Evaluation of the Current Status of Artificial Intelligence for Endourology Patient Education: A Blind Comparison of ChatGPT and Google Bard Against Traditional Information Resources.

Introduction: Artificial intelligence (AI) platforms such as ChatGPT and Bard are increasingly utilized to answer patient health care questions. We present the first study to blindly evaluate AI-generated responses to common endourology patient questions against official patient education materials. Methods: Thirty-two questions and answers spanning kidney stones, ureteral stents, benign prostatic hyperplasia (BPH), and upper tract urothelial carcinoma were extracted from official Urology Care Foundation (UCF) patient education documents. The same questions were input into ChatGPT 4.0 and Bard, limiting responses to within ±10% of the word count of the corresponding UCF response to ensure fair comparison. Six endourologists blindly evaluated responses from each platform using Likert scales for accuracy, clarity, comprehensiveness, and patient utility. Reviewers identified which response they believed was not AI generated. Finally, Flesch-Kincaid Reading Grade Level formulas assessed the readability of each platform response. Ratings were compared using analysis of variance (ANOVA) and chi-square tests. Results: ChatGPT responses were rated the highest across all categories, including accuracy, comprehensiveness, clarity, and patient utility, while UCF answers were consistently scored the lowest, all p < 0.01. A subanalysis revealed that this trend was consistent across question categories (i.e., kidney stones, BPH, etc.). However, AI-generated responses were more likely to be classified at an advanced reading level, while UCF responses showed improved readability (college or higher reading level: ChatGPT = 100%, Bard = 66%, and UCF = 19%), p < 0.001. When asked to identify which answer was not AI generated, 54.2% of responses indicated ChatGPT, 26.6% indicated Bard, and only 19.3% correctly identified it as the UCF response. Conclusions: In a blind evaluation, AI-generated responses from ChatGPT and Bard surpassed the quality of official patient education materials in endourology, suggesting that current AI platforms are already a reliable resource for basic urologic care information. AI-generated responses do, however, tend to require a higher reading level, which may limit their applicability to a broader audience.

Transurethral Resection of Bladder Tumor Outcomes Are Predicted by a 5-Item Frailty Index.

OBJECTIVE: To evaluate the mFI-5 as a predictor of postoperative outcomes following transurethral resection of bladder tumor (TURBT). METHODS: The National Surgical Quality Improvement Program database was queried for TURBT cases from 2015-2019. mFI-5 scores were calculated by assigning a point to chronic obstructive pulmonary disease, congestive heart failure, dependent functional status, hypertension, and diabetes. Patients were stratified by mFI-5 scores. Demographics and 30-day outcomes including Clavien-Dindo (CD) complications, mortality, and increased healthcare resource utilization (HCRU) were compared. HCRU outcomes included prolonged length of stay, unplanned readmission, and discharge to continued care. Multivariate regression assessed the predictive value of mFI-5 scores on outcomes. RESULTS: 40,278 TURBT cases were identified (mFI-5 =0: 12,400, mFI-5 =1: 17,328, mFI-5 =2: 9225, mFI-5 ≥3: 1416). Patients with higher mFI-5 scores were more likely to be older, male, White, and have larger tumors, all P < .05. Increasing mFI-5 scores resulted in increased frequency of all adverse outcomes, all P < .001. On multivariate analysis, mFI-5 ≥ 3 classification was a predictor of CD I/II (OR=1.280), CD IV (OR=2.539), mortality (OR=2.202), HCRU (OR=2.094), prolonged length of stay (OR=2.136), discharge to continued care (OR=3.401), and unplanned readmission (OR=1.705), all P < .05. A mFI-5 ≥ 3 demonstrated a sensitivity ranging from 6.0%-13.5% and a specificity ranging from 96.6%-97.0% for all outcomes. CONCLUSION: The mFI-5 is an easily ascertainable preoperative risk assessment tool that is a predictor of adverse clinical and HCRU outcomes following TURBT.

Comparison of metabolic parameters between pure-uric acid and mixed-uric acid kidney stone formers.

