Modern Cohorts Research Articles

Molecular and Seroepidemiologic Characteristics ofStaphylococcus aureus in Children with Cystic Fibrosis

Abstract Background Cystic fibrosis (CF), through altered sodium and chloride transport across the CF transmembrane receptor (CFTR), is associated with poor mucus clearance, bacterial colonization of the lower airway, chronic pulmonary disease punctuated by acute exacerbations, and chronic inflammation. With increased use of CFTR modulators, changes in the CF pulmonary microbiome have been observed, including decreased prevalence of Pseudomonas colonization; however, overall S. aureus prevalence remains largely unchanged. An important remaining question is whether changes in the CF pulmonary microbiome, while not affecting the overall prevalence of S. aureus colonization, has led to changes in S. aureus diversity or the strain types that are most frequently recovered from children with CF. It is also unknown whether the humoral immune response to S. aureus is altered in the presence of CFTR modulator therapy. Methods Genomic DNA was extracted from S. aureus isolates obtained from two cohorts: a historic cohort, comprised of children not receiving CFTR modulators, and a modern cohort, comprised of children receiving CFTR modulator therapy. Multilocus sequence typing (MLST) and whole genome sequencing (WGS) were used to identify clonotype and characterize virulence factors of interest. Serum was obtained from participants and antibody titers to the extracellular toxins LukAB and LukED were measured. Results One hundred participants were enrolled: 50 in cohort 1 (historic) and 50 in cohort 2 (modern). Compared to cohort 1, isolates identified in cohort 2 were less likely to contain ACME and mecA; similarly, cohort 2 isolates were more likely to contain PVL, sek, and sak. The frequency of specific clonotypes changed over time, with increased prevalence of CC8 and decreased prevalence of CC1, CC5, CC15, and CC30 in cohort 2 compared to cohort 1 (Figure 1A). Serum antibody concentrations to LukAB, a conserved toxin across S. aureus, were similar across cohorts (Figure 1B). Conclusion Over time, the clonotypes responsible for S. aureus colonization in patients receiving CFTR modulators have changed. Despite changes in clonotypes and receipt of CFTR modulators, serum concentrations of LukAB-specific antibodies did not differ. These data suggest that staphylococcal colonization in patients with CF is dynamic over time and may be modified based on the receipt of CFTR modulator therapy. Figure 1. (A) S. aureus clonal complexes, over time, demonstrating a relative increase in CC8 between 2012 and 2022; (B) serum concentrations of LukAB antibodies from 2012 (historic) and 2022 (modern) cohorts. No significant difference was observed in median anti-LukAB concentrations.

The Evolution of Hand Injuries at a State's Only Level I Trauma Center: A Look From the 1980s Through the Global Pandemic.

The purpose of this study is to evaluate any changes to hand trauma in the past three decades and through the COVID-19 pandemic. We hypothesized that improved consumer safety regulations, changes in access to care, and the impact of a global pandemic, among other variables, have significantly influenced the mechanisms and treatment of hand injuries between the 1980s, 2010s (pre-COVID-19), and 2020s (post-COVID-19). A retrospective single-center review was performed at the only level I trauma center in Mississippi, identifying all hand trauma consultations between 2012-2019 and 2020-2021, compared to aggregated data from 1989. Car accidents, gunshots, saw injuries, door injuries, and falls increased in 2012-2019 and 2020-2021 compared to 1989, whereas knife injuries, glass injuries, industrial injuries, and burns decreased. Crush injuries, de-gloving injuries, and lacerations with irregular edges were increased in recent cohorts, corresponding with increased amputations and tissue loss. Skin and subcutaneous injuries decreased in modern cohorts, corresponding with a decreased ability for primary skin repair and the need for more flaps. Additionally, while hospitalizations have increased, patients have improved follow-up. The nature of hand trauma has changed significantly over the past three decades. Increased numbers of cars and greater access to firearms might have led to increased rates of high-energy trauma, whereas burn and industrial injuries have decreased, potentially secondary to improved safety efforts. Despite increased overall hand trauma, time to treatment and follow-up have improved. Through this study, we can be more cognizant of the evolution of hand trauma in the modern era. This can allow improved access to care and further refine management to optimize functionality for hand injuries.

Perspectives on the Cardiovascular and Metabolic Effects of Androgen Deprivation Therapy in Prostate Cancer.

Cardiovascular disease (CVD) is the leading cause of non-cancer mortality in men with prostate cancer. This review summarizes the existing and emerging literature examining the cardiometabolic effects of androgen deprivation therapy (ADT) in prostate cancer. The evidence behind the metabolic effects of ADT is derived from older studies and has not been validated in modern cohorts. Most of the newer studies focus on the risk of cardiovascular disease (CVD) with ADT. Recently published studies like the HERO and PRONOUNCE trials have once again sparked debate about the effects of different types and durations of ADT on cardiovascular outcomes. The link between ADT and CVD is inherently complex with a majority of the evidence collected from population-based or non-randomized trials without enriching for high-risk populations. Ongoing clinical trials may provide more informative data to guide the cardiovascular care of prostate cancer survivors.

