Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies.

BACKGROUND: Long-term outcomes of rituximab-treated adult patients with podocytopathies (either minimal change disease or focal segmental glomerulosclerosis) are largely unknown. METHODS: A retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months. RESULTS: 183 adult patients (n=64 with focal segmental glomerulosclerosis and n=119 with minimal change disease) with difficult-to-treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-three of 151 (55%) initial responders achieved long-term relapse-free survival over three years. Maintenance therapy with rituximab was associated with a better relapse-free survival (HR 2.05, 95% CI: 1.07-3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared to 36% of patients without maintenance treatment (OR 2.69, 95% CI: 1.27-5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI: 1.0-1.7) before to 0.17 (95% CI: 0.00-0.24) relapses/year after rituximab initiation. Over the 36 months of follow-up, a stable course of estimated glomerular filtration rate (eGFR) was observed in those who initially responded with either complete or partial remission, whereas non-responders experienced a reduction in eGFR reaching -11 (95% CI: -18 to -8) mL/min/1.73m2 . CONCLUSIONS: Rituximab facilitated achievement of initial and long-term response in a majority of adult patients with difficult-to-treat podocytopathies. Maintenance treatment with rituximab further associated with long-term relapse-free survival over three years. Non-response to initial rituximab treatment was associated with poor kidney prognosis.

The importance of simultaneous oculoplastic surgery in quality of life related to vision in surgical resection of large vestibular schwannomas.

OBJECTIVES: Facial nerve palsy is one of the most important complications of vestibular schwannoma resection. When VII cranial nerve is damaged, ocular complications might appear, impacting patient´s quality of life. Therefore, standardized eye care must be a priority. This involves three key treatments: topical treatment, rehabilitation and oculoplastic surgery. The aim of this work is to review the results of oculoplastic surgery performed simultaneously with vestibular schwannoma resection in terms of vision-related quality of life, compared to deferred surgery. DESIGN: The study involved 177 patients who underwent vestibular schwannoma resection between 2015 and 2022. The incidence of facial palsy was registered. Of those patients who had the palsy, we selected 35 who also had oculoplastic surgery. 5 of them declined participating in the study. The final sample (n = 30) was divided in two groups depending on the timing of oculoplastic surgery: simultaneously- first group (n = 15) and deferred-second group (n = 15). The vision-related quality of life was measured using the NEI VFQ-25 test. RESULTS: 26.56% patients developed an immediate postoperative facial dysfunction, decreasing to 18.08% after one year of follow-up. Timing of oculoplastic surgery was associated with better results in quality of life; the first group of patients had a better quality of life (70.27/100) compared to the second group (53.73/100; p = 0.006). Moreover, worse results in quality of life were also associated with long-term postoperative facial palsy (p = 0.042). Current criteria for selecting patients were reliable, proving adequacy as we found worse long-term facial functions in patients who underwent simultaneous surgery (p = 0.01). CONCLUSIONS: Our current criteria for selecting candidates for simultaneous oculoplastic surgery are effective. When long-term facial nerve dysfunction is expected during vestibular schwannoma resection, oculoplastic surgery should be performed simultaneously to preserve the q vision-related quality of life. Long-term severe facial palsy is associated with poor vision-related quality of life.

Malthus Mysterious Orofacial Cleft Correction.

Thomas Malthus (1766-1834), distinguished English professor, is the father of modern demography and the most famous harelip carrier of history. Much is known of his orofacial cleft but nothing regarding its mysterious surgical correction. An 1833 portrait of Malthus by John Linnell, finished when he considered himself "handsome enough," for sitting does not show any upper lip scar. When this surgery took place? Although technically feasible in the 19th century, surgery of cleft lip and palate was complicated. Malthus would not risk his life to have his orofacial disability corrected shortly before his death. Linnell cunningly dissimulated his deformity.

Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.

C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

Otosyphilis: Two case reports and review of the English and Spanish literature of the last 24 years.

Syphilis has significantly increased its incidence in Europe and North America in the past 20 years. Although rare, sudden hearing loss might be a complication of syphilis infection. We present two cases of otosyphilis seen in our hospitals and review of the English and Spanish literature already published since 2000.

Long-term outcome of antineutrophil cytoplasmic antibody-associated small vessel vasculitis after renal transplantation.

