Metastatic cells exploit their stoichiometric niche in the network of cancer ecosystems.

Metastasis is a nonrandom process with varying degrees of organotropism-specific source-acceptor seeding. Understanding how patterns between source and acceptor tumors emerge remains a challenge in oncology. We hypothesize that organotropism results from the macronutrient niche of cells in source and acceptor organs. To test this, we constructed and analyzed a metastatic network based on 9303 records across 28 tissue types. We found that the topology of the network is nested and modular with scale-free degree distributions, reflecting organotropism along a specificity/generality continuum. The variation in topology is significantly explained by the matching of metastatic cells to their stoichiometric niche. Specifically, successful metastases are associated with higher phosphorus content in the acceptor compared to the source organ, due to metabolic constraints in proliferation crucial to the invasion of new tissues. We conclude that metastases are codetermined by processes at source and acceptor organs, where phosphorus content is a limiting factor orchestrating tumor ecology.

Radiomics using computed tomography to predict CD73 expression and prognosis of colorectal cancer liver metastases.

BACKGROUND: Finding a noninvasive radiomic surrogate of tumor immune features could help identify patients more likely to respond to novel immune checkpoint inhibitors. Particularly, CD73 is an ectonucleotidase that catalyzes the breakdown of extracellular AMP into immunosuppressive adenosine, which can be blocked by therapeutic antibodies. High CD73 expression in colorectal cancer liver metastasis (CRLM) resected with curative intent is associated with early recurrence and shorter patient survival. The aim of this study was hence to evaluate whether machine learning analysis of preoperative liver CT-scan could estimate high vs low CD73 expression in CRLM and whether such radiomic score would have a prognostic significance. METHODS: We trained an Attentive Interpretable Tabular Learning (TabNet) model to predict, from preoperative CT images, stratified expression levels of CD73 (CD73High vs. CD73Low) assessed by immunofluorescence (IF) on tissue microarrays. Radiomic features were extracted from 160 segmented CRLM of 122 patients with matched IF data, preprocessed and used to train the predictive model. We applied a five-fold cross-validation and validated the performance on a hold-out test set. RESULTS: TabNet provided areas under the receiver operating characteristic curve of 0.95 (95% CI 0.87 to 1.0) and 0.79 (0.65 to 0.92) on the training and hold-out test sets respectively, and outperformed other machine learning models. The TabNet-derived score, termed rad-CD73, was positively correlated with CD73 histological expression in matched CRLM (Spearman's ρ = 0.6004; P < 0.0001). The median time to recurrence (TTR) and disease-specific survival (DSS) after CRLM resection in rad-CD73High vs rad-CD73Low patients was 13.0 vs 23.6 months (P = 0.0098) and 53.4 vs 126.0 months (P = 0.0222), respectively. The prognostic value of rad-CD73 was independent of the standard clinical risk score, for both TTR (HR = 2.11, 95% CI 1.30 to 3.45, P < 0.005) and DSS (HR = 1.88, 95% CI 1.11 to 3.18, P = 0.020). CONCLUSIONS: Our findings reveal promising results for non-invasive CT-scan-based prediction of CD73 expression in CRLM and warrant further validation as to whether rad-CD73 could assist oncologists as a biomarker of prognosis and response to immunotherapies targeting the adenosine pathway.

Microalgae share key features with human erythrocytes and can safely circulate through the vascular system in mice.

As animal cells cannot produce oxygen, erythrocytes are responsible for gas interchange, being able to capture and deliver oxygen upon tissue request. Interestingly, several other cells in nature produce oxygen by photosynthesis, raising the question of whether they could circulate within the vascular networks, acting as an alternative source for oxygen delivery. To address this long-term goal, here some physical and mechanical features of the photosynthetic microalga Chlamydomona reinhardtii were studied and compared with erythrocytes, revealing that both exhibit similar size and rheological properties. Moreover, key biocompatibility aspects of the microalgae were evaluated in vitro and in vivo, showing that C. reinhardtii can be co-cultured with endothelial cells, without affecting each other's morphology and viability. Moreover, short-term systemic perfusion of the microalgae showed a thoroughly intravascular distribution in mice. Finally, the systemic injection of high numbers of microalgae did not trigger deleterious responses in living mice. Altogether, this work provides key scientific insights to support the notion that photosynthetic oxygenation could be achieved by circulating microalgae, representing another important step towards human photosynthesis. KEY POINTS: • C. reinhardtii and endothelial cells are biocompatible in vitro. • C. reinhardtii distribute throughout the entire vasculature after mice perfusion. • C. reinhardtii do not trigger deleterious responses after injection in mice.