Children and the Remaining Gender Gaps in the Labor Market

The past five decades have seen a remarkable convergence in the economic roles of men and women in society. Yet, persistently large gender gaps in terms of labor supply, earnings, and representation in top jobs remain. Moreover, in countries like the United States, convergence in labor market outcomes appears to have slowed in recent decades. In this article, we focus on the role of children and show that many potential explanations for the remaining gender disparities in labor market outcomes are related to the fact that children impose significantly larger penalties on the career trajectories of women relative to men. We document that, in the United States, more than two-thirds of the overall gender earnings gap can be accounted for by the differential impacts of children on women and men. We propose a simple model of household decision-making to motivate the link between children and gender gaps in the labor market, and to help rationalize how various factors potentially interact with parenthood to produce differential outcomes by gender. We discuss several forces that might make the road to gender equity even more challenging for modern cohorts of parents, and offer a critical discussion of public policies that seek to address the remaining gaps. (JEL D13, J12, J13, J16, J22, J31, J71)

Description of Cryptococcosis Following SARS-CoV-2 Infection: A Disease Survey Through the Mycosis Study Group Education and Research Consortium (MSG-19).

Invasive fungal infections have been described throughout the COVID-19 pandemic. Cryptococcal disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in several isolated case reports and 1 larger case series. We sought to describe cryptococcal infections following SARS-CoV-2 through establishing a database to investigate underlying risk factors, disease manifestations, and outcomes. We created a crowdsourced call for cases solicited through the Mycoses Study Group Education and Research Consortium, the Centers for Disease Control and Prevention Emerging Infectious Diseases Network, and infectious diseases Twitter groups. Data were collected in a web-based and secure REDCap survey without personal identifiers. Sixty-nine cases were identified and submitted by 29 separate institutional sites. Cryptococcosis was diagnosed a median of 22 days (interquartile range, 9-42 days) after SARS-CoV-2 infection. Mortality among those with available follow-up was 72% (26/36) for the immunocompetent group and 48% (15/31) for the immunocompromised group (likelihood ratio, 4.01; P = .045). We observed a correlation between disease manifestation (central nervous system infection, proven/probable disseminated disease, and respiratory) and mortality (P = .002). The mortality rate of 59% for patients with cryptococcosis following SARS-CoV-2 is higher than that of modern Cryptococcus cohorts. There was an association between immunocompromised status and cryptococcal disease manifestations as well as mortality. Moreover, our series emphasizes the need for clinical and laboratory assessment of opportunistic infections beyond 30 days when concerning symptoms develop.

Association of post-operative ICU requirements with early extubation in the fontan procedure.

This study investigated the association between early extubation (EE) and the degree of postoperative intensive care unit (ICU) support after the Fontan procedure, specifically evaluating the volume of postoperative intravenous fluid (IVF) and vasoactive-inotropic score (VIS). Retrospective analysis of patients who underwent Fontan palliation from 2008 to 2018 at a single center was completed. Patients were initially divided into pre-institutional initiative towards EE (control) and post-initiative (modern) cohorts. Differences between the cohorts were assessed using t-test, Wilcoxon, or chi-Square. Following stratification by early or late extubation, four groups were compared via ANOVA or Kruskal-Wallis Test. There was a significant difference in the rate of EE between the control and modern cohorts (mean 42.6 versus 75.7%, p = 0.01). The modern cohort demonstrated lower median VIS (5 versus 8, p = 0.002), but higher total mean IVF (101±42 versus 82 ±27 cc/kg, p < 0.001) versus control cohort. Late extubated (LE) patients in the modern cohort had the highest VIS and IVF requirements. This group received 67% more IVF (140 ± 53 versus 84 ± 26 cc/kg, p < 0.001) and had a higher median VIS at 24 hours (10 (IQR, 5-10) versus 4 (IQR, 2-7), p < 0.001) versus all other groups. In comparison, all EE patients had a 5-point lower median VIS when compared to LE patients (3 versus 8, p= 0.001). EE following the Fontan procedure is associated with reduced post-operative VIS. LE patients in the modern cohort received more IVF, potentially identifying a high-risk subgroup of Fontan patients deserving of further investigation.

Your New Year’s “resolution”—check your “screen!”

Your New Year’s “resolution”—check your “screen!”