The survival after renal transplantation of patients with antineutrophil cytoplasmic antibody (ANCA)-associated to systemic vasculitis is as good as in other diseases, although most of the reports are based on small numbers of patients. Furthermore, it is not known whether comorbidities (cardiovascular [CV] disease and cancer) are more frequent than in general population. We report our experience and the analysis of the published data on this topic. The outcome after transplantation in 49 patients with ANCA-associated small vessel vasculitis was compared with a control group. The relapse rate of vasculitis was 0.01 per patient per year. Comparison with the control patients revealed no difference in long-term outcome, CV mortality or incidence of malignancies. In the published literature, patients with ANCA at transplantation and with Wegener's granulomatosis are at greater risk of relapse. Taking our own results together with the review of the literature, we conclude that patient and graft survival rates compare favorably with those in control group that the recurrence rate is very low and that there is no increase in the incidence of cancer or in CV mortality. Patients with ANCA at transplantation and with Wegener's granulomatosis have a higher relapse rate.

The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes.

Background: Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR. Methods: We conducted an observational, multicentre and retrospective study of the pathological findings of renal biopsies from 832 consecutive patients with diabetes from 2002 to 2014 from 18 nephrology departments. The association of DR with kidney replacement therapy (KRT) or survival was assessed by Kaplan-Meier and Cox regression analyses. Results: Of 832 patients with diabetes and renal biopsy, 768 had a retinal examination and 221/768 (22.6%) had DR. During a follow-up of 10 years, 288/760 (37.9%) patients with follow-up data needed KRT and 157/760 (20.7%) died. The incidence of KRT was higher among patients with DN (alone or with NDKD) and DR [103/175 (58.9%)] than among patients without DR [88/216 (40.7%), P < .0001]. The incidence of KRT was also higher among patients with only NDKD and DR than among those without DR [18/46 (39.1%) versus 79/331 (23.9%), P < .0001]. In multivariate analysis, DR or DN were independent risk factors for KRT {hazard ratio [HR] 2.48 [confidence interval (CI) 1.85-3.31], P < .001}. DN (with or without DR) was also identified as an independent risk factor for mortality [HR 1.81 (CI 1.26-2.62), P = .001]. Conclusions: DR is associated with a higher risk of progression to kidney failure in patients with histological DN and in patients with NDKD.

Mitochondrial bioenergetic is impaired in Monocarboxylate transporter 1 deficiency: a new clinical case and review of the literature.

BACKGROUND: Monocarboxylate transporter 1 (MCT1) deficiency has recently been described as a rare cause of recurrent ketosis, the result of impaired ketone utilization in extrahepatic tissues. To date, only six patients with this condition have been identified, and clinical and biochemical details remain incomplete. RESULTS: The present work reports a patient suffering from severe, recurrent episodes of metabolic acidosis and psychomotor delay, showing a pathogenic loss-of-function variation c.747_750del in homozygosity in SLC16A1 (which codes for MCT1). Persistent ketotic and lactic acidosis was accompanied by an abnormal excretion of organic acids related to redox balance disturbances. Together with an altered bioenergetic profile detected in patient-derived fibroblasts, this suggests possible mitochondrial dysfunction. Brain MRI revealed extensive, diffuse bilateral, symmetric signal alterations for the subcortical white matter and basal ganglia, together with corpus callosum agenesia. CONCLUSIONS: These findings suggest that the clinical spectrum of MCT1 deficiency not only involves recurrent atacks of ketoacidosis, but may also cause lactic acidosis and neuromotor delay with a distinctive neuroimaging pattern including agenesis of corpus callosum and other brain signal alterations.

Low-dose sirolimus combined with angiotensin-converting enzyme inhibitor and statin stabilizes renal function and reduces glomerular proliferation in poor prognosis IgA nephropathy.

BACKGROUND: There is a lack of new therapeutic strategies for IgA nephropathy. Low-dose sirolimus inhibits mesangial cell proliferation and renal fibrosis in animal models. METHODS: We performed a pilot, randomized controlled trial to evaluate the efficacy and safety of low-dose sirolimus in patients with a high-risk IgA nephropathy. Twenty-three patients with a glomerular filtration rate (GFR) within 30-60 mL/min and/or proteinuria >1 g/day were randomly assigned to low-dose sirolimus plus enalapril and atorvastatin (SRL group, n = 14) or enalapril plus atorvastatin (CONTROL group, n = 9). Primary composite end point was variation of haematuria, proteinuria and blood pressure. Secondary end points were isotopic GFR, renal histology evaluated by Oxford classification and safety parameters evaluated at 6 and 12 months. RESULTS: Primary end point improved significantly in the SRL group at 12 months. Regarding isotopic GFR, patients included in the CONTROL group lost 8 mL/min/1.73 m(2), whereas those in the SRL arm improved 5 mL/min/1.73 m(2) (P = 0.03). Proteinuria decreased similarly in both study groups. At 1 year, SRL treatment was associated with a significant reduction of mesangial and endocapillary proliferation, whereas glomerular sclerosis, tubular atrophy and interstitial fibrosis were similar. Sirolimus was well tolerated; all patients remained on therapy at 12 months. CONCLUSION: The addition of low-dose sirolimus to enalapril and statin is safe, stabilizes renal function and reduces glomerular proliferative lesions in patients with poor prognosis IgA nephropathy.

