Cerebrovascular Complications Associated With Iatrogenic Fungal Meningitis Following Surgical Procedures in Mexico.

BACKGROUND: The current fungal meningitis outbreak caused by contaminated epidural anesthesia with Fusarium solani among patients who underwent surgical procedures in Matamoros, Mexico remains a cause of concern. Its association with an increased susceptibility for cerebrovascular complications (CVC) has not been reported. This single-center study describes 3 patients with a unique pattern of CVC attributed to fungal meningitis. METHODS: A retrospective case series of patients diagnosed with fungal meningitis following surgical procedures under contaminated epidural anesthesia who developed a unique pattern of CVC during their hospitalization. RESULTS: Three female patients (mean age, 35 years) with CVC due to iatrogenic fungal meningitis were included. Positive Fungitell ß-D-glucan assay in cerebrospinal fluid was documented in all cases, and F. solani was confirmed by polymerase chain reaction in case 3. All cases were complicated by severe vertebrobasilar circulation vasculopathy and arterial dissections with resultant subarachnoid hemorrhage and intraventricular hemorrhage, ultimately leading to patients' death. CONCLUSIONS: The death toll from the ongoing fungal meningitis outbreak keeps rising, underscoring the need for early recognition and aggressive treatment. We highlight the risk for vertebrobasilar circulation CVC among these patients. The angioinvasive nature of F. solani is yet to be clarified; however, a clear pattern has been observed. Public health awareness should be raised and a strong response should be pursued.

Minimizing Shivering During Targeted Normothermia: Comparison Between Novel Transnasal and Surface Temperature-Modulating Devices.

BACKGROUND: Shivering is a common adverse effect of achieving and maintaining normothermia in neurocritical care patients. We compared the burden of shivering and shivering-related interventions between a novel transnasal temperature-modulating device (tnTMD) and surface cooling temperature-modulating devices (sTMDs) during the first 24 h of targeted normothermia in mechanically ventilated febrile neurocritical care patients. METHODS: This is a case-control study controlling for factors that impact shiver burden: age, sex, body surface area. All patients underwent transnasal cooling (CoolStat, KeyTech, Inc.) as part of an ongoing multicenter clinical trial (NCT03360656). Patients undergoing treatment with sTMDs were selected from consecutively treated patients during the same time period. Data collected included the following: core body temperature (every 2 h), bedside shivering assessment scale (BSAS) score (every 2 h), and administration of antishivering medication for a BSAS score > 1. Time to normothermia (≤ 37.5 °C), as well as temperature burden > 37.5 °C (°C × h), were compared between groups using Student's t-test for mean differences. The proportion of patients requiring interventions, as well as the number of interventions per patient, was compared using the χ2 test. Significance was determined based on a p value < 0.05. RESULTS: There were 10 tnTMD patients and 30 sTMD patients included in the analysis (mean age: 62 ± 4, 30% women, body surface area = 1.97 ± 0.25). There were no differences between groups in temperature at cooling initiation (tnTMD: 38.5 ± 0.2 °C vs. sTMD: 38.7 ± 0.5 °C, p = 0.3), time to ≤ 37.5 °C (tnTMD: 1.8 ± 1.5 h vs. sTMD: 2.9 ± 1.4 h, p = 0.1), or temperature burden > 37.5 (tnTMD: - 0.4 ± 1.13 °C × h vs. sTMD median [IQR]: - 0.57 ± 0.58 °C × h, p = 0.67). The number of tnTMD patients who received pharmacologic shivering interventions was lower than the number of controls (20 vs. 67%, p = 0.01). tnTMD patients also had fewer shivering interventions per patient (0 [range: 0-3] vs. 4 [range: 0-23], p < 0.001). CONCLUSIONS: A transnasal cooling approach achieved similar time to normothermia and temperature burden with less shivering than surface cooling. This approach may be a feasible option to consider for mechanically ventilated febrile neurocritical care patients.

