Search

Abstract Background Proper blood pressure control during surgical procedures such as total joint arthroplasty (TJA) is considered critical to good outcome. There is poor understanding of the pre-operative risk factors for poor intra-operative hemodynamic control. The purpose of this study is to identify risk factors for poor hemodynamic control during TJA. Methods We performed a retrospective cohort analysis of 118 patients receiving TJA in the Dominican Republic. We collected patient demographic and comorbidity data. We developed an a priori definition for poor hemodynamic control: 1) Mean arterial pressure (MAP) 135% of preoperative MAP. We performed bivariate and multivariate analyses to identify risk factors for poor hemodynamic control during TJA. Results Hypertension was relatively common in our study population (76 of 118 patients). Average preoperative mean arterial pressure was 109.0 (corresponding to an average SBP of 149 and DBP of 89). Forty-nine (41.5%) patients had intraoperative blood pressure readings consistent with poor hemodynamic control. Based on multi-variable analysis preoperative hypertension of any type (RR 2.9; 95% CI 1.3-6.3) and an increase in BMI (RR 1.2 per 5 unit increase; 95% CI 1.0-1.5) were significant risk factors for poor hemodynamic control. Conclusions Preoperative hypertension and being overweight/obese increase the likelihood of poor blood pressure control during TJA. Hypertensive and/or obese patients warrant further attention and medical optimization prior to TJA. More work is required to elucidate the relationship between these risk factors and overall outcome.

Abstract Background Numerous papers have been published examining risk factors for revision of primary total hip arthroplasty (THA), but there have been no comprehensive systematic literature reviews that summarize the most recent findings across a broad range of potential predictors. Methods We performed a PubMed search for papers published between January, 2000 and November, 2010 that provided data on risk factors for revision of primary THA. We collected data on revision for any reason, as well as on revision for aseptic loosening, infection, or dislocation. For each risk factor that was examined in at least three papers, we summarize the number and direction of statistically significant associations reported. Results Eighty-six papers were included in our review. Factors found to be associated with revision included younger age, greater comorbidity, a diagnosis of avascular necrosis (AVN) as compared to osteoarthritis (OA), low surgeon volume, and larger femoral head size. Male sex was associated with revision due to aseptic loosening and infection. Longer operating time was associated with revision due to infection. Smaller femoral head size was associated with revision due to dislocation. Conclusions This systematic review of literature published between 2000 and 2010 identified a range of demographic, clinical, surgical, implant, and provider variables associated with the risk of revision following primary THA. These findings can inform discussions between surgeons and patients relating to the risks and benefits of undergoing total hip arthroplasty.

Abstract Background Pain variability in acute LBP has received limited study. The objectives of this pilot study were to characterize fluctuations in pain during acute LBP, to determine whether self-reported 'flares' of pain represent discrete periods of increased pain intensity, and to examine whether the frequency of flares was associated with back-related disability outcomes. Methods We conducted a cohort study of acute LBP patients utilizing frequent serial assessments and Internet-based data collection. Adults with acute LBP (lasting ≤3 months) completed questionnaires at the time of seeking care, and at both 3-day and 1-week intervals, for 6 weeks. Back pain was measured using a numerical pain rating scale (NPRS), and disability was measured using the Oswestry Disability Index (ODI). A pain flare was defined as 'a period of increased pain lasting at least 2 hours, when your pain intensity is distinctly worse than it has been recently'. We used mixed-effects linear regression to model longitudinal changes in pain intensity, and multivariate linear regression to model associations between flare frequency and disability outcomes. Results 42 of 47 participants (89%) reported pain flares, and the average number of discrete flare periods per patient was 3.5 over 6 weeks of follow-up. More than half of flares were less than 4 hours in duration, and about 75% of flares were less than one day in duration. A model with a quadratic trend for time best characterized improvements in pain. Pain decreased rapidly during the first 14 days after seeking care, and leveled off after about 28 days. Patients who reported a pain flare experienced an almost 3-point greater current NPRS than those not reporting a flare (mean difference [SD] 2.70 [0.11]; p < 0.0001). Higher flare frequency was independently associated with a higher final ODI score (ß [SE} 0.28 (0.08); p = 0.002). Conclusions Acute LBP is characterized by variability. Patients with acute LBP report multiple distinct flares of pain, which correspond to discrete increases in pain intensity. A higher flare frequency is associated with worse disability outcomes.

Abstract Background There is little prior research on the burden of arthritis in the developing world. We sought to document how patients with advanced arthritis living in the Dominican Republic are affected by and cope with their disease. Methods We conducted semi-structured, one-to-one interviews with economically disadvantaged Dominican patients with advanced knee and/or hip arthritis in the Dominican Republic. The interviews, conducted in Spanish, followed a moderator's guide that included topics such as the patients' understanding of disease etiology, their support networks, and their coping mechanisms. The interviews were audiotaped, transcribed verbatim in Spanish, and systematically analyzed using content analysis. We assessed agreement in coding between two investigators. Results 18 patients were interviewed (mean age 60 years, median age 62 years, 72% women, 100% response rate). Patients invoked religious and environmental theories of disease etiology, stating that their illness had been caused by God's will or through contact with water. While all patients experienced pain and functional limitation, the social effects of arthritis were gender-specific: women noted interference with homemaking and churchgoing activities, while men experienced disruption with occupational roles. The coping strategies used by patients appeared to reflect their beliefs about disease causation and included prayer and avoidance of water. Conclusions Patients' explanatory models of arthritis influenced the psychosocial effects of the disease and coping mechanisms used. Given the increasing reach of global health programs, understanding these culturally influenced perceptions of disease will be crucial in successfully treating chronic diseases in the developing world.

Abstract Background- Prior studies that have concluded that disk degeneration uniformly precedes facet degeneration have been based on convenience samples of individuals with low back pain. We conducted a study to examine whether the view that spinal degeneration begins with the anterior spinal structures is supported by epidemiologic observations of degeneration in a community-based population. Methods- 361 participants from the Framingham Heart Study were included in this study. The prevalences of anterior vertebral structure degeneration (disk height loss) and posterior vertebral structure degeneration (facet joint osteoarthritis) were characterized by CT imaging. The cohort was divided into the structural subgroups of participants with 1) no degeneration, 2) isolated anterior degeneration (without posterior degeneration), 3) combined anterior and posterior degeneration, and 4) isolated posterior degeneration (without anterior structure degeneration). We determined the prevalence of each degeneration pattern by age group < 45, 45-54, 55-64, ≥65. In multivariate analyses we examined the association between disk height loss and the response variable of facet joint osteoarthritis, while adjusting for age, sex, BMI, and smoking. Results- As the prevalence of the no degeneration and isolated anterior degeneration patterns decreased with increasing age group, the prevalence of the combined anterior/posterior degeneration pattern increased. 22% of individuals demonstrated isolated posterior degeneration, without an increase in prevalence by age group. Isolated posterior degeneration was most common at the L5-S1 and L4-L5 spinal levels. In multivariate analyses, disk height loss was independently associated with facet joint osteoarthritis, as were increased age (years), female sex, and increased BMI (kg/m2), but not smoking. Conclusions- The observed epidemiology of lumbar spinal degeneration in the community-based population is consistent with an ordered progression beginning in the anterior structures, for the majority of individuals. However, some individuals demonstrate atypical patterns of degeneration, beginning in the posterior joints. Increased age and BMI, and female sex may be related to the occurrence of isolated posterior degeneration in these individuals.

