Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer.

BACKGROUND: Identification of residual disease in patients with localized non-small cell lung cancer (NSCLC) following treatment with curative intent holds promise to identify patients at risk of relapse. New methods can detect circulating tumour DNA (ctDNA) in plasma to fractional concentrations as low as a few parts per million, and clinical evidence is required to inform their use. PATIENTS AND METHODS: We analyzed 363 serial plasma samples from 88 patients with early-stage NSCLC (48.9%/28.4%/22.7% at stage I/II/III), predominantly adenocarcinomas (62.5%), treated with curative intent by surgery (n = 61), surgery and adjuvant chemotherapy/radiotherapy (n = 8), or chemoradiotherapy (n = 19). Tumour exome sequencing identified somatic mutations and plasma was analyzed using patient-specific RaDaR™ assays with up to 48 amplicons targeting tumour-specific variants unique to each patient. RESULTS: ctDNA was detected before treatment in 24%, 77% and 87% of patients with stage I, II and III disease, respectively, and in 26% of all longitudinal samples. The median tumour fraction detected was 0.042%, with 63% of samples <0.1% and 36% of samples <0.01%. ctDNA detection had clinical specificity >98.5% and preceded clinical detection of recurrence of the primary tumour by a median of 212.5 days. ctDNA was detected after treatment in 18/28 (64.3%) of patients who had clinical recurrence of their primary tumour. Detection within the landmark timepoint 2 weeks to 4 months after treatment end occurred in 17% of patients, and was associated with shorter recurrence-free survival [hazard ratio (HR): 14.8, P <0.00001] and overall survival (HR: 5.48, P <0.0003). ctDNA was detected 1-3 days after surgery in 25% of patients yet was not associated with disease recurrence. Detection before treatment was associated with shorter overall survival and recurrence-free survival (HR: 2.97 and 3.14, P values 0.01 and 0.003, respectively). CONCLUSIONS: ctDNA detection after initial treatment of patients with early-stage NSCLC using sensitive patient-specific assays has potential to identify patients who may benefit from further therapeutic intervention.

ARMC5 Primary Bilateral Macronodular Adrenal Hyperplasia Associated with a Meningioma: A Family Report.

Primary bilateral adrenal macronodular hyperplasia is characterized by functioning adrenal macronodules and variable cortisol secretion. Familial clustering suggests a genetic cause that has been confirmed with the identification of some genetic mutations, including inactivating germline mutations, in armadillo repeat containing 5 (ARMC5) gene. The identification of the pathogenic variant enables the physician to identify and treat these patients earlier and more effectively. It has also been noticed that patients with germline causative variants show a different clinical spectrum, presenting specific clinical characteristics, as the association with the presence of meningiomas.

Effects of Ecuador's national monetary incentive program on adherence to treatment for drug-resistant tuberculosis.

BACKGROUND: Non-adherence to tuberculosis (TB) treatment jeopardizes patient health and promotes disease transmission. In July 2011, Ecuador's National Tuberculosis Program (NTP) enacted a monetary incentive program giving adherent drug-resistant TB (DR-TB) patients a US240 bonus each month. OBJECTIVE: To describe patients' experiences with the program qualitatively, and to assess its effects on treatment adherence. METHODS: We interviewed 92 current and five default patients about their treatment experience. NTP data on DR-TB patients receiving treatment were used to compare 12-month default rates among the incentive program group and non-program controls. RESULTS: Our interviews found that patients are financially challenged and use the bonus for a variety of expenses, most commonly food. The most common complaint was that bonus payments were frequently delayed. The 1-year default rate among program patients (9.5%) was significantly lower than the rate among pre-program patients (26.7%). CONCLUSION: Ecuador's monetary incentive program alleviates the economic burden placed by treatment on patients. The bonus does not, however, directly address other treatment barriers, including psychological distress and side effects. The program could benefit from timely delivery of payments. Further research is necessary to assess the program's effect on default rates.

Influence of tracheostomy on the incidence of central venous catheter-related bacteremia.