(107) Delayed Closed-Suction Drain Removal Following Inflatable Penile Prosthesis: A Multi-Institutional Experience

Abstract Introduction There is a paucity of outcome data for prolonged (&amp;gt;48 hours) closed-suction drains following inflatable penile prosthesis (IPP) placement. Tissue dissection and corporal dilation make scrotal hematomas a potential complication within the first 72 hours following surgery. Maintaining a closed-suction drain represents a method to reduce scrotal hematoma formation and prevent sequela such as infection. However, maintaining a percutaneous tract also represents a feasible pathway for bacterial seeding of a new prosthesis. Given the severe consequences of prosthetic infection, establishing comparable outcomes for delayed drain removal is necessary. Objective To evaluate rates of infection, hematoma and device explantation in a multi-institutional cohort of patients undergoing IPP placement with delayed closed-suction drain removal (48-hour duration or greater) and compare observed outcomes to published outcomes in modern IPP cohorts. Methods Data was collected retrospectively for 209 patients undergoing virgin IPP placement with delayed closed-suction drain removal. Cases were performed by three surgeons at three high-volume centers between 01/01/2020 and 3/31/2022. R for Statistical Computing was used to generate descriptive statistics (Figure 1) and categorical data visualization (Figure 2). No quantitative statistical analysis was performed regarding infection outcomes as the low observed rate would not accommodate robust quantitative analysis. Results Mean drain duration was 66 hours (48 – 312, SD 23). There were 3 device infections (1.4%). Mean patient age was 64.5 years. 84 (40.2%) patients were diabetic, with a mean hemoglobin A1c of 7.2 in these patients. Both penoscrotal and infrapubic approaches were performed (95 versus 114). Reservoir location was either space of Retzius (SOR) or high submuscular (HSM) with the former being more common (164 versus 45). There were 7 (3.3%) post-operative hematomas and 6 patients (2.9%) required device revision for non-infectious causes. Mean follow up interval postoperatively was 170 days (10 – 421 days, SD 78). Conclusions Delayed removal of closed-suction drains after virgin IPP is safe. The outcomes for this study cohort are similar to outcomes reported in other modern virgin IPP series where closed-suction drains were not routinely employed. Prospective studies to further characterize how closed-suction drain placement influences hematoma formation, infection rates, and postoperative pain are necessary to definitively establish the role of delayed drain removal following IPP implantation. Disclosure No

PD42-12 DELAYED CLOSED-SUCTION DRAIN REMOVAL AFTER INFLATABLE PENILE PROSTHESIS: A MULTI-INSTITUTIONAL EXPERIENCE

You have accessJournal of UrologyCME1 Apr 2023PD42-12 DELAYED CLOSED-SUCTION DRAIN REMOVAL AFTER INFLATABLE PENILE PROSTHESIS: A MULTI-INSTITUTIONAL EXPERIENCE Luke Shumaker, Nicholas Zulia, Jonathan Beilan, Emmett Kennady, Nicolas Ortiz, and Adam Baumgarten Luke ShumakerLuke Shumaker More articles by this author , Nicholas ZuliaNicholas Zulia More articles by this author , Jonathan BeilanJonathan Beilan More articles by this author , Emmett KennadyEmmett Kennady More articles by this author , Nicolas OrtizNicolas Ortiz More articles by this author , and Adam BaumgartenAdam Baumgarten More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003352.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is little published data regarding percutaneous drain (PD) duration after inflatable penile prosthesis (IPP) placement. The dissection associated makes scrotal hematomas common in the first 72 hours. Maintaining a percutaneous drain represents a strategy to reduce scrotal hematoma formation. However, a percutaneous tract also represents a feasible path for seeding of a new prosthesis. Given the severe consequences of infection, establishing comparable outcomes for delayed drain removal patients is necessary. Here we detail rates of infection, hematoma, device explantation and other standard post IPP metrics in a multi-institutional cohort with delayed PD removal (48-hours or greater). METHODS: Data was collected retrospectively for 224 patients undergoing virgin IPP placement with delayed PD removal. Cases were performed by three surgeons at three high-volume centers between 01/01/2020 and 3/31/2022. It was the practice of these surgeons to leave PDs 48 hours or greater. 15 patients had PDs removed before 48 hours due to scheduling, patient preference, or inadvertent removal. These patients were excluded leaving 209. R for Statistical Computing was used to generate statistics and data visualization. RESULTS: Mean drain duration was 2.8 days. Mean follow-up interval was 170 days. 84 patients (40%) carried the diagnosis of diabetes mellitus with a mean hemoglobin A1c of 7.2. Penoscrotal and infrapubic approaches were employed (114 versus 95). Reservoir location was split between space of Retzius (SOR) and high submuscular with SOR being more common (164 versus 45). 7 discrete hematomas were observed. Despite this small number, Fisher’s exact testing demonstrated significant association between hematoma formation and both anticoagulation and antiplatelet therapy (p<0.01 in both cases). There were 3 device infections (1.4%). 9 patients (4.3%) required revision for non-infectious causes. CONCLUSIONS: Rates of infection and explantation observed in virgin IPP implantation with delayed PD removal are similar to other modern virgin cohorts where drains were not employed. Additional prospective research would be useful to characterize effect of delayed drain removal on hematoma formation, postoperative pain, and interval to device use. Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1115 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luke Shumaker More articles by this author Nicholas Zulia More articles by this author Jonathan Beilan More articles by this author Emmett Kennady More articles by this author Nicolas Ortiz More articles by this author Adam Baumgarten More articles by this author Expand All Advertisement PDF downloadLoading ...

