Improving the WHO Surgical Safety Checklist sign-out.

BACKGROUND: The WHO Surgical Safety Checklist has been shown to reduce perioperative morbidity and mortality worldwide. There is evidence to suggest that sign-out is the most poorly performed phase of the checklist as it coincides with a period of high workload for team members. This study aimed to see whether modification of this process might result in greater compliance. METHODS: A controlled longitudinal (before and after) study was performed to evaluate the effect of a modified checklist sign-out on compliance in a single surgical department. Checklist quality was evaluated by measurement of checklist completion, active participation, and team member presence. Workload assessment was performed to identify the optimal moment for the sign-out process. The sign-out process was modified through an iterative multidisciplinary approach, informed by results from the workload assessment. Feedback was obtained through staff surveys. RESULTS: A total of 185 operations were used, with an intervention group in vascular surgery and a control group in orthopaedics. The optimal timing for sign-out was identified as after final wound closure. The modified sign-out process improved active participation of team members (21 of 34 versus 31 of 34; P = 0.010). In the control group, complete compliance improved (48 of 76 versus 30 of 41; P = 0.041). However, active participation decreased (53 of 76 versus 19 of 41; P = 0.022). No differences were noted between groups in team member presence. Eighteen of 21 staff questioned viewed the modifications positively. CONCLUSION: The optimal sign-out timing was identified as immediately after final wound closure prior to undraping the patient.

Relationship of depth of invasion to survival outcomes and patterns of recurrence for T3 oral tongue squamous cell carcinoma.

INTRODUCTION: Current research is elucidating how the addition of depth of invasion (DOI) to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging for oral cavity squamous cell carcinoma influences its prognostic accuracy. However, there is limited research on survival in pT3N0M0 oral tongue SCC (OTSCC) patients when stratifying by DOI. OBJECTIVES: Determine 5-year overall survival (OS), and cancer-specific survival (CSS) for patients with pT3N0M0 oral OTSCC based on shallow DOI (<10 mm) and deep DOI (10-20 mm). METHODS: Retrospective review involving three tertiary care cancer centers in North America. cT3N0M0 OTSCC patients receiving primary surgical treatment from 2004 to 2018 were identified. Inclusion: age > 18 years old and confirmation of pT3N0M0 OTSCC on surgical pathology. Exclusion: patients undergoing palliative treatment or previous head and neck surgery/radiotherapy. Analysis comprised two groups: shallow pT3 (tumor diameter > 4 cm, DOI < 10 mm) and deep pT3 (DOI 10 mm-20 mm). RESULTS: One hundred and four patients with pT3N0M0 OTSCC were included. Mean age was 59.1 years (range: 18-80.74). Age, gender, and Charlson Comorbidity Index were similar between the two groups (p > 0.05). Recurrence, LVI, PNI, and positive margins were more common in deep T3 tumors (P < 0.05). 5-year OS (50% vs 26%, p = 0.006) and CSS (72% vs 24%, p = 0.005) were worse in deep pT3 tumors. Deep pT3 disease was an independent predictor of OS (p = 0.004) and CSS (p = 0.01) on Cox-Regression analysis. CONCLUSION: DOI is an independent predictor of poor survival in pT3N0M0 OTSCC patients. Consideration should be given to escalating adjuvant therapy for deep pT3N0M0 OTSCC patients.

The darn technique for small (< 2 cm diameter) midline hernias.

PURPOSE: Primary midline hernias arising in the linea alba are common. While mesh repair has been shown to reduce recurrence rates even in small hernias, many surgeons still use a suture repair for defects of less than 2 cm. The recent European and Americas Hernia Societies Guidelines recommended suture repair only for hernias smaller than 1 cm. A suture repair implies edge-to-edge or overlapping fascial margins, which necessarily involves tension on the repair. A darn is a tension-free repair where, in effect, a "mesh" is hand-woven across the defect in situ. METHODS: The darn repair is a modification of the darn techniques for inguinal hernia repair. Eligible patients undergoing this repair at the Royal Infirmary of Edinburgh between 1 January 2008 and 31 December 2017 were identified from a prospective computer-based medical record system and their case notes reviewed. Inclusion criteria were adult patients with a primary midline abdominal wall defect smaller than 2 cm in the widest diameter of the hernia defect measured intra-operatively. Patients were followed up by telephone in 2019. Those who reported possible recurrence or other symptoms in the region of their hernia repair were reviewed in the outpatient clinic. RESULTS: 47 suture-darn repairs were undertaken over the 10-year period. Fifteen of the darn repair operations (32%) were performed under local anaesthesia. Forty-one patients were followed up with a mean of 80 ± 35 and median of 87 months after surgery. Six patients (13%) were lost to follow-up. Recurrence was found in two cases (5%) and one patient has since been diagnosed with a new epigastric hernia some 5 cm cranial to the previous repair. CONCLUSIONS: The darn repair for small primary midline hernias is quick and inexpensive with promising long-term results. It can be performed under local anaesthesia. It can serve as an alternative to mesh repair for defects less than 2 cm in maximum dimension.

