The uptake of robotic surgery has led to changes in potential operative complications, as many su... more The uptake of robotic surgery has led to changes in potential operative complications, as many surgeons learn minimally invasive surgery, and has allowed the documentation of such complications through the routine collection of intraoperative video. We documented intraoperative complications from robot-assisted radical prostatectomy (RARP) with the aim of reporting the mechanisms, etiology, and necessary steps to avoid them. Our goal was to facilitate learning from these complications to improve patient care. Contributors delivered videos of complications that occurred during laparoscopic and robotic prostatectomy between 2010 and 2015. Surgical footage was available for a variety of complications during RARP. Based on these videos, a literature search was performed using relevant terms (prostatectomy, robotic, complications), and the intraoperative steps of the procedures and methods of preventing complications were outlined. As a major surgical procedure, RARP has much potential f...
Methods. Questionnaires were mailed to 4998 randomly chosen working-aged patients from general pr... more Methods. Questionnaires were mailed to 4998 randomly chosen working-aged patients from general practices in Avon. We asked about upper limb pain, consulting, beliefs about symp- toms, dissatisfaction with care, somatizing tendency (using elements of the Brief Symptom Inventory) and mental well-being (using the Short-Form 36). Associations were explored by logistic regression. Results. Among 2632 responders, 1271 reported arm pain during the past 12 months, includ- ing 389 consulters. A third or more of responders felt that arm pain sufferers should avoid physical activity, that problems would persist beyond 3 months, that a doctor should be seen straightaway and that neglect could lead to permanent harm. Consulters were significantly more likely to agree with these statements than other upper limb pain sufferers. The pro- portion of consultations attributable to such beliefs was substantial. Dissatisfaction with care was commoner in those with poor mental health: the OR for being di...
Abstract Carbohydrate-binding agents (CBAs) are potential HIV microbicidal agents with a high gen... more Abstract Carbohydrate-binding agents (CBAs) are potential HIV microbicidal agents with a high genetic barrier to resistance. We wanted to evaluate whether two mannose-specific CBAs, recognizing multiple and often distinct glycan structures on the HIV envelope gp120, can interact synergistically against HIV-1, HIV-2, and HIV-1 strains that were selected for resistance against particular CBAs [i.e., 2G12 mAb and microvirin (MVN)]. Paired CBA/CBA combinations mainly showed synergistic activity against both wild-type HIV-1 and HIV-2 but also 2G12 mAb- and MVN-resistant HIV-1 strains as based on the median effect principle with combination indices (CIs) ranging between 0.29 and 0.97. Upon combination, an increase in antiviral potency of griffithsin (GRFT) up to ∼12-fold (against HIV-1), ∼8-fold (against HIV-2), and ∼6-fold (against CBA-resistant HIV-1) was observed. In contrast, HHA/GNA combinations showed additive activity against wild-type HIV-1 and HIV-2 strains, but remarkable synerg...
To assess the contribution of epilepsy and diabetes to occupational injury. The Clinical Practice... more To assess the contribution of epilepsy and diabetes to occupational injury. The Clinical Practice Research Datalink logs primary care data for 6% of the British population, coding all consultations and treatments. Using this, we conducted a population-based case-control study, identifying patients aged 16-64 years, who had consulted over two decades for workplace injury, plus matched controls. By conditional logistic regression, we assessed risks for diabetes and epilepsy overall, several diabetic complications and indices of poor control, occurrence of status epilepticus and treatment with hypoglycaemic and anti-epileptic agents. We identified 1348 injury cases and 6652 matched controls. A total of 160 subjects (2%) had previous epilepsy, including 29 injury cases, whereas 199 (2.5%) had diabetes, including 77 with eye involvement and 52 with a record of poor control. Odds ratios (ORs) for occupational injury were close to unity, both in those with epilepsy (1.07) and diabetes (0.9...
Methods in molecular biology (Clifton, N.J.), 2011
Recombinant protein pharmaceuticals are now widely used in treatment of chronic diseases, and sev... more Recombinant protein pharmaceuticals are now widely used in treatment of chronic diseases, and several recombinant protein subunit vaccines are approved for human and veterinary use. With growing demand for complex protein pharmaceuticals, such as monoclonal antibodies, manufacturing capacity is becoming limited. There is increasing need for safe, scalable, and economical alternatives to mammalian cell culture-based manufacturing systems, which require substantial capital investment for new manufacturing facilities. Since a seminal paper reporting immunoglobulin expression in transgenic plants was published in 1989, there have been many technological advances in plant expression systems to the present time where production of proteins in leaf tissues of nonfood crops such as Nicotiana species is considered a viable alternative. In particular, transient expression systems derived from recombinant plant viral vectors offer opportunities for rapid expression screening, construct optimiz...