MP28-01 CYTOREDUCTIVE NEPHRECTOMY PERIOPERATIVE OUTCOMES HAVE SIGNIFICANTLY IMPROVED IN RECENT YEARS

You have accessJournal of UrologyCME1 Apr 2023MP28-01 CYTOREDUCTIVE NEPHRECTOMY PERIOPERATIVE OUTCOMES HAVE SIGNIFICANTLY IMPROVED IN RECENT YEARS Arighno Das, Daniel Shapiro, Jose Karam, Viraj Master, Philippe Spiess, Jay Raman, Ashanda Esdaille, Logan Zemp, Pranav Sharma, Wade Sexton, Datta Patil, Glenn Allen, Surena Matin, and E. Jason Abel Arighno DasArighno Das More articles by this author , Daniel ShapiroDaniel Shapiro More articles by this author , Jose KaramJose Karam More articles by this author , Viraj MasterViraj Master More articles by this author , Philippe SpiessPhilippe Spiess More articles by this author , Jay RamanJay Raman More articles by this author , Ashanda EsdailleAshanda Esdaille More articles by this author , Logan ZempLogan Zemp More articles by this author , Pranav SharmaPranav Sharma More articles by this author , Wade SextonWade Sexton More articles by this author , Datta PatilDatta Patil More articles by this author , Glenn AllenGlenn Allen More articles by this author , Surena MatinSurena Matin More articles by this author , and E. Jason AbelE. Jason Abel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003256.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Few data are available describing perioperative outcomes for cytoreductive nephrectomy (CN) or how changes in patient selection may have impacted modern cohorts. This study investigated factors associated with perioperative outcomes in a multi-institutional cohort of patients treated with CN. METHODS: Data was analyzed for metastatic renal cell carcinoma patients treated with CN at 6 tertiary centers from 2005-2019. Outcomes included: Clavien-Dindo complications, mortality, length of hospitalization, and 30-day readmission rate. Multivariable logistic regression was used to evaluate variables associated with perioperative outcomes. Patients were stratified into 3 equal time periods to evaluate changes in outcomes over time. RESULTS: A total of 1,272 patients were treated with CN at 6 centers including 369 (29%) from 2005-2009, 557 (44%) from 2010-2014, and 346 (27%) from 2015-2019. Patients treated in 2015-2019 vs 2005-2009 were less likely to have received pre-surgical systemic therapy (19% vs 26%, p=0.02). Perioperative outcomes are shown in Table. Mortality at 90 days was lower for patients treated in 2015-2019 vs 2005-2009 (5% vs 10%, p=0.02). Patients treated in 2015-2019 vs 2005-2009 had lower overall (22% vs 39%, p<0.001) and major (Clavien-Dindo ≥ 3) complications from surgery (10% vs 16%, p=0.02). Median hospital stay was shorter for patients treated 2015-2019 vs 2005-2009 (4 days vs 5 days, p<0.001) but 30-day readmission rate was also higher (12% vs 7%, p=0.02). On multivariable analysis, patients undergoing CN in 2015-2019 had significantly lower odds of major complications (OR 0.57, 95%CI 0.36-0.90) and 90-day mortality (OR 0.49, 95%CI 0.27-0.89) compared to undergoing CN in 2005-2009. Receipt of presurgical systemic therapy was not associated with increased odds of high-grade complications (OR 0.79, 95%CI 0.52-1.19). CONCLUSIONS: In this large multi-institutional study, perioperative complications have significantly decreased over time. Prospective studies should investigate how to further improve outcomes and select patients. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e369 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Arighno Das More articles by this author Daniel Shapiro More articles by this author Jose Karam More articles by this author Viraj Master More articles by this author Philippe Spiess More articles by this author Jay Raman More articles by this author Ashanda Esdaille More articles by this author Logan Zemp More articles by this author Pranav Sharma More articles by this author Wade Sexton More articles by this author Datta Patil More articles by this author Glenn Allen More articles by this author Surena Matin More articles by this author E. Jason Abel More articles by this author Expand All Advertisement PDF downloadLoading ...