Cefalea mortal: aneurisma en espejo a propósito de un caso

Introducción: Los aneurismas intracerebrales son hallazgos incidentales en estudios de imágenes realizado por otros diagnósticos. Reporte de Caso: Paciente femenino de 35 años, que presentó sincope después de cefalea de gran intensidad sin ceder a tratamiento convencional de AINES; con antecedente de cefalea de larga data y tratamiento esporádico. Al examen: neurológico: despierta, asimetría facial, disartria, fuerza muscular disminuida en ambos miembros inferiores, no signos meníngeos; el informe tomográfico cerebral sin contraste indicó: lesiones cerebrales expansivas de etiología a determinar a nivel de ambos lados de diencéfalo: descartar glioma vs aneurismas; Angiotac cerebral con contraste, refleja aneurismas de carótida interna intracraneal bilateral y cerebral media (en espejo). Posteriormente la paciente fue evaluada por neurocirujano de turno, quien indica referir a centro de mayor complejidad, por no contar con instrumental necesario para intervención quirúrgica; paciente fallece camino a centro de referencia. Conclusiones: Al ser una patología poco frecuente, no es considerada como una primera opción de sospecha diagnostica tras un evento de cefalea.

Background: Intracerebral aneurysms are incidental findings in imaging studies performed for other diagnoses. Case Report: 35- year-old female patient, who presented syncope after severe headache without yielding to conventional treatment with NSAIDs; with a history of long-standing headache and sporadic treatment. On examination: neurological: awake, facial asymmetry, dysarthria, decreased muscle strength in both lower limbs, no meningeal signs; the brain tomographic report without contrast indicated: expansive brain lesions of etiology to be determined at both sides of the diencephalon: rule out glioma vs aneurysms; cerebral Angiotac with contrast, reflects bilateral intracranial internal carotid and middle cerebral (mirror) aneurysms. Subsequently the patient was evaluated by the neurosurgeon on duty, who indicated to refer to a center of higher complexity, for not having the necessary instruments for surgery; patient died on the way to the referral center. Conclusions: Being a rare pathology, it is not considered as a first option for diagnostic suspicion after a headache event.

Multiple cardiac rhabdomyomas, prenatal diagnosis. Case report / Rabdomiomas cardiacos múltiples, diagnóstico prenatal. Reporte de casos.

Cardiac tumors are rare in children, having a maximum reported incidence of 0.027% in prenatal diagnosis, increasing the incidence in necropsy diagnosis; rhabdomyomas are the most frequent cardiac tumors, some cases are associated with tuberous sclerosis. We present the report of two cases in our unit that were diagnosed prenatal with follow-up after birth and one of them was associated with tuberous sclerosis. Both cases were admitted in a third level center, uncomplicated, without requiring surgical treatment, and could be discharged.

Los tumores cardiacos son raros en la población infantil, teniendo una incidencia máxima reportada del 0.027% en el diagnóstico prenatal, incrementándose la incidencia en el diagnóstico por necropsia. Los rabdomiomas son los tumores cardiacos más frecuentes, algunos casos pueden asociarse con esclerosis tuberosa. Presentamos el reporte de dos casos en nuestra unidad a los cuales se les realizó diagnóstico prenatal con seguimiento posterior al nacimiento y asociándose uno de ellos a esclerosis tuberosa. Ambos casos recibieron atención en un centro de tercer nivel, sin complicaciones, sin requerir tratamiento quirúrgico, pudiendo ser egresados.

The Proportion of Preventable Thrombectomy Procedures with Improved Atrial Fibrillation Stroke Prevention.

BACKGROUND: Large vessel occlusion (LVO) strokes can in part be prevented with better atrial fibrillation (AF) stroke prevention strategies; thus we evaluated the rate of AF in patients presenting with acute LVO strokes undergoing mechanical thrombectomy (MT) and assessed patterns of oral anticoagulant (OAC) use prior to the index stroke. METHODS AND RESULTS: We identified 347 MT cases from February 2015 to September 2018. A retrospective chart review was conducted to identify patient sociodemographics, presence of AF, use of anticoagulation, stroke severity, CHA2DS2-VASc scores, and functional outcomes. AF was present in 161 (46%) cases. Patients with AF were older (mean 76 ± 11 years vs. 66 ± 15 years) and more likely to be female (56% vs. 46%) with higher rates of hypertension, dyslipidemia, heart failure and smoking. Of the 100 patients with known AF, 59 were not on anticoagulation prior to the index stroke. Of 39 patients with known AF on OAC, 57% were not therapeutic on warfarin and 20% were not taking prescribed direct OACs. A total of 72 (21%) thrombectomy cases were performed on patients with known AF who were not effectively anticoagulated. After multivariate adjustments, there was no significant difference in modified Rankin Scale score at discharge, in-hospital mortality, or symptomatic intracranial hemorrhage between the AF and non-AF groups. CONCLUSION: In our study, 21% of patients with LVO stroke had known AF and were not effectively anticoagulated. Improved stroke preventive measures could potentially reduce the occurrence of stroke and avoid unnecessary procedures for patients with AF.

