Risk factors for pediatric intracranial neoplasms in the Kids' Inpatient Database (KID).

INTRODUCTION: In children and adolescents brain and central nervous system (CNS) tumors are the leading types of cancers. Past studies have found differing rates of intracranial cancers among races and identified additional cancer risk factors. This study aims to see if these differences can be substantiated with further investigation of the latest version (2019) of the Kids' Inpatient Database (KID). METHODS: A total of 7,818 pediatric patients <21 years old in KID with ICD-10 codes consisting of malignant neoplasms of the brain, brainstem, and cerebral meninges (C700, C709-C719) were queried. Modifiable risk factors evaluated include: hospital region, insurance type, hospital city size, the average income of patient zip code, and location/teaching status of a hospital. Non-modifiable risk factors were race and sex at birth. Dependent variables were tested in Excel and GraphPad Prism 9 using a Chi-squared test with Yates' continuity correction and Tukey's one-way and two-way ANOVAs. RESULTS: Mortality rates of females (2.88%) compared to males (1.99%) were significant (p<0.05). Mortality was (4.17%) in Black patients compared to (1.68%) for White (p<0.0001), Hispanic mortality (2.95%) compared to White (p<0.01), and mortality of Asian/Pacific Islander (3.86%) compared to White (p<0.01). Black patients had significantly higher mortality than White, Hispanic, Asian/Pacific Islander, Native American, and other races overall (p<0.01). There was no significant difference in the mortality rates between children's hospitals and large hospitals for any race. After accounting for patient race, mortality was still not significantly different for patients with Medicaid insurance compared to non-Medicaid insurance types. Of the children treated at children's hospitals, the most transferred in from outside hospitals were Native American (20.00%) followed by Asian/PI (15.09%) then Hispanic patients (13.67%). A significant difference between races was also seen regarding length of stay (p<0.001) and number of charges (p<0.001). CONCLUSION: These findings confirm prior studies suggesting gender and race are significant factors in mortality rates for children with intracranial neoplasms. However, the findings do not identify the root causes of these discrepancies but may serve as an impetus for clinicians, healthcare administrators, and governmental leaders to improve national resource allocation to better care for pediatric patients with intracranial neoplasms.

MEK signaling represents a viable therapeutic vulnerability of KRAS-driven somatic brain arteriovenous malformations.

Brain arteriovenous malformations (bAVMs) are direct connections between arteries and veins that remodel into a complex nidus susceptible to rupture and hemorrhage. Most sporadic bAVMs feature somatic activating mutations within KRAS, and endothelial-specific expression of the constitutively active variant KRASG12D models sporadic bAVM in mice. By leveraging 3D-based micro-CT imaging, we demonstrate that KRASG12D-driven bAVMs arise in stereotypical anatomical locations within the murine brain, which coincide with high endogenous Kras expression. We extend these analyses to show that a distinct variant, KRASG12C, also generates bAVMs in predictable locations. Analysis of 15,000 human patients revealed that, similar to murine models, bAVMs preferentially occur in distinct regions of the adult brain. Furthermore, bAVM location correlates with hemorrhagic frequency. Quantification of 3D imaging revealed that G12D and G12C alter vessel density, tortuosity, and diameter within the mouse brain. Notably, aged G12D mice feature increased lethality, as well as impaired cognition and motor function. Critically, we show that pharmacological blockade of the downstream kinase, MEK, after lesion formation ameliorates KRASG12D-driven changes in the murine cerebrovasculature and may also impede bAVM progression in human pediatric patients. Collectively, these data show that distinct KRAS variants drive bAVMs in similar patterns and suggest MEK inhibition represents a non-surgical alternative therapy for sporadic bAVM.

The natural history of aneurysms incompletely occluded by placement of a flow diverter: a multiinstitutional study.

