Cannabis and pain: a scoping review.

For centuries, cannabis has been used with many different purposes, including medicinal use, usually bypassing any formal approval process. However, during the last decade, interest in cannabis in medicine has been increasing, and several countries, including the United States and Canada, have produced their own legislation about marihuana and cannabis-based medicines. Because of this, interest in research has been increasing and evidence about its medical effects is becoming necessary. We conducted a review examining the evidence of cannabis in pain. Cannabis had been shown to be useful in acute and chronic pain, however recently, these results have been controverted. Within the different types of chronic pain, it has a weak evidence for neuropathic, rheumatic pain, and headache, modest evidence for multiple sclerosis related pain, and as adjuvant therapy in cancer pain. There is no strong evidence to recommend cannabis in order to decrease opioids in patients with chronic use. Even though cannabis-based medications appear to be mostly safe, mild adverse effects are common; somnolence, sedation, amnesia, euphoric mood, hyperhidrosis, paranoia, and confusion may limit the use of cannabis in clinical practice. Risks have not been systematically analyzed. Special concern arises on how adverse effect might affect vulnerable population such as elderly patients. More research is needed in order to evaluate benefits and risks, as well as the ideal administration route and dosages. As cannabis use increases in several countries, answers to these questions might be coming soon.

Optical Coherence Tomography in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

Purpose: The use of optical coherence tomography (OCT) of the retina to detect inner retinal degeneration is being investigated as a potential biomarker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), and an overwhelming body of evidence indicates that discovery of disease-modifying treatments for AD should be aimed at the pre-dementia clinical stage of AD, i.e., MCI. We aimed to perform a systematic review and meta-analysis on retinal OCT in MCI. Methods: We performed a systematic review of the English literature in three databases (PubMed, Embase, and Latindex) for studies that measured retinal thickness using OCT in people with MCI and healthy controls, age 50 or older, between 1 January 2000 and 31 July 2019. Only cohort and case-control studies were reviewed, and independent extraction of quality data and established objective data was performed. We calculated the effect size for studies in the review that met the following criteria: (1) a statistically significant difference between MCI subjects and normal controls for several OCT variables, (2) use of spectral domain OCT, and (3) use of APOSTEL recommendations for OCT reporting. Weighted Hedges' g statistic was used to calculate the pooled effect size for four variables: ganglion cell layer-inner plexiform layer (GCL-IPL) complex thickness in micrometers (µm), circumpapillary retinal nerve fiber layer (pRNFL) thickness in µm, macular thickness in µm, and macular volume in µm3. For variables with high heterogeneity, a multivariate meta-regression was performed. We followed the PRISMA guidelines for systematic reviews. Results: Fifteen articles met the inclusion criteria. A total of 58.9% of MCI patients had statistically significant thinning of the pRNFL compared with normal subjects, while 61.6% of all MCI patients who had macular volume measured had a statistically significant reduction in volume compared with controls, and 50.0% of the macular GCL-IPL complexes measured demonstrated significant thinning in MCI compared with normal controls. Meta-analysis demonstrated a large effect size for decreased macular thickness in MCI subjects compared with normal controls, but there was a substantial heterogeneity for macular thickness results. The other variables did not demonstrate a significant difference and also had substantial heterogeneity. Meta-regression analysis did not reveal an explanation for the heterogeneity. Conclusions: A better understanding of the cause of retina degeneration and longitudinal, standardized studies are needed to determine if optical coherence tomography can be used as a biomarker for mild cognitive impairment due to Alzheimer's disease.

El cannabis en la enfermedad inflamatoria intestinal: un resumen narrativo / Cannabis in inflammatory bowel disease: a narrative summary