Risk factors for surgical site infections in abdominal surgeries in Ghana: emphasis on the impact of operating rooms door openings.

Major surgery carried out in low- and middle-income countries is associated with a high risk of surgical site infections (SSI), but knowledge is limited regarding contributory factors to such infections. This study explores factors related to patients developing an SSI in a teaching hospital in Ghana. A prospective cohort study of patients undergoing abdominal surgical procedures was conducted at Korle Bu Teaching Hospital. Patient characteristics, procedures and environmental characteristics were recorded. A 30-day daily surveillance was used to diagnose SSI, and Poisson regression analysis was used to test for association of SSI and risk factors; survival was determined by proportional hazard regression methods. We included 358 patients of which 58 (16.2%; 95% CI 12.7-20.4%) developed an SSI. The median number of door openings during an operation was 79, with 81% being unnecessary. Door openings greater than 100 during an operation (P = 0.028) significantly increased a patient's risk of developing an SSI. Such patients tended to have an elevated mortality risk (hazard ratio 2.67; 95% CI 0.75-9.45, P = 0.128). We conclude that changing behaviour and practices in operating rooms is a key strategy to reduce SSI risk.

Timing of Furlow Palatoplasty for Patients With Submucous Cleft Palate.

BACKGROUND: Submucous cleft palate (SMCP) is the most common form of cleft involving the posterior palate, resulting in variable degrees of velar dysfunction and speech disturbance. Although early surgical intervention is indicated for patients with true cleft palate, the indications for palatoplasty and timing of surgical intervention for patients with SMCP remain controversial. METHODS: Twenty-nine patients with SMCP were retrospectively reviewed. Patients treated with Furlow palatoplasty were dichotomized based on patient age at the time of surgical correction into early speech development and late speech development. Primary outcome measures included standardized assessments of hypernasal resonance and quantitative pre- and postoperative nasometry scores. Patients managed nonoperatively were included for comparison of early and late speech outcomes. RESULTS: Both early and late groups demonstrated improvement in qualitative assessment of hypernasal resonance following Furlow palatoplasty. Early and late groups also had significant improvement in pre- to postoperative nasometry scores from 7.4 to 2.3 SD from norm ( P = .01) and 6.0 to 3.6 SD from norm ( P = .02), respectively. There was no difference in postoperative nasometry scores between early and late groups, 2.3 and 3.6 SD ( P = .12). CONCLUSION: Furlow palatoplasty significantly improves the degree of hypernasality in patients with SMCP based on pre- and postoperative nasometry scores and on qualitative assessment of hypernasality. There were no differences in speech outcomes based on early compared with late operative intervention. Therefore, early palatal repair is not obligatory for optimal speech outcomes in children with SMCP and palatoplasty should be deferred until the emergence of overt velopharyngeal insufficiency.

Impact of Continuous Two-Team Approach in Autologous Breast Reconstruction.

