Characterization of digital annular pulleys and their entheses: an ultrasonographic study with anatomical and histological correlations.

OBJECTIVES: Digital annular pulleys (DAP) are important anatomical structures for finger function. The anatomy, histology, and imaging assessment of DAP, particularly at the level of their entheses is still not clearly defined. The advent of high-frequency ultrasound (US) transducers opened new perspectives in evaluating sub-millimeter scale structures, such as pulleys, paving the way for their global assessment. The study aimed at characterizing DAP from an anatomical, histological, and US perspective, focusing on the detection and complete description of pulley entheses. METHODS: US assessment and gross anatomy dissection were conducted on 20 cadaveric hands to study DAP thickness and structure including enthesis identification. The results of the US and anatomical measurements were correlated. DAP entheses identified by US were characterized via histological analysis. DAP in 20 healthy controls (HC) were detected and measured by US. The A1, A2, and A4 DAP entheses were assessed using a new dynamic maneuver to better evaluate those structures. RESULTS: 1200 DAP (400 cadaveric, 800 HC) were analyzed. The cadaveric study demonstrated strong correlation between anatomical and US measurement of DAP (r = 0.96). At histological level, DAP entheses at the volar plate, sesamoid bones, or phalangeal ridges contained fibrous and fibrocartilaginous tissue. The US assessment of A1, A2, and A4 DAP in HC allowed the identification of 718/720 (99.73%) entheses. CONCLUSION: US is an effective tool to detect and study DAP. DAP entheses reveal both fibrous and fibrocartilaginous characteristics. A newly described maneuver to optimize DAP enthesis visualization enhances their detection by US.

Ultrasonography in rheumatology: time to learn from patient views.

OBJECTIVE: The objective of this observational, descriptive, cross-sectional, multicentre study was to assess the perceived quality and grade of satisfaction expressed by patients with chronic arthropathies regarding the use of musculoskeletal (MSK) ultrasonography by rheumatologists as an integrated clinical care tool. METHODS: All Spanish rheumatology departments with MSK ultrasonography incorporated in their healthcare services were invited to participate in the study. A Spanish-language survey was offered to fill out anonymously to all consecutive patients with chronic arthropathies under follow-up in the rheumatology outpatient clinics who attended their centre for a period of 3 months. The survey consisted of three sections. The first section contained patients' demographics, disease data, frequency of performing rheumatological ultrasound and information about who performed their ultrasound assessments. The second section consisted of 14 questions about patient's experience and opinion on different aspects of the management, performance and perceived usefulness of performing ultrasound, to be answered on a Likert scale 1-5. The third section of the survey was addressed to the rheumatologist ultrasonographers. RESULTS: Nine hundred and four patients from 16 university hospital rheumatology departments completed the survey. All questions reached an overall favourable response ≥ 80%. Patients who reported usual ultrasound examinations in their rheumatology care and those in which it was their attending rheumatologist who performed the ultrasound assessments responded more favourably. CONCLUSION: Our encouraging patient-centred results may be useful in facilitating the implementation of rheumatological ultrasound in rheumatology care worldwide. Key Points • This is the largest multicentre survey carried out in patients with chronic joint diseases designed to assess their experience and perceived benefits with the use of ultrasonography performed by rheumatologists in daily practice. • Musculoskeletal ultrasound incorporated into rheumatology care was very well accepted and valued by most patients. • The patients perceived that ultrasonography helps not only their rheumatologist but also themselves to better understand their condition. • The patients believed that ultrasonography helps them accept and comply with the proposed treatment.

Prevalence of ultrasound and clinical findings suggestive of inflammatory arthritis in children with skin psoriasis.

OBJECTIVE: To evaluate the prevalence of clinical and ultrasound (grey-scale and Doppler) abnormalities in joints, periarticular structures and nails of children affected by skin psoriasis (PsO). METHODS: Cross-sectional study including consecutive children affected by PsO. A systematic clinical and ultrasound evaluation of joints, entheses, tendons and nails were performed by independent examiners blinded to each other assessment. RESULTS: 57 Children: 26 girls (46%), mean age of 9 ± 4 years, divided into two groups, asymptomatic (Asy, 42 children) and symptomatic (Sy, 15 children) according to musculoskeletal pain. Differences were observed between the two groups in relation to age (9 ± 3 in Asy vs 11 ± 4 yrs in Sy, p< 0.05), PsO duration (2.4 ± 2.4 vs 5.4 ± 3.9 yrs, p< 0.001), systemic treatment (23 [54.8%] vs 2 [13.3%], p< 0.01), tender joint count (0 vs 12 children [80%], p< 0.001), swollen joint count (0 vs 3 [20%], p< 0.01) and entheseal pain (0 vs 10 [66.7%], p< 0.001). Ultrasound evaluation showed statistically significant differences between Asy and Sy groups for the presence of ultrasound abnormalities (16/42 [38%] vs 12/15 [80%]), synovitis (1/42 [2%] vs 4/15 [25%]) and enthesitis (4/42 [9.5%] vs 5/15 [33%]). Three children in the Sy group were classified with juvenile psoriatic arthritis (JPsA). CONCLUSIONS: Ultrasound abnormalities were higher in the Sy group with synovitis and enthesitis as the most prevalent findings. Asy patients were more frequently under systemic treatment. Ultrasound and a systematic clinical evaluation are useful tools for detecting subclinical JPsA in children with PsO and musculoskeletal symptoms.

Nonunion of Diaphyseal Humerus Fracture in an Infant: A Case Report.

CASE: A 9-month-old infant girl with Down syndrome presented with an atrophic nonunion of the right humerus diaphysis secondary to birth trauma. Surgical intervention included open reduction and external fixation plus cadaveric cancellous bone allograft and platelet-rich plasma and then was changed to an external fixator in axial compression. At 16 months after surgery, bone healing was achieved. CONCLUSION: Nonunions in infants are rare, and their treatment is a challenge; an adequate vascular supply with good stabilization and reduction are keys to management. We believe that the improvement in reduction and stability under axial compression were the keys to achieve consolidation.

Multi-omics analysis identifies RFX7 targets involved in tumor suppression and neuronal processes.

Recurrently mutated in lymphoid neoplasms, the transcription factor RFX7 is emerging as a tumor suppressor. Previous reports suggested that RFX7 may also have a role in neurological and metabolic disorders. We recently reported that RFX7 responds to p53 signaling and cellular stress. Furthermore, we found RFX7 target genes to be dysregulated in numerous cancer types also beyond the hematological system. However, our understanding of RFX7's target gene network and its role in health and disease remains limited. Here, we generated RFX7 knock-out cells and employed a multi-omics approach integrating transcriptome, cistrome, and proteome data to obtain a more comprehensive picture of RFX7 targets. We identify novel target genes linked to RFX7's tumor suppressor function and underscoring its potential role in neurological disorders. Importantly, our data reveal RFX7 as a mechanistic link that enables the activation of these genes in response to p53 signaling.

p53-mediated AKT and mTOR inhibition requires RFX7 and DDIT4 and depends on nutrient abundance.

In recent years the tumor suppressor p53 has been increasingly recognized as a potent regulator of the cell metabolism and for its ability to inhibit the critical pro-survival kinases AKT and mTOR. The mechanisms through which p53 controls AKT and mTOR, however, are largely unclear. Here, we demonstrate that p53 activates the metabolic regulator DDIT4 indirectly through the regulatory factor X 7 (RFX7). We provide evidence that DDIT4 is required for p53 to inhibit mTOR complex 2 (mTORC2)-dependent AKT activation. Most strikingly, we also find that the DDIT4 regulator RFX7 is required for p53-mediated inhibition of mTORC1 and AKT. Our results suggest that AMPK activation plays no role and p53-mediated AKT inhibition is not critical for p53-mediated mTORC1 inhibition. Moreover, using recently developed physiological cell culture media we uncover that basal p53 and RFX7 activity can play a critical role in restricting mTORC1 activity under physiological nutrient conditions, and we propose a nutrient-dependent model for p53-RFX7-mediated mTORC1 inhibition. These results establish RFX7 and its downstream target DDIT4 as essential effectors in metabolic control elicited by p53.

Resección en bloque de un tumor de células gigantes del cúbito distal y estabilización del muñón cubital con autoinjerto de tendón palmaris longus: reporte de caso / En bloc resection of a giant cell tumor of the distal ulna and stabilization of the ulnar stump with palmaris longus tendon autograft: case report

Introducción: El tumor de células gigantes (TCG) es una neoplasia benigna pero localmente invasiva; la presentación en el extremo distal del cúbito es muy rara. En las lesiones de grado 3 de Campanacci del TCG del cúbito distal se recomienda la resección en bloque del tumor, con o sin la reconstrucción o estabilización del muñón cubital. Reporte del caso: Mujer de 29 años presentó un tumor de células gigantes en el cubito distal grado 3 de Campanacci; fue tratada con resección en bloque del tumor, incluyendo el extensor carpi ulnaris (ECU) debido a estar bien adherido al tumor; el defecto de tendón fue remplazado con autoinjerto de palmaris longus (PL), para luego estabilizar el muñón cubital con el tendón reconstruido. El seguimiento después de 2 años 5 meses no mostró evidencia de recurrencia del tumor, con un excelente resultado funcional y muñón cubital estable. Discusión: Actualmente no hay evidencia suficiente para apoyar el uso de una técnica de estabilización o no, sin embargo, se espera que sea de interés el tratamiento realizado y evitar posibles problemas de estabilidad del muñón cubital ante resecciones amplias que comprometan el ECU. Nivel de evidencia: IV

Introduction: Giant cell tumor (GCT) is a benign but locally invasive neoplasm; presentation at the distal end of the ulna is very rare. In Campanacci grade 3 GCT lesions of the distal ulna, en bloc resection of the tumor is recommended, with or without reconstruction or stabilization of the ulnar stump. Case report: A 29-year-old woman presented with a Campanacci grade 3 giant cell tumor in the distal ulna; was treated with en bloc resection of the tumor, including the extensor carpi ulnaris (ECU) due to being well adhered to the tumor; The tendon defect was replaced with palmaris longus (PL) autograft, and then the ulnar stump was stabilized with the reconstructed tendon. Follow-up after 2 years 5 months showed no evidence of tumor recurrence, with an excellent functional outcome and stable ulnar stump. Discussion: Currently there is not enough evidence to support the use of a stabilization technique or not, however, it is expected that the treatment performed will be of interest and avoid possible stability problems of the ulnar stump in the event of wide resections that compromise the ECU. Level of evidence: IV

Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress.

Despite its prominence, the mechanisms through which the tumor suppressor p53 regulates most genes remain unclear. Recently, the regulatory factor X 7 (RFX7) emerged as a suppressor of lymphoid neoplasms, but its regulation and target genes mediating tumor suppression remain unknown. Here, we identify a novel p53-RFX7 signaling axis. Integrative analysis of the RFX7 DNA binding landscape and the RFX7-regulated transcriptome in three distinct cell systems reveals that RFX7 directly controls multiple established tumor suppressors, including PDCD4, PIK3IP1, MXD4, and PNRC1, across cell types and is the missing link for their activation in response to p53 and stress. RFX7 target gene expression correlates with cell differentiation and better prognosis in numerous cancer types. Interestingly, we find that RFX7 sensitizes cells to Doxorubicin by promoting apoptosis. Together, our work establishes RFX7's role as a ubiquitous regulator of cell growth and fate determination and a key node in the p53 transcriptional program.

Prevalence and significance of ischemic cerebrovascular events in giant cell arteritis

Objectives: To determine the prevalence of cerebrovascular events (CVE) in giant cell arteritis (GCA) and to alert clinicians to the importance of early detection of CVE in this disease.MethodsRetrospective observational study involving a cohort of GCA patients. Demographic, clinical and laboratory data were collected. All patients fulfilled the American College of Rheumatology (ACR) 1990 GCA classification criteria and had a positive ultrasound test for GCA in agreement with the EULAR recommendations. Demographic and clinical parameters were recorded with special attention paid to ischemic cranial events.ResultsWe studied 123 consecutive GCA patients, 74 (60.2%) women with a mean age of 79 years. Twelve patients (9.75%) suffered from neurologic symptoms other than AION, of whom 9 (7.3%) experienced ischemic events related to GCA and 3 (2.44%) likely experienced CVE due to other common causes. Of the 9 patients with CVE caused by GCA, 5 were diagnosed with transient ischemic attacks (TIAs), 2 with ischemic stroke, and 2 were cases involving cranial nerve palsies. High rates of mortality were found in patients with a TIA or stroke, while polymyalgia rheumatica (PMR) appeared to confer some protection against ischemic pathologies in GCA patients.ConclusionsStroke and TIA are common presentation patterns associated with GCA and should be suspected in all CVE-related cases with high acute-phase reactants commonly present in the elderly. This ischemic subgroup exhibited a higher mortality rate. (AU)

Objetivos: Determinar la prevalencia de los accidentes cerebrovasculares (ACV) en la arteritis de células gigantes (ACG) y alertar a los facultativos sobre la importancia de la detección temprana de los ACV en esta enfermedad.MétodosEstudio observacional retrospectivo que incluyó una cohorte de pacientes de ACV. Se recabaron los datos demográficos, clínicos y de laboratorio. Todos los pacientes cumplieron los criterios de clasificación de ACV del American College of Rheumatology de 1990, y su ecografía fue positiva para ACG con arreglo a las recomendaciones EULAR. Se registraron los parámetros demográficos y clínicos, prestándose especial atención a los episodios cerebrales de isquemia.ResultadosEstudiamos 123 pacientes consecutivos de ACG, de los que 74 (60,2%) eran mujeres, con una edad media de 79 años. Doce pacientes (9,75%) tenían síntomas neurológicos distintos a AION, de los cuales 9 (7,3%) evidenciaron episodios isquémicos relacionados con ACG y 3 (2,44%) experimentaron previsiblemente ACV debido a causas comunes. De los 9 pacientes con ACV causado por ACG, 5 fueron diagnosticados de accidente isquémico transitorio (AIT), 2 de accidente isquémico y otros 2 de parálisis del nervio craneal. Se encontraron altas tasas de mortalidad en los pacientes con AIT o ictus, mientras que la polimialgia reumática pareció conferir cierta protección frente a afecciones isquémicas en los pacientes de ACG.ConclusionesLos ictus y los AIT son patrones de presentación comunes asociados a ACG y deberían sospecharse en todos los casos relacionados con ACV con altos reactantes de fase aguda que se presentan comúnmente en los ancianos. Este subgrupo isquémico reflejó una alta tasa de mortalidad. (AU)

Prevalence and significance of ischemic cerebrovascular events in giant cell arteritis.

OBJECTIVES: To determine the prevalence of cerebrovascular events (CVE) in giant cell arteritis (GCA) and to alert clinicians to the importance of early detection of CVE in this disease. METHODS: Retrospective observational study involving a cohort of GCA patients. Demographic, clinical and laboratory data were collected. All patients fulfilled the American College of Rheumatology (ACR) 1990 GCA classification criteria and had a positive ultrasound test for GCA in agreement with the EULAR recommendations. Demographic and clinical parameters were recorded with special attention paid to ischemic cranial events. RESULTS: We studied 123 consecutive GCA patients, 74 (60.2%) women with a mean age of 79 years. Twelve patients (9.75%) suffered from neurologic symptoms other than AION, of whom 9 (7.3%) experienced ischemic events related to GCA and 3 (2.44%) likely experienced CVE due to other common causes. Of the 9 patients with CVE caused by GCA, 5 were diagnosed with transient ischemic attacks (TIAs), 2 with ischemic stroke, and 2 were cases involving cranial nerve palsies. High rates of mortality were found in patients with a TIA or stroke, while polymyalgia rheumatica (PMR) appeared to confer some protection against ischemic pathologies in GCA patients. CONCLUSIONS: Stroke and TIA are common presentation patterns associated with GCA and should be suspected in all CVE-related cases with high acute-phase reactants commonly present in the elderly. This ischemic subgroup exhibited a higher mortality rate.

Desbridamiento apropiado y técnica de "pie crusting" en el manejo de herida traumática / Adequate debridement and pie-crusting technique in the management of traumatic injuries

Las heridas crónicas de origen traumático, con exposición de tejidos, requieren de un desbridamiento adecuado, lavado y una pronta cubierta para evitar la infección y la desecación. A veces, incluso deben ser ampliadas para realizar un adecuado desbridamiento quirúrgico; por lo que, al intentar una cobertura completa, el resultado es una herida a tensión, que se complica con inflamación, infección y la dehiscencia que se acentúa aún más si está en una zona de flexión, como la rodilla. Se presenta el caso de una paciente de 28 años, que acudió a emergencias con un antecedente de herida traumática en la rodilla derecha, signos de retraso de la cicatrización, tejido de granulación friable, exposición de la rótula, abundante secreción serosa y dolor al movimiento con rango limitado. Se la trató en un solo tiempo quirúrgico con desbridamiento, irrigación y cobertura completa de la herida mediante la técnica de "pie-crusting". Nivel de Evidencia: IV

Chronic wounds of traumatic origin, with tissue exposure, require adequate debridement, lavage and prompt coverage to prevent infection and desiccation. Wounds may even require to be enlarged in order to perform an adequate surgical debridement. Enlarged wound attempts to perform a complete coverage may result in tension wound closures, which are complicated by inflammation, infection, and dehiscence and aggravated when located on flexure areas, such as on the knee. We report the case of a 28-year female patient, who presented to the Emergency Department with a history of traumatic wound in the right knee and signs of delayed healing, friable granulation tissue, exposed patella, increased serous drainage, and painful limited range of motion. She underwent a single surgical time procedure with debridement, irrigation, and complete coverage of the wound with the help of the pie-crusting technique. Level of Evidence: IV

Immobilization of laccase of Pycnoporus sanguineus CS43.

Laccase from Pycnoporus sanguineus CS43 was successfully immobilized onto Immobead-150 and Eupergit-C by covalent binding and by entrapment in LentiKats. The highest immobilization was onto Immobead-150 (97.1±1.2%) compared to the other supports, LentiKats (89±1.1%) and Eupergit-C (83.2±1.4%). All three immobilized enzyme systems showed increased thermostability and better mechanical properties than free laccase. Moreover, after 5 cycles of reuse of these systems, 90% of initial laccase activity was retained. Immobead-150 and LentiKats systems exhibited the highest efficiencies in removal of m-cresol under the combined actions of biodegradation and adsorption, while laccase entrapped in LentiKats showed a high ability for degradation of m-cresol within 24h. In addition, the typical Michaelis-Menten enzymatic model effectively described the kinetic profile of m-cresol degradation by the enzyme entrapped in LentiKats. Based on the results obtained in the present study, it can be established that the immobilized biocatalysts developed here possess significant potential for wastewater treatment.

Insight into the Binding of DFG-out Allosteric Inhibitors to B-Raf Kinase Using Molecular Dynamics and Free Energy Calculations.

