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Abstract Background Wnt/β-catenin (or canonical) signalling pathway activity is necessary and used independently several times for specification of vegetal fate and endoderm, gut differentiation, maintenance of epithelium in adult intestine and the development of gut-derived organs in various vertebrate and non-vertebrate organisms. However, its conservation in later stages of digestive tract development still remains questionable due to the lack of detailed data, mainly from Spiralia. Results Here we characterize the Pdu-Tcf gene, a Tcf/LEF orthologue and a component of Wnt/β-catenin pathway from Platynereis dumerilii, a spiralian, marine annelid worm. Pdu-Tcf undergoes extensive alternative splicing in the C-terminal region of the gene generating as many as eight mRNA isoforms some of which differ in the presence or absence of a C-clamp domain which suggests a distinct DNA binding activity of individual protein variants. Pdu-Tcf is broadly expressed throughout development which is indicative of many functions. One of the most prominent domains that exhibits rather strong Pdu-Tcf expression is in the putative precursors of endodermal gut cells which are detected after 72 h post-fertilization (hpf). At day 5 post-fertilization (dpf), Pdu-Tcf is expressed in the hindgut and pharynx (foregut), whereas at 7 dpf stage, it is strongly transcribed in the now-cellularized midgut for the first time. In order to gain insight into the role of Wnt/β-catenin signalling, we disrupted its activity using pharmacological inhibitors between day 5 and 7 of development. The inhibition of Wnt/β-catenin signalling led to the loss of midgut marker genes Subtilisin-1, Subtilisin-2, α-Amylase and Otx along with a drop in β-catenin protein levels, Axin expression in the gut and nearly the complete loss of proliferative activity throughout the body of larva. At the same time, a hindgut marker gene Legumain was expanded to the midgut compartment under the same conditions. Conclusions Our findings suggest that high Wnt/β-catenin signalling in the midgut might be necessary for proper differentiation of the endoderm to an epithelium capable of secreting digestive enzymes. Together, our data provide evidence for the role of Wnt/β-catenin signalling in gut differentiation in Platynereis.

Background: The fatality rate of unstable pelvic fracture is still high [20-50%] due to acute phase hemorrhage or late multiple organ failure. The assurance for 100% survival in acute phase had been reported if the emergency room team have the right technique, right timing, and right protocol. The aim of this study was to evaluate and to date factors that influence the non-survival unstable pelvic fracture within 2x24 hours. Methods: This retrospective study was conducted in emergency unit of Dr. Soetomo General Hospital Surabaya during 2012-2016 for unstable pelvic fracture with unstable hemodynamic, without concomitant head or thoracic injury and admitted within 4 hours after the incident. All patients were handled according to the protocol for resuscitation and C-clamp insertion immediately. X-ray was taken after the insertion to check the C-clamp position and to confirm the diagnosis. The 2x24-hour data were taken whether the patient survive or not survive, including mean arterial pressure [MAP] pre-and post, heart rate [HR] pre-and post, and initial hemoglobin and platelet count. Data were analyzed with independent t-test and multiple regression analysis. Results: Twenty two patients were recorded as the inclusive criteria, separated into 17 survivors and 5 non-survivors. They were comprised of 14 males and 8 female patients, with an average of 31.9±15.3 years old. The MAP post, HR pre-and post, and platelet count were significantly different. The factor that influenced the survival within 2x24 hours was the MAP post C-clamp [>70 mmHg] [p<0.05]. Conclusion: The acute phase 2x24-hour outcome after C-clamp insertion and resuscitation was significantly influenced by MAP post C-clamp and resuscitation. [ABSTRACT FROM AUTHOR]