Resumen Introducción: si bien los cannabinoides se han utilizado durante varios años, apenas recientemente se han descrito los descubrimientos sobre sus mecanismos de acción y blancos terapéuticos, así como las alteraciones en el sistema endocannabinoide, observadas en diversas enfermedades y condiciones que se manifiestan con dolor, inflamación, patologías autoinmunes y distintos desórdenes específicos de los órganos. La enfermedad inflamatoria intestinal (EII) agrupa dos condiciones idiopáticas crónicas con patogénesis incierta, en las que se ha identificado que una desregulación del sistema inmune desempeña un papel importante. Así, pues se necesita desarrollar tratamientos alternativos para estos pacientes, ya que solo una minoría de ellos alcanza una remisión de la enfermedad. Nuestro objetivo es revisar las evidencias recientes relacionadas con el uso de cánnabis en la colitis ulcerativa (CU) y en la enfermedad de Crohn (EC). Métodos: se realizó una revisión narrativa focalizada, a partir de las bases de datos de búsqueda de Pubmed y Embase. Los artículos pertinentes fueron revisados y resumidos en forma narrativa. Resultados: los dos componentes principales del cannabis, el cannabidiol (CBD) y el tetrahidrocannabinol (THC), han sido estudiados extensivamente y han probado causar efectos antiinflamatorios y antinociceptivos. Se han descrito ampliamente las propiedades de estos componentes en el control sintomático de la CU y de la EC. No obstante, se sugieren estudios de alta calidad para seguir evaluando la eficacia y la seguridad del uso del cannabis en pacientes con la EII.

Abstract Introduction: Although cannabinoids have been used for several years, only recently have their mechanisms of action and therapeutic targets been described. Alterations in the endocannabinoid system have been observed in various diseases and conditions such as pain, inflammation, autoimmune diseases and various specific disorders. Inflammatory bowel disease groups two chronic idiopathic conditions with uncertain pathogeneses in which deregulation of the immune system plays an important role. Alternative treatments need to be developed for these patients since only a minority of patients achieve disease remission. Our goal is to review recent evidence related to the use of cannabis to treat ulcerative colitis and Crohn's disease. Methods: This is a focused narrative review based on searches of Pubmed and Embase. Relevant articles have been reviewed and summarized in narrative form. Results: The two main components of cannabis, CBD and THC, have been extensively studied, and their anti-inflammatory and antinociceptive effects have been tested. The effects of these components for control of the symptoms of ulcerative colitis and Crohn's disease have been widely described. However, high quality studies are needed to continue evaluating the efficacy and safety of cannabis use in patients with inflammatory bowel disease.

Geoepidemiology of Sjögren's syndrome in Latin America.

OBJECTIVE: To evaluate the geoepidemiology of Sjögren's syndrome (SS) in Latin America. METHODS: This was a three phase study in which original data from a Colombian cohort of patients with SS is presented, followed by a systematic review of Colombian and Latin American studies. Lastly, the geoepidemiology of SS in Latin America was assessed by comparing the clinical characteristics of the region with those of the rest of the world by means of a meta-analysis approach. RESULTS: Data from 2970 patients from Latin America and 18019 patients from Europe, North America and Asia were analyzed. Colombian patients have a lower age at disease onset than those from other Latin American countries and a higher rate of positivity of antinuclear antibodies and rheumatoid factor. A significant difference in the proportion of female patients in Latin America compared with Europe and North America was observed. The spectrum of disease in Latin American was similar to North American patients, while strong differences were noticed between Latin American and European and Asian patients. Noteworthy, a paucity of reports including African and African-descendent patients was observed. CONCLUSIONS: The clinical spectrum of SS differs between countries and continents. Genetic differences relying upon ancestry could explain these findings. However, environmental factors have proven to be important determinants in the development of autoimmune diseases (i.e., autoimmune ecology). Thus, ancestry and the autoimmune ecology should be considered in studies aimed to evaluate the geoepidemiology of SS and other autoimmune diseases.

Sjögren's Syndrome and Autoimmune Thyroid Disease: Two Sides of the Same Coin.

The coexistence of Sjögren's syndrome (SS) and autoimmune thyroid disease (AITD) has been documented. However, there is no consensus whether this coexistence should be considered as the same nosological condition or as polyautoimmunity. Thus, in this monocentric retrospective study, patients with SS alone (i.e., primary) were compared with patients with SS and AITD. In addition, a discussion of previous studies including those about genetic and environmental factors influencing the development of both conditions is presented. In our series, all patients with AITD had Hashimoto's thyroiditis (HT). No significant differences in age, gender, age of disease onset, and disease duration were found between the two groups. Lymphadenopathy and urticaria were more frequently registered in patients with SS-HT than in patients with SS alone (p < 0.05). Anti-Ro/SSA antibodies were more frequent in the primary SS group (p = 0.01). SS-HT patients were more likely to report a positive history of smoking (p = 0.03). The clinical expression of SS varies slightly when HT coexists. Although both entities share common physiopathological mechanisms as part of the autoimmune tautology, they are nosologically different and their coexistence should be interpreted as polyautoimmunity. Further studies based on polyautoimmunity would allow establishing a new taxonomy of autoimmune diseases.

