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ABSTRACT: The objective of this study was to examine the effects of prenatal supplementation and dose of rumen-protected choline (RPC) on neonatal calf growth, metabolism, and vaccine response. Parous Holstein cows were blocked by calving month and randomly assigned within block to receive 45 g/d of RPC [20.4 g/d of choline ions (CHOL45), n = 19], 30 g/d of RPC [13.6 g/d of choline ions (CHOL30), n = 22], or no RPC (CON, n = 19) as a top-dress, starting 24 d before expected calving. Calf body weights were recorded for the first 3 wk of life. All calves were fed colostrum replacer (300 g of IgG) at birth, and apparent efficiency of IgG absorption was calculated. On d 1, 7, 14, and 21, blood samples were taken to quantify plasma reactive oxygen and nitrogen species, antioxidant potential, haptoglobin, nonesterified fatty acids (NEFA), β-hydroxybutyrate, and glucose. Calves received an intranasal vaccine at birth, and nasal secretions were collected on d 0, 7, 10, 14, and 21 to quantify bovine respiratory syncytial virus-specific IgA. Data were analyzed using linear mixed models including the fixed effects of treatment, time (when applicable), calf sex, and prepartum dam data (−24 d) along with interactions. Treatment did not affect calf body weight, β-hydroxybutyrate, or glucose concentrations. For apparent efficiency of IgG absorption, treatment interacted with the dam's prepartum body condition score. Where the dam's body condition score was ≤3.25, IgG absorption was reduced in calves born from CHOL45 dams as compared with calves from either CHOL30 or CON dams. Calves from CHOL30 dams had a lesser oxidative stress index (OSi; reactive oxygen and nitrogen species/antioxidant potential) than calves from CON dams. Haptoglobin concentrations were less in heifer calves from CHOL45 dams as compared with heifers from CON dams. The dam's prepartum NEFA concentration interacted with treatment. When dam NEFA was minimal, calves from CHOL45 and CHOL30 dams had greater or tended to have greater NEFA, respectively. Conversely, when dam NEFA was greater, calves from CHOL30 and CHOL45 dams had lesser or tended to have lesser NEFA than calves from CON dams, respectively. For vaccine response, treatment interacted with the dam's prepartum OSi. Among calves born from dams with a greater OSi, calves from CHOL45 and CHOL30 dams had lesser bovine respiratory syncytial virus-specific IgA concentrations in nasal secretions as compared with CON. Prenatal RPC supplementation during late gestation affected IgG absorption, neonatal calf metabolism, and vaccine response with some effects dependent on the dam's prepartum parameters.

Summary: Immunoglobulin G (IgG) antibodies that activate Fc-mediated immune functions have been correlated with vaccine efficacy, but it is difficult to unravel the relative roles of multiple IgG and Fc receptor (FcR) features that have the capacity to influence IgG-FcR complex formation but vary on a personalized basis. Here, we develop an ordinary differential-equation model to determine how personalized variability in IgG subclass concentrations and binding affinities influence IgG-FcγRIIIa complex formation and validate it with samples from the HIV RV144 vaccine trial. The model identifies individuals who are sensitive, insensitive, or negatively affected by increases in HIV-specific IgG1, which is validated with the addition of HIV-specific IgG1 monoclonal antibodies to vaccine samples. IgG1 affinity to FcγRIIIa is also prioritized as the most influential parameter for dictating activation broadly across a population. Overall, this work presents a quantitative tool for evaluating personalized differences underlying FcR activation, which is relevant to ongoing efforts to improve vaccine efficacy.

Summary: Skilled movements rely on a coordinated cortical and subcortical network, but how this network supports motor recovery after stroke is unknown. Previous studies focused on the perilesional cortex (PLC), but precisely how connected subcortical areas reorganize and coordinate with PLC is unclear. The dorsolateral striatum (DLS) is of interest because it receives monosynaptic inputs from motor cortex and is important for learning and generation of fast reliable actions. Using a rat focal stroke model, we perform chronic electrophysiological recordings in motor PLC and DLS during long-term recovery of a dexterous skill. We find that recovery is associated with the simultaneous emergence of reliable movement-related single-trial ensemble spiking in both structures along with increased cross-area alignment of spiking. Our study highlights the importance of consistent neural activity patterns across brain structures during recovery and suggests that modulation of cross-area coordination can be a therapeutic target for enhancing motor function post-stroke.