Objectives: To report our experience of regional referral center for the pelvis. Methods: We treated 526 pelvic fractures from January 2004 to December 2014 in three regional reference centers for pelvic trauma. Men were 480 and women were 46 and ages ranged from 16 to 93 years old. Car (65%) and farm (20%) crashes were the most frequent causes of pelvis fractures. Injury severity scores ranged from 9.0 to 75.0, with a mean of 37.5. A defined algorithm for fracture management has been in place and employed to assure adequate resuscitation and fracture care. Results: There were 24 deaths in total (4.56%). Sixty three (11.98%) patients underwent angio-embolization for control of bleeding (12 deaths). The average amount of blood transfused was 8.3 IU. Hospital lengths of stay ranged between 1-35 days. Among the 502 alive patients, 55.98% were able to be discharged at home while the remaining 44.02% being transferred to various rehabilitation facilities or extended care facilities. Conclusions: The goal of initial management is to restore vital indicators, urinary excretion function and protect the patient from infectious complications. An emergency decisional algorithm helps manage hemodynamic instability. Initial bone and ligament procedures should reduce displacement and make it possible for the patient to wait until his condition is stable enough for definitive surgical fixation.

T-cell Factor/Lymphoid Enhancer Factor (TCF/LEF) transcription factors are major regulators of Wnt targets, and the products of the TCF7 and TCF7L2 genes have both been implicated in the progression of colorectal cancer in animal models and humans. TCFs recognize specific DNA sequences through their high mobility group (HMG) domains, but invertebrate TCFs and some isoforms of vertebrate TCF7 and TCF7L2 contain a second DNA binding domain known as the C-clamp. This review will cover the basic properties of C-clamps and their importance in Wnt signaling, using data from Drosophila, C. elegans, and mammalian cell culture. The connection between C-clamp containing TCFs and colorectal cancer will also be discussed. [ABSTRACT FROM AUTHOR]

We previously found that TCF7L2 could activate the TMEPAI gene efficiently, whereas LEF1 could not nearly augment its transcription. When we comprehended the functional difference(s) between TCF7L2 and LEF1 with respect to the activation of the TMEPAI gene, the C-terminal tail of TCF7L2 was needed to reveal its transcriptional activity as well as its interaction with Smad3. Consistently, both TCF7/ TCF7L2 and LEF1/TCF7L2 chimeric proteins exhibited an activity similar to TCF7L2 in transcription and Smad3 binding in contrast with LEF1 and TCF7. Our data elaborated on the diverse activity among TCF/LEF family members with respect to the transcriptional regulation of the TMEPAI gene. [ABSTRACT FROM AUTHOR]

Objectives To report our experience of regional referral center for the pelvis. Methods We treated 526 pelvic fractures from January 2004 to December 2014 in three regional reference centers for pelvic trauma. Men were 480 and women were 46 and ages ranged from 16 to 93 years old. Car (65%) and farm (20%) crashes were the most frequent causes of pelvis fractures. Injury severity scores ranged from 9.0 to 75.0, with a mean of 37.5. A defined algorithm for fracture management has been in place and employed to assure adequate resuscitation and fracture care. Results There were 24 deaths in total (4.56%). Sixty three (11.98%) patients underwent angio-embolization for control of bleeding (12 deaths). The average amount of blood transfused was 8.3 IU. Hospital lengths of stay ranged between 1-35 days. Among the 502 alive patients, 55.98% were able to be discharged at home while the remaining 44.02% being transferred to various rehabilitation facilities or extended care facilities. Conclusions The goal of initial management is to restore vital indicators, urinary excretion function and protect the patient from infectious complications. An emergency decisional algorithm helps manage hemodynamic instability. Initial bone and ligament procedures should reduce displacement and make it possible for the patient to wait until his condition is stable enough for definitive surgical fixation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Emergency devices for pelvic ring stabilization include circumferential sheets, pelvic binders, and c-clamps. Our knowledge of the outcome of these techniques is currently based on limited information. Methods: Using the dataset of the German Pelvic Trauma Registry, demographic and injury-associated characteristics as well as the outcome of pelvic fracture patients after sheet, binder, and c-clamp treatment was compared. Outcome parameters included transfusion requirement of packed red blood cells, length of hospital stay, mortality, and incidence of lethal pelvic bleeding. Results: Two hundred seven of 6137 (3.4%) patients documented in the German Pelvic Trauma Registry between April 30th 2004 and January 19th 2012 were treated by sheets, binders, or c-clamps. In most cases, c-clamps (69%) were used, followed by sheets (16%), and binders (15%). The median age was significantly lower in patients treated with binders than in patients treated with sheets or c-clamps (26 vs. 47 vs. 42years, p =0.01). Sheet wrapping was associated with a significantly higher incidence of lethal pelvic bleeding compared to binder or c-clamp stabilization (23% vs. 4% vs. 8%). No significant differences between the study groups were found in sex, fracture type, blood haemoglobin concentration, arterial blood pressure, Injury Severity Score, the incidence of additional pelvic packing and arterial embolization, need of red blood cell transfusion, length of hospitalisation, and mortality. Conclusions: The data suggest that emergency stabilization of the pelvic ring by binders and c-clamps is associated with a lower incidence of lethal pelvic bleeding compared to sheet wrapping. Level of evidence: Level III. [Copyright &y& Elsevier]

