Data-Driven Surveillance Protocol for Patients at Risk for Peritoneal Recurrence of Primary Colon Cancer: Surveillance for Peritoneal Carcinomatosis.

Peritoneal carcinomatosis (PC) is rarely discovered early due to low sensitivity of screening imaging and tumor markers, however, earlier identification may improve outcomes. This study assesses risk factors and time to recurrence of PC and implementation of a surveillance system. Patients with stage II-III colon adenocarcinoma undergoing curative colectomy between 2005-2022 were retrospectively reviewed at a single tertiary care institution. Patients were divided into three cohorts: no recurrence (NR), PC, and other types of recurrence (OTR). Baseline characteristics between cohorts were compared with univariate analysis. Overall survival and PC risk were assessed using multivariate analysis with Cox's proportional-hazard modelling. 412 patients were included; 78.4% had NR, 7.8% had PC, and 13.8% had OTR. Patient demographics, comorbidities, tumor side, and histologic features were similar between cohorts. Patients with PC were more likely to have microscopic tumor perforation (25% vs. 8.8% vs. 6.8%, p = 0.002), margin involvement (25% vs. 8.8% vs. 4.6%, p < 0.001), lymphovascular invasion (56.2% vs. 33.3%, vs. 24.5%, p < 0.001), perineural invasion (28.1% vs. 15.8% vs. 11.5%, p = 0.026) compared to OTR or NR. Median time to PC after colectomy was 11 months. Tumor characteristics of stage II-III colon cancer define a high-risk profile for PC. An early surveillance program sensitive for peritoneal disease should be adopted for these patients.

Increasing Adoption of Laparoscopy in Urgent and Emergent Colectomies for Pediatric Ulcerative Colitis.

INTRODUCTION: While minimally invasive surgery (MIS) approaches are commonly utilized in the elective surgical setting for pediatric ulcerative colitis (UC), their role in urgent and emergent disease is less clear. We aim to assess trends in the surgical approaches for pediatric UC patients requiring urgent and emergent colectomies and their associated outcomes. METHODS: Retrospective review of 81 pediatric UC patients identified in National Surgical Quality Improvement Program Pediatric who underwent urgent or emergent colectomy (2012-2019). Trends in approach were assessed using linear regression. Patient characteristics and clinical outcomes were stratified by approach and compared using standard univariate statistics. Multivariable analysis was used to model the influence of covariates on postoperative length of stay. RESULTS: The proportion of MIS cases increased by 5.53% per year (P = 0.01) over the study interval. Sixty-three patients (77.8%) received MIS resections and 18 patients (22.2%) received open resections. Patients undergoing open colectomies were younger and had a higher proportion of preoperative conditions, most notably preoperative sepsis (27.8% versus 4.8%, P = 0.01), and higher American Society of Anesthesiologists [III-IV] classification (83.3% versus 58.8%, P = 0.004). Mean operative time was comparable (open, 173.6 versus MIS, 206.1 min). In the univariate analysis, open approach was associated with increased postoperative length of stay (13.1 versus 7.2 d, P = 0.002). However, after adjusting for confounders, there was no significant difference. CONCLUSIONS: There has been a steady increase in the adoption of laparoscopy in urgent and emergent colectomy for pediatric UC. Short-term outcomes between approaches appear comparable.

Ogilvie Syndrome, Bradycardia, and Neostigmine.

Acute colonic pseudo-obstruction (ACPO), known as Ogilvie Syndrome, is an acute dilation of the colon in the absence of an underlying mechanical or anatomic cause. Neostigmine treatment is indicated following failed conservative management of ACPO, however neostigmine has its contraindications. This is a report of a unique case of a patient with a past medical history of symptomatic first degree heart block with a permanent pacemaker who received a bolus dosage of neostigmine treatment for ACPO in an ICU setting.

Patients', carers' and clinicians' attitudes towards alternative terms to describe the at-risk for psychosis state.

