica [SEDEN]), con el soporte metodológico del Centro Cochrane Iberoamericano, ha realizado una actualización de la Guía del Acceso Vascular para Hemodiálisis publicada en 2005. Esta guía mantiene una estructura similar, revisando la evidencia sin renunciar a la vertiente docente, pero se aportan como novedades, por un lado, la metodología en su elaboración, siguiendo las directrices del sistema GRADE con el objetivo de traducir esta revisión sistemática de la evidencia en recomendaciones que faciliten la toma de decisiones en la práctica clínica habitual y, por otro, el establecimiento de indicadores de calidad que permitan monitorizar la calidad asistencial. Vascular access for haemodialysis is key in renal patients both due to its associated morbidity and mortality and due to its impact on quality of life. The process, from the creation and maintenance of vascular access to the treatment of its complications, represents a challenge when it comes to decision-making, due to the complexity of the existing disease and the diversity of the specialities involved. With a view to finding a common approach, the Spanish Multidisciplinary Group on Vascular Access (GEMAV), which includes experts from the five scientific societies involved (nephrology [S.E.N.], vascular surgery [SEACV], vascular and interventional radiology [SERAM-SERVEI], infectious diseases [SEIMC] and nephrology nursing [SEDEN]), along with the methodological support of the Cochrane Center, has updated the Guidelines on Vascular Access for Haemodialysis, published in 2005. These guidelines maintain a similar structure, in that they review the evidence without compromising the educational aspects. However, on one hand, they provide an update to methodology development following the guidelines of the GRADE system in order to translate this systematic review of evidence into recommendations that facilitate decision-making in routine clinical practice, and, on the other hand, the guidelines establish quality indicators which make it possible to monitor the quality of healthcare.