A clinical practice guideline for the management of the foot and ankle in rheumatoid arthritis.

Rheumatoid arthritis causes progressive joint destruction in the long term, causing a deterioration of the foot and ankle. A clinical practice guideline has been created with the main objective of providing recommendations in the field of podiatry for the conservative management of rheumatoid arthritis. Thus, healthcare professionals involved in foot care of adults with rheumatoid arthritis will be able to follow practical recommendations. A clinical practice guideline was created including a group of experts (podiatrists, rheumatologists, nurses, an orthopaedic surgeon, a physiotherapist, an occupational therapist and patient with rheumatoid arthritis). Methodological experts using GRADE were tasked with systematically reviewing the available scientific evidence and developing the information which serves as a basis for the expert group to make recommendations. Key findings include the efficacy of chiropody in alleviating hyperkeratotic lesions and improving short-term pain and functionality. Notably, custom and standardized foot orthoses demonstrated significant benefits in reducing foot pain, enhancing physical function, and improving life quality. Therapeutic footwear was identified as crucial for pain reduction and mobility improvement, emphasizing the necessity for custom-made options tailored to individual patient needs. Surgical interventions were recommended for cases which were non-responsive to conservative treatments, aimed at preserving foot functionality and reducing pain. Moreover, self-care strategies and education were underscored as essential components for promoting patient independence and health maintenance. A series of recommendations have been created which will help professionals and patients to manage podiatric pathologies derived from rheumatoid arthritis.

Agreement Among Multiple Observers on Crystal Identification by Synovial Fluid Microscopy.

OBJECTIVE: Despite the fact that polarized microscopy remains the gold standard for diagnosing crystal arthritis, some uncertainties hamper full implementation in clinical practice. We undertook this study to analyze the agreement among multiple observers in crystal identification using compensated polarized microscopy, as well as to assess potential outcome modifiers. METHODS: This was a cross-sectional, observational study with consecutive synovial fluid sampling. Samples were immediately analyzed when possible or kept refrigerated at 4°C. Five observers analyzed them separately, blinded to clinical data, using a compensated polarized optical microscope (400×), through 3 stages (ordinary, simple polarized, and compensated polarized light) to detect and identify crystals. They recorded the presence and type of crystal (no crystals, monosodium urate [MSU], and calcium pyrophosphate dihydrate [CPP]). Interrater agreement was measured by Cohen's kappa. Subanalyses were performed on visualization delay and cumulative expertise. Discrepancies between each stage of the microscopy and the final decision were also examined. RESULTS: A total of 250 observations from 50 samples completed full assessment. Overall, κ = 0.74 (95% confidence interval [95% CI] 0.64-0.84), indicating good agreement. Agreement for crystal detection was κ = 0.71 (95% CI 0.59-0.82), for MSU was κ = 0.88 (95% CI 0.75-1.0), and for CPP was κ = 0.69 (95% CI 0.56-0.82). Most of the crystal identifications were already made by ordinary light. No differences between observations made before or after 24 hours (P = 0.859) or in expertise on crystal analysis (P = 0.989) were found. Observations performed under ordinary light matched the final diagnosis in 96.8% of cases (242 of 250). CONCLUSION: Compensated polarized microscopy remained consistent in detecting and identifying crystals in synovial fluid, even when examined among multiple observers, confirming its high utility for clinical practice.

Gouty Involvement of Foot and Ankle: Beyond Flares / Implicación de los tobillos y pies en gota: Algo más que ataques

The foot and ankle are common locations of deposition of monosodium urate (MSU) crystals, as indicated by the clinical manifestations presented by patients with gout, which are not limited to the acute inflammation of the big toe. We present a narrative literature review aimed to update the gout involvement of foot and ankle and how it affects the quality of life. Cumulative reports indicate that gout, even at the non-tophaceous stage, could cause pain, gait impairment and limit the mobility at lower limbs. These patients may present difficulties in some activities of daily living such as choosing footwear, thus leading to an impaired quality of life. Gout is a curable disease by dissolving MSU crystals but remains unclear how this could modify some of these foot and ankle manifestations, especially when structural damage has already occurred. Furthermore, a collaboration between rheumatologists and podiatrists seems helpful to understand, relieve these symptoms and improve the quality of life in gouty patients.(AU)