OBJECTIVE: Language used in psychiatry is important because it provides an understandable and accurate way of describing clinical and theoretical concepts. The use of labels in psychiatry has often been associated with stigma and reduced engagement with clinical services. This studys aims were to generate new terms for the 'at-risk mental state' (ARMS) concept and to investigate what young people, their caregivers and clinicians thought about them as well as terms commonly used in early intervention clinics. Another aim was to understand participants preference related to the best timing to introduce the at-risk concept and the extent and context of the information presented. METHODS: New terms illustrating the at-risk concept have been generated by a youth reference group with lived experience of mental illness: 'pre-diagnosis stage' (PDS), potential of developing a mental illness (PDMI) and disposition for developing a mental illness (DDMI). A specifically designed questionnaire was administered to 46 patients with ARMS, 24 caregivers and 52 clinicians to obtain their feedback on newly proposed terms and on the terms already used in clinical practice and research. RESULTS: The preferred terms were PDS, PDMI and ARMS. The least favoured terms were Ultra High Risk and Attenuated Psychosis Syndrome, which were thought to be associated with the most stigma. Most participants agreed that disclosure about diagnosis should be delivered early by the key clinician. CONCLUSIONS: Patients generated terms such as PDS, PDMI, alongside ARMS should be considered to be used in clinical practice. They present with low stigma and are illustrative of young peoples difficulties.

Hematogenous Donor Cell Routing Pathway After Transamniotic Stem Cell Therapy.

Donor mesenchymal stem cells (MSCs) have been documented in fetal and maternal circulations after plain intra-amniotic injection, with diverse therapeutic effects. We sought to determine the pathway of this unique cell kinetic route. Rat fetuses (n = 226) were divided into two groups based on the content of intra-amniotic injections performed on gestational day 17 (E17): either a concentrated suspension of luciferase-labeled syngeneic amniotic fluid-derived MSCs (afMSCs; n = 111), or acellular luciferase (n = 115). Samples from placenta, chorion, amnion, amniotic fluid, stomach fluid, peripheral blood, and umbilical cord were procured at five daily time points thereafter until term (E18-22) for luminometry. In addition, 53 sets of fresh gestational membranes (chorion/amnion combined) from nonmanipulated term fetuses were secured to transwell inserts for in vitro analysis of MSC migration using luciferase-labeled afMSCs. Statistical analyses included the Mann-Whitney U-test, Wald test, nonlinear regression modeling, and Fisher's exact test. In vivo, luciferase activity was observed in the amnion, chorion, and placenta of fetuses receiving cells, but not in those receiving acellular luciferase (P < 0.001). There was a consistent nonlinear age-dependent relationship of luciferase activity between the amnion, chorion, and placenta following a parabolic bimodal pattern characterized by significantly higher early preterm (E18) and late-term (E22) activities (P < 0.001), with no differences between E21 and E22 (P = 0.12). In vitro, the presence of cells was documented by luminometry in 21/53 (39.6%) of the assays, in suspension and/or attached to the plastic substrate, and within all screened gestational membrane sets, irrespective of stimuli with collagen coating or fetal bovine serum. We conclude that, after intra-amniotic injection, donor MSCs undergo controlled cell routing, as opposed to passive clearance. Transgestational membrane transport appears to constitute the path for donor cells to reach the placenta, a known gateway to the fetal circulation, significantly expanding the potential applications of transamniotic stem cell therapy.

Postnatal fate of donor mesenchymal stem cells after transamniotic stem cell therapy in a healthy model.

PURPOSE: We sought to examine donor mesenchymal stem cell (MSC) fate after birth following transamniotic stem cell therapy (TRASCET) in a healthy model. METHODS: Lewis rat fetuses (n = 91) were divided into two groups based on the content of volume-matched intraamniotic injections performed on gestational day 17 (term = 21-22 days): either a suspension of amniotic fluid-derived MSCs (afMSCs) labeled with luciferase (n = 38) or acellular luciferase only (n = 53). Infused afMSCs consisted of syngeneic Lewis rat cells phenotyped by flow cytometry. Samples from 14 anatomical sites (heart, lung, brain, liver, spleen, pancreas, bowel, kidney, thyroid, skin, skeletal muscle, thymus, peripheral blood and bone marrow) from survivors were screened for luciferase activity 16 days after birth. Statistical analysis was by logistic regression and the Wald test (p < 0.05). RESULTS: Overall survival was 32% (29/91). When controlled by the acellular luciferase injections, donor afMSCs were not identified at any anatomical site in any neonate as measured by relative light units (all p > 0.05). Donor afMSC viability was confirmed in term placentas. CONCLUSIONS: Donor mesenchymal stem cells are not detectable in the neonate after intraamniotic injection in a normal syngeneic rodent model. This finding suggests that clinical trials of transamniotic stem cell therapy may be amenable to regulatory approval. LEVEL OF EVIDENCE: N/A (animal and laboratory study).

Trends of INR and Fecal Excretion of Vitamin K During Cholestasis Reversal: Implications in the Treatment of Neonates With Intestinal Failure-Associated Liver Disease.

