The potential of Senolytics in transplantation.

Older organs provide a substantial unrealized potential with the capacity to close the gap between demand and supply in organ transplantation. The potential of senolytics in improving age-related conditions has been shown in various experimental studies and early clinical trials. Those encouraging data may also be of relevance for transplantation. As age-differences between donor and recipients are not uncommon, aging may be accelerated in recipients when transplanting older organs; young organs may, at least in theory, have the potential to 'rejuvenate' old recipients. Here, we review the relevance of senescent cells and the effects of senolytics on organ quality, alloimmune responses and outcomes in solid organ transplantation. This article is part of the Special Issue - Senolytics - Edited by Joao Passos and Diana Jurk.

In vitro reconstructed 3D corneal tissue models for ocular toxicology and ophthalmic drug development.

Testing of all manufactured products and their ingredients for eye irritation is a regulatory requirement. In the last two decades, the development of alternatives to the in vivo Draize eye irritation test method has substantially advanced due to the improvements in primary cell isolation, cell culture techniques, and media, which have led to improved in vitro corneal tissue models and test methods. Most in vitro models for ocular toxicology attempt to reproduce the corneal epithelial tissue which consists of 4-5 layers of non-keratinized corneal epithelial cells that form tight junctions, thereby limiting the penetration of chemicals, xenobiotics, and pharmaceuticals. Also, significant efforts have been directed toward the development of more complex three-dimensional (3D) equivalents to study wound healing, drug permeation, and bioavailability. This review focuses on in vitro reconstructed 3D corneal tissue models and their utilization in ocular toxicology as well as their application to pharmacology and ophthalmic research. Current human 3D corneal epithelial cell culture models have replaced in vivo animal eye irritation tests for many applications, and substantial validation efforts are in progress to verify and approve alternative eye irritation tests for widespread use. The validation of drug absorption models and further development of models and test methods for many ophthalmic and ocular disease applications is required.

Light promoted brown staining of protoplasm by Ag+ is ideal to test wheat pollen viability rapidly.

Pollen viability is crucial for wheat breeding programs. The unique potential of the protoplasm of live cells to turn brown due to the synthesis of silver nanoparticles (AgNPs) through rapid photoreduction of Ag+, was exploited for testing wheat pollen viability. Ag+-viability test medium (consisting of 0.5 mM AgNO3 and 300 mM KNO3) incubated with wheat pollen turned brown within 2 min under intense light (~600 µmol photon flux density m-2s-1), but not in dark. The brown medium displayed AgNPs-specific surface plasmon resonance band in its absorption spectrum. Light microscopic studies showed the presence of uniformly stained brown protoplasm in viable pollen incubated with Ag+-viability medium in the presence of light. Investigations with transmission electron microscope coupled with energy dispersive X-ray established the presence of distinct 5-35 nm NPs composed of Ag. Powder X-ray diffraction analysis revealed that AgNPs were crystalline and biphasic composed of Ag0 and Ag2O. Conversely, non-viable pollen and heat-killed pollen did not turn brown on incubation with Ag+-medium in light. We believe that the viable wheat pollen turn brown rapidly by bio-transforming Ag+ to AgNPs through photoreduction. Our findings furnish a novel simplest and rapid method for testing wheat pollen viability.

Comparison of Islet Characterization from Use of Standard Crude Collagenase to GMP-Grade Collagenase Enzyme Blends in Preweaned Porcine Islet Isolations.