Molecular mimicry and autoimmunity.

Molecular mimicry is one of the leading mechanisms by which infectious or chemical agents may induce autoimmunity. It occurs when similarities between foreign and self-peptides favor an activation of autoreactive T or B cells by a foreign-derived antigen in a susceptible individual. However, molecular mimicry is unlikely to be the only underlying mechanism for autoimmune responses; other factors such as breach in central tolerance, non-specific bystander activation, or persistent antigenic stimuli (amongst others) may also contribute to the development of autoimmune diseases. Host genetics, exposure to microbiota and environmental chemicals are additional links to our understanding of molecular mimicry. Our current knowledge of the detailed mechanisms of molecular mimicry is limited by the issues of prolonged periods of latency before the appearance of disease, the lack of enough statistical power in epidemiological studies, the limitations of the potential role of genetics in human studies, the relevance of inbred murine models to the diverse human population and especially the limited technology to systematically dissect the human T-cell repertoire and B-cell responses. Nevertheless, studies on the role of autoreactive T-cells that are generated secondary to molecular mimicry, the diversity of the T-cell receptor repertoires of auto-reactive T-cells, the role of exposure to cryptic antigens, the generation of autoimmune B-cell responses, the interaction of microbiota and chemical adjuvants with the host immune systems all provide clues in advancing our understanding of the molecular mechanisms involved in the evolving concept of molecular mimicry and also may potentially aid in the prevention and treatment of autoimmune diseases.

Atosiban efficacy and safety in pregnant women with threatened preterm delivery: systematic review of the literature with network meta-analysis / Eficacia y seguridad de atosiban en mujeres gestantes con diagnóstico de amenaza de parto pretérmino: revisión sistemática de la literatura con metaanálisis en red

ABSTRACT Objective: To assess the efficacy and safety of atosiban in pregnant women with risk of preterm delivery as compared to nifedipine, indomethacin, terbutaline, fenoterol and placebo. Materials and methods: A systematic literature review was carried out in eight electronic databases, including Medline, Central, and Embase, using free and standardized search terms. Outcomes assessment included time delay until delivery, neonatal mortality, ratio of adverse maternal events, and ratio of neonatal complications. The quality of the evidence was evaluated per study and for the body of evidence and, whenever feasible, the information was synthesized into a meta-analysis. Alternatively, a narrative summary was presented. Results: Eleven studies were included. Atosiban did not show any statistically significant differences in terms of delaying delivery versus other uterine contraction inhibitors. The neonatal mortality was lower compared to indomethacin (RR = 0.21; 95% CI: 0.05 to 0.92), and the percentage of total maternal adverse events was lower compared to fenoterol (RR = 0.16; 95% CI: 0.08 to 0.31), nifedipine (RR = 0.48; 95% CI: 0.3 to 0.78), and terbutaline (RR = 0.44; 95% CI: 0.28 to 0.71). Conclusions: Atosiban has similar efficacy for delivery delay in patients with risk of preterm delivery as compared to other agents (moderate certainty), showing some advantages regarding neonatal mortality (low certainty) versus indomethacin, and compared to fenoterol, nifedipine and terbutaline in terms of maternal adverse events (moderate certainty).