PURPOSE: We seek to compare clinical and 24-h urine parameters between pure-uric acid (UA) and UA-CaOx stone formers in our practice and explore how any differences in metabolic profiles could suggest different prevention strategies between the two groups. METHODS: We retrospectively reviewed patients with either pure- or mixed-UA nephrolithiasis from 2020 to 2023 at a tertiary care center. We included patients with a 24-h urine collection and a stone analysis detecting any amount of UA. Patients were organized into two cohorts: (1) those with 100% UA stones and (2) < 100% UA stones. Differences in demographic characteristics were compared between pure-UA and UA-CaOx stone formers. Twenty-four hour urine metabolic parameters as well as metabolic abnormalities were compared between the pure-uric acid and mixed-uric acid groups. RESULTS: We identified 33 pure-UA patients and 33 mixed-UA patients. Patient demographics were similar between the groups (Table 1). Pure- and mixed-UA patients had a similar incidence of metabolic syndrome, diabetes, history of stones, and stone burden. Table 1 Demographic and baseline characteristics among pure- and mixed-uric acid stone formers Pure-uric acid stones (n = 33) Mixed-uric acid stones (n = 33) p-value Median age [IQR] 63.00 [58.00-72.50] 63.00 [53.50-68.00] 0.339 Median BMI [IQR] 28.79 [25.81-33.07] 27.96 [25.81-29.55] 0.534 Gender, n (%) 1.000  Male 21 (63.6) 21 (63.6)  Female 12 (36.4) 12 (36.4) Metabolic syndrome, n (%) 17 (51.5) 16 (48.5) 0.806 Diabetes, n (%) 13 (39.4) 12 (36.4) 0.800 History of stones, n (%) 23 (69.7) 22 (66.7) 0.792 Median total stone burden, mm [IQR] 12.00 [6.00-26.50] 13.00 [7.05-20.00] 0.995 Median serum uric acid, mg/dL [IQR] 6.20 [4.80-7.15] 5.90 [4.98-6.89] 0.582 IQR Interquartile range BMI Body Mass Index n number We found the pure-UA cohort to have 24-h lower urine volume (1.53 vs. 1.96 L/day, p = 0.045) and citrate levels (286 vs. 457 mg/day, p = 0.036). UA-CaOx stone formers had higher urinary calcium levels (144 vs. 68 mg/day, p = 0.003), higher urinary oxalate levels (38 vs. 30 mg/day, p = 0.017), and higher median urinary calcium oxalate super-saturation (3.97 vs. 3.06, p = 0.047). CONCLUSIONS: Pure-UA kidney stone formers have different urinary metabolic parameters when compared with UA-CaOx stone formers, thus requiring different and tailored medical management.

Differences in cancer presentation, treatment, and mortality between rural and urban patients diagnosed with kidney cancer in the United States.

INTRODUCTION: Rural-urban discrepancies in care and outcomes for kidney cancer (KCa) in the United States remains poorly understood. Our study aims to improve our understanding of the influence of rurality on KCa outcomes in the United States by analyzing differences in presentation, treatment, and mortality between urban areas (UAs) and rural areas (RAs) in the Surveillance, Epidemiology, and End Results (SEERs) database. METHODS: SEERs data was queried from 2000 to 2019 for KCa patients. Patient counties were classified as UAs, rural adjacent areas (RAAs), or rural nonadjacent areas (RNAs) using Rural Urban Continuum Codes. Demographic, tumor characteristics, and treatment variables were compared. Propensity score matching was performed to create matched UA-RAA and UA-RNA cohorts. Multivariate regression evaluated rural-urban status as a predictor of treatment selection. Multivariate cox regression assessed the predictive value of rural-urban status for overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analysis was used to generate survival curves for OS and CSS. RESULTS: 179,509 KCa patients were identified (UA = 87.0%, RAA = 7.7%, RNA = 5.3%). Patients in RAs were more likely to present with tumors of higher grade and stage than UAs. Following multivariate analysis, rural residency predicted undergoing nephrectomy (RAA: OR = 1.177, RNA: OR = 1.210) but was a negative predictor of receiving partial nephrectomy (RAA: OR = 0.744, RNA: OR = 0.717), all P < 0.001. Multivariate cox regression demonstrated that RAA or RNA residency was predictive of overall and cause-specific mortality. After matching, median OS was 151, 124, and 118 months for UA, RAA, and RNA cohorts respectively; mean CSS was 152, 147, and 144 months for UA, RAA, and RNA cohorts, respectively, all P < 0.001. Stage-specific analysis of CSS demonstrated significantly poorer CSS among RNA patients for localized, regionalized, and distant KCa after matching. Only RAA patients with localized KCa experienced significantly lower CSS than UA patients. CONCLUSIONS: Patients in RAs are more likely to present with advanced KCa at diagnosis compared to those in UAs and may also experience different treatment options including a lesser likelihood of undergoing partial nephrectomy. Rural patients with KCa also demonstrated significantly worse OS and CSS compared to their urban counterparts. Further patient-level studies are required to better understand the discrepancy in CSS between urban and rural patients diagnosed with KCa.