Re-evaluating the health impact and cost-effectiveness of tuberculosis preventive treatment for modern HIV cohorts on antiretroviral therapy: a modelling analysis using data from Tanzania

BackgroundIsoniazid preventive therapy (IPT) can prevent tuberculosis among people receiving antiretroviral therapy (ART). HIV programmes are now initiating patients on ART with higher average CD4 cell counts and lower tuberculosis risks under test-and-treat guidelines. We aimed to investigate how this change has affected the health impact and cost-effectiveness of IPT.MethodsWe constructed a tuberculosis–HIV microsimulation model parameterised using data from a large HIV treatment programme in Dar es Salaam, Tanzania. We simulated long-term health and cost outcomes for the 211 748 individuals initiating ART between Jan 1, 2014, and Dec 31, 2020, under three scenarios: no IPT access; observed levels of IPT access (75%) and completion (71%); and full (100%) IPT access and completion. We stratified results by ART initiation year and starting CD4 cell count.FindingsObserved levels of IPT access were estimated to have averted 12 800 (95% uncertainty interval 7300 to 21 600) disability-adjusted life-years (DALYs) and saved US$23 000 (–2 268 000 to 1 388 000). Full IPT access would have averted 24 500 (15 100 to 38 300) DALYs and cost $825 000 (–1 594 000 to 4 751 000), equivalent to $23·4 per DALY averted. Lifetime health benefits of IPT were estimated to be greater for more recent ART cohorts, while lifetime costs were stable. In subgroup analyses, a higher CD4 cell count at ART initiation was associated with greater health gains from IPT (15 900 [10 300 to 22 500] DALYs averted by full IPT per 100 000 patients for CD4 count >500 cells per μL at ART initiation, versus 7400 [4500 to 11 600] for CD4 count <100 cells per μL) and lower incremental lifetime costs.InterpretationIPT remains highly cost-effective or cost-saving for recent ART cohorts. The health impact and cost-effectiveness of IPT are estimated to improve as patients initiate ART earlier in the course of infection.FundingUS National Institutes of Health.

121 Analysis of Post-traumatic Epilepsy After Severe Traumatic Brain Injury in a Modern Series Identifies an Increasing Incidence and Novel Risk Factors

INTRODUCTION: Post-traumatic epilepsy (PTE) accounts for 20% of symptomatic epilepsy with rates highest after severe Traumatic Brain Injury (TBI). PTE has not been well studied in modern cohorts and its risk factors are poorly understood. METHODS: We retrospectively reviewed severe TBI patients from a prospective database treated from 2002 through 2018 at a single level 1 trauma center, excluding those with alcohol withdrawal seizures, prior epilepsy, or death at discharge. Using definitions from the International League Against Epilepsy, a seizure was defined as a witnessed clinical event confirmed to be a seizure by the treating healthcare team or electroencephalography, and PTE as two or more seizures. We collected timing of seizures, follow up, demographic, clinical information, and Glasgow Outcomes Scale (GOS). Because more severe injury predisposes to both death and PTE, we developed a competing hazards model to identify independent predictors of PTE. RESULTS: We identified 393 patients after exclusions. The rate of early seizures within 7 days was 2.8% (11). The cumulative incidence of PTE was 11% by one year and 25% overall, with 29% of PTE patients requiring multiple anti-seizure medications.Patients with PTE had more severe injuries with higher rates of unreactive pupils, subdural hematomas, obliteration of the basal cisterns, skull fractures, Marshall CT classification, decompressive hemicraniectomies (DHC), lobectomies, and shunting, as well as increased length of stay (LOS), younger age, and intracranial infections (all p &lt; 0.01). Our adjusted model identified age (subdistribution hazard 0.75; 95% confidence interval [95% CI]: 0.62 – 0.93]), DHC (3.3; 95% CI: 2.0-5.5), lobectomy (2.2; 95% CI: 2.6 – 4.2), and infection (1.9; 95% CI: 1.1 – 3.3) as predictors of PTE. Patients with PTE had worse functional outcomes (GOS 1-3 versus 4-5) at 6, 12, and 24 months (p &lt; 0.03). CONCLUSION: The incidence of PTE after severe TBI is higher than historical cohorts suggest and continues to increase though fifteen years post-trauma. Patients with PTE have more severe injuries with worse functional outcomes.

Outcome-Guided Sparse K-Means for Disease Subtype Discovery via Integrating Phenotypic Data with High-Dimensional Transcriptomic Data

Abstract The discovery of disease subtypes is an essential step for developing precision medicine, and disease subtyping via omics data has become a popular approach. While promising, subtypes obtained from existing approaches are not necessarily associated with clinical outcomes. With the rich clinical data along with the omics data in modern epidemiology cohorts, it is urgent to develop an outcome-guided clustering algorithm to fully integrate the phenotypic data with the high-dimensional omics data. Hence, we extended a sparse K-means method to an outcome-guided sparse K-means (GuidedSparseKmeans) method. An unified objective function was proposed, which was comprised of (i) weighted K-means to perform sample clusterings; (ii) lasso regularizations to perform gene selection from the high-dimensional omics data; and (iii) incorporation of a phenotypic variable from the clinical dataset to facilitate biologically meaningful clustering results. By iteratively optimizing the objective function, we will simultaneously obtain a phenotype-related sample clustering results and gene selection results. We demonstrated the superior performance of the GuidedSparseKmeans by comparing with existing clustering methods in simulations and applications of high-dimensional transcriptomic data of breast cancer and Alzheimer's disease. Our algorithm has been implemented into an R package, which is publicly available on GitHub ( https://github.com/LingsongMeng/GuidedSparseKmeans).