Abstract Background A high quality decision requires that patients who meet clinical criteria for surgery are informed about the options (including non-surgical alternatives) and receive treatments that match their goals. The aim of this study was to evaluate the psychometric properties and clinical sensibility of a patient self report instrument, to measure the quality of decisions about total joint replacement for knee or hip osteoarthritis. Methods The performance of the Hip/Knee Osteoarthritis Decision Quality Instrument (HK-DQI) was evaluated in two samples: (1) a cross-sectional mail survey with 489 patients and 77 providers (study 1); and (2) a randomized controlled trial of a patient decision aid with 138 osteoarthritis patients considering total joint replacement (study 2). The HK-DQI results in two scores. Knowledge items are summed to create a total knowledge score, and a set of goals and concerns are used in a logistic regression model to develop a concordance score. The concordance score measures the proportion of patients whose treatment matched their goals. Hypotheses related to acceptability, feasibility, reliability and validity of the knowledge and concordance scores were examined. Results In study 1, the HK-DQI was completed by 382 patients (79%) and 45 providers (58%), and in study 2 by 127 patients (92%), with low rates of missing data. The DQI-knowledge score was reproducible (ICC = 0.81) and demonstrated discriminant validity (68% decision aid vs. 54% control, and 78% providers vs. 61% patients) and content validity. The concordance score demonstrated predictive validity, as patients whose treatments were concordant with their goals had more confidence and less regret with their decision compared to those who did not. Conclusions The HK-DQI is feasible and acceptable to patients. It can be used to assess whether patients with osteoarthritis are making informed decisions about surgery that are concordant with their goals.

Abstract Background Musculoskeletal disorders affect all racial and ethnic groups, including Hispanics. Because these disorders are not life-threatening, decision-making is generally preference-based. Little is known about whether Hispanics in the U.S. differ from non-Hispanic Whites with respect to key decision making preferences. Methods We assembled six focus groups of Hispanic and non-Hispanic White patients with chronic back or knee pain at an urban medical center to discuss management of their conditions and the roles they preferred in medical decision-making. Hispanic groups were further stratified by socioeconomic status, using neighborhood characteristics as proxy measures. Discussions were led by a moderator, taped, transcribed and analyzed using a grounded theory approach. Results The analysis revealed ethnic differences in several areas pertinent to medical decision-making. Specifically, Hispanic participants were more likely to permit their physician to take the predominant role in making health decisions. Also, Hispanics of lower socioeconomic status generally preferred to use non-internet sources of health information to make medical decisions and to rely on advice obtained by word of mouth. Hispanics emphasized the role of faith and religion in coping with musculoskeletal disability. The analysis also revealed broad areas of concordance across ethnic strata including the primary role that pain and achieving pain relief play in patients' experiences and decisions. Conclusions These findings suggest differences between Hispanics and non-Hispanic Whites in preferred information sources and decision-making roles. These findings are hypothesis-generating. If confirmed in further research, they may inform the development of interventions to enhance preference-based decision-making among Hispanics.

Abstract Background No prior studies have examined systematic bias in the musculoskeletal physical examination. The objective of this study was to assess the effects of bias due to prior knowledge of lumbar spine magnetic resonance imaging findings (MRI) on perceived diagnostic accuracy of the physical examination for lumbar radiculopathy. Methods This was a cross-sectional comparison of the performance characteristics of the physical examination with blinding to MRI results (the 'independent group') with performance in the situation where the physical examination was not blinded to MRI results (the 'non-independent group'). The reference standard was the final diagnostic impression of nerve root impingement by the examining physician. Subjects were recruited from a hospital-based outpatient specialty spine clinic. All adults age 18 and older presenting with lower extremity radiating pain of duration ≤ 12 weeks were evaluated for participation. 154 consecutively recruited subjects with lumbar disk herniation confirmed by lumbar spine MRI were included in this study. Sensitivities and specificities with 95% confidence intervals were calculated in the independent and non-independent groups for the four components of the radiculopathy examination: 1) provocative testing, 2) motor strength testing, 3) pinprick sensory testing, and 4) deep tendon reflex testing. Results The perceived sensitivity of sensory testing was higher with prior knowledge of MRI results (20% vs. 36%; p = 0.05). Sensitivities and specificities for exam components otherwise showed no statistically significant differences between groups. Conclusions Prior knowledge of lumbar MRI results may introduce bias into the pinprick sensory testing component of the physical examination for lumbar radiculopathy. No statistically significant effect of bias was seen for other components of the physical examination. The effect of bias due to prior knowledge of lumbar MRI results should be considered when an isolated sensory deficit on examination is used in medical decision-making. Further studies of bias should include surgical clinic populations and other common diagnoses including shoulder, knee and hip pathology.

Abstract Background Venous thromboembolism is a common, fatal, and costly injury which complicates major surgery in older adults. The American College of Chest Physicians recommends high potency prophylaxis regimens for individuals undergoing total hip or knee replacement (THR or TKR), but surgeons are reluctant to prescribe them due to fear of excess bleeding. Identifying a high risk cohort such as older adults with comorbidities and co-occurring comorbidities who might benefit most from high potency prophylaxis would improve how we currently perform preoperative assessment. Methods Using the Nationwide Inpatient Sample, we identified older adults who underwent THR or TKR in the U.S. between 2003 and 2006. Our outcome was VTE, including any pulmonary embolus or deep venous thrombosis. We performed multivariate logistic regression analyses to assess the effects of comorbidities on VTE occurrence. Comorbidities under consideration included coronary artery disease, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), diabetes, and cerebrovascular disease. We also examined the impact of co-occurring comorbidities on VTE rates. Results CHF increased odds of VTE in both the THR cohort (OR = 3.08 95% CI 2.05-4.65) and TKR cohort (OR = 2.47 95% CI 1.95-3.14). COPD led to a 50% increase in odds in the TKR cohort (OR = 1.49 95% CI 1.31-1.70). The data did not support synergistic effect of co-occurring comorbidities with respect to VTE occurrence. Conclusions Older adults with CHF undergoing THR or TKR and with COPD undergoing TKR are at increased risk of VTE. If confirmed in other datasets, these older adults may benefit from higher potency prophylaxis.

Abstract Background Studies on critical pathway use have demonstrated decreased length of stay and cost without compromise in quality of care. However, pathway effectiveness is difficult to determine given methodological flaws, such as small or single center cohorts. We studied the effect of critical pathways on total knee replacement outcomes in a large population-based study. Methods We identified hospitals in four US states that performed total knee replacements. We sent a questionnaire to surgical administrators in these hospitals including items about critical pathway use and hospital characteristics potentially related to outcomes. Patient data were obtained from Medicare claims, including demographics, comorbidities, 90-day postoperative complications and length of hospital stay. The principal outcome measure was the risk of having one or more postoperative complications. Results Two hundred ninety five hospitals (73%) responded to the questionnaire, with 201 reporting the use of critical pathways. 9,157 Medicare beneficiaries underwent TKR in these hospitals with a mean age of 74 years (± 5.8). After adjusting for both patient and hospital related variables, patients in hospitals with pathways were 32% less likely to have a postoperative complication compared to patients in hospitals without pathways (OR 0.68, 95% CI 0.50-0.92). Patients managed on a critical pathway had an average length of stay 0.5 days (95% CI 0.3-0.6) shorter than patients not managed on a pathway. Conclusion Medicare patients undergoing total knee replacement surgery in hospitals that used critical pathways had fewer postoperative complications than patients in hospitals without pathways, even after adjusting for patient and hospital related factors. This study has helped to establish that critical pathway use is associated with lower rates of postoperative mortality and complications following total knee replacement after adjusting for measured variables.

Abstract Background In this cross-sectional study, we conducted a comprehensive assessment of all articular elements that could be measured using knee MRI. We assessed the association of pathological change in multiple articular structures involved in the pathoanatomy of osteoarthritis. Methods Knee MRI scans from patients over 45 years old were assessed using a semi-quantitative knee MRI assessment form. The form included six distinct elements: cartilage, bone marrow lesions, osteophytes, subchondral sclerosis, joint effusion and synovitis. Each type of pathology was graded using an ordinal scale with a value of zero indicating no pathology and higher values indicating increasingly severe levels of pathology. The principal dependent variable for comparison was the mean cartilage disease score (CDS), which captured the aggregate extent of involvement of articular cartilage. The distribution of CDS was compared to the individual and cumulative distributions of each articular element using the Chi-squared test. The correlations between pathological change in the various articular structures were assessed in a Spearman correlation table. Results Data from 140 patients were available for review. The cohort had a median age of 61 years (range 45-89) and was 61% female. The cohort included a wide spectrum of OA severity. Our analysis showed a statistically significant trend towards pathological change involving more articular elements as CDS worsened (p-value for trend < 0.0001). Comparison of CDS to change in the severity of pathology of individual articular elements showed statistically significant trends towards more severe pathology as CDS worsened for osteophytes (p-value for trend < 0.0001), bone marrow lesions (p = 0.0003), and subchondral sclerosis (p = 0.009), but not joint effusion or synovitis. There was a moderate correlation between cartilage damage, osteophytes and BMLs as well as a moderate correlation between joint effusion and synovitis. However, cartilage damage and osteophytes were only weakly associated with synovitis or joint effusion. Conclusion Our results support an inter-relationship of multiple articular elements in the pathoanatomy of knee OA. Prospective studies of OA pathogenesis in humans are needed to correlate these findings to clinically relevant outcomes such as pain and function.

