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Objective: To evaluate the development process and clinical impact of implementing a standardized perioperative clinical care pathway for cleft palate repair. Design: Medical records of patients undergoing primary cleft palate repair prior to pathway implementation were retrospectively reviewed as a historical control group (N = 40). The historical cohort was compared to a prospectively collected group of patients who were treated according to the pathway (N = 40). Patients: Healthy, nonsyndromic infants undergoing primary cleft palate repair at a tertiary care pediatric hospital. Interventions: A novel, standardized pathway was created through an iterative process, combining literature review with expert opinion and discussions with institutional stakeholders. The pathway integrated multimodal analgesia throughout the perioperative course and included intraoperative bilateral maxillary nerve blocks. Perioperative protocols for preoperative fasting, case timing, antiemetics, intravenous fluid management, and postoperative diet advancement were standardized. Main Outcome Measures: Primary outcomes include: (1) length of hospital stay, (2) cumulative opioid consumption, (3) oral intake postoperatively. Results: Patients treated according to the pathway had shorter mean length of stay (31 vs 57 hours, P < .001), decreased cumulative morphine consumption (77 vs 727 μg/kg, P < .001), shorter time to initiate oral intake (9.3 vs 22 hours, P = .01), and greater volume of oral intake in first 24 hours postoperatively (379 vs 171 mL, P < .001). There were no differences in total anesthesia time, total surgical time, or complication rates between the control and treatment groups. Conclusions: Implementation of a standardized perioperative clinical care pathway for primary cleft palate repair is safe, feasible, and associated with reduced length of stay, reduced opioid consumption, and improved oral intake postoperatively.

Suprazygomatic maxillary nerve blocks (SMB) are used in adult and pediatric patients to provide analgesia for midface surgery and chronic maxillofacial pain syndromes. The ultrasound-guided SMB technique ensures visualisation of the needle tip, avoidance of the maxillary artery and confirmation of local anesthetic spread. The goal of this study was to correctly identify SMB sonoanatomical landmarks to ensure the nerve block is performed safely and effectively. Following an ultrasound-guided SMB with dye injection on 2 embalmed cadavers, pre-tragal face-lift style incision with a full thickness flap dissection was performed allowing accurate visualization of the bony landmarks being used for sonography and identification of the location of the injected dye. This study identifies the correct sonoanatomic landmarks as the maxilla and the coronoid process of the mandible which suggests that the block needle tip and local anesthetic injection are within the infratemporal fossa as opposed to the previously reported pterygopalatine fossa. An improved understanding of the sonoanatomy will aid clinicians who are learning, performing and teaching the ultrasound-guided suprazygomatic approach to the maxillary nerve block.

PURPOSE To examine common themes and synthesize data surrounding pregnancy and parenthood during surgical residency training. METHOD The authors conducted a systematic search of the literature in March 2019. They searched MEDLINE, EMBASE, and Scopus, seeking articles published from 2003 to 2018 that focused on pregnancy, parenthood, and the experience of surgical residents. They excluded articles that examined nonsurgical programs, as well as editorials, abstracts, and commentaries. Two investigators independently reviewed all citations, selected articles for full-text review, and extracted data from the selected articles. RESULTS Of 523 titles and abstracts screened, 27 were included. Overall, female surgical residents had fewer children during residency training than their male counterparts (18%-28% vs 32%-54%). As compared with the general population, surgical residents had their first child later in life (30-34 vs 25 years old), and had fewer children overall (0.6-2.1 vs 2.7). Infertility rates were higher among female surgeons than in the general population (30%-32% vs 11%), as were assisted reproductive technology rates (8%-13% vs 1.7%). Pregnant surgical residents experienced a high rate of obstetrical complications; working more than 6 overnight calls shifts per month or 60 hours per week were predictors of increased complication rates. The authors noted no differences in attrition, caseload, or exam pass rates amongst female surgical residents who had become pregnant as compared with other residents. Despite these similar academic outcomes, negative attitudes and perceptions toward pregnancy during residency were consistently identified. CONCLUSIONS Female surgical residents experience high rates of infertility and obstetrical complications, contend with negative attitudes and stigma during their pregnancies, and voluntarily delay childbearing. Formal maternity policies, a shift in surgical culture, and ongoing discussion with all stakeholders are needed to attract and retain female surgical residents.

