Gender Differences in Case Volume Among Ophthalmology Residents.

IMPORTANCE: Although almost equal numbers of male and female medical students enter into ophthalmology residency programs, whether they have similar surgical experiences during training is unclear. OBJECTIVE: To determine differences for cataract surgery and total procedural volume between male and female residents during ophthalmology residency. DESIGN, SETTING, PARTICIPANTS: This retrospective, longitudinal analysis of resident case logs from 24 US ophthalmology residency programs spanned July 2005 to June 2017. A total of 1271 residents were included. Data were analyzed from August 12, 2017, through April 4, 2018. MAIN OUTCOMES AND MEASURES: Variables analyzed included mean volumes of cataract surgery and total procedures, resident gender, and maternity or paternity leave status. RESULTS: Among the 1271 residents included in the analysis (815 men [64.1%]), being female was associated with performing fewer cataract operations and total procedures. Male residents performed a mean (SD) of 176.7 (66.2) cataract operations, and female residents performed a mean (SD) of 161.7 (56.2) (mean difference, -15.0 [95% CI, -22.2 to -7.8]; P < .001); men performed a mean (SD) of 509.4 (208.6) total procedures and women performed a mean (SD) of 451.3 (158.8) (mean difference, -58.1 [95% CI, -80.2 to -36.0]; P < .001). Eighty-five of 815 male residents (10.4%) and 71 of 456 female residents (15.6%) took parental leave. Male residents who took paternity leave performed a mean of 27.5 (95% CI, 13.3 to 41.6; P < .001) more cataract operations compared with men who did not take leave, but female residents who took maternity leave performed similar numbers of operations as women who did not take leave (mean difference, -2.0 [95% CI, -18.0 to 14.0]; P = .81). From 2005 to 2017, each additional year was associated with a 5.5 (95% CI, 4.4 to 6.7; P < .001) increase in cataract volume and 24.4 (95% CI, 20.9 to 27.8; P < .001) increase in total procedural volume. This increase was not different between genders for cataract procedure volume (ß = -1.6 [95% CI, -3.7 to 0.4]; P = .11) but was different for total procedural volume such that the increase in total procedural volume over time for men was greater than that for women (ß = -8.0 [95% CI, -14.0 to -2.1]; P = .008). CONCLUSIONS AND RELEVANCE: Female residents performed 7.8 to 22.2 fewer cataract operations and 36.0 to 80.2 fewer total procedures compared with their male counterparts from 2005 to 2017, a finding that warrants further exploration to ensure that residents have equivalent surgical training experiences during residency regardless of gender. However, this study included a limited number of programs (24 of 119 [20.2%]). Future research including all ophthalmology residency programs may minimize the selection bias issues present in this study.

Predictors of Clinical Outcomes After Hip Arthroscopy: A Prospective Analysis of 1038 Patients With 2-Year Follow-up.

BACKGROUND: As hip arthroscopy has expanded in popularity and volume, more information is needed about indications for the procedure and the predictive factors of clinical outcomes. PURPOSE: To evaluate clinical outcomes of hip arthroscopy in a prospective study and to analyze the cohort to identify factors that are predictive of improvement. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Data were collected prospectively on all patients undergoing hip arthroscopy between February 2008 and June 2012. We included all patients undergoing hip arthroscopy who agreed to participate and who completed 4 patient-reported outcome (PRO) instruments at a minimum 2-year follow-up: the modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sport-Specific Subscale. The NAHS was selected as our primary outcome instrument. All patients with any previous hip conditions were excluded. We analyzed 34 preoperative and intraoperative variables using bivariate and multivariate analyses compared with NAHS. RESULTS: The cohort consisted of 1038 patients with a mean follow-up of 30.1 months (range, 24.0-61.2 months). Mean age was 36.4 years (range, 13.2-76.4 years). All postoperative PRO scores showed significant improvement ( P < .001) at 2 years compared with preoperative scores. Bivariate analysis identified 15 variables (7 categorical and 8 continuous) and multivariate analysis identified 10 variables that were predictive of 2-year postoperative NAHS. Preoperative NAHS, preoperative HOS-ADL, preoperative mHHS, age, duration of symptoms, body mass index (BMI), and revision hip arthroscopy were identified as predictive factors in both bivariate and multivariate analyses. The predictive value of preoperative NAHS was accentuated for patients with higher BMI. CONCLUSION: This study reports favorable clinical outcomes in the largest cohort of hip arthroscopies with a minimum 2-year follow-up in the literature to date. Factors identified as predictive in both bivariate and multivariate analyses included preoperative NAHS, HOS-ADL, and mHHS; age; duration of symptoms; BMI; and revision hip arthroscopy. These predictive factors may be useful to the clinician in determining prognosis and operative indications for hip arthroscopy.