Background: Pelvic ring injuries with associated hemorrhage from the presacral venous plexus are major contributors to morbidity and mortality in trauma patients. The Pelvic C-Clamp is an often discussed, yet seldom used device for both skeletal and hemodynamic stabilization. In a recent study we have addressed this issue and have stressed the importance of regular training sessions with the device. This study is aimed as an extended follow up with a special focus on how trained skills are retained over time. Materials and methods: 32 participants with various levels of training were taught to use the clamp. Thirty-six hours later, a hands-on session was performed where the time needed for placement and accuracy of placement were evaluated on a model in individual and team settings. 12 months later a re-evaluation was performed. Results: Evaluation showed that during the first session, 57/64 pins (89.15 %) were placed inside the safe area. The team training results showed reduced times for assembly and more exact pin placement. In the re-evaluation 1 year later, 75 % of all pins were safely placed and the time needed for assembly was significantly longer. Conclusions: The majority of 57 pins were placed in the safe area within 6 min after one single training session. This reproduces the Australian data and supports the theory that adequately educated and skilled physicians should be able to handle the device properly. The data from the re-evaluation suggest that repeating the training session with the device improves performance. [ABSTRACT FROM AUTHOR]

Abstract: Background: Unstable pelvic fractures with associated haemodynamic instability are major contributors of mortality and morbidity after blunt trauma. The pelvic C-clamp is one of the methods for emergency skeletal stabilization for pelvic ring injuries with posterior instability. The application of this device is taught on courses, but it is seldom used. The safety and efficiency of C-clamp application by trained first time users is unknown. We hypothesised that the pelvic C-clamp cannot be safely positioned on a training model after one training session. Methods and materials: A theoretical and a practical session on the application of the pelvic C-clamp was held within an interval of 11.2±4.4. Twenty-seven participants of various levels of training were assessed on accuracy and efficacy of the application of the pelvic C-clamp was applied to a pelvic model (Pelvic Trainer™). Results: 70.4% of all participants were able to place both pins inside the safe zone, whilst 81.5% of all pins were positioned safe. 18.5% were considered to be in unsafe position. The distance to optimal target point was 9.6±7.8mm on the left (injured) hemipelvis and 8.7±7.8mm on the right (uninjured). The time needed for assembly was 99.7±39.7s, for placement it averaged at 133.9±74s. Conclusions: The majority of pins were placed into the safe zone on a training model within 4min after one training session. 18.5% dangerous pin placement within 11 days of the training requires careful consideration (risk/benefit) in the context of a critically injured dying patient. [Copyright &y& Elsevier]