Introduction: Early appendectomy in patients diagnosed with acute appendicitis is the current standard of treatment in North America. Timely intervention is suggested to avoid the complications associated with perforated appendicitis; however, safety of nighttime operating is a competing concern, with mixed results demonstrated thus far., Objectives: This multi-center prospective randomized controlled trial aims to assess whether delaying appendectomy until the following morning versus early appendectomy overnight affects the rate of surgical complications in adult patients diagnosed with acute appendicitis in the evening hours., Methods: This is a randomized, controlled trial across two academic institutions with blinded outcome assessors. Patients presenting with imaging-confirmed appendicitis with an expected appendectomy between 8 pm and 4 am and within 6 h of decision to operate will be randomized to early appendectomy (with 6 h of randomization, control arm) or delayed to the following morning (after 6 am, intervention arm). Primary outcome will be 30 day postoperative complications, defined as a composite of: mortality, readmission to hospital, emergency department visit, percutaneous drain insertion, reoperation, prolonged hospital stay (>7 days), and postoperative complications. Secondary outcome measures are operative time, length of stay, time to emergency department visit and compliance to treatment., Discussion: This is a feasible and pragmatic clinical trial, intended to provide evidence for challenging decision making for the most common surgical disease worldwide. Results of this study will aid surgeons and health care administrators on how to appropriately triage appendectomies for patients with acute appendicitis who present overnight., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Red blood cell transfusions (RBCT) remain a concern for patients undergoing hepatectomy. The effect of tranexamic acid (TXA), an anti-fibrinolytic, on receipt of RBCT in colorectal liver metastases (CRLM) resection was examined., Methods: Hepatectomies for CRLM over 2009-2014 were included. Primary outcome was 30-day receipt of RBCT. Secondary outcomes were 30-day major morbidity (Clavien-Dindo III-V) and 90-day mortality. Multivariable modelling examined the adjusted association between TXA and outcomes., Results: Of 433 included patients, 146 (34%) received TXA. TXA patients were more likely to have inflow occlusion (41.8% vs. 23.1%; p < 0.01) and major hepatectomies (56.1% vs. 45.6%; p = 0.0193). TXA was independently associated with lower risk of RBCT (Relative risk (RR) 0.59; 95% confidence interval (95%CI): 0.42-0.85), but not with 30-day major morbidity (adjusted RR 1.02; 95%CI: 0.64-1.60) and 90-day mortality (univariable RR 0.99; 95%CI: 0.95-1.03)., Conclusion: Intraoperative TXA was associated with a 41% reduction in risk of 30 -day receipt of RBCT after hepatectomy for CRLM. This finding is important to potentially improve healthcare resource allocation and patient outcomes. Pending further evidence, intraoperative TXA may be an effective method of reducing RBCT in hepatectomy for CRLM., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Risk of red blood cell transfusion (RBCT) in partial hepatectomy is 17-27%; strategies to reduce transfusions can be targeted in patients at increased risk. A Three Point Transfusion Risk Score (TRS) was previously developed to predict patients' risk of transfusion during and following hepatectomy. Here, it was subject to external validation using the ACS-NSQIP database., Methods: TRIPOD guidelines were followed. A validation cohort was created with the ACS-NSQIP dataset. Risk groups for RBCT were created using the TRS: anemia (hematocrit ≤36%), major liver resection (≥4 segments) and primary liver malignancy. Concordance index was used to assess the discrimination. The Hosmer-Lemeshow test for goodness of fit and calibration curves were used to assess calibration., Results: Of 2854 hepatectomies, 18.9% received RBCT. The TRS stratified patients from low (8.5% risk of RBCT) to very high risk (40.6%) of RBCT. The concordance was 0.68 (95% CI 0.66-0.70). Hosmer-Lemeshow test and calibration curves supported good predictive performance of the model., Conclusion: The TRS adequately discriminated risk of RBCT in an external sample of patients undergoing hepatectomy. It provides a simple method to identify patients at high transfusion risk. It can be used to tailor patient blood management initiatives and reduce the use of RBCT., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Recent advances in care for colorectal liver metastases (CRLM) have lengthened 5-year survival. In this new era, prognostic tools such as the clinical risk score (CRS) for colorectal liver metastases require reevaluation., Methods: Patients undergoing resection for CRLM between 2008 and 2012 at 4 specialty hepatobiliary centers in Canada (N = 740) were stratified by CRS and analyzed in Kaplan-Meier survival curves. Primary outcome of overall survival (OS) and secondary outcome of recurrence-free survival (RFS). Multivariate Cox regression compared CRS to patient factors., Results: Median OS not reached (>60 months), median RFS 16 months. Original CRS strata was a significant (p < 0.001) predictor of both OS (5-year OS: 0; 75%, 1; 71%, 2; 57%, 3; 57%, 4; 46%) and RFS (5-year RFS: 0; 39%, 1; 33%, 2; 21%, 3; 21%, 4; 8%). The presence of extrahepatic colorectal metastatic disease increased recurrence risk (RFS hazard ratio of 1.32 (1.06-1.65)), and the use of intraoperative portal pedicle clamping reduced recurrence risk (RFS hazard ratio of 0.78 (0.61-0.99))., Conclusions: The CRS remains a relevant tool for predicting long-term outcomes for patients undergoing resection of CRLM. Additional factors such as the presence