INTRODUCTION AND OBJECTIVE: Efforts to control postoperative opioid prescriptions (opioid-Rx) giv... more INTRODUCTION AND OBJECTIVE: Efforts to control postoperative opioid prescriptions (opioid-Rx) given after major urologic surgery have yielded mixed results. Since, even a transient exposure to opioids can increase the risk of opioid abuse, the goal should be to prescribe the fewest number of opioids without compromising pain control. We designed a prospective intervention study, No Opioids Prescriptions at Discharge After Surgery (NOPIODS study) to test the feasibility of eliminating opioid-Rx at discharge following major urologic surgery. METHODS: This study included 686 consecutive patients, who underwent open or robotic, prostatectomy, radical or partial nephrectomy and radical cystectomy from May 2017 to June 2021. The preintervention, control group, included patients receiving opioid-Rx at discharge at the prescriber's discretion (N[202). We implemented the opioid-Rx elimination protocol in 2 phases, 1. Lead-in phase (N[ 100): prescriber instructions to minimize opioid-Rx to 4 days, based on pain assessment at discharge; 2. NOPIOIDS phase (N[384): policy of no opioid-Rx unless necessary per patients' requirements. Patients in both phases received education on expected levels of pain and multimodal analgesia protocol. Patient satisfaction was assessed through surrogates including phone calls for pain and requirement for additional opioid-Rx within 30 days of discharge as confirmed by I-STOP (Prescription monitoring program). Categorical and continuous variables were compared using Chi-square and oneway ANOVA, as applicable. RESULTS: The proportion of patients discharged without any opioid-Rx in the control, lead-in and NOPIOIDS group was 19.1%, 42.1% and 97.8%, respectively. All patients receiving opioid-Rx in the NOPIODS group had renal surgery (partial or radical nephrectomy). The median (IQR) number of 5 mg-oxycodone equivalents prescribed per patient was 14 (10-20), 4 (0-5.3), and 0 (0-0), in control, lead-in, and NOPIOIDS group, respectively (p <0.001). Phone calls related to inadequate pain control were similar amongst the control, lead-in, and NOPIOIDS group at 4.1%, 2.1% and 3.1% (p[0.64), respectively. Patients requiring additional opioid-Rx within 30 days of discharge, were similar amongst the control, lead-in and NOPIOIDS group at 4.1%, 0% and 2.2% (p[0.10), respectively. CONCLUSIONS: This study highlights the feasibility of eliminating opioid-Rx after major urologic surgery without compromising analgesia. This intervention is easy to implement, does not require additional resources, and should be the new standard of care following major urologic surgery.
The implications of intubation timing in COVID-19 patients remain highly debatable due to the sca... more The implications of intubation timing in COVID-19 patients remain highly debatable due to the scarcity of available evidence. Our study aims to assess the clinical characteristics and outcomes of COVID-19 patients undergoing early intubation compared to those undergoing late intubation. This is a single-center retrospective study of adult COVID-19 patients admitted between March 1, 2020 and January 10, 2021. Early intubation was defined as intubation within 24 hours of a) hospital admission; b) respiratory status deterioration requiring FiO 2 60% and higher; or c) moderate/severe acute respiratory distress syndrome (ARDS) diagnosis. Among the 128 COVID-19 patients included, 66.4% required early intubation, and 33.6% required late intubation. The 28-day all-cause mortality and other outcomes of mechanical ventilation duration, hospital and ICU length of stay were equal regardless of intubation timing. Clinical characteristics, inflammatory markers, COVID-19 therapies, PaO 2 /FiO 2 ratio, and pH were comparable for both groups. Better lung compliance was observed during early intubation than late intubation based on plateau (mean 21.3 vs. 25.5 cmH 2 O; P < 0.01) and peak pressure (mean 24.1 vs. 27.4 cmH 2 O; P = 0.04). In critically ill COVID-19 patients, the timing of intubation was not significantly associated with poor clinical outcomes in the setting of matching clinical characteristics. More research is needed to determine which subset of patients may benefit from intubation and the predictors for optimal intubation timing.