For the advancement of porcine xenotransplantation for clinical use in type 1 diabetes mellitus, the concerns of a sustainable and safe digestion enzyme blend must be overcome. Incorporating good manufacturing practices (GMP) can facilitate this through utilizing GMP-grade enzymes. In conjunction, still taking into account the cost-effectiveness, a wide concern. We evaluated how GMP-grade enzyme blends impact our piglet islets and their long-term effects. Preweaned porcine islets (PPIs) were isolated from 8- to 10-day-old pigs. Digestion enzyme blends, collagenase type V (Type V), collagenase AF-1 GMP-grade with collagenase NB 6 GMP-grade (AF-1 and NB 6), and collagenase AF-1 GMP-grade with collagenase neutral protease AF GMP-grade (AF-1 and NP AF) were compared. Islet quality control assessments, islet yield, viability, and function, were performed on days 3 and 7, and cell content was performed on day 7. GMP-grade AF-1 and NB 6 (17,209 ± 2,730 islet equivalent per gram of pancreatic tissue [IE/g] on day 3, 9,001 ± 1,034 IE/g on day 7) and AF-1 and NP AF (17,214 ± 3,901 IE/g on day 3, 8,833 ± 2,398 IE/g on day 7) showed a significant increase in islet yield compared to Type V (4,618 ± 1,240 IE/g on day 3, 1,923 ± 704 IE/g on day 7). Islet size, viability, and function showed comparable results in all enzyme blends. There was no significant difference in islet cellular content between enzyme blends. This study demonstrated a comparison of GMP-grade collagenase enzyme blends and a standard crude collagenase enzyme in preweaned-aged porcine, a novel topic in this age. GMP-grade enzyme blends of AF-1 and NB 6 and AF-1 and NP AF resulted in substantially higher yields and as effective PPIs compared to Type V. In the long run, considering costs, integrity, and sustainability, GMP-grade enzyme blends are more favorable for clinical application due to high reproducibility in comparison to undefined manufacturing processes of standard enzymes.

New Role for Growth/Differentiation Factor 15 in the Survival of Transplanted Brown Adipose Tissues in Cooperation with Interleukin-6.

To identify factors involved in the earliest phase of the differentiation of human embryonic stem cells (hESCs) into brown adipocytes (BAs), we performed multi-time point microarray analyses. We found that growth/differentiation factor 15 (GDF15) expressions were specifically upregulated within three days of differentiation, when expressions of immature hESC markers were sustained. Although GDF15 expressions continued to increase in the subsequent differentiation phases, GDF15-deficient hESCs differentiated into mature BAs (Day 10) without apparent abnormalities. In addition, GDF15-deficient mice had normal brown adipose tissue (BAT) and were metabolically healthy. Unexpectedly, we found that interleukin-6 (IL6) expression was significantly lowered in the BAT of GDF15-/- mice. In addition, GDF15-/- hESCs showed abortive IL6 expressions in the later phase (>Day 6) of the differentiation. Interestingly, GDF15 expression was markedly repressed throughout the whole course of the differentiation of IL6-/- hESCs into BAs, indicating IL6 is essential for the induction of GDF15 in the differentiation of hESCs. Finally, intraperitoneally transplanted BAT grafts of GDF15-/- donor mice, but not those of wild-type (WT) mice, failed in the long-term survival (12 weeks) in GDF15-/- recipient mice. Collectively, GDF15 is required for long-term survival of BAT grafts by creating a mutual gene induction loop with IL6.

Ex vivo model for elucidating the functional and structural differentiation of the embryonic mouse thyroid.

Terminal thyroid gland differentiation - the last developmental step needed to enable thyroid hormone (T4) synthesis - involves profound structural and biochemical changes in the thyroid follicular cells (TFCs). We aimed to develop an ex vivo thyroid model of embryonic mouse thyroid that would replicate the in vivo TFC differentiation program. E13.5 thyroid explants were cultured ex vivo in chemically defined medium for 7 days. Immunostaining and qPCR of thyroid explants showed thyroglobulin production onset, follicle formation, and T4 synthesis onset in 1-, 3-, and 5-day-old cultures, respectively. Differentiation was maintained and follicular growth continued throughout the 7-day culture period. Pharmacological approaches to culture inhibition were performed successfully in the ex vivo thyroids. Our robust and well described ex vivo thyroid culture model replicates the sequence of thyroid differentiation to T4 synthesis seen in vivo. This model can be used to test the effects of pharmacological inhibitors on thyroid hormone production.

In silico and in vivo investigations using an endocavitary photoplethysmography sensor for tissue viability monitoring.