A systematic approach for successful repair of radiated and non-radiated ureteral injuries.

BackgroundSuccessful ureteral reconstruction is challenging, particularly in radiated fields. We characterize and directly compare surgical outcomes in modern cohorts of radiated and non-radiated patients undergoing ureteral reconstruction utilizing a systematic approach to pre-operative assessment. We hypothesize that radiated patients will undergo more complex ureteral reconstructions and experience higher rates of surgical failure and complications compared to nonradiated patients.MethodsConsecutive cases of ureteral reconstruction for acquired ureteral injury performed by a single surgeon from 2010–2018 were retrospectively reviewed. Clinical data were collected including pre-operative bladder capacity, ureteral injury characteristics, and surgical technique. Ileal ureter and autotransplantation were classified as “complex” ureteral repairs, and surgical success was defined as freedom from surgical revision of the ureteral anastomosis and/or ureteral stenting.ResultsThere were 47 ureteral reconstructions performed including 17 (36%) radiated patients. Radiated patients had lower pre-operative bladder capacity and were more likely to undergo complex repairs compared to non-radiated patients (35% vs. 7%, P=0.01). Overall surgical success was high (98%) and similar between radiated (94%) and non-radiated groups (100%) at median follow up of 30 months. Clavien grade 3–4 complications occurred in 18% of radiated and 10% of non-radiated patients (P=0.48).ConclusionsCareful pre-operative evaluation and appropriate selection of surgical technique facilitates high and similar success of ureteral reconstruction in radiated and non-radiated patients. Complex ureteral repairs were more common in radiated patients, however the majority of radiated ureteral injuries (65%) were reconstructed without tissue transfer. Radiated patients had lower pre-operative bladder capacities, but similar surgical morbidity, renal function, and persistent urge incontinence compared to non-radiated patients.

Patterns and Predictors of Distant Failure After Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Retrospective Multi-Institutional Analysis

Stereotactic body radiation therapy (SBRT) has emerged as a promising modality for the treatment of prostate cancer (PCa) and involves the delivery of ablative doses of radiation to the prostate. The patterns of failure at the time of biochemical recurrence (BCR) after SBRT remain unknown. The purpose of this study is to explore the development of distant metastasis (DM) following the diagnosis of BCR.We queried a multi-institutional database of 2,430 patients who were prospectively treated with SBRT on single institution phase II trials or registries to identify patients who developed a BCR by the Phoenix criteria or by initiation of salvage therapy for PSA rise at a lower threshold. Patterns of distant failure were obtained for patients who had BCR, including presence and sites of DM. Multivariable analysis (MVA) using logistic regression was used to evaluate the association between multiple clinicopathologic and treatment variables and DM.150 patients with BCR were identified (6.2% of total). Of these, 19% presented with low-risk, 42% with intermediate-risk, and 39% with high-risk disease. The median PSA at BCR was 4.56, median time to BCR was 36 months, and median follow-up after BCR was 15.5 months. Sixty-seven patients (44.7%) had DM identified at or after the time of BCR. Among those with DM, 13 had M1a disease, 50 had M1b disease, 3 had M1c disease, and 1 had an unknown distribution of disease. Time to BCR was significantly shorter in patients with DM compared to those who did not have DM (28.1 vs. 41.4 months, P = 0.002) and initial PSA (iPSA) was significantly greater (11.0 vs. 8.0, P = 0.03). On MVA, Gleason Grade Group (GG) 4 (vs. GG 1, OR 3.76, P = 0.047) and higher SBRT dose (36.25 Gy vs. 35 Gy: OR 4.03, P = 0.02; 40 Gy vs. 35 Gy: OR 3.73, P = 0.03) were significantly associated with DM.A substantial proportion of patients with BCR after SBRT for localized PCa ultimately develop DM, particularly those with higher iPSA and shorter time to BCR. The association with SBRT dose is likely reflective of the use of higher doses in more modern cohorts with higher-risk disease, while the association with GG likely reflects the more aggressive biology of these tumors at presentation. Further research into patterns of failure after SBRT is needed, especially in the context of more sensitive nuclear imaging. Early predictors of treatment failure are needed to facilitate timely treatment intensification.