Customized normothermic machine perfusion decreases ischemia-reperfusion injury compared with static cold storage in a porcine model of liver transplantation.

BACKGROUND: Liver transplantation has been demonstrated to be the best treatment for several liver diseases, while grafts are limited. This has caused an increase in waiting lists, making it necessary to find ways to expand the number of organs available for transplantation. Normothermic perfusion (NMP) of liver grafts has been established as an alternative to static cold storage (SCS), but only a small number of perfusion machines are commercially available. METHODS: Using a customized ex situ machine perfusion, we compared the results between ex situ NMP and SCS preservation in a porcine liver transplant model. RESULTS: During NMP, lactate concentrations were 80% lower after the 3-h perfusion period, compared with SCS. Bile production had a 2.5-fold increase during the NMP period. After transplantation, aspartate transaminase (AST) and alanine transaminase (ALT) levels were 35% less in the NMP group, compared to the SCS group. In pathologic analyses of grafts after transplant, tissue oxidation did not change between groups, but the ischemia-reperfusion injury score was lower in the NMP group. CONCLUSION: NMP reduced hepatocellular damage and ischemia-reperfusion injury when compared to SCS using a customized perfusion machine. This could be an alternative for low-income countries to include machine perfusion in their therapeutic options.

Implementation and design of customized ex vivo machine perfusion. Analysis of its first results.

The lack of organs available for transplantation is a global problem. The high mortality rates on the waiting list and the high number of discarded livers are reasons to develop new tools in the preservation and transplantation process. New tools should also be available for low-income countries. This article reports the development of customized normothermic machine perfusion (NMP). An ex vivo dual perfusion machine was designed, composed of a common reservoir organ box (CRO), a centrifugal pump (portal system, low pressure), and a roller pump (arterial system, high pressure). Porcine livers (n = 5) were perfused with an oxygenated normothermic (37℃) strategy for 3 hours. Hemodynamic variables, metabolic parameters, and bile production during preservation were analyzed. Arterial and portal flow remain stable during perfusion. Total bilirubin production was 11.25 mL (4-14.5) at 180 minutes. The median pH value reached 7.32 (7.25-7.4) at 180 minutes. Lactate values decreased progressively to normalization at 120 minutes. This perfusion setup was stable and able to maintain the metabolic activity of a liver graft in a porcine animal model. Design and initial results from this customized NMP are promising for a future clinical application in low-income countries.

Validity Argument for a Simulation-Based Objective Structured Clinical Examination Scenario for Evaluation of Surgical Skills in Trauma.

BACKGROUND: Trauma is one of the main causes of death globally, and appropriate surgical care is crucial to impact mortality. However, resident-performed trauma cases have diminished in the last 10 years. Simulation-based tools have proven to be effective to evaluate practical skills in a variety of settings. However, there is a lack of evidence regarding proper validation of trauma surgery models. OBJECTIVE: The aim of this study was to evaluate under a contemporary validity framework, an objective structured clinical evaluation (OSCE) scenario for the assessment of basic and advanced surgical skills in trauma and emergency surgery. METHODS: An OSCE-type simulation assessment program was developed incorporating six stations representing basic and advanced surgical skills that are essential in trauma surgery. Each station was designed using ex-vivo animal tissue. The stations included basic knots and sutures, bowel resection and anastomosis, vascular end-to-end anastomosis, lung injury repair, cardiac injury repair, and laparoscopic suturing. Eight postgraduate year 2 (PY-2), eight recently graduated surgeons (RGS), and 3 experts were recruited, and their performance was blindly assessed by experts using the validated general rating scale OSATS (Objective Structured Assessment of Technical Skills) as well as the time taken to complete the procedure. RESULTS: Significant differences were identified among groups. The average OSATS score was 82 for the PY2 group, 113 for the RGS group, and 147 for the experts (P < 0.01). The average procedural time to complete all the stations was 98 minutes for the PY2 group, 68 minutes for the RGS group, and 35 minutes for the expert surgeons (P < 0.01). CONCLUSION: An OSCE scenario designed using ex-vivo tissue met 4 out of 5 criteria of the Messick validity framework: content, relation to other variables, response process and consequences of the test. The results show it is a valid strategy for the evaluation of practical skills in trauma surgery.