Abstract Background While musculoskeletal problems are leading sources of disability, there has been little research on measuring the number of functionally limiting musculoskeletal problems for use as predictor of outcome in studies of chronic disease. This paper reports on the development and preliminary validation of a self administered musculoskeletal functional limitations index. Methods We developed a summary musculoskeletal functional limitations index based upon a six-item self administered questionnaire in which subjects indicate whether they are limited a lot, a little or not at all because of problems in six anatomic regions (knees, hips, ankles and feet, back, neck, upper extremities). Responses are summed into an index score. The index was completed by a sample of total knee replacement recipients from four US states. Our analyses examined convergent validity at the item and at the index level as well as discriminant validity and the independence of the index from other correlates of quality of life. Results 782 subjects completed all items of the musculoskeletal functional limitations index and were included in the analyses. The mean age of the sample was 75 years and 64% were female. The index demonstrated anticipated associations with self-reported quality of life, activities of daily living, WOMAC functional status score, use of walking support, frequency of usual exercise, frequency of falls and dependence upon another person for assistance with chores. The index was strongly and independently associated with self-reported overall health. Conclusion The self-reported musculoskeletal functional limitations index appears to be a valid measure of musculoskeletal functional limitations, in the aspects of validity assessed in this study. It is useful for outcome studies following TKR and shows promise as a covariate in studies of chronic disease outcomes.

Abstract Background Comorbid psychopathology is an important predictor of poor outcome for many types of treatments for back or neck pain. But it is unknown if this applies to the results of medial branch blocks (MBBs) for chronic low back or neck pain, which involves injecting the medial branch of the dorsal ramus nerves that innervate the facet joints. The objective of this study was to determine whether high levels of psychopathology are predictive of pain relief after MBB injections in the lumbar or cervical spine. Methods This was a prospective cohort study. Consecutive patients in a pain medicine practice undergoing MBBs of the lumbar or cervical facets with corticosteroids were recruited to participate. Subjects were selected for a MBB based on operationalized selection criteria and the procedure was performed in a standardized manner. Subjects completed the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression Scale (HADS) just prior to the procedure and at one-month follow up. Scores on the HADS classified the subjects into three groups based on psychiatric symptoms, which formed the primary predictor variable: Low, Moderate, or High levels of psychopathology. The primary outcome measure was the percent improvement in average daily pain rating one-month following an injection. Analysis of variance and chi-square were used to analyze the analgesia and functional rating differences between groups, and to perform a responder analysis. Results Eighty six (86) subjects completed the study. The Low psychopathology group (n = 37) reported a mean of 23% improvement in pain at one-month while the High psychopathology group (n = 29) reported a mean worsening of -5.8% in pain (p < .001). Forty five percent (45%) of the Low group had at least 30% improvement in pain versus 10% in the High group (p < .001). Using an analysis of covariance, no baseline demographic, social, or medical variables were significant predictors of pain improvement, nor did they mitigate the effect of psychopathology on the outcome. Conclusion Psychiatric comorbidity is associated with diminished pain relief after a MBB injection performed with steroid at one-month follow-up. These findings illustrate the importance of assessing comorbid psychopathology as part of a spine care evaluation.

Standard treatment approaches for localized prostate cancer remain limited to active surveillance, radiotherapy, and radical prostatectomy. We present a case of transition zone prostate cancer that was treated with holmium laser enucleation of the prostate, a procedure that is normally reserved for the management of benign prostatic hyperplasia.

Introduction: COVID-19 has had a devastating impact on people's lives since its initial outbreak and global spread in 2020. While the U.S. government and public health officials have recommended best practices such as social distancing, wearing a mask, and avoiding large public gatherings, these orders have been met with varying levels of acceptance from the public. Given the disparate compliance, this study builds on Social Cognitive Theory (SCT) to explore individual differences and personal motivation factors in order to better understand what may influence one's likelihood to adhere to COVID-19 protective measures., Methods: A U.S. national survey ( N  = 2,049) was conducted April-May 2020, roughly one month after stay-at-home orders were issued in some states. Participants were asked to report their likelihood of taking individual and community protective measures. Multivariate hierarchical linear regressions were run to analyze the extent to which participants' concerns about COVID-19's impact, individual and collective self-efficacy, coping behaviors, and personality traits influenced the dependent variables., Results: Findings showed that COVID-19-related health concerns, collective efficacy, and proactive coping strategies were positively related to participants' likelihood of taking protective measures. Those with greater concerns about their general well-being and the economy, adverse coping strategies like denial and joking, as well as sensation-seeking personalities, were less likely to take protective measures., Conclusion: The discussion considers how individual differences fit into broader global efforts to stem COVID-19. Practical implications for public health messaging are that communication may focus on facilitating efficacy in order to boost compliance with protective measures.

Three-dimensional (3D) in vitro models are essential in cancer research, but they often neglect physical forces. In our study, we combined patient-derived tumor organoids with a microfluidic organ-on-chip system to investigate colorectal cancer (CRC) invasion in the tumor microenvironment (TME). This allowed us to create patient-specific tumor models and assess the impact of physical forces on cancer biology. Our findings showed that the organoid-on-chip models more closely resembled patient tumors at the transcriptional level, surpassing organoids alone. Using 'omics' methods and live-cell imaging, we observed heightened responsiveness of KRAS mutant tumors to TME mechanical forces. These tumors also utilized the γ-aminobutyric acid (GABA) neurotransmitter as an energy source, increasing their invasiveness. This bioengineered model holds promise for advancing our understanding of cancer progression and improving CRC treatments., Competing Interests: DECLARATION OF INTEREST The authors declare no competing interest.