SIGNIFICANCE: Colorectal cancer is one of the major causes of cancer-related deaths worldwide. Surgical removal of the cancerous growth is the primary treatment for this disease. A colorectal cancer surgery, however, is often unsuccessful due to the anastomotic failure that may occur following the surgical incision. Prevention of an anastomotic failure requires continuous monitoring of intestinal tissue viability during and after colorectal surgery. To date, no clinical technology exists for the dynamic and continuous monitoring of the intestinal perfusion. AIM: A dual-wavelength indwelling bowel photoplethysmography (PPG) sensor for the continuous monitoring of intestinal viability was proposed and characterized through a set of in silico and in vivo investigations. APPROACH: The in silico investigation was based on a Monte Carlo model that was executed to quantify the variables such as penetration depth and detected intensity with respect to the sensor-tissue separations and tissue perfusion. Utilizing the simulated information, an indwelling reflectance PPG sensor was designed and tested on 20 healthy volunteers. Two sets of in vivo studies were performed using the driving current intensities 20 and 40 mA for a comparative analysis, using buccal tissue as a proxy tissue-site. RESULTS: Both simulated and experimental results showed the efficacy of the sensor to acquire good signals through the "contact" to a "noncontact" separation of 5 mm. A very slow wavelength-dependent variation was shown in the detected intensity at the normal and hypoxic states of the tissue, whereas a decay in the intensity was found with the increasing submucosal-blood volume. The simulated detected-to-incident-photon-ratio and the experimental signal-to-noise ratio exhibited strong positive correlations, with the Pearson product-moment correlation coefficient R ranging between 0.65 and 0.87. CONCLUSIONS: The detailed feasibility analysis presented will lead to clinical trials utilizing the proposed sensor.

Bed rest: outdated following traumatic solid organ injury?

INTRODUCTION: This systematic review aimed to evaluate early ambulation protocols implemented for traumatic solid organ injury. METHODS: The electronic databases PubMed, Medline (Ovid), Embase and Cochrane Library were searched without time constraint to identify prospective and retrospective analyses, randomised controlled trials, cohort studies, and case series that investigated early ambulation in solid organ trauma. RESULTS: Six studies met the predefined inclusion criteria and were reviewed. Three studies investigated early ambulation protocols in direct comparison with bed rest. The remaining three studies were early ambulation case series. In all studies there was no convincing evidence to suggest differences in clinical outcomes between early ambulation and bed rest protocols. In all studies early ambulation resulted in a reduced length of hospitalisation and decreased cost to national healthcare services. CONCLUSIONS: This systematic review has found preliminary evidence that suggests bed rest has no clinical benefit in those with low-grade to mid-grade (grades 1-2) solid organ injury. Further studies are required to inform guidance to improve trauma patient outcomes.

Intermittent application of external positive pressure helps to preserve organ viability during ex vivo perfusion and culture.

The perfusion of medium through blood vessels allows the preservation of donor organs and culture of bioengineered organs. However, tissue damage due to inadequate perfusion remains a problem. We evaluated whether intermittent external pressurization would improve the perfusion and viability of organs in culture. A bioreactor system was used to perfuse and culture rat small intestine and femoral muscle preparations. Intermittent positive external pressure (10 mmHg) was applied for 20 s at intervals of 20 s. Intermittent pressurization resulted in uniform perfusion of small intestine preparations and minimal tissue damage after 20 h of perfusion, whereas non-pressurized (control) preparations exhibited significantly worse perfusion of the upper surface than the lower surface and histologic evidence of tissue damage. Longer term studies were undertaken in luciferase-expressing rat femoral muscle preparations. Compared with non-pressurized controls, intermittent pressurization led to better perfusion throughout the 14-day experimental period, improved organ viability as indicated by a higher bioluminescence intensity after perfusion with luciferin, and reduced levels of tissue necrosis with better preservation of vascular structures and skeletal muscle nuclei (histologic analyses). Therefore, intermittent application of external positive pressure improved the perfusion of small intestine and skeletal muscle preparations and enhanced tissue viability when compared with controls. We anticipate that this innovative perfusion technique could be used to improve the preservation of donor organs and culture of bioengineered organs.

Skin graft storage in platelet rich plasma (PRP).

Storage of skin grafts for later use is one of the standard applications in surgery. It is the most preferred method to maintain at +4°C in refrigeration after wrapping the surplus grafts into sterile gauze pad moistened with saline. Although there are many studies on the storage of skin grafts, less is known about storing skin grafts with PRP. Twenty-five pieces of 1 × 1 cm2 partial thickness skin graft were harvested from 12 patients during the reduction mammoplasty operation. Twenty-four grafts were divided into 4 groups, and each group consisted of 6 grafts, 1 graft was analyzed as Day 0. Grafts in Group 1, 2, and 3 were wrapped by sterile gauze pad moistened by either saline (Group 1) or Hartman (Group 2) or PRP (Group 3). Grafts were analyzed macroscopically and microscopically. There were no significant differences between media for the first 10 days. Decrease in viability was less in saline and PRP wrapped grafts at 20 day, viability decreased significantly in all environments after 20 days. Although there was no significant difference in saline or PRP storage, it was observed macroscopically that the grafts stored in the PRP appeared better.