Medical students need more exposure to and a greater understanding of their role in public health... more Medical students need more exposure to and a greater understanding of their role in public health throughout their training, which may influence more of them to pursue careers in public health or change how they practice medicine in the future. A novel colorectal cancer education session was created for first year medical students to attempt to increase public health interest, improve colorectal cancer knowledge and discuss barriers to colorectal cancer screening. We constructed a novel integrated interactive peer led colorectal cancer educational session of panelists with a wide range of experiences in colorectal cancer and colorectal cancer screening. The session involved a didactic component, case presentation, and group exercises followed by assembly discussion. We surveyed first-year medical students over two consecutive years to assess their interest in public health, knowledge of colorectal cancer, and perceptions of barriers to colorectal cancer screening before and after the educational session. We also evaluated student satisfaction with the session. We compared the pre-and post-survey results to assess for changes in interest, knowledge and perceptions. 74.63% of students in 2018 and 67.7% in 2019 evaluated the session as excellent or good, with knowledge regarding colorectal cancer screening markedly increased after the educational session. Students reported knowledge and access to healthcare among the biggest patient barriers to colorectal cancer screening. Interest in public health increased by 7.5% and 5.6% in 2018 and 2019, respectively. The implementation of this interactive educational peer led exercise can increase interest in public health, improve knowledge of colorectal cancer prevention and facilitate discussions of colorectal cancer screening barriers. We hope to encourage other programs to adopt this preliminary model.
INTRODUCTION: We studied the impact of pre-existing hypertension on the management of severe hype... more INTRODUCTION: We studied the impact of pre-existing hypertension on the management of severe hypertension in patients diagnosed with preeclampsia. METHODS: We analyzed 227 antepartum patients who developed severe blood pressures (systolic >=160 mmHg and/or diastolic >=110 mmHg) requiring IV labetalol over a 2-year period. Patients were grouped by diagnosis of chronic hypertension with superimposed preeclampsia with severe features (CHTN, n=82) versus preeclampsia with severe features (preE, n=142). Electronic records were reviewed for anthropomorphic data. Blood pressure was extracted every 15 minutes starting after the first dose of labetalol. We performed a repeated-measures analysis of variance for statistical modeling, controlling for patient-patient variance. RESULTS: The baseline systolic (SBP) and mean arterial pressure (MAP) did not differ significantly between CHTN and preE groups (SBP of 164 vs. 167 mmHg, p=0.2; MAP of 119 vs. 121 mmHg, p=0.2). ANOVA revealed a signi...
readmission reduction intervention (ERþ) was associated with significantly reduced hospital readm... more readmission reduction intervention (ERþ) was associated with significantly reduced hospital readmissions compared to traditional ER alone (ERþ 5.9%, traditional ER 20.3%, p[0.017). CONCLUSIONS: ER protocols consistently demonstrate reductions in LOS, and should be the standard of care following RC. In order to reduce hospital readmissions, the urologic community must expand beyond traditional ER pathways. We report significant reductions in hospital readmission among RC patients receiving a targeted post-discharge intervention beyond traditional ER alone.
Microglia are well known to play a critical role in maintaining brain homeostasis. However, their... more Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention.
The purpose of this study is to assess the efficacy and safety profile of AFPep, a 9-amino acid c... more The purpose of this study is to assess the efficacy and safety profile of AFPep, a 9-amino acid cyclic peptide prior to its entry into pre-clinical toxicology analyses en route to clinical trials. AFPep was assessed for anti-estrogenic activity in a mouse uterine growth assay and for breast cancer therapeutic efficacy in a human tumor xenograft model in mice. AFPep was assessed for tolerability in a variety of in vivo models, notably including assessment for effects on rat liver and human hepatocellular carcinoma cell lines and xenografts. AFPep arrests the growth of human MCF-7 breast cancer xenografts, inhibits the estrogen-induced growth of mouse uteri, and does not affect liver growth nor stimulate growth of human hepatocellular carcinoma cell lines when growing in vitro or as xenografts in vivo. AFPep is well tolerated in mice, rats, dogs, and primates. AFPep is effective for the treatment of ER-positive breast cancer and exhibits a therapeutic index that is substantially wider...