OBJECTIVE: Treatment of intracranial aneurysms by flow diversion is safe and effective and is increasingly popular. However, the correct treatment paradigm for aneurysms incompletely treated by initial placement of a flow diverter has not been established, nor have the subsequent natural history and occlusion rates of such aneurysms. The authors sought to outline the natural history of such aneurysms, which to date have been considered partially treated. METHODS: The authors retrospectively reviewed consecutive cases from 6 high-volume neurointerventional services, including all cases in which the first follow-up imaging after placement of a flow diverter showed incomplete occlusion of the aneurysm, and for which subsequent clinical and/or radiological follow-up was available. All included patients were treated with the Pipeline Flex embolization device or the Pipeline Flex embolization device with Shield Technology. Subsequent radiographic and clinical outcome data were collected and analyzed using the Kaplan-Meier survival function. RESULTS: A total of 263 patients with persistently patent aneurysms on first follow-up imaging after flow diversion were identified. Of these, 204 had clinical follow-up and 152 had additional imaging follow-up. Of this final cohort, 148 aneurysms were unruptured, and 4 were ruptured. The average aneurysm size by maximum dimension was 10.8 mm. The average recorded follow-up was 27.8 months in the cohort, with some patients followed for as long as 9 years from treatment. Over the course of 403 person-years of follow-up, no delayed aneurysm ruptures were recorded. Both with and without retreatment, aneurysms showed a trend toward progressive occlusion over time. Complications related to device placement were low. CONCLUSIONS: Aneurysms that have been incompletely treated by flow diversion have a benign natural history with progression toward occlusion over time, with or without retreatment.

Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus.

OBJECTIVE: To assess thrombotic risk with PAI-1 levels in patients with COVID-19, to evaluate PAI-1 differences between hyperglycemic and/or Type 2 Diabetes Mellitus (T2DM) versus non-hyperglycemic patients, and to analyze the association of plasminogen activator inhibitor-1 (PAI-1) with hyperglycemia and T2DM. METHODS: A cross-sectional study carried out in 181 patients hospitalized for COVID-19. Two groups were formed: the patients with hyperglycemia at admission and/or previously diagnosed T2DM group and the non-hyperglycemic group. Fibrinolysis was assessed by measuring PAI-1 levels by ELISA. RESULTS: The mean age was 59.4±16.1 years; 55.8% were male 54.1% of patients presented obesity, 38.1% had pre-existing T2DM and 50.8% had admission hyperglycemia and/or pre-existing T2DM. The patients with admission hyperglycemia and/or preexisting T2DM had higher PAI-1 compared with non-hyperglycemic patients [197.5 (128.8-315.9) vs 158.1 (113.4-201.4) ng/mL; p=0.031]. The glucose levels showed a positive correlation with PAI-1 levels (r=0.284, p=0.041). A multivariate logistic regression analysis showed association of PAI-1 level and hyperglycemia and pre-existing T2DM with severity of COVID-19. CONCLUSION: Patients hospitalized for COVID-19 infection with preexisting T2DM or hyperglycemia detected during their hospitalization presented a greater increase in PAI-1 levels, which suggests that hyperglycemia contributes directly to the hypercoagulable state and probably a worse outcome from the patients.

Treatment of intraorbital arteriovenous fistulas with direct puncture: a case series and review of treatments since 1978.

Intraorbital arteriovenous fistulas (IOAVFs) are rare vascular pathologies that may be effectively treated with direct puncture (DP) of the venous supply and may offer a definitive and safe cure when done under ultrasound or stereotactic guidance. Here we present three new cases of DP treatment of IOAVFs, indications for safe use, and their potential complications in comparison to the existing literature on DP and other modalities.Three patients with IOAVFs were treated with DP with ultrasound guidance, stereotactic guidance, and fluoroscopy. Final digital subtraction angiography (DSA) revealed complete cure of IOAVFs. A literature review via PubMed was performed on treatments of IOAVFs since 1978.All three cases of DP resulted in successful cures with 2/3 cases resulting in complications from orbital hematoma formation. 49 total treatments including the cases herein have been documented. DP treatment constituted 5/49, conservative management 17/49, transarterial 8/49, transvenous 18/49, and surgical 3/49. Some cases received more than one mode of treatment. Transarterial and surgical managements were found to have higher complication rates than transvenous and DP.DP is a safe and effective treatment of IOAVFs that can be performed via multiple image guided methods and guarantees a definitive cure. Orbital hematomas are a potential complication of which operators should be aware.

Development of a rabbit human glioblastoma model for testing of endovascular selective intra-arterial infusion (ESIA) of novel stem cell-based therapeutics.