Friction Injury Versus Deep Tissue Injury: Level of Tissue Involvement: A Comparison of 2 Cases.

BACKGROUND: Friction injuries are postulated to be caused by acute or chronic abrasive/friction forces during sliding, scooting, or slouching behaviors prevalent in individuals with impaired mobility and particularly when transferring and repositioning. CASES: Patient histories for 2 cases were collected for determination of wound etiology. Outpatient wound clinic visits including photographic documentation for both cases were reviewed, compared, and contrasted for level of tissue involvement with each wound type/etiology. With serial sharp debridement of both wounds, differences were noted in level of tissue involvement/destruction. Healing progression and scarring were also different for both wounds. CONCLUSION: A comparison of 2 cases is presented to compare and contrast level of tissue involvement and destruction in an acute friction injury (top-down) versus a deep tissue injury (bottom-up). The importance of knowing a wound's history is critical for accurate diagnosis and coding.

FGF21 augments autophagy in random-pattern skin flaps via AMPK signaling pathways and improves tissue survival.

Random-pattern skin flap is commonly used for surgical tissue reconstruction due to its ease and lack of axial vascular limitation. However, ischemic necrosis is a common complication, especially in distal parts of skin flaps. Previous studies have shown that FGF21 can promote angiogenesis and protect against ischemic cardiovascular disease, but little is known about the effect of FGF21 on flap survival. In this study, using a rat model of random skin flaps, we found that the expression of FGF21 is significantly increased after establishment skin flaps, suggesting that FGF21 may exert a pivotal effect on flap survival. We conducted experiments to elucidate the role of FGF21 in this model. Our results showed that FGF21 directly increased the survival area of skin flaps, blood flow intensity, and mean blood vessel density through enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Our studies also revealed that FGF21 administration leads to an upregulation of autophagy, and the beneficial effects of FGF21 were reversed by 3-methyladenine (3MA), which is a well-known inhibitor of autophagy, suggesting that autophagy plays a central role in FGF21's therapeutic benefit on skin flap survival. In our mechanistic investigation, we found that FGF21-induced autophagy enhancement is mediated by the dephosphorylation and nuclear translocation of TFEB; this effect was due to activation of AMPK-FoxO3a-SPK2-CARM1 and AMPK-mTOR signaling pathways. Together, our data provides novel evidence that FGF21 is a potent modulator of autophagy capable of significantly increasing random skin flap viability, and thus may serve as a promising therapy for clinical use.

The tissue viability imaging system-Suitable method for discovering minimal skin changes in occupational screenings? Results of a cross-sectional field study.

BACKGROUND: For early detection of initial skin changes in occupational screenings, only few objective assessment systems are available. OBJECTIVES: With the aim of assessing an objective measurement method for hand eczema, we trialed the application of the tissue viability imaging (TiVi) system, quantifying erythema non-invasively by polarized light spectroscopy. MATERIALS AND METHODS: In a field study with 625 employees of a semiconductor production company, 411 were exposed to prolonged wearing of occlusive gloves in the clean room. TiVi system and Hand Eczema Score for Occupational Screenings (HEROS), a quantitative skin score for the hands, were used, supplemented by a standardized personal interview. RESULTS: TiVi values of 65 up to 246 for each hand (palm or back), for each participant summed to overall 289 up to 848 (median 389), were measured. Higher TiVi values were noted for men, smokers, and with increasing age. Correlation between TiVi and HEROS was only weak. Several factors like skin pigmentation, thickness of the skin, or tattoos seem to influence TiVi results. CONCLUSIONS: The practical relevance of one-time measurements with the TiVi system in occupational screenings seems to be limited. Specifically, the TiVi system cannot replace dermatological examinations at the workplace. Notwithstanding, the application for other scientific purposes might be useful.

Evaluation of myocardial viability in patients with acute myocardial infarction: Layer-specific analysis of 2-dimensional speckle tracking echocardiography.