Monoamine oxidases (MAOA/MAOB) are enzymes known for their role in neurotransmitter regulation in the central nervous system (CNS). Irreversible and non-selective MAO inhibitors (MAOi's) were the first class of antidepressants, thus subsequent work on drugs such as the selective MAOA inhibitor clorgyline has focussed on selectivity and increased CNS penetration. MAOA is highly expressed in high grade and metastatic prostate cancer with a proposed effect on prostate cancer growth, recurrence, and drug resistance. A Phase II Clinical Trial has demonstrated the therapeutic effects of the irreversible nonselective MAOi phenelzine for prostate cancer. However, neurologic adverse effects led to early withdrawal in 25% of the enrolled patient-population. In this work, we revised the clorgyline scaffold with the goal of decreasing CNS penetration to minimize CNS-related side effects while retaining or enhancing MAOA inhibition potency and selectivity. Using the known co-crystal structure of clorgyline bound with FAD co-factor in the hMAOA active site as a reference, we designed and synthesized a series of compounds predicted to have lower CNS penetration (logBB). All synthesized derivatives displayed favorable drug-like characteristics such as predicted Caco-2 permeability and human oral absorption, and exhibited highly selective hMAOA binding interactions. Introduction of an HBD group (NH 2 or OH) at position 5 of the phenyl ring clorgyline resulted in 3x more potent hMAOA inhibition with equivalent or better hMAOB selectivity, and similar prostate cancer cell cytotoxicity. In contrast, introduction of larger substituents at this position or at the terminal amine significantly reduced the hMAOA inhibition potency, attributed in part to a steric clash within the binding pocket of the MAOA active site. Replacement of the N-methyl group by a more polar, but larger 2-hydroxyethyl group did not enhance potency. However, introduction of a polar 2-hydroxy in the propyl chain retained the highly selective MAOA inhibition and cancer cell cytotoxicity of clorgyline while reducing its CNS score from 2 to 0. We believe that these results identify a new class of peripherally directed MAOIs that may allow safer therapeutic targeting of MAOA for a variety of anti-cancer and anti-inflammatory indications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To improve upon prior attempts to predict which patients will pass their obstructing ureteral stones, we developed a machine learning algorithm to predict the passage of obstructing ureteral stones using only the CT scan at a patient's initial presentation., Methods: We obtained Institutional Review Board approval to conduct a retrospective study by extracting data from all patients with an obstructing 3-10 mm ureteral stone. We included patients with sufficient data to be categorized as having either passed or failed to pass an obstructing ureteral stone. We developed a 3D-convolutional neural network (CNN) model using a dynamic learning rate, the Adam optimizer, and early stopping with 10-fold cross-validation. Using this model, we calculated the area under the curve (AUC) and developed a model confusion matrix, which we compared with a model based only on the largest dimension of the stone., Results: A total of 138 patients met inclusion criteria and had adequate images that could be preprocessed and included in the study. Seventy patients failed to pass their ureteral stones, and 68 patients passed their stones. For the 3D-CNN model, the mean AUC was 0.95 with an overall mean sensitivity of 95% and mean specificity of 77%, which outperformed the model based on stone-size., Conclusion: The 3D-CNN model predicts which patients will pass their obstructing ureteral stones based on CT scan alone and does not require any further measurements. This can provide useful clinical information which may help obviate the need for a delay in care for patients who inevitably require surgical intervention., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is a movement disorder characterized by neuroinflammation, α-synuclein pathology, and neurodegeneration. Most cases of PD are non-hereditary, suggesting a strong role for environmental factors, and it has been speculated that disease may originate in peripheral tissues such as the gastrointestinal (GI) tract before affecting the brain. The gut microbiome is altered in PD and may impact motor and GI symptoms as indicated by animal studies, although mechanisms of gut-brain interactions remain incompletely defined. Intestinal bacteria ferment dietary fibers into short-chain fatty acids, with fecal levels of these molecules differing between PD and healthy controls and in mouse models. Among other effects, dietary microbial metabolites can modulate activation of microglia, brain-resident immune cells implicated in PD. We therefore investigated whether a fiber-rich diet influences microglial function in α-synuclein overexpressing (ASO) mice, a preclinical model with PD-like symptoms and pathology. Feeding a prebiotic high-fiber diet attenuates motor deficits and reduces α-synuclein aggregation in the substantia nigra of mice. Concomitantly, the gut microbiome of ASO mice adopts a profile correlated with health upon prebiotic treatment, which also reduces microglial activation. Single-cell RNA-seq analysis of microglia from the substantia nigra and striatum uncovers increased pro-inflammatory signaling and reduced homeostatic responses in ASO mice compared to wild-type counterparts on standard diets. However, prebiotic feeding reverses pathogenic microglial states in ASO mice and promotes expansion of protective disease-associated macrophage (DAM) subsets of microglia. Notably, depletion of microglia using a CSF1R inhibitor eliminates the beneficial effects of prebiotics by restoring motor deficits to ASO mice despite feeding a prebiotic diet. These studies uncover a novel microglia-dependent interaction between diet and motor symptoms in mice, findings that may have implications for neuroinflammation and PD., Competing Interests: RA, JS, JB, TT, MZ, JB, TK, SC, LM, GH, JK, MT, RK, VG, CG No competing interests declared, TC, AK, BH has equity in RiteCarbs, a company developing prebiotic diets for Parkinson's disease, SM has equity in Axial Therapeutics, a company developing gut-restricted drugs for Parkinson's disease, (© 2022, Abdel-Haq et al.)

Unilateral acquired diaphragmatic paresis is a known complication of thoracic surgeries. Direct mechanical injury to the phrenic nerve during surgery results in this complication. However its occurrence post-percutaneous nephrolithotomy (PCNL) has not been described. We report a 43-year-old man who underwent prone PCNL for endourological management of left complete staghorn calculus. Access via the 10 th left intercostal space, under fluoroscopy, was carried out to remove the calculus. Post-operative, the routine chest radiograph revealed left hemidiaphragmatic blunting. Computerized tomography of the chest confirmed left hemidiaphragmatic elevation, suggesting unilateral diaphragmatic paresis. He did not have any respiratory symptoms, was managed conservatively with chest physiotherapy and incentive spirometry and responded extremely well. The absence of reported cases of diaphragmatic paresis post PCNL lends to a dearth in knowledge regarding recognition and management. This case report aims to acquaint urologists with this rare complication associated with supracostal PCNL and provide a rational management plan., Competing Interests: None

Purpose: The aim of the study was to prospectively evaluate safety and efficacy of bilateral same session ureterorenoscopy (BSS-FURS) for management of bilateral renal calculi., Methods: A prospective comparative study was designed to compare the results of BSS-FURS with unilateral flexible ureterorenoscopy (U-FURS) for management of renal calculi between June 2003 and May 2016. A sample size of 55 patients in each arm was calculated considering a 20% increase in the incidence of complications with BSS-FURS over 15% complication rate in U-FURS (alpha = 0.05; Beta = 0.90). Patient demographics, stone burden, total operative time, postoperative creatinine level, duration of hospital stay, perioperative complications and stone free rate (SFR) were compared in both the groups. The literature pertaining to BSS-FURS was reviewed., Results: Although the study group patients had higher overall stone burden (18.60 ± 7.70 mm vs. 13.32 ± 6.43 mm) and significantly longer operative time (48.30 ± 16.71 min vs. 32.95 ± 13.05 min; p  < 0.05) as compared to the control group, the length of hospital stay, SFR (67.85% vs. 78.5%; p  = 0.436) and perioperative complications were comparable in both the groups. Most patients who developed postoperative fever from both groups had struvite stones., Conclusion: BSS-FURS is a safe and efficient procedure for the management of bilateral renal calculi in the hands of an experienced endourologist. It has comparable SFR and morbidity compared to U-FURS. Caution should be exercised in patients with struvite stones, as they are more likely to develop postoperative fever.

Objective: The primary purpose was to compare the completeness of adenomectomy and zonal anatomy of prostate on magnetic resonance imaging prostate after transurethral resection of prostate and Holmium enucleation of prostate. The secondary purpose was to investigate the relationship between preoperative total prostate volume and postoperative transition zone and peripheral zone volume after both procedures., Material and Methods: A retrospective review of all patients who underwent transurethral resection of pros- tate or Holmium enucleation of prostate over 3 years (2017-2020) and had at least 1 postoperative magnetic resonance imaging prostate was performed. Volume estimations of the prostate and individual zones were per- formed, and statistical comparisons were made to evaluate morphometric changes between the 2 procedures., Results: A total of 9 patients (mean age, 71.8 years) underwent transurethral resection of prostate and 12 patients (mean age, 66.9 years) underwent Holmium enucleation of prostate. The median pre-operative prostate volume in the Holmium enucleation of prostate group was higher than the transurethral resection of prostate group (101.5 g vs. 62 g; P =.102). However, there was a significant difference in the resected tissue weight favoring Holmium enucleation of prostate over transurethral resection of prostate (P value=.004). The postoperative transition zone and peripheral zone volume as calculated by magnetic resonance imaging remained relatively constant in both procedures. The peripheral zone volume on postoperative magnetic res- onance imaging was found to be independent of transition zone volume even for very large-sized prostates., Conclusion: A well-performed transurethral resection of prostate or Holmium enucleation of prostate cannearly completely eliminate the transition zone volume, irrespective of the size of the prostate as confirmed by magnetic resonance imaging prostate. Additionally, the peripheral zone volume is consistent across the entire spectrum of the prostate size.

Objectives: To prospectively evaluate safety and efficacy of holmium laser enucleation of prostate (HoLEP) for surgical treatment of recurrent symptoms due to prostatomegaly after prior transurethral resection of prostate (TURP)., Materials and Methods: We prospectively evaluated 43 patients with a history of TURP who underwent HoLEP (study group). Patients in chronological order who underwent HoLEP without prior TURP were included in the control group. We hypothesized that prior TURP would increase technical difficulties, thereby leading to a reduction in procedure efficiency by 25%. Patients' demographic, intraoperative, and postoperative data were compared, and statistical analysis was performed., Results: Demographic data in both groups were comparable. The average interval between past TURP and HoLEP was 4.22 years. There was no difficulty in identifying the dissection plane in the study group and the difference in the procedure efficiency between the study and the control groups were statistically insignificant (0.75 ± 0.31 g/min-study group vs. 0.69 ± 0.36 g/min-control group; P = 0.665). The intraoperative parameters and postoperative outcomes were comparable in both groups., Conclusions: Prior TURP does not negatively impact the outcome of HoLEP in treating symptomatic recurrence for enlarged prostate after initial TURP., Competing Interests: Dr. Hemendra N. Shah served as trainer for HoLEP for LUMENIS and received 1000$ remuneration in 2018. All other authors have no disclosures or conflicts of interest., (Copyright: © 2022 Urology Annals.)