Pain and Other Neurological Symptoms Are Present at 3 Months After Hospitalization in COVID-19 Patients.

COVID-19 is an ongoing pandemic with a devastating impact on public health. Acute neurological symptoms have been reported after a COVID-19 diagnosis, however, the long-term neurological symptoms including pain is not well established. Using a prospective registry of hospitalized COVID-19 patients, we assessed pain and neurological function (including functional, cognitive and psychiatric assessments) of several hospitalized patients at 3 months. Our main finding is that 60% of the patients report pain symptoms. 71% of the patients still experienced neurological symptoms at 3 months and the most common symptoms being fatigue (42%) and PTSD (25%). Cognitive symptoms were found in 12%. Our preliminary findings suggests the importance of investigating long-term outcomes and rationalizes the need for further studies investigating the neurologic outcomes and symptoms of pain after COVID-19.

Severe Neovascular Glaucoma Exacerbation as a Complication of Carotid Artery Stenting: A Case Report.

INTRODUCTION: Neovascular glaucoma (NVG) has been rarely reported as an acute complication of carotid endarterectomy, but there is scant literature available regarding this potential condition following carotid artery stenting (CAS). We present a case of severe worsening of NVG occurring after bilateral CAS with progressive deterioration of vision ultimately leading to blindness. CASE DESCRIPTION: A 66-year-old male with multiple stroke risk factors, bilateral cataract extraction, proliferative diabetic retinopathy of left eye, and nonproliferative diabetic retinopathy of right eye, and prior left eye pars plana vitrectomy presented with episodes of transient right eye vision loss in context of bilateral high-grade internal carotid artery stenoses. He underwent right CAS with subsequent elevation of bilateral intraocular pressures (IOPs) concerning for acute NVG. Over time, the patient had some interval improvement in IOPs and underwent planned left CAS. After the procedure, he again developed elevated IOPs, concerning for acute NVG which eventually led to right eye pars plana vitrectomy for vitreous hemorrhage and refractory IOP elevation. At 6-month follow-up from initial stenting, the patient was blind in both eyes. DISCUSSION: We present a case of recurrent IOP elevations following CAS eventually resulting in bilateral eye blindness. This case is important not only as an illustration of an underrecognized postprocedural CAS complication but also as a demonstration of likely elevated risk of NVG following CAS for patients with other predisposing risk factors for ocular hypertension such as glaucoma, proliferative diabetic retinopathy, prior cataract extraction, and prior pars plana vitrectomy.

Patrones de uso de fármacos antidemencia en un grupo de pacientes de Colombia / Patterns of antidemential drug use in a group of patients from Colombia

Introducción. Los beneficios del manejo farmacológico con medicamentos antidemencia aún no están del todo demostrados, e incluso hay carencia de trabajos que describan su perfil de utilización. El presente trabajo buscó determinar los patrones de prescripción de fármacos antidemencia en una población de Colombia. Pacientes y métodos. Estudio descriptivo de corte transversal. Mediante una base de datos sistematizada de 3,5 millones de afiliados al sistema de salud colombiano, se seleccionó a pacientes con dispensaciones ininterrumpidas de fármacos antidemencia entre agosto y octubre de 2016. Se analizaron variables sociodemográficas, farmacológicas y comedicaciones. Se estimaron los costes de las terapias a partir del precio de referencia de los medicamentos. Resultados. Se identificó a 8.372 pacientes con una edad media de 79,5 ± 8,7 años; el 65,3% (n = 5.471) fueron mujeres. El fármaco más utilizado fue la rivastigmina (69,6%), principalmente en presentación transdérmica, seguida de la memantina (31,4%). En general, la dosis media administrada por día fue inferior a la dosis diaria definida. Solamente 568 pacientes (6,7%) usaron terapia combinada. El 84,3% de los pacientes (n = 7.061) usó medicamentos para alguna comorbilidad y el 54,2% (n = 4.535) tenía otro neurofármaco. El coste por 1.000 habitantes/día de la rivastigmina fue de 3,47 dólares, y de la memantina, de 0,30 dólares. Conclusión. Los pacientes con medicamentos antidemencia los están empleando en dosis inferiores a las definidas y presentan una importante frecuencia de comorbilidades y comedicaciones