Third Molar Agenesis in Post-Medieval Chichester

Third molar agenesis is a dental anomaly that occurs in approximately 25% of people worldwide and results in the complete absence of one or more of the third molars in the dentition. A rise in the prevalence of congenitally absent third molars has been noted in modern populations, and it has been proposed as the final evolutionary step in the dental reduction of the human dentition. &#x0D; Whilst much research has been conducted in modern cohorts, relatively little has been published on third molar agenesis in archaeological assemblages. A post-medieval assemblage from Chichester was visually and radiographically analysed to determine the prevalence of this anomaly. Third molars were measured to determine if there was an association between agenesis and size reduction. Prevalence of agenesis was found to be relatively high at 42.7% and 2 of 8 measurements were found to produce significant differences.&#x0D; Consequently, it can be said that high rates of third molar agenesis are not solely a modern phenomenon, as many prevalence rates in recent populations are lower. However, if we are to assess the significance of size differences in third molars of those with agenesis and those without, and to detect patterns within and between these groups, assemblages with larger sample sizes are needed. In order to better understand the trajectory and evolution of this anomaly, more archaeological assemblages must be examined.

Clinical Characteristics and Outcomes of Myeloma Patients Exhibiting Translocation (14;16): An Ultra-High-Risk Group of Myeloma Patients

BackgroundImportant advancements in anti-myeloma treatments resulted in significant survival benefits for myeloma patients. While the patients presenting with standard risk cytogenetics have enjoyed these advantages, the outcome of patients exhibiting high-risk cytogenetic abnormalities remains poor. According to IMWG, high risk cytogenetics are defined as the presence of del17p, t(4;14) and t(14;16). The first two abnormalities occur in an appreciable number if patients and have been analyzed in several studies. However, the subgroup of patients harboring t (14;16) has not been well described due to its low incidence, and some prior studies have questioned its prognostic value. We have embarked on describing the clinical presentation and the prognostication of myeloma patients exhibiting t(14;16)MethodsWe performed an IRB-approved outcome analysis of myeloma patients with t(14;16) from the Winship Cancer Institute (WCI) at Emory University, USA and Department of Clinical Therapeutics , National and Kapodistrian University (NKU) of Athens, Greece. The cohort for this analysis consisted of myeloma patients diagnosed with symptomatic myeloma from February 2008 until March 2017. Descriptive information of clinical characteristics and outcomes were analyzed.ResultsIn total 47 patients (29 patients from the WCI and 18 patients from NKU) were included in this analysis. The median age at diagnosis was 64 years (range 37-82), 57% had anemia (hemoglobin < 10 gr/dl), 19% had platelets counts <100x109/L, 35% had hypercalcemia (corrected serum calcium ≥11 mg/dl), 31% had serum creatinine ≥2 mg/dl and 32% had elevated LDH (≥ Upper limit of normal) and per ISS stage, 49% were stage 3. Other cytogenetic abnormalities were also present including del17p in 27%, amp1q21 in 55%, del13q in 67%; importantly in 6% a t(4;14) and in 5% a t(11;14) was also present. Post-induction 81% achieved ≥PR (30% sCR/CR, 28% VGPR and 23% PR) ;44% of the patients received ASCT1 in 1st remission, 21% received post-ASCT consolidation and 48% received maintenance after induction or intensification and the best response for all patients was sCR/CR in 43%, VGPR in 23% and PR in 17%. The use of a PI+IMiD combination was associated with higher and deeper response rates (≥VGPR in 68% vs 43%, p=0.025). After a median follow up of 29 months, the PFS1 was 20 months for the entire cohort and the estimated median OS is 46 months.In univariate analysis, factors associated with poor PFS1 included age >65 years (p=0.024), the presence of amp1q21 (p=0.017), but not of other abnormalities while use of PI+IMiD combination (p=0.043), ASCT at 1st remission (P<0.001) and the use of maintenance therapy after induction (P=0.007) were associated with longer PFS1. In multivariate analysis for PFS1, transplant in 1st remission (HR 3.93, 95% CI1.43-10.83, p=0.008) and maintenance (HR 2.4. 95% CI 0.97-5.95, p=0.059) were identified as independent prognostic factors. Interestingly, among the 13 patients that progressed at WCI, 5 patients progressed as extramedullary relapses (3 with CNS involvement). The aggressiveness of the disease relapses precluded further treatments and most patients at time of death were naïve to a multitude of anti-myeloma therapies. Regarding OS, in univariate analysis, the presence of hypercalcemia at diagnosis (p=0.001) and elevated LDH (p=0.004) were associated with poor OS, while, the presence of additional cytogenetic abnormalities (del17p, or del13q or amp1q21) was not associated with survival in this population of patients with t(14;16).ConclusionThis analysis highlights the poor prognosis of myeloma patients harboring the t (14;16) chromosomal abnormality. Such patients commonly present with poor prognostic features, including hypercalcemia, elevated LDH, increased creatinine, ISS-3 disease and also have increased frequency of other high risk cytogenetic aberrations such as del13q, amp1q21 in more than 50% of patients and del17p in 25% of patients. The use of PI+IMiD regimens probably helps with obtaining deeper responses. The inferior median PFS1 and OS seen in the modern day cohorts and the inability to use the novel regimens in the later course of the disease due to disease aggressiveness prompts us to use active regimens upfront, which can aid in preventing relapse. DisclosuresNooka:Amgen, Novartis, Spectrum, Adaptive tecnologies: Consultancy. Kastritis:Takeda: Honoraria; Amgen: Research Funding; Genesis: Honoraria; Janssen: Honoraria, Research Funding. Kaufman:Amgen, Novartis: Research Funding; Amgen, Roche, BMS, Seattle Genetics, Sutro Biopharma, Pharmacyclics: Consultancy. Boise:Abbvie: Consultancy; Eli Lilly and Company: Research Funding. Terpos:Amgen: Honoraria, Other: SC member, Research Funding; GSK: Honoraria; Janssen: Honoraria, Research Funding; Genesis/Celgene: Honoraria, Other: DMC member, Research Funding; Abbvie: Honoraria; Takeda: Honoraria, Other: SC member; BMS: Honoraria. Dimopoulos:Novartis: Consultancy, Honoraria; Genesis Pharma: Research Funding; Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology: Consultancy, Honoraria, Other: Advisory Committee: Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology.