Several diseases associated with erectile dysfunction (ED), such as type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), are known to have seasonal variation, with increased incidence during winter months. However, no literature exists on whether this chronological-seasonal evolution is also present within ED symptomatology. We hypothesized ED would follow the seasonal pattern of its lifestyle-influenced comorbid conditions and exhibit increased incidence during winter months. In order to investigate the seasonal variation of ED in the United States between 2009 and 2019, Internet search query data were obtained using Google Trends. Normalized search volume was determined during the winter and summer seasons for ED, other diseases known to be significantly associated with ED (T2DM and CAD), kidney stones (positive control), and prostate cancer (negative control). There were significantly more internet search queries for ED during the winter than during the summer (p = 0.001). CAD and T2DM also had significantly increased search volume during winter months compared to summer months (p < 0.001 and p = 0.011, respectively). By contrast, searches for kidney stones were significantly increased in the summer than in the winter (p < 0.001). There was no significant seasonal variation in the relative search frequency for prostate cancer (p = 0.75). In conclusion, Google Trends internet search data across a ten-year period in the United States suggested a seasonal variation in ED, which implies an increase in ED during winter. This novel finding in ED epidemiology may help increase awareness of ED's associated lifestyle risk factors, which may facilitate early medical evaluation and treatment for those at risk of both ED and cardiovascular disease., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Purpose: To evaluate safety and efficacy of Holmium laser enucleation of Prostate (HoLEP) for management of persistent or recurrent lower urinary tract symptoms after prior prostate artery embolization (PAE). We also evaluated histopathological changes in prostate after PAE., Methods: Ten patients who underwent HoLEP after prior PAE were matched according to age, weight of resected prostate tissue, and anticoagulation status in 1:2 ratio with patients who underwent HoLEP without prior PAE by a researcher who was blinded to patient's outcome at the time of matching. Histopathological examination of prostate tissue was performed to look for changes related to prior PAE. Patient's demographics, perioperative parameters, and follow-up data were retrospectively compared., Results: The median interval between PAE and HoLEP was 25 months [IQR 14.5-37.5]. Patients demographic were comparable in both groups. Intra-operatively plane of enucleation were well-maintained in spite of prior PAE. The differences in duration of surgery, enucleation efficiency, hemoglobin drop, duration of catheterization and hospital stay, and complications were statistically insignificant. Incidental prostate cancer was identified in 10% specimens from both groups. Post-PAE prostate specimens demonstrated evidence of remote-healed infarction represented by dense hyalinized paucicellur connective tissue with surrounding squamous metaplasia. There were no statistically significant differences in AUA symptom scores, maximum urine flow rate, post-void residual urine volume, and PSA at 3- and 6-month follow-up between both groups., Conclusions: Plane of enucleation is well-maintained after prior PAE. Salvage HoLEP is safe and effective after previous PAE and provide outcome comparable with HoLEP as a primary procedure., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Urolithiasis is a growing issue globally, but it is heterogeneous, with a different epidemiology and pathophysiology for each different stone composition., Objective: The purpose of this study is to describe the incidence of urinary stones in the USA from 2016 to 2019 by chemical composition and to investigate the influence of age and geography on these stone types., Design Setting and Participants: We obtained compositional analyses for all urinary stones submitted to a national laboratory over an approximately 3-yr period., Outcome Measurements and Statistical Analysis: Data collected included the chemical constituents of a stone, patient age, and geographical origin. We describe the incidence of each stone type by frequency. Statistical testing was performed to determine the influence of age and geographical region on overall incidence of each stone composition., Results and Limitations: In total, 99 908 specimens were analyzed. When pure stones were ordered by frequency, we found that the most common stone type was calcium oxalate (CaOx) (79.2%), followed by uric acid (UA; 14.3%), calcium phosphate (CaPO 4 ; 3.7%), cystine (0.51%), drug induced (0.12%), and magnesium ammonium phosphate (0.04%). CaOx, UA, and CaPO 4 were often mixed with one another. Among CaOx stones, the plurality (28.0%) was made of pure calcium oxalate monohydrate (COM), and only 0.002% was pure calcium oxalate dihydrate. There was an overall association between stone composition and both geographical distribution and age ( p < 0.001)., Conclusions: CaOx stones comprise the majority of urinary stones in the USA, of which almost 28% were pure COM. Additionally, age and geographical region are significantly associated with variations in stone composition., Patient Summary: We evaluated the incidence of urinary stones in the USA based on their chemical composition. The most common stone type was calcium oxalate, the majority of which was pure calcium oxalate monohydrate. We also found age and geographical region to be significantly associated with variations in stone composition., (© 2021 The Author(s).)