Introduction. The benefits of pharmacological therapy with anti-dementia drugs are not yet fully demonstrated and there is even a lack of publications describing their use profile. The present work sought to determine the prescription patterns of anti-dementia drugs in a Colombian population. Patients and methods. Descriptive cross-sectional study. Through a systematized database of 3.5 million affiliates to the Colombian health system, patients with uninterrupted dispensing of anti-dementia drugs between August-October/2016 were selected. Sociodemographic, pharmacological and comedication variables were analyzed. The costs of the therapies were estimated from the reference price of the medicines. Results. We identified 8372 patients with a mean age of 79.5 ± 8.7 years and 65.3% (n = 5471) were women. The most widely used medication was rivastigmine (69.6%), mainly in transdermal presentation, followed by memantine (31.4%). In general, the average dose administered per day was lower than the defined daily dose. Only 568 patients (6.7%) used combination therapy. 84.3% of patients (n = 7061) used some additional medication and 54.2% (n = 4535) had another neurologic medication. The cost per 1000 inhabitants/day of rivastigmine was 3.47 USD and for memantine 0.30 USD. Conclusion. Patients with anti-dementia drugs are using them at doses lower than those defined and they present an important frequency of comorbidities and comedications

Efecto del tratamiento con calcifediol, sobre los episodios cardiovasculares en pacientes revascularizados tras síndrome coronario agudo / Effect of calcifediol treatment on cardiovascular outcomes in patients with acute coronary syndrome and percutaneous revascularization

Antecedentes y objetivos: El déficit de 25(OH)D se ha relacionado con un riesgo cardiovascular aumentado, aunque los estudios de intervención son contradictorios. El objetivo principal fue evaluar el efecto del tratamiento con calcifediol (25(OH)D3) sobre el sistema cardiovascular en pacientes con síndrome coronario agudo sin elevación de segmento ST. Pacientes y método: Estudio prospectivo que incluyó a 41 pacientes (70,6±6,3 años) ≥60 años con síndrome coronario agudo sin elevación de segmento ST y enfermedad coronaria revascularizada percutáneamente. Se aleatorizaron a recibir calcifediol+tratamiento habitual o tratamiento habitual exclusivo, con evaluación de major adverse cardiovascular events (MACE, «episodios cardiovasculares mayores adversos») a los 3 meses. Se estudió la 25(OH)D en relación con otras variables analíticas y con la extensión de la enfermedad coronaria. Resultados: Niveles basales de 25(OH)D≤50nmol/l se asociaron a enfermedad coronaria multivaso (RR: 2,6 [IC 95%: 1,1-7,1], p=0,027) y 25(OH)D≤50nmol/l+paratohormona≥65pg/ml identificaron a pacientes con mayor riesgo de MACE (RR: 4 [IC 95%: 1,1-21,8], p=0,04). Se registró un MACE en el grupo de pacientes suplementados y 5 en el de tratamiento convencional (p=0,66). Entre los pacientes con niveles séricos de 25(OH)D≤50nmol/l al final del estudio el 28,6% presentaron MACE frente al 0% si los niveles eran>50nmol/l (RR: 1,4; p=0,037). Conclusiones: El déficit de vitamina D que implica un hiperparatiroidismo secundario puede ser un buen predictor de MACE. En pacientes suplementados con calcifediol se observó una tendencia a la disminución de MACE en el seguimiento. Niveles finales de 25(OH)D≤50nmol/l se asociaron significativamente a un mayor número de MACE, por lo que la normalización de 25(OH)D, además de mejorar la salud ósea, puede mejorar la salud cardiovascular

