Long-term outcomes with multi-targeted immunosuppressive protocol in children with severe proliferative lupus nephritis.

We have previously reported the one-year outcomes of 16 children with severe proliferative lupus nephritis (LN) who were treated using a multi-targeted induction protocol based on intravenous (IV) pulse methylprednisolone (MP), mycophenolate mofetil (MMF) and cyclosporine (CSA). This study examined the long-term renal outcomes of these 16 children, followed up for a median duration of 9.2 years (range 5.8-14.2 years). Primary treatment outcome was complete renal remission. Secondary outcomes included patient and renal survival as well as relapse-free and event-free survival. All patients achieved complete renal remission within 24 months (median 8.7 months, range 4.0-24.0 months). Comparing clinical and laboratory parameters at induction and last follow-up, respectively, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (25.4 ± 8.7 vs. 0.4 ± 0.8), serum complement C3 (47 ± 21 vs. 107 ± 27 mg/dL), estimated glomerular filtration rate (eGFR) (72 ± 57 vs. 109.7 ± 43 ml/min/1.73 m2) and urine protein (6.97 ± 7.09 vs. 0.2 ± 0.02 g/day/1.73 m2) improved significantly (p < 0.05). Kaplan-Meier survival analysis showed a cumulative ten-year renal relapse-free survival of 73.3% when considering relapses with severe proteinuria >1 g/day/1.73 m2. Cumulative probability that hospitalization would not be required was 93.8% at one year, and 71.4% at ten years. Our multi-targeted protocol for induction and maintenance therapy in Asian children with severe proliferative LN resulted in good long-term patient survival and renal preservation, with a good safety profile.

[Depression in patients with epilepsy. Pathophysiological and clinical concepts and therapeutic strategies]. / Depresión en pacientes con epilepsia. Conceptos fisiopatológicos, clínicos y estrategias terapéuticas.

INTRODUCTION: Depression and epilepsy are highly prevalent diseases and represent a worldwide public health problem. DEVELOPMENT: A non-systematic search was performed in PubMed (MEDLINE) considering current topics in pathophysiological, clinical concepts and treatment strategies in people with epilepsy and depression. RESULTS AND CONCLUSIONS: Depression and epilepsy have a bidirectional relationship and share some pathophysiological substrates. Depression is the most common neuropsychiatric manifestation in epilepsy; screening and diagnosis are important to start a timely treatment. Antidepressant drugs does not increase the frequency of seizures, on the contrary, it is believed that antidepressants may help reducing the frequency of seizures. In addition, other antidepressant therapies such as Cognitive Behavioral Therapy and neuromodulation may be also effective for reducing the frequency of seizures. However the evidence regarding antidepressant treatment(s) in epilepsy is limited and further prospective studies are needed to better characterize the possible therapeutic strategies and develop standarized treatment guidelines.

TITLE: Depresión en pacientes con epilepsia. Conceptos fisiopatológicos, clínicos y estrategias terapéuticas.Introducción. La depresión y la epilepsia son entidades altamente prevalentes y representan un problema de salud pública a nivel mundial. Desarrollo. Realizamos una búsqueda no sistemática en PubMed (MEDLINE) acerca de los conceptos fisiopatológicos y clínicos y las estrategias terapéuticas en pacientes con epilepsia y depresión. Resultados y conclusiones. La depresión y la epilepsia tienen una relación bidireccional y comparten algunos sustratos fisiopatológicos. La depresión es la manifestación neuropsiquiátrica más frecuente en la epilepsia; es importante el cribado y el diagnóstico para el manejo oportuno. El tratamiento con la mayoría de los medicamentos antidepresivos no incrementa la frecuencia de crisis, al contrario, se cree que puede incluso ayudar a disminuir el número de crisis de epilepsia. Además, existen otras terapias antidepresivas, como la terapia cognitivo-conductual y terapias con neuromodulación, que también llegan a ser eficaces en la reducción de la frecuencia de las crisis de epilepsia. Sin embargo, la evidencia respecto al tratamiento es limitada y se requiere un mayor número de estudios prospectivos para la caracterización de las estrategias terapéuticas y la creación de guías estandarizadas.