BACKGROUND: Endovascular selective intra-arterial (ESIA) infusion of cellular oncotherapeutics is a rapidly evolving strategy for treating glioblastoma. Evaluation of ESIA infusion requires a unique animal model. Our goal was to create a rabbit human GBM model to test IA infusions of cellular therapies and to test its usefulness by employing clinical-grade microcatheters and infusion methods to deliver mesenchymal stem cells loaded with an oncolytic adenovirus, Delta-24-RGD (MSC-D24). METHODS: Rabbits were immunosuppressed with mycophenolate mofetil, dexamethasone, and tacrolimus. They underwent stereotactic xenoimplantation of human GBM cell lines (U87, MDA-GSC-17, and MDA-GSC-8-11) into the right frontal lobe. Tumor formation was confirmed on magnetic resonance imaging, histologic, and immunohistochemistry analysis. Selective microcatheter infusion of MSC-D24 was performed via the ipsilateral internal carotid artery to assess model utility and the efficacy and safety of this approach. RESULTS: Twenty-five rabbits were implanted (18 with U87, 2 MDA-GSC-17, and 5 MDA-GSC-8-11). Tumors formed in 68% of rabbits (77.8% for U87, 50.0% for MDA-GSC-17, and 40.0% for MDA-GSC-8-11). On MRI, the tumors were hyperintense on T2-weighted image with variable enhancement (evidence of blood brain barrier breakdown). Histologically, tumors showed phenotypic traits of human GBM including varying levels of vascularity. ESIA infusion into the distal internal carotid artery of 2 ml of MSCs-D24 (107 cells) was safe in the model. Examination of post infusion specimens documented that MSCs-D24 homed to the implanted tumor at 24 hours. CONCLUSIONS: The intracranial immunosuppressed rabbit human GBM model allows testing of ESIA infusion of novel therapeutics (eg, MSC-D24) in a clinically relevant fashion.

Stereotactic-guided direct orbital puncture for treatment of orbital arteriovenous fistula.

The patient presented with left-sided chemosis, exophthalmos, and progressive visual loss. Cerebral angiography ed a left orbital arteriovenous malformation and an associated hematoma, with the point of fistulation between the left ophthalmic artery and the anterior section of the inferior ophthalmic vein, with retrograde flow through the superior ophthalmic vein. Transvenous embolization through the anterior facial and angular veins was unsuccessful, with residual shunting. Stereotactic-guided direct venous puncture and Onyx embolization was subsequently performed in the hybrid operating room (OR) to cure the fistula. A subciliary incision allowed for retraction of the orbital contents, creating an optimal trajectory. An endonasal endoscopic approach was performed after the embolization to decompress the orbit. This procedure is shown in video 11-11 neurintsurg;16/4/429/V1F1V1Video 1 .

Safe driving recommendations following lower extremity orthopedic surgery: a systematic review.

PURPOSE: We analyzed the published literature on return-to-driving (RTD) recommendations following lower extremity orthopedic surgery, including knee and hip arthroplasty and ankle and foot surgery. METHODS: We conducted a PubMed MEDLINE database search for the relevant literature spanning from 1988 to 2022. Data were extracted from the selected articles independently by six investigators, and the mean, standard deviation, and range of RTD recommendations for each surgical region and procedure were calculated. RESULTS: The 34 studies included in our review evaluated brake response time, reaction time, movement time, braking force, and other parameters. Average RTD recommendations in weeks were: hip surgeries, 4.1 (± 2.7); foot surgeries, 6.67 (± 0.94); Achilles surgeries, 6.67 (± 0.25); ankle surgeries, 4 (± 2); knee surgeries, 5.42 (± 0.77); and multiple lower extremity surgeries, 3.85 (± 0.15). CONCLUSION: Our findings can assist physicians in providing informed recommendations to patients, promoting safe driving practices, and optimizing postoperative recovery. LEVEL OF EVIDENCE: Therapeutic, Level III: Retrospective comparative study.

The Role and Therapeutic Implications of Inflammation in the Pathogenesis of Brain Arteriovenous Malformations.