BACKGROUND: The value of layer-specific two-dimensional speckle tracking echocardiography (LS2D-STE) for evaluating viable myocardium (VM) in patients with acute myocardial infarction (AMI) was unclear, this study provides new insights into it and to make a comparison with dualisotope simultaneous acquisition single photon emission computed tomography ( DISA-SPECT). METHODS: Forty hospitalized patients with AMI and left ventricular systolic dysfunction (left ventricular ejection fraction <50%) underwent LS2D-STE and DISA-SPECT before percutaneous coronary intervention (PCI). The longitudinal, circumferential, and radial peak systolic strains and the peak systolic strain rates of 3 myocardiallayers (endocardium, mid-myocardium, and epicardium), as well as the total wall thickness, were determined by LS2D-STE. Routine echocardiography was followedup at 1, 3, 6 months after PCI, with the improvement of the wall motion as the goldenstandard for evaluating VM. RESULTS: The sensitivity, specificity and accuracy of DISA-SPECT for evaluating VM were 82.1%, 74.3%, and 79.3%, respectively. Among the layer-specific parameters, only endocardial (endo-) longitudinal strain (LS) and endo- longitudinal strain rate (LSr) were used as independent parameters for evaluating VM (P < .05), and the sensitivity, specificity and accuracy of endo-LS and endo-LSr in evaluation of VM were 77.1%, 65.4%, and 72.9% vs 72.9%, 65.4%, and 69.7%. Endo-LS and endo-LSr were superior to total wall thickness LS and LSr (AUC endo-LS 0.767 vs total-LS 0.669; endo-LSr 0.743 vs total-LSr 0.682). The parallel test and the serial test of combination of endo-LS and endo-LSr showed similar sensitivity, specificity and accuracy to DISA-SPECT (P > .05). CONCLUSION: The endo-LS and endo-LSr analysis of LS2D-STE can evaluate the VM well, and its sensitivity, specificity and accuracy in detection of VM are similar to those of DISA-SPECT, resulting in LS2D-STE being a good option for the assessment of VM.

A Systematic Review of Testicle Survival Time After a Torsion Event.

BACKGROUND: The time window for possible salvage and survival of a torsed testicle is commonly thought to be 6 to 8 hours. However, survival of torsed testicles with or without subsequent atrophy is known to occur outside that critical time window. In this article, we performed a systematic review of the English literature to provide a more accurate understanding of reported time frames of testicle survival after a torsion event. OBJECTIVES: The primary research question was to determine the relationship between time to treatment and the rate of survival for testicles of male patients presenting with testicular torsion (TT). METHODS: A systematic review of the literature was performed and structured according to PRISMA guidelines. An exhaustive library search was performed after search strategies were developed for multiple databases that included PubMed, Cochrane library, Ovid MEDLINE, Web of Science, and ProQuest Theses and Dissertations. Two different searches were developed including "testicular torsion" and TT with the search term "time" added. Articles specifically reporting TT case series, testicle outcomes, and time to surgical or manual treatment were selected for review. In addition to and preceding the systematic review, an exhaustive manual search of the literature was also performed by the authors. As a result of these searches, a total of 30 studies with data considered relevant to the research question were included. The information extracted from the articles was tabulated with regard to time intervals to treatment and survival outcome. RESULTS: The systematic review process and protocol are reported in this article. A total of 30 studies were found that reported case series of TT patients and their outcomes as well as time to treatment reported in useful time frames. From these reports, a total of 2116 TT patients were culled, and their outcomes and time to treatment are reported. Because the time to treatment was reported variously in different case series, the 3 most common formats for reporting time to treatment and outcome were used. When overlap between the tables existed, the data were tallied and reported cumulatively. When reported in 6-hour intervals (1,283 patients), survival at 0 to 6 hours was 97.2%; 7 to 12 hours, 79.3%; 13 to 18 hours, 61.3%; 19 to 24 hours, 42.5%; 25 to 48 hours, 24.4%; and greater than 48 hours, 7.4%. Moreover, we reported cumulative survival data based on reporting for all 3 groups of patients. Testicular salvage in the first 12 hours is 90.4%, from 13 to 24 hours survival is 54.0%, and beyond 24 hours survival is 18.1%. Testicle survival after TT was significant beyond the commonly held 6 to 8 hour time frame and even after more than 24 hours of ischemia. CONCLUSIONS: Survival of the testicle irrespective of subsequent atrophy, decreased spermatogenesis or impaired endocrine function after TT can be much longer than the 6 to 8 hours that is commonly taught. Our systematic review of the literature demonstrates that survival percentages are significant even past 24 hours of torsion. This information should encourage aggressive management of patients presenting with TT pain that has been ongoing for many hours.