BACKGROUND: Vitamin K is a fat-soluble compound that plays important roles in coagulation. In children with intestinal failure-associated liver disease (IFALD), the disrupted enterohepatic circulation can lead to intestinal loss of vitamin K. Fish oil-based lipid emulsion (FOLE) has proven effective in treating IFALD. As biliary excretion is restored during cholestasis reversal, the accelerated vitamin K loss can pose a risk for deficiency. METHODS: Ten neonates with IFALD and receiving FOLE monotherapy were prospectively enrolled in the study from 2016 to 2018. In addition to weekly measurements of international normalized ratio (INR) and direct bilirubin (DB), ostomy output was collected for determination of fecal concentrations of phylloquinone (PK). Trends of DB, INR, and fecal PK concentrations were summarized with locally estimated scatterplot smoothing. RESULTS: The median time (interquartile range) from FOLE initiation to cholestasis reversal was 59 (19-78) days. During cholestasis reversal, INR remained relatively unchanged, whereas the mean (95% confidence interval) daily fecal excretion of PK increased from 25.1 (5.0-158.5) ng at the time of FOLE initiation to 158.5 (31.6-1000.0) ng at complete reversal. Examination of individual trends in fecal PK excretion and INR revealed little correlation between the 2 measurements (r = -0.10; P = 0.50). CONCLUSION: Children with IFALD are at risk for vitamin K deficiency during cholestasis reversal. Close monitoring and quantified supplementation of vitamin K may be warranted during this period. However, this should not be guided by INR alone, as it is a poor indicator of vitamin K status.

Donor mesenchymal stem cell kinetics after transamniotic stem cell therapy (TRASCET) in a rodent model of gastroschisis.

PURPOSE: We sought to comprehensively scrutinize donor mesenchymal stem cell kinetics following transamniotic stem cell therapy (TRASCET) in experimental gastroschisis. METHODS: A gastroschisis was surgically created in 102 rat fetuses at gestation day 18 (term = 22 days), immediately followed by volume-matched amniotic injections of either amniotic fluid mesenchymal stem cells (afMSCs) labeled with a luciferase reporter gene (n = 58), or luciferase protein alone (n = 44). Samples from multiple anatomical sites from survivors were screened for luciferase activity via microplate luminometry at term. Statistical analysis included Mann-Whitney U-test, Wald test, and kappa coefficient (p < 0.05). RESULTS: Overall survival was 42% (43/102), with no significant difference between the two groups (p = 0.82). When controlled by acellular luciferase, donor afMSCs were identified selectively in the placenta (p < 0.001) and bowel (p = 0.005), independently of the dams (respectively, p < 0.001 and p = 0.041). Bowel homing was documented exclusively in areas exposed to the amniotic cavity. There was no mutual correlation between placental and bowel homing (kappa = -0.02; p = 0.91). CONCLUSIONS: Amniotic mesenchymal stem cells home to specific sites after TRASCET in the setting of gastroschisis. Placental homing and intestinal homing are central yet seemingly independent constituents of cell trafficking, suggesting that both direct amniotic seeding and hematogenous routing take place. LEVEL OF EVIDENCE: N/A (animal and laboratory study).

Metabolic and Inflammatory Effects of an ω-3 Fatty Acid-Based Eucaloric Ketogenic Diet in Mice With Endotoxemia.

BACKGROUND: Dietary strategies can aid in the management of critically ill patients. Very-low-carbohydrate diets have been shown to improve glucose control and the inflammatory response. We aimed to determine the effects of a eucaloric ketogenic diet (EKD) enriched with ω-3 fatty acids (O3KD) on glucose levels and inflammation in mice with endotoxemia. METHODS: Adult mice were fed 1 of 3 diets (control diet [CD], EKD, or O3KD). After 4 weeks, each group received saline or Escherichia coli lipopolysaccharide (LPS) (5 mg/kg) intraperitoneally during the postprandial (PPP) or postabsorptive (PAP) periods. Blood glucose was measured at 0, 15, 30, 60, 90, 120, 180, and 240 minutes. Serum tumor necrosis factor (TNF)-α and interleukin (IL) 6 were measured by enzyme-linked immunosorbent assay. Distribution of serum fatty acids was determined by gas liquid chromatography. Hepatic expression of genes involved in inflammation, as well as glucose and lipid metabolism, were determined by quantitative polymerase chain reaction. RESULTS: During the PPP, glucose curves were comparable among the experimental groups. During the PAP, EKD showed a more pronounced increase in glucose levels at the first hour after LPS challenge compared with the CD-LPS group. During the PAP, IL6 was lower in O3KD-LPS compared with CD-LPS and EKD-LPS groups. These differences disappeared in the PPP. Similarly, TNF-α was lower in the O3KD-LPS group compared with the EKD-LPS group. The O3KD significantly increased the serum levels of the ω-3 eicosapentaenoic and docosahexaenoic acids and decreased the ω-6 arachidonic acid. CONCLUSION: An O3KD leads to reduced inflammation and maintains glucose homeostasis in mice with endotoxemia.