Central Acetabular Impingement Is Associated With Femoral Head and Ligamentum Teres Damage: A Cross-Sectional Matched-Pair Analysis of Patients Undergoing Hip Arthroscopy for Acetabular Labral Tears.

PURPOSE: The primary purpose of this study was to report the prevalence of femoral head articular damage in patients with a central acetabular osteophyte (CAO) that was identified during hip arthroscopy and compare it with that in a matched control group without a CAO. A secondary purpose was to identify rates of coexisting intra-articular pathology in both patient groups. METHODS: Intraoperative data were collected prospectively on all hip arthroscopy patients at our institution between 2008 and 2015. The inclusion criteria for this study were CAOs identified during hip arthroscopy for a labral tear and/or femoroacetabular impingement. The exclusion criteria were Tönnis grade greater than 0, previous hip conditions, and prior surgical interventions. The matched control group was selected based on sex, age ± 5 years, body mass index, and Workers' Compensation claim at a 3:1 ratio and comprised patients who underwent hip arthroscopy for a labral tear and/or femoroacetabular impingement without a CAO. The size and location of labral tears and chondral lesions were recorded in square millimeters with a 5-mm probe and by the clock-face method. RESULTS: The CAO group consisted of 126 patients, who were matched to 378 patients in the control group. Femoral and acetabular chondral damage grades were significantly different between the 2 groups (P < .001). Of patients with CAOs, 55% had femoral head chondral damage compared with 24% of the control patients. The mean size of femoral chondral damage was 3.2 cm2 in the CAO group and 1.7 cm2 in the control group. The mean size of acetabular chondral damage was 1.7 cm2 in the CAO group and 1.2 cm2 in the control group. Both femoral and acetabular chondral damage sizes were significantly larger in the CAO group (P ≤ .007). The prevalence of ligamentum teres tears was significantly different between the 2 groups (P < .001). There were no statistically significant differences in the types of labral tears between the 2 groups (P = .625). CONCLUSIONS: This study showed that patients with CAOs had a significantly higher prevalence of femoral chondral damage and ligamentum teres tears than matched controls. LEVEL OF EVIDENCE: Level III, comparative study.

Bilateral Central Retinal Artery Occlusion Associated with Bilateral Lymphoproliferative Infiltrative Optic Neuropathy.

BACKGROUND: Leukemic infiltration of the optic nerve is relatively rare. While previously described in acute leukemia, the infiltration in our case represents central nervous system (CNS) metastasis of Burkitt-type lymphoma that developed as a complication of solid-organ transplantation, resulting in a bilateral infiltrative optic neuropathy with sequential, bilateral central retinal artery occlusion (CRAO) and devastating vision loss. METHODS: The medical record, serial ophthalmic examination findings, clinical course, and imaging including magnetic resonance imaging (MRI), fundus photographs, and fluorescein angiography of a single patient were retrospectively reviewed. RESULTS: MRI demonstrated multifocal cortical and leptomeningeal CNS involvement, including the left optic nerve. Serial fundus examination/photography and fluorescein angiography showed that despite urgent whole-brain irradiation and systemic chemotherapy, CNS disease progressed to bilateral optic nerve infiltration and CRAO with no light perception vision in both eyes. CONCLUSION: CRAO can occur as a devastating and irreversible complication of lymphoproliferative optic nerve infiltration.

Robotic-arm assisted total hip arthroplasty results in smaller acetabular cup size in relation to the femoral head size: a matched-pair controlled study.