Background Autologous breast reconstruction has been noted in the literature to provide superior aesthetic outcomes and patient satisfaction. Additionally, free perforator flap tissue transfer has the potential for lower abdominal donor site morbidity. However, it has been noted that the percentage of women who are undergoing autologous breast reconstruction in the United States is decreasing. Factors related to the technical difficulty, prolonged operative times, and decreasing reimbursement have been implicated as the causes. Methods A retrospective review of electronic medical records over a 5-year period was performed with evaluation of 77 autologous breast reconstructions at a single institution. Patient demographics, comorbidities, number of surgeons involved, operative times, length of stay, and postoperative complications were measured. Wilcoxon rank-sum, Pearson's chi-squared, and proportional odds likelihood ratio tests were performed to compare continuous, categorical, and ordinal outcomes, respectively. Propensity score weighting was used to adjust for presurgical covariates and laterality. Results Operative time and length of stay were both significantly lower in the two- versus the single-microsurgeon groups in the unadjusted setting. When covariates and laterality were adjusted for, operative times still remained significantly shorter in the two-microsurgeon group; there were no differences in complications. Conclusion Based on our findings, we propose that the two-microsurgeon approach can be utilized in more time-consuming microsurgical cases, such as autologous breast reconstruction, to safely decrease operative times and potentially alleviate surgeon fatigue, reduce operative costs, and thus increase overall surgeon productivity.

Surgical Pulmonary Embolectomy: Experience in a Series of 37 Consecutive Cases.

BACKGROUND: Massive pulmonary embolism is a poorly tolerated condition. Treatment options in this condition include anticoagulation and primary reperfusion therapy - systemic thrombolysis, catheter based treatments or surgical embolectomy. There is little data on the relative efficacy of each treatment. METHODS: The preoperative characteristics and outcomes of patients referred for surgical embolectomy between 2000-2014 was reviewed. Echocardiography was performed in the majority of patients before and after surgery. RESULTS: Thirty-seven patients underwent pulmonary embolectomy between 2000-2014. One patient died within 30 days, another before leaving hospital. All other patients were alive at the time of follow-up (survival 94.6% at median 36 months). Median ventilation time was 24hours. Median hospital length of stay was 10.5 days. There was echocardiographic evidence of severe right ventricular strain (increased size and decreased function) before surgery, which was significantly improved to within the normal range by discharge, and follow-up. CONCLUSIONS: Surgical embolectomy is a safe procedure, with low mortality, improved postoperative right ventricular function and pulmonary pressure, and good long-term outcome. Early relief of a large proportion of the clot burden can be life-saving. There should be consideration for its use as an initial treatment strategy in patients with massive or submassive pulmonary embolus with a large burden of proximal clot. A multidisciplinary approach for the treatment of these patients is required.

Análisis de las características clínicas y patológicas de pacientes HER2 positivo: estudio en dos poblaciones socioculturales diferentes / Analysis of clinical and pathological features of HER2-positive patients: study in two different socio-cultural populations

Introducción: La sobreexpresión del receptor de membrana HER2/neu se ha asociado a un pronóstico más desfavorable. La importancia clínica de medición, radica en que la sobreexpresión de la proteína sugiere peor pronóstico; por lo tanto, se ha convertido en mandatorio su estudio. Objetivo: Analizar las cualidades clínicas y patológicas de tumores que sobreexpresan HER2 en dos poblaciones con diferente nivel sociocultural y económico, subagrupadas acorde a su atención hospitalaria o a través de una cobertura médica. Resultados: Se observó que la proteína se encontraba sobreexpresada en un 13,42%,con una mediana de edad de 59,19 años. La mediana de tamaño tumoral fue de 22,58 mm, encontrándose una diferencia significativa entre el grupo hospitalario (27,76 mm) y el de atención privada (17,15 mm). Un 65,10% de estas pacientes presentaban un tamaño tumoral menor a 1 cm, pero un 55,82% de las pacientes presentaban compromiso ganglionar axilar y un 11,63% eran estadio IV. Al analizar el compromiso metastásico, se observó un mayor porcentaje en el subgrupo HER+ con respecto al RH+ HER–, pero menor al subgrupo TN (11,63% vs. 7,48% vs. 37,03%), teniendo valor estadísticamente significativo (p<0,0001). Conclusión: A pesar de no encontrar datos fidedignos que nos permitan aseverar la vinculaciónentre el "ambioma" a través de mecanismos epigenéticos, en la diferenciación tumoral, creemos probable que las diferencias socioculturales tengan injerencia directa o indirectamente en la promoción, supresión o diferenciación tumoral.

Evaluation of long-term clinical and health service outcomes following coronary artery revascularisation in Western Australia (WACARP): a population-based cohort study protocol.

