Age and Computed Tomography and Invasive Coronary Angiography in Stable Chest Pain: A Prespecified Secondary Analysis of the DISCHARGE Randomized Clinical Trial.

Importance: The effectiveness and safety of computed tomography (CT) and invasive coronary angiography (ICA) in different age groups is unknown. Objective: To determine the association of age with outcomes of CT and ICA in patients with stable chest pain. Design, Setting, and Participants: The assessor-blinded Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial was conducted between October 2015 and April 2019 in 26 European centers. Patients referred for ICA with stable chest pain and an intermediate probability of obstructive coronary artery disease were analyzed in an intention-to-treat analysis. Data were analyzed from July 2022 to January 2023. Interventions: Patients were randomly assigned to a CT-first strategy or a direct-to-ICA strategy. Main Outcomes and Measures: MACE (ie, cardiovascular death, nonfatal myocardial infarction, or stroke) and major procedure-related complications. The primary prespecified outcome of this secondary analysis of age was major adverse cardiovascular events (MACE) at a median follow-up of 3.5 years. Results: Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 2360 (66.3%) were younger than 65 years, 982 (27.6%) were between ages 65 to 75 years, and 219 (6.1%) were older than 75 years. The primary outcome was MACE at a median (IQR) follow-up of 3.5 (2.9-4.2) years for 3523 patients (99%). Modeling age as a continuous variable, age, and randomization group were not associated with MACE (hazard ratio, 1.02; 95% CI, 0.98-1.07; P for interaction = .31). Age and randomization group were associated with major procedure-related complications (odds ratio, 1.15; 95% CI, 1.05-1.27; P for interaction = .005), which were lower in younger patients. Conclusions and Relevance: Age did not modify the effect of randomization group on the primary outcome of MACE but did modify the effect on major procedure-related complications. Results suggest that CT was associated with a lower risk of major procedure-related complications in younger patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02400229.

Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke.

Ambroxol is a well-known mucolytic expectorant, which has gained much attention in amyotrophic lateral sclerosis, Parkinson's and Gaucher's disease. A specific focus has been placed on ambroxol's glucocerebrosidase-stimulating activity, on grounds that the point mutation of the gba1 gene, which codes for this enzyme, is a risk factor for developing Parkinson's disease. However, ambroxol has been attributed other characteristics, such as the potent inhibition of sodium channels, modification of calcium homeostasis, anti-inflammatory effects and modifications of oxygen radical scavengers. We hypothesized that ambroxol could have a direct impact on neuronal rescue if administered directly after ischaemic stroke induction. We longitudinally evaluated 53 rats using magnetic resonance imaging to examine stroke volume, oedema, white matter integrity, resting state functional MRI and behaviour for 1 month after ischemic stroke onset. For closer mechanistic insights, we evaluated tissue metabolomics of different brain regions in a subgroup of animals using ex vivo nuclear magnetic resonance spectroscopy. Ambroxol-treated animals presented reduced stroke volumes, reduced cytotoxic oedema, reduced white matter degeneration, reduced necrosis, improved behavioural outcomes and complex changes in functional brain connectivity. Nuclear magnetic resonance spectroscopy tissue metabolomic data at 24 h post-stroke proposes several metabolites that are capable of minimizing post-ischaemic damage and that presented prominent shifts during ambroxol treatment in comparison to controls. Taking everything together, we propose that ambroxol catalyzes recovery in energy metabolism, cellular homeostasis, membrane repair mechanisms and redox balance. One week of ambroxol administration following stroke onset reduced ischaemic stroke severity and improved functional outcome in the subacute phase followed by reduced necrosis in the chronic stroke phase.

Occurrence and Severity of Venous Air Embolism During Neurosurgical Procedures: Semisitting Versus Supine Position.