Although there are many studies on catheter-related infection, there are scarce data about the influence of tracheostomy in the incidence of central venous catheter-related bacteremia (CRB). In this cohort study, we found a higher incidence of CRB in patients with tracheostomy than without (11.25 vs. 1.43 per 1,000 catheter-days; odds ratio [OR] = 7.99; 95% confidence interval [CI] = 4.38-infinite; P < 0.001). Besides, we found a higher incidence of CRB in patients with tracheostomy using the jugular access compared to subclavian access (21.64 vs. 5.11 per 1,000 catheter-days; OR = 4.23; 95% CI = 1.44-infinite; P = 0.0097).

Catheter-related bacteremia from femoral and central internal jugular venous access.

The objective of this prospective observational study was to determine the influence of femoral and central internal jugular venous catheters on the incidence of catheter-related bacteremia (CRB). We included patients admitted to a 12-bed polyvalent medico-surgical intensive care unit over 4 years who received one or more femoral or central internal jugular venous catheters. We diagnosed 16 cases of CRB in 208 femoral catheters and 22 in 515 central internal jugular venous catheters. We found a higher incidence of CRB with femoral (9.52 per 1,000 catheter days) than with central internal jugular venous access (4.83 per 1,000 catheter days; risk ratio = 1.93; 95% confidence interval: 1.03-3.73; P = 0.04). Central internal jugular venous access could be considered a safer route of venous access than femoral access in minimizing the risk of central venous catheter-related bacteremia.

[White matter anatomy using tensor diffusion tractography]. / Anatomía de la sustancia blanca mediante tractografía por tensor de difusión.

Tractography of cerebral white matter fibers based on diffusion tensor imaging (DTI) is a recent magnetic resonance technique that enables the visualization of the anatomy and integrity of white matter tracts. This article aims to provide two- and three-dimensional representations of the main white matter tracts in the brain from high spatial resolution DTI data and to explain the physical basis of the technique, its main clinical applications, and how we use it. We provide examples of the use of DTI in the study of the corpus callosum, the anterior white commissure, the corticospinal tract, the limbic system, the long association fibers, the cerebellar peduncles, and the optic tract.

Anatomía de la sustancia blanca mediante tractografía por tensor de difusión / White matter anatomy using tensor diffusion tractography

La tractografía de las fibras de la sustancia blanca cerebral basada en el tensor de difusión es una reciente técnica de resonancia magnética que proporciona la visualización de la anatomía y la integridad de los tractos de dicha sustancia blanca. El propósito de este trabajo es representar de forma bidimensional y tridimensional las principales vías de la sustancia blanca cerebral a partir de los datos de la imagen del tensor de difusión de alta resolución espacial, y exponer las bases físicas de la técnica, nuestra metodología y sus principales aplicaciones clínicas. Se estudian y representan el cuerpo calloso, la comisura blanca anterior, el tracto corticoespinal, el sistema límbico, las fibras largas de asociación, los pedúnculos cerebelosos y la vía óptica (AU)

Tractography of cerebral white matter fibers based on diffusion tensor imaging (DTI) is a recent magnetic resonance technique that enables the visualization of the anatomy and integrity of white matter tracts. This article aims to provide two- and three-dimensional representations of the main white matter tracts in the brain from high spatial resolution DTI data and to explain the physical basis of the technique, its main clinical applications, and how we use it. We provide examples of the use of DTI in the study of the corpus callosum, the anterior white commissure, the corticospinal tract, the limbic system, the long association fibers, the cerebellar peduncles, and the optic tract (AU)

Surgical treatment of symptomatic cavernous malformations of the brainstem.

INTRODUCTION AND OBJECTIVES: Cavernous malformations (CM) at the level of the brainstem, continue to present a challenge in therapeutic terms and are an important source of controversy. Here we present our experience and the results obtained by adopting surgical treatment. MATERIALS AND METHODS: The results of a consecutive series of 17 patients were studied. The surgical intervention was designed after: 1. A neurological examination. 2. MRI and cerebral angiography. 3. Correlation with anatomical brainstem maps. The surgical intervention was approached from the most damaged zone or through a zone which was functionally least important. RESULTS: Complete extirpation was achieved in 15 patients without mortality. In a few patients the surgical intervention temporarily aggravated the prior lesion of the cranial nerves (2/17) or damage new sensory tracts (2/17). The functional post-operative recovery was good, in terms of consciousness (4/5), cranial nerves (11/17), the pyramidal tract (3/5) and the cerebellum (2/4). Of the patients that were operated, 14 of 17 returned to their professional activities. CONCLUSIONS: The results of surgery can surpass the morbidity-mortality of the natural history or treatment with radiosurgery. There is a clear consensus in recommending surgical intervention for CMs that are superficially located, in young patients and in those with a risk of further bleeding. It is probably best that the surgery is performed during the subacute period, when the MRI offers a clear image confirming the presence of the CM.