Brain arteriovenous malformations (bAVMs) are focal vascular lesions composed of abnormal vascular channels without an intervening capillary network. As a result, high-pressure arterial blood shunts directly into the venous outflow system. These high-flow, low-resistance shunts are composed of dilated, tortuous, and fragile vessels, which are prone to rupture. BAVMs are a leading cause of hemorrhagic stroke in children and young adults. Current treatments for bAVMs are limited to surgery, embolization, and radiosurgery, although even these options are not viable for ~20% of AVM patients due to excessive risk. Critically, inflammation has been suggested to contribute to lesion progression. Here we summarize the current literature discussing the role of the immune system in bAVM pathogenesis and lesion progression, as well as the potential for targeting inflammation to prevent bAVM rupture and intracranial hemorrhage. We conclude by proposing that a dysfunctional endothelium, which harbors the somatic mutations that have been shown to give rise to sporadic bAVMs, may drive disease development and progression by altering the immune status of the brain.

Microsurgical Clipping of a Middle Cerebral Artery Aneurysm After Woven Endobridge Embolization Recurrence.

We present the case of a 67-year-old patient with a left middle cerebral artery (MCA) aneurysm treated with a Woven EndoBridge (WEB) device, who experienced neck recurrence after initial complete obliteration. The initial angiogram showed a wide-necked left MCA aneurysm that measured 8 × 7 mm with a 5-mm neck, treated with a WEB device. Post implantation, the initial follow-up angiogram showed complete obliteration. However, subsequent angiogram showed neck recurrence measuring 6.6 × 1.7 mm. The WEB device has become a popular alternative to traditional clipping and coiling procedures, with studies reporting successful treatment of 85%. However, concerns have been raised regarding the device's efficacy in achieving complete aneurysm obliteration, with a lower rate of complete aneurysm occlusion and a higher rate of recurrence compared with surgical clipping. The decision was made to retreat with clipping, and the surgery was successful in completely obliterating the aneurysm. The patient had no residual MCA aneurysm, with both M2 branches patent on postoperative angiogram. Literature review of retreatment options for WEB device failures highlights that the retreatment rate after WEB embolization is approximately 10%. For surgically accessible aneurysms, surgical clipping is an effective retreatment strategy after WEB failure given the compressibility of the device. Video 1 and our literature review provide valuable insights into a rare case of aneurysm recurrence after complete obliteration at initial follow-up after WEB embolization that was successfully treated with surgical clipping.1-8.

Validation of an automated machine learning algorithm for the detection and analysis of cerebral aneurysms.

OBJECTIVE: Machine learning algorithms have shown groundbreaking results in neuroimaging. The authors herein evaluated the performance of a newly developed convolutional neural network (CNN) to detect and analyze intracranial aneurysms (IAs) on CTA. METHODS: Consecutive patients with CTA studies between January 2015 and July 2021 at a single center were identified. The ground truth determination of cerebral aneurysm presence or absence was made from the neuroradiology report. The primary outcome was the performance of the CNN in detecting IAs in an external validation set, measured using area under the receiver operating characteristic curve statistics. Secondary outcomes included accuracy for location and size measurement. RESULTS: The independent validation imaging data set consisted of 400 patients with CTA studies, median age 40 years (IQR 34 years) and 141 (35.3%) of whom were male; 193 patients (48.3%) had a diagnosis of IA on neuroradiologist evaluation. The median maximum IA diameter was 3.7 mm (IQR 2.5 mm). In the independent validation imaging data set, the CNN performed well with 93.8% sensitivity (95% CI 0.87-0.98), 94.2% specificity (95% CI 0.90-0.97), and a positive predictive value of 88.2% (95% CI 0.80-0.94) in the subgroup with an IA diameter ≥ 4 mm. CONCLUSIONS: The described Viz.ai Aneurysm CNN performed well in identifying the presence or absence of IAs in an independent validation imaging set. Further studies are necessary to investigate the impact of the software on detection rates in a real-world setting.

Automated detection and analysis of subdural hematomas using a machine learning algorithm.