Background and objectives: Vitamin D deficiency has been consistently linked with cardiovascular diseases. However, results of intervention studies are contradictory. The aim of this study was to evaluate the effect of treatment with calcifediol (25(OH)D3) on the cardiovascular system of patients with non-ST-elevation acute coronary syndrome after percutaneous coronary intervention. Patients and methods: A prospective study assessing≥60-year-old patients with non-ST-elevation acute coronary syndrome, coronary artery disease and percutaneous revascularisation. We randomly assigned 41 patients (70.6±6.3 years) into 2 groups: Standard treatment+25(OH)D3 supplementation or standard treatment alone. Major adverse cardiovascular events (MACE) were evaluated at the conclusion of the 3-month follow-up period. 25(OH)D levels were analysed with regard to other relevant analytical variables and coronary disease extent. Results: Basal levels of 25(OH)D≤50nmol/L were associated with multivessel coronary artery disease (RR: 2.6 [CI 95%:1.1-7.1], P=.027) and 25(OH)D≤50nmol/L+parathormone ≥65pg/mL levels correlated with increased risk for MACE (RR: 4 [CI 95%: 1.1-21.8], P=.04]. One MACE was detected in the supplemented group versus five in the control group (P=.66). Among patients with 25(OH)D levels≤50nmol/L at the end of the study, 28.6% had MACE versus 0% among patients with 25(OH)D>50nmol/L (RR: 1,4; P=.037). Conclusions: Vitamin D deficiency plus secondary hyperparathyroidism may be an effective predictor of MACE. A trend throughout the follow up period towards a reduction in MACE among patients supplemented with 25(OH)D3 was detected. 25(OH)D levels≤50nmol/L at the end of the intervention period were significantly associated with an increased number of MACE, hence, 25(OH)D level normalisation could improve cardiovascular health in addition to bone health

Time to and factors associated with initiation of biological therapy in patients with rheumatoid arthritis in Colombia / Tiempo y factores asociados con el inicio de terapia biológica con antirreumáticos modificadores de enfermedad en pacientes con Artritis Reumatoide en Colombia

ABSTRACT Aims: To determine the time Colombian patients with rheumatoid arthritis (RA) are treated with non-biological disease-modifying antirheumatic drugs (DMARDs) before changing to biological therapy. Methods: A retrospective cohort study that collected information about the start of antirheumatic treatment in patients of all ages with a diagnosis of RA until the change to biological DMARD therapy. Survival analysis using Kaplan-Meier curves, from 1 January 2007 until 31 December 2013 by SPSS 23.0 for Windows, was made. Results: A total of 3880 patients (75.3% women) with a mean age of 51.3 years started non-biological DMARDs. After 5 years, 234 patients (6.0%) initiated biological DMARD therapy in 17.5 ± 13.9 months. The use of glucocorticoids (OR: 2.49; 95% CI: 1.658-3.732), having any comedication (OR: 1.83; 95%CI: 1.135-2.966) and being treated in the city of Bogota (OR: 2.30; 95%CI: 1.585-3.355) or in the cities of the Colombian Atlantic coast (OR: 2.848; 95%CI: 1.468-5.524) were associated with a higher likelihood of biological DMARD initiation. Whereas the initiation of therapy with methotrexate (OR: 0.04; 95% CI: 0.014-0.108; p < 0.001) or chloroquine (OR: 0.13; 95% CI: 0.092-0.187; p < 0.001) or receiving antihypertensive medication (OR: 0.64; 95% CI: 0.421-0.960; p = 0.031) was associated with a significant reduce in likelihood. Conclusion: After 5 years of non-biological DMARD therapy, 6.0% of people with RA started biological DMARDs. Receiving glucocorticoids, having any comedication, being treated in Bogota City or cities of the Colombian Atlantic coast affected the probability of switching to biological therapy in these patients.

RESUMEN Objetivo: Determinar el tiempo transcurrido desde que pacientes de Colombia con artritis reumatoide (AR) en tratamiento con fármacos antirreumáticos modificadores de enfermedad no biológicos (FAMEs) cambian a terapia con biológicos. Materiales y métodos: Estudio de cohorte retrospectiva que recogió información sobre inicio de tratamiento antirreumático en pacientes de todas las edades con diagnóstico de AR hasta que pasaron a terapia con FAMEs biológicos. Se hizo un análisis de sobrevida, utilizando curvas de Kaplan-Meier, desde el 1 de enero de 2007 hasta el 31 de diciembre de 2013 mediante SPSS 23.0 para Windows. Resultados: Un total de 3880 pacientes iniciaron terapia con FAMEs no biológicos, (75,3% fueron mujeres) con una edad media de 51,3 anos. Tras cinco años de seguimiento, 234 pacientes (6,0%) iniciaron FAMEs biológicos en promedio a los 17,5 ± 13,9 meses. El uso de corticoides (OR: 2,49; IC95%: 1,658-3,732; p<0,001), recibir alguna comedicación (OR: 1,83; IC95%: 1,135-2,966), ser tratado en Bogotá (OR: 2,30; IC95%: 1,585-3,355), en las ciudades de la costa Atlántica (OR: 2,848; IC95%: 1,468-5,524) estuvieron asociados con una mayor probabilidad de inicio de biológicos mientras que el uso de metotrexate (OR: 0,04; IC95%: 0,014-0,108) o cloroquina (OR: 0,13; IC95%: 0,092-0,187) o recibir medicación antihipertensiva (OR: 0,64; IC95%: 0,421-0,960) redujeron la posibilidad. Conclusiones: Después de cinco años de terapia antirreumática convencional, un 6,0% de pacientes con AR inició terapia con FAMEs biológicos. Recibir corticoides, recibir comedicación, ser tratado en Bogotá o la costa Atlántica afectan la probabilidad de cambiar a terapia biológica.