SELF-CONFIDENCE ON ACQUIRED SURGICAL SKILLS TO DEAL WITH SEVERE TRAUMA PATIENTS IN RECENTLY GRADUATED SURGEONS.

BACKGROUND: Level of competence by procedure. Trauma is one of the leading causes of death in the world and proper surgical care is critical to impact mortality. In Chile, trauma associated death ranks first as mortality cause in population between 20 and 59 years old. Appropriate surgical skills are required to deal with these complex patients. Self-confidence to practice trauma procedures after the General Surgery Residency have not been reported in our country. AIM: Describe the level of self-confidence to deal with trauma procedures of surgeons who recently graduated from a General Surgery Residency. METHOD: Descriptive cross-sectional study. We designed and applied a survey in 2015, 2016 and 2017 to recently graduated surgeons, to inquire about self-confidence of surgical skills to deal with trauma scenarios. Eighteen trauma surgery procedures (including cervical, thoracic, abdominal and vascular procedures) were evaluated using a 5-grade Likert scale. The number of procedures performed during the residency was also queried. RESULTS: Eighty-eight recently graduated surgeons from 11 different training programs in Chile were included. The report of competencies was high in procedures such as intestinal injuries, were 98% felt competent or very competent in their repair. On the other hand, in complex traumas such as major vessel injury, up to 76% reported not being competent. Self-confidence on procedures was directly associated with the number of procedures performed during residency. CONCLUSIONS: Recently graduated surgeons from General Surgery Programs report high levels of confidence to deal with low and intermediate complexity traumas, but a lower level of confidence to treat high complexity cases.

Methylprednisolone Treatment in Brain Death-Induced Lung Inflammation-A Dose Comparative Study in Rats.

Background: The process of brain death (BD) leads to a pro-inflammatory state of the donor lung, which deteriorates its quality. In an attempt to preserve lung quality, methylprednisolone is widely recommended in donor lung management. However, clinical treatment doses vary and the dose-effect relation of methylprednisolone on BD-induced lung inflammation remains unknown. The aim of this study was to investigate the effect of three different doses methylprednisolone on the BD-induced inflammatory response. Methods: BD was induced in rats by inflation of a Fogarty balloon catheter in the epidural space. After 60 min of BD, saline or methylprednisolone (low dose (5 mg/kg), intermediate dose (12.5 mg/kg) or high dose (22.5 mg/kg)) was administered intravenously. The lungs were procured and processed after 4 h of BD. Inflammatory gene expressions were analyzed by RT-qPCR and influx of neutrophils and macrophages were quantified with immunohistochemical staining. Results: Methylprednisolone treatment reduced neutrophil chemotaxis as demonstrated by lower IL-8-like CINC-1 and E-selectin levels, which was most evident in rats treated with intermediate and high doses methylprednisolone. Macrophage chemotaxis was attenuated in all methylprednisolone treated rats, as corroborated by lower MCP-1 levels compared to saline treated rats. Thereby, all doses methylprednisolone reduced TNF-α, IL-6 and IL-1ß tissue levels. In addition, intermediate and high doses methylprednisolone induced a protective anti-inflammatory response, as reflected by upregulated IL-10 expression when compared to saline treated brain-dead rats. Conclusion: We showed that intermediate and high doses methylprednisolone share most potential to target BD-induced lung inflammation in rats. Considering possible side effects of high doses methylprednisolone, we conclude from this study that an intermediate dose of 12.5 mg/kg methylprednisolone is the optimal treatment dose for BD-induced lung inflammation in rats, which reduces the pro-inflammatory state and additionally promotes a protective, anti-inflammatory response.

Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation.

Oxygen is the key molecule for aerobic metabolism, but no animal cells can produce it, creating an extreme dependency on external supply. In contrast, microalgae are photosynthetic microorganisms, therefore, they are able to produce oxygen as plant cells do. As hypoxia is one of the main issues in organ transplantation, especially during preservation, the main goal of this work was to develop the first generation of perfusable photosynthetic solutions, exploring its feasibility for ex vivo organ preservation. Here, the microalgae Chlamydomonas reinhardtii was incorporated in a standard preservation solution, and key aspects such as alterations in cell size, oxygen production and survival were studied. Osmolarity and rheological features of the photosynthetic solution were comparable to human blood. In terms of functionality, the photosynthetic solution proved to be not harmful and to provide sufficient oxygen to support the metabolic requirement of zebrafish larvae and rat kidney slices. Thereafter, isolated porcine kidneys were perfused, and microalgae reached all renal vasculature, without inducing damage. After perfusion and flushing, no signs of tissue damage were detected, and recovered microalgae survived the process. Altogether, this work proposes the use of photosynthetic microorganisms as vascular oxygen factories to generate and deliver oxygen in isolated organs, representing a novel and promising strategy for organ preservation.