OBJECTIVE: Machine learning algorithms have shown groundbreaking results in neuroimaging. Herein, the authors evaluate the performance of a newly developed convolutional neural network (CNN) to detect and quantify the thickness, volume, and midline shift (MLS) of subdural hematoma (SDH) from noncontrast head CT (NCHCT). METHODS: NCHCT studies performed for the evaluation of head trauma in consecutive patients between July 2018 and April 2021 at a single institution were retrospectively identified. Ground truth determination of SDH, thickness, and MLS was established by the neuroradiology report. The primary outcome was performance of the CNN in detecting SDH in an external validation set, as measured using area under the receiver operating characteristic curve analysis. Secondary outcomes included accuracy for thickness, volume, and MLS. RESULTS: Among 263 cases with valid NCHCT according to the study criteria, 135 patients (51%) were male, the mean (± standard deviation) age was 61 ± 23 years, and 70 patients were diagnosed with SDH on neuroradiologist evaluation. The median SDH thickness was 11 mm (IQR 6 mm), and 16 patients had a median MLS of 5 mm (IQR 2.25 mm). In the independent data set, the CNN performed well, with sensitivity of 91.4% (95% CI 82.3%-96.8%), specificity of 96.4% (95% CI 92.7%-98.5%), and accuracy of 95.1% (95% CI 91.7%-97.3%); sensitivity for the subgroup with an SDH thickness above 10 mm was 100%. The maximum thickness mean absolute error was 2.75 mm (95% CI 2.14-3.37 mm), whereas the MLS mean absolute error was 0.93 mm (95% CI 0.55-1.31 mm). The Pearson correlation coefficient computed to determine agreement between automated and manual segmentation measurements was 0.97 (95% CI 0.96-0.98). CONCLUSIONS: The described Viz.ai SDH CNN performed exceptionally well at identifying and quantifying key features of SDHs in an independent validation imaging data set.

A steroid receptor coactivator small molecule "stimulator" attenuates post-stroke ischemic brain injury.

Introduction: Pathologic remodeling of the brain following ischemic stroke results in neuronal loss, increased inflammation, oxidative stress, astrogliosis, and a progressive decrease in brain function. We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia. Since steroid receptor coactivators are ubiquitously expressed in the brain, we reasoned that an MCB-613 derivative (MCB-10-1), could protect the brain following ischemic injury. To test this, we administered MCB-10-1 to rats following middle cerebral artery occlusion and reperfusion. Methods: Neurologic impairment and tissue damage responses were evaluated on day 1 and day 4 following injury in rats treated with control or 10-1. Results: We show that 10-1 attenuates injury post-stroke. 10-1 decreases infarct size and mitigates neurologic impairment. When given within 30 min post middle cerebral artery occlusion and reperfusion, 10-1 induces lasting protection from tissue damage in the ischemic penumbra concomitant with: (1) promotion of reparative microglia; (2) an increase in astrocyte NRF2 and GLT-1 expression; (3) early microglia activation; and (4) attenuation of astrogliosis. Discussion: Steroid receptor coactivator stimulation with MCB-10-1 is a potential therapeutic strategy for reducing inflammation and oxidative damage that cause neurologic impairment following an acute ischemic stroke.

Flow diversion of a dissecting PICA aneurysm.

A 47-year-old female with a history of a ruptured left posterior inferior cerebellar artery (PICA) aneurysm, status post coil embolization and retreatment for recurrence, presented with evidence of a recurrent dissecting PICA aneurysm. Given that these aneurysms are considered high risk and have a greater propensity for rupture than anterior circulation aneurysms, retreatment was recommended. With the patient's strong preference for endovascular therapy, flow diversion with a Silk Vista Baby was performed. Given the low-profile design of the device, a radial artery approach and coaxial technique were used to deploy the flow diverter. The device was successfully placed, with complete obliteration of the aneurysm after 1 year. The video can be found here: https://stream.cadmore.media/r10.3171/2022.7.FOCVID2247.

A wireless millimetric magnetoelectric implant for the endovascular stimulation of peripheral nerves.

Implantable bioelectronic devices for the simulation of peripheral nerves could be used to treat disorders that are resistant to traditional pharmacological therapies. However, for many nerve targets, this requires invasive surgeries and the implantation of bulky devices (about a few centimetres in at least one dimension). Here we report the design and in vivo proof-of-concept testing of an endovascular wireless and battery-free millimetric implant for the stimulation of specific peripheral nerves that are difficult to reach via traditional surgeries. The device can be delivered through a percutaneous catheter and leverages magnetoelectric materials to receive data and power through tissue via a digitally programmable 1 mm × 0.8 mm system-on-a-chip. Implantation of the device directly on top of the sciatic nerve in rats and near a femoral artery in pigs (with a stimulation lead introduced into a blood vessel through a catheter) allowed for wireless stimulation of the animals' sciatic and femoral nerves. Minimally invasive magnetoelectric implants may allow for the stimulation of nerves without the need for open surgery or the implantation of battery-powered pulse generators.

