Epidemiological and clinical description of patients with oropharyngeal cancer treated in a public oncology referral hospital in Chile.

Introduction: The incidence of squamous carcinoma of the oropharynx (OPSCC) has presented an increase worldwide, a fact that occurs along with a phenomenon of epidemiological transition, whose pathogenesis is linked to human papilloma virus (HPV) in a significant part of the cases. Published evidence at the Latin American level is scarce. The present study aims to evaluate the epidemiological and clinical characteristics of patients with oropharyngeal cancer treated in a public oncology reference centre in Chile. Methodology: A cross-sectional study was carried out. Patients with histological confirmation of OPSCC aged 18 years or older, referred to the National Cancer Institute of Chile between 2012 and 2023 were included. The association with HPV was determined by immunohistochemistry for p16. Results: 178 patients were analysed, most of them in locoregionally advanced stages involving the palatine tonsil. Seventy-seven percent were male, with a median age of 60 years. Sixty-seven percent of patients were positive for p16, with a progressive increase to 85% in the last 2 years of the study. The p16(+) patients were younger and had fewer classical risk factors. Primary treatment was radiotherapy in 94% of patients. Conclusion: The epidemiological profile of patients with OPSCC treated in a Chilean public oncology referral centre reflects the epidemiological transition observed in developed countries. This change justifies the need to adapt health policies and conduct research that considers the characteristics of this new epidemiological profile.

Tic-Tac: A Translational Approach in Mechanisms Associated with Irregular Heartbeat and Sinus Rhythm Restoration in Atrial Fibrillation Patients.

Atrial fibrillation (AF) is a prevalent cardiac condition predominantly affecting older adults, characterized by irregular heartbeat rhythm. The condition often leads to significant disability and increased mortality rates. Traditionally, two therapeutic strategies have been employed for its treatment: heart rate control and rhythm control. Recent clinical studies have emphasized the critical role of early restoration of sinus rhythm in improving patient outcomes. The persistence of the irregular rhythm allows for the progression and structural remodeling of the atria, eventually leading to irreversible stages, as observed clinically when AF becomes permanent. Cardioversion to sinus rhythm alters this progression pattern through mechanisms that are still being studied. In this review, we provide an in-depth analysis of the pathophysiological mechanisms responsible for maintaining AF and how they are modified during sinus rhythm restoration using existing therapeutic strategies at different stages of clinical investigation. Moreover, we explore potential future therapeutic approaches, including the promising prospect of gene therapy.

Neuro-Sjögren: A clinical-radiological paradox affecting the central nervous system.

Neurological manifestations can occur in up to 67% of patients with primary Sjögren's Syndrome, also known as Neuro-Sjogren's syndrome (NSS), and a 5% can present central nervous system involvement, with severe and possibly lethal consequences. We present the radiological follow-up of a patient with NSS who consulted for limb weakness and visual loss, and fourteen years later developed sicca symptoms. She was diagnosed with a saliva gland biopsy, and started treatment with steroids, cyclophosphamide, and then rituximab, achieving a favourable clinical response and stabilization of lesions. We discuss key aspects regarding the clinical presentation, diagnosis, imaging, and treatment of this elusive disease.

High Plasma Levels of Fibroblast Growth Factor 23 Are Associated with Increased Risk of COVID-19 in End-Stage Renal Disease Patients on Hemodialysis: Results of a Prospective Cohort.

End-stage renal disease (ESRD) patients are a population with high rates of COVID-19 and mortality. These patients present a low response to anti-SARS-CoV-2 immunization, which is associated with immune dysfunction. ESRD patients also present high plasma titers of Fibroblast Growth Factor 23 (FGF23), a protein hormone that reduces immune response in vivo and in vitro. Increased FGF23 levels associate with higher infection-related hospitalizations and adverse infectious outcomes. Thus, we evaluated whether ESRD patients with high FGF23 titers have an increased rate of SARS-CoV-2 infection. METHODS: We performed a prospective cohort of ESRD patients in hemodialysis who had measurements of plasma intact FGF23 in 2019. We determined COVID-19 infections, hospitalizations, and mortality between January 2020 and December 2021. RESULTS: We evaluated 243 patients. Age: 60.4 ± 10.8 years. Female: 120 (49.3%), diabetes: 110 (45.2%). During follow-up, 45 patients developed COVID-19 (18.5%), 35 patients were hospitalized, and 12 patients died (mortality rate: 26.6%). We found that patients with higher FGF23 levels (defined as equal or above median) had a higher rate of SARS-CoV-2 infection versus those with lower levels (18.8% versus 9.9%; Hazard ratio: 1.92 [1.03-3.56], p = 0.039). Multivariate analysis showed that increased plasma FGF23 was independently associated with SARS-CoV-2 infection and severe COVID-19. DISCUSSION: Our results suggest that high plasma FGF23 levels are a risk factor for developing COVID-19 in ESRD patients. These data support the potential immunosuppressive effects of high circulating FGF23 as a factor implicated in the association with worse clinical outcomes. Further data are needed to confirm this hypothesis.