Self-confidence on acquired surgical skills to deal with severe trauma patients in recently graduated surgeons / Autoconfiança nas habilidades cirúrgicas adquiridas para lidar com pacientes com trauma grave em cirurgiões recém-formados

ABSTRACT Background: Trauma is one of the leading causes of death in the world and proper surgical care is critical to impact mortality. In Chile, trauma associated death ranks first as mortality cause in population between 20 and 59 years old. Appropriate surgical skills are required to deal with these complex patients. Self-confidence to practice trauma procedures after the General Surgery Residency have not been reported in our country. Aim: Describe the level of self-confidence to deal with trauma procedures of surgeons who recently graduated from a General Surgery Residency. Method: Descriptive cross-sectional study. We designed and applied a survey in 2015, 2016 and 2017 to recently graduated surgeons, to inquire about self-confidence of surgical skills to deal with trauma scenarios. Eighteen trauma surgery procedures (including cervical, thoracic, abdominal and vascular procedures) were evaluated using a 5-grade Likert scale. The number of procedures performed during the residency was also queried. Results: Eighty-eight recently graduated surgeons from 11 different training programs in Chile were included. The report of competencies was high in procedures such as intestinal injuries, were 98% felt competent or very competent in their repair. On the other hand, in complex traumas such as major vessel injury, up to 76% reported not being competent. Self-confidence on procedures was directly associated with the number of procedures performed during residency. Conclusions: Recently graduated surgeons from General Surgery Programs report high levels of confidence to deal with low and intermediate complexity traumas, but a lower level of confidence to treat high complexity cases.

RESUMO Racional: Trauma é uma das principais causas de morte no mundo e cuidados cirúrgicos adequados são críticos para determinar a mortalidade. No Chile, morte associada a trauma é a primeira causa de mortalidade na população entre 20 e 59 anos. Para lidar com esses pacientes complexos, são necessárias habilidades cirúrgicas precisas para esses procedimentos. Autoconfiança de cirurgiões recentemente graduados na Residência em Cirurgia Geral para práticas de procedimentos de trauma no nosso país não tem sido reportada. Objetivo: Descrever nível de autoconfiança para lidar com procedimentos de trauma em cirurgiões recentemente graduados na residência de cirurgia geral. Método: Estudo transversal. Foi desenhada e aplicada uma enquete em 2015, 2016 e 2017 a cirurgiões recentemente graduados para pesquisar sobre autoconfiança e habilidades cirúrgicas para lidar com cenários de trauma. Foram avaliados 18 procedimentos cirúrgicos de trauma (incluindo procedimentos cervicais, torácicos, abdominais e vasculares) usando a 5-grade Likert Scale. O número total de procedimentos feitos durante a residência foi avaliado. Resultados: Foram incluídos 88 cirurgiões recentemente graduados. O nível de competência foi reportado como alto em procedimentos como trauma intestinal, onde 98% sentiu-se competente ou muito competente em sua reparação. Por outro lado, em traumas complexos como dano vascular maior, até 76% reportaram não se sentirem competentes. A autoconfiança nos procedimentos esteve diretamente associada com o número de procedimentos realizados. Conclusões: Cirurgiões recentemente graduados na residência de cirurgia geral reportam níveis altos de confiança para lidar com traumas de complexidade baixa e média, mas um nível menor de confiança para tratar casos de complexidade alta.

Rat donor lung quality deteriorates more after fast than slow brain death induction.