Neuromodulation: Technology at the Neural Interface, 2017
Background: Subthalamic nucleus deep brain stimulation (STN DBS) is an established treatment in P... more Background: Subthalamic nucleus deep brain stimulation (STN DBS) is an established treatment in Parkinson's disease (PD). We investigate the effect of eye opening on neuronal activity and local field potentials (LFPs) in the STN. Methods: We prospectively enrolled 25 PD patients undergoing STN DBS in our institution. During DBS, single-unit activity (SUA) and LFPs were measured when eyes were open and closed. As movement is known to result in changes in LFPs, we tested response to eye opening in the presence and absence of movement. Results: Neither eye state nor arm movement has a significant influence on SUA recordings. There is a statistically significant interaction between eye state and arm movement (p < 0.05). In the presence of movement, STN SUA increase when eyes open (p < 0.05). When eyes are closed, STN SUA decrease with movement (p < 0.05). STN theta LFP oscillations decrease when eyes are open compared to closed, irrespective of movement status (p < 0.05). Discussion: STN activity is influenced by eye state and arm movement. It is unclear whether this is attributed to a change in the STN's role in oculomotor control or from a change in attentional state. Understanding how physiologic normal activity alters neural activity is critical for the optimization of DBS therapy, particularly in closed-loop neuromodulation.
Journal of Cardiothoracic and Vascular Anesthesia, 2017
This author helped statistical analysis of the collected data and helped writing the results sect... more This author helped statistical analysis of the collected data and helped writing the results section of the manuscript.
Although early Sacral Neuromodulation (SNM) trials excluded patients with neurologic lower urinar... more Although early Sacral Neuromodulation (SNM) trials excluded patients with neurologic lower urinary tract dysfunction (NLUTD), an increasing number of small studies show outcomes in these patients are similar to those without NLUTD. The use of SNM in NLUTD remains off label. The aim of this study was to compare SNM in patients with NLUTD to those without NLUTD and determine clinical factors associated with successful utilization of SNM. METHODS: A retrospective review of patients who underwent SNM between 2011 and 2015 was completed. Patients with a neurologic diagnosis in the electronic chart were identified and placed in the NLUTD cohort. Demographic and clinical characteristics of the NLUTD and non-NLUTD cohort were identified. Rates of progression to stage 2, revision and explant were analyzed. The data were examined using Pearson's chi-square and Fisher exact tests as appropriate. RESULTS: Out of 412 patients, 80 (19.4%) had NLUTD at time of SNM with a mean age was 54 AE17 years. 75% of the NLUTD group was female (N¼60). The neurogenic diagnoses were: spinal cord injury 28.8% (N¼23), multiple sclerosis 23.8% (N¼19), Stroke 15% (N¼12), cerebral palsy12.5% (N¼10), peripheral nervous system disorders 12.5% (N¼10) and Parkinson's disease 7.5% (N¼6). The primary indication for SNM was urgency incontinence in 62.5% of the NLUTD group (N¼50) and 59.5% in the non-NLUTD group (N¼197). Progression to stage 2 SNM was similar in both groups, 90% in NLUTD versus 87% in non-NLUTD. Revision rates were higher in the NLUTD cohort compared to non-NLTUD, 46% versus 35%, but this trend did not reach statistical significance (p¼0.09). There was a statistically significant higher explant rate in the NLUTD group, 33% vs 20% (p¼0.0194) and the most common reason for explant in both groups was loss of efficacy. Progression to stage 2, revision rates, and explant rates for each type of neurologic diagnosis did not have any statistically significant difference. CONCLUSIONS: The primary indication for SNM in both NLUTD and non-NLUTD was urgency incontinence. The specific neurologic diagnosis is not predictive of SNM success, revision, or explants rates. However, patients with NLUTD appear more likely to need the device explanted when compared to patients with non-NLUTD.
To determine the relative concentrations of enclomiphene (ENC) and zuclomiphene (ZUC) isomers in ... more To determine the relative concentrations of enclomiphene (ENC) and zuclomiphene (ZUC) isomers in hypogonadal men (HM) on long-term clomiphene citrate (CC) therapy. To determine whether patient age, body mass index, or duration of therapy were predictive of relative concentrations of ENC and ZUC. Men already on CC 25 mg daily therapy for secondary hypogonadism for a minimum of six weeks were recruited to have their ENC and ZUC levels assessed. Total testosterone (T), free testosterone, estradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH) prior to initiation of and while on CC therapy were recorded for all patients. Patient demographics including age, body mass index, and medical comorbidites were recorded. Serum samples were obtained at the time of enrollment to determine ENC and ZUC concentrations. A total of 15 men were enrolled from June 2015 to August 2015. Median patient age was 36 (range 22-70) years, median body mass index 32.0 (range 21.1-40.3)kg/m 2 , and median duration of treatment 25.9 (range 1.7-86.6) months. Baseline median total T, estradiol, and LH were 205.0 ng/dL, 17.0 pg/mL, and 4.0 mlU/mL, respectively. Post-treatment median total T, estradiol, and LH increased to 488.0 ng/dL 34.0 pg/mL, and 6.1 mIU/mL, respectively (all p<0.001). Median ENC and ZUC concentrations were 2.2 and 44.0 ng/mL, respectively. After at least six weeks of CC therapy median ZUC: ENC serum concentration ratio was 21.3. On linear regression analysis patient age, body mass index, duration of treatment and serum T levels were not predictive of ENC or ZUC concentrations. Long-term CC therapy resulted in a significant alteration of ENC and ZUC concentrations, with ZUC as the predominant isomer. Given the vastly different biochemical and toxicological properties of ENC and ZUC, this study supports the need for development of a pure selective estrogen receptor antagonist for the treatment of HM.