Open retropubic prostatectomy in a patient with bladder exstrophy for management of hematuria and urethral discharge - A case report.

Bladder exstrophy (BE) is a rare congenital disorder causing bladder and urethral malformation due to an abdominal wall embryological defect. Traditionally, BE had a poor life expectancy, but advances now offer a normal lifespan. A 57-year-old male with BE history and ureterosigmoidostomy repair presented with intractable hematuria, urethral discharge, and recurrent prostatic infections. He underwent retropubic subtotal prostatectomy without major complications, resolving urinary symptoms. Advances in BE management extend patient lifespans. This case demonstrates successful surgical management of hematuria and urethral discharge through radical prostatectomy in an adult with a history of BE.

Adjuvant intraluminal therapies for upper tract urothelial carcinoma.

Upper urinary tract urothelial carcinomas (UTUCs) are often identified and first treated endoscopically. After proper risk stratification, adjuvant treatment may be recommended. Consequently, as adjuvant therapy becomes more common place in the oncological armamentarium, we seek to better characterize its existing and future therapeutic landscape. In this article, we present an overview of the most up-to-date information about intracavitary instillations as an adjuvant therapy in the context of UTUC. We reviewed the current literature on the epidemiology, disease characteristics, treatment, and outcomes of UTUC with a particularly focus on intraluminal adjuvant therapy for UTUC. This review provides a comprehensive overview of the most recent available data regarding adjuvant therapies used for UTUC. Intraluminal therapy plays an increasingly important role in the management of UTUC. Mitomycin C is the most common adjuvant treatment for UTUC with bacillus Calmette-Guerin (BCG) being utilized to a lesser extent. UGN-101 is a novel topical gel-based therapy that has shown promising results and thus recently garnered Food and Drug Administration (FDA) approval for UTUC. Other treatments such as BCG-IFN, gemcitabine, docetaxel, and drug-eluting stents (DES) may play a future role in UTUC treatment given further research. It is important to caveat that current studies on topical adjuvant treatments demonstrate varying degrees of effectiveness. This is largely due to limited research on UTUC, consisting of small sample sizes, and mostly retrospective experiences. Accordingly, further clinical trials are needed to evaluate the true benefit of these treatments.

Drivers of calcium oxalate stone formation in the octogenarian population.

