Evaluation of ultrasound as diagnostic tool in patients with clinical features suggestive of carpal tunnel syndrome in comparison to nerve conduction studies: Study protocol for a diagnostic testing study.

BACKGROUND: Carpal Tunnel Syndrome (CTS) is the most common compressive neuropathy, accounting for 90% of all neuropathies. Its prevalence ranges from 3.8%-7.8% in the population. The gold standard for its diagnosis is the neurophysiological study (85% sensitivity and 95% specificity), with the disadvantage of being invasive, complex and expensive, which means an increase in cost and time for the diagnosis of the disease. The main objective of this diagnostic test evaluation study is to investigate the value of ultrasound in the diagnosis of CTS, and among the secondary objectives, to establish the ultrasound parameters that are predictors of CTS in comparison with neurophysiological studies, attempting to standardize a protocol and reference values that determine the presence or absence of CTS. METHODS: Prospective, cross-sectional study. The reference test with which we compared the ultrasound is the neurophysiological test (NPT). Patients will come consecutively from the Neurophysiology Department of the Virgen Macarena Hospital, with clinical suspicion of CTS and fulfilling the inclusion/exclusion criteria. To calculate the sample size (EPIDAT program) we proposed a sensitivity of 78% and specificity of 87% with a confidence level of 95%, requiring 438 patients (264 NPT positive, 174 NPT negative). We followed an ultrasound study protocol that included the ultrasound variables: cross-sectional area at the entrance and exit of the tunnel, range of nerve thinning, wrist-forearm index, flexor retinaculum bulging, power Doppler uptake and the existence of adjacent wrists or masses. We propose a timeline for the study to be performed between 2020 and 2023. Finally, we propose a cost-effectiveness analysis. DISCUSSION: Ultrasound not only allows to objectify the alterations of the median nerve but also the underlying pathological mechanisms in CTS. A multitude of ultrasound parameters have been described that should be regarded in syndrome's study, among which we included the cross-sectional area, the range of nerve thinning, the wrist-forearm index, flexor retinaculum bulging, power Doppler uptake and assessment of anatomical alterations. The use of ultrasound as a diagnostic tool in CTS has many advantages for both doctors and the patients, as it is a non-invasive, convenient, and fast tool increasingly accessible to professionals. TRIAL REGISTRATION: Trials registry number: NCT05556278.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories.

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: What parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile? / Documento de consenso para la determinación e informe del perfil lipídico en laboratorios clínicos españoles: ¿Qué parámetros debe incluir un perfil lipídico básico?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Long Term Response to Circulating Angiogenic Cells, Unstimulated or Atherosclerotic Pre-Conditioned, in Critical Limb Ischemic Mice.

Critical limb ischemia (CLI), the most severe form of peripheral artery disease, results from the blockade of peripheral vessels, usually correlated to atherosclerosis. Currently, endovascular and surgical revascularization strategies cannot be applied to all patients due to related comorbidities, and even so, most patients require re-intervention or amputation within a year. Circulating angiogenic cells (CACs) constitute a good alternative as CLI cell therapy due to their vascular regenerative potential, although the mechanisms of action of these cells, as well as their response to pathological conditions, remain unclear. Previously, we have shown that CACs enhance angiogenesis/arteriogenesis from the first days of administration in CLI mice. Also, the incubation ex vivo of these cells with factors secreted by atherosclerotic plaques promotes their activation and mobilization. Herein, we have evaluated the long-term effect of CACs administration in CLI mice, whether pre-stimulated or not with atherosclerotic factors. Remarkably, mice receiving CACs and moreover, pre-stimulated CACs, presented the highest blood flow recovery, lower progression of ischemic symptoms, and decrease of immune cells recruitment. In addition, many proteins potentially involved, like CD44 or matrix metalloproteinase 9 (MMP9), up-regulated in response to ischemia and decreased after CACs administration, were identified by a quantitative proteomics approach. Overall, our data suggest that pre-stimulation of CACs with atherosclerotic factors might potentiate the regenerative properties of these cells in vivo.

Atherosclerotic Pre-Conditioning Affects the Paracrine Role of Circulating Angiogenic Cells Ex-Vivo.

In atherosclerosis, circulating angiogenic cells (CAC), also known as early endothelial progenitor cells (eEPC), are thought to participate mainly in a paracrine fashion by promoting the recruitment of other cell populations such as late EPC, or endothelial colony-forming cells (ECFC), to the injured areas. There, ECFC replace the damaged endothelium, promoting neovascularization. However, despite their regenerative role, the number and function of EPC are severely affected under pathological conditions, being essential to further understand how these cells react to such environments in order to implement their use in regenerative cell therapies. Herein, we evaluated the effect of direct incubation ex vivo of healthy CAC with the secretome of atherosclerotic arteries. By using a quantitative proteomics approach, 194 altered proteins were identified in the secretome of pre-conditioned CAC, many of them related to inhibition of angiogenesis (e.g., endostatin, thrombospondin-1, fibulins) and cell migration. Functional assays corroborated that healthy CAC released factors enhanced ECFC angiogenesis, but, after atherosclerotic pre-conditioning, the secretome of pre-stimulated CAC negatively affected ECFC migration, as well as their ability to form tubules on a basement membrane matrix assay. Overall, we have shown here, for the first time, the effect of atherosclerotic factors over the paracrine role of CAC ex vivo. The increased release of angiogenic inhibitors by CAC in response to atherosclerotic factors induced an angiogenic switch, by blocking ECFC ability to form tubules in response to pre-conditioned CAC. Thus, we confirmed here that the angiogenic role of CAC is highly affected by the atherosclerotic environment.