RESULTS: Of 589 men who underwent RP, 334 subjects reported use of at least one erectile aid at 2... more RESULTS: Of 589 men who underwent RP, 334 subjects reported use of at least one erectile aid at 2 years. Frequency of use, and effectiveness of erectile aids, is summarized in Table . Factors associated with responsiveness to ED treatment included age, number of comorbidities, baseline PSA, prostate volume, and D'Amico risk stratification. Effectiveness of oral PDE5i was the best predictor of erection quality, defined as erection firm enough for penetration, and sexual satisfaction two years after RP. Of the 140 men in whom PDE5i were ineffective, 35, 39, and 39 subjects tried IA, ICI, and/or VED, respectively; there was no significant difference in the effectiveness of these three aids in this subset of men. Only 4/140 subjects reported achieving an erection firm enough for penetration using these three aids. CONCLUSIONS: Almost all men seeking treatment for ED try PDE5i following surgery. Over 50% of these men report effectiveness of PDE5i 2 years following RP. In cases where PDE5i are ineffective, IA, ICI, and VED may be used for treatment of ED, but erection quality remains poor despite the use of these erectile aids.
Using middle cerebral artery occlusion in the cat as a model of focal cerebral ischemia, we inves... more Using middle cerebral artery occlusion in the cat as a model of focal cerebral ischemia, we investigated the effect of naloxone on both neurologic deficit and regional cortical blood flow during cerebral ischemia. In all animals with major strokes, 2 mg/ml naloxone administered intravenously produced a dramatic reversal of neurologic symptoms four hours after the ischemic lesion. Animals were then anesthetized and cortical blood flow was measured by the hydrogen clearance method. Blood flow in the ischemic cortex was noted to be approximately 55% that of the control side. Naloxone produced a significant decrease of approximately 20% in cortical blood flow in the ischemic hemisphere while no effect on blood flow on the control side was noted. Thus, naloxone appears to reverse the neurologic deficits following middle cerebral artery occlusion in the cat.
While medication trials frequently involve a placebo arm to more fairly assess efficacy of the st... more While medication trials frequently involve a placebo arm to more fairly assess efficacy of the study drug, benign prostatic hyperplasia (BPH) surgery trials rarely include a sham surgery group due to the inherent risks associated with simulating treatment in these patients. Resultantly, the placebo response to a sham surgery for BPH is largely unknown. A systematic review of available literature was undertaken looking for randomized controlled trials (RCTs) involving endoscopic or intraprostatic injection BPH treatments that included a sham surgical arm from January 1990 to February 2015. Studies that included an objective symptom questionnaire and maximum urinary flow (Qmax) at 3 months were included. Results were analyzed together with weighting based on study sample size. Initial search yielded a total of 1998 potential studies. After review of abstracts and full text articles, a total of 14 RCTs were included in some part. An average decrease from 22.3 to 16.7 (-27%) was seen in...
Training programs must ensure residents are competent to practice independently. For surgical fie... more Training programs must ensure residents are competent to practice independently. For surgical fields, this is generally done by the faculty who graduate the residents, but there has been no accepted methodology for this process. As part of a generalized survey, attending physicians performing an operation were asked to assess resident competency to perform the operation independently in an average patient, using a single global question. Residents, in a blinded manner, were asked to answer the same question. Urology Residency Program, Albany Medical College, Albany, NY. Participants included 12 resident physicians and 10 attending physicians. There is a large variation in attending physician assessment of resident surgical competency, and the assessment varies by attending physician and by resident. Generally, attending physicians rated residents lower than the residents rated themselves. The discrepancy was largest for residents early in training and lessened as resident experience...