INTRODUCTION: American Urological Association (AUA) guidelines suggest metabolic testing via 24-h urine studies in high-risk, interested first-time stone formers, and recurrent stone formers. If metabolic testing is not available or otherwise not feasible, clinicians may need to utilize empiric therapy. Debility and social barriers, particularly in the elderly population, may limit the practicality of metabolic testing, and therefore, empiric therapy is of particular importance. The aim of this study is to identify whether unique urinary metabolic abnormality profiles exist for octogenarians with calcium oxalate kidney stones, as this may guide empiric stone prevention therapy more precisely in this population. MATERIALS AND METHODS: Patients with calcium oxalate stones from a single academic kidney stone center in New York, NY, were retrospectively identified in our prospectively managed database. Patient data, including demographic, clinical information, and baseline 24-h urine studies, were collected before initiating any treatment. Subjects were stratified by age (≤ 40, 41-59, 60-79, and ≥ 80 years) to compare the metabolic urinary abnormality profiles between octogenarians and other age groups. Subgroup analyses were also performed to compare results by gender and by the presence of underlying kidney dysfunction. Comparative statistical analysis was carried out using Chi-square tests, Mann-Whitney U tests, and t-tests where appropriate. RESULTS: Hypocitraturia, low urine pH, and low urine volume were most common in older patients, particularly in octogenarians. Hypercalciuria, hypernatriuria, and hyperuricosuria were more apparent in younger groups. CONCLUSION: With increasing age, hypocitraturia, low urine pH, and low urine volume were more prevalent on 24-h urine metabolic testing. We hypothesize increased comorbidity, including medical renal disease, polypharmacy, and dehydration are possible factors contributing to this unique profile. We suggest that empiric therapy targeted towards this profile is important in very elderly stone formers in whom 24-h urine testing may not be possible. Increased hydration, increased fruit and vegetable intake, and low-dose alkali therapy are easy measures to accomplish this.

Opioid-free percutaneous nephrolithotomy: an initial experience.

INTRODUCTION: The opioid epidemic in the United States is an ongoing public health crisis that is in part fueled by excessive prescribing by physicians. Percutaneous nephrolithotomy (PCNL) is a procedure that conventionally involves opioid prescriptions for adequate post-operative pain control. We aimed to evaluate the feasibility of a non-opioid pain regimen by evaluating post-operative outcomes in PCNL patients discharged without opioids. MATERIALS AND METHODS: As a quality improvement measure to reduce opioid consumption our department began routinely prescribing oral ketorolac instead of oxycodone-acetaminophen for pain control after PCNL. We retrospectively compared patients undergoing PCNL who had received ketorolac prescriptions (NSAID) to those who received oxycodone-acetaminophen prescriptions (NARC). Demographic, operative, and post-operative factors were obtained and compared in both groups. Peri-operative factors and demographics were compared using either Chi-squared tests, Mann-Whitney U tests. Surgical outcomes were compared between the two groups using Chi-squared tests and Fisher's exact tests. Multivariate logistic regression analysis was performed to determine whether ketorolac use was an independent predictor of post-surgical pain-related encounters. Primary outcome was unplanned pain-related healthcare encounters inclusive of office phone calls, unscheduled office visits, and emergency department (ED) visits. Secondary outcome measures were non-pain-related healthcare encounters, hospital readmissions, pain-related rescue medications prescribed, and post-op complications. RESULTS: There were similar demographics and peri-operative characteristics amongst patients in both cohorts. There was no significant difference identified between NSAID and NARC regarding unplanned pain-related encounters (8/70, 11.4% vs. 10/70, 14.3%, p = 0.614). However, NARC experienced more unplanned phone calls (42, 60% vs. 24, 34.3%, p = 0.004). Multivariate analysis revealed only prior stone surgery was predictive of pain-related encounters after PCNL (p = 0.035). CONCLUSION: Our results show that there were no significant differences in pain-related encounters between those who received ketorolac and oxycodone-acetaminophen following PCNL. A non-opioid pathway may mitigate the potential risk associated with opioid prescription without compromising analgesia. Prospective comparative studies are warranted to confirm feasibility.

Selecting an Endourology Society Fellowship Program: The Candidates' Perspectives.