Pearls & Oy-sters: Managing Cholesterol in a Patient With Statin Intolerance Due to Anti-HMG-CoA Reductase-Associated Myopathy.

Statins are the first line of treatment for hypercholesterolemia and of prevention of atherosclerotic cardiovascular disease (ASCVD). It is estimated that one in four Americans over the age of 40 years use statins. In rare cases patients may develop an autoimmune myopathy associated with antibodies against 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Anti-HMGCR associated myopathy requires immediate discontinuation of statins plus initiation of immunosuppressive therapy. Suspension of statin treatment worsens low-density lipoprotein-cholesterol (LDL-C) control, leading to an increased risk of ASCVD and necessitating commencement of another treatment for dyslipidemia. Unfortunately, the management of dyslipidemia in these patients is still unclear. Herein, we describe the case of a 65-year-old woman with dyslipidemia treated with atorvastatin, who consulted for long-standing muscle pain associated with symmetrical proximal weakness. Laboratory tests showed elevated levels of creatine kinase and anti-HMGCR antibodies. She was diagnosed with an anti-HMGCR associated myopathy and was successfully treated with corticosteroids and azathioprine as immunosuppressive therapy, followed by ezetimibe for LDL-C reduction. We present key findings for early recognition and treatment of anti-HMGCR associated myopathy and give recommendations on how to manage hypercholesterolemia in a patient with statin intolerance due to this disease.

LAPAROSCOPIC REDO FUNDOPLICATION ALONE, REDO NISSEN FUNDOPLICATION, OR TOUPET FUNDOPLICATION COMBINED WITH ROUX-EN-Y DISTAL GASTRECTOMY FOR TREATMENT OF FAILED NISSEN FUNDOPLICATION.

BACKGROUND: Laparoscopic Nissen fundoplication fails to control the gastroesophageal reflux in almost 15% of patients, and most of them must be reoperated due to postoperative symptoms. Different surgical options have been suggested. AIMS: This study aimed to present the postoperative outcomes of patients submitted to three different procedures: redo laparoscopic Nissen fundoplication alone (Group A), redo laparoscopic Nissen fundoplication combined with distal gastrectomy (Group B), or conversion to laparoscopic Toupet combined with distal gastrectomy with Roux-en-Y gastrojejunostomy (Group C). METHODS: This is a prospective study involving 77 patients who were submitted initially to laparoscopic Nissen fundoplication and presented recurrence of gastroesophageal reflux after the operation. They were evaluated before and after the reoperation with clinical questionnaire and objective functional studies. After reestablishing the anatomy of the esophagogastric junction, a surgery was performed. None of the patients were lost during follow-up. RESULTS: Persistent symptoms were observed more frequently in Group A or B patients, including wrap stricture, intrathoracic wrap, or twisted fundoplication. In Group C, recurrent symptoms associated with this anatomic alteration were infrequently observed. Incompetent lower esophageal sphincter was confirmed in 57.7% of patients included in Group A, compared to 17.2% after Nissen and distal gastrectomy and 26% after Toupet procedure plus distal gastrectomy. In Group C, despite the high percentage of patients with incompetent lower esophageal sphincter, 8.7% had abnormal acid reflux after surgery. CONCLUSIONS: Nissen and Toupet procedures combined with Roux-en-Y distal gastrectomy are safe and effective for the management of failed Nissen fundoplication. However, Toupet technique is preferable for patients suffering from mainly dysphagia and pain.

Humoral Immune Response of BNT162b2 and CoronaVac Vaccinations in Hemodialysis Patients: A Multicenter Prospective Cohort.