Thirty-day mortality in patients with a proximal femur fracture during the COVID-19 pandemic in Biscay (Basque Country). / [Artículo traducido] Mortalidad a 30 días en pacientes con fractura de fémur proximal durante la pandemia COVID-19 en Vizcaya (País Vasco).

OBJECTIVES: Compare 30-day mortality rate following a proximal femur fracture (PFF) and SARS-CoV-2 infection versus a PFF and no SARS-CoV-2 infection. DESIGN: Retrospective comparative study. SETTING: Three university hospitals in Biscay province (Basque Country, Spain). PATIENTS: 77 patients over 65 years-old with PFF (AO 31-A and 31-B). INTERVENTION: Study conducted between 9 March and 15 April 2020. The COVID-19 group included only patients with SARS-CoV-2 infection, confirmed by a positive RT-PCR test. MAIN OUTCOME MEASUREMENTS: 30-Day mortality rate and risk factors for mortality. RESULTS: Of a total 77 patients, 10 were diagnosed with SARS-CoV-2 infection. Mean age was 85 years. Patients with SARS-CoV-2 infection had higher BMI (29.53 kg/m2) compared to patients without infection (24.09 kg/m2) (p = 0.001). No significant differences were found between both groups in terms of the Charlson Comorbidity Index, ASA score, use of oral anticoagulants or presence of cognitive impairment. Seven of the 10 patients in the COVID-19 group developed (viral) pneumonia, as compared to one single case (1/67) of (bacterial) pneumonia in the control group (p < 0.001). Thirty-days mortality was higher (p = 0.03) in COVID-19 patients (40%) than in those in the control group (11.9%). In the multivariate analysis, age ≥ 91 years-old, ASA class IV and BMI > 25 kg/m2 were significant predictors of 30-day mortality. All deaths in the COVID-19 group occurred while the patients were hospitalized. CONCLUSIONS: SARS-CoV-2 infection in patients with a PFF was seen to result in higher rates of early mortality, with COVID-19-related pneumonia being the leading direct cause of mortality. LEVEL OF EVIDENCE: Level III study.

Thirty-day mortality in patients with a proximal femur fracture during the COVID-19 pandemic in Biscay (Basque Country).

Objectives: Compare 30-day mortality rate following a proximal femur fracture (PFF) and SARS-CoV-2 infection versus a PFF and no SARS-CoV-2 infection. Design: Retrospective comparative study. Setting: Three university hospitals in Biscay province (Basque Country, Spain). Patients: 77 patients over 65 years-old with PFF (AO 31-A and 31-B). Intervention: Study conducted between 9 March and 15 April 2020. The COVID-19 group included only patients with SARS-CoV-2 infection, confirmed by a positive RT-PCR test. Main outcome measurements: 30-day mortality rate and risk factors for mortality. Results: Of a total 77 patients, 10 were diagnosed with SARS CoV-2 infection. Mean age was 85 years. Patients with SARS-Cov-2 infection had higher BMI (29.53 kg/m2) compared to patients without infection (24.09 kg/m2) (p = 0.001). No significant differences were found between both groups in terms of the Charlson Comorbidity Index, ASA score, use of oral anticoagulants or presence of cognitive impairment. Seven of the 10 patients in the COVID-19 group developed (viral) pneumonia, as compared to one single case (1/67) of (bacterial) pneumonia in the control group (p < 0.001). Thirty-days mortality was higher (p = 0.03) in COVID-19 patients (40%) than in those in the control group (11.9%). In the multivariate analysis, age ≥91 years-old, ASA class IV and BMI >25 kg/m2 were significant predictors of 30-day mortality. All deaths in the COVID-19 group occurred while the patients were hospitalized. Conclusions: SARS CoV-2 infection in patients with a PFF was seen to result in higher rates of early mortality, with COVID-19-related pneumonia being the leading direct cause of mortality.