[Epidural fat in various diseases: contribution of magnetic resonance imaging and potential implications for neuro axial anesthesia]. / La grasa epidural en diferentes patologías. Aportaciones de la resonancia magnética y posibles implicaciones en la anestesia neuroaxial.

Epidural fat is a reservoir of lipophilic substances that cushions the pulsatile movements of the dural sac, protects nerve structures, and facilitates the movement of the dural sac over the periosteum of the spinal canal during flexion and extension. Excessive epidural fat can compress the underlying structures, however, and affect the placement of catheters and the distribution of injected solutions. This review discusses changes in epidural fat related to various diseases and events: lipomatosis, epidural lymphoma, arachnoid cysts, epidural hematoma, meningiomas, angiolipomas, spondylolysis, scoliosis, spinal stenosis, and liposarcoma. Also discussed are the sequencing and protocols for magnetic resonance imaging that enable epidural fat to be observed and distinguished from neighboring structures. The relevance of epidural fat in spinal surgery is considered. Finally, we discuss the possible anesthetic implications of the abnormal deposition of epidural fat, to explain the unexpected complications that can arise during performance of epidural anesthesia.

La grasa epidural en diferentes patologías. Aportaciones de la resonancia magnética y posibles implicaciones en la anestesia neuroaxial / Epidural fat in various diseases: contribution of magnetic resonance imaging and potential implications for neuro axial anesthesia

La grasa epidural (GE) constituye un reservorio farmacológico de sustancias lipofílicas que permite un adecuado almohadillado de los movimientos pulsátiles del saco dural, protege las estructuras nerviosas y facilita el deslizamiento del saco dural sobre el periostio del canal vertebral durante los movimientos de flexo-extensión. No obstante, un desarrollo exagerado de la GE puede comprimir las estructuras que le rodean e influir en la ubicación final de catéteres y en la distribución de las soluciones inyectadas. Esta es una revisión de las modificaciones que sufre la GE asociada a diferentes patologías: lipomatosis, linfoma epidural, quistes aracnoideos, hematoma epidural, meningiomas, angiolipomas, espondilolisis, escoliosis, estenosis espinal, liposarcomas; de las diferentes secuencias y protocolos de la resonancia magnética que permiten evidenciar su presencia y diferenciarla de sus tejidos vecinos; de su importancia en la cirugía de columna; y por último, de las implicaciones anestésicas que podría tener el desarrollo patológico de la GE para poder justificar diferentes situaciones no esperadas durante la realización de una anestesia epidural

Epidural fat is a reservoir of lipophilic substances that cushions the pulsatile movements of the dural sac, protects nerve structures, and facilitates the movement of the dural sac over the periosteum of the spinal canal during flexion and extension. Excessive epidural fat can compress the underlying structures, however, and affect the placement of catheters and the distribution of injected solutions. This review discusses changes in epidural fat related to various diseases and events: lipomatosis, epidural lymphoma, arachnoid cysts, epidural hematoma, meningiomas, angiolipomas, spondylolysis, scoliosis, spinal stenosis, and liposarcoma. Also discussed are the sequencing and protocols for magnetic resonance imaging that enable epidural fat to be observed and distinguished from neighboring structures. The relevance of epidural fat in spinal surgery is considered. Finally, we discuss the possible anesthetic implications of the abnormal deposition of epidural fat, to explain the unexpected complications that can arise during performance of epidural anesthesia

[Characteristics and distribution of normal human epidural fat]. / Características y distribución de la grasa epidural humana normal.