Comparative safety and costs of transparent versus gauze wound dressings in intravenous catheterization.

The type of dressing selected for intravascular catheters may influence costs and complications. We carried out a clinical trial to compare the safety and costs of transparent and gauze dressings. We did not find differences in complication rates between transparent (34.1%) and gauze (26.5%) dressings (P = .62). The total cost per patient was $24.82 for transparent and $38.85 for gauze. The results indicate similar safety but increased cost associated with gauze dressings.

[Health of family physicians: do we practice what we preach?]. / La salud de los médicos de familia: ¿practicamos lo que predicamos?

AIMS: To describe the lifestyle of primary care physicians, their adherence to cancer screening tests and to describe basic aspects of occupational, mental and sexual health. DESIGN: Cross-sectional study. SETTING: Primary Care. Health Area 7, Madrid. PARTICIPANTS: Family Physicians. METHODS: An anonymous survey sent through the internal mail was completed by the participants. The questionnaire was based on the Cardiovascular Disease Prevention European Guidelines, Health Prevention and Promotion Activities Program (Programa de Actividades Preventivas y de Promoción de la Salud) and the World Health Organisation document on physical activity and health. The Hamilton Anxiety Scale was used to measure anxiety. RESULTS: A total of 114 primary care physicians participated in the study. The average years of medical practice was 18.29 years (SD: 8.2). Adherence to cardiovascular screening was 70%. Adherence to cervix, breast and colorectal cancer screening was of 73%, 86% and 24%, respectively. Vaccination records were up to date in 51.8% of the participants. A total of 81.6% had a stable sexual partner and 75.2% were satisfied with their sexual relationships. The condom was always used by just 21.1% of the participants. Hamiltons anxiety scale was abnormal in 74.3% of the physicians, but 90.4% reported to feel good or very good. CONCLUSIONS: Adherence to cardiovascular and female cancer screening is adequate, but insufficient in colorectal cancer. Vaccination among the participants was adequate.

Rheumatoid meningitis as a complication of long-standing rheumatoid arthritis: a case treated with rituximab.

Rheumatoid meningitis is a rare complication of long-standing rheumatoid arthritis. We present the case of a 39-year-old Bolivian woman with a history of seropositive rheumatoid arthritis of 12 years of evolution without extra-articular manifestations that develops a severe headache with vomiting. The diagnosis of rheumatoid meningitis was performed based on clinical history, blood count and biochemistry results, cerebrospinal fluid analysis and cranial magnetic resonance imaging findings. High-dose intravenous glucocorticoids were started, followed by rituximab. After treatment, a significant clinical improvement was observed and repeat magnetic resonance imaging scan confirmed an improvement of the meningeal lesions.

Prevalence of adverse drug events in emergency departments. FARM-URG multi-center project.

OBJECTIVE: Adverse drug events are a well-known cause of emergency department admissions. FARM-URG is a project promoted by  the REDFASTER working group of the Spanish Society of Hospital  Pharmacy. Its aim is to evaluate these adverse events through regular  prevalence measurements. The present study shows the results of the first observations. The goal was to determine the prevalence of adverse drug  events with respect to the total number of patients treated in emergency  departments and carry out a description of the different events identified. METHOD: This is a multicenter cross-sectional study carried out in the emergency room of 13 Spanish hospitals. The identification and  registration of patients were obtained from the emergency department  patient census at the time of the first prevalence measurement (16 June  2020). The REDCap® platform was used for patient registration. RESULTS: The 2020 FARM-URG registry, which included 13 hospitals, evaluated 772 patients, of whom 57 (7.4%) consulted for  adverse drug events. Antithrombotic drugs were responsible for most of  these episodes, acenocoumarol being the main drug involved (22.8%).  Nine (15.8%) adverse drug events were caused by inappropriate drug  prescriptions according to the STOPP-START criteria. Nineteen (33.0%)  patients returned to the emergency service within 30 days from discharge. CONCLUSIONS: Adverse drug events are a frequent cause of emergency department visits and are commonly associated with a  significant percentage of re-visits. The FARM-URG project has been created with the purpose of obtaining dynamic and updated information on such  events.