RESUMEN Objetivo: evaluar la eficacia y seguridad de atosiban en gestantes con amenaza de parto pretérmino comparado con nifedipino, indometacina, terbutalina, fenoterol y placebo. Materiales y métodos: se realizó una revisión sistemática de la literatura en ocho bases de datos electrónicas (Medline, Central, Embase, entre otras), mediante términos de búsqueda libres y estandarizados. Los desenlaces evaluados incluyeron tiempo de retardo del parto, mortalidad neonatal, proporción de eventos adversos maternos y proporción de complicaciones neonatales. Se evaluó la calidad de la evidencia por estudio y para el cuerpo de evidencia, y se sintetizó la información mediante metaanálisis, cuando fue posible; de lo contrario, se resumió de forma narrativa. Resultados: se incluyeron once estudios. Atosiban no mostró diferencias estadísticamente significativas en retardo del parto contra otros uteroinhibidores. Mostró menor mortalidad neonatal que la indometacina (RR = 0,21; IC 95 %: 0,05 a 0,92), y menor proporción de eventos adversos maternos totales que el fenoterol (RR = 0,16; IC 95 %: 0,08 a 0,31), el nifedipino (RR = 0,48; IC 95 %: 0,3 a 0,78) y la terbutalina (RR = 0,44; IC 95 %: 0,28 a 0,71). Conclusiones: atosiban tiene una eficacia similar para retardar el parto ante la amenaza de un parto pretérmino con otros comparadores (certeza moderada), con ventajas frente a indometacina en mortalidad neonatal (certeza baja) y frente a fenoterol, nifedipino y terbutalina en eventos adversos maternos (certeza moderada).

Etiopathogenesis of autoimmune hepatitis.

Autoimmune hepatitis is a chronic inflammatory liver disease characterized by hypergammaglobulinemia, the presence of autoantibodies, and inflammation within the liver, including lymphocytic infiltrates and interface hepatitis. Autoimmune hepatitis shows a female predominance and can present at any age and in any ethnicity. The disease is thought to be a consequence of a break of immune tolerance leading to an autoimmune process that induces liver injury. The self-attack is triggered by T-helper cell-mediated liver autoantigen recognition and B-cell production of autoantibodies, and is sustained by impaired regulatory T cells number and function. Superimposed on a genetic predisposition, infections and environmental factors have been studied as triggering factors for the disease. Allelic variants in the HLA locus have been associated with susceptibility; associations with single nucleotide polymorphisms within non-HLA genes have also been assessed. Several factors have been described as triggers of autoimmune responses in predisposed individuals, including infections, alcohol, vitamin D deficiency, and an altered composition of the intestinal microbiome. Importantly, drugs and herbal agents may trigger classical autoimmune hepatitis, or may induce a liver disease with autoimmune features. Interactions between female hormones and genetic factors have been hypothesized to play a role in autoimmunity, although the exact role for these factors has not been fully established. Herein we present a review of the etiology of autoimmune hepatitis including de novo autoimmune hepatitis post-liver transplantation as well as animal models for its study.

The immunotherapy of Guillain-Barré syndrome.

INTRODUCTION: Guillain-Barré syndrome is the most common cause of acute flaccid paralysis worldwide. Microorganisms such as Campylobacter jejuni, Cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, Haemophilus influenzae and Zika virus have been linked to the disease. The most common clinical variants are acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. Plasma exchange and intravenous immunoglobulins are the standard therapy for the disease. AREAS COVERED: Research to elucidate the pathophysiology of Guillain-Barré syndrome has led to the development of drugs directed towards new potential therapeutic targets. This review offers a comprehensive view of the current treatment based upon the physiopathology. EXPERT OPINION: Patients with Guillain-Barré syndrome need a multidisciplinary approach, limitation to walk unaided and disability score are indicators for treatment as well as the presence of autonomic dysfunction and pain. Admission to intensive care units should be considered for those patients presenting with respiratory failure, bulbar involvement and progression of the disease. Research aimed to deciphering the pathophysiology of the disease, discovering new biomarkers and establishing algorithms of prediction of both the disease and its outcomes is warranted.

The autoimmune ecology: an update.

PURPOSE OF REVIEW: The autoimmune ecology refers to the interactions between individuals and their environment leading to a breakdown in immune tolerance and, therefore, to the development of one or more autoimmune diseases in such an individual. Herein, an update is offered on four specific factors associated with autoimmune diseases, namely, vitamin D, smoking, alcohol and coffee consumption from the perspective of exposome and metabolomics. RECENT FINDINGS: Smoking is associated with an increased risk for most of the autoimmune diseases. Carbamylation of proteins as well as NETosis have emerged as possible new pathophysiological mechanisms for rheumatoid arthritis. Low-to-moderate alcohol consumption seems to decrease the risk of systemic lupus erythematosus and rheumatoid arthritis, and studies of vitamin have suggested a beneficial effect on these conditions. Coffee intake appears to be a risk factor for type 1 diabetes mellitus and rheumatoid arthritis and a protective factor for multiple sclerosis and primary biliary cholangitis. SUMMARY: Recent studies support the previously established positive associations between environmental factors and most of the autoimmune diseases. Nevertheless, further studies from the perspective of metabolomics, proteomics and genomics will help to clarify the effect of environment on autoimmune diseases.