Chondrosarcoma local recurrence in the Cancer Registry of Norway cohort (1990-2013): Patterns and impact.

There appears to be an association between local recurrence (LR) and risk of metastasis and death in central conventional chondrosarcoma (CCCS) of bone, but this has not been quantified in modern cohorts at a subtype level. We identified nonmetastatic cases of CCCS (N = 180) from the Cancer Registry of Norway. We present prognostic analysis of LR accounting for immortal time bias by descriptive statistics and multivariable Cox models. Of 40 LR, one case demonstrated upgrading while two dedifferentiation. LR was associated with increased risk of metastasis (hazard ratio [HR] = 4.1 [confidence interval, 1.5-10.7]) and death (HR = 9.3 [5.0-17.5]) overall. LR was associated with significant increased risk of metastasis for those with a soft tissue component, axial location, malignancy grade 2, but not atypical cartilaginous tumor's, appropriately treated curettage patients, intramedullary tumors, grade 1 histology, extremity location or "Oslo low risk" group status. We found an increased risk of death for all groups except for those treated by appropriate curettage or belonging to the "Oslo low risk" group. About 50% of LR CCCS were asymptomatic and revealed by routine follow-up. Upgrading of LR for CCCS was a seldom event. LR was associated with significant increased risk of metastasis and death overall, but not for appropriately treated curettage patients or "Oslo low risk" status.

Improving Outcomes for Patients With Epidermal Necrolysis

Epidermal necrolysis (EN), encompassing the spectrum of Stevens-Johnson syndrome and toxic EN, is a rare, severe cutaneous drug reaction with an estimated mortality in modern cohorts of 15% to 23%.1-3 The rarity of the disease makes rigorous prospective clinical research difficult, highlighting the need for multicenter, multinational collaborations as well as iterative efforts to validate and build on prior work.

Cardiovascular risk factors control according to diabetes status and prior cardiovascular events in patients managed in different settings

AimsTo document in recent cohorts the degree of control of major cardiovascular (CV) risk factors according to diabetes status and prior CV disease in different settings. MethodsWe studied men and women aged 50–75 years of whom 3028 with type 2 diabetes mellitus (T2DM) managed at diabetes clinics participants of the TOSCA.IT (NCT00700856) study recruited in 2008–2014; 742 with T2DM managed mainly in primary care and 6753 without diabetes participating in the Moli-sani (NCT03242109) study and recruited in 2005–2010 from an adult general population. ResultsAmong people without a prior CV event people with diabetes managed at diabetes clinics have lower LDL-cholesterol and blood pressure and a more frequent use of lipid-lowering and antihypertensive medications as compared to people with diabetes managed mainly in primary care and to people without diabetes. The proportions achieving the recommended treatment targets are respectively 47.4% vs 33.4% vs 29.5% for LDL-cholesterol and 42.6% vs 9.5% vs 47.4% for blood pressure. Figures for the participants with prior CV events were 26.8% vs 15.1% vs 42.5% for LDL-cholesterol and 43.8% vs 8.5% vs 43.6% for blood pressure. ConclusionsThe study documents that in modern cohorts a large proportion of people with or without diabetes does not achieve the treatment targets for LDL-cholesterol and blood pressure, both in primary and secondary CV prevention. People with diabetes attending diabetes clinics achieve a better control of major CV risk factors than those managed mainly in primary care, thus highlighting the relevant role of a structured model of care.