PURPOSE: To compare the acetabular component size relative to the patient's native femoral head size between conventional THA (CTHA) approach and robotic-arm assisted THA (RTHA) to infer which of these techniques preserved more acetabular bone. METHODS: Patients were included if they had primary osteoarthritis (OA) and underwent total hip replacement between June 2008 and March 2014. Patients were excluded if they had missing or rotated postoperative anteroposterior radiographs. RTHA patients were matched to a control group of CTHA patients, in terms of preoperative native femoral head size, age, gender, body mass index (BMI) and approach. Acetabular cup size relative to femoral head size was used as a surrogate for amount of bone resected. We compared the groups according to 2 measures describing acetabular cup diameter (c) in relation to femoral head diameter (f): (i) c-f, the difference between cup diameter and femoral head diameter and (ii) (c-f)/f, the same difference as a fraction of femoral head diameter. RESULTS: 57 matched pairs were included in each group. There were no significant differences between groups for demographic measures, femoral head diameter, or acetabular cup diameter (p>0.05). However, measures (i) and (ii) did differ significantly between the groups, with lower values in the RTHA group (p<0.02). CONCLUSIONS: Using acetabular cup size relative to femoral head size as an approximate surrogate measure of acetabular bone resection may suggest greater preservation of bone stock using RTHA compared to CTHA. Further studies are needed to validate the relationship between acetabular cup size and bone loss in THA.

Arthroscopic Capsular Plication and Labral Seal Restoration in Borderline Hip Dysplasia: 2-Year Clinical Outcomes in 55 Cases.

PURPOSE: To report clinical outcomes in patients with borderline dysplasia undergoing an arthroscopic technique of labral seal restoration with minimal acetabular rim resection and capsular plication. METHODS: Patients younger than 40 years with a lateral center-edge angle of 18° greater and 25° or less and 2-year follow-up after undergoing an arthroscopic technique of labral seal restoration with minimal rim resection (≤2 mm) and capsular plication (3-5 sutures placed in an oblique orientation to create an imbrication and inferior shift) were included. Patients underwent arthroscopy for symptoms that had marginal improvement with a minimum 6-week structured physical therapy program. Patients with a Tönnis grade of 1 or greater, a center-edge angle of 17° or less, and Legg-Calvé-Perthes disease were excluded. The following patient-reported outcomes (PROs) were recorded prospectively but retrospectively reviewed: modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score-Sports-Specific Subscale, and Hip Outcome Score-Activities of Daily Living. The visual analog scale score, patient satisfaction score, complications, and revision procedures were also recorded. A 2-tailed paired t test was used to analyze change in preoperative to postoperative PRO scores. Significance was defined as P < .05. RESULTS: During the study period, 232 hip arthroscopies were performed in patients with a lateral center-edge angle between 18° and 25°. The inclusion criteria were met by 59 procedures. Of these procedures, 55 (93.2%) were available for follow-up. The labrum was repaired, debrided, and reconstructed in 37 procedures, 17 procedures, and 1 procedure, respectively. The iliopsoas was released in 34 procedures, the ligamentum teres was debrided in 29, and femoral osteoplasty was performed in 32. At 2-year follow-up, there was significant improvement in the mean scores of all PROs compared with baseline. Mean improvements for the modified Harris Hip Score, Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sports-Specific Subscale, and Non-Arthritic Hip Score were 20.7, 17.5, 27.6, and 20.0, respectively. There was significant improvement in the visual analog scale score at 2 years, decreasing by 3.16 compared with baseline, and the mean patient satisfaction score was 8.09, with 83.6% of patients achieving a good to excellent result (patient satisfaction score ≥7). No complications were related to the procedure, and 6 patients (11%) required revision procedures (4 for labral retear, 1 for painful iliopsoas internal snapping, and 1 for removal of a symptomatic loose body). CONCLUSIONS: Arthroscopic intervention that encompasses minimal rim resection, restoration of labral function, and capsular plication significantly improves outcomes in patients with borderline dysplasia who do not warrant a periacetabular osteotomy. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Patient reported outcomes for patients who returned to sport compared with those who did not after hip arthroscopy: minimum 2-year follow-up.