Background:. Abdominal anterior cutaneous nerve entrapment syndrome (ACNES) is an emerging diagnosis, with estimated incidence of 13%–30% of the adult population. It is a syndrome characterized by chronic abdominal pain caused by entrapment of cutaneous branches of thoracoabdominal nerves at the lateral border of the rectus abdominis muscle. If conservative treatment with pain medication, botulinum toxin, or lidocaine injections is inadequate, surgical management is indicated. Methods:. We present a case of a 40-year-old woman presenting with a 1-year history of daily right anterior abdominal wall pain, consistent with a diagnosis of ACNES. We describe our approach for an anterior neurectomy of the intercostal nerve with closure of its fascial foramen. Results:. Three months after surgery, she remained pain free and was back to work full time. At a 13-month follow-up, the patient reported that her pain had resolved completely following surgery. Conclusions:. Results are encouraging following anterior neurectomy for ACNES. Surgical descriptions in the literature are brief, with limited pictorial account. Our detailed surgical approach is provided along with a review of the existing literature on the management of ACNES.

​PURPOSE: Suprazygomatic maxillary nerve blocks (SMB) are used in adult and pediatric patients to provide analgesia for midface surgery and chronic maxillofacial pain syndromes. The ultrasound-guided SMB technique ensures visualisation of the needle tip, avoidance of the maxillary artery and confirmation of local anesthetic spread. The goal of this study was to correctly identify SMB sonoanatomical landmarks to ensure the nerve block is performed safely and effectively.Following an ultrasound-guided SMB with dye injection on 2 embalmed cadavers, pre-tragal face-lift style incision with a full thickness flap dissection was performed allowing accurate visualization of the bony landmarks being used for sonography and identification of the location of the injected dye.This study identifies the correct sonoanatomic landmarks as the maxilla and the coronoid process of the mandible which suggests that the block needle tip and local anesthetic injection are within the infratemporal fossa as opposed to the previously reported pterygopalatine fossa.An improved understanding of the sonoanatomy will aid clinicians who are learning, performing and teaching the ultrasound-guided suprazygomatic approach to the maxillary nerve block.

Background: In the course of developing a standardized pathway for alveolar cleft repair, we conducted a systematic review comparing minimally invasive trephine with conventional open technique for iliac crest bone graft harvest in a pediatric population. Methods: A systematic review was conducted of studies comparing open with minimally invasive trephine techniques in pediatric populations undergoing alveolar cleft repair. Exclusion criteria included reviews, case series, editorials, abstracts, and those with adult-only populations. Data were compiled with outcome variables selected a priori. Results: Of 422 manuscripts screened, five met criteria. These comprised 257 patients (116 open, 141 trephine). Average age was 11 years. Patients undergoing trephine harvest had reduced length of stay (1.0-5.0 days trephine vs 1.25-5.4 days open), time to unassisted ambulation (16-46 hours vs 20-67 hours open), and less postoperative narcotic use (0.31 mg/kg vs 1.64 mg/kg IV morphine). Volume of cancellous bone was reported as 2.53 mL for open versus 1.22 mL for trephine in one study, and trephine graft was supplemented with demineralized bone in 54% of cases in another study. The use of anesthetic adjuncts was inconsistent but had a significant effect on postoperative pain and ambulation. Conclusions: Compared to open techniques, the minimally invasive trephine bone graft harvest is associated with a shorter time to discharge, slightly lower infection rates, and reduced opioid use. The possible benefits of trephine harvest must however be balanced against the risk of insufficient graft harvest. Finally, the choice of perioperative analgesic adjuncts significantly impacts patient outcomes regardless of the technique employed.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development., Studying the spatial mutational and gene expression alterations in breast cancer could impact our understanding of breast cancer development. Here, the authors analyse a unique dataset of epithelial samples that highlight potential field cancerisation surrounding the primary tumour.