El pie y el tobillo son lugares comunes de depósito de cristales de urato monosódico (UMS), como indican las manifestaciones clínicas que presentan los pacientes con gota, que no se limitan a la inflamación aguda del primer dedo del pie. Presentamos una revisión narrativa de la literatura con el objetivo de actualizar la implicación de la gota en pie y tobillo y cómo afecta a la calidad de vida. En la literatura se describe que la gota, incluso en la etapa no tofácea, podría causar dolor, deterioro de la marcha y limitaciones de la movilidad en las extremidades inferiores. Estos pacientes pueden presentar dificultades en algunas actividades de la vida diaria, como la elección de calzado, lo cual implica una calidad de vida deteriorada. La gota es una enfermedad curable si se disuelven los cristales de UMS, pero resulta incierto cómo esto podría modificar algunas de estas manifestaciones en pie y el tobillo, especialmente cuando el daño estructural ya ha ocurrido. Además, una colaboración entre reumatólogos y podólogos sería de utilidad para comprender y aliviar estos síntomas así como mejorar la calidad de vida de los pacientes con gota.(AU)

Gouty Involvement of Foot and Ankle: Beyond Flares.

The foot and ankle are common locations of deposition of monosodium urate (MSU) crystals, as indicated by the clinical manifestations presented by patients with gout, which are not limited to the acute inflammation of the big toe. We present a narrative literature review aimed to update the gout involvement of foot and ankle and how it affects the quality of life. Cumulative reports indicate that gout, even at the non-tophaceous stage, could cause pain, gait impairment and limit the mobility at lower limbs. These patients may present difficulties in some activities of daily living such as choosing footwear, thus leading to an impaired quality of life. Gout is a curable disease by dissolving MSU crystals but remains unclear how this could modify some of these foot and ankle manifestations, especially when structural damage has already occurred. Furthermore, a collaboration between rheumatologists and podiatrists seems helpful to understand, relieve these symptoms and improve the quality of life in gouty patients.

Persistence of Crystals in Stored Synovial Fluid Samples.

OBJECTIVE: Lack of access to polarized light microscopy is often cited as an argument to justify the clinical diagnosis of crystal-related arthritis. We assessed the influence of time since sampling and preservation methods on crystal identification in synovial fluid (SF) samples under polarized light microscopy. METHODS: This was a prospective, longitudinal, observational factorial study, analyzing 30 SF samples: 12 with monosodium urate (MSU) crystals and 18 with calcium pyrophosphate (CPP) crystals. Each SF sample was divided into 4 subsamples (120 subsamples in total). Two were stored in each type of preserving agent, heparin or ethylenediamine tetraacetic acid (EDTA), at room temperature or at 4°C. Samples were analyzed the following day (T1), at 3 days (T2), and at 7 days (T3) by simple polarized light microscopy, and the presence of crystals was recorded. RESULTS: The identification of crystals in the MSU group was similar between groups, with crystals observed in 11/12 (91.7%) room temperature samples and in 12/12 (100%) refrigerated samples at T3. Identification of CPP crystals tended to decrease in all conditions, especially when preserved with EDTA at room temperature [12/18 (66.7%) at T3], while less reduction was seen in refrigerated heparin-containing tubes. CONCLUSION: Preserving samples with heparin in refrigerated conditions allows delayed microscopic examination for crystals. Avoiding crystal-proven diagnosis because of the immediate unavailability of microscopy no longer appears justified.

Cardiovascular risk of patients with gout seen at rheumatology clinics following a structured assessment.