Introduction: Understanding the factors that influence the decision of urology residents to pursue an Endourology Society (ES) fellowship and the criteria used by applicants to rank programs may help residents and program directors (PDs) optimize the match process. In the present study, we surveyed current ES fellows to gain better insight surrounding their decision-making process. Materials and Methods: A survey was emailed to all ES fellows, comprising Endourology and Stone Disease (ESD), Laparoscopic and Robotic Surgery (MIS), and combination of ESD/MIS (COM) programs. A Likert scale ranging from 1 to 5 was used. The survey captured demographics such as geographic region, program type, duration, applicants' reasons for pursuing fellowship, criteria for ranking programs, and perceived improvements in surgical comfort levels at the end of their training. Results: Out of the 60 fellows who were surveyed, 40 (66.7%) responded. Among the respondents, 9 (22.5%) pursued ESD, 10 (25%) pursued MIS, and 21 (52.5%) pursued COM programs. The primary reason for seeking a fellowship was to improve surgical skills while increasing earning potential and enhancing research opportunities were deemed the least important. Fellows enrolled in 1-year programs were less likely to pursue fellowships for academic reasons. The two most significant factors in selecting a program were both related to gaining operative experience. Lastly, there was an increase in the level of comfort performing all endourological surgeries independently after fellowship. Conclusions: ES fellowship is seen as an opportunity to hone surgical skills and increase job competitiveness. When selecting a program, operative experience is the most important factor, and fellowship improves operative confidence. The information obtained from this study may mutually help guide future applicants and PDs in the decision process of the Endourology Match.

The Role of Experience: How Case Volume and Endourology-Fellowship Training Impact Surgical Outcomes for Ureteroscopy.

Introduction: Surgical experience is associated with superior outcomes in complex urologic cases, such as prostatectomy, nephrectomy, and cystectomy. The question remains whether experience is predictive of outcomes for less complex procedures, such as ureteroscopy (URS). Our study examined how case volume and endourology-fellowship training impacts URS outcomes. Methods: We retrospectively reviewed URS cases from 2017 to 2019 by high ureteroscopy volume urologists (HV), low ureteroscopy volume urologists (LV), endourology-fellowship trained (FT), and non-endourology FT (NFT) urologists. Surgical outcomes including stone-free rate (SFR), complication and reoperation rates, and postoperative imaging follow-up were analyzed between groups. Results: One thousand fifty-seven cases were reviewed across 23 urologists: 6 HV, 17 LV, 3 FT, and 20 NFT. Both FT and HV operated on more complex cases with lower rates of pre-stented patients. HV also operated on patients with higher rates of renal stones, lower pole involvement, and prior failed procedures. Despite this, FT and HV showed between 11.7% and 14.4% higher SFR, representing 2.7- to 3.6-fold greater odds of stone-free outcomes for primary and secondary stones. Additionally, HV and FT had a 4.9% to 7.8% lower rate of postoperative complications and a 3.3% to 4.3% lower rate of reoperations, representing 1.9- to 4.0-fold lower odds of complications. Finally, their patients had a 1.6- to 2.1-fold higher odds of postoperative imaging follow-up with a greater proportion receiving postoperative imaging within the recommended 3-month postoperative period. Conclusions: More experienced urologists, as defined by higher case volume and endourology-fellowship training, had higher SFR, lower complication and reoperation rates, and better postoperative imaging follow-up compared with less experienced urologists. Although less experienced urologists had outcomes in-line with clinical and literature standards, continued training and experience may be a predictor of better outcomes across multiple URS modalities.

Evaluating the safety of same-day discharge following pediatric pyeloplasty and ureteral reimplantation; A NSQIP analysis 2012-2020.

INTRODUCTION: Same-day discharge (SDD) is a safe option for several adult urologic surgeries, benefiting patients and hospitals. By decreasing length of stay while maintaining patient safety, SDD is in-line with recent goals to provide high value care while minimizing costs. Literature on SDD in the pediatric population, however, is scarce, and no study has identified the efficacy of SDD for pediatric pyeloplasty (PP) and ureteral reimplantation (UR). OBJECTIVE: The aim of this study was to identify trends in the usage of SDD as well as its efficacy and safety based on surgical outcomes for pediatric PP and UR. STUDY DESIGN: The 2012-2020 files of the American College of Surgeon's National Surgical Quality Improvement Project pediatric database were queried for PP and UR. Patients were stratified as SDD or standard-length discharge (SLD). Trends in SDD usage, differences in baseline characteristics, surgical approach, and surgical outcomes including 30-day readmission, complication, and reoperation rates were analyzed between SDD and SLD groups. RESULTS: 8213 PP (SDD: 202 [2.46%]) and 10,866 UR (469 [4.32%]) were included in analysis. There were no significant changes in SDD rates between 2012 and 2020, averaging 2.39% (PP), and 4.39% (UR). For both procedures, SDD was associated with higher rates of open versus minimally invasive (MIS) surgical approach and with shorter operative and anesthesia durations. For PP, there were no differences in readmission, complication, or reoperation rates in the SDD group. For UR, there was a 1.69% increase in CD I/II complications in those receiving SDD, correlating to 1.96-fold higher odds of CD I/II in all SDD patients compared to SLD patients. DISCUSSION: These results suggest that while the rate of SDD has not increased in recent years, the current screening methods for SDD have been generally effective in maintaining the safety of SDD for pediatric procedures. Though SDD for UR did show a very small increase in minor complications, this may be due to less strict screening protocols, and may be alleviated via MIS surgical approach. While this is the first paper to investigate SDD for pediatric urology procedures, these results are similar to those found for adult procedures. This study is limited by the lack of clinical data reported in the database. CONCLUSION: SDD is a generally safe option for pediatric PP and UR, and further research should identify proper screening protocols to continue to allow for safe SDD.

