Structure and Innervation of the Extrahepatic Biliary System in the Australian Possum, Trichosurus Vulpecula

The morphology, microanatomy and innervation of the biliary tree of the Australian possum, Trichosurus vulpecula, was examined. The gross morphology of the gallbladder, hepatic and cystic ducts, and the course of the common bile duct, conforms to those of other species. The sphincter of Oddi has an extraduodenal segment that extends 15mm from the duodenal wall; within this segment the pancreatic and common bile ducts are ensheathed together by sphincter muscle. Their lumens unite to form a common channel within the terminal intraduodenal segment

Seven-month developmental outcomes of very low birth weight infants enrolled in a randomized controlled trial of delayed versus immediate cord clamping

Objective: The results from our previous trial revealed that infants with delayed cord clamping (DCC) had significantly lesser intraventricular hemorrhage (IVH) and late-onset sepsis (LOS) than infants with immediate cord clamping (ICC). A priori, we hypothesized that infants with DCC would have better motor function by 7 months corrected age. Study Design: Infants between 24 and 31 weeks were randomized to ICC or DCC and follow-up evaluation was completed at 7 months corrected age. Result: We found no differences in the Bayley Scales of Infant Development (BSID) scores between the DCC and ICC groups. However, a regression model of effects of DCC on motor scores controlling for gestational age, IVH, bronchopulmonary dysplasia, sepsis and male gender suggested higher motor scores of male infants with DCC. Conclusion: DCC at birth seems to be protective of very low birth weight male infants against motor disability at 7 months corrected age

Interaction between toothbrushes and toothpaste abrasive particles in simulated tooth cleaning

There are currently many toothbrush designs on the market incorporating different filament configurations such as filaments at various angles and different lengths and made from several different materials. In order to understand how the tooth cleaning process occurs there is a need to investigate in detail how the abrasive particles in a toothpaste interact with the filaments in a teeth cleaning contact and cause material removal from a plaque or stain layer. The following describes the development of optical apparatus to enable the visualisation of simulated teeth cleaning contacts. Studies have been carried out using the apparatus to investigate particle entrainment into the contact and how it differs with varying bristle configurations. The effects of filament stiffness and tip shape were also investigated. Various types of electric toothbrushes were also tested. The studies have shown how particles are trapped at the tips of toothbrush filaments. Particles, suspended in fluid, approach the filament tips, as they pass through they may become trapped. Greater particle entrainment into the filament tip contact occurs with a reciprocating action at low filament loads and deflections than with a sliding motion. Large particles are less likely to enter tip contacts and are trapped between tips or under the filament bend at higher loads. Whether the particles are likely to be trapped and how long they remain so depends on the filament stiffness and degree of splay on loading and the filament configuration. The direction the filaments point in, the number of filaments in a tuft, the spacing of the tufts and the way the filaments splay when deflected all have an influence on entrainment of particles. Tufts with tightly packed stiff filaments which deflected together on loading were more effective at trapping particles than more flexible filaments that splayed out on loading as they present more of a barrier to particle entry and exit from the tip region

In Vitro and In Vivo Evidence for Lack of Endovascular Remodeling by Third Trimester Trophoblasts

The placental–decidual interaction through invading trophoblasts determines whether a physiological transformation of the uterine spiral arteries is established or not. Trophoblast-orchestrated artery remodeling is central to normal placentation. Dysregulated uteroplacental interaction and vascular remodeling are thought to be associated with the molecular events underlying the pathology of late pregnancy anomalies including preeclampsia. Although the exact gestational age at which trophoblast invasion ceases is not known, it remains unclear whether late pregnancy trophoblasts retain the ability to transform the uterine arteries. Here, we have developed a dual cell, in vitro culture system that mimics the vascular remodeling events during normal pregnancy. We demonstrate that first and third trimester trophoblasts respond differentially to interactive signals from endothelial cells when cultured on matrigel. Term primary trophoblasts or immortalized third trimester extravillous TCL1 trophoblasts not only fail to respond to signals from endothelial cells but also inhibit endothelial cell tube formation. In contrast, HTR8 cells, representing a first trimester trophoblast cell line with invasive properties, undergo spontaneous migration and synchronize with the endothelial cells in a capillary network. This disparity in behavior was confirmed in vivo using a matrigel plug assay. Poor expression of VEGF C and VEGF receptors coupled with high E-cadherin expression by term primary trophoblasts and TCL1 cells contributed to their restricted interactive and migratory properties. We further show that the kinase activity of VEGF R2 is essential for proactive crosstalk by HTR8 cells. This unique behavior of first trimester trophoblasts in the presence of endothelial cells offers a potential approach to study cell–cell interactions and to decipher modulatory components in the serum samples from adverse pregnancy outcomes