OBJECTIVES: Gout-associated cardiovascular (CV) risk relates to comorbidities and crystal-led inflammation. The aim was to estimate the CV risk by prediction tools in new patients with gout and to assess whether ultrasonographic carotid changes are present in patients without high CV risk. METHODS: Cross-sectional study. Consecutive new patients with crystal-proven gout underwent a structured CV consultation, including CV events, risk factors and two risk prediction tools-the Systematic COronary Evaluation (SCORE) and the Framingham Heart Study (FHS). CV risk was stratified according to current European guidelines. Carotid ultrasound (cUS) was performed in patients with less than very high CV risk. The presence of carotid plaques was studied depending on the SCORE and FHS by the area under the curve (AUC) of receiver operating curves. RESULTS: 237 new patients with gout were recruited. CV stratification by scores showed a predominance of very high (95 patients, 40.1%) and moderate (72 patients, 30.5%) risk levels. cUS was performed in 142 patients, finding atheroma plaques in 66 (46.5%, 95% CI 37.8 to 54.2). Following cUS findings, patients classified as very high risk increased from 40.1% up to 67.9% (161/237 patients). SCORE and FHS predicted moderately (AUC 0.711 and 0.683, respectively) the presence of atheroma plaques at cUS. CONCLUSIONS: The majority of patients presenting with gout may be at very high CV risk, indicating the need for initiating optimal prevention strategies at this stage. Risk prediction tools appear to underestimate the presence of carotid plaque in patients with gout.

Primoinfección tuberculosa en pacientes con anti-TNF-α y cribado inicial negativo / Primary tuberculosis infection in patients treated with tumor necrosis factor-alpha antagonists and a negative initial screening

Introducción. A pesar de las medidas de cribado de tuberculosis (TB) siguen detectándose casos en pacientes tratados con anti-TNF-α y cribado inicial negativo, algunos tras largo tiempo de tratamiento, lo que apunta más a una nueva infección. Objetivos. Describir los casos que presumiblemente han desarrollado primoinfección tuberculosa durante el tratamiento con fármacos anti-TNF-α. Métodos. Revisión retrospectiva (1999-2012), seleccionando según los siguientes criterios: a) tratamiento anti-TNF-α; b) cribado de TB inicial negativo; c) TB diagnosticada durante tratamiento anti-TNF-α, y d) sospecha de primoinfección tuberculosa (tras mínimo 12 meses de anti-TNF-α). Se han revisado sus variables clínicas, epidemiológicas, terapéuticas y de desenlace. Resultados. Dos casos de primoinfección tuberculosa de 771 pacientes tratados con anti-TNF-α (0,2%). Una mujer de 41 años y 35 meses de tratamiento con adalimumab y un varón de 37 años y 107 meses de tratamiento con infliximab. La mujer presentó una neumonía y el varón una TB diseminada. Conclusiones. Durante la terapia anti-TNF-α persiste el riesgo de TB a pesar de cribado inicial negativo, por lo que el grado de sospecha debe ser elevado durante todo el tratamiento (AU)

Introduction. Despite screening for latent tuberculosis (TB), new cases of TB infection are detected in patients treated with anti-TNF-α and negative initial screening, some of them after long treatment, which points more to a new infection. Objectives. To describe the cases that have presumably developed a primary tuberculous infection during treatment with anti-TNF-α drugs. Methods. Retrospective audit (1999-2012). Inclusion criteria were: a) anti-TNF-α treatment; b) initial latent TB screening negative; c) TB diagnosed during anti-TNF-α treatment; d) suspected primary TB infection (diagnosis after at least 12 months on anti-TNF-α). Clinical, epidemiological, therapeutic and outcome variables were reviewed. Results. Two cases of primary TB infection were found out of of 771 anti-TNF-α treated patients (0.2%). One woman aged 41 suffered TB pneumonia after 35 months of treatment with adalimumab, and a male aged 37 who developed disseminated TB after 107 months of treatment with infliximab. Conclusions. Although uncommon, during TNF antagonist therapy, TB risk persists despite negative initial screening, so clinicians should be aware of TB during the entire treatment (AU)

Gout: optimizing treatment to achieve a disease cure.