Protonation of P-Stereogenic Phosphiranes: Phospholane Formation via Ring Opening and C-H Activation.

Protonation of cyclopropanes and aziridines is well-studied, but reactions of phosphiranes with acids are rare and have not been reported to result in ring opening. Treatment of syn-Mes*PCH2CHR (Mes* = 2,4,6-(t-Bu)3C6H2, R = Me or Ph, syn-1-2) or anti-Mes*PCH2CHPh (anti-2) with triflic acid resulted in regiospecific anti-Markovnikov C-protonation with ring opening and cyclophosphination of a Mes* ortho-t-Bu group to yield the phospholanium cations [PH(CH2CH2R)(4,6-(t-Bu)2-2-CMe2CH2C6H2)][OTf] (R = Me or Ph, 3-4), which were deprotonated with NEt3 to give phospholanes 5-6. Enantioenriched or racemic syn-1 both gave racemic 3. The byproduct [Mes*PH(CH2CH2Me)(OH)][OTf] (7) was formed from syn-1 and HOTf in the presence of water. Density functional theory calculations suggested that P-protonation followed by ring opening and hydride migration to C yields the phosphenium ion, [Mes*P(CH2CH2Me)][OTf], which undergoes C-H oxidative addition of an o-t-Bu methyl group. This work established a new reactivity pattern for phosphiranes.

Pharmacokinetics of Cefazolin in Patients With Obesity Undergoing Surgery Requiring Cardiopulmonary Bypass.

OBJECTIVE: The authors' objective was to determine the adequacy of an institutional standard dosing practice for infection prophylaxis in open cardiac surgery in patients heavier than 120 kg undergoing cardiopulmonary bypass. DESIGN: A prospective, single-center, open-label study was used to determine if cefazolin serum concentrations were maintained above the minimum inhibitory concentration (MIC) throughout surgery. A pharmacokinetic model describing cefazolin disposition was developed for perioperative patients with morbid obesity, based on these values. Probability of target attainment was evaluated across the clinically relevant MIC spectrum. SETTING: Maine Medical Center is an academic hospital in Portland, Maine, affiliated with Tufts University School of Medicine. PARTICIPANTS: Twenty patients scheduled for cardiac surgery requiring cardiopulmonary bypass who weighed at least 120 kg. INTERVENTIONS: All patients received 2 g of cefazolin intravenously (IV) within 1 hour before incision, an additional 1 g injected into the cardiopulmonary bypass circuit at the initiation of bypass, and 2 g administered IV every 3 hours after the initial IV dose. MEASUREMENTS AND MAIN RESULTS: Cefazolin serum concentrations were collected after incision, after initiation of bypass, each hour of bypass, at the end of bypass, and at sternal closure. For patients weighing >120 kg undergoing cardiac surgery, the studied dosing regimen met or exceeded targeted cefazolin concentrations for all study patients. The authors conducted probability of target attainment analyses using both 65% and 100% of time with unbound drug concentrations across clinically relevant MICs. CONCLUSION: The authors found that their current dosing strategy achieved a probability of target attainment >90% throughout surgery for both total and unbound cefazolin concentrations, independent of cardiopulmonary bypass times.