Previous studies assessed elite athletes' return to sport (RTS) after hip arthroscopy, but few investigated a cohort including athletes from all levels of sport. This study compared athletes who returned to sport to those who did not, based on four patient-reported outcome (PRO) scores, including the Hip Outcome Score-Sports Specific Subscale (HOS-SSS). Between September 2008 and April 2012, hip arthroscopies were performed on 157 patients (168 hips) who reported playing a sport preoperatively and indicated their level of sports activity post-operatively. Two-year follow-up was available for 148 (94%) amateur and professional athletes with a total of 158 hips. Of these 60 cases (65 hips) did not return to sports (NRTS) and were in the NRTS group. The remaining 88 cases (93 hips) constituted the RTS group. The modified Harris Hip Score, Non-Arthric Hip Score, Hip Outcome-Activities of Daily Living (HOS-ADL), and HOS-SSS were used to assess outcomes. The HOS-SSS was used to assess specific sport-related movement. Both groups demonstrated significant improvement at 2 years post-operatively in visual analog score and four PRO scores (P < 0.001). There was no significant preoperative differences in HOS-SSS scores between groups; however, the RTS group had significantly higher HOS-SSS scores at 1 and 2 years post-surgery. Post-operatively, the RTS group had significantly better ability to jump, land from a jump, stop quickly and perform cutting/lateral movements (P < 0.05). In summary, patients who indicated RTSs demonstrated significantly higher PRO scores and abilities to perform several sport-related movements, compared with patients who did not.

Arthroscopic Central Acetabular Decompression: Clinical Outcomes at Minimum 2-Year Follow-up Using a Matched-Pair Analysis.

PURPOSE: To assess 2-year clinical outcomes of patients who underwent hip arthroscopy for central acetabular osteophytes (CAO) treated with central acetabular decompression (CAD), and to compare these outcomes with those of a matched control group. METHODS: Data were prospectively gathered for patients undergoing CAD during hip arthroscopy from February 2008 to July 2012. All patients were assessed pre- and postoperatively at 3 months, 1 year, and 2 years with modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sport-Specific Subscale, and visual analog scale (VAS) for pain. Patient satisfaction (0 to 10) was collected. A matched control group of patients without CAOs who did not undergo CAD was selected on a 1:3 ratio. RESULTS: Forty-nine hips were included in the CAD group and 147 in the control group. The mean change in patient-reported outcome (PRO) scores at 2-year follow-up in the CAD group for modified Harris Hip Score, Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sport-Specific Subscale, Non-Arthritic Hip Score, and VAS was 11.0, 19.6, 15.2, 21.4, and -2, respectively. The mean change in PRO scores at 2-year follow-up in the control group was 17.0, 19.8, 24.0, 20.9, and -2.75, respectively. All improvements in PRO scores for both groups were statistically significant compared with the data collected preoperatively (P < .001). There was no statistically significant difference in postoperative PRO scores and VAS between the groups. Postoperative patient satisfaction at the latest follow-up was 7.14 and 7.60 for CAD and control groups, respectively. CONCLUSIONS: This study showed that patients with a CAO treated with CAD during hip arthroscopy had favorable outcomes at minimum 2 years postoperatively. Furthermore, the study group showed similar PRO scores and VAS to the control group. We conclude that CAD is a viable treatment option for CAO, yielding clinical improvement at short-term follow-up. LEVEL OF EVIDENCE: Level III, prospective comparative study.

Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid injection in the hip.

The primary purpose of this review article is to discuss the role of diagnostic, corticosteroid, hyaluronic acid (HA) and platelet rich plasma (PRP) in the treatment of osteoarthritis (OA) and femoroacetabular impingement (FIA). These treatments play an important biological role in the non-operative management of these conditions. Two independent reviewers performed an search of PubMed for articles that contained at least one of the following search terms pertaining to intra-articular hip injection-local anaesthetic, diagnostic, ultrasound, fluoroscopic, image guided, corticosteroid, HA, PRP, OA, labral tears and FAI. Seventy-two full text articles were suitable for inclusion. There were 18 articles addressing the efficacy of diagnostic intra-articular hip injections. With respect to efficacy in OA there were 25 articles pertaining to efficacy of corticosteroid, 22 of HA and 4 of PRP. There were three articles addressing the efficacy of biologics in FAI. Diagnostic intra-articular hip injections are sensitive and specific for differentiating between intra-articular, extra-articular and spinal causes of hip symptoms. Ultrasound and fluoroscopy improves the precision of intra-articular positioning of diagnostic injections. Corticosteroids are more effective than HA and PRP in alleviating pain from hip OA. A higher dose of corticosteroids produces a longer benefit but volume of injection has no significant effect. Intra-articular corticosteroids do not increase infection rates of subsequent arthroplasty. There is currently limited evidence to warrant the routine use of therapeutic injections in the management of labral tears and FIA.

Arthroscopic reconstruction of the Ligamentum Teres: a case series in four patients with connective tissue disorders and generalized ligamentous laxity.