Effect of calcifediol treatment on cardiovascular outcomes in patients with acute coronary syndrome and percutaneous revascularization. / Efecto del tratamiento con calcifediol, sobre los episodios cardiovasculares en pacientes revascularizados tras síndrome coronario agudo.

BACKGROUND AND OBJECTIVES: Vitamin D deficiency has been consistently linked with cardiovascular diseases. However, results of intervention studies are contradictory. The aim of this study was to evaluate the effect of treatment with calcifediol (25(OH)D3) on the cardiovascular system of patients with non-ST-elevation acute coronary syndrome after percutaneous coronary intervention. PATIENTS AND METHODS: A prospective study assessing≥60-year-old patients with non-ST-elevation acute coronary syndrome, coronary artery disease and percutaneous revascularisation. We randomly assigned 41 patients (70.6±6.3 years) into 2 groups: Standard treatment+25(OH)D3 supplementation or standard treatment alone. Major adverse cardiovascular events (MACE) were evaluated at the conclusion of the 3-month follow-up period. 25(OH)D levels were analysed with regard to other relevant analytical variables and coronary disease extent. RESULTS: Basal levels of 25(OH)D≤50nmol/L were associated with multivessel coronary artery disease (RR: 2.6 [CI 95%:1.1-7.1], P=.027) and 25(OH)D≤50nmol/L+parathormone ≥65pg/mL levels correlated with increased risk for MACE (RR: 4 [CI 95%: 1.1-21.8], P=.04]. One MACE was detected in the supplemented group versus five in the control group (P=.66). Among patients with 25(OH)D levels≤50nmol/L at the end of the study, 28.6% had MACE versus 0% among patients with 25(OH)D>50nmol/L (RR: 1,4; P=.037). CONCLUSIONS: Vitamin D deficiency plus secondary hyperparathyroidism may be an effective predictor of MACE. A trend throughout the follow up period towards a reduction in MACE among patients supplemented with 25(OH)D3 was detected. 25(OH)D levels≤50nmol/L at the end of the intervention period were significantly associated with an increased number of MACE, hence, 25(OH)D level normalisation could improve cardiovascular health in addition to bone health.

Large Amount of Cannabis Ingestion Resulting in Spontaneous Intracerebral Hemorrhage: A Case Report.

Although multiple cases of cannabis-associated ischemic stroke have been reported, there are only 2 reported cases of hemorrhagic stroke with an associated cerebral vasoconstriction. To our knowledge, we present the first case of basal ganglia hemorrhage after a large-volume oral ingestion of cannabis without other identified risk factors. In our case, cerebral digital subtraction angiography within 24 hours of presentation did not reveal vasoconstriction leading to a possible alternative explanation for hemorrhagic stroke, including cannabis-induced transient arterial hypertension and autoregulation disruption.

Nuclear unphosphorylated STAT3 correlates with a worse prognosis in human glioblastoma.