The CoronaVac vaccine is the most used anti-SARS-CoV-2 vaccine worldwide. Previous data indicate that this vaccine produces a lower immune response than RNA vaccines such as BNT162b2. End-stage renal disease (ESRD) patients have an increased rate of COVID-19 and a reduced immune response to vaccinations. Currently, there is little data on this population's immune response induced by CoronaVac. Methods: This study involved a prospective cohort of ESRD patients in chronic hemodialysis who received a two-dose immunization scheme of either CoronaVac (Sinovac Biotech) or BNT162b2 vaccines (Pfizer-BioNTech). We measured the plasma levels of anti-SARS-CoV-2 IgG antibodies. We determined antibody titers before immunization, 2 and 4 months after two doses, plus 4 months after a booster dose. Results: We evaluated 208 patients in three hemodialysis centers. The mean age was 62.6 ± 15.6 years, of whom 91 were female (41.75%). Eighty-one patients (38.94%) received the BNT162b2 vaccine and 127 (61.06%) received the CoronaVac vaccine. Patients who received the BNT162b2 vaccine had a higher humoral response compared to those who received the CoronaVac vaccine (4 months after the second dose: BNT162b2: 88.89%, CoronaVac: 51.97%, p < 0.001; 4 months after the booster: BNT162b2: 98.77%, CoronaVac: 86.61%, p < 0.001). Conclusions: Our results suggest that the CoronaVac vaccine induced a lower humoral response than the BNT162b2 vaccine in ESRD patients on hemodialysis.

Clinical Efficacy of SARS-CoV-2 Vaccination in Hemodialysis Patients.

Introduction: The COVID-19 pandemic is a global public health problem. Patients with end-stage renal disease on hemodialysis are at a higher risk of infection and mortality than the general population. Worldwide, a vaccination campaign has been developed that has been shown to reduce severe infections and deaths in the general population. However, there are currently limited data on the clinical efficacy of vaccinations in the hemodialysis population. Methods: A national multicenter observational cohort was performed in Chile to evaluate the clinical efficacy of anti-SARS-CoV-2 vaccination in end-stage renal disease patients on chronic hemodialysis from February 2021 to August 2021. In addition, the BNT162b2 (Pfizer-BioNTech) and CoronaVac (Sinovac) vaccines were evaluated. The efficacy of vaccination in preventing SARS-CoV-2 infection, hospitalizations, and deaths associated with COVID-19 was determined. Results: A total of 12,301 patients were evaluated; 10,615 (86.3%) received a complete vaccination (2 doses), 490 (4.0%) received incomplete vaccination, and 1196 (9.7%) were not vaccinated. During follow-up, 1362 (11.0%) patients developed COVID-19, and 150 died (case fatality rate: 11.0%). The efficacy of the complete vaccination in preventing infection was 18.1% (95% confidence interval [CI]:11.8-23.8%), and prevention of death was 66.0% (95% CI:60.6-70.7%). When comparing both vaccines, BNT162b2 and CoronaVac were effective in reducing infection and deaths associated with COVID-19. Nevertheless, the BNT162b2 vaccine had higher efficacy in preventing infection (42.6% vs. 15.0%) and deaths (90.4% vs. 64.8%) compared to CoronaVac. Conclusion: The results of our study suggest that vaccination against SARS-CoV-2 in patients on chronic hemodialysis was effective in preventing infection and death associated with COVID-19.

New Opportunities in Heart Failure with Preserved Ejection Fraction: From Bench to Bedside and Back.

Heart failure with preserved ejection fraction (HFpEF) is a growing public health problem in nearly 50% of patients with heart failure. Therefore, research on new strategies for its diagnosis and management has become imperative in recent years. Few drugs have successfully improved clinical outcomes in this population. Therefore, numerous attempts are being made to find new pharmacological interventions that target the main mechanisms responsible for this disease. In recent years, pathological mechanisms such as cardiac fibrosis and inflammation, alterations in calcium handling, NO pathway disturbance, and neurohumoral or mechanic impairment have been evaluated as new pharmacological targets showing promising results in preliminary studies. This review aims to analyze the new strategies and mechanical devices, along with their initial results in pre-clinical and different phases of ongoing clinical trials for HFpEF patients. Understanding new mechanisms to generate interventions will allow us to create methods to prevent the adverse outcomes of this silent pandemic.