Achenbach's syndrome: Case report and systematic review of the literature / Síndrome de Achenbach: presentación de un caso y revisión sistemática de la literatura

Abstract Introduction: Achenbach's syndrome is a vascular disorder of the hands and feet. It is of unknown etiology and has a benign course. Because of its low prevalence, available literature is limited, and most publications are case reports. No Latin-American publications were found on the subject. The case of a 58 year-old man is presented, along with a systematic review of the literature to describe its clinical characteristics. Methods: A literature search was conducted in PubMed, Embase and Lilacs using free terms and controlled vocabulary (MeSH, Emtree, and DeCS). Results: An analysis was made on a total of 23 articles, 19 of which were case reports, with a total of 46 patients, 43 women and 3 men, from 7 countries. The disorder occurs most often in women over 50 years, and is manifested by the sudden appearance of a blue coloration of the palmar surface of the fingers. It is less common in the feet. Conclusions: Achenbach's syndrome is benign, and does not require medical intervention. Diagnostic methods are of little use. Therefore, identification is important to avoid unnecessary procedures.

Resumen Introducción: El síndrome de Achenbach es un trastorno vascular de manos y pies, de etiología desconocida y de curso benigno. Dada su baja frecuencia de presentación, la literatura disponible es escasa; la mayoría son reportes de casos. No se encontraron publicaciones latinoamericanas sobre el tema. Aquí se presenta un caso clínico, en un hombre de 58 anos, y se hace una revisión sistemática de la literatura para describir sus características clínicas. Métodos: Se realizó una búsqueda de literatura en PubMed, Embase y Lilacs utilizando términos libres y vocabulario controlado (MeSH, Emtree y DeCS). Resultados: Se evaluaron 23 artículos de los cuales 19 fueron reportes de caso. Los reportes de caso muestran la historia de 46 pacientes, 43 mujeres y 3 hombres, en 7 países. El trastorno se presenta más frecuentemente en mujeres mayores de 50 anos y se manifiesta por la aparición súbita de una coloración azul de la cara palmar de los dedos y menos frecuente en los pies. Conclusiones: El síndrome de Achenbach es benigno y no requiere intervenciones médicas. Los métodos diagnósticos son de poca utilidad. Es necesario reconocerlo para evitar procedimientos innecesarios.

Pen Devices for Insulin Self-Administration Compared With Needle and Vial: Systematic Review of the Literature and Meta-Analysis.

OBJECTIVES: Pen devices offer advantages compared with vial and syringe (VaS). The purpose of this article was to evaluate efficacy of pen devices compared to VaS. METHODS: A systematic review of literature was performed in 8 different databases. References were independently screened and selected. Primary observational or experimental studies comparing pen devices with VaS for insulin administrations were included. Studies on specific populations were excluded. Risk of bias was evaluated using appropriate tools. Data on glycosylated hemoglobin (HbA1c), hypoglycemia, adherence, persistence, patient preference, and quality of life (QOL) were collected. Meta-analysis was performed when appropriate. Heterogeneity and risk of publication bias were evaluated. Otherwise, descriptive analyses of the available data was done. RESULTS: In all, 10 348 articles were screened. A total of 17 studies were finally selected: 7 experimental and 10 analytical. The populations of the included articles were mainly composed of adults with type 2 diabetes mellitus. Important risk of bias was found in all of the articles, particularly experimental studies. Meta-analyses were performed for HbA1c, hypoglycemia, adherence and persistence. Pen device showed better results in mean HbA1c change, patients with hypoglycemia, adherence and persistence compared to VaS. No difference was observed in number of patients achieving <7% HbA1c. Preference studies showed a tendency favoring pen devices, however nonvalidated tools were used. One QoL study showed improvements in some subscales of SF-36. CONCLUSIONS: There is evidence that pen devices offer benefits in clinical and, less clearly, patient-reported outcomes compared to VaS for insulin administration. However, these results should be taken with caution.