INTRODUCTION AND OBJECTIVE: Efforts to control postoperative opioid prescriptions (opioid-Rx) giv... more INTRODUCTION AND OBJECTIVE: Efforts to control postoperative opioid prescriptions (opioid-Rx) given after major urologic surgery have yielded mixed results. Since, even a transient exposure to opioids can increase the risk of opioid abuse, the goal should be to prescribe the fewest number of opioids without compromising pain control. We designed a prospective intervention study, No Opioids Prescriptions at Discharge After Surgery (NOPIODS study) to test the feasibility of eliminating opioid-Rx at discharge following major urologic surgery. METHODS: This study included 686 consecutive patients, who underwent open or robotic, prostatectomy, radical or partial nephrectomy and radical cystectomy from May 2017 to June 2021. The preintervention, control group, included patients receiving opioid-Rx at discharge at the prescriber's discretion (N[202). We implemented the opioid-Rx elimination protocol in 2 phases, 1. Lead-in phase (N[ 100): prescriber instructions to minimize opioid-Rx to 4 days, based on pain assessment at discharge; 2. NOPIOIDS phase (N[384): policy of no opioid-Rx unless necessary per patients' requirements. Patients in both phases received education on expected levels of pain and multimodal analgesia protocol. Patient satisfaction was assessed through surrogates including phone calls for pain and requirement for additional opioid-Rx within 30 days of discharge as confirmed by I-STOP (Prescription monitoring program). Categorical and continuous variables were compared using Chi-square and oneway ANOVA, as applicable. RESULTS: The proportion of patients discharged without any opioid-Rx in the control, lead-in and NOPIOIDS group was 19.1%, 42.1% and 97.8%, respectively. All patients receiving opioid-Rx in the NOPIODS group had renal surgery (partial or radical nephrectomy). The median (IQR) number of 5 mg-oxycodone equivalents prescribed per patient was 14 (10-20), 4 (0-5.3), and 0 (0-0), in control, lead-in, and NOPIOIDS group, respectively (p <0.001). Phone calls related to inadequate pain control were similar amongst the control, lead-in, and NOPIOIDS group at 4.1%, 2.1% and 3.1% (p[0.64), respectively. Patients requiring additional opioid-Rx within 30 days of discharge, were similar amongst the control, lead-in and NOPIOIDS group at 4.1%, 0% and 2.2% (p[0.10), respectively. CONCLUSIONS: This study highlights the feasibility of eliminating opioid-Rx after major urologic surgery without compromising analgesia. This intervention is easy to implement, does not require additional resources, and should be the new standard of care following major urologic surgery.
The implications of intubation timing in COVID-19 patients remain highly debatable due to the sca... more The implications of intubation timing in COVID-19 patients remain highly debatable due to the scarcity of available evidence. Our study aims to assess the clinical characteristics and outcomes of COVID-19 patients undergoing early intubation compared to those undergoing late intubation. This is a single-center retrospective study of adult COVID-19 patients admitted between March 1, 2020 and January 10, 2021. Early intubation was defined as intubation within 24 hours of a) hospital admission; b) respiratory status deterioration requiring FiO 2 60% and higher; or c) moderate/severe acute respiratory distress syndrome (ARDS) diagnosis. Among the 128 COVID-19 patients included, 66.4% required early intubation, and 33.6% required late intubation. The 28-day all-cause mortality and other outcomes of mechanical ventilation duration, hospital and ICU length of stay were equal regardless of intubation timing. Clinical characteristics, inflammatory markers, COVID-19 therapies, PaO 2 /FiO 2 ratio, and pH were comparable for both groups. Better lung compliance was observed during early intubation than late intubation based on plateau (mean 21.3 vs. 25.5 cmH 2 O; P < 0.01) and peak pressure (mean 24.1 vs. 27.4 cmH 2 O; P = 0.04). In critically ill COVID-19 patients, the timing of intubation was not significantly associated with poor clinical outcomes in the setting of matching clinical characteristics. More research is needed to determine which subset of patients may benefit from intubation and the predictors for optimal intubation timing.