Laparoscopic redo fundoplication alone, redo nissen fundoplication, or toupet fundoplication combined with roux-en-y distal gastrectomy for treatment of failed nissen fundoplication / Refazer fundoplicatura laparoscópica, refazer fundoplicatura a nissen ou toupet combinada com gastrectomia distal em y-roux para tratamento de recidiva após fundoplicatura a nissen

ABSTRACT BACKGROUND: Laparoscopic Nissen fundoplication fails to control the gastroesophageal reflux in almost 15% of patients, and most of them must be reoperated due to postoperative symptoms. Different surgical options have been suggested. AIMS: This study aimed to present the postoperative outcomes of patients submitted to three different procedures: redo laparoscopic Nissen fundoplication alone (Group A), redo laparoscopic Nissen fundoplication combined with distal gastrectomy (Group B), or conversion to laparoscopic Toupet combined with distal gastrectomy with Roux-en-Y gastrojejunostomy (Group C). METHODS: This is a prospective study involving 77 patients who were submitted initially to laparoscopic Nissen fundoplication and presented recurrence of gastroesophageal reflux after the operation. They were evaluated before and after the reoperation with clinical questionnaire and objective functional studies. After reestablishing the anatomy of the esophagogastric junction, a surgery was performed. None of the patients were lost during follow-up. RESULTS: Persistent symptoms were observed more frequently in Group A or B patients, including wrap stricture, intrathoracic wrap, or twisted fundoplication. In Group C, recurrent symptoms associated with this anatomic alteration were infrequently observed. Incompetent lower esophageal sphincter was confirmed in 57.7% of patients included in Group A, compared to 17.2% after Nissen and distal gastrectomy and 26% after Toupet procedure plus distal gastrectomy. In Group C, despite the high percentage of patients with incompetent lower esophageal sphincter, 8.7% had abnormal acid reflux after surgery. CONCLUSIONS: Nissen and Toupet procedures combined with Roux-en-Y distal gastrectomy are safe and effective for the management of failed Nissen fundoplication. However, Toupet technique is preferable for patients suffering from mainly dysphagia and pain.

RESUMO RACIONAL: A fundoplicatura de Nissen laparoscópica falha em controlar o refluxo gastroesofágico em quase 15% dos pacientes e a maioria deles deve ser reoperada devido aos sintomas. Diferentes técnicas cirúrgicas têm sido sugeridas. OBJETIVOS: Apresentar os resultados pós-operatórios de pacientes submetidos a 3 procedimentos diferentes: Reoperação e fundoplicatura de Nissen laparoscópica apenas (Grupo A), reoperação e fundoplicatura de Nissen laparoscópica combinado com gastrectomia distal (Grupo B) ou reoperação e conversão para Toupet laparoscópico combinado com gastrectomia distal e reconstrução em Y-Roux (Grupo C). MÉTODOS: estudo prospectivo incluindo 77 pacientes submetidos inicialmente a fundoplicatura de Nissen laparoscópica que apresentaram recidiva do refluxo gastroesofágico após a operação. Eles foram avaliados antes e após a reoperação com questionário clínico e estudos funcionais específicos. Reestabelecida a anatomia da junção esôfago-gástrica, procedeu-se às referidas cirurgias. Nenhum paciente perdeu seguimento. RESULTADOS: Os sintomas persistentes foram observados com maior frequência nos pacientes dos Grupos A ou B, associados à estenose da fundoplicatura, fundoplicatura intratorácico ou fundoplicatura torcida. No Grupo C, os sintomas recorrentes associados a essa alteração anatômica foram observados com pouca frequência. Esfincter esofágico inferior incompetente foi confirmado em 57,7% dos pacientes pertencentes ao Grupo A em comparação com 17,2% após fundoplicatura de Nissen laparoscópica combinado com gastrectomia distal, e 26% após a Toupet laparoscópico combinado com gastrectomia distal e reconstrução em Y-Roux. Nesse grupo, apesar do alto percentual de pacientes com esfincter esofágico inferior incompetente, 8,7% apresentaram refluxo ácido anormal após a cirurgia. CONCLUSÕES: As técnicas de Nissen ou Toupet combinados com a gastrectomia distal em Y de Roux são seguras e eficazes para o manejo da falha da fundoplicatura a Nissen. A técnica de Toupet é preferível para pacientes que sofrem principalmente com disfagia e dor.