Purpose: To prospectively investigate the efficacy and safety of high-power (100 W) vs low-power (20 W) laser settings for transurethral laser lithotripsy in the management large vesical calculi (> 4 cm)., Methods: All patients with vesical calculi > 4 cm in the maximum dimension and scheduled for transurethral holmium laser lithotripsy were invited to participate in the study. Every alternate patient was treated with either the low- or high-power laser settings. We used a continuous irrigation resectoscope with laser bridge or a laser working element (Karl Storz) for laser lithotripsy of bladder stones. We compared the operative time, intra-operative/post-operative complications (up to 1 year), and stone-free rates between the treatment groups using IBM SPSS Statistics 24 software. Comparisons between treatment groups for continuous variables were assessed using the Welch test, while categorical variables were compared with either the Chi-square or Fisher's exact test. A p value < 0.05 was considered statistically significant., Results: Twenty patients with ten in each cohort were recruited. Preoperative data and mean bladder stone size were comparable in both groups. The duration of surgery was significantly reduced from 70.80 ± 25.28 min in low-power cohort to 40.90 ± 15.01 min in the high-power group (p = 0.005). There were no significant intra-operative complications in either group. All patients were stone-free following the procedure., Conclusion: High-power laser setting of up to 100 W results in a significant reduction in duration of surgery without any increase in the complication rate for treatment of large bladder stones., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: To demonstrate technique of salvage thylium fiber laser enucleation of prostate in men with history of prior prostatic urethral lift (PUL) implant. PUL is an accepted treatment modality for benign prostatic hyperplasia (BPH) and is currently recommended for surgical management of prostates <80 g in size. 1 However, in reality some patients with prostate >80 g also receive PUL. 2 A substantial number of these patients may requirement re-treatment for recurrent or persistent lower urinary tract symptoms after PUL. 3-5 Patients with larger prostates who fail PUL might be better managed with endoscopic enucleation which is a size-independent modality for treatment of BPH. 1 , 6 Endoscopic enucleation can be accomplished via a variety of energy sources. Thulium fiber laser is a new addition to urologist armamentarium for endoscopic enucleation of prostate. We hereby present a video demonstrating salvage thulium fiber laser enucleation of 198 cc prostate in a men with history of prior PUL., Methods: A 66-year-old male presented with a history of recurrent urine retention after prior PUL done 2 years prior at an outside institution. Pre-operative international prostate symptom score was 13, maximum uroflow rate was 6.1 ml/sec, residual urine was 26 ml despite maximal medical management. MRI demonstrated a 198 g prostate and PSA was 13.4 ng/dl with negative prostate biopsy. After a detailed discussion of options, he elected endoscopic enucleation. We employed a 550-micron Soltive superpulsed laser fiber set at 2 J and 30 Hz to perform en-bloc enucleation of prostate, and morcellation was performed with the VersaCut Morcellator. We edited the video to demonstrate the technical nuances of this procedure., Results: Surgery was uneventful with enucleation time of 70 minutes and morcellation time of 142 minutes. Implants encountered during enucleation were easily separated with the thulium fiber laser. No attempt was made to remove implants segments extending beyond the plane of enucleation. Morcellation was challenging, with evidence of damage to morcellation probes requiring replacement of 3 morcellator probes. The patient was discharged on post-operative day one after successful voiding trial. At six-week follow up, his international prostate symptom score of 3 with maximum urinary flow rate of 50 mL/sec. He reported no urinary incontinence and his pathology demonstrated BPH., Conclusion: This video demonstrates the feasibility of thulium fiber laser enucleation of prostate after PUL, however the findings need to be reproduced in cohort studies. It also demonstrates difficulties encountered during morcellation. For smaller prostates, vaporization may be preferable, thereby avoiding difficulties associated with morcellation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To report the results of a randomized controlled trial comparing outcomes between medium power (MP) and high power (HP) laser settings for HoLEPs., Methods: The primary objective was to compare the enucleation efficiency (EE) of HP- HoLEP (80-100 W) with MP-HoLEP (50 - 60 W). The secondary objectives were to compare treatment efficacy and safety between both groups. To show a 25% difference in EE, a sample size of 45 individuals per treatment arm was required (alpha = 0.05; Beta = 0.80). Patients demographic and perioperative factors were analyzed, including EE, hemoglobin drop, duration of catheterization, and length of hospital stay. The surgical outcome was evaluated with AUA symptom score, maximum flow rate, postvoid residual urine, and complications to assess differences between MP and HP HoLEP at baseline, 3 months, 1, and 5 years. Quantitative outcomes were compared with independent sample t tests (2-tailed) and qualitative outcomes were compared with chi-square tests., Results: Preoperative data with the exception of indication for surgery were comparable in both treatment arms. There was no statistically significant difference in enucleation efficiency between the HP-HoLEP and MP-HoLEP laser setting (0.97 ± 0.47 vs. 0.85 ± 0.47 gm/min, p = 0.209). MP laser settings did not increase perioperative or postoperative complications and resulted in durable outcome comparable with HP laser settings at 5-year follow-up., Conclusions: MP-HoLEP is safe and efficient and does not compromise the outcome for HoLEPs when compared with HP-HoLEP., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Osteitis pubis is a rare but known complication of multiple urological procedures including transurethral resection of the prostate, prostate cryotherapy, photovaporisation of the prostate, high-intensity focused ultrasound treatment of the prostate, prostatectomy and cystectomy, especially in the context of salvage therapy for prostate cancer. Patients can present with significant often intractable pain secondary to this condition. We report a case of a patient with a history of radiation therapy and salvage cryoablation who presented with osteitis pubis, calcification of the prostatic tissue bed which was inseparable from the pubic symphysis. Treatment with salvage holmium laser enucleation of the prostate and holmium lithotripsy was demonstrated to be effective for palliative management of osteitis pubis from prostatic calcification ossifying into the pubic symphysis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Colorectal cancer (CRC) progression is a complex process that is not well understood. We describe an in vitro organ-on-chip model that emulates in vivo tissue structure and the tumor microenvironment (TME) to better understand intravasation, an early step in metastasis. The CRC-on-chip incorporates fluid flow and peristalsis-like cyclic stretching and consists of endothelial and epithelial compartments, separated by a porous membrane. On-chip imaging and effluent analyses are used to interrogate CRC progression and the resulting cellular heterogeneity. Mass spectrometry-based metabolite profiles are indicative of a CRC disease state. Tumor cells intravasate from the epithelial channel to the endothelial channel, revealing differences in invasion between aggressive and non-aggressive tumor cells. Tuning the TME by peristalsis-like mechanical forces, the epithelial:endothelial interface, and the addition of fibroblasts influences the invasive capabilities of tumor cells. The CRC-on-chip is a tunable human-relevant model system and a valuable tool to study early invasive events in cancer., Competing Interests: The authors declare no competing interest., (© 2021 The Author(s).)

Nephropleural fistula is a rarely encountered complication of percutaneous nephrolithotomy (PCNL). Only 11 cases have been reported in literature to date. Often associated with supracostal punctures, the presentation is frequently delayed. Diagnosis is based on imaging, mainly X-rays and CT along with retrograde pyelography that establishes the fistulous connection. A difficult to diagnose condition, any patient with a supracostal access PCNL who presents with delayed symptoms of breathlessness and has leucocytosis with fluid in the lungs on chest imaging should be suspected to have a nephropleural fistula. The management involves intercostal tube thoracostomy to relieve symptoms and drainage of the operated kidney by double-J stent placement, if not placed already. Prompt recognition and management results in excellent recovery with no sequelae. We present our experience with two such cases and our aim was to familiarise the practising urologist regarding the diagnosis and management of this infrequent condition., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Migration of abdominal wall mesh in an augmented bladder is a rarely encountered complication leading to formation of bladder stones causing recurrent urinary tract symptoms. The usual management of this condition involves either open surgical or a percutaneous approach for removal of the stone and migrated portion of mesh. Diagnosis of a migrated mesh is usually made intraoperatively during cystolitholapaxy. Appropriate management results in symptomatic improvement. Endoscopic management through catheterisable continent appendicovesicostomy has not been described to manage this challenging condition. To the best of our knowledge, we describe herewith the first report of endoscopic management of a large bladder stone formed over migrated mesh which involved removal of migrated mesh with holmium laser via a Mitrafanoff., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction and Objectives: Published literature on damages to a digital flexible ureteroscope (DFU) examines a limited number of ureteroscopes and shows wide variation in its durability. The aim of this study was to compare the primary damage location, causes of DFU damages, and the durability of Karl Storz Flex-Xc digital ureteroscope between University Hospital (UH) and Ambulatory Care Surgery Center (ASC). We also evaluated the available literature on the durability of DFU. Methods: Each damaged DFU prospectively underwent a manufacturer's evaluation to determine the reason for return and primary site of damage. Hospital data on the number of ureteroscopic procedures and damaged DFUs over 3 years were retrospectively reviewed. The possible reason for the damage was classified as either intraoperative or between the procedures. The durability of DFUs, type, and cause of damage were compared between the UH and nonteaching ASC. A chi-square test was utilized for categorical variables. When cell frequencies were <5, Fisher's exact test was used. Results: During the study period, 1211 ureteroscopies were performed and 143 ureteroscopes were returned to the manufacturer. The mean number of uses was 7.45 at the UH and 16.5 at the ASC. The location and cause of damage were similar at both locations. The most common locations of primary damage were at the angle cover (70.6%) and instrument channel (19.2%). Most damage occurred during the handling of the ureteroscopes between surgical procedures (78%). On review of the literature, we found that DFUs were 6 times more durable in a nonteaching hospital. Conclusions: The DFU was more than two times as durable in the ASC as in the UH. Most incidents occurred during handling between surgical procedures. Future research is needed to examine the impact of training and certification of support staff on durability of DFUs.

