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"Metcalfe, Michael"
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Oncologic outcomes of patients with positive surgical margin after partial nephrectomy: a 25-year single institution experience
PurposeTo evaluate oncologic outcomes and management of patients with microscopic positive surgical margin (PSM) after partial nephrectomy (PN) for renal cell carcinoma (RCC).MethodsWe reviewed our database to identify patients who underwent PN between 1990 and 2015 for RCC and had PSM on final pathology. A 1:3 matching was performed to a negative surgical margin (NSM) cohort. Kaplan–Meier method and log-rank test were used to estimate survival and differences in outcomes, respectively. Cox proportional hazards models were conducted to estimate the Hazards ratio.ResultsA total of 2297 patients underwent PN at our institution, of which 1863 (81%) had RCC. Microscopic PSM was found in 34 (1.8%) RCC patients who were matched to 100 patients with NSM. Of these 34 patients, local recurrence (n = 4), distant kidney recurrences (n = 4), and metastases (n = 5) developed during a median follow-up of 62 months. Bilateral tumors/tumors in a solitary kidney (n = 12/13, 92%), and multifocal tumors (n = 7/13, 54%) were found in patients who developed recurrence/metastasis. PSM patients were at a higher risk of shorter overall survival (p = 0.001), local recurrence-free survival (p = 0.003), distant recurrence-free survival (p = 0.032) and metastasis-free survival (p = 0.018). There was statistically significant association between PSM and bilateral tumors, prior treated RCC at presentation and higher nephrometry score in multivariable model.ConclusionsThere was a low rate of microscopic PSM in our large cohort of patients undergoing PN despite tumor complexity. Higher nephrometry score, bilateral tumors, and prior treated RCC independently predicted PSM which showed worse survival, recurrence and metastasis compared to patients with NSM.
Journal Article
Salvage topical therapy for upper tract urothelial carcinoma
PurposeTopical therapy (TT) for upper tract urothelial carcinoma (UTUC) has been explored as a kidney sparing approach to treat carcinoma in situ (CIS) and as adjuvant for endoscopically treated Ta/T1 tumors. In bladder cancer, data support use of salvage TT for repeat induction. We investigate the outcomes of salvage TT for UTUC in patients ineligible for or refusing nephroureterectomy.MethodsA single-center retrospective review on patients receiving salvage TT via percutaneous nephrostomy tube or cystoscopically placed ureteral catheters was performed. Primary outcome was response to therapy based on International Bladder Cancer Group criteria.Results51 patients with 58 renal units (RUs) received TT. Of these, 17 patients with 18 RUs received the second-line TT, with a median follow-up of 36.5 months (IQR 24.5–67 months). 44% (8/18) received salvage TT for refractory disease and 56% (10/18) as reinduction. 5 RUs with CIS were unresponsive to initial TT and went on to receive salvage TT, of which 20% (1/5) responded. 13 RUs recurred or relapsed following initial TT and received salvage TT for papillary tumors, with 62% (8/13) responding.ConclusionOur data provide preliminary clinical rationale for the second-line TT for refractory and recurrent, endoscopically managed papillary UTUC in patients ineligible for or refusing nephroureterectomy. However, refractory upper tract CIS appears to have poor response to salvage TT.
Journal Article
Solubilization and Stability of Mitomycin C Solutions Prepared for Intravesical Administration
Background
Mitomycin C (MMC) is an antitumor agent that is often administered intravesically to treat bladder cancer. Pharmacologically optimized studies have suggested varying methods to optimize delivery, with drug concentration and solution volume being the main drivers. However, these MMC concentrations (e.g. 2.0 mg/mL) supersede its solubility threshold, raising major concerns of inferior drug delivery.
Objective
In this study, we seek to confirm that the pharmacologically optimized MMC concentrations are achievable in clinical practice through careful modifications of the solution preparation methods.