Donor brain death (BD) is initiated by an increase in intracranial pressure (ICP), which subsequently damages the donor lung. In this study, we investigated whether the speed of ICP increase affects quality of donor lungs, in a rat model for fast versus slow BD induction. Rats were assigned to 3 groups: 1) control, 2) fast BD induction (ICP increase over 1 min) or 3) slow BD induction (ICP increase over 30 min). BD was induced by epidural inflation of a balloon catheter. Brain-dead rats were sacrificed after 0.5 hours, 1 hour, 2 hours and 4 hours to study time-dependent changes. Hemodynamic stability, histological lung injury and inflammatory status were investigated. We found that fast BD induction compromised hemodynamic stability of rats more than slow BD induction, reflected by higher mean arterial pressures during the BD induction period and an increased need for hemodynamic support during the BD stabilization phase. Furthermore, fast BD induction increased histological lung injury scores and gene expression levels of TNF-α and MCP-1 at 0.5 hours after induction. Yet after donor stabilization, inflammatory status was comparable between the two BD models. This study demonstrates fast BD induction deteriorates quality of donor lungs more on a histological level than slow BD induction.

Reconstructing ecological networks with noisy dynamics.

Ecosystems functioning is based on an intricate web of interactions among living entities. Most of these interactions are difficult to observe, especially when the diversity of interacting entities is large and they are of small size and abundance. To sidestep this limitation, it has become common to infer the network structure of ecosystems from time series of species abundance, but it is not clear how well can networks be reconstructed, especially in the presence of stochasticity that propagates through ecological networks. We evaluate the effects of intrinsic noise and network topology on the performance of different methods of inferring network structure from time-series data. Analysis of seven different four-species motifs using a stochastic model demonstrates that star-shaped motifs are differentially detected by these methods while rings are differentially constructed. The ability to reconstruct the network is unaffected by the magnitude of stochasticity in the population dynamics. Instead, interaction between the stochastic and deterministic parts of the system determines the path that the whole system takes to equilibrium and shapes the species covariance. We highlight the effects of long transients on the path to equilibrium and suggest a path forward for developing more ecologically sound statistical techniques.

Laparoscopic Versus Open Distal Pancreatectomy: Comparative Analysis of Clinical Outcomes at a Single Institution.

PURPOSE: Undertake a comparison between laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP) for the management of benign and malignant lesions. METHODS: A case series study of 93 consecutive patients subjected to a distal pancreatectomy for pancreatic tumors between 2001 and 2015. In each patient, clinical and surgical characteristic, postoperative course, histopathologic examination, and survival were analyzed. RESULTS: LDP was associated with significantly less operative blood loss (50 mL vs. 300 mL; P<0.01), higher spleen preservation rate (52.6% vs. 19.2%; P<0.01) and shorter hospital stay (5 d vs. 8 d; P<0.01). In patients with adenocarcinoma, survival at 1 and 5 years were 63.5% and 15.9% in the ODP group versus 66.7% and 33.3% in the LDP group (P=0.43). CONCLUSIONS: LDP is a safe and feasible procedure for DP resections. LDP offers advantages over ODP in terms of reduction of operative blood loss, higher spleen preservation rate, and shorter hospital stay.

On the proportional abundance of species: Integrating population genetics and community ecology.

The frequency of genes in interconnected populations and of species in interconnected communities are affected by similar processes, such as birth, death and immigration. The equilibrium distribution of gene frequencies in structured populations is known since the 1930s, under Wright's metapopulation model known as the island model. The equivalent distribution for the species frequency (i.e. the species proportional abundance distribution (SPAD)), at the metacommunity level, however, is unknown. In this contribution, we develop a stochastic model to analytically account for this distribution (SPAD). We show that the same as for genes SPAD follows a beta distribution, which provides a good description of empirical data and applies across a continuum of scales. This stochastic model, based upon a diffusion approximation, provides an alternative to neutral models for the species abundance distribution (SAD), which focus on number of individuals instead of proportions, and demonstrate that the relative frequency of genes in local populations and of species within communities follow the same probability law. We hope our contribution will help stimulate the mathematical and conceptual integration of theories in genetics and ecology.

Resultados del tratamiento laparoscópico de los quistes hidatídicos hepáticos no complicados / Results of laparoscopic treatment of uncomplicated hepatic hydatid cysts