Objetivos: Comparar la tasa de mortalidad a 30 días en los pacientes con fractura de fémur proximal (FFP) y coinfección por SARS-CoV-2 frente a FFP sin coinfección. Diseño: Estudio retrospectivo comparativo. Escenario: Tres hospitales universitarios en Vizcaya (País Vasco, España). Pacientes: Setenta y siete pacientes mayores de 65 años con FFP (AO 31-A y 31-B). Intervención: Entre el 9 de marzo y el 15 de abril de 2020. El grupo COVID-19 incluía pacientes con infección confirmada mediante el test PCR-RT. Medidas de resultados principales: Tasa de mortalidad a 30 días y factores de riesgo de mortalidad. Resultados: Diez de los 77 pacientes presentaron coinfección por SARS-CoV-2. La edad media fue de 85 años. Los pacientes infectados presentaban un IMC mayor (29,53 kg/m2) frente a los no infectados (24,09 kg/m2) (p = 0,001). No hubo diferencias significativas en el índice de comorbilidad de Charlson, la puntuación ASA, el uso de anticoagulantes o el deterioro cognitivo. Siete pacientes del grupo COVID-19 (7/10) desarrollaron neumonía (vírica), frente a un solo caso (1/67) de neumonía (bacteriana) en el grupo control (p < 0,001). La mortalidad a 30 días fue mayor (p = 0,03) en los pacientes con COVID-19 (40%) que en el grupo control (11,9%). La edad ≥ 91 años, la clase IV ASA y el IMC > 25 kg/m2 fueron predictores significativos de mortalidad a 30 días. Todas las muertes en el grupo COVID-19 ocurrieron intrahospitalariamente. Conclusiones: La infección por SARS-CoV-2 en pacientes con PFF resultó en tasas más altas de mortalidad temprana, siendo la neumonía por COVID-19 la principal causa directa de mortalidad.Nivel de evidencia: Estudio nivel III.

[Perineal endometriosis with anal external sphincter involvement: a case-report]. / Endometrioma perianal involucrando esfínter anal externo: reporte de un caso.

The presence of perianal endometriosis involving the anal sphincter is a rare presentation of this disease, most cases are diagnosed late and few are reported in the literature despite the number of episiotomies performed today. We present a case in a female with perianal symptoms after an episiotomy 15 years ago and visualized by endoanal ultrasound. We also review the literature of this condition. The treatment of choice is wide excision of the lesion involving the anal sphincter so the sphincter defect should be repaired by sphincteroplasty. According to the literature, early diagnosis by clinical suspicion and confirmation by endoanal ultrasound, with wide excision of endometrioma gives satisfactory results regarding anal continence.

Numerical Estimation and Mathematical Learning Methodology in Preschoolers.

One of the means for representing quantities/magnitudes is the mental number line. It is still a nonsolved question as to whether the method of learning mathematics in the early years could improve this type of estimating. A total of 233 students, aged four and five years, who learned mathematics with a new method called Open Algorithm Based on Number or the more traditional Closed Based on Ciphers approach, were evaluated with a reliable estimation on the number line test. Results revealed significant differences in participants' estimation functions based on the learning method used. Students who learned mathematics through the Open Algorithm Based on Number method used a linear representation more efficiently than those who were taught with the Closed Based on Ciphers methodology. This group exhibited a logarithmic function in their approach. We discussed whether these differences can be attributed to a recurrent practice in estimation tasks at school, characterized by the Open Algorithm Based on Number methodology.

Good outcomes with mycophenolate-cyclosporine-based induction protocol in children with severe proliferative lupus nephritis.

The outcomes of children with severe proliferative lupus nephritis (LN) were examined using a new mycophenolate and cyclosporine-based (MMF-CSA) induction protocol. Sixteen children with LN (WHO class III and IV), 31.3% of whom required dialysis at induction, were retrospectively studied. Median MMF dose was 942 mg/m( 2)/day. Thirteen patients (81%) with persistent proteinuria received CSA. Clinical and laboratory parameters were compared at pre-induction, 6 and 12 months. Treatment outcome was defined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal function, haematuria, proteinuria and serological markers (complements C3, C4 and anti-dsDNA). Comparing these parameters at induction, 6 months and 12 months, respectively, SLEDAI (25.4 +/- 8.7 versus 3.2 +/- 2.9 versus 2.9 +/- 2.8), serum C3 (47 +/- 21 versus 107 +/- 27 versus 111 +/- 38 mg/dl), C4 (12 +/- 14 versus 23 +/- 14 versus 22 +/- 11 mg/dl) and urine protein (6.97 +/- 7.09 versus 0.98 +/- 1.56 versus 0.21 +/- 0.13 g/ day/1. 73 m(2)) improved significantly (p < 0.05). Anti-dsDNA titres decreased in 73% by 6 and 12 months (p < 0.05). Complete renal remission was achieved in 7/16 (43.8%) at 6 months and 12/16 (75%) at 12 months, the rest achieving partial remission with no treatment failures. In conclusion, a combination MMF-CSA protocol is an effective therapeutic alternative for induction of children with severe proliferative LN, resulting in significant clinical and serological improvement with minimal adverse effects.