Comparación del tipo de cirugía bariátrica sobre la reducción de peso corporal y su relación con la ghrelina / Comparison between type of bariatric surgery on reduction of body weight and its ghrelin relationship

Resumen Objetivo: La cirugía bariátrica es un procedimiento para disminuir de peso a largo plazo en pacientes con obesidad. El objetivo de este estudio fue evaluar los niveles de ghrelina y la reducción del peso de acuerdo al tipo de cirugía bariátrica, comparando el bypass de una sola anastomosis y la gastrectomía formadora de manga. Materiales y Métodos: Estudio de cohorte que incluyó a 50 pacientes con obesidad, 22 mini-bypass y 28 mangas gástricas. Se evaluó el peso corporal y las concentraciones de ghrelina en la etapa prequirúrgica, en el día 7 y en los meses 1, 3 y 6 después de la cirugía. Resultados: Del total de pacientes, el 86% presentaron > 50% pérdida del exceso de peso (PEPP) a los 6 meses. La concentración de ghrelina disminuyó desde la primera semana en el grupo total de participantes. A los 6 meses, se observó mayor reducción de ghrelina en los pacientes con la manga gástrica (4.636 ± 2.535 vs 1.340 ± 1.001 pg/mL, p < 0,0001). El PEPP en pacientes con mini-bypass fue superior, en comparación con manga gástrica. Conclusiones: La comparación entre las técnicas indicó que, a los 6 meses de evolución posquirúrgica, los pacientes con mini-bypass presentaron mayor reducción de peso corporal y del nivel de ghrelina, en comparación con el grupo de manga gástrica. La concentración de ghrelina es una variable que participa en el control de peso; sin embargo, el tipo de abordaje quirúrgico probablemente tiene mayor relación con la pérdida de peso en estos pacientes.

Introduction: Bariatric surgery is a procedure to reduce weight in the long term in patients with obesity. The objective of this study was to evaluate ghrelin levels and weight reduction according to the type of bariatric surgery, comparing the single anastomosis bypass and the sleeve-forming gastrectomy. Materials and Method: Cohort study that included 50 patients with obesity, 22 Mini-Bypass and 28 gastric sleeve. Body weight and ghrelin concentrations were evaluated in the presurgical stage, on day 7 and in months 1, 3 and 6 after surgery. Results: Of the total of patients, 86% had > 50% excess weight loss (PEPP) at 6 months. The concentration of ghrelin decreased within the first week of the intervention. At 6 months, greater reduction of ghrelin was observed in patients with gastric sleeve (4636 ± 2535 vs 1340 ± 1001 pg/mL, p < 0.0001). The PEPP in patients with Mini-Bypass was superior, compared to gastric sleeve. Conclusion: The comparison between the techniques indicated that, after 6 months of post-surgical evolution, patients with Mini-Bypass had a greater reduction in body weight and ghrelin levels, compared to the gastric sleeve group. Ghrelin concentration is a variable that participates in weight control; however, the type of surgical approach is probably more related to weight loss in these patients.

The colors of adipose tissue and the relationship with irisin.

Excess adipose tissue is considered one of the main causes of metabolic and cardiovascular diseases. Initially, the adipose tissue was considered the main lipid and energy storage of the organism. Subsequently it was discovered that adipose tissue had other functions such as endocrine, controlling different metabolic and immune processes. Currently, different types of adipose tissue are recognized. The white adipocyte represents the main energy reserve, on the contrary the brown adipocyte is responsible for the oxidation of lipids for thermogenesis. The beige adipocyte originates from the white adipocyte, by a process known as "browning", which leads to lipolysis and thermogenesis. The 3 previous types have recently joined the blue adipocyte, which has a role in liver retinoid homeostasis and the pink adipocyte that participates in lactogenesis and is present in the mammary gland of animals; its role is still unknown in humans. The newly identified hormone Irisin is secreted by the skeletal muscle and promotes browning of white to beige adipose tissue, thus favoring thermogenesis. Another interesting aspect of this hormone is that it represents a connection between muscle activity and lipolysis. The above suggests that Irisin may be the key in the prevention and treatment of obesity.