Epidural fat provides sufficient cushion for the pulsatile movements of the dural sac, protects nerve structures, facilitates the movement of the dural sac over the periosteum of the spinal column during flexion and extension, and forms a pharmacologic reservoir of lipophilic substances. We review epidural fat and related structures, including their development during the fetal period when the epidural space is filled by undifferentiated loose, areolar mesenchymal tissue that surrounds the dural sac. In the adult, epidural fat has a continuous distribution and follows a certain metameric pattern. It is located mainly on the dorsal side of the epidural space, where it is organized in triangular capsules joined to the midline of the ligamentum flavum by a vascular pedicle. We consider the distribution of epidural fat in the axial and sagittal planes; its presence in the anterior, lateral and posterior epidural space; its presence in the cervical, thoracic and lumbar portions of the spinal column; and its characteristics and variations according to differing body habits and sex. Finally, we speculate on the possible anesthetic implications of epidural fat in terms of the pharmacokinetics of drugs injected into the epidural space and the tasks of locating the epidural space and inserting an epidural catheter during anesthetic procedures.

Características y distribución de la grasa epidural humana normal / Characteristics and distribution of normal human epidural fat

La grasa epidural (GE) permite un adecuado almohadilladode los movimientos pulsátiles del saco dural, protegea estructuras nerviosas, y facilita el deslizamientodel saco dural sobre el periostio del canal vertebraldurante los movimientos de flexo-extensión, formandoun reservorio farmacológico de sustancias lipofílicas.Revisamos la GE y las estructuras anatómicas relacionadas;su desarrollo en el feto donde el espacio epidural(EE) está ocupado por un tejido laxo, areolar,mesenquimatoso indiferenciado organizado a todo alrededordel saco dural. En el adulto, la GE epidural tieneuna distribución discontinua y responde a un patróndeterminado, con una topografía metamérica, localizadaprincipalmente en la parte posterior del EE, donde estáorganizada en paquetes de forma triangular que estánadheridos a la línea media del ligamento amarillo por unpedículo vascular.Evaluamos su distribución en los planos axiales ysagitales, su presencia dentro del EE anterior, lateral yposterior; en la porción cervical, torácica y lumbar de lacolumna; sus características y variaciones según los diferenteshábitos corporales y sexo. Por último, se planteanhipótesis sobre posibles implicaciones anestésicas quepodría tener la GE en la farmacocinética de las sustanciasinyectadas dentro del EE, en aspectos de la localizacióndel EE y en la ubicación de catéteres epiduralesdurante la realización de anestesias epidurales

Epidural fat provides sufficient cushion for the pulsatilemovements of the dural sac, protects nerve structures,facilitates the movement of the dural sac over theperiosteum of the spinal column during flexion andextension, and forms a pharmacologic reservoir of lipophilicsubstances.We review epidural fat and related structures, includingtheir development during the fetal period when theepidural space is filled by undifferentiated loose, areolarmesenchymal tissue that surrounds the dural sac. In theadult, epidural fat has a continuous distribution andfollows a certain metameric pattern. It is located mainlyon the dorsal side of the epidural space, where it is organizedin triangular capsules joined to the midline of theligamentum flavum by a vascular pedicle.We consider the distribution of epidural fat in theaxial and sagittal planes; its presence in the anterior,lateral and posterior epidural space; its presence in thecervical, thoracic and lumbar portions of the spinalcolumn; and its characteristics and variations accordingto differing body habits and sex. Finally, we speculate onthe possible anesthetic implications of epidural fat interms of the pharmacokinetics of drugs injected into theepidural space and the tasks of locating the epiduralspace and inserting an epidural catheter during anestheticprocedures

Neumonía por Pneumocystis carinii asociada a cirrosis hepática y tratamiento con corticoides en un pacienteseronegativo para el virus de la inmunodeficiencia humana / Pneumocystis carnii pneumonia in a patient without human immunodeficiency virus: association with liver cirrhosis and corticosteroid treatment

Se presenta el caso de un paciente de 44 años, diagnosticado de cirrosis e insuficiencia hepática de origen enólico, que 2 meses antes recibió tratamiento con 40 mg/día de prednisona por un brote de hepatitis alcohólica. En el momento del ingreso presentaba una descompensación hepática de origen multifactorial que evolucionó a insuficiencia respiratoria aguda, patrón alveolointersticial difuso en la radiografía de tórax, disfunción orgánica y fallecimiento. Se estableció el diagnóstico de neumonía por Pneumocystis carinii al observar quistes en muestras de lavado broncoalveolar y catéter telescopado protegido. La serología para el virus de la inmunodeficiencia humana fue negativa, con valores normales de linfocitos CD4+ y CD8+. El estudio necroscópico confirmó el diagnóstico de cirrosis hepática y neumonía por P. carinii. Tras revisar la bibliografía hemos comprobado la infrecuente asociación entre neumonía por P. carinii y cirrosis hepática con tratamiento corticoideo (AU)