of extrahepatic colorectal metastatic disease and the use of intraoperative portal pedicle clamping may improve the prognostic power of the CRS., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Intraoperative cell salvage (ICS) can reduce allogeneic transfusions but with notable direct costs. This study assessed whether routine use of ICS is cost minimizing in hepatectomy and defines a subpopulation of patients where ICS is most cost minimizing based on patient transfusion risk., Methods: A decision model from a health systems perspective was developed to examine adoption and non-adoption of ICS use for hepatectomy. A prospectively maintained database of hepatectomy patients provided data to populate the model. Probabilistic sensitivity analysis was used to determine the probability of ICS being cost-minimizing at specified transfusion risks. One-way sensitivity analysis was used to identify factors most relevant to institutions considering adoption of ICS for hepatectomies., Results: In the base case analysis (transfusion risk of 28.8%) the probability that routine utilization of ICS is cost-minimizing is 64%. The probability that ICS is cost-minimizing exceeds 50% if the patient transfusion risk exceeds 25%. The model was most sensitive to patient transfusion risk, variation in costs of allogeneic blood, and number of appropriate cases the device could be used for., Conclusions: ICS is cost-minimizing for routine use in liver resection, particularly when used for patients with a risk of transfusion of 25% or greater., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Neo-adjuvant chemoradiotherapy reduces local recurrence in rectal cancer, but there is a paucity of evidence regarding its role for colon cancer. The aim of this study was to evaluate the feasibility and outcomes of a neo-adjuvant chemoradiotherapy (NCRT) approach for locally recurrent adherent colon cancer (LRACC)., Methods: All patients with non-metastatic LRACC treated with NCRT and multi-visceral resection (MVR) from January 2000 to July 2010 were included. The primary outcome was the rate of R0 resection (negative microscopic margins). Secondary outcomes were toxicities, post-operative morbidity and mortality, local recurrence, overall survival (OS) and disease-free survival (DFS)., Results: Fifteen patients were identified. Nine primary cancers were located in the sigmoid and 4 in the left colon. Patients were treated with 45-50 Gy in 25 daily fractions and concurrent 5-FU infusion (225 mg/m(2)/day). En-bloc MVR included between 2 and 5 adjacent organs/structures. All but two resulted in R0 resection. One patient had a complete pathologic response and one had minimal residual tumour cells in the resected specimen. Post-operative major morbidity was 33.3%. No mortality occurred. At a median follow-up of 54 months, there were 2 local, 1 regional, and 2 distant lung recurrences. No grade 3 or 4 acute or late toxicities were observed. 5-year OS and DFS were 90.0% and 63.5% respectively., Conclusions: NCRT followed by MVR is a feasible option for the treatment of highly selected LRACC to achieve R0 resection, while maintaining acceptable treatment toxicity. Short-term oncological results appear satisfactory, including good local control., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: While most patients with depression respond to combinations of pharmacotherapy, psychotherapy, and electroconvulsive therapy (ECT), there are patients requiring other treatments. Deep brain stimulation (DBS) allows modulation of brain regions that are dysfunctional in depression. Since anhedonia is a feature of depression and there is evidence of dysfunction of the reward system, DBS to the nucleus accumbens (NAcc) might be promising., Methods: Ten patients suffering from very resistant forms of depression (treatment-resistant depression [TRD]), not responding to pharmacotherapy, psychotherapy, or ECT, were implanted with bilateral DBS electrodes in the NAcc. The mean (+/-SD) length of the current episode was 10.8 (+/-7.5) years; the number of past treatment courses was 20.8 (+/-8.4); and the mean Hamilton Depression Rating Scale (HDRS) was 32.5 (+/-5.3)., Results: Twelve months following initiation of DBS treatment, five patients reached 50% reduction of the HDRS (responders, HDRS = 15.4 [+/-2.8]). The number of hedonic activities increased significantly. Interestingly, ratings of anxiety (Hamilton Anxiety Scale) were reduced in the whole group but more pronounced in the responders. The [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography data revealed that NAcc-DBS decreased metabolism in the subgenual cingulate and in prefrontal regions including orbital prefrontal cortex. A volume of interest analysis comparing responders and nonresponders identified metabolic decreases in the amygdala., Conclusions: We demonstrate antidepressant and antianhedonic effects of DBS to NAcc in patients suffering from TRD. In contrast to other DBS depression studies, there was also an antianxiety effect. These effects are correlated with localized metabolic changes.

Alterations in water content and total tissue Na+ and Mg++ of rat spinal cord tissue were followed over time after a 100 g-cm impact injury to the T-9 spinal cord segment. Rats subjected to laminectomy but not trauma served as controls. In the injured segment there was a progressive increase in water content with increased Na+ and decreased Mg++ at 1 hour and 24 hours after trauma. At seven days, water and Na+ content remained elevated, whereas Mg++ levels had returned to preinjury baseline values. Because of its important role in many metabolic and physiological regulatory processes the early decline in Mg++ concentration after trauma may contribute to the development of secondary tissue damage after spinal cord injury.