This study presents the results of four Ligamentum Teres (LT) reconstruction procedures for hip instability with an average of 21.4 months follow-up (range 16.4-27.8). The indication for reconstruction was patients who complained of hip instability (hip giving way on gait or activities of daily living) on a background of a connective tissue disorder and generalized ligamentous laxity. The following data were recorded: age, sex, body mass index, hip range of motion, impingement signs, acetabular coverage (lateral center edge angle and acetabular inclination), acetabular retroversion (ischial spine sign and a crossover sign), femoral alpha angles and femoral neck shaft angles. Four patient recorded outcomes (PROs) were collected at 3 months, 12 months and 24 months. Three patients were female. Three out of four procedures had an improvement in PROs. One patient with bilateral procedures had an improvement in PROs on one side at 1 year but a failure of the graft on the contralateral side. There were no complications reported with the technique. LT reconstruction and concomitant capsular plication in this case series is associated with an improvement in outcomes in three out of four of the patients with hip instability associated with a full thickness tear of the LT and who presented with hip instability on a background of generalized ligamentous laxity and a connective tissue disorder. However, the physical examination, radiographic and intra-operative findings which may help predict who would benefit from LT reconstruction require further investigation.

Incidence and types of complications after ablative oral cancer surgery with primary microvascular free flap reconstruction.

BACKGROUND: The aims of the study were 1) to evaluate the incidence and types of postoperative complications after ablative oral cancer surgery with primary free flap reconstruction and 2) identify prognostic variables for postoperative complications. MATERIAL AND METHODS: Desired data was retrieved from a computer database at the department of Oral and Maxillofacial Department, Queen Elisabeth hospital Birmingham, United Kingdom, between June 2007 and October 2012. Logistic regression was used to study relationships between preoperative variables and postoperative outcomes. RESULTS: The study population consisted 184 patients, comprising 189 composite resections with reconstruction. Complications developed in 40.2% of the patients. Three patients (1.6%) died, 11.1% returned to the operating room, 5.3% developed donor site complications and 6.9% flap complications of which 3.2% total flap failure. In the multivariable analysis systemic complications were associated with anaesthesia time and hospital stay with red cell transfusion. CONCLUSIONS: A significant proportion of the patients with primary free flap reconstructions after oral cancer surgery develops postoperative complications. Prolonged anaesthesia time and red cell transfusion are possible predictors for systemic complications and hospital stay respectively. Preoperative screening for risk factors is advocated for patient selection and to have realistic information and expectations.

Outcomes of Open Versus Endoscopic Repair of Abductor Muscle Tears of the Hip: A Systematic Review.

PURPOSE: To compare the outcome of open versus endoscopic gluteal tendon repair. METHODS: An extensive review of PubMed was conducted by 2 independent reviewers for articles containing at least 1 of the following search terms: gluteus medius, gluteus medius tear, gluteus medius tendinopathy, gluteus medius repair, hip abductors, hip abductor tears, hip abductor repair, hip rotator cuff, hip rotator cuff repair, trochanteric bursa, trochanteric bursitis, trochanteric bursectomy, peritrochanteric procedures, peritrochanteric repair, and peritrochanteric arthroscopy. This yielded 313 articles. Of these articles, 7 satisfied the following inclusion criteria: description of an open or endoscopic gluteal repair with outcomes consisting of patient-reported outcome scores, patient satisfaction, strength scores, pain scores, and complications. RESULTS: Three studies on open gluteal repairs and 4 on endoscopic gluteal repairs met the inclusion criteria. In total, there were 127 patients who underwent open procedures and 40 patients who underwent endoscopic procedures. Of the 40 patients who underwent endoscopic procedures, 15 had concomitant intra-articular procedures documented, as compared with 0 in the open group. The modified Harris Hip Score was common to 1 study on open repairs and 3 studies on endoscopic repairs. The scores were similar for follow-up periods of 1 and 2 years. Visual analog pain scale scores were reported in 1 study on open gluteal repairs and 1 study on endoscopic repairs and were similar between the 2 studies. Improvement in abductor strength was also similarly reported in selected studies between the 2 groups. The only difference between the 2 groups was the reported incidence of complications, which was higher in the open group. CONCLUSIONS: Open and endoscopic gluteal repairs have similar patient-reported outcome scores, pain scores, and improvement in abduction strength. Open techniques have a higher reported complication rate. Randomized studies of sufficient numbers of patients are required to ultimately determine if one technique produces superior patient outcomes over the other. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

Arthroscopic Technique of Capsular Plication for the Treatment of Hip Instability.