Delayed Cord Clamping in Very Preterm Infants Reduces the Incidence of Intraventricular Hemorrhage and Late-Onset Sepsis: A Randomized, Controlled Trial

Objective: This study compared the effects of immediate (ICC) and delayed (DCC) cord clamping on very low birth weight (VLBW) infants on 2 primary variables: bronchopulmonary dysplasia (BPD) and suspected necrotizing enterocolitis (SNEC). Other outcome variables were late-onset sepsis (LOS) and intraventricular hemorrhage (IVH). Study Design: This was a randomized, controlled unmasked trial in which women in labor with singleton fetuses \u3c32 weeks’ gestation were randomly assigned to ICC (cord clamped at 5–10 seconds) or DCC (30–45 seconds) groups. Women were excluded for the following reasons: their obstetrician refused to participate, major congenital anomalies, multiple gestations, intent to withhold care, severe maternal illnesses, placenta abruption or previa, or rapid delivery after admission. Results: Seventy-two mother/infant pairs were randomized. Infants in the ICC and DCC groups weighed 1151 and 1175 g, and mean gestational ages were 28.2 and 28.3 weeks, respectively. Analyses revealed no difference in maternal and infant demographic, clinical, and safety variables. There were no differences in the incidence of our primary outcomes (BPD and suspected NEC). However, significant differences were found between the ICC and DCC groups in the rates of IVH and LOS. Two of the 23 male infants in the DCC group had IVH versus 8 of the 19 in the ICC group. No cases of sepsis occurred in the 23 boys in the DCC group, whereas 6 of the 19 boys in the ICC group had confirmed sepsis. There was a trend toward higher initial hematocrit in the infants in the DCC group. Conclusions: Delayed cord clamping seems to protect VLBW infants from IVH and LOS, especially for male infants

Treatment of a Giant Haemangioma of the Liver With Kasabach-Merritt Syndrome by Orthotopic Liver Transplant

We describe a case of giant cavernous haemangioma of the liver with disseminated intravascular coagulopathy (Kasabach-Merritt syndrome) which was cured by orthotopic liver transplant

Effects of Placental Transfusion on Neonatal and 18 Month Outcomes in Preterm Infants: A Randomized Controlled Trial

Objective: To assess the effect of delayed cord clamping (DCC) vs immediate cord clamping (ICC) on intraventricular hemorrhage (IVH), late onset sepsis (LOS), and 18-month motor outcomes in preterm infants. Study Design: Women (n = 208) in labor with singleton fetuses (\u3c32 weeks gestation) were randomized to either DCC (30-45 seconds) or ICC (\u3c10 seconds). The primary outcomes were IVH, LOS, and motor outcomes at 18-22 months corrected age. Intention-to-treat was used for primary analyses. Results: Cord clamping time was 32 ± 16 (DCC) vs 6.6 ± 6 (ICC) seconds. Infants in the DCC and ICC groups weighed 1203 ± 352 and 1136 ± 350 g and mean gestational age was 28.3 ± 2 and 28.4 ± 2 weeks, respectively. There were no differences in rates of IVH or LOS between groups. At 18-22 months, DCC was protective against motor scores below 85 on the Bayley Scales of Infant Development, Third Edition (OR 0.32, 95% CI 0.10-0.90, P = .03). There were more women with preeclampsia in the ICC group (37% vs 22%, P = .02) and more women in the DCC group with premature rupture of membranes/preterm labor (54% vs 75%, P = .002). Preeclampsia halved the risk of IVH (OR 0.50, 95% CI 0.2-1.0) and premature rupture of membranes/preterm labor doubled the risk of IVH (OR 2.0, 95% CI 1.2-4.3). Conclusions: Although DCC did not alter the incidence of IVH or LOS in preterm infants, it improved motor function at 18-22 months corrected age

Value of magnetic resonance cholangiopancreatography in the diagnosis of biliary abnormalities in postcholecystectomy patients: A probabilistic cost-effectiveness analysis of diagnostic strategies