Transcatheter aortic valve replacement (TAVR) leads to an increase in the subendocardial viability ratio assessed by pulse wave analysis.

BACKGROUND: Pulse wave analysis (PWA) is a useful tool for non-invasive assessment of central cardiac measures as subendocardial perfusion (Subendocardial Viability Ratio, SEVR) or contractility (dP/dtmax). The immediate influence of transcatheter aortic valve replacement (TAVR) on these indices has not been investigated yet. METHODS: We prospectively enrolled 40 patients presenting with severe aortic stenosis receiving TAVR. Central pressure curves were derived from radial and carotid sites using PWA up to 2 days before and 7 days after TAVR. Parameters were compared between peripheral measurement sites. Changes in SEVR, dP/dtmax and in indices of vascular stiffness were assessed. Additionally, association of these variables with clinical outcome was evaluated during a 12-month follow-up. RESULTS: Central waveform parameters were comparable between measurement sites. SEVR, but not dP/dtmax, augmentation Index (AIx) or augmentation pressure height (AGPH) correlated significantly with disease severity reflected by peak transvalvular velocity and mean transvalvular pressure gradient over the aortic valve (Vmax, ΔPm) [r = -0.372,p = 0.029 for Vmax and r = -0.371,p = 0.021 for ΔPm]. Vmax decreased from 4.5m/s (IQR:4.1-5.0) to 2.2m/s (IQR:1.9-2.7), (p<0.001). This resulted in a significant increase in SEVR [135.3%(IQR:115.5-150.8) vs. 140.3%(IQR:123.0-172.5),p = 0.039] and dP/dtmax [666mmHg(IQR:489-891) vs. 927mmHg(IQR:693-1092),p<0.001], and a reduction in AIx [154.8%(IQR:138.3-171.0) vs. 133.5%(IQR:128.3-151.8),p<0.001] and AGPH [34.1%(IQR:26.8-39.0) vs. 25.0%(IQR 21.8-33.7),p = 0.002], confirming the beneficial effects of replacing the stenotic valve. No association of these parameters could be revealed with outcome. CONCLUSIONS: PWA is suitable for assessing coronary microcirculation and contractility mirrored by SEVR and maxdP/dt in the setting of aortic stenosis. PWA parameters attributed to vascular properties should be interpreted with caution.

Angiotensin-(1-7) attenuates organ injury and mortality in rats with polymicrobial sepsis.

BACKGROUND: Sepsis and related multiple organ dysfunction result in high morbidity and mortality. Angiotensin (Ang)-(1-7), a biologically active peptide, has various opposing effects of Ang II. Because the effect of Ang-(1-7) on sepsis is unknown, in this study we aimed to determine the impact of Ang-(1-7) on pathophysiologic changes in a clinically relevant model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). METHODS: Sepsis was induced by CLP in rats under anesthesia. Rats were randomized to one of the following five groups: (1) sham-operated group, (2) Ang-(1-7) (1 mg/kg intravenously infused for 1 h) at 3 h and 6 h after sham operation, (3) CLP, (4) Ang-(1-7) at 3 h after CLP, and (5) Ang-(1-7) at 3 h and 6 h after CLP. Rats were observed for 24 h after CLP surgery and then killed for subsequent histological examination. RESULTS: Ang-(1-7) significantly improved the survival of septic rats (83.3% vs. 36.4% at 24 h following CLP; p = 0.009). Ang-(1-7) attenuated the CLP-induced decreased arterial pressure and organ dysfunction, indicated by diminished biochemical variables and fewer histological changes. Ang-(1-7) significantly reduced the level of plasma interleukin-6 and pulmonary superoxide production (p < 0.05). Moreover, caspase-3 and cytoplasmic IκB expression in liver was significantly lower in the Ang-(1-7)-treated CLP rats (p < 0.05). CONCLUSIONS: In this clinically relevant model of sepsis, Ang-(1-7) ameliorates CLP-induced organ dysfunction and improves survival, possibly through suppressing the inflammatory response, oxidative stress, and apoptosis, suggesting that Ang-(1-7) could be a potential novel therapeutic approach to treatment of peritonitis and polymicrobial sepsis.