Atraumatic instability or microinstability of the hip is a recognized cause of groin pain and hip instability. Risk factors include female sex, ligamentous laxity, and borderline dysplasia. Arthroscopically, the joint may distract easily, and there may be associated ligamentum teres tears and laxity of the capsule on manual probing. The use of arthroscopic capsular plication in this cohort of patients has shown good to excellent results. Biomechanically, a capsular plication aims to create an imbrication and inferior shift of the capsule to augment the screw-home mechanism of the capsuloligamentous structures and thereby improve stability in extension and external rotation. The purpose of this article is to detail the step-by-step surgical technique of arthroscopic capsular plication, in addition to the indications, pearls, and pitfalls of the technique.

What are the current indications for use of radiofrequency devices in hip arthroscopy? A systematic review.

The role of radiofrequency energy (RFE) devices has been minimally studied in hip arthroscopy. The purpose of this study was to determine the role of RFE devices in hip arthroscopy through a systematic review of the literature. We searched the PubMed database using the following Medical Subject Heading terms: hip arthroscopy, hip radiofrequency, thermal capsulorrhaphy, thermal chondroplasty and radiofrequency debridement. Two authors independently reviewed the literature and included articles based on predetermined inclusion criteria. We excluded review, technique and experimental articles. After title and abstract review, we selected 293 articles for full-text review. Ten articles met the inclusion and exclusion criteria. For the included articles, a total of 305 hips underwent arthroscopy with concomitant RFE treatment at a mean age of 25.7 years. Eight articles presented patient-reported outcome (PRO) instruments, one study did not report an outcome instrument but utilized an evaluation of postoperative range of motion (ROM) and 1 year magnetic resonance image (MRI) and computed tomography (CT) imaging. The remaining article measured only the ROM pre- and postoperatively. Only one of the articles reviewed reported complications. Current evidence on the safety and indications for use of RFE devices in hip arthroscopy is insufficient. The literature shows mixed results regarding its use in hip arthroscopy. Although the use of thermal energy is not without risk, if used judiciously and appropriate precautions are taken to avoid damage to adjacent tissues, those devices can be useful for the treatment of certain intra-articular hip pathologies arthroscopically.

A novel uHPLC-MS/MS method for the quantitation of AZD7451 (AZ12607092) in human plasma.

Tropomyosin-related kinases (Trk) are tyrosine kinase receptors implicated in tumor proliferation, invasion, and survival signaling across a number of tumors, making them potentially attractive targets for the treatment of cancer. AZD7451 is a potent and selective inhibitor of Trk kinases currently undergoing a Phase I dose escalation in glioblastoma multiforme at the National Cancer Institute. A key part of early clinical testing for AZD7451 involves demonstrating that pharmacokinetic half-life and clinical exposures of AZD7451 are sufficient to inhibit Trk receptors in preclinical models. To address this need, an ultra sensitive analytical method was developed to measure the AZD7451 profile in human plasma. A liquid-liquid extraction recovered >80% of AZD7451 before quantitative analysis by ultra HPLC-MS/MS. A Varian Polaris(®) C18-A column and a mass transition of m/z 383.5→340.5 (m/z 389.6→342.0 for the internal standard [(2)H6]-AZD7451) was used, and a dynamic calibration range of 0.5-1000ng/mL was established, which provided a sensitive (<8.5% deviation), and precise (<6%) quantitative assay for AZD7451. AZD7451 demonstrated stability in human plasma at room temperature for 24h (<7% change) and after extraction at 4°C for 24h (<8% change), and was stable through 4 freeze/thaw cycles (<8% change). This method was used to measure AZD7451 plasma levels in clinical samples to confirm the sensitivity at several time points following AZD7451 treatment in subjects with glioblastoma.

Uncovering the genetic landscape driving castration-resistant prostate cancer.

Identification of the mechanisms that drive progression of metastatic castration-resistant prostate cancer (CRPC) has fostered interest since early androgen studies in the 1940s. Little knowledge has surfaced about the role mutations play in prostate cancer development. A group at the Michigan Center for Translation Pathology studied exomes of lethal, metastatic CRPC and documented the overall mutation rates. In classifying these mutations, the monoclonal cause of CRPC was recognized. Nine identified genes showed significant mutations. Six of these genes had previously been reported as mutated in prostate cancer. The analysis also found significantly mutated androgen receptor (AR) cofactors and linked proteins, including FOXA1 and MLL2. Another finding concerned an aberration in CHD1. Prostate cancers with deletions or mutations in CHD1 showed a strong correlation with ETS gene family fusion negative prostate cancers (96%). In profiling these exomes, this group provides an original method to identify deletions and mutations that drive CRPC progression.