To analyze the continence outcomes of robot assisted radical prostatectomy (RARP) in suboptimal p... more To analyze the continence outcomes of robot assisted radical prostatectomy (RARP) in suboptimal patients that have challenging continence recovery factors: enlarged prostates, elderly patients, higher Body Mass Index (BMI), salvage prostatectomy and bladder neck procedures prior to RARP MATERIAL & METHODS: From January 2008 through November 2012, 4023 patients underwent RARP by a single surgeon at our institution. Retrospective analysis of prospectively collected data identified 3362 men who had minimum of one year of follow-up. This cohort of patients was stratified into six groups: Group I, age 70 and over (n=451); Group II, BMI 35 and over (n=197); Group III, prior bladder neck procedures (n=103); Group IV, prostate weight 80 g and over (n=280); and Group V, salvage prostatectomy patients (n=41). Group VI consisted of patients (n=2447) with none of these risk factors. Continence outcomes at follow-up were analyzed for all groups. The continence rate at 1 year and mean time to con...
During robot-assisted radical prostatectomy (RARP), the quality of nerve sparing (NS) was usually... more During robot-assisted radical prostatectomy (RARP), the quality of nerve sparing (NS) was usually classified by laterality of NS (none, unilateral, and bilateral) or degree of NS (none, partial, and full). Recently, side-specific NS have been more frequently performed, but previous NS grading system might not reflect the differential NS in each side. Herein, we assessed whether a subjective NS score (NSS) incorporating both degree of NS and NS laterality can predict the time to potency recovery following RARP. Data were analyzed from 1,898 patients who had left and right neurovascular bundle sparing quality scores and at least one year of follow-up after RARP was performed between January 2008 and October 2011. Cox proportional hazard method analyses were used to determine predictive factors for early recovery. Multivariate linear regression models were used to assess subjective NSS in an effort to predict time to potency recovery. Subjective NSSs were compared to a model based on t...
In addition to their traditional role as a source of natural medicines, it is now possible to gen... more In addition to their traditional role as a source of natural medicines, it is now possible to genetically engineer plants to produce pharmaceuticals. Transgenic plants expressing antigens from pathogenic microorganisms offer many advantages as low-cost production systems and effective delivery systems for vaccines. This new technology might contribute to global vaccine programs and might have a dramatic impact on health
To better use virtual reality robotic simulators and offer surgeons more practical exercises, we ... more To better use virtual reality robotic simulators and offer surgeons more practical exercises, we developed the Tube 3 module for practicing vesicourethral anastomosis (VUA), one of the most complex steps in the robot-assisted radical prostatectomy procedure. Herein, we describe the principle of the Tube 3 module and evaluate its face, content, and construct validity. Residents and attending surgeons participated in a prospective study approved by the institutional review board. We divided subjects into 2 groups, those with experience and novices. Each subject performed a simulated VUA using the Tube 3 module. A built-in scoring algorithm recorded the data from each performance. After completing the Tube 3 module exercise, each subject answered a questionnaire to provide data to be used for face and content validation. The novice group consisted of 10 residents. The experienced subjects (n = 10) had each previously performed at least 10 robotic surgeries. The experienced group outper...
We present a propensity-matched analysis of patients undergoing placement of dehydrated human amn... more We present a propensity-matched analysis of patients undergoing placement of dehydrated human amniotic membrane (dHAM) around the neurovascular bundle (NVB) during nerve-sparing (NS) robot-assisted laparoscopic prostatectomy (RARP). From March 2013 to July 2014, 58 patients who were preoperatively potent (Sexual Health Inventory for Men [SHIM] score >19) and continent (no pads) underwent full NS RARP. Postoperative outcomes were analyzed between propensity-matched graft and no-graft groups, including time to return to continence, potency, and biochemical recurrence. dHAM use was not associated with increased operative time or blood loss or negative oncologic outcomes (p>0.500). Continence at 8 wk returned in 81.0% of the dHAM group and 74.1% of the no-dHAM group (p=0.373). Mean time to continence was enhanced in group 1 patients (1.21 mo) versus (1.83 mo; p=0.033). Potency at 8 wk returned in 65.5% of the dHAM patients and 51.7% of the no-dHAM group (p=0.132). Mean time to pot...