Introducción: La cirugía es el tratamiento más efectivo para los pacientes portadores de quistes hidatídicos hepáticos (QHH). Actualmente no existe consenso si la cirugía abierta o laparoscópica es la mejor vía de tratamiento. El objetivo del presente estudio es describir la técnica quirúrgica y los resultados de la cirugía radical (periquistectomía) por vía laparoscópica. Materiales y métodos: Estudio de cohorte no concurrente. Se incluyeron a los pacientes portadores de QHH no complicados en los que se realizó periquistectomía radical laparoscópica entre los años 2007 y 2015 en el Hospital Clínico de la Pontificia Universidad Católica de Chile. Se consignaron variables demográficas, clínicas, características del QHH, morbimortalidad y recurrencia en el seguimiento. Resultados: Se operaron 24 pacientes. La mediana de edad fue de 35 años (3-79). La mediana de tamaño del QHH fue de 8 cm (3-15). Las complicaciones postoperatorias se presentaron en 4 casos (16%); un paciente presentó una fístula biliar (4,1%). No hubo mortalidad en este estudio y la estadía hospitalaria fue de 3 días (2-25). La mediana de seguimiento fue de 57,5 meses (9-106); se observó un caso de recurrencia a nivel hepático que requirió otra cirugía. Conclusiones: El tratamiento radical de los QHH no complicados por vía laparoscópica es factible y seguro; al compararlo con la literatura existente no se aprecian diferencias en la morbimortalidad ni recurrencia.

Introduction: Surgery is the most effective treatment for patients with hepatic hydatid cysts (HHC). Currently there is no consensus whether open or laparoscopic surgery is the best treatment. The aim of this study is to describe the surgical technique and the results of laparoscopic radical surgery (pericystectomy). Material and methods: Non-concurrent cohort study. We included patients with uncomplicated HHC in which it was performed a laparoscopic radical pericystectomy between 2007 and 2015 at the Clinical Hospital of the Pontificia Universidad Catolica de Chile. Demographic and clinical variables, HHC characteristics, morbi-mortality and recurrence at follow-up were recorded. Results: Twenty-four patients were operated. The median age was 35 years (3-79). The median HHC size was 8 centimeters (3-15). Postoperative complications occurred in 4 cases (16%); one patient had a biliary fistula (4.1%). There was no mortality in this study and the hospital stay was 3 days (2-25). Median follow-up was 57.5 months (9-106); a case of hepatic recurrence requiring another surgery was observed. Conclusions: The radical treatment of uncomplicated HHC by laparoscopic surgery is feasible and safe; when compared with existing literature there is no differences in morbi-mortality or recurrence.

Inadequate Antioxidative Responses in Kidneys of Brain-Dead Rats.

BACKGROUND: Brain death (BD)-related lipid peroxidation, measured as serum malondialdehyde (MDA) levels, correlates with delayed graft function in renal transplant recipients. How BD affects lipid peroxidation is not known. The extent of BD-induced organ damage is influenced by the speed at which intracranial pressure increases. To determine possible underlying causes of lipid peroxidation, we investigated the renal redox balance by assessing oxidative and antioxidative processes in kidneys of brain-dead rats after fast and slow BD induction. METHODS: Brain death was induced in 64 ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Fast and slow inductions were achieved by an inflation speed of 0.45 and 0.015 mL/min, respectively, until BD confirmation. Healthy non-brain-dead rats served as reference values. Brain-dead rats were monitored for 0.5, 1, 2, or 4 hours, after which organs and blood were collected. RESULTS: Increased MDA levels became evident at 2 hours of slow BD induction at which increased superoxide levels, decreased glutathione peroxidase (GPx) activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased plasma creatinine levels were evident. At 4 hours after slow BD induction, superoxide, MDA, and plasma creatinine levels increased further, whereas GPx activity remained decreased. Increased MDA and plasma creatinine levels also became evident after 4 hours fast BD induction. CONCLUSION: Brain death leads to increased superoxide production, decreased GPx activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased MDA and plasma creatinine levels. These effects were more pronounced after slow BD induction. Modulation of these processes could lead to decreased incidence of delayed graft function.

Reversal of the Hartmann's procedure: A comparative study of laparoscopic versus open surgery.

BACKGROUND: The Hartmann's operation, although less frequently performed today, is still used when initial colonic anastomosis is too risky in the short term. However, the subsequent procedure to restore gastrointestinal continuity is associated with significant morbidity and mortality. PATIENTS AND METHODS: The review of an institutional review board (IRB)-approved prospectively maintained database provided data on the Hartmann's reversal procedure performed by either laparoscopic or open technique at our institution. The data collected included: demographic data, operative approach, conversion for laparoscopic cases and perioperative morbidity and mortality. RESULTS: Over a 14-year period from January 1997 to August 2011, 74 Hartmann's reversal procedures were performed (laparoscopic surgery-49, open surgery-25). The average age was 55 years for the laparoscopic and 57 years for the open surgery group, respectively. Male patients represent 61% of both groups. There was no significant difference in operative time between the two groups (149 min vs 151 min; P = 0.95), and there was a tendency to lower morbidity (3/49-7.3% vs 4/25-16%; P = 0.24) in the laparoscopic surgery group. In the laparoscopic group, eight patients (16.3%) were converted to open surgery, mostly due to severe adhesions. The length of hospital stay was significantly shorter for the laparoscopic group (5 days vs 7 days; P = 0.44). CONCLUSIONS: The Hartmann's reversal procedure can be safely performed in the majority of the cases using a laparoscopic approach with a low morbidity rate and achieving a shorter hospital stay.