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia.

BACKGROUND: Critical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities. Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization. Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues. METHODS: Balb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 µl physiological serum (SC, n:8) or 5 × 105 human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related. RESULTS: Administration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown. CONCLUSIONS: Our results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.

Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide.

Lack of endothelial nitric oxide causes endothelial dysfunction and circulating monocyte infiltration, contributing to systemic atheroma plaque formation in arterial territories. Among the different inflammatory products, macrophage-derived foam cells and smooth muscle cells synthesize matrix metalloproteinases (MMPs), playing a pivotal role in early plaque formation and enlargement. We found increased levels of MMP-9 and MMP-13 in human endarterectomies with advanced atherosclerosis, together with significant amounts of extracellular matrix (ECM) metalloproteinase inducer EMMPRIN. To test whether the absence of NO may aggravate atherosclerosis through EMMPRIN activation, double NOS3/apoE knockout (KO) mice expressed high levels of EMMPRIN in carotid plaques, suggesting that targeting extracellular matrix degradation may represent a new mechanism by which endothelial NO prevents atherosclerosis. Based on our previous experience, by using gadolinium-enriched paramagnetic fluorescence micellar nanoparticles conjugated with AP9 (NAP9), an EMMPRIN-specific binding peptide, magnetic resonance sequences allowed non-invasive visualization of carotid EMMPRIN in NOS3/apoE over apoE control mice, in which atheroma plaques were significantly reduced. Taken together, these results point to EMMPRIN as a new therapeutic target of NO-mediated protection against atherosclerosis, and NAP9 as a non-invasive molecular tool to target atherosclerosis.

Enfermedad multianeurismática: a propósito de un caso / Multi-aneurysmal disease: a case report

Resumen Introducción: La enfermedad multianeurismática es una entidad patológica poco conocida, la cual presenta diversas etiologías, por lo que su localización, morfología y formas de presentación varían de un caso a otro. Caso clínico: Mujer de 51 años dislipémica. Acude por epigastralgia. Se realiza TC abdominal con resultados de hematoma retroperitoneal y aneurisma en arteria pancreática duodenal. Se practica cirugía urgente para evacuación del hematoma sin encontrarse más hallazgos. Durante el ingreso presenta crisis hipertensivas y se realiza nuevo AngioTC donde se visualizan múltiples lesiones en distintas arterias viscerales con posibilidad diagnóstica de vasculitis. Se decide no intervención en el momento actual y estudio de filiación. Discusión: La enfermedad multianeurismática es una entidad poco común, cuya etiología se determina de acuerdo con su correlación clínica e histopatológica con diversas posibles causas; sin embargo, establecer un diagnóstico en donde el cuadro clínico coincida al 100%, es un desafío. Es muy frecuente la afectación de las arterias viscerales a diferencia de los aneurismas de origen ateroesclerótico. El tratamiento quirúrgico es seguro y deberá iniciarse en los segmentos que estén causando la sintomatología. El tratamiento endovascular es menos invasivo siendo la técnica de elección en pacientes con elevada comorbilidad y en los casos de cirugía complicada con rotura.

Introduction: Multiple artery aneurysms are a rare pathological condition which may be caused by different etiologies. Therefore, its location, morphology and clinical presentation may vary in a case to case basis. Case report: A 51-year-old woman, prior history of dyslipedemia presents with upper abdominal pain. Abdominal tomographic scans showed aneurysm of the pancreaticduodenal artery and retroperitoneal hematoma. Emergent surgical evacuation of the hematoma was performed, with no other findings. In the postoperative period, the patient suffers hypertensive crisis and a new tomographic scan is conducted observing multiple dilations in different visceral arteries. The patient is treated conservatively and is being studied for a possible vasculitis. Discussion: Multi-aneurysmatic artery disease is a very rare entity, its etiology is determined by clinical and histopathological correlation. Although establishing a diagnosis in which the clinical presentation completely corresponds, is a real challenge. Unlike degenerative aneurysms due to atherosclerosis, multi-aneurysmatic disease commonly involves visceral arteries. Open surgery is considered safe treatment option and should be established in the segments causing symptoms. Endovascular treatment is less invasive, being the technique of choice in patients with high comorbidity and in cases of complicated surgery with rupture.