Background Handheld ultrasound is emerging as an important tool for point-of-care cardiac assessment. Although cardiac ultrasound skills are traditionally introduced during postgraduate training, the optimal time and methodology to initiate training in focused cardiac ultrasound (FCU) are unknown. The objective of this study was to develop and evaluate a novel curriculum for training medical students in the use of FCU. Methods The study was conducted in two phases. In the first phase, 12 first-year medical students underwent FCU training over an 8-week period. In the second phase, 45 third-year medical students were randomized to one of three educational programs. Program 1 consisted of a lecture-based approach with scan training by a sonographer. Program 2 coupled electronic education modules with sonographer scan training. Program 3 was fully self-directed, combining electronic modules with scan training on a high-fidelity ultrasound simulator. Image interpretation skills and scanning technique were evaluated after each program. Results First-year medical students were able to modestly improve interpretation ability and acquire limited scanning skills. Third-year medical students exhibited similar improvement in mean examination score for image interpretation whether a lecture-based program or electronic modules was used. Students in the self-directed group using an ultrasound simulator had significantly lower mean quality scores than students taught by sonographers. Conclusions Third-year medical students were able to acquire FCU image acquisition and interpretation skills after a novel training program. Self-directed electronic modules are effective for teaching introductory FCU interpretation skills, while expert-guided training is important for developing scanning technique.

We conducted a retrospective review following concerns involving a suspected increase in the requirement for surgical re-exploration for hematoma evacuation when ketorolac was administered perioperatively in patients undergoing reduction mammoplasty. Following ethics approval, a retrospective chart review was conducted of all patients who underwent reduction mammoplasty at our two institutions from the time ketorolac became available in 2004 until surgeons requested its use discontinued in 2007. The data we collected included patient demographics, ketorolac administration, requirement for surgical re-exploration, documented hematoma formation not requiring surgical re-exploration, and excessive bleeding in the perioperative period. Three hundred and seventy-nine patient records were reviewed; 127 of the patients received a single intravenous dose of ketorolac (15 or 30 mg), and 252 of the patients did not receive ketorolac. Patients who received ketorolac were at an increased risk of requiring surgical re-exploration for hematoma evacuation (relative risk [RR] = 3.6; 95% confidence interval [CI], 1.4 to 9.6) and hematoma formation not requiring re-exploration (RR = 2.2; 95% CI, 1.3 to 3.6). A single perioperative intravenous dose of ketorolac was associated with a greater than three-fold increase in the likelihood of requirement for surgical hematoma evacuation. Our data suggest that it may be prudent to consider carefully whether the potential risks associated with the use of ketorolac outweigh the potential benefits of using ketorolac in patients undergoing reduction mammoplasty.

BACKGROUND: Breast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays. METHODS AND FINDINGS: Differential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p

Abl interactor 1 (Abi1) is an adaptor protein involved in cell migration. Previous in vitro work suggested that Abi1 is a regulator of breast cancer proliferation, migration, and invasion. In the present study, we explore the expression of Abi1 and its downstream effector phospho-Akt (p-Akt) in a series of breast cancers and correlate their expression with clinicopathological and survival data. Using tissue microarrays, 988 patients with invasive breast carcinoma were evaluated by immunohistochemistry. Statistical correlation was performed to determine associations between Abi1 and p-Akt expression and standard breast clinicopathological factors. The prognostic value of Abi1 and p-Akt for disease-free (DFS) and overall survival (OS) was also evaluated. Abi1 expression was demonstrated in 33.7% (314/933) of invasive carcinomas, while p-Akt was expressed in 46.7% (441/944). There was a significant association between Abi1 and p-Akt expression (P = 0.001). Abi1 expression showed significant positive correlation with older age at diagnosis and the Ki67 index. Most importantly, it was demonstrated to be an independent predictor of both DFS and OS (HR = 1.6 and 1.5, P < 0.001, respectively). There was no association between p-Akt expression and survival. To the best of our knowledge, this is the first study evaluating Abi1 expression in a large group of breast cancers. Our analysis demonstrated that tumors expressing high levels of Abi1 are significantly associated with early recurrence and worse survival on multivariate analysis. This suggests that Abi1 expression has potential as a molecular marker to refine outcome prediction in breast cancer patients.