El exceso de tejido adiposo representa una de las principales causas de las enfermedades metabólicas y cardiovasculares. Inicialmente al tejido adiposo se le consideró el almacén de lípidos y energía del organismo. Posteriormente se descubrió que presentaba otras funciones, como la endocrina, controlando diferentes procesos metabólicos e inmunitarios. Por sus características funcionales y estructurales, se reconocen varios tipos de tejido adiposo. El adipocito blanco representa la reserva energética y el adipocito marrón se encarga de la oxidación de los lípidos para la termogénesis. El adipocito beige se origina del adipocito blanco, mediante un proceso que conduce a la lipólisis y la termogénesis. A los anteriores se han sumado el adipocito azul, en el hígado, que interviene en la homeostasis de retinoides, y el adipocito rosa, que participa en la lactogénesis y se ha identificado en la glándula mamaria de animales. La irisina es una hormona secretada principalmente por el músculo esquelético, que promueve el pardeamiento del tejido adiposo blanco a beige, favoreciendo así la termogénesis. Otro aspecto interesante de esta hormona es que representa una conexión entre la actividad muscular y la lipólisis. Por lo anterior, la irisina puede ser una clave en la prevención y el tratamiento de la obesidad.

Differences between metabolically healthy and unhealthy obesity in PAI-1 level: Fibrinolysis, body size phenotypes and metabolism.

BACKGROUND: Different studies have recognized the existence of subtypes of obesity and normal weight, in which it is reported that not all patients show the same cardiometabolic risk, called "metabolically healthy" and "metabolically unhealthy". In several reviews, differences in the inflammatory profile have been studied, but there is not information on the relationship of body size phenotypes with thrombosis risk. OBJECTIVE: Determine the association between body size phenotypes and fibrinolytic activity by measuring the concentration of plasminogen activator inhibitor-1 (PAI-1). METHODS: A cross-sectional study was conducted in women aged 40 to 65 years. Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Karelis criteria were used to define metabolic status. Four groups were formed: Metabolically healthy normal weight (MHNW), Metabolically unhealthy normal weight (MUNW), Metabolically healthy obese (MHO) and Metabolically unhealthy obese (MUO). RESULTS: 230 women were included in our study with a mean age 52.3 ±â€¯5.9 years. The concentration of PAI-1 showed a significant difference between the groups MHNW, MUNW, MHO, MUO [2.3 (0.08, 13.6), 12.7, (0.08, 33.1), 23.4 (2.6, 28.8) and 22.8 (2.0, 46.7) ng/mL, respectively, p = 0.006]. Multiple regression analysis identified that BMI and HOMA-IR were independent factors influencing PAI-1 levels. CONCLUSION: This study is the first one that recognizes differences in the fibrinolytic activity between body size phenotypes. The groups with the lowest fibrinolytic activity were MUO and MHO, however, MUNW also present alterations of fibrinolysis, thus suggesting a prothrombotic state.

Circulating levels of plasminogen activator inhibitor-1 are associated with metabolic syndrome rather than with menopause.

The plasminogen activator inhibitor type 1 (PAI-1) is the major determinant of fibrinolytic activity. PAI-1 concentrations are elevated in obesity, type 2 diabetes and metabolic syndrome (MetS). On the other hand, during menopause, fibrinolytic activity decreases and, consequently, PAI-1 concentration increases; however, it is debated whether menopause is an independent determinant factor of PAI-1 levels. The objective of this study was to evaluate the effect of hormonal and metabolic status on the concentration of PAI-1 in pre-and post-menopausal women. A case-control study was conducted in ninety pre-and post-menopausal women aged 45 to 55 years, matched by body mass index (BMI). Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Of all the women, 30% presented MetS. Women with MetS had higher values of PAI-1 (36.0 ± 19.1 vs 19.3 ± 14.8 ng/mL, p < .001); in contrast, no differences were observed when compared by hormonal status (20.7 ± 18.10 vs 20.2 ± 17.0 ng/mL, NS). The results of this study suggest that in women, MetS plays a more important role in the deterioration of the fibrinolytic mechanisms rather than their hormonal status. Therefore, the identification of cardio-metabolic factors is relevant to reduce the presence of thrombosis in post-menopausal women.