INTRODUCTION: Coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI) are procedures commonly performed on patients with significant obstructive coronary artery disease to relieve symptoms of ischaemia, improve survival or both. Although the efficacy of both procedures at the individual level has been established, the impact of advances in coronary artery revascularisation procedures (CARP) on long-term outcomes and cost-effectiveness at the population level are yet to be assessed. Our aim is to evaluate a minimum of 6-year outcomes and costs for the total population of patients who had CARP in Western Australia (WA) in 2000-2005. METHODS AND ANALYSIS: This retrospective population cohort study will link clinical and administrative health data for a previously defined cohort including all patients in WA who had a CARP in the period 2000-2005. The cohort consists of 19,014 patients who had 21,175 procedures (15,429 PCI and 5746 CABG). We are now collecting a minimum of 6 years follow-up of morbidity and mortality data for the cohort using the WA Data Linkage System, clinical registries and hospital records, with 12 years follow-up for cases in the year 2000. Comparison of long-term outcomes for different CARP will be reported (PCI vs CABG; bare metal stents vs drug-eluting stents vs CABG). Cost-effectiveness analysis of CARP from the perspective of the healthcare sector will be performed using individual level cost data and average costs from Australian Refined Diagnosis Related Groups. ETHICS AND DISSEMINATION: This study has received ethics approval from the University of Western Australia, the Western Australian Department of Health and all participating hospitals. Being a large population cohort study, approval included a waiver of informed consent. All findings will be presented at local, national and international healthcare/academic conferences and published in peer-reviewed journals.

Tibial tuberosity transposition-advancement for lateralization of the tibial tuberosity: an ex vivo canine study.

OBJECTIVES: To evaluate the degree of lateralization achievable and strength of tibial tuberosity transposition and advancement (TTTA) relative to pin and tension band wiring (PTBW) for lateral tibial tuberosity transposition. METHODS: Six pairs of cadaveric tibiae were used. Tibial tuberosity position was determined with computed tomography (CT); bones were then randomly assigned into TTTA and PTBW groups. The PTBW group had a tibial tuberosity osteotomy and fixation with pin and tension band wiring. The TTTA group had a tibial tuberosity advancement performed with lateralization of the tibial tuberosity by 50% of cage depth, using spacers on the cranial cage screw. Postoperative CT images showed lateralization and craniocaudal deviation. Single axial distractive loading was applied to the patella at 90˚ to the tibial plateau, and peak load, energy, and stiffness were calculated. RESULTS: There were significant differences in lateralization (PTBW: 67.92 ± 5.1 %; TTTA: 88.51 ± 5.5 %) (p = 0.0173) and craniocaudal deviation (PTBW: -8.30 ± 1.4 %; TTTA: 6.83 ± 0.6) (p = 0.0001). There were no significant differences in peak load to failure (N) (PTBW: 1448 ± 121; TTTA: 1597 ± 43) (p = 0.4541), energy to failure (N/mm) (PTBW: 15013 ± 2719; TTTA: 17314 ± 887) (p = 0.646), or stiffness (N/mm)(PTBW: 102.8 ± 4.7; TTTA: 92.9 ± 4.8) (p = 0.2716). CLINICAL SIGNIFICANCE: The TTTA was more effective at lateralization of the tibial tuberosity, and of comparable strength to PTBW. Greater support of the osteotomized fragment with TTTA may resist cyclic loading, and requires evaluation.

Lack of high-dose radiation mediated prostate cancer promotion and low-dose radiation adaptive response in the TRAMP mouse model.

Cancer of the prostate is a highly prevalent disease with a heterogeneous aetiology and prognosis. Current understanding of the biological mechanisms underlying the responses of prostate tissue to ionizing radiation exposure, including cancer induction, is surprisingly limited for both high- and low-dose exposures. As population exposure to radiation increases, largely through medical imaging, a better understanding of the response of the prostate to radiation exposure is required. Low-dose radiation-induced adaptive responses for increased cancer latency and decreased cancer frequency have been demonstrated in mouse models, largely for hematological cancers. This study examines the effects of high- and low-dose whole-body radiation exposure on prostate cancer development using an autochthonous mouse model of prostate cancer: TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP). TRAMP mice were exposed to single acute high (2 Gy), low (50 mGy) and repeated low (5 × 50 mGy) doses of X rays to evaluate both the potential prostate cancer promoting effects of high-dose radiation and low-dose adaptive response phenomena in this prostate cancer model. Prostate weights and histopathology were examined to evaluate gross changes in cancer development and, in mice exposed to a single 2 Gy dose, time to palpable tumor was examined. Proliferation (Ki-67), apoptosis, DNA damage (γ-H2AX) and transgene expression (large T-antigen) were examined within TRAMP prostate sections. Neither high- nor low-dose radiation-induced effects on prostate cancer progression were observed for any of the endpoints studied. Lack of observable effects of high- or low-dose radiation exposure suggests that modulation of tumorigenesis in the TRAMP model is largely resistant to such exposures. However, further study is required to better assess the effects of radiation exposure using alternative prostate cancer models that incorporate normal prostate and in those that are not driven by SV40 large T antigen.