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard for imaging of the biliary tract but is associated with complications. Less invasive imaging techniques, such as magnetic resonance cholangiopancreatography (MRCP), have a much lower complication rate. The accuracy of MRCP is comparable to that of ERCP, and MRCP may be more effective and cost-effective, particularly in cases for which the suspected prevalence of disease is low and further intervention can be avoided. A model was constructed to compare the effectiveness and cost-effectiveness of MRCP and ERCP in patients with a previous history of cholecystectomy, presenting with abdominal pain and/or abnormal liver function tests. Methods: Diagnostic accuracy estimates came from a systematic review of MRCP. A decision analytic model was constructed to represent the diagnostic and treatment pathway of this patient group. The model compared the following two diagnostic strategies: (i) MRCP followed with ERCP if positive, and then management based on ERCP; and (ii) ERCP only. Deterministic and probabilistic analyses were used to assess the likelihood of MRCP being cost-effective. Sensitivity analyses examined the impact of prior probabilities of common bile duct stones (CBDS) and test performance characteristics. The outcomes considered were costs, quality-adjusted life years (QALYs), and cost per additional QALY. Results: The deterministic analysis indicated that MRCP was dominant over ERCP. At prior probabilities of CBDS, less than 60 percent MRCP was the less costly initial diagnostic test; above this threshold, ERCP was less costly. Similarly, at probabilities of CBDS less than 68 percent, MRCP was also the more effective strategy (generated more QALYs). Above this threshold, ERCP became the more effective strategy. Probabilistic sensitivity analyses indicated that, in this patient group for which there is a low to moderate probability of CBDS, there was a 59 percent likelihood that MRCP was cost-saving, an 83 percent chance that MRCP was more effective with a higher quality adjusted survival, and an 83 percent chance that MRCP had a cost-effectiveness ratio more favorable than $50,000 per QALY gained. Conclusions: Costs and cost-effectiveness are dependent upon the prior probability of CBDS. However, probabilistic analysis indicated that, with a high degree of certainty, MRCP was the more effective and cost-effective initial test in postcholecystectomy patients with a low to moderate probability of CBDS.Kirsten Howard, Sarah J. Lord, Anthony Speer, Robert N. Gibson, Robert Padbury and Brendon Kearne

Association of BMI with overall survival in patients with mCRC who received chemotherapy versus EGFR and VEGF-targeted therapies

Although a raised body mass index (BMI) is associated with increased risk of colorectal cancer (CRC) and recurrence after adjuvant treatment, data in the metastatic setting is limited. We compared overall survival (OS) across BMI groups for metastatic CRC, and specifically examined the effect of BMI within the group of patients treated with targeted therapies (TT). Retrospective data were obtained from the South Australian Registry for mCRC from February 2006 to October 2012. The BMI at first treatment was grouped as underweight <18.5 kg/m(2) , Normal = 18.5 to <25 kg/m(2) , Overweight = 25 to <30 kg/m(2) , Obese I = 30 to <35 kg/m(2) , Obese II ≥35 kg/m(2) . Of 1174 patients, 42 were underweight, 462 overweight, 175 Obese I, and 77 Obese II. The OS was shorter for patients who were underweight and overweight compared to normal (OS 13.7 and 22.3 vs. 24.1 months, respectively, hazard ratio [HR] 2.21 and 1.23). The adjusted median OS was longer for normal versus overweight or obese I patients receiving chemotherapy + targeted therapy (35.7 vs 25.1 or 22.8 months, HR 1.59 and 1.63, respectively) with no difference in OS for chemotherapy alone. On breakdown by type of targeted therapy, overweight and obese I patients had a poorer outcome with Bevacizumab. The BMI is predictive of a poorer outcome for underweight and overweight patients in the whole population. Of those receiving chemotherapy and targeted therapy, BMI is an independent predictor for OS for overweight and obese I patients, specifically for those treated with Bevacizumab. Patients who are overweight or obese (group I) may be a target group for lifestyle and nutrition advice to improve OS with TT.Gargi S. Patel, Shahid Ullah, Carol Beeke, Paul Hakendorf, Robert Padbury, Timothy J. Price and Christos S. Karapeti

Guidelines for Perioperative Care for Liver Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations 2022.

Enhanced Recovery After Surgery (ERAS) has been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016. The aim of the present article was to update the ERAS guidelines in liver surgery using a modified Delphi method based on a systematic review of the literature. A systematic literature review was performed using MEDLINE/PubMed, Embase, and the Cochrane Library. A modified Delphi method including 15 international experts was used. Consensus was judged to be reached when &gt;80% of the experts agreed on the recommended items. Recommendations were based on the Grading of Recommendations, Assessment, Development and Evaluations system. A total of 7541 manuscripts were screened, and 240 articles were finally included. Twenty-five recommendation items were elaborated. All of them obtained consensus (&gt;80% agreement) after 3 Delphi rounds. Nine items (36%) had a high level of evidence and 16 (64%) a strong recommendation grade. Compared to the first ERAS guidelines published, 3 novel items were introduced: prehabilitation in high-risk patients, preoperative biliary drainage in cholestatic liver, and preoperative smoking and alcohol cessation at least 4 weeks before hepatectomy. These guidelines based on the best available evidence allow standardization of the perioperative management of patients undergoing liver surgery. Specific studies on hepatectomy in cirrhotic patients following an ERAS program are still needed