Objetivo: Los acontecimientos adversos por medicamentos son una causa conocida de asistencia a los servicios de urgencias. El objetivo del  proyecto FARM-URG, impulsado por el Grupo de Trabajo REDFASTER de la  Sociedad Española de Farmacia Hospitalaria, es evaluar estos  acontecimientos adversos mediante cortes periódicos. En este estudio se  muestran los resultados del primer registro. Sus objetivos fueron  determinar la prevalencia de acontecimientos adversos respecto al total de pacientes atendidos y caracterizarlos.Método: Estudio multicéntrico transversal realizado en los servicios de urgencias de hospitales españoles. La identificación y registro de  pacientes se obtuvo a partir del censo de pacientes atendidos en urgencias en el momento del corte (16 de junio de 2020). Se revisaron las historias  clínicas retrospectivamente y se registraron los datos en la plataforma  REDCap®.Resultados: En este corte FARM-URG de 2020 participaron 13 hospitales, que evaluaron 772 pacientes, de los cuales 57 (7,4%) habían consultado por un acontecimiento adverso por medicamentos. El grupo de  fármacos antitrombóticos fue responsable de la mayor parte de estos  episodios, siendo acenocumarol (22,8%) el principal fármaco implicado.  Nueve (15,8%) de los acontecimientos adversos fueron causados por  fármacos con prescripción inapropiada según los criterios STOPP-START.  Diecinueve (33,0%) pacientes volvieron a visitar el servicio de urgencias  antes de los 30 días del alta.Conclusiones: Los acontecimientos adversos por medicamentos son un motivo frecuente de visita a los servicios de urgencias y están  asociados a un importante porcentaje de visitas posteriores tras el alta. El  proyecto FARM-URG nace con el propósito de obtener información  periódicamente para la posible implementación de medidas preventivas.

Risk factors for non-diabetic renal disease in diabetic patients.

BACKGROUND: Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. METHODS: Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. RESULTS: In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2-5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02-1.05, P < 0.001], microhaematuria (OR = 1.51, 95% CI: 1.03-2.21, P = 0.033) and absence of diabetic retinopathy (DR) (OR = 0.28, 95% CI: 0.19-0.42, P < 0.001) were independently associated with NDRD. Kaplan-Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P = 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P = 0.002), higher creatinine (P = 0.01) and DN (P = 0.015) were independent risk factors for mortality. CONCLUSIONS: The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.

Anti-phospholipase A2 receptor antibody and spontaneous remission in membranous nephropathy.

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in native kidney biopsies from adults. In 2009, antibodies to the M-type receptor of phospholipase A2 (anti-PLA2R) were identified in idiopathic MN patients, both within the kidney and in the circulation. The clinical course of idiopathic MN is variable and ranges from spontaneous remission to end-stage renal disease. Clinical variables such as proteinuria levels, patient sex, age and renal function at diagnosis have been associated with renal MN progression. In this editorial, we update the importance of anti-PLA2R levels as a prognostic marker in idiopathic MN at the diagnosis of the disease.

Efficacy of mycophenolate treatment in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome.

BACKGROUND: This study assessed the efficacy of therapy with mycophenolate (MF) and reduced doses of steroids in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome (SD/FR-INS). METHODS: Twenty-nine nephrotic patients (including 16 males and 13 females; mean age: 40 years, range: 18-74) were treated. Starting doses of MF were 2000 mg/day for mofetil MF (1500 mg/day in one patient) or 1440 mg/day for sodium MF. The initial prednisone (PDN) dose was 10 mg/day in 14 patients, 5 mg/day in two patients and no steroids in one patient. In the remaining 12 patients, moderate initial doses of PDN were administered (mean: 23.7 mg/day, range: 15-40), tapering to 10 mg/day after 1 month. RESULTS: Nephrotic syndrome remission was achieved in 27/29 cases (93.1%) (25 complete, 2 partial). Two patients showed resistance to the prescribed schedule. The first cycle of MF therapy was concluded in 20 patients after a mean (range) of 16.9 months (12-49). Maintenance of remission was observed in 11 of these 20 cases (55%) after a mean follow-up of 32.8 months (12-108). In nine patients with nephrotic syndrome relapse after tapering of MF (MF dependency), the same MF-PDN schedule was restarted, leading again to remission in all nine. The remaining seven MF-sensitive patients are still receiving their first therapeutic cycle. To date, the mean time under therapy in the 27 MF-sensitive patients is 38 months (4-216). Regarding complications, only minor digestive disorders and a slight decrease in blood haemoglobin levels were observed in a few patients. CONCLUSIONS: MF plus reduced doses of PDN is an effective and well-tolerated therapy for adult SD/FR-INS. Though MF dependence is observed, its low toxicity could allow long periods of therapy if it is required to maintain nephrotic syndrome remission.