Two fast methods for high-quality line visibility.

Lines drawn over or in place of shaded 3D models can often provide greater comprehensibility and stylistic freedom than shading alone. A substantial challenge for making stylized line drawings from 3D models is the visibility computation. Current algorithms for computing line visibility in models of moderate complexity are either too slow for interactive rendering, or too brittle for coherent animation. We introduce two methods that exploit graphics hardware to provide fast and robust line visibility. First, we present a simple shader that performs a visibility test for high-quality, simple lines drawn with the conventional implementation. Next, we offer a full optimized pipeline that supports line visibility and a broad range of stylization options.

Blended learning in orthodontic diagnosis: an interactive approach.

Interactive multimedia programs can provide an opportunity for authentic learning both inside and outside the classroom. McGill University designed an interactive Orthodontic Diagnosis program on CD-ROM that has been used successfully in the faculty of dentistry to provide undergraduate students with interactive tutorials and exercises to help them recognize developing malocclusions. Key aspects of this multimedia program are the use of an outside-in approach to diagnosis as well as sound instructional design that provides practice opportunities and feedback to students. The goal is to bridge the gap between theoretical knowledge and the practical skills needed to be a successful dentist.

Learning while evaluating: the use of an electronic evaluation portfolio in a geriatric medicine clerkship.

BACKGROUND: Electronic evaluation portfolios may play a role in learning and evaluation in clinical settings and may complement other traditional evaluation methods (bedside evaluations, written exams and tutor-led evaluations). METHODS: 133 third-year medical students used the McGill Electronic Evaluation Portfolio (MEEP) during their one-month clerkship rotation in Geriatric Medicine between September 2002 and September 2003. Students were divided into two groups, one who received an introductory hands-on session about the electronic evaluation portfolio and one who did not. Students' marks in their portfolios were compared between both groups. Additionally, students self-evaluated their performance and received feedback using the electronic portfolio during their mandatory clerkship rotation. Students were surveyed immediately after the rotation and at the end of the clerkship year. Tutors' opinions about this method were surveyed once. Finally, the number of evaluations/month was quantified. In all surveys, Likert scales were used and were analyzed using Chi-square tests and t-tests to assess significant differences in the responses from surveyed subjects. RESULTS: The introductory session had a significant effect on students' portfolio marks as well as on their comfort using the system. Both tutors and students reported positive notions about the method. Remarkably, an average (+/- SD) of 520 (+/- 70) evaluations/month was recorded with 30 (+/- 5) evaluations per student/month. CONCLUSION: The MEEP showed a significant and positive effect on both students' self-evaluations and tutors' evaluations involving an important amount of self-reflection and feedback which may complement the more traditional evaluation methods.

Caudal migration of endoprostheses after treatment of abdominal aortic aneurysms.

BACKGROUND: The purpose of this study is to assess the migration of endoprostheses 2 years after endovascular abdominal aortic aneurysm repair. METHODS: Ten patients underwent placement of bifurcated endoprostheses for infrarenal aneurysm and had 2-year CT follow-up. Standardized contrast-enhanced CT with 1.5- or 2-mm overlapping slice thickness was used. Four independent observers measured the distance from the lowest renal artery to the craniad end of the graft. RESULTS: As a whole, the endoprostheses migrated an average of 2.7 +/- 2.6 mm caudad at 24 months compared with baseline (P < 0.001). Four patients (40%) experienced > or =3-mm migration of the endoprostheses. On review of the 6- and 12-month follow-up CT scans, movement occurred at both the first- and the second-year intervals. CONCLUSIONS: Endovascular stent-grafts frequently migrate away from the renal arteries. This may be due to natural elongation of the native infrarenal aortic segment, but could also result from inadequate attachment of the proximal stent-graft. Although there have been no adverse clinical events in this group, continued close follow-up is mandatory following endovascular aneurysm repair.