Urologic Oncology: Seminars and Original Investigations, 2014
Robotic-assisted laparoscopic radical prostatectomy is a current standard treatment for localized... more Robotic-assisted laparoscopic radical prostatectomy is a current standard treatment for localized prostate cancer, with treatment failure defined by biochemical recurrence (BCR). Open radical prostatectomy series have identified the presence of a positive surgical margin (PSM) as a predictor of long-term recurrence, a measure that is affected by the surgeon׳s skill. We evaluate the effect of PSM parameters on BCR rates from robotic-assisted laparoscopic radical prostatectomy, across 3 high-volume institutions. De-identifiable clinicopathological and histopathological data were prospectively collected for 4,001 patients with at least 3 years of follow-up. Kaplan-Meier plots and 3 statistical models were used to evaluate the effect of margin parameters on BCR, via crude rates, traditional multivariable Cox regression, and a propensity-adjusted Cox regression model. Overall, 37% of men with a PSM developed BCR compared with 10% of men with negative margins (hazard ratio [HR] = 1.81, 95% CI: 1.47-2.22). Length ≥3mm or a multifocal positive margin was associated with a higher risk of BCR compared with negative margin cases. On multivariable Cox regression analysis of the positive margin cohort, only apical margins significantly predicted BCR relative to basal margins (HR = 2.03, 95% CI: 1.01-4.09), whereas there was no significant difference in BCR rates for posterolateral margins relative to basal margins (HR = 1.62, 95% CI: 0.84-3.11). Propensity-adjusted modeling confirmed a greater effect of apical compared with posterolateral PSM. A PSM length ≥3mm is predictive of BCR, as is to a lesser extent multiple positive margins. In contrast to open prostatectomy series, posterolateral margins carry a smaller risk of BCR compared with apical margins.
The uptake of robotic surgery has led to changes in potential operative complications, as many su... more The uptake of robotic surgery has led to changes in potential operative complications, as many surgeons learn minimally invasive surgery, and has allowed the documentation of such complications through the routine collection of intraoperative video. We documented intraoperative complications from robot-assisted radical prostatectomy (RARP) with the aim of reporting the mechanisms, etiology, and necessary steps to avoid them. Our goal was to facilitate learning from these complications to improve patient care. Contributors delivered videos of complications that occurred during laparoscopic and robotic prostatectomy between 2010 and 2015. Surgical footage was available for a variety of complications during RARP. Based on these videos, a literature search was performed using relevant terms (prostatectomy, robotic, complications), and the intraoperative steps of the procedures and methods of preventing complications were outlined. As a major surgical procedure, RARP has much potential f...
Methods. Questionnaires were mailed to 4998 randomly chosen working-aged patients from general pr... more Methods. Questionnaires were mailed to 4998 randomly chosen working-aged patients from general practices in Avon. We asked about upper limb pain, consulting, beliefs about symp- toms, dissatisfaction with care, somatizing tendency (using elements of the Brief Symptom Inventory) and mental well-being (using the Short-Form 36). Associations were explored by logistic regression. Results. Among 2632 responders, 1271 reported arm pain during the past 12 months, includ- ing 389 consulters. A third or more of responders felt that arm pain sufferers should avoid physical activity, that problems would persist beyond 3 months, that a doctor should be seen straightaway and that neglect could lead to permanent harm. Consulters were significantly more likely to agree with these statements than other upper limb pain sufferers. The pro- portion of consultations attributable to such beliefs was substantial. Dissatisfaction with care was commoner in those with poor mental health: the OR for being di...