Oxcarbazepine monotherapy in carbamazepine-unresponsive trigeminal neuralgia.

The objective of this prospective open-label study was to evaluate the efficacy and tolerability of oxcarbazepine in trigeminal neuralgia (TN) unresponsive to treatment with the standard antiepileptic drug, carbamazepine. Thirty-five patients with idiopathic TN, who underwent treatment with oxcarbazepine monotherapy for at least 12 weeks, were studied. Pain was assessed using mean pain frequency, responder rate, pain-free patients and clinical global impression. The mean maintenance dose was 773.7 mg/day. There was a significant decrease in the mean of the main scores following 12 weeks of treatment (p<0.05) compared with baseline. Oxcarbazepine was effective from the first month of treatment. There was a significant reduction in pain frequency, leading to improvements in patient satisfaction. In general, oxcarbazepine was well tolerated. Oxcarbazepine appears to be an important alternative therapeutic approach for patients affected by TN. This study adds to the existing literature arriving at the same findings.

[Topiramate in comorbid disorders: epilepsy and migraine]. / Topiramato en enfermedades comórbidas: epilepsia y migraña.

INTRODUCTION: With relative frequency epilepsy and migraine are associated in a same patient. Some times it is difficult to distinguish an attack of others. Reason why it would be of utility to have a treatment effective in both pathologies. It is tried to study in patients with this comorbidity, how of effective it is a drug indicated in the two pathologies, as it is topiramate. PATIENTS AND METHODS: An observational, longitudinal and prospective study is made, where 15 patients are recruited with this association, and which they were treated with topiramate. They are revaluated at three and six months of treatment. RESULTS: Significant differences are obtained (p < 0.05) in all the studied variables (severity and duration of the migraine attacks and frequency of the migraine and epileptic attacks), with a medium dose of 100 mg/day of topiramate, at the end of the study. Not serious adverse effects were observed. CONCLUSIONS: Topiramate in monotherapy seems to be a suitable treatment in patients who undergo epileptic and migrainous attacks jointly.

Mexiletine. Long-term efficacy and side effects in patients with chronic drug-resistant potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy of mexiletine hydrochloride (Mexitil) was evaluated in 100 patients with potentially lethal and drug-resistant ventricular arrhythmia. The efficacy of arrhythmia suppression was assessed by Holter monitoring. The overall arrhythmia suppression of ventricular premature contractions of 70% and greater was low and seen in only 22% of patients, with an additional 16% responding to a combination of mexiletine and an additional antiarrhythmic drug. The suppression of high-grade forms, couplets of 90% and greater, and complete abolition of nonsustained runs of ventricular tachycardia was achieved in 22% of patients, with 9% responding to the addition of another antiarrhythmic agent. Ventricular premature contractions, couplets, and nonsustained ventricular tachycardia were suppressed in only 16% of the cohort. The drug was poorly tolerated, with intolerable side effects developing in 49% of patients receiving mexiletine alone and in 57% of patients receiving a combination of antiarrhythmic agents. Tolerable adverse effects were relatively common but transient and dose related.

In vitro assessment of the genotoxicity of ethyl paraoxon in newborns and adults.