Medical students need more exposure to and a greater understanding of their role in public health... more Medical students need more exposure to and a greater understanding of their role in public health throughout their training, which may influence more of them to pursue careers in public health or change how they practice medicine in the future. A novel colorectal cancer education session was created for first year medical students to attempt to increase public health interest, improve colorectal cancer knowledge and discuss barriers to colorectal cancer screening. We constructed a novel integrated interactive peer led colorectal cancer educational session of panelists with a wide range of experiences in colorectal cancer and colorectal cancer screening. The session involved a didactic component, case presentation, and group exercises followed by assembly discussion. We surveyed first-year medical students over two consecutive years to assess their interest in public health, knowledge of colorectal cancer, and perceptions of barriers to colorectal cancer screening before and after the educational session. We also evaluated student satisfaction with the session. We compared the pre-and post-survey results to assess for changes in interest, knowledge and perceptions. 74.63% of students in 2018 and 67.7% in 2019 evaluated the session as excellent or good, with knowledge regarding colorectal cancer screening markedly increased after the educational session. Students reported knowledge and access to healthcare among the biggest patient barriers to colorectal cancer screening. Interest in public health increased by 7.5% and 5.6% in 2018 and 2019, respectively. The implementation of this interactive educational peer led exercise can increase interest in public health, improve knowledge of colorectal cancer prevention and facilitate discussions of colorectal cancer screening barriers. We hope to encourage other programs to adopt this preliminary model.
INTRODUCTION: We studied the impact of pre-existing hypertension on the management of severe hype... more INTRODUCTION: We studied the impact of pre-existing hypertension on the management of severe hypertension in patients diagnosed with preeclampsia. METHODS: We analyzed 227 antepartum patients who developed severe blood pressures (systolic >=160 mmHg and/or diastolic >=110 mmHg) requiring IV labetalol over a 2-year period. Patients were grouped by diagnosis of chronic hypertension with superimposed preeclampsia with severe features (CHTN, n=82) versus preeclampsia with severe features (preE, n=142). Electronic records were reviewed for anthropomorphic data. Blood pressure was extracted every 15 minutes starting after the first dose of labetalol. We performed a repeated-measures analysis of variance for statistical modeling, controlling for patient-patient variance. RESULTS: The baseline systolic (SBP) and mean arterial pressure (MAP) did not differ significantly between CHTN and preE groups (SBP of 164 vs. 167 mmHg, p=0.2; MAP of 119 vs. 121 mmHg, p=0.2). ANOVA revealed a signi...
readmission reduction intervention (ERþ) was associated with significantly reduced hospital readm... more readmission reduction intervention (ERþ) was associated with significantly reduced hospital readmissions compared to traditional ER alone (ERþ 5.9%, traditional ER 20.3%, p[0.017). CONCLUSIONS: ER protocols consistently demonstrate reductions in LOS, and should be the standard of care following RC. In order to reduce hospital readmissions, the urologic community must expand beyond traditional ER pathways. We report significant reductions in hospital readmission among RC patients receiving a targeted post-discharge intervention beyond traditional ER alone.
Microglia are well known to play a critical role in maintaining brain homeostasis. However, their... more Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention.
The purpose of this study is to assess the efficacy and safety profile of AFPep, a 9-amino acid c... more The purpose of this study is to assess the efficacy and safety profile of AFPep, a 9-amino acid cyclic peptide prior to its entry into pre-clinical toxicology analyses en route to clinical trials. AFPep was assessed for anti-estrogenic activity in a mouse uterine growth assay and for breast cancer therapeutic efficacy in a human tumor xenograft model in mice. AFPep was assessed for tolerability in a variety of in vivo models, notably including assessment for effects on rat liver and human hepatocellular carcinoma cell lines and xenografts. AFPep arrests the growth of human MCF-7 breast cancer xenografts, inhibits the estrogen-induced growth of mouse uteri, and does not affect liver growth nor stimulate growth of human hepatocellular carcinoma cell lines when growing in vitro or as xenografts in vivo. AFPep is well tolerated in mice, rats, dogs, and primates. AFPep is effective for the treatment of ER-positive breast cancer and exhibits a therapeutic index that is substantially wider...
