Optimizing Outcomes After Cleft Palate Repair: Design and Implementation of a Perioperative Clinical Care Pathway.

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 block: an ultrasound and cadaveric study to identify correct sonoanatomical landmarks.

​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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Iliac Crest Bone Graft Harvest for Alveolar Cleft Repair: A Systematic Review Comparing Minimally Invasive Trephine and Conventional Open Techniques.

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.

Contexte: Dans le cours de l'élaboration d'une méthode standardisée de réparation des fentes palatines, nous avons réalisé une revue systématique comparant la technique par tréphine peu invasive à la technique conventionnelle ouverte pour la collecte d'os de la crête iliaque dans une population pédiatrique. Méthodes: Une revue systématique a été réalisée sur les études comparant les techniques ouvertes avec les techniques utilisant une tréphine peu invasive dans des populations pédiatriques subissant une réparation de fente palatine. Les critères d'exclusion incluaient les revues, les séries de cas, les éditoriaux, les résumés et les études ne portant que sur une population adulte. Les données ont été compilées avec des variables de résultats sélectionnées a priori. Résultats: Parmi les 422 manuscrits sélectionnés, cinq répondaient aux critères. Ils incluaient 257 patients (116 techniques ouvertes, 141 tréphines). L'âge moyen des patients était de 11 ans. Les patients pour lesquels une collecte avait été obtenue par tréphine avaient une durée de séjour plus courte (tréphine : 1,0 à 5,0 jours; contre technique ouverte : 1,25 à 5,4 jours), un délai de déambulation non aidée plus court (16 à 46 heures contre 20 à 67 heures pour la technique ouverte) et un moindre recours aux antalgiques postopératoires (0,31 mg/kg contre 1,64 mg/kg de morphine IV). Le volume d'os spongieux collecté était de 2,53 ml avec les techniques ouvertes contre 1,22 ml avec la tréphine; le greffon par tréphine a été complété par de l'os déminéralisé dans 54% des cas dans une autre étude. L'utilisation de suppléments anesthésiques n'était pas homogène, mais a eu un effet significatif sur la douleur postopératoire et la déambulation. Conclusions: Comparativement aux techniques ouvertes, la collecte peu invasive de greffon osseux par tréphine est associée à une délai de congé plus court, des taux d'infections légèrement inférieurs et à une moindre utilisation d'opioïdes. Toutefois, les avantages éventuels de la collecte par tréphine doivent être soupesés par rapport au risque de collecte insuffisante de greffon. Enfin, le choix de suppléments analgésiques périopératoires a des répercussions significatives sur l'évolution des patients, indépendamment de la technique employée.

Management of Brachial Plexus Birth Injury: The SickKids Experience.

This article describes the approach utilized by the multidisciplinary team at Sick Kids Hospital to evaluate and treat patients with brachial plexus birth injury (BPBI). This approach has been informed by more than 30 years of experience treating over 1,800 patients with BPBI and continues to evolve over time. The objective of this article is to provide readers with a practical overview of the Sick Kids approach to the management of infants with BPBI.

Retrospective analysis of perioperative ketorolac and postoperative bleeding in reduction mammoplasty.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Expression of Abl interactor 1 and its prognostic significance in breast cancer: a tissue-array-based investigation.

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.

Surgical Management of Abdominal Anterior Cutaneous Nerve Entrapment Syndrome: Case Report, Surgical Technique, and Literature Review.

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.

Pregnancy and Parenthood Remain Challenging During Surgical Residency: A Systematic Review.

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.

Probing the kinetics and thermodynamics of copper(II) binding to Bacillus subtilis Sco, a protein involved in the assembly of the Cu(A) center of cytochrome c oxidase.

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.

Infantile Hemangiomas of the Lip: Complications and Need for Surgical Intervention.

BACKGROUND: Infantile lip hemangiomas are challenging to manage due to the functional and aesthetic importance of the lips. Hemangiomas in this region may lead to significant complications including ulceration, feeding difficulties, and lip contour distortion requiring surgical intervention. METHODS: A retrospective chart review of children with focal lip hemangiomas treated at our institution between January 2000 and December 2016 was conducted. Patient demographics, lesion characteristics, complications, treatments, and outcomes were collected. Lesions were classified based on depth (superficial, deep, or mixed depth), vermillion border involvement, and location. RESULTS: One hundred and two patients with focal lip hemangiomas were identified; 45.1% were managed expectantly, 43.1% were treated medically, and 18.6% required surgery. Residual lip contour deformity following involution was the most common complication (26.5% of patients). Ulceration during the proliferation phase was reported in 14.7% of patients, leading to significant feeding difficulties in 9.8% of patients. All ulcerations occurred in lesions with a superficial component. None of the patients with superficial lesions underwent surgery; 27.1% of patients with deep or mixed depth hemangiomas required surgical treatment to restore lip contour. CONCLUSIONS: Lip hemangiomas have high rates of complications that seem to be related to lesion morphology and phase of growth. Ulceration occurs during the early proliferative phase and is most frequently associated with mixed depth hemangiomas. Residual lip contour deformities are identified in the involution phase; presence of a deep component is the primary factor in predicting the need for surgical intervention in these patients.

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

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.

Development and evaluation of methodologies for teaching focused cardiac ultrasound skills to medical students.

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.

Proteomic analyses reveal high expression of decorin and endoplasmin (HSP90B1) are associated with breast cancer metastasis and decreased survival.

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<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients also appear to benefit significantly from hormonal treatment. CONCLUSIONS: Using quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features.