This in vitro experiment measured the genotoxic effects of ethyl paraoxon, the active metabolite of ethyl parathion. To assess genotoxicity, we used the micronuclei (MN) technique by blocking cytokinesis, and the 'comet' assay. We cultured peripheral blood samples from healthy adults and umbilical cord blood samples from four clinically healthy newborns to identify the frequency of MN. After 48 hours, we added the following ethyl paraoxon concentrations to the cultures: 0.0, 0.075, 0.100, 0.160, and 0.200 microg/mL. For the comet assay, following Singh's technique, we treated the blood samples for 2 hours with similar doses of the metabolite. The comet assay results, at a concentration of 0.075 microg/mL, showed that ethyl paraoxon causes a greater DNA migration that followed a dose-response pattern, a greater intensity being observed in lymphocytes from newborns. A comparison of the treatment and control groups indicated that only the 0.200 microg/mL concentration produced a slight increase in MN. In conclusion, our study identified primary DNA damage due to ethyl paraoxon, with a major effect on newborn lymphocytes, as well as an effect on the frequency of MN in the study groups at high concentrations only.

Long-term efficacy and toxicity of high- and low-dose amiodarone regimens.

Amiodarone is an effective antiarrhythmic drug for the control of potentially lethal and lethal ventricular arrhythmias (VA). In the United States, a high-dose regimen has been used at the expense of a high toxicity profile for the control of lethal VAs. Significant antiarrhythmic efficacy has also been established with low-dose regimens, which carry a low rate of intolerable side effects (5.4%) when compared with the high-dose regimen (16.7%). The high incidence of tolerable and intolerable adverse side effects is probably related to high amiodarone loading (31.92 g) and maintenance doses (520 mg/d). In contrast, the low-dose regimen uses much lower loading (7.2 g) and maintenance (280 mg/d) doses.

Potentially lethal ventricular arrhythmias: from mundane to esoteric.

Patients with potentially lethal ventricular arrhythmias (VAs) represent a heterogenous group with frequent and high grade ventricular arrhythmias (including couplets and runs of nonsustained ventricular tachycardia), structural heart disease and decreased left ventricular function. This is a group at intermediate risk of sudden death, with risks varying from 10% to 38%. The electrical and mechanical risks of patients with potentially lethal VA is discussed in relation to their ability of promoting sudden death. The studies reviewing the impact of antiarrhythmic treatment on survival of patients with potentially lethal VA is discussed.

Long-term efficacy, safety and survival of patients with potentially lethal ventricular arrhythmias treated with low-dose amiodarone.

The effect of low-dose amiodarone was prospectively evaluated in 110 patients with potentially lethal ventricular arrhythmias and structural heart disease. The patient population had frequent and high-grade ventricular premature complexes (VPCs) (greater than or equal to 39/h) (multifocal, couplets, nonsustained ventricular tachycardia) refractory to conventional antiarrhythmic drugs. All patients had structural heart disease (coronary artery disease in 61%) and also a decreased left ventricular ejection fraction (LVEF) (43 +/- 16%). Patients were treated with low-dose amiodarone (maintenance dose of 275 +/- 102 mg/day.) During follow-up over a period of 15 +/- 11.5 months, 24 patients died of cardiac cause and, of these, 13 died of sudden death. Ventricular arrhythmia suppression at 1, 2, 3, and 4 years was 69%, 80%, 78%, 92% for VPCs, respectively; 96%, 90%, 92%, and 98% for couplets, respectively, and 57%, 57%, 97%, and 91% for nonsustained VTs (NVTs), respectively. Intolerable, reversible side effects requiring withdrawal were encountered in 24 patients (22%) (neurologic 10%, gastrointestinal 6.5%, skin 3.7%, proarrhythmic 0.9%, and cardiac 0.9%). Except for keratopathy (less than or equal to grade II) seen in all patients, the tolerable side effects were transient with dose adjustment. The study population was divided into two groups according to LVEF: Group A (LVEF greater than or equal to 40%, mean 54.4 +/- 9.7) and Group B (LVEF less than 40% mean, 27.7 +/- 7.2). The patients were further classified into responders (suppression of at least 70% of VPCs, 90% of couplets, and 100% of NVTs) and nonresponders. The difference in survival between responders and nonresponders in groups A and B was not statistically significant. Cumulative survival at 1, 2, 3, and 4 years was 90%, 85%, 85%, and 85%, respectively. In conclusion, low-dose amiodarone treatment: 1) Is effective in controlling VPCs and its complex forms and maintains long-term arrhythmia suppression. 2) The side effect profile compares favorably with conventional antiarrhythmics; severe side effects associated with high dosages (pulmonary, hepatic, neurologic, etc.) were rare or absent. 3) Amiodarone improves survival of patients with potentially lethal ventricular arrhythmias.