Neuromodulation: Technology at the Neural Interface, 2017
Background: Subthalamic nucleus deep brain stimulation (STN DBS) is an established treatment in P... more Background: Subthalamic nucleus deep brain stimulation (STN DBS) is an established treatment in Parkinson's disease (PD). We investigate the effect of eye opening on neuronal activity and local field potentials (LFPs) in the STN. Methods: We prospectively enrolled 25 PD patients undergoing STN DBS in our institution. During DBS, single-unit activity (SUA) and LFPs were measured when eyes were open and closed. As movement is known to result in changes in LFPs, we tested response to eye opening in the presence and absence of movement. Results: Neither eye state nor arm movement has a significant influence on SUA recordings. There is a statistically significant interaction between eye state and arm movement (p < 0.05). In the presence of movement, STN SUA increase when eyes open (p < 0.05). When eyes are closed, STN SUA decrease with movement (p < 0.05). STN theta LFP oscillations decrease when eyes are open compared to closed, irrespective of movement status (p < 0.05). Discussion: STN activity is influenced by eye state and arm movement. It is unclear whether this is attributed to a change in the STN's role in oculomotor control or from a change in attentional state. Understanding how physiologic normal activity alters neural activity is critical for the optimization of DBS therapy, particularly in closed-loop neuromodulation.
Journal of Cardiothoracic and Vascular Anesthesia, 2017
This author helped statistical analysis of the collected data and helped writing the results sect... more This author helped statistical analysis of the collected data and helped writing the results section of the manuscript.
Although early Sacral Neuromodulation (SNM) trials excluded patients with neurologic lower urinar... more Although early Sacral Neuromodulation (SNM) trials excluded patients with neurologic lower urinary tract dysfunction (NLUTD), an increasing number of small studies show outcomes in these patients are similar to those without NLUTD. The use of SNM in NLUTD remains off label. The aim of this study was to compare SNM in patients with NLUTD to those without NLUTD and determine clinical factors associated with successful utilization of SNM. METHODS: A retrospective review of patients who underwent SNM between 2011 and 2015 was completed. Patients with a neurologic diagnosis in the electronic chart were identified and placed in the NLUTD cohort. Demographic and clinical characteristics of the NLUTD and non-NLUTD cohort were identified. Rates of progression to stage 2, revision and explant were analyzed. The data were examined using Pearson's chi-square and Fisher exact tests as appropriate. RESULTS: Out of 412 patients, 80 (19.4%) had NLUTD at time of SNM with a mean age was 54 AE17 years. 75% of the NLUTD group was female (N¼60). The neurogenic diagnoses were: spinal cord injury 28.8% (N¼23), multiple sclerosis 23.8% (N¼19), Stroke 15% (N¼12), cerebral palsy12.5% (N¼10), peripheral nervous system disorders 12.5% (N¼10) and Parkinson's disease 7.5% (N¼6). The primary indication for SNM was urgency incontinence in 62.5% of the NLUTD group (N¼50) and 59.5% in the non-NLUTD group (N¼197). Progression to stage 2 SNM was similar in both groups, 90% in NLUTD versus 87% in non-NLUTD. Revision rates were higher in the NLUTD cohort compared to non-NLTUD, 46% versus 35%, but this trend did not reach statistical significance (p¼0.09). There was a statistically significant higher explant rate in the NLUTD group, 33% vs 20% (p¼0.0194) and the most common reason for explant in both groups was loss of efficacy. Progression to stage 2, revision rates, and explant rates for each type of neurologic diagnosis did not have any statistically significant difference. CONCLUSIONS: The primary indication for SNM in both NLUTD and non-NLUTD was urgency incontinence. The specific neurologic diagnosis is not predictive of SNM success, revision, or explants rates. However, patients with NLUTD appear more likely to need the device explanted when compared to patients with non-NLUTD.
To determine the relative concentrations of enclomiphene (ENC) and zuclomiphene (ZUC) isomers in ... more To determine the relative concentrations of enclomiphene (ENC) and zuclomiphene (ZUC) isomers in hypogonadal men (HM) on long-term clomiphene citrate (CC) therapy. To determine whether patient age, body mass index, or duration of therapy were predictive of relative concentrations of ENC and ZUC. Men already on CC 25 mg daily therapy for secondary hypogonadism for a minimum of six weeks were recruited to have their ENC and ZUC levels assessed. Total testosterone (T), free testosterone, estradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH) prior to initiation of and while on CC therapy were recorded for all patients. Patient demographics including age, body mass index, and medical comorbidites were recorded. Serum samples were obtained at the time of enrollment to determine ENC and ZUC concentrations. A total of 15 men were enrolled from June 2015 to August 2015. Median patient age was 36 (range 22-70) years, median body mass index 32.0 (range 21.1-40.3)kg/m 2 , and median duration of treatment 25.9 (range 1.7-86.6) months. Baseline median total T, estradiol, and LH were 205.0 ng/dL, 17.0 pg/mL, and 4.0 mlU/mL, respectively. Post-treatment median total T, estradiol, and LH increased to 488.0 ng/dL 34.0 pg/mL, and 6.1 mIU/mL, respectively (all p<0.001). Median ENC and ZUC concentrations were 2.2 and 44.0 ng/mL, respectively. After at least six weeks of CC therapy median ZUC: ENC serum concentration ratio was 21.3. On linear regression analysis patient age, body mass index, duration of treatment and serum T levels were not predictive of ENC or ZUC concentrations. Long-term CC therapy resulted in a significant alteration of ENC and ZUC concentrations, with ZUC as the predominant isomer. Given the vastly different biochemical and toxicological properties of ENC and ZUC, this study supports the need for development of a pure selective estrogen receptor antagonist for the treatment of HM.