Glioblastoma (GBM) is currently the most aggressive form of brain tumor identified, and STAT3 is known to play an important role in gliomagenesis. Moreover, while several studies have used pharmacological approaches to modulate STAT3 activity, the results have been contradictory. In this study, expressions of STAT3, pSTAT3 (Y705), and pSTAT3 (S727) were evaluated using immunohistochemistry assays of tissue microarrays containing non-neoplastic tissue (NN, n=12), grade II astrocytomas (n=33), grade III astrocytomas (n=12), and GBM (n=85) specimens. In GBM specimens, STAT3 was overexpressed and exhibited greater nuclear localization compared with lower grade astrocytomas and NN. Conversely, nuclear localization of pSTAT3 (Y705) and pSTAT3 (S727) exhibited a similar phenotype in both GBMs and NNs. MET was also detected as a non-canonical pathway marker for STAT3. For tumors with higher levels of STAT3 nuclear localization, and not pSTAT3 (Y705) and pSTAT3 (S727), these specimens exhibited increased levels of MET expression. Thus, a non-canonical pathway may mediate a proportion of the STAT3 that translocates to the nucleus. Moreover, tumors which exhibited greater nuclear localization of STAT3 corresponded with patients that presented with lower rates of recurrence-free survival and overall survival. In contrast, the phosphorylated forms of STAT3 did not correlate with patient survival. These findings suggest that phosphorylation-independent mechanisms may mediate the nuclear translocation and activation of STAT3. Further studies are needed to identify the mechanisms involved, especially those that provide targets to achieve efficient inhibition and control of GBM progression.

Analysis of cyclitols in different Quercus species by gas chromatography-mass spectrometry.

BACKGROUND: The carbohydrate profile of some woods used for aging wines and spirits has been recently studied using a pressurized liquid extraction method, the main differences found being related to cyclitol content. The aim of this study was to perform a detailed study of these compounds in woods of different Quercus species in order to identify two unknown compounds which appeared in the extracts and to verify whether the obtained profile was homogeneous for other Quercus species. RESULTS: Besides the known monosaccharides and five cyclitols previously described, three deoxy-inositols (epi-, vibo- and scyllo-quercitol) were identified. The presence of these eight cyclitols was confirmed in all subgenera and species of Quercus analyzed, allowing a characteristic cyclitol profile. CONCLUSIONS: Three deoxy-inositols (quercitols) have been identified in the carbohydrate profile of oak wood. All examined Quercus species displayed a common profile consisting of four inositols and four quercitols, which represent a good dataset for characterization of this genus.

Wavefront-guided laser in situ keratomileusis in the treatment of high myopia by using the CustomVue wavefront platform.

PURPOSE: To assess the efficacy, predictability, and safety of wavefront-guided laser in situ keratomileusis (LASIK) in the treatment of high myopia by using the Visx S4 CustomVue wavefront platform. METHODS: A retrospective analysis of consecutive cases of eyes with high myopia (manifest refraction spherical equivalent >or= -6.00 D) that underwent non-physician-adjusted wavefront-guided LASIK by using the Visx S4 CustomVue wavefront platform. Forty-three eyes of 29 patients were included. Preoperative best spectacle-corrected visual acuity (BSCVA), manifest refraction, WaveScan refraction, postoperative uncorrected visual acuity (UCVA) and BSCVA, and manifest refraction were determined. The clinical outcomes were evaluated on the basis of standard formats and criteria. Data at 3 months postoperatively are presented. RESULTS: Preoperatively, we found mean sphere was -6.89 +/- 1.08 D, mean cylinder was -0.97 +/- 0.75 D, and mean spherical equivalent (SE) was -7.38 +/- 1.20 D. Postoperatively, mean sphere was 0.02 +/- 0.40 D, mean cylinder was -0.40 +/- 0.40 D, and mean SE was -0.18 +/- 0.43 D. UCVA was 20/15 or better in 27.9% and cumulatively 20/20 or better in 58% of eyes. All eyes treated had at least 20/50 UCVA. Efficacy index was 0.94. Eighty-two percent of eyes were within 0.50 D and 97.6% were within 1.00 D of emmetropia at the 3-month follow-up visit. Ninety-one percent of eyes either maintained or gained 1 line of BSCVA. No eye lost >1 line of BSCVA. The safety index was 1.1. CONCLUSIONS: The 3-month follow-up results of our study indicate that wavefront-guided LASIK by using the Visx S4 CustomVue wavefront platform is an effective, predictable, and safe treatment of high myopia.

Photorefractive keratectomy for the correction of residual refractive error with Intacs intrastromal corneal ring segments in place.