Objective: To evaluate the safety and efficacy of performing Holmium laser enucleation of the prostate (HoLEP) for the treatment of bladder outlet obstruction secondary to an enlarged prostate within 6-weeks of a transrectal ultrasound (TRUS) guided prostate biopsy., Materials and Methods: We performed a retrospective review of patients who underwent a HoLEP at our institution, excluding any patients with a confounding urologic history and compared patients who underwent a TRUS-guided 6- or 12-core prostate biopsy, and then underwent a HoLEP within 6 weeks (study group) with all other patients (control group). Our primary outcomes were enucleation efficiency (EE) and perioperative complication rate. Our secondary outcomes included postoperative drop in hemoglobin, duration of catheterization, length of hospital stay, voiding metrics at 1 and 6 months and rate of incidental prostate cancer diagnosed on histopathological examination of prostate specimens after HoLEP. To test for differences between the study and control groups, we performed independent sample t-test (2-tailed) and chi-square tests for quantitative and qualitative variables, respectively. P values of < 0.05 were considered statistically significant., Results: 552 patients met inclusion criteria and 84 patients underwent prostate biopsy within a period of 45 days prior to HoLEP. Enucleation efficiency was higher in the study group (P = 0.00). There was no significant difference between the 2 groups regarding perioperative complications, postoperative voiding outcomes, or rate of incidental prostate cancer detection., Conclusions: TRUS prostate biopsy performed within 6 weeks of HoLEP does not negatively impact operative difficulty or treatment outcome., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship of preoperative prostate size, urinary retention, positive urine culture, and histopathological evidence of prostatitis or incidental prostate cancer on baseline and 3-month nadir prostate-specific antigen (PSA) value after Holmium laser enucleation of prostate (HoLEP)., Patients and Methods: Data from 90 patients who underwent a HoLEP by En-bloc technique were analyzed. PSA values at baseline and at 3-month follow-up, preoperative urinary retention and urine culture status, weight of resected tissue, and histopathological evidence of prostatitis or prostate cancer were recorded. We performed univariable and multivariable gamma-regression analyses to determine the impact of the aforementioned perioperative variables on preoperative PSA, 3-month postoperative PSA, and change in PSA., Results: Serum PSA reduced significantly at 3 months from 6.3 ± 5.9 ng/mL to 0.6 ± 0.6 ng/mL. On both univariable and multivariable analysis, 3-month nadir level was independent of all preoperative factors examined, except preoperative urinary retention status. Although patients with smaller prostate (resected tissue weight <40 g) had less percentile reduction in PSA when compared with those with larger prostate (resected tissue weight >80 g) (77.67% vs 89.06%; P  < .001), patients from both these groups noted a similar PSA nadir level after 3 months (0.54 vs 0.56 ng/dL). The drop in PSA level after HoLEP remained stable up to 1-year follow-up., Conclusions: PSA nadir 3 months after HoLEP remains relatively consistent across patients, regardless of preoperative prostate size, PSA value, urine culture status, and histopathological evidence of prostatitis or incidental prostate cancer., Competing Interests: The authors declare no competing financial interests., (© 2021 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

There are many advantages for deploying a mass spectrometry workflow to the cloud. While "cloud computing" can have many meanings, in this case, I am simply referring to a virtual computer that is remotely accessible over the Internet. This "computer" can have as many or few resources (CPU, RAM, disk space, etc.) as your demands require and those resources can be changed as you need without requiring complete reinstalls. Systems can be easily "checkpointed" and restored. I will describe how to deploy virtualized, remotely accessible computers on which you can perform your basic mass spectrometry data analysis. This use is a quite restricted microcosm of what is available under the umbrella of "cloud computing" but it is also the (useful!) niche use for which straightforward how-to documentation is lacking.This chapter is intended for people with little or no experience in creating cloud computing instances. Executing the steps in this chapter, will empower you to instantiate a computer with the performance of your choosing with preconfigured software already installed using the Amazon Web Service (AWS) suite of tools. You can use this for use cases that span when you need limited access to high end computing thru when you give your collaborators access to preconfigured computers to look at their data.

Background: Although the prostatic urethral stents are no longer used in the United States for treatment of prostatomegaly, urologists will encounter patients with complications of previously placed permanent prostatic stents. We report two cases of persistent bothersome lower urinary tract symptoms (LUTS) after prostatic stent placement treated with simultaneous holmium laser enucleation of prostate (HoLEP) with endoscopic removal of the prostatic urethral stent using high-power holmium laser. We also reviewed the literature regarding the removal of prostatic stents with holmium laser combined with surgical management of benign prostatic hyperplasia. Case Presentation: A 71-year-old man who presented with LUTS, recurrent gross hematuria, and urinary infection, which developed after placement of a prostatic stent 10 years prior for urinary retention secondary to prostatomegaly (80 g). He underwent combined HoLEP with endoscopic removal of the prostatic stent using 100 W holmium laser at a power setting of 2 J and 30 Hz. The surgical steps comprised fragmentation of the stent in situ by making incisions at 5, 7, and 12 o'clock positions followed by enucleation of the prostate. The stent was then separated from enucleated tissue in the urinary bladder. The remaining prostate adenoma was then morcellated and removed. The patient remained asymptomatic at 10-year follow-up. Another patient was 62-year-old man who developed recurrence of bothersome LUTS, 1 year after placement a prostatic stent for urinary retention. On investigation his prostate was 105 g and stent showed partial migration in the bladder with overlying calcification. HoLEP and stent removal was performed in a manner similar to the first patient. This patient also remained asymptomatic at a 1-year follow-up. Conclusion: Combined HoLEP with removal of a prostatic urethral stent using a high-power holmium laser is safe and effective with long-term durable outcome., Competing Interests: No competing financial interests exist., (Copyright 2020, Mary Ann Liebert, Inc., publishers.)

Background: NEO212 is a novel small-molecule anticancer agent that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH) to the alkylating agent temozolomide (TMZ). It is undergoing preclinical development as a therapeutic for brain-localized malignancies. The aim of this study was to characterize metabolism and pharmacokinetic (PK) properties of NEO212 in preclinical models., Methods: We used mass spectrometry (MS) and modified high-performance liquid chromatography to identify and quantitate NEO212 and its metabolites in cultured glioblastoma cells, in mouse plasma, brain, and excreta after oral gavage., Results: Our methods allowed identification and quantitation of NEO212, POH, TMZ, as well as primary metabolites 5-aminoimidazole-4-carboxamide (AIC) and perillic acid (PA). Intracellular concentrations of TMZ were greater after treatment of U251TR cells with NEO212 than after treatment with TMZ. The half-life of NEO212 in mouse plasma was 94 min. In mice harboring syngeneic GL261 brain tumors, the amount of NEO212 was greater in the tumor-bearing hemisphere than in the contralateral normal hemisphere. The brain:plasma ratio of NEO212 was greater than that of TMZ. Excretion of unaltered NEO212 was through feces, whereas its AIC metabolite was excreted via urine., Conclusions: NEO212 preferentially concentrates in brain tumor tissue over normal brain tissue, and compared to TMZ has a higher brain:plasma ratio, altogether revealing favorable features to encourage its further development as a brain-targeted therapeutic. Its breakdown into well-characterized, long-lived metabolites, in particular AIC and PA, will provide useful equivalents for PK studies during further drug development and clinical trials with NEO212., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Introduction: The objective of this study was to identify risk factors and urodynamic parameters predictive of mid-urethral sling (MUS) revision surgery that can be used for counseling patients and individualizing risk prediction., Methods: Retrospective case-control analysis of 40 sling revisions performed during the 12-year study period were compared to 123 control cases that did not require revision to obtain a 1:3 case-to-control ratio. Demographic, perioperative, and urodynamic data were analyzed, with p < 0.05 as significant. Independent predictors of sling revision were assessed by binary logistic regression models, with risk expressed as adjusted odds ratios., Results: After multiple regression analysis, younger age at time of index MUS placement (aOR 0.93, 95% CI 0.88-0.97), increasing number of cesarean deliveries (CD) (aOR 2.00, 95% CI 1.01-3.96), and concomitant apical prolapse repair during index MUS procedure (aOR 4.63, 95% CI 1.34-15.93) were significant predictors of sling revision., Conclusions: Young age at the time of placement, multiple CD, and concomitant apical prolapse repair were independent factors predictive of sling revision. Giving consideration to risk factors could improve patient counseling and surgical candidate selection.