Obstructive sleep apnea after dynamic sphincter pharyngoplasty.

INTRODUCTION: In patients who require additional surgery for velopharyngeal insufficiency (VPI), a higher incidence of obstructive sleep apnea (OSA) may be incurred. Although this phenomenon has been demonstrated with the posterior pharyngeal flap, the effect of dynamic sphincter pharyngoplasty (DSP) on OSA is less clear. The purposes of this case series were to (1) determine the incidence of OSA after DSP, (2) assess the changes in polysomnography after DSP, and (3) identify risk factors for the development of OSA after DSP. Our global hypothesis is that OSA and VPI exist on a continuum and that speech outcomes should not be considered in isolation. METHODS: For a 13-year period, 146 patients with idiopathic VPI, submucous cleft palate, cleft palate only, or cleft lip and palate underwent DSP for VPI. The diagnosis of OSA was defined as the prescription of continuous positive airway pressure therapy by a pediatric sleep medicine physician. The incidence of OSA preoperatively and postoperatively was compared using Fisher exact test. When available, preoperative and postoperative apnea-hypopnea indices (AHIs) were compared using the pairwise, 2-tailed, Student's t-test. Patient factors, such as obesity (body mass index ≥ 95th percentile), the presence of a craniofacial syndrome, surgical history, and a preexisting OSA diagnosis, were noted. A multiple logistic regression was performed to elucidate risk factors for the development of OSA. RESULTS: The average age at surgery was 9.2 years (range, 4-40 y), and the mean follow-up time was 4.5 years (range, 1 mo to 12 y). The incidence of OSA increased after DSP, from 2 to 33 patients (1.4%-22%, respectively; P = 0.05). In 23 patients (16%), both preoperative and postoperative AHIs were available. There was a significant increase in AHI after DSP, from 3.1 to 8.4 episodes per hour of sleep (P = 0.001). Previous tonsillectomy/adenoidectomy was predictive of OSA after DSP (relative risk = 2.4; P = 0.04). CONCLUSIONS: We report an increased incidence of OSA and higher-than-average AHIs postoperatively after DSP. Preoperative tonsillectomy/adenoidectomy predicted the development of OSA after DSP. A high index of suspicion for development of OSA must be maintained in patients who undergo secondary speech operations for VPI. Clinical screening for OSA should be used in this population, with a low threshold for polysomnographic evaluation. The surgeon must be wary that improvements in speech after DSP may change airway dynamics and increase the risk of OSA.

Factores asociados a recidiva en tratamiento conservador del cáncer de mama invasivo / Factors associated with recurrence in conservative treatment of breast invasive cancer

Introducción: el tratamiento de elección en los estadios iniciales del cáncer de mama invasivo es el conservador. La tasa de recidiva local/regional luego del mismo varía entre 3% y 18%. Objetivo: determinar la tasa y características de recidiva en tratamiento conservador de cáncer de mama invasivo y analizar los factores relacionados con el aumento de riesgo de las mismas.Material y métodos: el presente es un estudio analítico, retrospectivo, de casos y controles, en el cual se incluyen 413 pacientes operadas en el período 01/01/1990 al 31/12/2006. Con un seguimiento a 124 meses, se presentaron 37 mujeres con recidiva local/ regional (8,96%). Resultados: en la rama que presentó recurrencia de enfermedad, el 45,9% (n=17) eran pacientes en premenopausia y el 51,3% (n=19) tenían menos de 55 años. Por el contrario, en la rama contraria, el 15,9% (n=60) eran pacientes en premenopausia y el 28,9% (n=109) eran menores de 55 años. Con relación a los márgenes quirúrgicos pequeños, el 62,2% (n=23) de las pacientes con recaída tenía como antecedente margen quirúrgico menor a 5 mm, lo cual sólo ocurría en el 25,8% (n=97) del grupo restante. Conclusión: los factores de riesgo que presentaron diferencias estadísticamente significativas fueron la edad, £55 años (p=0,0054), el estado de premenopausia(p=0,000056) y los márgenes de resección quirúrgica menores a 5 mm(p=0,000009)

Immediate management of inadvertent dural puncture during insertion of a labour epidural: a survey of Australian obstetric anaesthetists.