Background: Exsanguinating hemorrhage is the major cause of death in patients with pelvic ring disruption. Aims: The aim of this study was to document outcomes after the stabilization of pelvic ring injuries by a C-clamp and control of hemorrhage by pelvic packing. Physiological parameters were tested as prognostic factors. Setting and Design: This was a retrospective study at a level I trauma center. The study period was from January 1996 to December 2007. Materials and Methods: Fifty patients with pelvic ring disruption and hemorrhagic shock were analyzed. The pelvic rings were fixed by a C-clamp, and patients with ongoing hemorrhage underwent laparotomy and extra- and/or intra-peritoneal pelvic packing. Clinical parameters (heart rate, mean arterial pressure) and physiological parameters (lactate levels, hemoglobin, hematocrit) were documented at admission and at different time points during the initial treatment (1, 2, 3, 4, 6, 8, and 12h after admission). Results: Within 12 h of admission, 16 patients died (nonsurvivors) due to hemorrhagic shock (n=13) or head injuries (n=3). In this group, 12 patients underwent laparotomy with pelvic packing. Thirty-four patients survived the first 12 h (early survivors) after fixation by a C-clamp and additional packing in 23 patients. Four of these patients died 12.3±7.1 days later due to multiple organ failure (n=3) or severe head injury (n=1). The blood lactate level at admission was significantly higher in the group of nonsurvivors (7.2±0.8 mmol/L) compared to the early survivors (4.3±0.5 mmol/L, P<0.05). While hemoglobin values improved within the first 2 h in nonsurvivors, lactate levels continued to increase. Conclusion: Pelvic packing in addition to the C-clamp fixation effectively controls severe hemorrhage in patients with pelvic ring disruption. Early sequential measurements of blood lactate levels can be used to estimate the severity of shock and the response to the shock treatment. [ABSTRACT FROM AUTHOR]

Abstract: Bleeding pelvic fractures that result in haemodynamic instability have a reported mortality rate as high as 40%. Because of the extreme force needed to disrupt the pelvic ring, associated injuries are common and mortality is usually from uncontrolled haemorrhage from extra-pelvic sources. Identifying and controlling all sources of bleeding is a complex challenge and is best managed by a multi-disciplinary team, which include trauma surgeons, orthopaedic surgeons and interventional radiologists. Once the pelvis is identified as the major source of haemorrhage, component therapy reconstituting whole blood should be used and the pelvic region wrapped circumferentially with a sheet or pelvic binder. Patients at risk for arterial bleeding who continue to show haemodynamic instability despite resuscitative efforts should undergo immediate arteriography and embolisation of bleeding pelvic vessels. If this is unavailable or delayed, or the patient has other injuries (i.e., head, chest, intra-abdominal, long bone), external fixation and pelvic packing, performed concomitantly with other life-saving procedures, may be used to further reduce pelvic venous bleeding. If however, the patient remains haemodynamically labile without apparent source of blood loss, transcatheter angiographic embolisation should be attempted to locate and stop pelvic arterial bleeding. Institutional practice guidelines have been shown to reduce mortality and should be developed by all centres treating pelvic fractures. [Copyright &y& Elsevier]

Abstract: Pelvic angiography is an established technique that has evolved into a highly effective means of controlling arterial pelvic haemorrhage. The current dominant paradigm for haemodynamically unstable patients with pelvic fractures is angiographic management combined with mechanical stabilisation of the pelvis. However, an effective rapid screening tool for arterial bleeding in pelvic fracture patients has yet to be identified. There is also no precise way to determine the major source of bleeding responsible for haemodynamic instability. In many pelvic fracture patients, bleeding is from venous lacerations which are not effectively treated with angiography to fractured bony surfaces. Modern pelvic packing consists of time-saving and minimally invasive techniques which appear to result in effective control of the haemorrhage via tamponade. This review article focuses on the recent body of knowledge on angiography and pelvic packing. We propose the optimal role for each modality in trauma centres. [Copyright &y& Elsevier]

