The Efficacy and Safety of Lenalidomide plus Rituximab in an Orbital Relapse of Diffuse Large B-Cell Lymphoma.

A 74-year-old male with diffuse large B-cell lymphoma, with an Ann Arbor stage IV-A, was submitted to immune-chemotherapy in 2014, with complete remission of the disease. Two years later, he presented with a left eye swelling leading to exophthalmos and blurred vision. A core biopsy was performed and revealed a local relapse of the disease. He was considered unfit for intensive salvage chemotherapy and was treated with a combination of rituximab and lenalidomide. After six courses of rituximab plus lenalidomide, the patient showed complete remission and was submitted to maintenance therapy with lenalidomide. After 24 months since the start of lenalidomide monotherapy, we did not observe any progression. In this experience, rituximab plus lenalidomide, without radiotherapy, was a safe and effective therapeutic combination in an elderly patient with a localized relapse of DLBCL who was unfit to receive more aggressive therapies.

Venetoclax: Bcl-2 inhibition for the treatment of chronic lymphocytic leukemia.

Venetoclax (ABT-199) is a small-molecule selective oral inhibitor of the antiapoptotic protein Bcl-2 that promotes programmed cell death of chronic lymphocytic leukemia (CLL) cells regulating the release of proapoptotic factors, such as Smac/Diablo, apoptosis-inducing factor (AIF) and cytochrome c. In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to venetoclax for patients diagnosed with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. This review will focus on the mechanism of action, preclinical studies and clinical development of venetoclax both as a monotherapy and in combination with other drugs for CLL in the current milieu of therapy dominated by novel tyrosine kinase inhibitors such as ibrutinib and idelalisib.

Neuroprotective action and free radical scavenging activity of Guttiferone-A, a naturally occurring prenylated benzophenone.

Reactive oxygen species (ROS) are important mediators in a number of neurodegenerative diseases and molecules capable of scavenging ROS may be a feasible strategy for protecting neuronal cells. We previously demonstrated a powerful iron-chelating action of Guttiferone-A (GA), a naturally occurring polyphenol, on oxidative stress injuries initiated by iron overload. Here we addressed the neuroprotective potential of GA in hydrogen peroxide and glutamate-induced injury on rat's primary culture of cortical neurons and PC12 cells, respectively, and antioxidant properties concerning scavenging and anti-lipoperoxidative activities in cell-free models. The decrease in cell viability induced by each of the toxins, assessed by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay, was significantly attenuated by GA. In addition, GA was found to be a potent antioxidant, as shown by (i) inhibition of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical reduction (EC50=20.0 µM), (ii) prevention against chemically or electrochemically generated superoxide radicals, (iii) inhibition of spontaneous brain lipid peroxidation and (iv) interference with the Fenton reaction. These results indicate that GA exerts neuroprotective effects against H2O2 or glutamate toxicity and its antioxidant activity, demonstrated in vitro, could be at least partly involved. They also suggest a promising potential for GA as a therapeutic agent against neurodegenerative diseases involving ROS and oxidative damage.

[Diagnosis of delayed cerebral ischaemia and cerebral vasospasm in subarachnoid haemorrhage]. / Diagnóstico de la isquemia cerebral tardía y el vasospasmo cerebral en la hemorragia subaracnoidea.

OBJECTIVE: A review of current foundations for the medical diagnosis of vasospam and delayed cerebral ischaemia due to spontaneous subarachnoid haemorrhage. DEVELOPMENT: A review of available tests for the investigation of vasospasm (transcraneal Doppler, angiographic methods) and delayed cerebral ischaemia (clinical exam, computerised tomography by X rays, magnetic resonance, emission computerised tomography, electroencephalography, microdialysis) based on type and quality of information, advantages and limitations. Grading and trends for application were also considered for differential diagnosis. CONCLUSIONS: In current clinical practice the most advisable guideline for screening and diagnosis monitoring of vasospasm and delayed cerebral ischaemia is in the first place, based on clinical examination and transcraneal Doppler. The electroencephalographic monitoring, computerised tomography techniques and multi-modal magnetic resonance are justified in specific situations. Digital subtraction angiography is the current gold standard for diagnosis of cerebral vasospasm. There is a need for more and higher quality articles about the utility of diagnostic tests in this context.

[Clinical techniques for use in neurological physical examinations. III. Sensory functions]. / Técnicas clínicas para el examen físico neurológico. III. Función sensitiva.