Rheumatoid meningitis: report of two cases.

Rheumatoid meningitis (RM) is a rare complication of rheumatoid arthritis (RA). RM mimics many other conditions such as subdural empyema, unsteady gait, focal brain dysfunction, stroke, relapsing-remitting motor signs, headache, neuropsychiatric disorders, seizures, parkinsonism, and meningeal tumors. RM is considered a disease with poor prognosis. However, cases reported in the last decade show a good outcome. We report two cases with a favorable outcome. A 48-year-old man with a three-year history of RA admitted for headache, sensory disturbances, and speech difficulties. Brain magnetic resonance imaging (MRI) showed a left parietal subdural laminar lesion with restricted diffusion and a small left superior frontal acute infarction. A subdural empyema was originally suspected, and antimicrobials were prescribed. A follow-up MRI did not show progression of the subdural lesion and the patient was discharged 14 days after admission without focal deficits. A 44-year-old female patient with two years of seronegative RA was admitted for severe headache, confusion, nausea and vomiting. Brain MRI showed subtle supra and infratentorial leptomeningeal involvement and a left cerebellar acute infarct. A meningoencephalitis due to etanercept was initially thought and treated with dexamethasone. The patient was discharged but had to be admitted again and a new MRI showed a progression of the leptomeningeal involvement. She worsened and required endotracheal intubation. Cyclophosphamide was started and the patient became asymptomatic three months later. We propose that treatment should not be delayed waiting a biopsy when a diagnosis of RM is made and after a cerebrospinal fluid infection has been ruled out.

Surgical resection versus stereotactic radiosurgery on local recurrence and survival for patients with a single brain metastasis: a systematic review and meta-analysis.

BACKGROUND: Brain metastases (BM) are the most frequent intracranial tumours in adults. In patients with solitary BM, surgical resection (SR) or stereotactic radiosurgery (SRS) is performed. There is limited evidence comparing one treatment over the other. OBJECTIVE: To compare SR versus SRS on patients with solitary BMs, regarding local recurrence (LR) and overall survival (OS) conducting a systematic review and meta-analysis. METHODS: Systematic review of literature following PRISMA guidelines, using the databases of Medline, Clinicaltrials.gov, Embase, Web of Science, Sciencedirect, CINAHL, Wiley Online Library, Springerlink and LILACS. Following study selection based on inclusion and exclusion criteria, data extraction and a critical analysis of the literature was performed according to the GRADE scale. For quantitative analysis, a random effects model was used. Data were synthetized and evaluated on a forest plot and funnel plot. RESULTS: Two randomized clinical trials, four cohort studies and one case-control studies met our inclusion criteria for the qualitative analysis. None was excluded subsequently. Overall, 614 patients with single metastasis were included. Studies had high heterogeneity. Multiple significant variables affecting the outcome were signalized. Meta-analysis showed no significant differences for survival (HR, 1.10; 95% CI, 0.75-1.45) or LR (HR, 0.81; 95% CI, 0.42-1.20). CONCLUSIONS: According to current evidence, in patients with a single small metastasis there is no statistically significant difference in OS or LR among the chosen techniques (SR or SRS). Multiple significant co-variables may affect both outcomes. Different outcomes better than OS should be evaluated in further randomized studies.