PURPOSE: To evaluate the efficacy and safety of photorefractive keratectomy (PRK) for residual refractive errors in patients who had previous insertion of intrastromal corneal ring segments (Intacs, Addition Technology, Inc.) for treatment of low myopia. SETTING: Shiley Eye Center, University of California San Diego, La Jolla, California, USA. METHODS: This retrospective case series comprised patients who had Intacs segment implantation and subsequently developed myopic regression. Eight eyes of 5 patients had PRK over the Intacs in situ for the correction of the residual refractive error. RESULTS: Six (75%) of the 8 eyes had plano refraction with 20/20 or better uncorrected visual acuity (UCVA) 1 month after PRK enhancement. Three months postoperatively, all eyes had plano refraction with 20/20 or better acuity. At the last follow-up examination (up to 2 years), all eyes had near plano vision (20/10 to 20/25). The corneal surface epithelium in all eyes healed in 3 to 5 days. One patient had subepithelial haze in both eyes, which resolved with epithelial scraping with mitomycin-C (MMC) application and a phototherapeutic keratectomy enhancement. CONCLUSIONS: This small series showed that PRK can be used to treat residual refractive error after Intacs insertion. The UCVA was 20/25 or better in all cases after PRK enhancement. The incidence of post-PRK haze in this series of patients was high; topical MMC might be used in future cases to mitigate the problem.

Early postoperative pain following Epi-LASIK and photorefractive keratectomy: a prospective, comparative, bilateral study.

PURPOSE: To compare postoperative pain associated with epi-LASIK versus photorefractive keratectomy (PRK). METHODS: This prospective observer-masked randomized study included 40 eyes of 20 patients with myopia and astigmatism who received epi-LASIK (Moria Epi-K) in one eye and PRK in the contralateral eye. Corneal ablation was done using the NIDEK EC-5000 excimer laser. Patients were seen at days 1, 3, and 6 to rate their pain via three measuring tools: 1) a global subjective rating, 2) a 10-cm visual analog scale, and 3) an 11-point numeric scale of pain. RESULTS: On postoperative day 1, 19 of 20 patients reported pain in both eyes. Using the global subjective rating scale, patients reported more pain for those eyes treated by PRK. Although clinically relevant, this difference was not statistically significant (P = .56). Based on the 11-point numeric scale of pain and visual analog scale, mean pain scores were similar for both groups. On day 3, using the global subjective rating scale, 11 of 12 patients who had pain reported more in the epi-LASIK treated eye (P = .0005). In addition, epi-LASIK eyes demonstrated higher mean pain scores based on the other two scales (visual analog scale, P = .045 and 11-point numeric scale of pain, P = .023). Only 6 patients reported minimal pain on day 6. It was more frequently reported and slightly more marked in epi-LASIK eyes, but did not reach statistical significance. CONCLUSIONS: Epi-LASIK and PRK have similar pain on postoperative day 1, but epi-LASIK demonstrated statistically more pain than PRK on days 3 and 6.

In vivo architectural analysis of 3.2 mm clear corneal incisions for phacoemulsification using optical coherence tomography.

PURPOSE: To analyze in vivo the architecture of clear corneal incisions (CCIs) for phacoemulsification using optical coherence tomography (OCT). SETTING: Anterior Segment Department, Asociacion Para Evitar la Ceguera en Mexico, Hospital Dr Luis Sanchez Bulnes, Mexico. METHODS: A prospective masked study analyzed 20 unsutured CCIs placed superiorly and created in a uniplanar fashion with a 3.2 mm slit-angled metal keratome. All wounds were evaluated with a retinal OCT model 1, 3, and 30 days postoperatively. Intraocular pressure (IOP) and incision leakage were checked. The architecture was described according to the angle of incidence, apposition of the epithelial and endothelial margins, and wound sealing. RESULTS: No leakage was detected. The angle varied from 33 to 85 degrees; angles greater than 75 degrees were done by a surgeon in training. Wound apposition at the epithelial margin was achieved in all cases. In contrast, imperfect apposition of the endothelial margin was seen in 45% of incisions on day 1 and in 15% on day 30. Incomplete sealing of the wound was seen by OCT in 25% of cases at 24 hours and persisted in 10% of all cases at 1 month. This gaping occurred on the endothelial side and never translated to the epithelial margin. No statistical correlation was found between gaping and the angle of the incision, IOP variations, or surgeon experience. CONCLUSIONS: Although in vivo CCIs caused minor anatomic imperfections, they were clinically stable independent of incision angle, IOP variation, and surgeon experience. Incision stability may be related to careful wound construction, epithelial viability, stromal edema, and efficient endothelial pumping.