Methods
MMC admixtures (1.0 and 2.0 mg/mL) were prepared in normal saline using conventional and alternative compounding methods. Conventional methodology resulted in poorly soluble solutions, with many visible particulates and crystallates. However, special compounding methods, which included incubation of solutions at 50 °C for 50 min followed by storage at 37 °C, were sufficient to solubilize drug. Chemical degradation of MMC solutions was determined over 6 h using high-performance liquid chromatography (HPLC) analytics, while physical stability was tested in parallel.
Results
Immediately following the 50 min incubation, both MMC solutions exhibited approximately 5–7% drug degradation. Based on the measured concentrations and linear regression of degradation plots, additional storage of these solutions at 37 °C for 5 h retained chemical stability criterion (< 10% overall drug loss). No physical changes were observed in any solutions at any test time points.
Conclusion
We recommend that the described alternative preparation methods may improve intravesicular delivery of MMC in this urological setting, and advise that clinicians employing these changes should closely monitor patients for MMC toxicities and pharmacodynamics (change in clinical outcomes) that result from the potential enhancement of MMC exposure in the bladder.
Journal Article
New discoveries in the molecular landscape of bladder cancer
We are currently on the cusp of exponential growth in the understanding of the molecular landscape of bladder cancer. Emerging data regarding the mutational burden and targetable genomic and protein alterations in bladder cancer have allowed us to tap into treatments directed toward specific molecular characteristics of bladder cancer. In parallel, these developments will enable us to better select patients for existing treatments of bladder cancer in a step toward personalized therapy. The present article reviews select discoveries that have advanced our understanding of bladder cancer and gives a glimpse of the exciting opportunities on the not-so-distant horizon.
Journal Article
Stopping smokeless tobacco with varenicline: randomised double blind placebo controlled trial
Objective To assess the efficacy and safety of varenicline (a licensed cigarette smoking cessation aid) in helping users of smokeless tobacco to quit.Design Double blind, placebo controlled, parallel group, multicentre, randomised controlled trial.Setting Medical clinics (mostly primary care) in Norway and Sweden.Participants Men and women aged ≥18 who used smokeless tobacco at least eight times a day, with no abstinence period over three months within one year before screening, who wanted to quit all tobacco use. Participants were excluded if they used any other form of tobacco (except smokeless tobacco) or medication to stop smoking within three months of screening or had any pre-existing medical or psychiatric condition.Interventions Varenicline 1 mg twice daily (titrated during the first week) or placebo for 12 weeks, with 14 weeks’ follow-up after treatment.Main outcome measures The primary end point was the four week continuous abstinence rate at the end of treatment (weeks 9-12) confirmed with cotinine concentration. A secondary end point was continuous abstinence rate for weeks 9-26. Safety and tolerability were also evaluated.Results 431 participants (213 varenicline; 218 placebo) were randomised and received at least one dose of study drug. Participants’ demographics and baseline use of smokeless tobacco were similar (89% (189) and 90% (196), respectively, were men; mean age in both groups was 43.9; participants used smokeless tobacco products about 15 times a day, and about 80% first used smokeless tobacco within 30 minutes after awakening). Continuous abstinence rate at week 9-12 was higher in the varenicline group than the placebo group (59% (125) v 39% (85); relative risk 1.60, 95% confidence interval 1.32 to 1.87, P<0.001; risk difference 20%; number needed to treat 5). The advantage of varenicline over placebo persisted through 14 weeks of follow-up (continuous abstinence rate at week 9-26 was 45% (95) v 34% (73); relative risk 1.42, 1.08 to 1.79, P=0.012; risk difference 11%; number needed to treat 9). The most common adverse events in the varenicline group compared with the placebo group were nausea (35% (74) v 6% (14)), fatigue (10% (22) v 7% (15)), headache (10% (22) v 9% (20)), and sleep disorder (10% (22) v 7% (15)). Few adverse events led to discontinuation of treatment (9% (19) and 4% (9), respectively), and serious adverse events occurred in two (1%) and three (1%) participants, respectively.Conclusion Varenicline can help people to give up smokeless tobacco and has an acceptable safety profile. The response rate in the placebo group in this study was high, suggesting a population less resistant to treatment than smokers.Trial Registration NCT00717093.