BsSco is a member of the Sco protein family involved in the assembly of the Cu(A) center within cytochrome c oxidase. BsSco forms a complex with Cu(II) that has properties consistent with dithiolate ligation. Stopped-flow UV-visible absorbance and fluorescence coupled with multiwavelength analysis reveal biphasic binding kinetics between BsSco and Cu(II). An initial species appears with absorbance centered at 382 nm at a copper concentration-dependent rate (2.9 x 10(4) M(-1) s(-1)). The initial species decays at a first-order rate (1.5 s(-1)) to the equilibrium form with a maximum at 352 nm. Formation of the BsSco-Cu(II) complex is accompanied by quenching of protein fluorescence. The copper concentration-dependent phase gives 70% of the total quenching, while the final 30% develops during the second phase of the absorbance change. The pH dependence of copper binding shows that the copper-dependent rate increases by 50-fold as the pH decreases from 8.5 to 5.5 with an apparent pK(a) of 6.7. The slower phase rate is independent of pH. Comparison of circular dichroism spectra between apo-BsSco and the BsSco-Cu(II) complex reveals a small change in the UV region consistent with a subtle conformational change upon copper binding. There is formation of a distinctive visible CD spectrum in the BsSco-Cu(II) complex. A model is presented in which the kinetic and thermodynamic stability of the BsSco-Cu(II) complex results from a two-step mechanism. Release of copper would be facilitated in the intermediate form of BsSco, and attaining such a low-Cu(II) affinity state may be important for BsSco's function in Cu(A) assembly.

Breast cancer is a clinically heterogeneous disease, making it imperative to use biomarkers, such as the estrogen receptor (ER) and human epidermal growth factor 2 (HER2), to stratify patients into specific prognostic groups. Biomarker stratification provides patients with more accurate diagnoses, predictions of clinical outcomes, and offers targeted therapeutic options. SPAG5 (Sperm Associated Antigen 5) is involved in the maintenance of spindle-pole integrity, efficient chromosomal alignment, and cell proliferation. Its role in cell division may be a cancer susceptibility factor. Low expression of SPAG5 has been correlated with good prognosis and absence of metastases in ER+ breast cancer. However, its relationship to other molecular subtypes of breast cancer and its functional role in the disease are relatively unknown. The purpose of this study was to investigate the role of SPAG5 in breast cancer through (i) microarray analysis and (ii) correlating its expression with invasiveness, a factor involved in disease progression. In part (i), SPAG5 expression in breast cancers was evaluated by using five Affymetrix, three Agilent and one Illumina microarray datasets. The associations between SPAG5 expression and various tumor pathologies were analyzed via log2 expression ratios. Pathologies that were investigated included the ER+ subtype, HER2 overexpression, lymph node metastasis, and breast cancer stem cell-like/undifferentiated tumors. In part (ii), SPAG5 expression across five breast cancer epithelial cell lines of varying invasive ability (MDA-MB-231, MDA-MB-157, BT549, MCF-7, and CAMA1) was investigated. The cells were cultured at normal conditions and lysed using the CytoBusterTM protein extraction reagent. The supernatants were collected by microcentrifugation at 16,000 rcf at 4°C for 5 minutes. Western blotting was completed using standard techniques. From the microarray analysis, overexpression of SPAG5 showed strong associations with HER2 overexpression, ER-negative and triple-negative cancers, high grade tumors, metastasis, and poor clinical outcomes in a total of 1595 breast cancers. Via immunoblotting, it was shown that higher levels of SPAG5 accompanied highly invasive cell lines (MDA-MB-231, MDA-MB-157, and BT549) and lower levels occurred in weakly invasive cells (MCF-7 and CAMA1). These results suggest that SPAG5 is a biomarker of malignancy and invasiveness and may be a novel therapeutic target for the prevention of metastasis. Stratification into specific prognostic groups using SPAG5 as a biomarker could lead to early detection and intervention of breast cancers likely to metastasize. It is possible that treatments targeting the modulation of SPAG5 expression levels may also aid in improving clinical outcomes. Ongoing functional analysis of SPAG5 will elucidate its role in breast cancer and metastasis and aid in further characterization of SPAG5. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3303.