BACKGROUND: At our institution, patients undergoing neurosurgical procedures in the posterior cranial fossa are placed either in the semisitting or in the supine position. The major risk of the semisitting positioning is a venous air embolism (VAE), which may, however, also occur in the supine position. METHODS: In a prospective single-center study with 137 patients, we evaluated the occurrence of VAEs in patients in the supine and in the semisitting position during the period from January 2014 until April 2015. All patients were monitored for VAE by the use of a transesophageal echocardiography (TEE). RESULTS: In total, 50% of the patients experienced a VAE (56% of these patients underwent surgery in the semisitting and 11% in the supine position). In total, 86% of the VAEs were detected by the use of a TEE and did not lead to any changes in the end-expiratory CO2. We only observed VAEs with a decrease in end-expiratory CO2 in the semisitting position. However, none of the patients had any hemodynamic changes due to the VAE. CONCLUSIONS: The semisitting position with TEE monitoring and a standardized protocol is a safe and advantageous technique, taking account of a significant rate of VAEs. VAEs also occur in the supine position, but less frequently.

Treatment of Post-biopsy Arteriovenous Fistula of a Renal Graft by Selective Embolization.

The development of an arteriovenous fistula (AVF) after renal graft biopsy is a rare complication, it is associated in most cases with spontaneous resolution. However, interventional therapies are required in some cases, to prevent graft loss. Selective embolization has been described as an alternative treatment. In the present study, we describes our experience on AVF after biopsy in kidney transplant patients, which was managed with selective embolization. From 2005 to 2015, a total of 452 kidney transplant biopsies were performed, 12 had an AVF requiring embolization. In 92% of cases, this was successful. Beforehand, mean serum creatinine levels were 2.45 mg/dL, after the procedure, that increased to 3.05, however, 3 months later, mean creatinine levels dropped to 1.85 mg/dL. Graft survival after 2 follow-up years was 72%. Our experience demonstrates that selective embolization of the AVF after kidney transplant biopsy is a safe procedure, and that transplant function can be maintained in patients with this complication.

Neurofilament light chain is a cerebrospinal fluid biomarker in hereditary spastic paraplegia.

OBJECTIVE: Despite the need for diagnostics and research, data on fluid biomarkers in hereditary spastic paraplegia (HSP) are scarce. We, therefore, explore Neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of patients with hereditary spastic paraplegia and provide information on the influence of demographic factors. METHODS: The study recruited 59 HSP cases (33 genetically confirmed) and 59 controls matched in age and sex. Neurofilament light chain levels were assessed by enzyme-linked immunosorbent assay. The statistical analysis included the effects of age, sex, and genetic status (confirmed vs. not confirmed). RESULTS: Levels of CSF NfL were significantly increased in patients with hereditary spastic paraplegia compared to controls (median 741 pg/mL vs. 387 pg/mL, p < 0.001). Age (1.4% annual increase) and male sex (81% increase) impacted CSF NfL levels in patients. The age-dependent increase of CSF NfL levels was steeper in controls (2.6% annual increase). Thus, the CSF NfL ratio of patients and matched controls-expressing patients' fold increases in CSF NfL-declined considerably with age. INTERPRETATION: CSF NfL is a reliable cross-sectional biomarker in hereditary spastic paraplegia. Sex is a relevant factor to consider, as male patients have remarkably higher CSF NfL levels. While levels also increase with age, the gap between patients and controls is narrowing in older subjects. This indicates distinct temporal dynamics of CSF NfL in patients with hereditary spastic paraplegia, with a rise around phenotypic conversion and comparatively static levels afterward.

Respuesta al comentario de «Peritonitis asociada a la diálisis peritoneal, 27 años de experiencia en un único centro, Medellín, Colombia» / Response to Comment on "Peritoneal dialysis-related peritonitis: twenty-seven years of experience in a Colombian medical centre"

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Peritoneal dialysis-related peritonitis: twenty-seven years of experience in a Colombian medical center