Immediate management of inadvertent dural puncture during insertion of an epidural needle during labour is controversial and evidence to guide clinical practice is limited. We surveyed Australian obstetric anaesthetists by anonymous postal questionnaire. Of the 671 surveys sent, 417 (62%) were returned. Following dural puncture, 265 respondents (64%) indicated that they "would usually remove the Tuohy needle and resite". The most common reason for this decision was concern regarding the safety of intrathecal catheters (ITC) (n = 236, 89%), in particular, the risk of misuse (n = 182, 70%). The most frequently reported reason for "usually inserting an ITC" was that this reduced the incidence (n = 120, 84%) and severity (n = 110, 77%) of post dural puncture headache. Increased frequency of ITC insertion was reported by respondents who practised more frequent sessions of obstetric anaesthesia, had fewer years of experience as a consultant anaesthetist and worked in a public hospital. The more widespread use of ITCs seems to be limited by safety concerns.

Dermatological reactions to the multitargeted tyrosine kinase inhibitor sunitinib.

BACKGROUND: The multikinase inhibitor sunitinib has enhanced the treatment of renal cell carcinoma and gastrointestinal stromal tumor through an improved clinical response with decreased systemic toxicities. However, sunitinib is frequently associated with dermatological adverse reactions. The physical and psychosocial impact of frequent dermatological toxicities can affect consistent antineoplastic therapy and quality of life. PATIENTS AND METHODS: Dermatological adverse reaction information was compiled from Pfizer Medical Information and from abstracts from the 2007 American Society of Clinical Oncology annual meeting, Prostate Cancer Symposium, and Gastrointestinal Cancers Symposium. Published clinical trials of sunitinib in MEDLINE, Cochrane Library, Cochrane Controlled Trials Register, and EMBASE Drugs and Pharmacology databases were also included. Information was accessed on or before June 30, 2007. RESULTS: In the pooled analysis, all-grade hand-foot skin reaction occurred in 19% of patients (5% grades 3-4), skin discoloration in 28% (0% grades 3-4), dry skin in 16% (1% grades 3-4), skin rash in 13% (1% grades 3-4), dermatitis in 8% (2% grades 3-4), hair color changes in 10% (0% grades 3-4), alopecia in 6% (0% grades 3-4), and phototoxicity in <0.1%. CONCLUSIONS: Dermatological reactions associated with sunitinib occur frequently. Evidence-based treatment recommendations are needed in order to maximize quality of life and optimize clinical outcome.

Effects of treatment with parathyroid hormone 1-84 on quantity and biomechanical properties of thoracic vertebral trabecular bone in ovariectomized rhesus monkeys.

Osteoporosis is characterized by impaired bone quality leading to increased susceptibility to fracture, particularly of the thoracic spine. However, the lumbar spine is studied most commonly. We investigated the effects of 16 months of treatment with full-length parathyroid hormone (PTH) 1-84 (5, 10, or 25 microg/kg) on bone mineral density (BMD) and on architecture and biomechanical properties of trabecular bone at the thoracic spine of ovariectomized (OVX) adult rhesus monkeys and compared the results with those from the lumbar spine. At baseline, 9 months after surgery, dual-energy X-ray absorptiometric BMD at T9-T12 was 7% lower in OVX than in sham animals. All PTH(1-84) doses increased BMD to sham levels within 7 months. Micro-computed tomography of T10 vertebrae showed that trabecular bone volume and connectivity were higher in PTH(1-84)-treated animals than in sham controls, primarily through a significantly greater trabecular number. Peripheral quantitative computed tomography of trabecular bone cores from T11 and T12 confirmed that PTH(1-84) increased BMD. Compression testing of the cores showed that PTH(1-84) treatment increased stiffness, modulus, yield load, and yield stress to levels significantly greater than in sham animals, with the largest effect in the 10 microg/kg group (35-54% greater than in OVX controls). Thus, PTH(1-84) treatment increased BMD and the biomechanical properties of trabecular bone at the thoracic spine of OVX rhesus monkeys. The 10 microg/kg dose produced the greatest effect on trabecular strength, possibly because the highest dose stimulated bone remodeling excessively. Importantly, the changes observed were similar to those in lumbar vertebrae, thereby validating extrapolation of results from the lumbar to the thoracic spine.

Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

BACKGROUND: The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery. METHODS AND RESULTS: We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level > or = 10x upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted P<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 -572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703). CONCLUSIONS: Functional genetic variants in cytokine and leukocyte-endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.

Angular nerve: new insights on innervation of the corrugator supercilii and procerus muscles.

BACKGROUND: Elimination of glabellar frown lines by direct denervation of the corrugator and procerus muscles has proven elusive. Furrows often persist after the frontal branch of the facial nerve has been divided. In order to find an explanation for these observations and to provide an anatomic basis for future surgical strategies, the pattern of innervation of these muscles was studied. METHODS: Two separate investigations were performed: (1) cadaveric anatomical dissection in 18 fresh cadaver hemi-faces utilizing loupe magnification, operating microscope, and template tracings; and (2) electrophysiologic testing performed in 12 healthy volunteers utilizing a Viking Ile nerve stimulator (Nicolet, Madison, WI). RESULTS: The corrugator was found to have a dual nerve supply with contributions from branches of the frontal, zygomatic and buccal branches of the facial nerve. The frontal branch passes deep to the orbicularis at the level of the eyebrow; and the buccal branch, after receiving a contribution from the zygomatic, forms the angular nerve, which then passes superiorly in front of the medial canthus to supply both corrugator and procerus. The procerus muscle was found to receive contributions from the angular nerve exclusively. CONCLUSIONS: Procedures designed to denervate the corrugator should be directed at both components of its redundant nerve supply, the frontal branch as well as the angular nerve. Division of the angular nerve will also denervate the procerus muscle. Both frontal nerve branches and angular nerve components are accessible through an upper blepharoplasty incision.

Inhibition of complement activation by pexelizumab reduces death in patients undergoing combined aortic valve replacement and coronary artery bypass surgery.

OBJECTIVE: We sought to evaluate the effects of pexelizumab, a C5 complement inhibitor, on death and myocardial infarction in patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery. METHODS: The Pexelizumab for Reduction in Myocardial Infarction and Mortality in Coronary Artery Bypass Graft surgery trial, a phase III prospective, randomized, double-blind, placebo-controlled study, enrolled 3099 patients at 205 centers. The primary end point was the composite of death, myocardial infarction, or both at postoperative day 30 in patients undergoing coronary artery bypass grafting without valve surgery. Postoperative myocardial infarction was defined as a creatine kinase MB fraction value of 100 ng/mL or greater, Q-wave myocardial infarction with a creatine kinase MB fraction value of 70 ng/mL or greater, or new Q-wave evidence of myocardial infarction by postoperative day 30. Because patients undergoing coronary artery bypass grafting with a valve procedure were not included in the primary population, separate analysis of death and myocardial infarction was conducted in 218 patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery. RESULTS: Of the 353 patients randomized to any valve procedure, 106 (61%) underwent combined aortic valve replacement and coronary artery bypass grafting in the pexelizumab treatment group compared with 112 (63%) patients in the placebo group. Coronary artery bypass grafting was performed with 1 or more internal thoracic artery grafts in 139 (64%) patients and with 1 or more saphenous vein grafts in 179 (82%) patients. There were 4 (3.8%) deaths in the pexelizumab group versus 11 (9.9%) in the placebo group by postoperative day 30 and 6 (5.7%) deaths in the active group versus 16 (14.4%) in the placebo group by postoperative day 180 (P =.107 and P =.043, respectively, Fisher exact test). The incidence of myocardial infarction 30 days after surgical intervention was identical in the 2 groups, but the study was not designed to detect differences in this cohort of patients. CONCLUSIONS: Inhibition of complement activation by pexelizumab resulted in a decreased mortality at 180 days among 218 patients who underwent combined aortic valve replacement and coronary artery bypass grafting surgery. Additional studies are warranted to confirm this decrease in mortality with pexelizumab in combined aortic valve replacement and coronary artery bypass grafting procedures.