Journal Article
Electromyography of Shoulder Muscles During Upper Extremity Plyometrics
Plyometric exercises are often used to dynamically strengthen the shoulder muscles for overhead athletes. The purpose of this study was to examine differences in relative muscular activation of four shoulder muscles and four upper extremity plyometric exercises. It was hypothesized that the upper trapezius would be most active in the standing scaption exercise, that the lower trapezius and posterior deltoid would be most active in the prone external rotation exercise, and that the infraspinatus would be most active in the kneeling 90/90 exercise. 30 healthy, recreationally active subjects were tested using surface EMG during a five-repetition set of each of the four exercises: kneeling diagonal plyometric, kneeling 90/90 plyometric, prone ER plyometric, and standing scaption plyometric exercises using a 1kg soft plyoball. Electrodes were attached to the upper trapezius (UT), lower trapezius (LT), posterior deltoid (PD), and infraspinatus (IS) muscles. Normalized peak and mean EMG amplitudes were expressed as % MVIC. Results showed LT > UT for the kneeling diagonal, 90/90, and prone ER exercises. The highest peak and mean LT activation was in the prone ER exercise. Highest peak IS activation in the kneeling 90/90 and highest mean IS activation in the prone ER. The results demonstrated that body position affects muscle activation, and in the dynamic, overhead exercises, good LT:UT activation occurred.
Dissertation
Dual Role Athletic Trainer/Strength Coach
SOME EMPLOYERS HIRE ONE INDIVIDUAL TO FILL AN ALLIED HEALTH AND PERFORMANCE ENHANCEMENT POSITION. THIS PRACTICE IS CONTROVERSIAL. AS THE FIELD EVOLVES, CAREFUL CONSIDERATION OF THE SCOPE OF PRACTICE FOR STRENGTH AND CONDITIONING PROFESSIONALS IS REQUIRED BOTH IN TRADITIONAL AND NONTRADITIONAL ROLES. [PUBLICATION ABSTRACT]
Journal Article
A new microwave resonator readout scheme for superconducting qubits
Quantum computation is a relatively new field of research, which uses the properties of quantum mechanical systems for information processing. While most proposals for constructing such a quantum computer involve using microscopic degrees of freedom such as those of trapped ions or nuclear spins, this thesis concentrates on using the collective electromagnetic response of a macroscopic electrical circuit to construct the fundamental building block of a quantum computer—a qubit. These macroscopic systems are inherently more difficult to protect from decoherence compared to the microscopic qubit systems because of strong environmental coupling through, for example, the measurement leads. However, superconducting quantum circuits should be easier to scale to large multi qubit systems since they involve simple electrical elements, such as inductors and capacitors for coupling qubits. Furthermore, they can be produced using the highly developed fabrication techniques of integrated circuits. One of the outstanding issues in superconducting qubit circuits is to read out the qubit state without introducing excessive noise. Such a readout scheme requires speed, sensitivity and should minimally disturb the qubit state. To meet these requirements we have developed a new type of dispersive bifurcating amplifier, called the cavity bifurcation amplifier (CBA), which consists of a Josephson junction imbedded in a microwave on-chip resonator. The optimum resonator design is based on a simple coplanar waveguide (CPW), imposing a pre-determined frequency and whose other RF characteristics like the quality factor are easily controlled and optimized. The CBA is sensitive to the susceptibility of the superconducting qubit with respect to an external control parameter (e.g., flux) and hence during both qubit manipulation and readout sequences, the qubit can be biased on a so-called \"sweet spot\", where it is immune to first order fluctuations in this parameter. This readout has no on-chip dissipation, minimizing the back-action on the qubit states. Furthermore, due to the CBA's megahertz repetition rate and large signal to noise ratio, we can measure drifts in qubit parameters in real time and either compensate for these drifts as they are detected, or simply study them to discover their source. In addition, the CPW resonator architecture of the CBA is easily multiplexed on-chip, enabling the simultaneous readout of several qubits at different frequencies; opening the door to scalable quantum computing.
Dissertation