Peritonitis has been the most common complication of continues ambulatory peritoneal dialysis (CAPD) since it was first implemented, and it remains the leading cause of treatment failure and transfer to other renal replacement therapies. This study presents a Colombian series with a total of 2,469 episodes of peritonitis in 914 patients from a cohort of 1,497 patients on PD, who were followed for almost three decades at a single center. This is the largest Latin American series of patients with PD-related peritonitis. Objective: To describe the CAPD-related peritonitis in a cohort of patients followed for 27 years at a single center, and compare the results with those observed elsewhere in the world. Study Design: Prospective study of incident patients on CAPD from March 1981 to December 2008. Results: In our center, the rate of peritonitis has been steady between 0.8 and 0.9 since 1981 and no significant changes have been noticed in the 27 years of follow up. The rate remains similar to that described nowadays by other large dialysis centers in the world, which have reported significant improvements in recent decades. No significant differences were found in the isolates of gram-positive and gram-negative microorganisms or fungi with respect to those reported by other large series, or in the frequency of culture-negative peritonitis. Conclusion: This study presents the largest Latin American series of patients with CAPD-related peritonitis with a total of 2,469 patients. In this study, the rate of CAPD-related peritonitis remained almost the same during the three decades of observation despite having used three different CAPD systems. Our hypothesis is that the socio-economic conditions of the patients admitted for peritoneal dialysis influences the rate of peritonitis (AU)

Desde que se implementó por primera vez, la peritonitis ha sido la complicación más común de la diálisis peritoneal ambulatoria continua (DPAC) y sigue siendo la causa principal del fracaso del tratamiento y del cambio a otros tratamientos renales sustitutivos. En este estudio se presenta una serie colombiana de un total de 2469 episodios de peritonitis en 914 pacientes de una cohorte de 1497 pacientes en diálisis peritoneal (DP), que fueron sometidos a seguimiento durante casi tres décadas en un único centro. Se trata de la mayor serie de Latinoamérica de pacientes con peritonitis asociada con DP. Objetivo: Describir la peritonitis asociada con la DPAC en una cohorte de pacientes sometidos a seguimiento durante 27 años en un único centro y comparar los resultados con los observados en otras partes del mundo. Diseño del estudio: Estudio prospectivo de pacientes incidentes de DPAC desde marzo de 1981 hasta diciembre de 2008. Resultados: En nuestro centro, la tasa de peritonitis ha permanecido estable entre 0,8 y 0,9 desde 1981 y no se han observado cambios significativos en los 27 años de seguimiento. La tasa es similar a la descrita actualmente por otros grandes centros de diálisis del mundo, que han registrado importantes mejoras en las últimas décadas. No se detectaron diferencias significativas en las muestras aisladas de microorganismos gram positivos o gram negativos u hongos en lo que respecta a los registrados en otras grandes series ni en la frecuencia de peritonitis con cultivo negativo. Conclusión: En este estudio se presenta la mayor serie de Latinoamérica de pacientes con peritonitis asociada con DPAC con un total de 2469 pacientes. La tasa de peritonitis asociada con DPAC permaneció prácticamente inalterable durante las tres décadas de observación, a pesar de haber utilizado tres sistemas diferentes de DPAC. Nuestra hipótesis es que las condiciones socioeconómicas de los pacientes ingresados para diálisis peritoneal influyen en la tasa de peritonitis

Tratamiento exitoso de mucormicosis rino-órbito-cerebral en un paciente trasplantado renal / Successful treatment of rhino-orbital-cerebral mucormycosis in a kidney transplant patient

La mucormicosis rino-órbito-cerebral es una infección micótica potencialmente mortal en los pacientes inmunosuprimidos. Los principales factores de riesgo para adquirirla son la diabetes mellitus mal controlada, la sobrecarga de hierro, la inmunosupresión potente y el uso crónico de esteroides. En esta revisión presentamos el caso de un paciente trasplantado de riñón que, luego del tratamiento de un rechazo agudo con dosis altas de esteroides e inmunosupresión potente con tacrolimus más micofenolato, presentó mucormicosis rino-órbito-cerebral de rápida progresión con necesidad de tratamiento quirúrgico agresivo, suspensión de la inmunosupresión y tratamiento antifúngico potente (AU)

Rhino-orbital-cerebral mucormycosis is a potentially fatal mycotic infection in immunosuppressed patients. The main risk factors for acquiring this infection are poorly controlled diabetes mellitus, iron overload, potent immunosuppression and chronic steroid use. In this review, we present the case of a kidney transplant patient who, after treatment of an acute rejection episode with high doses of steroids and potent immunosuppression with tacrolimus and mycophenolate, presented with rapidly progressing rhino-orbital-cerebral mucormycosis that required aggressive surgical treatment, immunosuppression discontinuation and potent antifungal treatment (AU)

Response to the comment on 'IgM nephropathy in children: clinicopathologic analysis'

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[Successful treatment of rhino-orbital-cerebral mucormycosis in a kidney transplant patient]. / Tratamiento exitoso de mucormicosis rino-órbito-cerebral en un paciente trasplantado renal.