[Quality of life associated with the health of patients with HIV infection measured with the Health Questionnaire SF-36]. / Calidad de vida relacionada con la salud de pacientes infectados por VIH medida por el Cuestionario de Salud SF-36.

OBJECTIVES: The aim of the study was to known the influence of HIV-infection in health related quality of life (HRQL). We have used clinico-immune variables and progression mortality presented by the disease. PATIENTS AND METHODS: From March 1997 through March 1998 a total of 300 HIV-infected patients were carried out the Health Survey SF-36. We included a control group (also 300 patients) who suffered chronic viral hepatitis and potentials risks for the HIV-infection. We calculated the Cronbach s alpha coefficient to measure the reliability. We used clinical and biological data (count of CD4 lymphocytes in periphery blood) to related the IIRQL to the severity of the disease. To decide the progression mortality of the disease it was carried out a continuation along six mouths. RESULTS: The HIV-infected patients had lower punctuations in all dimensions of SF-36 that control group and population values of reference. The values of Cronbach s alpha coefficient are situated up of 0.7 (range 0.75-0.91) in all measurements. The critical phaseAIDS patients (with AIDS diagnosis and/or CD4 lymphocytes < 200 mm3) showed lower punctuations in all measurements except for mental health. Thirty-seven patients (14.2%) displayed new events to AIDS diagnosis and twenty-one died (8.1%). The severe immunodepresion (OR: 4.3; CI 95%: 1.6-11.8), previous AIDS diagnosis (OR: 3.4; CI 95%: 1.48.1), the physical function dimension in the SF-36 (OR: 0.3; CI 95%: 0.1-1.1) and the body pain (OR: 0.2; CI 95%: 0.1-0.8) were predictor factors to the progression-mortality of the disease. CONCLUSIONS: The SF-36 as a measure of the HRQL in HIV-infected population show a high internal consistency, that is able to discriminate patients with severe immunodepression and could help to predict more appropriately the progression of the disease.

Meningoencephalitis: an atypical presentation of herpes simplex type 2 central nervous system infection.

Encephalitis is the best recognized form of central nervous system (CNS) infection with the herpes simplex virus. We present a case of meningoencephalitis with a benign course caused by herpes simplex virus type 2. The patient had no focal abnormalities on either brain magnetic resonance imaging scan or electroencephalogram. The cerebrospinal fluid profile was that of aseptic meningitis, with a lymphocytic pleocytosis. The clinical spectrum of herpes simplex infections in the CNS is broad. Specifically, herpes simplex type 2 can cause a benign meningoencephalitis with scant focal findings, in addition to the known encephalitis and more recently recognized benign recurrent lymphocytic meningitis.

[Management of onychocryptosis in primary care: A clinical case]. / Manejo de la onicocriptosis en atención primaria. Caso clínico.

Onychocryptosis (ingrown toenail) is a condition commonly seen in Primary Care clinics. It is uncomfortable and restrictive for patients and has a high incidence in males between second and third decades of life. It is of unknown origin, with a number of predisposing triggering factors being involved. Treatment depends on the stage of the ingrown nail and the procedures may range from conservative to minor surgery that can be performed by the Primary Care physician in the health centre. We report the case of a 25-year onychocryptosis that did not respond to conservative management, and was extracted with partial matricectomy of the nail.

Determination of the risk of self-ignition of coals and biomass materials.

The safe storage, processing and handling of coals and biomass resources requires their tendency to self-ignite be understood; fires caused by self-ignition have occurred on many occasions in ports and at industrial plants. This work provides information on the tendency of several types of coal and four types of biomass to self-ignite. Data were obtained using the isothermal oven procedure and analyzed using the Frank-Kamenetskii method and a scaling procedure, both contemplated in standard EN15188. The results obtained throw light on the optimum volumes and storage times of the studied materials. The results also validate the methodology followed for determining the risk of self-ignition.