Gout is one of the most common inflammatory arthritides. The disease is due to the deposition of monosodium urate crystals. These deposits are reversible with proper treatment, suggesting that gout is a curable disease. The main aim in gout is to lower serum uric acid levels to a pre-established target; there are different urate-lowering drugs (xanthine oxidase inhibitors, uricosurics and uricases) through which this can be achieved. Proper treatment of gout also involves correct management of acute flares and their prevention. To ensure treatment adherence it is necessary to explain to the patient what the objectives are.

Primary tuberculosis infection in patients treated with tumor necrosis factor-alpha antagonists and a negative initial screening.

INTRODUCTION: Despite screening for latent tuberculosis (TB), new cases of TB infection are detected in patients treated with anti-TNF-α and negative initial screening, some of them after long treatment, which points more to a new infection. OBJECTIVES: To describe the cases that have presumably developed a primary tuberculous infection during treatment with anti-TNF-α drugs. METHODS: Retrospective audit (1999-2012). Inclusion criteria were: a) anti-TNF-α treatment; b) initial latent TB screening negative; c) TB diagnosed during anti-TNF-α treatment; d) suspected primary TB infection (diagnosis after at least 12 months on anti-TNF-α). Clinical, epidemiological, therapeutic and outcome variables were reviewed. RESULTS: Two cases of primary TB infection were found out of of 771 anti-TNF-α treated patients (0.2%). One woman aged 41 suffered TB pneumonia after 35 months of treatment with adalimumab, and a male aged 37 who developed disseminated TB after 107 months of treatment with infliximab. CONCLUSIONS: Although uncommon, during TNF antagonist therapy, TB risk persists despite negative initial screening, so clinicians should be aware of TB during the entire treatment.

Single-channel study of the binding-gating coupling in the slowly desensitizing chimeric alpha7-5HT3A receptor.

We have studied the role of the highly conserved residue alphaLysine145 in the early steps of activation by acetylcholine of the nicotinic acetylcholine receptor (nAChR). Both macroscopic and single-channel currents were recorded in the slowly desensitizing chimeric mutant receptor alpha7V201-5HT3A/R432Q/R436D/R440A, made of alpha7 nAChRs and serotonin receptors of subtype 3A (ch1), and its corresponding mutant K145A (ch1/K145A) expressed in Xenopus oocytes. Mutant ch1/K145A receptors had a reduced gating function similar to that produced by the same mutation in the wild type receptor alpha7. The mutated receptor has reduced opening rate constants, beta, and increased closing rate constants, alpha.

Binding-gating coupling in a nondesensitizing alpha7 nicotinic receptor A single channel pharmacological study.

The highly conserved alphaLys145 has been suggested to play an important role in the early steps of activation of the nicotinic acetylcholine receptor (nAChR) by acetylcholine. Both macroscopic and single channel currents were recorded in the slowly desensitizing mutants L248T- and K145A-L248T-alpha7 receptors expressed in Xenopus oocytes. On ACh-evoked currents, substitution of Lys145 by alanine showed the same effects that in wild type receptors: moderately decreased gating function and a more-than-expected loss of ACh potency, thus validating the experimental model. Single channel analysis quantitatively agreed with macroscopic data and revealed that impaired gating function in the double mutant alpha7K145A/L248T is the consequence of a slower opening rate, beta. Several nicotinic agonists were also studied, showing important features. Particularly, dimethylphenylpiperazinium (DMPP), acting as an antagonist in alpha7K145A, became a full agonist in alpha7K145A/L248T. Single channel analysis of DMPP-evoked currents showed effects of Lys145 removal similar to those observed with ACh. Data suggest that alpha7Lys145 facilitates the early steps of channel activation. Moreover, the slowly desensitizing mutant alpha7L248T could be an interesting tool for the study of channel activation in alpha7 receptors. Nevertheless, its extensively altered pharmacology precludes the simple extrapolation of pharmacological data obtained in singly mutated alpha7 receptors.

Improved gating of a chimeric alpha7-5HT3A receptor upon mutations at the M2-M3 extracellular loop.