Introduction: Over the past decade, low-intensity extracorporeal shockwave therapy (Li-ESWT) has emerged as a treatment modality for erectile dysfunction (ED). To better appreciate the differences between the various devices for the treatment of ED, it is imperative for physicians to understand the underlying physics of the different shockwave generators., Aim: In this article, we explain the physics of shockwaves by establishing a foundation regarding the basics of waves, specifically soundwaves. We also describe the different shockwave generators available and assess their potential clinical utility., Methods: We reviewed basic principles of wave propagation, randomized controlled trials investigating Li-ESWT for ED and other medical diseases, and individual industry shockwave generator websites, in order to describe the basic physics underlying Li-ESWT., Main Outcome Measure: We primarily aimed to describe the physics underlying shockwave generators and to provide a framework for understanding the relevant subtypes and adjustable parameters., Results: A wave is a disturbance in a medium that transports energy without permanently transporting matter. In shockwaves, a soundwave is generated with a speed faster than the local speed of sound. Shockwaves are classically generated by three different types of energy sources: electrohydraulic, electromagnetic, or piezoelectric, which all create a shockwave through the conversion of electric potential energy to mechanical energy. Importantly, radial pressure waves do not behave the same as conventional shockwaves and are more like "ordinary" sound waves in that they achieve a significantly lower peak pressure, a slower rise time, and propagate outwards without a focal point., Clinical Implications: Li-ESWT is not currently approved by the U.S. Food and Drug Administration and is considered investigational in the United States. However, it is currently available to patients under clinical trial protocols and it is important to understand the basic physics of shockwaves to understand the differences between the different shockwave devices., Strength & Limitations: This is a comprehensive review of the physics underlying Li-ESWT but only tangentially explores the biological impact of shockwaves., Conclusion: Physicians currently using or those contemplating purchasing a Li-ESWT device should understand the basic physics underlying the device, as well as which treatment protocols were used to demonstrate clinical efficacy in treating ED. Katz JE, Clavijo RI, Rizk P, et al. The Basic Physics of Waves, Soundwaves, and Shockwaves for Erectile Dysfunction. Sex Med Rev 2020;8:100-105., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Anterior gradient 2 (AGR2) is a member of the protein disulfide isomerase (PDI) family, which plays a role in the regulation of protein homeostasis and the unfolded protein response pathway (UPR). AGR2 has also been characterized as a proto-oncogene and a potential cancer biomarker. Cellular localization of AGR2 is emerging as a key component for understanding the role of AGR2 as a proto-oncogene. Here, we provide evidence that extracellular AGR2 (eAGR2) promotes tumor metastasis in various in vivo models. To further characterize the role of the intracellular-resident versus extracellular protein, we performed a comprehensive protein-protein interaction screen. Based on these results, we identify AGR2 as an interacting partner of the mTORC2 pathway. Importantly, our data indicates that eAGR2 promotes increased phosphorylation of RICTOR (T1135), while intracellular AGR2 (iAGR2) antagonizes its levels and phosphorylation. Localization of AGR2 also has opposing effects on the Hippo pathway, spheroid formation, and response to chemotherapy in vitro. Collectively, our results identify disparate phenotypes predicated on AGR2 localization. Our findings also provide credence for screening of eAGR2 to guide therapeutic decisions.

Background: Non-Hispanic Black (NHB) men are at an increased risk for aggressive prostate cancer (PCa), making active surveillance (AS) potentially less optimal in this population. This concern has not been explored in other minority populations-specifically, Hispanic/Latino men. We recently found that Mexican-American men demonstrate an increased risk of PCa-specific mortality, and we hypothesized that they may also be at risk for an adverse outcome on AS., Methods: Using the Surveillance, Epidemiology, and End Results (SEER) program, we extracted a population-based cohort of men diagnosed from 2004 to 2013 with localized or regional PCa, who had ≤2 cores of only Grade Group (GG) 1 cancer, and underwent radical prostatectomy (RP) with available biopsy and surgical pathology results. We measured discovery of high-risk PCa at RP and collected socioeconomic status (SES) data across different racial/ethnic groups. We defined aggressive tumors as either an upgrade to GG 3 or higher (GG3+) cancer or non-organ-confined disease (≥pT3a or N1). Univariate and multivariate logistic regression models were developed to assess the association between racial/ethnic categories and the previously mentioned adverse oncologic outcomes both with and without adjusting for SES factors., Results: NHB and Mexican-American men were significantly more likely to have aggressive PCa, following RP. In multivariable logistic regression adjusting for SES factors and relative to non-Hispanic White (NHW) men, Mexican-American men had at increased odds of upgrading to GG3+ (OR 1.67; 95% CI [1.00-2.90]). NHB men were more likely to have non-organ-confined disease (OR 1.34; 95% CI [1.06-1.69]), while Mexican-American men had a similar risk to NHW men., Conclusion: Among individuals with low-risk PCa and eligible for AS, Mexican-American and NHB men are at an increased risk of harboring more aggressive disease at RP. This novel finding among Mexican-Americans deserves further evaluation.

The cancer-associated protein Anterior Gradient 2 (AGR2) has been described, predominantly in adenocarcinomas. Increased levels of extracellular AGR2 (eAGR2) have been correlated with poor prognosis in cancer patients, making it a potential biomarker. Additionally, neutralizing AGR2 antibodies showed preclinical effectiveness in murine cancer models suggesting eAGR2 may be a therapeutic target. We set out to identify a peptide by mRNA display that would serve as a theranostic tool targeting AGR2. This method enables the selection of peptides from a complex (>10 11 ) library and incorporates a protease incubation step that filters the selection for serum stable peptides. We performed six successive rounds of enrichment using a 10-amino acid mRNA display library and identified several AGR2 binding peptides. One of these peptides (H10), demonstrated high affinity binding to AGR2 with a binding constant (K D ) of 6.4 nM. We developed an AGR2 ELISA with the H10 peptide as the capture reagent. Our H10-based ELISA detected eAGR2 from cancer cell spent media with a detection limit of (20-50 ng/ml). Furthermore, we investigated the therapeutic utility of H10 and discovered that it inhibited cell viability at IC 50 (9-12 μmoles/L) in cancer cell lines. We also determined that 10 μg/ml of H10 was sufficient to inhibit cancer cell migration in breast and prostate cancer cell lines. A control peptide did not show any appreciable activity in these cells. The H10 peptide showed promise as both a novel diagnostic and a potential therapeutic peptide., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest was reported by the authors.

Preliminary results from our study provide further evidence that low-intensity extracorporeal shockwave therapy is a safe and effective treatment modality for erectile dysfunction. Our treatment protocol with shockwaves given to men over 2 wk had the most robust effect., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Agencies are increasingly called upon to implement their natural resource management programs within an adaptive management (AM) framework. This article provides the background and motivation for the R package, AMModels. AMModels was developed under R version 3.2.2. The overall goal of AMModels is simple: To codify knowledge in the form of models and to store it, along with models generated from numerous analyses and datasets that may come our way, so that it can be used or recalled in the future. AMModels facilitates this process by storing all models and datasets in a single object that can be saved to an .RData file and routinely augmented to track changes in knowledge through time. Through this process, AMModels allows the capture, development, sharing, and use of knowledge that may help organizations achieve their mission. While AMModels was designed to facilitate adaptive management, its utility is far more general. Many R packages exist for creating and summarizing models, but to our knowledge, AMModels is the only package dedicated not to the mechanics of analysis but to organizing analysis inputs, analysis outputs, and preserving descriptive metadata. We anticipate that this package will assist users hoping to preserve the key elements of an analysis so they may be more confidently revisited at a later date.

Mutations or deletions in exons 18-21 in the EGFR ) are present in approximately 15% of tumors in patients with non-small cell lung cancer (NSCLC). They lead to activation of the EGFR kinase domain and sensitivity to molecularly targeted therapeutics aimed at this domain (gefitinib or erlotinib). These drugs have demonstrated objective clinical response in many of these patients; however, invariably, all patients acquire resistance. To examine the molecular origins of resistance, we derived a set of gefitinib-resistant cells by exposing lung adenocarcinoma cell line, HCC827, with an activating mutation in the EGFR tyrosine kinase domain, to increasing gefitinib concentrations. Gefitinib-resistant cells acquired an increased expression and activation of JUN, a known oncogene involved in cancer progression. Ectopic overexpression of JUN in HCC827 cells increased gefitinib IC 50 from 49 nmol/L to 8 μmol/L ( P < 0.001). Downregulation of JUN expression through shRNA resensitized HCC827 cells to gefitinib (IC 50 from 49 nmol/L to 2 nmol/L; P < 0.01). Inhibitors targeting JUN were 3-fold more effective in the gefitinib-resistant cells than in the parental cell line ( P < 0.01). Analysis of gene expression in patient tumors with EGFR-activating mutations and poor response to erlotinib revealed a similar pattern as the top 260 differentially expressed genes in the gefitinib-resistant cells (Spearman correlation coefficient of 0.78, P < 0.01). These findings suggest that increased JUN expression and activity may contribute to gefitinib resistance in NSCLC and that JUN pathway therapeutics merit investigation as an alternate treatment strategy. Mol Cancer Ther; 16(8); 1645-57. ©2017 AACR ., (©2017 American Association for Cancer Research.)