Rheumatoid meningitis: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Rheumatoid meningitis (RM) is a neurological complication of rheumatoid arthritis (RA). Current evidence is based on case reports and partial reviews. METHODS: This is a systematic review and meta-analysis following the PRISMA statement. The aim is to describe the characteristics of the disease, including clinical, imaging and laboratory findings, treatment, outcomes and prognosis reported in the literature. RESULTS: In all, 103 studies with 130 cases were included. RM affected adults with an average age of 62 years, with or without a previous RA diagnosis. RA activity and time with the disease were associated with a worse prognosis. Most common clinical manifestations were transient focal neurological signs (64.6%), systemic symptoms (51.3%), episodic headache (50.4%) and neuropsychiatric alterations (47.7%). Joint manifestations were present in only 27.4% of cases. Brain magnetic resonance imaging showed unilateral or bilateral involvement, predominantly frontoparietal. Both pachymeninges and leptomeninges were affected, the latter more frequently (82.88%). The laboratory findings included increased levels of rheumatoid factor (89.71%), anti-cyclic citrullinated peptide (89.47%), C-reactive protein (82.54%) and erythrocyte sedimentation rate (81.81%). Cerebrospinal fluid analysis showed an increase in the protein level (76.14%), with pleocytosis (85.19%) of mononuclear predominance (89.19%). Biopsy was performed in 72.52% of the patients. Corticosteroid pulse therapy was the main induction therapy. Disease relapse occurred in 31.17% of patients, whilst 54.54% had a full recovery. CONCLUSIONS: Rheumatoid meningitis must be considered in adult patients with or without RA diagnosis, high-dose corticosteroid induction therapy should be installed and maintenance therapy plays a key role. It is not recommended to use anti-TNF as an induction therapy. Nowadays, RM has a significantly better outcome. These findings may aid clinicians in timely RM diagnosis and treatment, thus improving its outcomes.

Erratum to: Rheumatoid meningitis: report of two cases / Fe de errata: Meningitis reumatoide. Informe de dos casos

Rheumatoid meningitis (RM) is a rare complication of rheumatoid arthritis (RA). RM mimics many other conditions such as subdural empyema, unsteady gait, focal brain dysfunction, stroke, relapsing-remitting motor signs, headache, neuropsychiatric disorders, seizures, parkinsonism, and meningeal tumors. RM is considered a disease with poor prognosis. However, cases reported in the last decade show a good outcome. We report two cases with a favorable outcome. A 48-year-old man with a three-year history of RA admitted for headache, sensory disturbances, and speech difficulties. Brain magnetic resonance imaging (MRI) showed a left parietal subdural laminar lesion with restricted diffusion and a small left superior frontal acute infarction. A subdural empyema was originally suspected, and antimicrobials were prescribed. A follow-up MRI did not show progression of the subdural lesion and the patient was discharged 14 days after admission without focal deficits. A 44-year-old female patient with two years of seronegative RA was admitted for severe headache, confusion, nausea and vomiting. Brain MRI showed subtle supra and infratentorial leptomeningeal involvement and a left cerebellar acute infarct. A meningoencephalitis due to etanercept was initially thought and treated with dexamethasone. The patient was discharged but had to be admitted again and a new MRI showed a progression of the leptomeningeal involvement. She worsened and required endotracheal intubation. Cyclophosphamide was started and the patient became asymptomatic three months later. We propose that treatment should not be delayed waiting a biopsy when a diagnosis of RM is made and after a cerebrospinal fluid infection has been ruled out.

Meningitis reumatoide es una complicación rara de la artritis reumatoide. Esta enfermedad simula varias afecciones neurológicas, como empiema subdural, marcha inestable, accidente cerebrovascular, signos motores recurrentes-remitentes, cefalea, trastornos neuropsiquiátricos, convulsiones, parkinsonismo y tumores de las meninges. Es considerada de mal pronóstico, sin embargo, casos en la última década muestran lo contrario. Informamos dos casos con buen pronóstico. Un hombre de 48 años con tres años de artritis reumatoide ingresado por cefalea, trastornos sensoriales y dificultades del habla. La resonancia magnética (RM) cerebral mostró una lesión laminar subdural parietal izquierda y un pequeño infarto agudo frontal izquierdo. Inicialmente se sospechó un empiema subdural y se trató con antibióticos. Una RM de control no mostró progresión de la lesión subdural y el paciente fue dado de alta 14 días después del ingreso sin déficit focales. Una mujer de 44 años con dos años de artritis reumatoide seronegativa fue ingresada por cefalea, confusión náuseas y vómitos. La RM cerebral mostró un compromiso sutil leptomeníngeo supra e infratentorial y un infarto agudo cerebeloso izquierdo. Inicialmente se consideró una meningoencefalitis debido a etanercept y se trató con dexametasona. Fue dada de alta pero debió ingresar al hospital nuevamente y una nueva RM mostró progresión del compromiso leptomeníngeo. Ella se agravó y requirió intubación endotraqueal. Se inició ciclofosfamida y la paciente se hizo asintomática tres meses después. Proponemos que el tratamiento no debe retrasarse esperando una biopsia de meninges cuando se realiza un diagnóstico clínico de meningitis reumatoide, después de descartar infecciones meníngeas.