Partitioning of organochlorine pesticides from water to polyethylene passive samplers.

The mass transfer rates and equilibrium partitioning behaviour of 14 diverse organochlorine pesticides (OCP) between water and polyethylene (PE) passive samplers, cut from custom made PE sheets and commercial polyethylene plastic bags, were quantified. Overall mass transfer coefficients, k(O), estimated PE membrane diffusion coefficients, D(PE), and PE-water partitioning coefficients, K(PE-water,) are reported. In addition, the partitioning of three polycyclic aromatic hydrocarbons (PAHs) from water to PE is quantified and compared with literature values. K(PE-water) values agreed mostly within a factor of two for both passive samplers and also with literature values for the reference PAHs. As PE is expected to exhibit similar sorption behaviour to long-chain alkanes, PE-water partitioning coefficients were compared to hexadecane-water partitioning coefficients estimated with the SPARC online calculator, COSMOtherm and a polyparameter linear free energy relationship based on the Abraham approach. The best correlation for all compounds tested was with COSMOtherm estimated hexadecane-water partitioning coefficients.

Options for upper lip reconstruction: a survey-based analysis.

BACKGROUND: Clinical factors such as size and location, but also surgeon experience and comfort level, may influence decisions in reconstructive methods. OBJECTIVE: To survey a select group of surgeons for their reconstructive choices for a moderate-sized upper lip defect. METHODS: Surveys were mailed to 313 facial plastic surgeons. Survey recipients were asked to rank reconstructive preferences for a specific upper lip defect. Response choices were correlated to predictor variables such as surgeon experience and comfort level. RESULTS: Survey response was 45.6%. Cheek advancement flap was the first choice in 34.4%, followed by Abbé flap (31.2%), myocutaneous rotation flap (20.5%), and nasolabial flap (13.9%), with the nasolabial flap being statistically the least popular (p<.01). For surgeons with more than 20 years' experience and those with less than 10 years' experience, the Abbé flap was the most common first choice (38.9% and 32.4%, respectively). For surgeons with 11 to 20 years experience, the cheek advancement flap was the most common first choice (46.2%). CONCLUSIONS: A poll of a select group of surgeons demonstrated variability in their choice of upper lip reconstruction options, although the nasolabial flap was found to be the least-chosen option. Trends in choices based upon experience and comfort level were demonstrated.

Transcervical resection of the styloid process in Eagle syndrome.

We conducted a retrospective study to determine the treatment outcomes of 6 patients who had either unilateral or bilateral elongated styloid processes and symptoms consistent with Eagle syndrome. Five of these patients had undergone transcervical resection of the styloid process, with relief of symptoms over the follow-up period (mean: 8 mo). Two of the 5 patients experienced a transient weakness in the marginal mandibular nerve, and both recovered completely. The transcervical surgical approach to resection in patients with elongated styloid processes and Eagle syndrome appears to be safe and effective, although the risk for transient marginal mandibular nerve weakness is notable.

Long-term efficacy of intra-oral surgery for sialorrhea.

OBJECTIVES: To investigate the efficacy and quality of life impact of intra-oral surgery for sialorrhea and to provide long-term outcome measures. METHODS: A retrospective review and telephone survey of patients seen in a multi-disciplinary saliva control clinic who underwent surgery between 1999 and 2003. RESULTS: Sixteen of 31 patients underwent 4-duct ligation, 12 patients underwent submandibular gland duct ligation, and three patients underwent a 3-duct ligation procedure. The mean presurgical drooling score (maximum 10) was 9.5, 8.8, and 9, respectively. Recurrence was seen in 68% of patients at a mean of four months. Additional surgery was required in five patients. Phone survey was accomplished in 10 patients. Two of 10 caregivers reported sustained improvement of sialorrhea at two and three years. CONCLUSIONS: Intra-oral surgery provides minimal long-term control of sialorrhea. Additional medical and surgical therapy was needed in a significant portion of patients in this long-term review.