Management of a Patient Requiring Intrathecal Drain Insertion and Removal in the Setting of Concomitant Dual Antiplatelet Therapy With Clopidogrel and Aspirin: A Case Report.

We report a case of deliberate intrathecal catheter insertion and removal in the setting of continuous dual-antiplatelet therapy with clopidogrel and aspirin. A patient with recently sited bare metal intracerebral stents developed severe symptomatic hydrocephalus and required temporary cerebrospinal fluid diversion. The risks of intracerebral in-stent thrombosis or delayed intervention precluded following guidelines for the management of clopidogrel in neuraxial procedures. Options to mitigate the risk of and facilitate the early detection of epidural hematoma are discussed when neuraxial instrumentation is indicated in the setting of clopidogrel and aspirin therapy.

Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery.

Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug target for diabetes and cancer that catalyzes the dephosphorylation of numerous substrates in essential signaling pathways. By combining new experimental and computational data on WT-PTP1B and ≥10 PTP1B variants in multiple states, we discovered a fundamental and evolutionarily conserved CH/π switch that is critical for positioning the catalytically important WPD loop. Furthermore, our data show that PTP1B uses conformational and dynamic allostery to regulate its activity. This shows that both conformational rigidity and dynamics are essential for controlling protein activity. This connection between rigidity and dynamics at different timescales is likely a hallmark of all enzyme function.

Custom Titanium Ridge Augmentation Matrix (CTRAM): A Case Report.

This is a case report of a custom titanium ridge augmentation matrix (CTRAM). Using cone beam computed tomography (CBCT), a custom titanium space-maintaining device was developed. Alveolar ridges were virtually augmented, a matrix was virtually designed, and the CTRAM was additively manufactured with titanium (Ti6Al4V). Two cases are presented that resulted in sufficient increased horizontal bone volume with successful dental implant placement. The CTRAM design allows for preoperative planning for increasing alveolar ridge dimensions to support dental implants, reduces surgical time, and prevents the need for a second surgical site to gain sufficient alveolar ridge bone volume for dental implant therapy.

Paravertebral analgesia in transapical transcatheter aortic valve replacement.

INTRODUCTION: Transapical transcatheter aortic valve replacement is an option for patients who are not candidates for traditional aortic valve surgery but have severe aortic stenosis and unfavorable ileo-femoral anatomy. Epidural analgesia in these cases has been associated with improved morbidity and mortality. The following manuscript presents the findings of an initial clinical experience employing paravertebral analgesia for patients undergoing transapical transcatheter aortic valve replacement. METHODS: A retrospective review was performed of 61 transapical transcatheter aortic valve replacement cases over a two-year period from November 2012 through July 2014. Paravertebral analgesia was provided as left sided single injections covering 1-3 dermatome levels using 0.2% ropivicaine with supplemental clonidine to 48 patients. The following outcome metrics were collected: 1) peri-operative opiate administration, 2) rate of extubation in the operating room, 3) new atrial fibrillation, 4) duration of intensive care stay, 5) 30-day mortality. RESULTS: The mean opiate administration was less in patients with paravertebral analgesia (128.65mcg vs. 163.46mcg fentanyl, p value 0.05) and these patients were more frequently extubated in the operating room (83.3% vs. 46.2%, p-value 0.0107). Incidence of atrial fibrillation was less in patients who received paravertebral analgesia (18.8% vs. 75.0%, p-value 0.0048). There was a non-significant trend towards decreased intensive care stay in patients who received paravertebral analgesia (58.3 hrs vs 75.8 hrs, p value 0.35). There was no difference in 30-day mortality. No complications resulted from paravertebral analgesia. CONCLUSIONS: This is the first reported case series of paravertebral blockade in transapical transcatheter aortic valve replacement  patients. The findings suggest that paravertebral single shot blocks are both safe and practical for use in this patient population. A formal prospective investigation of paravertebral analgesia in these patients is warranted.

PTP1B inhibition suggests a therapeutic strategy for Rett syndrome.

The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs.