Identifying the Gate-Opening Mechanism in the Flexible Metal-Organic Framework UTSA-300.

Atomic-level understanding of the gate-opening phenomenon in flexible porous materials is an important step toward learning how to control, design, and engineer them for applications such as the separation of gases from complex mixtures. Here, we report such mechanistic insight through an in-depth study of the pressure-induced gate-opening phenomenon in our earlier reported metal-organic framework (MOF) Zn(dps)2(SiF6) (dps = 4,4'-dipyridylsulfide), also called UTSA-300, using isotherm and calorimetry measurements, in situ infrared spectroscopy, and ab initio simulations. UTSA-300 is shown to selectively adsorb acetylene (C2H2) over ethylene (C2H4) and ethane (C2H6) and undergoes an abrupt gate-opening phenomenon, making this framework a highly selective gas separator of this complex mixture. The selective adsorption is confirmed by pressure-dependent in situ infrared spectroscopy, which, for the first time, shows the presence of multiple C2H2 species with varying strengths of bonding. A rare energetic feature at the gate-opening condition of the flexible MOF is observed in our differential heat energies, directly measured by calorimetry, showcasing the importance of this tool in adsorption property exploration of flexible frameworks and offering an energetic benchmark for further energy-based fundamental studies. Based on the agreement of this feature with ab initio-based adsorption energies of C2H2 in the closed-pore structure UTSA-300a ("a" refers to the activated form), this feature is assigned to the weakening of the H-bond C-H···F formed between C2H2 and fluorine of the MOF. Our analysis identifies the weakening of this H-bond, the expansion of the closed-pore MOF upon successive C2H2 coadsorption until its volume is close to that of the open-pore MOF, and the spontaneous gate opening to energetically favor C2H2 adsorption in the open-pore structure as crucial steps in the gate-opening mechanism in this system.

Impact of prebiopsy magnetic resonance imaging on biopsy and radical prostatectomy grade concordance.

BACKGROUND: Adoption of prostate magnetic resonance imaging (MRI) before biopsy is based on evidence demonstrating superior detection of clinically significant prostate cancer on biopsy. Whether this is due to the detection of otherwise occult higher grade cancers or preferential sampling of higher grade areas within an otherwise low-grade cancer is unknown. METHODS: To distinguish these two possibilities, this study examined the effect of prebiopsy MRI on the rate of pathologic upgrading and downgrading at prostatectomy in Surveillance, Epidemiology, and End Results-Medicare linked data from 2010 to 2015. Logistic regression was performed to assess the effect of MRI use on the Gleason grade change between biopsy and prostatectomy. RESULTS: Among biopsy-naive men, those who underwent prebiopsy MRI had higher odds of downgrading at prostatectomy (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.05-1.66). In contrast, the odds of upgrading were significantly lower for men who underwent prebiopsy MRI (OR, 0.78; 95% CI, 0.61-0.99). Limitations included a low overall rate of MRI-utilization prior to biopsy and an inability to distinguish between template, software-assisted and cognitive fusion biopsy. CONCLUSIONS: Prebiopsy MRI is associated with both oversampling of higher grade areas, which results in downgrading at prostatectomy, and the detection of otherwise occult higher grade lesions, which results in less upgrading at prostatectomy.

Fluid Intake and Urinary Symptoms in Patients with Multiple Sclerosis.

PURPOSE: The relationship between fluid intake and lower urinary tract symptoms in individuals with neurogenic bladder is unknown. We investigated the association between fluid intake and urinary symptoms in patients with multiple sclerosis. MATERIALS AND METHODS: A prospective cross-sectional study of patients with multiple sclerosis presenting to the neurology office was conducted. Fluid intake and lower urinary tract symptoms were assessed by the questionnaire based voiding diary and the American Urological Association Symptom Score, respectively. The relationship between fluid intake and lower urinary tract symptoms was assessed using univariate and multivariate analyses. RESULTS: Among 200 individuals with multiple sclerosis the mean total daily fluid intake was 2,489 ml (SD 1,883) and did not differ according to severity (ie mild, moderate, severe) of lower urinary tract symptoms (F=0.30, p=0.74). Fluid restricting behavior to control urinary symptoms was reported by 47% of subjects. Subjects who reported fluid restricting were more likely to have worse urinary symptoms (OR 1.95, 95% CI 1.53-2.47, p <0.01). After accounting for fluid restricting behavior on multivariate analysis, there was a minimal relationship between caffeinated fluid intake and lower urinary tract symptom severity (OR 1.00, 95% CI 1.00-1.01, p=0.01), and there was no relationship between total fluid intake and lower urinary tract symptom severity (OR 1.00, 95% CI 1.00-1.00, p=0.07). CONCLUSIONS: Caffeinated fluid intake has a minimal effect on lower urinary tract symptoms in patients with multiple sclerosis. On average, patients with multiple sclerosis do not hydrate excessively and a considerable proportion restrict fluid intake to control urinary symptoms. Fluid intake may not contribute considerably to lower urinary tract symptoms in patients with multiple sclerosis.

Variation in Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy Outcomes in Asian American Men: A Multicenter Study.

PURPOSE: Asian American men have distinctly different prostate cancer epidemiology than other men. To our knowledge the role of multiparametric magnetic resonance imaging and targeted biopsy for elevated prostate specific antigen in this population has not been assessed. We sought to define imaging and targeted biopsy outcomes in Asian American men compared to other men. MATERIALS AND METHODS: We accrued a multicenter, prospective cohort of men who underwent magnetic resonance imaging targeted and systematic biopsy for elevated prostate specific antigen. The outcome of interest was a diagnosis of clinically significant prostate cancer (Gleason Grade Group 2 or greater) stratified by the PI-RADS™ (Prostate Imaging-Reporting and Data System) score and a history of negative biopsy. Multivariable logistic regression was used to assess the effect of Asian American race on cancer detection. RESULTS: Of the 2,571 men 275 (11%) were Asian American. Clinically significant prostate cancer was detected in 37% of Asian American men compared to 48% of men of other races (p <0.001). Asian American men were also less likely to be diagnosed with Grade Group 1 cancer (12% vs 18%, p=0.007). Additionally, there was significantly lower detection of significant cancer using PI-RADS 3 in Asian American men vs men of other races (12% vs 21%, p=0.032). On adjusted analysis Asian American men were less likely to be diagnosed with significant cancer (OR 0.57, 95% CI 0.42-0.79, p <0.001) and Grade Group 1 cancer (OR 0.57, 95% CI 0.38-0.84, p=0.005) than nonAsian men. CONCLUSIONS: Asian American men are less likely to be diagnosed with clinically significant prostate cancer on targeted biopsy, illustrating the different performance of PI-RADS in this population. Conventional risk assessment tools should be modified when selecting Asian American men for biopsy.

SPARED Collaboration: Patient Selection for Partial Gland Ablation in Men with Localized Prostate Cancer.

PURPOSE: The SPARED CRN (Study of Prostate Ablation Related Energy Devices Coordinated Registry Network) is a private-public partnership between academic and community urologists, the FDA (U.S. Food and Drug Administration), the Medical Device Epidemiology Network and device manufacturers to examine the safety and effectiveness of technologies for partial gland ablation in men with localized prostate cancer. MATERIALS AND METHODS: We report on a recent workshop at the FDA with thought leaders to discuss a critical framework for partial gland ablation, focusing on patient selection, surgical planning, followup, study design and appropriate comparators in terms of adverse events and cancer control outcomes. We summarize salient points from experts in urology, oncology and epidemiology that were presented and discussed in an open forum. RESULTS: Given the challenges in achieving patient and physician equipoise to perform a randomized trial, as well as an inherent paradigm shift when comparing partial gland ablation (inability to assess prostate specific antigen recurrence) to whole gland treatments, the group focused on objective performance criteria and goals as a platform to guide the creation of single arm studies in the SPARED CRN. CONCLUSIONS: This summit lays the foundation for prospective, multi-center data collection and evaluation of novel medical devices and drug/device combinations for partial gland ablation.

Large-Pore Functionalized Mesoporous Silica Nanoparticles as Drug Delivery Vector for a Highly Cytotoxic Hybrid Platinum-Acridine Anticancer Agent.

Large-pore mesoporous silica nanoparticles (MSN) were prepared and functionalized to serve as a highly robust and biocompatible delivery platform for platinum-acridine (PA) anticancer agents. The material showed a high loading capacity for the dicationic, hydrophilic hybrid agent [PtCl(en)(N-[acridin-9-ylaminoethyl]-N-methylpropionamidine)] dinitrate salt (P1A1) and virtually complete retention of payload at neutral pH in a high-chloride buffer. In acidic media mimicking the pH inside the cell lysosomes, rapid, burst-like release of P1A1 from the nanoparticles is observed. Coating of the materials in phospholipid bilayers resulted in nanoparticles with greatly improved colloidal stability. The lipid and carboxylate-modified nanoparticles containing 40 wt % drug caused S-phase arrest and inhibited cell proliferation in pancreatic cancer cells at submicromolar concentrations similar to carrier-free P1A1. The most striking feature of nanoparticle-delivered P1A1 was that the payload did not escape from the acidified lysosomal vesicles into the cytoplasm, but was shuttled to the nuclear membrane and released into the nucleus.

Fast updating feedback from piriform cortex to the olfactory bulb relays multimodal reward contingency signals during rule-reversal.

While animals readily adjust their behavior to adapt to relevant changes in the environment, the neural pathways enabling these changes remain largely unknown. Here, using multiphoton imaging, we investigated whether feedback from the piriform cortex to the olfactory bulb supports such behavioral flexibility. To this end, we engaged head-fixed mice in a multimodal rule-reversal task guided by olfactory and auditory cues. Both odor and, surprisingly, the sound cues triggered cortical bulbar feedback responses which preceded the behavioral report. Responses to the same sensory cue were strongly modulated upon changes in stimulus-reward contingency (rule reversals). The re-shaping of individual bouton responses occurred within seconds of the rule-reversal events and was correlated with changes in the behavior. Optogenetic perturbation of cortical feedback within the bulb disrupted the behavioral performance. Our results indicate that the piriform-to-olfactory bulb feedback carries reward contingency signals and is rapidly re-formatted according to changes in the behavioral context.

Donor-Derived Renal Cell Carcinoma in a Kidney Allograft: A Case Report.

Renal cell carcinoma (RCC) in the kidney allograft is a relatively rare complication most commonly seen approximately a decade or more after transplant. We report a case of diffuse multifocal RCC within 6 months of transplant. The initial signal leading to an abnormality in the graft was an elevated routine cell-free DNA. Initial imaging findings appeared consistent with post-transplant lymphoproliferative disorder; however, biopsy would ultimately yield RCC. The patient's diffuse disease necessitated radical nephrectomy. Tumor DNA fingerprinting was employed in this case to show the tumor originated from donor tissue rather than host, indicating primary rather than metastatic disease. Early RCC is a rare complication. Most cases are detected at an early stage, likely as a result of increased surveillance with ultrasound imaging. A donor's social history including significant tobacco use should be considered when evaluating the risk of malignancy transmission in the allograft. Clinicians should be aware of multifocal RCC as a potential differential diagnosis for diffuse nodular infiltrates in the allograft.

Trends of Mesh Utilization for Stress Urinary Incontinence Before and After the 2011 Food and Drug Administration Notification Between FPMRS-Certified and Non-FPMRS-Certified Physicians: A Statewide All-Payer Database Analysis.

OBJECTIVES: To investigate the utilization of mesh slings for stress urinary incontinence (SUI) across time - before and after the 2011 US Food and Drug Administration (FDA) public health notification regarding an increase in adverse events related to transvaginal mesh (TVM) for pelvic organ prolapse (POP) repair - and among FPMRS-certified urologists and gynecologists and non-FPMRS counterparts using a statewide database. METHODS: The New York Statewide Planning and Research Cooperative System all-payer database was utilized to extract outpatient Current Procedural Terminology procedure codes for SUI mesh sling utilization and revision or removal performed between 2007 and 2015. RESULTS: After the 2011 FDA warning on POP with TVM, sling placement decreased by 43% from 5214 cases in 2011 to 2958 in 2015. However, over the study period, the rate of sling revision remained stable relative to total sling placement. The rise and fall in mesh sling usage for SUI was primarily driven by non-FPMRS providers. FPMRS providers performed a higher proportion of sling procedures. The number of FPMRS physicians also increased from 2011 to 2015, and each individual physician had a higher median case volume for sling placements and revisions. CONCLUSION: In New York state, utilization of mesh slings for SUI has significantly decreased since the 2011 FDA public health notification, without any specific warning for the utilization of mesh in this setting. This trend was mainly driven by a decrease in mesh usage among non-FPMRS physicians, although the specific causality is likely complex.

Persistent Discordance in Grade, Stage, and NCCN Risk Stratification in Men Undergoing Targeted Biopsy and Radical Prostatectomy.

OBJECTIVE: To elucidate the accuracy of MRI and MRI-ultrasound fusion guided targeted biopsy (TBx) on risk stratification in men who underwent subsequent radical prostatectomy (RP). MATERIALS AND METHODS: A single-center, retrospective study was performed in men at risk for prostate cancer who (n = 140) underwent TBx and RP between November 2012 and August 2018. Comparisons were made between patients clinically staged by preoperative MRI and TBx Gleason grade group (GGG) and stage after RP. Multivariable regression was performed to identify factors associated with MRI and TBx compared to RP grading, staging, and consistency with National Comprehensive Cancer Network (NCCN) risk stratification. RESULTS: There was an increase in NCCN risk stratification in 47 men (33.6%) and a decrease in 17 men (12.1%) compared to the resected prostate. GGG upgrading and downgrading occurred in 35 (25.0%) and 31 men (22.1%), respectively. Upstaging occurred in 41 men (29.3%). In adjusted analysis for age, BMI, PSA Density (PSAD), median maximal diameter of the regions of interest, and PIRADS, men with PIRADS 4 were less likely to be upgraded (OR 0.26, 95% CI 0.08-0.81, P = .020) than PIRADS 3. PSAD ≥ 0.15 ng/mL/cc was associated with upstaging (OR 3.92, 95% CI 1.60-9.62, P = .003). CONCLUSION: Accurate risk stratification is critical for disease management, mandated by the increasing use of active surveillance, partial gland ablation, and androgen deprivation therapy with radiation therapy for men with unfavorable intermediate and high-risk prostate cancer. This study confirms the need for advances in imaging and biomarker to increase the accuracy of pretreatment staging.

Multicenter analysis of clinical and MRI characteristics associated with detecting clinically significant prostate cancer in PI-RADS (v2.0) category 3 lesions.

OBJECTIVES: We sought to identify clinical and magnetic resonance imaging (MRI) characteristics in men with the Prostate Imaging - Reporting and Data System (PI-RADS) category 3 index lesions that predict clinically significant prostate cancer (CaP) on MRI targeted biopsy. MATERIALS AND METHODS: Multicenter study of prospectively collected data for biopsy-naive men (n = 247) who underwent MRI-targeted and systematic biopsies for PI-RADS 3 index lesions. The primary endpoint was diagnosis of clinically significant CaP (Grade Group ≥2). Multivariable logistic regression models assessed for factors associated with clinically significant CaP. The probability distributions of clinically significant CaP based on different levels of predictors of multivariable models were plotted in a heatmap. RESULTS: Men with clinically significant CaP had smaller prostate volume (39.20 vs. 55.10 ml, P < 0.001) and lower apparent diffusion coefficient (ADC) values (973 vs. 1068 µm2/s, P = 0.013), but higher prostate-specific antigen (PSA) density (0.21 vs. 0.13 ng/ml2, P = 0.027). On multivariable analyses, lower prostate volume (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92-0.97), lower ADC value (OR: 0.99, 95% CI: 0.99-1.00), and Prostate-specific antigen density >0.15 ng/ml2 (OR: 3.51, 95% CI 1.61-7.68) were independently associated with significant CaP. CONCLUSION: Higher PSA density, lower prostate volume and ADC values are associated with clinically significant CaP in biopsy-naïve men with PI-RADS 3 lesions. We present regression-derived probabilities of detecting clinically significant CaP based on various clinical and imaging values that can be used in decision-making. Our findings demonstrate an opportunity for MRI refinement or biomarker discovery to improve risk stratification for PI-RADS 3 lesions.

Concordance Between Biopsy and Radical Prostatectomy Pathology in the Era of Targeted Biopsy: A Systematic Review and Meta-analysis.

CONTEXT: Multiparametric magnetic resonance imaging (mpMRI)-targeted transrectal prostate biopsy (TBx) may better predict pathology at radical prostatectomy than systematic transrectal prostate biopsy (SBx). OBJECTIVE: To assess concordance between biopsy and radical prostatectomy pathology in men undergoing a TBx as compared with those undergoing an SBx. EVIDENCE ACQUISITION: Four electronic databases (Ovid MEDLINE, Ovid EMBASE, the Cochrane Library [Wiley], and EBSCHOHost) were searched from inception until July 2018. Studies were included if they were published after 2012, conducted both SBx and TBx, and compared the biopsy results with final pathology after radical prostatectomy for ≥50 patients. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized. Bias was appraised using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. EVIDENCE SYNTHESIS: Our search yielded 10 studies including 1215 men. However, our inclusion criteria applied only to a proportion of men included in these studies. The median age was 65 yr and the median prostate-specific antigen level was 7.2 ng/ml. In the eight studies examining upgrading at prostatectomy, pathology from SBx was significantly more likely to be upgraded relative to TBx (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.48-4.14, p = 0.001). We found no significant difference in downgrading (OR 1.13, 95% CI 0.48-2.67, p = 0.783) between TBx and SBx. For both biopsy-naïve men and men with a prior negative biopsy, results from SBx were more likely to be upgraded than TBx at prostatectomy (OR 1.6 [95% CI 1.02-2.27, p < 0.001] and OR 4.23 [95% CI 1.68-8.48, p = 0.003], respectively). CONCLUSIONS: Pathologic upgrading at prostatectomy was less likely with mpMRI-targeted biopsy versus systematic biopsy alone, without concurrent increase in downgrading. This increased accuracy should improve confidence in management decisions based on MRI-targeted biopsy pathology. PATIENT SUMMARY: We reviewed the ability of multiparametric magnetic resonance imaging -targeted biopsy to predict cancer grade at radical prostatectomy. We found that targeted biopsy provides more accurate assessment of Gleason score at prostatectomy than systematic biopsy.

Prostate Multiparametric Magnetic Resonance Imaging Features Following Partial Gland Cryoablation.

OBJECTIVE: To assess the qualitative and quantitative changes on prostate multiparametric magnetic resonance imaging (mpMRI) following partial gland ablation (PGA) with cryotherapy and correlate with histopathology. METHODS: We used 3D Slicer to generate prostate models and segment ipsilateral (treated) and contralateral peripheral and transition zones in 10 men who underwent MRI/transrectal ultrasound fusion-guided PGA during 2017-2018. Pre- and post-PGA volumes of prostate segments were compared. Post-PGA mpMRI were categorized according to PI-RADS v2 and treatment response on mpMRI was assessed in a manner similar to the radiology evaluation framework following liver lesion ablation. RESULTS: Median volume of ipsilateral peripheral and transition zones decreased from 10.9 mL and 13.0 mL to 7.2 mL and 10.8 mL (P = .005), respectively. Median volume of contralateral peripheral and transition zones also decreased from 12.1 mL and 12.5 mL to 9.9 mL to 10.4 mL (P = .005), respectively. Five men had clinically significant disease (Grade group ≥2) on post-PGA biopsy (3 within treatment field and 2 outside). Of the men with clinically significant prostate cancer, mpMRI revealed PI-RADS 3 lesions in 2. However, the treatment response framework did not detect residual disease. CONCLUSION: PGA results in asymmetrical and significant reductions in prostate volume. Our results highlight the need for a separate assessment framework to enable standardization of the interpretation and reporting of post-PGA surveillance mpMRI. Moreover, our findings have significant implications for MRI-targeted surveillance biopsy following PGA with cryotherapy.

Assessing Treatment-Related Toxicity Using Administrative Data, Patient-Reported Outcomes, or Physician-Graded Toxicity: Where Is the Truth?

The accurate determination of the frequency and severity of treatment-related complications is vital to informing patients and clinicians in their decision-making process. In published studies, complications are assed via administrative data, patient-reported outcomes, and physician-graded toxicity, each with their strengths and limitations. Administrative data provide a vast, accessible history of patient data, but are limited in the ability to accurately capture diagnosis and causality, and are subject to differing interpretations of billing codes. Patient-reported outcomes provide direct and nuanced descriptions of both symptoms and bother; but are by definition subjective, affected by nonrespondents, and results (scores) are often difficult to interpret for patients and clinicians alike. Physician-graded toxicity is a relatively more objective measure, but relies on both clinicians fully assessing all relevant symptoms and patients accurately reporting them to the clinician. Understanding these strengths and limitations will help clinicians become more informed readers of the published literature.

Data on the quality and methods of studies reporting healthcare costs of post-prostate biopsy sepsis.

This data article presents the supplementary material for the review paper "Healthcare Costs of Post-Prostate Biopsy Sepsis" (Gross et al., 2019). A general overview is provided of 18 papers, including the details about year and journal of publication, country of dataset, data population characteristics, cost basis, and potential for bias evaluation. Quality assessment and the risk of bias of the 18 papers are detailed and summarized.

Healthcare Costs of Post-Prostate Biopsy Sepsis.

Sepsis following transrectal prostate biopsy occurs in 2%-5% of cases and the risk is increasing. We performed a comprehensive literature search for the cost of post-prostate biopsy sepsis to define the potential cost savings of reducing infectious complications. Reporting of cost is varied and presents a challenge to interpretation. Length of hospitalization ranged from 1.1 to 14 days and the percent admitted to an ICU ranged from 1.1% to 25%. The estimated cost of sepsis post-prostate biopsy, adjusted for inflation, ranged from $8,672 to $19,100. Healthcare costs of treating post-biopsy infection are substantial. Our findings should guide payers and policymakers, especially in value-based care models.