Rheumatoid meningitis: report of two cases / Meningitis reumatoide. Informe de dos casos

ABSTRACT Rheumatoid meningitis (RM) is a rare complication of rheumatoid arthritis (RA). RM mimics many other conditions such as subdural empyema, unsteady gait, focal brain dysfunction, stroke, relapsing-remitting motor signs, headache, neuropsychiatric disorders, seizures, parkinsonism, and meningeal tumors. RM is considered a disease with poor prognosis. However, cases reported in the last decade show a good outcome. We report two cases with a favorable outcome. A 48-year-old man with a three-year history of RA admitted for headache, sensory disturbances, and speech difficulties. Brain magnetic resonance imaging (MRI) showed a left parietal subdural laminar lesion with restricted diffusion and a small left superior frontal acute infarction. A subdural empyema was originally suspected, and antimicrobials were prescribed. A follow-up MRI did not show progression of the subdural lesion and the patient was discharged 14 days after admission without focal deficits. A 44-year-old female patient with two years of seronegative RA was admitted for severe headache, confusion, nausea and vomiting. Brain MRI showed subtle supra and infratentorial leptomeningeal involvement and a left cerebellar acute infarct. A meningoencephalitis due to etanercept was initially thought and treated with dexamethasone. The patient was discharged but had to be admitted again and a new MRI showed a progression of the leptomeningeal involvement. She worsened and required endotracheal intubation. Cyclophosphamide was started and the patient became asymptomatic three months later. We propose that treatment should not be delayed waiting a biopsy when a diagnosis of RM is made and after a cerebrospinal fluid infection has been ruled out.

Meningitis reumatoide es una complicación rara de la artritis reumatoide. Esta enfermedad simula varias afecciones neurológicas, como empiema subdural, marcha inestable, accidente cerebrovascular, signos motores recurrentes-remitentes, cefalea, trastornos neuropsiquiátricos, convulsiones, parkinsonismo y tumores de las meninges. Es considerada de mal pronóstico, sin embargo, casos en la última década muestran lo contrario. Informamos dos casos con buen pronóstico. Un hombre de 48 años con tres años de artritis reumatoide ingresado por cefalea, trastornos sensoriales y dificultades del habla. La resonancia magnética (RM) cerebral mostró una lesión laminar subdural parietal izquierda y un pequeño infarto agudo frontal izquierdo. Inicialmente se sospechó un empiema subdural y se trató con antibióticos. Una RM de control no mostró progresión de la lesión subdural y el paciente fue dado de alta 14 días después del ingreso sin déficit focales. Una mujer de 44 años con dos años de artritis reumatoide seronegativa fue ingresada por cefalea, confusión náuseas y vómitos. La RM cerebral mostró un compromiso sutil leptomeníngeo supra e infratentorial y un infarto agudo cerebeloso izquierdo. Inicialmente se consideró una meningoencefalitis debido a etanercept y se trató con dexametasona. Fue dada de alta pero debió ingresar al hospital nuevamente y una nueva RM mostró progresión del compromiso leptomeníngeo. Ella se agravó y requirió intubación endotraqueal. Se inició ciclofosfamida y la paciente se hizo asintomática tres meses después. Proponemos que el tratamiento no debe retrasarse esperando una biopsia de meninges cuando se realiza un diagnóstico clínico de meningitis reumatoide, después de descartar infecciones meníngeas.

Inclusion of the Symbol Digit Modalities Test in a revised assessment of 'no evidence of disease activity-4 (NEDA-4)' in Latin-American patients with multiple sclerosis.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), no evidence of disease activity-3 (NEDA-3) is defined as the absence of: (1) relapses; (2) disability progression; (3) MRI activity (new/enlarged T2 lesions and/or gadolinium-enhanced T1 lesions). NEDA-4 status is defined as meeting all NEDA-3 criteria plus having an annualized percentage brain volume change (a-PBVC) >-0.4%. In individual patients, brain volume assessment is confounded with normal aging, methodological limitations and fluid-shift related fluctuations in brain volume. Cognitive impairment has been proposed as another component that should be integrated into therapeutic algorithms for RRMS. We aim to determine the proportion of patients failing to meet NEDA-4 criteria and to appraise whether the Symbol Digit Modalities Test (SDMT) is capable of replacing a-PBVC as one of the components of NEDA-4. We hypothesize that NEDA-4 has the potential to capture the impact of DMT therapies in RRMS. METHODS: Forty-five patients were prospectively followed 1 and 2 years after their baseline assessment at the University of Chile Hospital. SIENA software was used to assess a-PBVC. RESULTS: At baseline, the patients had a mean age of 33.0 years (range 18-57), disease duration of 1.9 years (0.4-4), Expanded Disability Status Scale score of 1.3 (0-4), and 67% were female. The majority had RRMS (91% while 9% had clinically isolated syndrome (CIS)). Seventy-three percent were on the so-called first line DMTs such as interferons (53%), glatiramer acetate (13%), teriflunomide (9%), and 18% were on fingolimod. There was a serial decline in the proportion of NEDA: after 1 and 2 years of follow-up 60% and 47% met NEDA-3 status, and 38% and 27% met NEDA-4, respectively. At the last follow-up 21% remained on interferons, 47% were now on fingolimod, 4% on alemtuzumab and 2% on natalizumab. At year 1 and year 2, with the replacement of a-PBVC by SDMT, 53% and 40% of patients achieved a putative NEDA-4 status, respectively. CONCLUSION: Brain volumetric MRI has yet to be translated into clinical practice and SDMT may qualify as the fourth component of NEDA-4 definition. NEDA-4 has the potential to capture the impact of DMT therapies in RRMS earlier in the disease course of RRMS.

Chemical Characterization and Enzymatic Control of Stickies in Kraft Paper Production.

Paper recycling has increased in recent years. A principal consequence of this process is the problem of addressing some polymeric components known as stickies. A deep characterization of stickies sampled over one year in a recycled paper industry in México was performed. Based on their chemical structure, an enzymatic assay was performed using lipases. Compounds found in stickies by Fourier-transform infrared spectrometry were poly (butyl-acrylate), dioctyl phthalate, poly (vinyl-acetate), and poly (vinyl-acrylate). Pulp with 4% (w/w) consistency and pH = 6.2 was sampled directly from the mill once macrostickies were removed. Stickies were quantified by counting the tacky macrostructures in the liquid fraction of the pulp using a Neubauer chamber before the paper was made, and they were analyzed with rhodamine dye and a UV lamp. Of the two commercial enzymes evaluated, the best treatment condition used Lipase 30 G (Specialty Enzymes & Biotechnologies Co®, Chino, CA, USA) at a concentration of 0.44 g/L, which decreased 35.59% of stickies. SebOil DG (Specialty Enzymes & Biotechnologies®) showed a stickies reduction of 21.5% when used at a concentration of 0.33 g/L. Stickies in kraft paper processes were actively controlled by the action of lipases, and future research should focus on how this enzyme recognizes its substrate and should apply synthetic biology to improve lipase specificity.

Effect of Laccase-Mediated Biopolymer Grafting on Kraft Pulp Fibers for Enhancing Paper's Mechanical Properties.

High-resistance paper was manufactured by laccase-grafting of carboxymethyl cellulose (CMC) and chitosan (CPX) on Kraft pulp fiber. The reaction was mediated in the presence of laccase by one of the following polyphenols in the presence of air: gallic acid (GA), vanillic acid (VA) and catechol (1,2⁻DHB). Enzyme was added at constant loading (24 kg ton-1), 1% pulp consistency, 0.005% CMC, pH = 6.3 ± 0.5 and 2 mM of mediator. CPX content was assessed at two levels (0% and 0.005%). Treated pulps were analyzed by different mechanical tests (ring crush, mullen, corrugating medium test (CMT) flat crush of corrugating medium test and tension). An improvement in these parameters was obtained by biopolymer coupling and selected mediator. When using GA, three parameters increased more than 40%, while ring crush increased 120%. For the case of VA, properties were enhanced from 74% to 88% when CPX was added. For 1,2⁻DHB, there was not found a statistically significant difference between the results in the presence of CPX. Scanning electron microscopy, confocal microscopy, FTIR and 13C NMR were used in all papers in order to evaluate grafting. Hence, it was possible to correlate polymerization with an improvement of paper's mechanical properties.