Esclerosis Múltiple en la infancia / Childhood multiple sclerosis

La esclerosis múltiple (EM) es una enfermedad que suele presentarse en la edad adulta, aunque algunos casos pueden debutar en la infancia. En niños, esta entidad resulta de especial interés por varias razones: en primer lugar, es relativamente infrecuente; en segundo lugar, los datos clínicos y los hallazgos de laboratorio son a menudo diferentes de los que se observan en la población adulta, y por último, dada la dificultad de la evaluación clínica, sobre todo en la edad preescolar, es muy importante la integración de todas las determinaciones paraclínicas para obtener un diagnóstico diferencial precoz y para el correcto tratamiento del paciente pediátrico (AU)

Blood-derived phagocytes in the cerebellar cortex of the rat after chronic alcohol consumption.

Past work showed that chronic alcohol consumption induces massive degeneration in the rat cerebellar cortex. To study the subsequent process of nervous tissue repair, followed itself by a remodelling activity, groups of alcohol-treated rats for 3 and 6 months were used and the results compared with the respective age-matched controls. From the wide variety of cells which display phagocytic activity in the mammalian brain it was found, based on qualitative observations, that two types were clearly involved in the removal of the alcohol-induced degenerated debris: the resident microglial cells and the non-resident brain macrophages. This assumption was corroborated by the study of their origin, using carbon particles and latex beeds intravenously injected, which showed that brain macrophages were the sole population to be labelled. These observations fit with the multiple origin concept for neural phagocytosis which postulates that different cell types can be recruited for the removal of the damaged neural tissue depending on the severity of the lesions and on the extension of the blood vessels damage.

Cell loss in the cerebellum and hippocampal formation of adult rats after long-term low-protein diet.

Whereas quite a number of previous reports have shown that the developing brain is vulnerable to protein deprivation, the mature CNS is usually considered resistant to this condition. To explore this assumption the present experimental model was built on groups of 2-month-old rats fed with a low-protein diet (8% casein) for 6, 12, and 18 months and respective age-matched controls fed for the same periods with a standard laboratory chow (27% casein). The numerical density of cerebellar granule cells was estimated using three different stereological procedures (classical, unfolding, and disector). By all methods a significant cell loss was demonstrated. In the hippocampal region the numerical densities of dentate gyrus granule cells and the CA3 pyramidal cells were estimated using the unbiased disector method. A significative and progressive loss of neurons was likewise found. The occurrence of cell loss after lengthy periods of undernutrition in adulthood is thus an issue of paramount importance if extrapolation can be made to the human brain.

Efecto antiarritmico de la mexiletina en la miocarditis chagasica cronica / Antiarrhythmic effect of the mexiletine in the chronicle miocardite chagasica

La mexiletina, un agente antirritmico disponible en forma oral, fue administrada a 20 pacientes chagasticos. Todos tenian >30 extrasistoles ventriculares por 15 minutos. El estudio se realizo en 3 etapas. Durante la etapa I, se determino el No. de extrasistoles ventriculares y el grado segun el sistema gradativo de Lown y Wolff. En la etapa II, se observo el efecto inmediato de la droga . En la etapa III, se observo el efecto a corto plazo (72h). De los 20 pacientes estudiados, 15 (75%) presentaron una respuesta satisfactoria a las 2 h. De los 13 pacientes que ingresaron a la face III, 9 (69.2%) presentaron una respuesta satisfactoria. Los efectos adversos se observaron en 18 pacientes . En 7 obligaron a suspender la medicacion durante la face II. De los 13 pacientes que ingresaron a la face III, en 11 se observaron efectos colaterales leves. Los efectos adversos mas frecuentes fueron los relacionados con el aparato digestivo y con el sistema nervioso central