B-Raf mutations are identified in 40-50% of patients with melanoma and among them, the substitution of valine for glutamic acid at position 600 ((V600E)B-Raf) is the most frequent. Treatment of these patients with B-Raf inhibitors has been associated with a clear clinical benefit. Unfortunately, multiple resistance mechanisms have been identified and new potent and selective inhibitors are currently needed. In this work, five different type II inhibitors, which bind (V600E)B-Raf in its DFG-out conformation, have been studied using molecular dynamics, free energy calculations and energy decomposition analysis. The ranking of calculated MM-PB/GBSA binding affinities is in good agreement with the experimentally measured ones. The per-residue decomposition of ΔGbinding, within the MM-GBSA approach, has been used to identify the key residues governing the allosteric binding of the studied compounds to the (V600E)B-Raf protein kinase. Results indicate that although van der Waals interactions are key determinants for binding, hydrogen bonds also play an important role. This work also provides a better structural understanding of the binding of DFG-out inhibitors to (V600E)B-Raf, which can be used in a further step for rational design of a new class of B-Raf potent inhibitors.

Comparación de sistema de sellado de vasos y ligadura convencional en tiroidectomías / Comparison of vessel sealing system and conventional ligation in thyroidectomy

Cada día es más frecuente en la cirugia tiroidea, el uso de sistemas electromecánicos como método hemostático, en oposicion a la hemostasia convencional. Se realiza un estudio comparativo entre el sistema de sellado de vasos sanguíneos LigaSure® y la hemostasia convencional con ligadura. Se analizaron 113 historias de pacientes sometidos a cirugia tiroidea, evaluando estudios preoperatorios, indicación quirúrgica, complicaciones intra y postoperatorias, reintervención, tiempo quirúrgico, días de hospitalización y resultados de anatomía patológica. Entre enero 2002 y diciembre del 2012, se realizaron 113 tiroidectomías; 52 con el método habitual de ligadura y en 61 pacientes se utilizó como método hemostático el LigaSure®. El promedio de edad fue de 41,3 y 46 años respectivamente; el diagnóstico fue de carcinoma papilar en 19,2% y 22,9%. El tiempo de duración del acto quirúrgico en el grupo de hemostasia convencional fue de 78,8 minutos y en el grupo con sellado de vaso de 74,4 minutos, con un drenaje postoperatorio de 85 y 71 cc para cada grupo. Los días de hospitalizacion fue 3,1 y 2,19. En cuanto a complicaciones: el hematoma post operatorio, con reintervencion (2 casos en ligadura convencional, 1 con el LigaSure®); lesión del nervio recurrente laríngeo (1 caso en cada grupo), hipocalcemia transitoria (3 casos en el grupo convencional y 1 caso en el grupo de LigaSure®); un paciente ameritó traqueostomía en el grupo de LigaSure®. En conclusión, la hemostasia en la tiroidectomía utilizando el metodo de sellado de vasos con LigaSure®, permite la realización del acto quirurgico con comodidad y seguridad, con una ligera ventaja que al utilizar métodos convencionales.

Every day, it is more common in thyroid surgery, the use of electromechanical systems, as hemostatic method in thyroid surgery, as opposed to conventional hemostasis. A comparative study between blood vessel sealing system LigaSure® and conventional hemostasis with ligation was carried out. 113 patients records who underwent thyroid surgery, evaluating preoperative studies, surgical indication, intra and postoperative complications, reoperation, surgical time, days of hospitalization and pathological anatomy results were analized. Between january 2002 and december 2012, 113 thyroidectomies were performed; 52 with the usual ligature method and 61 patients with the LigaSure® hemostatic method. The average age was 41.3 and 46 years respectively; papillary carcinoma was diagnosed in 19,2% and 22,9%. The duration of surgery in the conventional hemostasis group was 78.8 minutes and 74.4 minutes in the vessel sealing group, with a postoperative drainage of 85 and 71 cc for each group. The days of hospitalization were 3.1 and 2.19. In terms of complications: postoperative hematoma with reoperation (2 cases in the conventional group and 1 case in the LigaSure® group); recurrent laryngeal nerve lesion (1 case in each group), transient hypocalcemia (3 cases in the conventional group and 1 case in the LigaSure® group); one patient required tracheostomy in the LigaSure® group. In conclusion, hemostasis in thyroidectomy using the LigaSure® vessel sealing method, allows the realization of surgery in comfort and safety with a slight advantage to conventional methods.