Reparación endovascular del aneurisma de aorta abdominal. Papel del deterioro postoperatorio de la función renal en la supervivencia / Endovascular aortic repair of abdominal aortic aneurysm: Role of post-surgical renal function decline in survival

Introducción: La reparación endovascular del aneurisma de aorta abdominal (EVAR) ha supuesto desde su llegada y desarrollo una disminución en la mortalidad precoz con respecto a la cirugía convencional. Como factores predictivos de mortalidad se han identificado el deterioro de función renal preoperatorio, la enfermedad pulmonar obstructiva crónica y la cardiopatía isquémica. Objetivo: Evaluar la influencia en la supervivencia a largo plazo de los factores de riesgo preoperatorios y del deterioro de función renal perioperatorio en los pacientes sometidos a EVAR en nuestro centro. Material y métodos: Se realizó un estudio observacional retrospectivo en pacientes sometidos a EVAR en nuestro centro entre los años 2008 y 2012. Se hizo un análisis de la supervivencia a medio y largo plazo, llevado a cabo mediante curvas de Kaplan-Meier. Se estudió la influencia de los factores de riesgo preoperatorios y del deterioro de función renal perioperatorio sobre la supervivencia empleando el modelo de regresión de Cox. Resultados: Se incluyeron 79 pacientes con una edad media de 75,2 años (57,6-85,9). La mediana del tiempo de seguimiento fue de 38 meses (0,4-83,4). Durante este periodo de tiempo se registraron 26 muertes (32,9%). La probabilidad de supervivencia al cabo de un año fue del 93,7%; a los 2 años del 82,3%; a los 4 años del 68,9%; y a los 6 años del 56,5%. Una mayor tasa de supervivencia se asoció con cifras analíticas de creatinina menores de 1,2 mg/dl a las 24 h y a los 7 días, y filtrado glomerular mayor de 60 ml/min a las 24 h y a los 7 días. El análisis multivariante evidenció una probabilidad de muerte 2,39 veces mayor en los pacientes que presentaron un valor analítico de creatinina a las 24 h mayor de 1,2 mg/dl con respecto a los que mostraron una cifra menor de 1,2 mg/dl (HR: 2,39; IC95%: 1,06-5,42); p = 0,037). Conclusión: El deterioro de función renal tras la EVAR es un factor independiente de mal pronóstico a largo plazo. Tanto en la preparación preoperatoria como durante el postoperatorio deben ponerse los medios necesarios encaminados a corregir las circunstancias que provoquen un deterioro de la función renal

Background: Since its introduction and development, endovascular aortic repair (EVAR) has shown an improvement in short-term mortality compared to conventional surgery. Pre-operative renal function impairment, chronic obstructive pulmonary disease, and ischaemic heart disease, have been identified as mortality predictors. Objective:To assess the influence on long-term survival of pre-operative risk factors and peri-operative renal function impairment in patients that underwent EVAR in our centre. Material and methods: A retrospective observational study was conducted on patients subjected to EVAR in our centre between the years 2008 and 2012. The Kaplan-Meier curve was used to analyse the long and medium-term survival. The influence of pre-operative risk factors and perioperative renal impairment on survival was analysed using the Cox regression model. Results: A total of 79 patients were finally included in the study. The mean age was 75.2 years (57.6-85.9). The mean follow-up period was 38 months (0.4-83.4). During this period 26 (32.9%) deaths were registered. Survival probabilities during the first, second, fourth, and sixth years were 93.7%, 82.3%, 68.9%, and 56.5%, respectively. A greater survival rate was associated with creatinine levels lower than 1.2mg/dL at 24hours and at 7 days, and a glomerular filtration rate higher than 60mL/min at 24hours and at 7 days. Multivariate analysis showed a HR 2.39 higher in patients with a creatinine level higher than 1.2mg/dL at 24hours compared to patients with a creatinine level lower than 1.2mg/dL (HR: 2.39, 95% CI: 1.06-5.42; P=.037). Conclusion: Renal function impairment after endovascular aortic repair of abdominal aortic aneurysm represents an independent long-term poor prognosis factor. During pre-operative preparation and post-operative care necessary steps should be taken aimed at correcting the circumstances that cause renal function impairment