Liposarcoma retroperitoneal complicado: a propósito de un caso / Complicated retroperitoneal liposarcoma: a case report

Resumen Las neoplasias retroperitoneales suponen un reto para el profesional sanitario, tanto en el diagnóstico como en el tratamiento. Caso clínico: Varón de 56 años diabético tipo 2. Acude por edema en extremidad inferior derecha y parestesias. Se realiza ecografía doppler con resultados de trombosis venosa profunda y conglomerado adenopático. En TAC abdominal se observa gran masa retroperitoneal que engloba paquete vasculonervioso iliaco derecho. Se realiza vaciamiento ganglionar con resultado inicial de hamartoma. Se practica cirugía de resección de la masa y ligadura de la vena iliaca externa trombosada preservando la arteria iliaca. Anatomía patológica intraoperatoria sugestiva de sarcoma y definitiva de liposarcoma. Reingresa por shock hipovolémico y rotura de la arteria iliaca derecha. Se realiza ligadura y bypass femoro-femoral izquierdo-derecho. Al alta es derivado a oncología, falleciendo a los 6 meses. Discusión: El sarcoma es el tumor primario más frecuente a nivel retroperitoneal (15%). De difícil diagnóstico y tardío tratamiento, suelen ser asintomáticos hasta que debutan como una masa y clínica de compresión local o afectación de estructuras vasculonerviosas. El TAC es la prueba diagnóstica de elección. El tratamiento del tumor localizado es la cirugía; la radioterapia y quimioterapia se reservan para tumores irresecables o de alto grado.

Abstract Retroperitoneal neoplasias may be a diagnostic and therapeutic challenge for the clinician. Case report: A 56 year old male with prior history of type 2 diabetes consults with right inferior limb edema and paresthesias. He was diagnosed of deep vein thrombosis and lymph node conglomerate by ultrasound. A CT scan was performed, observing great retro peritoneal mass enclosing vascular and nervous structures. An initial histological diagnosis of hamartoma was made. Surgery was scheduled to remove the tumour, ligation of thrombosed external iliac vein and the external iliac artery was preserved. Intraoperative histological findings suggested sarcoma, definite studies showed presence of high grade liposarcoma. Two weeks after the intervention, the patient presents in hypovolemic shock due to rupture of the right external iliac artery. Emergent ligation of the artery and femorofemoral bypass was performed, with adequate postoperatory recovery. The patient was discharged and continued adjuvant oncology treatment and was exitus six months later. Discussion: Sarcomas are the most frequent primary retroperitoneal tumours. They are difficult to diagnose and often have untimely treatment. Sarcomas tend to be asymptomatic, or present with local compression symptoms, affecting vascular and nervous structures. CT scan is the gold standard for diagnostic imaging. Treatment requires a multidisciplinary approach, surgical resection as the main therapy; radio and chemotherapy represents a solution for irresectable or high grade malignancies.

Aneurisma gigante de arteria iliaca interna roto / Giant ruptured internal iliac aneurysm

Objetivo: Presentar un caso infrecuente de aneurisma gigante de arteria iliaca interna roto. Caso clínico: Varón de 68 años de edad con antecedentes de hipertensión arterial crónica, dislipidemia, cardiopatía valvular, cor pulmonale con hipertensión pulmonar moderada, portador de marcapasos definitivo, obesidad y alergia a la plata. Ingresa de urgencia por dolor brusco en fosa iliaca izquierda, irradiado periumbilicalmente sin cortejo vegetativo. En el TC abdominal se objetiva la presencia de un aneurisma gigante de la arteria hipogástrica izquierda con diámetro de 6,8 cm y signos de rotura. Se realiza de forma urgente cirugía endovascular mediante implante de prótesis Endurant® y embolización de arterias glúteas con Coils Interlock®. Control al mes y a los 6 meses sin endofugas ni crecimiento del saco. Discusión: El tratamiento de elección de los aneurismas iliacos sigue siendo la cirugía, de forma electiva cuando el diámetro de la arteria es mayor de 3 cm y urgente cuando debutan con rotura. La terapia endovascular es una alternativa segura y eficaz a la cirugía convencional, con resultados satisfactorios a corto y medio plazo.

Aim: To present an infrequent broken giant Iliac artery aneurysms. Case report: In the current study, we report a case of a 68-year-old male patient with chronic high blood pressure, cholesterol, valvular heart disease, cor pulmonale, pacemaker, obesity and silver allergic. He presented sudden onset of abdominal pain. Computed tomography (CT) revealed a large ruptured left hypogastric aneurysm (diameter of 6.8 cm). Hypogastric aneurysm was repaired by an endovascular graft repair: Endurant® endogratf and coils embolization of gluteal arteries (Interlock®). The patient had a satisfactory clinical progression and recovery. At one and six months after the operation TC revealed not Type II endoleaks. Discussion: Isolated aneurysms of the iliac arteries are rare. Surgical treatment is recommended for iliac artery aneurysms larger than 3 cm. Endovascular repair is an attractive method to repair isolated iliac artery aneurysms with lower morbidity and mortality rates than open surgery.