RESULTS: Of 589 men who underwent RP, 334 subjects reported use of at least one erectile aid at 2... more RESULTS: Of 589 men who underwent RP, 334 subjects reported use of at least one erectile aid at 2 years. Frequency of use, and effectiveness of erectile aids, is summarized in Table . Factors associated with responsiveness to ED treatment included age, number of comorbidities, baseline PSA, prostate volume, and D'Amico risk stratification. Effectiveness of oral PDE5i was the best predictor of erection quality, defined as erection firm enough for penetration, and sexual satisfaction two years after RP. Of the 140 men in whom PDE5i were ineffective, 35, 39, and 39 subjects tried IA, ICI, and/or VED, respectively; there was no significant difference in the effectiveness of these three aids in this subset of men. Only 4/140 subjects reported achieving an erection firm enough for penetration using these three aids. CONCLUSIONS: Almost all men seeking treatment for ED try PDE5i following surgery. Over 50% of these men report effectiveness of PDE5i 2 years following RP. In cases where PDE5i are ineffective, IA, ICI, and VED may be used for treatment of ED, but erection quality remains poor despite the use of these erectile aids.
Using middle cerebral artery occlusion in the cat as a model of focal cerebral ischemia, we inves... more Using middle cerebral artery occlusion in the cat as a model of focal cerebral ischemia, we investigated the effect of naloxone on both neurologic deficit and regional cortical blood flow during cerebral ischemia. In all animals with major strokes, 2 mg/ml naloxone administered intravenously produced a dramatic reversal of neurologic symptoms four hours after the ischemic lesion. Animals were then anesthetized and cortical blood flow was measured by the hydrogen clearance method. Blood flow in the ischemic cortex was noted to be approximately 55% that of the control side. Naloxone produced a significant decrease of approximately 20% in cortical blood flow in the ischemic hemisphere while no effect on blood flow on the control side was noted. Thus, naloxone appears to reverse the neurologic deficits following middle cerebral artery occlusion in the cat.
While medication trials frequently involve a placebo arm to more fairly assess efficacy of the st... more While medication trials frequently involve a placebo arm to more fairly assess efficacy of the study drug, benign prostatic hyperplasia (BPH) surgery trials rarely include a sham surgery group due to the inherent risks associated with simulating treatment in these patients. Resultantly, the placebo response to a sham surgery for BPH is largely unknown. A systematic review of available literature was undertaken looking for randomized controlled trials (RCTs) involving endoscopic or intraprostatic injection BPH treatments that included a sham surgical arm from January 1990 to February 2015. Studies that included an objective symptom questionnaire and maximum urinary flow (Qmax) at 3 months were included. Results were analyzed together with weighting based on study sample size. Initial search yielded a total of 1998 potential studies. After review of abstracts and full text articles, a total of 14 RCTs were included in some part. An average decrease from 22.3 to 16.7 (-27%) was seen in...
Training programs must ensure residents are competent to practice independently. For surgical fie... more Training programs must ensure residents are competent to practice independently. For surgical fields, this is generally done by the faculty who graduate the residents, but there has been no accepted methodology for this process. As part of a generalized survey, attending physicians performing an operation were asked to assess resident competency to perform the operation independently in an average patient, using a single global question. Residents, in a blinded manner, were asked to answer the same question. Urology Residency Program, Albany Medical College, Albany, NY. Participants included 12 resident physicians and 10 attending physicians. There is a large variation in attending physician assessment of resident surgical competency, and the assessment varies by attending physician and by resident. Generally, attending physicians rated residents lower than the residents rated themselves. The discrepancy was largest for residents early in training and lessened as resident experience...
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