Acetylcholine-evoked currents of the receptor chimera alpha7-5HT3A V201 expressed in Xenopus oocytes are strikingly small when compared to the amount of alpha-bungarotoxin binding sites detected at the oocyte membrane. Since the chimeric receptor is made of the extracellular N-terminal region of the rat alpha7 nicotinic acetylcholine receptor and the C-terminal region of the mouse 5-HT3A receptor, which includes the ion channel, we hypothesized that communication between these two regions was not optimal. Here, we show that mutating to aspartate several adjacent positions in the M2-M3 extracellular linker increases current amplitudes to different extents, thus confirming the important role of this region on receptor gating.

Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite.

The effects of various Flustra foliacea metabolites on different types of human neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated. Whereas most of the compounds tested had a small blocking effect, one of them, deformylflustrabromine, selectively increased the current obtained in alpha4beta2 receptors when co-applied with acetylcholine (ACh). The current increase was reversible and concentration-dependent. This potentiating effect was still present at saturating concentrations of acetylcholine, and no changes in single-channel conductance or reversal potential were observed, thus suggesting a modification in the gating of alpha4beta2 receptors. Dwell time analysis of single channel records indicates that the mechanism of action of deformylflustrabromine could be both an increase of the opening rate constant and a decrease of the closing rate constant on alpha4beta2 receptors. Thus, deformylflustrabromine may constitute an excellent starting point for the future development of related agents able to potentiate human neuronal nicotinic receptor function.

Síndrome de contracción capsular posterior a cirugía de facoemulsificación. Reporte de un caso / Posterior capsular contraction syndrome after facoemulsification surgery. Case report

Objetivo: Reportar un caso con el síndrome de contracción capsular. Métodos: Descripción de la exploración oftalmógica y de los diferentes procedimientos quirúrgicos realizados. Resultados: Caso clínico de un paciente masculino de 53 años de edad, postoperado de catarata congénita con técnica de facoemulsificación con implante de lente intraocular de silicona, que a los 2 años de operado desarrolló un síndrome de contracción capsular, bajando su capacidad visual de 20/50 a cuenta dedos a 5 pies, requiriendo una nueva intervención quirúrgica consistente en capsulotomía anterior quirúrgica, bajo anestesia local, y posteriormente una capsulotomía posterior con láser de Nd: Yag, recuperando una capacidad visual de 20/80. Conclusiones: Se recomienda no realizar capsulorrexis pequeña; ésta debe ser del tamaño del óptico del lente intraocular a utilizarse, sobre todo en aquellos pacientes de alto riesgo en el desarrollo de esta patología.

Síndrome de Weill-Marchesani: Presentación de un caso / Weill-Marchesani syndrome. Case report

El síndrome de Weill-Marchesani es un trastorno raro de herencia recesiva, caracterizado por talla corta, dedos rollizos y cortos y, en ocasiones, retraso mental. Entre las manifestaciones oculares la más importante es la microesferofaquia que, durante la adolescencia o al principio de la segunda década de la vida, puede cursar con una dislocación del cristalino hacia abajo. En ocasiones este síndrome se puede asociar a anomalías del ángulo camerular por disgenesias mesodérmicas y a glaucoma por bloqueo pupilar. El tratamiento en este síndrome dependerá de cada caso.

Evaluación clínica de la solución intraocular de carbacol al 0.01 por ciento / Clinic evaluation of the efficacy and safety of Carbacol 0.01 percent in ophthalmic solution

Se realizó un estudio prospectivo abierto para evaluar la eficacia y seguridad de la solución oftálmica de Carbacol al 0.01 por ciento, incluyendo sesenta pacientes sometidos tanto a extracción extracapsular de catarata como a facoemulsificación, enrolados en dos centros de atención oftlamológica de la Ciudad de México. Se reportó la disminución satisfactoria del diámetro popular después del procedimiento quirúrgico, así como un adecuado mantenimiento de los niveles de presión intraocular. Esto permitió que el implante intraocular permaneciera en su sitio adecuadamente y evitó la posibilidad de incrementos tensionales riesgosos. El medicamento posee mínimos efectos inflamatorios y poca interferencia con otras sustancias empleadas durante la cirugía, pudiendo modularse sus acciones según los requerimientos del cirujano y del paciente.