Abstract Carbohydrate-binding agents (CBAs) are potential HIV microbicidal agents with a high gen... more Abstract Carbohydrate-binding agents (CBAs) are potential HIV microbicidal agents with a high genetic barrier to resistance. We wanted to evaluate whether two mannose-specific CBAs, recognizing multiple and often distinct glycan structures on the HIV envelope gp120, can interact synergistically against HIV-1, HIV-2, and HIV-1 strains that were selected for resistance against particular CBAs [i.e., 2G12 mAb and microvirin (MVN)]. Paired CBA/CBA combinations mainly showed synergistic activity against both wild-type HIV-1 and HIV-2 but also 2G12 mAb- and MVN-resistant HIV-1 strains as based on the median effect principle with combination indices (CIs) ranging between 0.29 and 0.97. Upon combination, an increase in antiviral potency of griffithsin (GRFT) up to ∼12-fold (against HIV-1), ∼8-fold (against HIV-2), and ∼6-fold (against CBA-resistant HIV-1) was observed. In contrast, HHA/GNA combinations showed additive activity against wild-type HIV-1 and HIV-2 strains, but remarkable synerg...
To assess the contribution of epilepsy and diabetes to occupational injury. The Clinical Practice... more To assess the contribution of epilepsy and diabetes to occupational injury. The Clinical Practice Research Datalink logs primary care data for 6% of the British population, coding all consultations and treatments. Using this, we conducted a population-based case-control study, identifying patients aged 16-64 years, who had consulted over two decades for workplace injury, plus matched controls. By conditional logistic regression, we assessed risks for diabetes and epilepsy overall, several diabetic complications and indices of poor control, occurrence of status epilepticus and treatment with hypoglycaemic and anti-epileptic agents. We identified 1348 injury cases and 6652 matched controls. A total of 160 subjects (2%) had previous epilepsy, including 29 injury cases, whereas 199 (2.5%) had diabetes, including 77 with eye involvement and 52 with a record of poor control. Odds ratios (ORs) for occupational injury were close to unity, both in those with epilepsy (1.07) and diabetes (0.9...
Methods in molecular biology (Clifton, N.J.), 2011
Recombinant protein pharmaceuticals are now widely used in treatment of chronic diseases, and sev... more Recombinant protein pharmaceuticals are now widely used in treatment of chronic diseases, and several recombinant protein subunit vaccines are approved for human and veterinary use. With growing demand for complex protein pharmaceuticals, such as monoclonal antibodies, manufacturing capacity is becoming limited. There is increasing need for safe, scalable, and economical alternatives to mammalian cell culture-based manufacturing systems, which require substantial capital investment for new manufacturing facilities. Since a seminal paper reporting immunoglobulin expression in transgenic plants was published in 1989, there have been many technological advances in plant expression systems to the present time where production of proteins in leaf tissues of nonfood crops such as Nicotiana species is considered a viable alternative. In particular, transient expression systems derived from recombinant plant viral vectors offer opportunities for rapid expression screening, construct optimiz...
To analyze the continence outcomes of robot assisted radical prostatectomy (RARP) in suboptimal p... more To analyze the continence outcomes of robot assisted radical prostatectomy (RARP) in suboptimal patients that have challenging continence recovery factors: enlarged prostates, elderly patients, higher Body Mass Index (BMI), salvage prostatectomy and bladder neck procedures prior to RARP MATERIAL & METHODS: From January 2008 through November 2012, 4023 patients underwent RARP by a single surgeon at our institution. Retrospective analysis of prospectively collected data identified 3362 men who had minimum of one year of follow-up. This cohort of patients was stratified into six groups: Group I, age 70 and over (n=451); Group II, BMI 35 and over (n=197); Group III, prior bladder neck procedures (n=103); Group IV, prostate weight 80 g and over (n=280); and Group V, salvage prostatectomy patients (n=41). Group VI consisted of patients (n=2447) with none of these risk factors. Continence outcomes at follow-up were analyzed for all groups. The continence rate at 1 year and mean time to con...
During robot-assisted radical prostatectomy (RARP), the quality of nerve sparing (NS) was usually... more During robot-assisted radical prostatectomy (RARP), the quality of nerve sparing (NS) was usually classified by laterality of NS (none, unilateral, and bilateral) or degree of NS (none, partial, and full). Recently, side-specific NS have been more frequently performed, but previous NS grading system might not reflect the differential NS in each side. Herein, we assessed whether a subjective NS score (NSS) incorporating both degree of NS and NS laterality can predict the time to potency recovery following RARP. Data were analyzed from 1,898 patients who had left and right neurovascular bundle sparing quality scores and at least one year of follow-up after RARP was performed between January 2008 and October 2011. Cox proportional hazard method analyses were used to determine predictive factors for early recovery. Multivariate linear regression models were used to assess subjective NSS in an effort to predict time to potency recovery. Subjective NSSs were compared to a model based on t...