Rhino-orbital-cerebral mucormycosis is a potentially fatal mycotic infection in immunosuppressed patients. The main risk factors for acquiring this infection are poorly controlled diabetes mellitus, iron overload, potent immunosuppression and chronic steroid use. In this review, we present the case of a kidney transplant patient who, after treatment of an acute rejection episode with high doses of steroids and potent immunosuppression with tacrolimus and mycophenolate, presented with rapidly progressing rhino-orbital-cerebral mucormycosis that required aggressive surgical treatment, immunosuppression discontinuation and potent antifungal treatment.

Peritoneal dialysis-related peritonitis: twenty-seven years of experience in a Colombian medical center.

UNLABELLED: Peritonitis has been the most common complication of continues ambulatory peritoneal dialysis (CAPD) since it was first implemented, and it remains the leading cause of treatment failure and transfer to other renal replacement therapies. This study presents a Colombian series with a total of 2,469 episodes of peritonitis in 914 patients from a cohort of 1,497 patients on PD, who were followed for almost three decades at a single center. This is the largest Latin American series of patients with PD-related peritonitis. OBJECTIVE: To describe the CAPD-related peritonitis in a cohort of patients followed for 27 years at a single center, and compare the results with those observed elsewhere in the world. STUDY DESIGN: Prospective study of incident patients on CAPD from March 1981 to December 2008. RESULTS: In our center, the rate of peritonitis has been steady between 0.8 and 0.9 since 1981 and no significant changes have been noticed in the 27 years of follow up. The rate remains similar to that described nowadays by other large dialysis centers in the world, which have reported significant improvements in recent decades. No significant differences were found in the isolates of gram-positive and gram-negative microorganisms or fungi with respect to those reported by other large series, or in the frequency of culture-negative peritonitis. CONCLUSION: This study presents the largest Latin American series of patients with CAPD-related peritonitis with a total of 2,469 patients. In this study, the rate of CAPD-related peritonitis remained almost the same during the three decades of observation despite having used three different CAPD systems. Our hypothesis is that the socio-economic conditions of the patients admitted for peritoneal dialysis influences the rate of peritonitis.

Nefropatía IgM en niños: análisis clinicopatológico / IgM nephropathy in children: clinicopathologic analysis

INTRODUCCIÓN: La nefropatía IgM (NIgM) es una glomerulonefritis caracterizada por depósitos mesangiales difusos de inmunoglobulina M (IgM), que suele manifestarse con proteinuria en rango nefrótico y que, según algunos trabajos previos, se presenta más frecuentemente en pacientes que son resistentes o dependientes del tratamiento con esteroides. OBJETIVO: Realizar una descripción clínica, histológica e inmunopatológica, y evaluar la respuesta al tratamiento esteroideo de los pacientes pediátricos con diagnóstico de síndrome nefrótico y depósitos mesangiales y difusos de IgM. MÉTODOS: Estudio descriptivo, retrospectivo, realizado en dos centros hospitalarios, donde se analizaron los registros clínicos de pacientes pediátricos con diagnóstico de NIgM y se revaluaron los cortes histológicos. RESULTADOS: Trece niños fueron incluidos en el presente estudio. La NIgM correspondió al 5,17 % de todas las biopsias renales pediátricas. La edad de los pacientes estuvo entre 1 y 12 años (mediana: 2 años); el 46,7 % fueron mujeres. El hallazgo morfológico más frecuente fue hipercelularidad mesangial difusa (46,1 %), seguido de glomeruloesclerosis focal y segmentaria (30,8 %) y cambios glomerulares mínimos (23,1 %). Todos los pacientes recibieron esteroides, en 4 de ellos (30,7 %) como el único medicamento inmunosupresor; 3 (23,1 %) recibieron además ciclofosfamida, 5 (38,4 %) micofenolato y 1 (7,7 %) ciclosporina. Siete pacientes (53,8 %) presentaron recaídas frecuentes, 5 (38,5 %) fueron corticorresistentes y 1 (7,7 %) corticodependiente. Dos pacientes (15,38 %) presentaron alteración crónica de la función renal. CONCLUSIÓN: La presencia de IgM mesangial difusa en pacientes pediátricos con síndrome nefrótico no es un hallazgo muy infrecuente, su presentación clínica se ha asociado con menor respuesta a esteroides. Sin embargo, su pronóstico a largo plazo aún no se conoce