AIMS: The purpose of this work is to focus on the main practical aspects of the techniques used for the neurological physical examination of the sensory functions and to present an approach for the practice of this study. DEVELOPMENT: Despite the difficulty often involved in interpreting its results, today the formal examination of sensation is still an important part of a complete neurological evaluation and remains valid in the search for a correct diagnosis and suitable treatment. We recommend clinicians to carry out a brief but consistent and effective exploration in a systematic, flexible and orderly manner to check for abnormalities in the sensory functions. Should any anomalies be detected, then a more detailed and thorough neurological exploration must be performed selectively. We present a detailed review of the practical aspects of the main techniques used in the physical examination of this neurological category. In addition to the tests used to examine the peripheral and cortical sensory systems, we also describe other techniques designed to trigger pain or other sensory symptoms due to radicular lesions or injury to the median nerve. CONCLUSIONS: We present a detailed description of the main clinical techniques used in the neurological physical examination of the sensory functions, as well as an approach that allows them to be performed on adult patients. In addition, we underline the importance of physically examining the sensory functions in contemporary medicine and the need to continually perfect the way these techniques are performed in order to achieve an efficient clinical practice.

[Clinical techniques for use in neurological physical examinations. II. Motor and reflex functions]. / Técnicas clínicas para el examen físico neurológico. II. Función motora y refleja.

AIMS: The aim of this study is to highlight the chief practical aspects of the techniques used in the neurological physical examination of the motor and reflex functions. DEVELOPMENT: We recommend clinicians to carry out a brief but consistent and effective exploration in a systematic, flexible and orderly manner to check for abnormalities in the motor and reflex functions of the nervous system. Should any anomalies be detected, then a more detailed and thorough neurological exploration must be performed selectively. We present a detailed review of the practical aspects of the main techniques used in the physical examination of these neurological categories. The motor function is explored using techniques that examine muscle tone, muscle strength, muscle fatigability, hypokinesia, tremor, coordination and gait. Lastly, in this category several manoeuvres that are useful in hysterical or mimicking paralyses are also dealt with. Reflexes to examination are usually divided into: 1. Myotatic reflexes; 2. Cutaneomucous reflexes; 3. Spinal cord or defence automatism reflexes; 4. Posture and attitude reflexes. We also add the study of primitive pathological reflexes, remote reflexes, synkinesias and signs of meningeal irritation. CONCLUSIONS: We present a detailed description of the main clinical techniques used in the neurological physical examination of motility and reflexes, as well as an approach that allows them to be performed on adult patients. In addition, we underline the importance of physically examining the nervous system in contemporary medicine and the need to continually perfect the way these techniques are performed in order to achieve an efficient clinical practice.

[Clinical techniques for use in neurological physical examinations. I. General organisation, cranial and peripheral spinal nerves]. / Técnicas clínicas para el examen físico neurológico. I. Organización general, nervios craneales y nervios raquídeos periféricos.

AIMS: The purpose of this work is to focus on the main practical aspects of the techniques used for the physical examination of the nervous system and to present an approach for the practice of this study in adult patients. DEVELOPMENT: We recommend clinicians to carry out a brief but consistent and effective exploration in a systematic, flexible and orderly manner to check for alterations in the functioning of the nervous system. Should any anomalies be detected, then a more detailed and thorough neurological exploration must be performed selectively. The techniques and data from this examination are organised into five broad categories: mental status, cranial nerves, motor function, reflex function and sensory function. The practical aspects of the main techniques used in the physical exploration are reviewed and we also describe the technique to be employed for palpating the main peripheral nerves. CONCLUSIONS: The study offers a detailed description of the chief clinical techniques used in the physical exploration of the cranial nerves and for the palpation of the peripheral nerves; we also present an approach to performing the neurological examination. Furthermore, we highlight the importance of physically examining the nervous system in contemporary medicine and the need to continually perfect the way these techniques are performed in order to achieve an efficient clinical practice.

[Foundations of the diagnosis of clinical syndromes]. / Bases para el diagnóstico de los síndromes clínicos.

AIMS: The aim of this paper is to offer a reflection on the principles used to define a syndromic entity and for the evaluation of its manifestations and the aetiopathogenesis. METHOD: First, the paper looks at several of the different definitions of syndrome available and examines which are the essential features for this term to be employed in a clinical entity. The topographical and semiological perspectives are then dealt with, so as to be able to sort clinical syndromes and charts are used to offer representative examples. The main deficiencies in the use of terms to describe syndromes and the possible causes of such situations are also investigated. Following that, the chief semiological aspects in the diagnosis of a syndrome are assessed. Emphasis is placed on the factors that influence the variability of clinical behaviour, on the factors that come to bear on the recognition of the manifestations using the research methods available to us, on the rule of iterative confirmation of the symptom and on the characterisation and coordination of the symptom with other related phenomena. Lastly, the aetiopathological foundations of clinical syndromes are evaluated. We highlight the importance of determining the underlying anatomofunctional disorder, the classical distinctions concerning this, and the relation between syndrome and disease. The diagnostic criteria from numerous neurological syndromes are used as examples. CONCLUSIONS: The concept of syndrome has been defined in an attempt to illustrate the presence of inappropriate, incorrect terms with adverse repercussions in the theoretical and practical areas. We also propose ways of resolving the faults found.