In addition to their traditional role as a source of natural medicines, it is now possible to gen... more In addition to their traditional role as a source of natural medicines, it is now possible to genetically engineer plants to produce pharmaceuticals. Transgenic plants expressing antigens from pathogenic microorganisms offer many advantages as low-cost production systems and effective delivery systems for vaccines. This new technology might contribute to global vaccine programs and might have a dramatic impact on health
To better use virtual reality robotic simulators and offer surgeons more practical exercises, we ... more To better use virtual reality robotic simulators and offer surgeons more practical exercises, we developed the Tube 3 module for practicing vesicourethral anastomosis (VUA), one of the most complex steps in the robot-assisted radical prostatectomy procedure. Herein, we describe the principle of the Tube 3 module and evaluate its face, content, and construct validity. Residents and attending surgeons participated in a prospective study approved by the institutional review board. We divided subjects into 2 groups, those with experience and novices. Each subject performed a simulated VUA using the Tube 3 module. A built-in scoring algorithm recorded the data from each performance. After completing the Tube 3 module exercise, each subject answered a questionnaire to provide data to be used for face and content validation. The novice group consisted of 10 residents. The experienced subjects (n = 10) had each previously performed at least 10 robotic surgeries. The experienced group outper...
We present a propensity-matched analysis of patients undergoing placement of dehydrated human amn... more We present a propensity-matched analysis of patients undergoing placement of dehydrated human amniotic membrane (dHAM) around the neurovascular bundle (NVB) during nerve-sparing (NS) robot-assisted laparoscopic prostatectomy (RARP). From March 2013 to July 2014, 58 patients who were preoperatively potent (Sexual Health Inventory for Men [SHIM] score >19) and continent (no pads) underwent full NS RARP. Postoperative outcomes were analyzed between propensity-matched graft and no-graft groups, including time to return to continence, potency, and biochemical recurrence. dHAM use was not associated with increased operative time or blood loss or negative oncologic outcomes (p>0.500). Continence at 8 wk returned in 81.0% of the dHAM group and 74.1% of the no-dHAM group (p=0.373). Mean time to continence was enhanced in group 1 patients (1.21 mo) versus (1.83 mo; p=0.033). Potency at 8 wk returned in 65.5% of the dHAM patients and 51.7% of the no-dHAM group (p=0.132). Mean time to pot...
Urologic Oncology: Seminars and Original Investigations, 2014
Robotic-assisted laparoscopic radical prostatectomy is a current standard treatment for localized... more Robotic-assisted laparoscopic radical prostatectomy is a current standard treatment for localized prostate cancer, with treatment failure defined by biochemical recurrence (BCR). Open radical prostatectomy series have identified the presence of a positive surgical margin (PSM) as a predictor of long-term recurrence, a measure that is affected by the surgeon׳s skill. We evaluate the effect of PSM parameters on BCR rates from robotic-assisted laparoscopic radical prostatectomy, across 3 high-volume institutions. De-identifiable clinicopathological and histopathological data were prospectively collected for 4,001 patients with at least 3 years of follow-up. Kaplan-Meier plots and 3 statistical models were used to evaluate the effect of margin parameters on BCR, via crude rates, traditional multivariable Cox regression, and a propensity-adjusted Cox regression model. Overall, 37% of men with a PSM developed BCR compared with 10% of men with negative margins (hazard ratio [HR] = 1.81, 95% CI: 1.47-2.22). Length ≥3mm or a multifocal positive margin was associated with a higher risk of BCR compared with negative margin cases. On multivariable Cox regression analysis of the positive margin cohort, only apical margins significantly predicted BCR relative to basal margins (HR = 2.03, 95% CI: 1.01-4.09), whereas there was no significant difference in BCR rates for posterolateral margins relative to basal margins (HR = 1.62, 95% CI: 0.84-3.11). Propensity-adjusted modeling confirmed a greater effect of apical compared with posterolateral PSM. A PSM length ≥3mm is predictive of BCR, as is to a lesser extent multiple positive margins. In contrast to open prostatectomy series, posterolateral margins carry a smaller risk of BCR compared with apical margins.
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