Introduction: Hemorrhage is the leading cause of death in patients with a pelvic fracture. The majority of blood loss derives from injured retroperitoneal veins and broad cancellous bone surfaces. The emergency management of multiply injured patients with pelvic ring disruption and severe hemorrhage remains controversial. Although it is well accepted that the displaced pelvic ring injury must be rapidly reduced and stabilized, the methods by which control of hemorrhagic shock is achieved remain under discussion. It has been proposed to exclusively use external pelvic ring stabilization for control of hemorrhage by producing a 'tamponade effect' of the pelvis. However, the frequency of clinically important arterial bleeding after external fixation of the pelvic ring remains unclear. We therefore undertook this retrospective review to attempt to answer this one important question: How frequently is arterial embolization necessary to control hemorrhage and restore hemodynamic stability after external pelvic ring fixation? Materials and methods: We performed a retrospective review of 55 consecutive patients who presented with unstable types B and C pelvic ring fractures. Those patients designated as being in hemorrhagic shock (defined as a systolic blood pressure less than 90 mmHg after receiving 2 L of intravenous crystalloid) were treated by application of the pelvic C-clamp. Patients who remained in hemorrhagic shock, or were determined to be in severe shock (defined as mandatory catecholamines or more than 12 blood transfusions over 2 h), underwent therapeutic angiography within 24 h in order to control bleeding. Results: Fourteen patients were identified as being hemodynamically unstable (ISS 30.1±11.3 points) and were treated with a C-clamp. In those patients with persistent hemodynamic instability, arterial embolization was performed. After C-clamp application, 5 of 14 patients required therapeutic angiography to control bleeding. Two patients died, one from multiple sources of bleeding and the other from an open pelvic fracture (total mortality 2/14, 14%). Conclusions: Although the C-clamp is effective in controlling hemorrhage, one must be aware of the need for arterial embolization to restore hemodynamic stability in a select subgroup of patients. [ABSTRACT FROM AUTHOR]

Background: Wnt/β-catenin (or canonical) signalling pathway activity is necessary and used independently several times for specification of vegetal fate and endoderm, gut differentiation, maintenance of epithelium in adult intestine and the development of gut-derived organs in various vertebrate and non-vertebrate organisms. However, its conservation in later stages of digestive tract development still remains questionable due to the lack of detailed data, mainly from Spiralia. Results: Here we characterize the Pdu-Tcf gene, a Tcf/LEF orthologue and a component of Wnt/β-catenin pathway from Platynereis dumerilii, a spiralian, marine annelid worm. Pdu-Tcf undergoes extensive alternative splicing in the C-terminal region of the gene generating as many as eight mRNA isoforms some of which differ in the presence or absence of a C-clamp domain which suggests a distinct DNA binding activity of individual protein variants. Pdu-Tcf is broadly expressed throughout development which is indicative of many functions. One of the most prominent domains that exhibits rather strong Pdu-Tcf expression is in the putative precursors of endodermal gut cells which are detected after 72 h post-fertilization (hpf). At day 5 post-fertilization (dpf), Pdu-Tcf is expressed in the hindgut and pharynx (foregut), whereas at 7 dpf stage, it is strongly transcribed in the now-cellularized midgut for the first time. In order to gain insight into the role of Wnt/β-catenin signalling, we disrupted its activity using pharmacological inhibitors between day 5 and 7 of development. The inhibition of Wnt/β-catenin signalling led to the loss of midgut marker genes Subtilisin-1, Subtilisin-2, α-Amylase and Otx along with a drop in β-catenin protein levels, Axin expression in the gut and nearly the complete loss of proliferative activity throughout the body of larva. At the same time, a hindgut marker gene Legumain was expanded to the midgut compartment under the same conditions. Conclusions: Our findings suggest that high Wnt/β-catenin signalling in the midgut might be necessary for proper differentiation of the endoderm to an epithelium capable of secreting digestive enzymes. Together, our data provide evidence for the role of Wnt/β-catenin signalling in gut differentiation in Platynereis. [ABSTRACT FROM AUTHOR]