The Crosstalk between ROS and Autophagy in the Field of Transplantation Medicine.

Many factors during the transplantation process influence posttransplant graft function and survival, including donor type and age, graft preservation methods (cold storage, machine perfusion), and ischemia-reperfusion injury. Successively, they will lead to cellular and molecular alterations that determine cell and ultimately organ fate. Oxidative stress and autophagy are implicated in posttransplant outcome since they are both affected by the stress responses triggered in each step (donor, preservation, and recipient) of the transplantation process. Furthermore, oxidative stress influences autophagy and vice versa. Interestingly, both processes have positive as well as negative effects on graft outcome, suggesting they are tightly linked during the transplantation process. In this review, we discuss the importance, regulation and crosstalk of oxidative signals, and autophagy in the field of transplantation medicine.

Laparoscopy-Assisted Trans-Gastric Rendez-vous for the Treatment of Common Bile Duct Stones in Patients with Prior Roux-en-Y Gastric Bypass.

BACKGROUND: Common bile duct (CBD) stones in a Roux-en-Y gastric bypass (RYGB) represent a major challenge for ERCP due to long-limb anatomy. Trans-gastric approach has been proposed but entails high ERCP-related risks. Laparoscopy assisted trans-gastric rendez-vous (LATG-RV) is a one-step procedure that may lower the risks of these patients. METHODS: We describe our initial experience in four patients with past history of RYGB and CBD stones. RESULTS: All patients underwent LATG-RV and had successful CBD stone clearance. Postoperative course was uneventful with normal amylase levels. Average procedure time was 105 min and postoperative stay 2 days. CONCLUSION: LATG-RV is a safe and effective procedure for the clearance of CBD stones in RYGB patients. It may have fewer complications and shorter operative time than regular trans-gastric ERCP.

Effects of dexmedetomidine and esmolol on systemic hemodynamics and exogenous lactate clearance in early experimental septic shock.

BACKGROUND: Persistent hyperlactatemia during septic shock is multifactorial. Hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation together with impaired lactate clearance have been implicated. An excessive adrenergic response could contribute to persistent hyperlactatemia and adrenergic modulation might be beneficial. We assessed the effects of dexmedetomidine and esmolol on hemodynamics, lactate generation, and exogenous lactate clearance during endotoxin-induced septic shock. METHODS: Eighteen anesthetized and mechanically ventilated sheep were subjected to a multimodal hemodynamic/perfusion assessment including hepatic and portal vein catheterizations, total hepatic blood flow, and muscle microdialysis. After monitoring, all received a bolus and continuous infusion of endotoxin. After 1 h they were volume resuscitated, and then randomized to endotoxin-control, endotoxin-dexmedetomidine (sequential doses of 0.5 and 1.0 µg/k/h) or endotoxin-esmolol (titrated to decrease basal heart rate by 20 %) groups. Samples were taken at four time points, and exogenous lactate clearance using an intravenous administration of sodium L-lactate (1 mmol/kg) was performed at the end of the experiments. RESULTS: Dexmedetomidine and esmolol were hemodynamically well tolerated. The dexmedetomidine group exhibited lower epinephrine levels, but no difference in muscle lactate. Despite progressive hypotension in all groups, both dexmedetomidine and esmolol were associated with lower arterial and portal vein lactate levels. Exogenous lactate clearance was significantly higher in the dexmedetomidine and esmolol groups. CONCLUSIONS: Dexmedetomidine and esmolol were associated with lower arterial and portal lactate levels, and less impairment of exogenous lactate clearance in a model of septic shock. The use of dexmedetomidine and esmolol appears to be associated with beneficial effects on gut lactate generation and lactate clearance and exhibits no negative impact on systemic hemodynamics.