INTRODUCTION: IgM nephropathy (IgMN) is a glomerulonephritis characterized by diffuse mesangial deposits of immunoglobulin M (IgM), which usually presents with nephrotic range proteinuria and, according to some previous studies, occurs most often in patients who are resistant or dependent of steroid treatment. AIM: To perform a clinical, histological and inmunopathological description, and assess response to steroid treatment of pediatric patients diagnosed with nephrotic syndrome and diffuse mesangial deposits of IgM. METHODS: This is a descriptive, retrospective study done in two hospitals. Clinical data were taken from medical records. All the slides with the histologic sections were re-evaluated. RESULTS: thirteen children were included in this study. IgMN corresponded to 5.17% of all pediatric renal biopsies. The age of patients ranged from 1 year to 12 years (median: 2 years), 46,15% were women. The most common morphological finding was diffuse mesangial hypercellularity (46,1%), followed by focal segmental glomerulosclerosis (30,8%) and minimal glomerular changes (23,1%). All patients received steroids, in 4 cases (30,7%) as the only immunosuppressant medication, 3 (23,1%) also received cyclophosphamide, 5 (38,4%) mycophenolate, and 1 (7.7%) cyclosporine. Seven patients (53,8%) had frequent relapses, 5 (38.5%) were cortico-resistant, and 1 (7.7%) corticodependent. Two patients (15,38%) had chronic impairment of renal function. CONCLUSION: The presence of diffuse mesangial IgM in pediatric patients with nephrotic syndrome is not a too uncommon finding, the clinical presentation has been associated with lower response to steroids, but their longterm prognosis is still unknown

IgM nephropathy in children: clinicopathologic analysis.

INTRODUCTION: IgM nephropathy (IgMN) is a glomerulonephritis characterised by diffuse mesangial immunoglobulin M (IgM) deposits. It usually presents with nephrotic range proteinuria and, according to some previous work, it occurs most often in patients who are resistant to or dependent on steroid treatment. OBJECTIVE: To perform a clinical, histological and immunopathological description and assess the response to steroid treatment of paediatric patients diagnosed with nephrotic syndrome and diffuse mesangial IgM deposits. METHOD: This is a descriptive, retrospective study carried out in two hospitals, where the clinical records of paediatric patients with IgMN were analysed and the histological sections were re-assessed. RESULTS: thirteen children were included in this study. IgMN corresponded to 5.17% of all paediatric renal biopsies. The age of patients ranged from 1 year to 12 years (median: 2 years), 46.7% were women. The most common morphological finding was diffuse mesangial hypercellularity (46.1%), followed by focal segmental glomerulosclerosis (30.8%) and minimal glomerular changes (23.1%). All patients received steroids; in 4 cases (30.7%) as the only immunosuppressant medication, 3 (23.1%) also received cyclophosphamide, 5 (38.4%) mycophenolate, and 1 (7.7%) cyclosporine. Seven patients (53.8%) had frequent relapses, 5 (38.5%) were cortico-resistant and 1 (7.7%) cortico-dependent. Two patients (15.38%) had chronic impairment of renal function. CONCLUSION: The presence of diffuse mesangial IgM in paediatric patients with nephrotic syndrome is not a very uncommon finding; its clinical presentation has been associated with lower response to steroids. However, the long-term prognosis of these patients is still unknown.