bluuebunny/crossref_metadata_2025 huggingface dataset:
Private Autonomous Vehicles and Their Impacts on Near-Activity Location Travel Patterns: Integrated Mode Choice and Parking Assignment Model
Authors: Bahk Younghun , Hyland Michael F. , An Sunghi
Published: February 2022

The goal of this study was to analyze the impact of private autonomous vehicles (PAVs), specifically their near-activity location travel patterns, on vehicle miles traveled (VMT). The study proposes an integrated mode choice and simulation-based parking assignment model, along with an iterative solution approach, to analyze the impacts of PAVs on VMT, mode choice, parking lot usage, and other system performance measures. The dynamic simulation-based parking assignment model determines the parking location choice of each traveler as a function of the spatial–temporal demand for parking from the mode choice model, whereas the multinomial logit mode choice model determines mode splits based on the costs and service quality of each travel mode coming, in part, from the parking assignment model. The paper presents a case study to illustrate the power of the modeling framework. The case study varies the percentage of persons with a private vehicle (PV) who own a PAV versus a private conventional vehicle (PCV). The results indicated that PAV owners traveled an extra 0.11 to 1.51 mi compared with PCV owners on average, and the PV mode share was significantly higher for PAV owners. Therefore, as PCVs are converted into PAVs in the future, the results indicate substantial increases in VMT near activity destinations. However, the results also indicated that adjusting parking fees and redistributing parking lot capacities could reduce VMT. The significant increase in VMT from PAVs implies that planners should develop policies to reduce PAV deadheading miles near activity locations, as the automated era comes closer.
Documenting insanity: Paperwork and patient narratives in psychiatric history
Authors: Glew Liana
Published: February 2022

Paperwork plays a key role in a how institutions accommodate, refuse, or manage disabled people. This article develops modes for reading paperwork that build on each other, beginning with (a) recognizing the institutional pressures at work in shaping bureaucratic practices, then (b) considering how a person's relationship to disability influences how they might encounter these practices, and ultimately (c) noticing how the encounter between disabled/mad people and an institution might create something new, what the author calls archival excess. These methods for reading are in conversation with disability studies, medical humanities, and document studies, and ultimately work toward a goal adapted from the principles of Disability Justice: recognizing the wholeness of disabled subjects in institutional archives.
A Feminist Relational Discourse Analysis of mothers’ voiced accounts of the “duty to protect” children from fatness and fatphobia
Authors: Gillborn Sarah , Rickett Bridgette , Woolhouse Maxine
Published: February 2022

Research has highlighted damaging contradictions in the responsibilisation of mothers over children's health, at once held responsible for tackling “childhood obesity” while being cautious not to encourage children to become obsessive with their bodies. While research has highlighted discourses of blame and elucidated mothers’ experiences, less is known about how mothers negotiate discourse in their voiced accounts. Utilising Feminist Relational Discourse Analysis, this study analysed interviews with 12 mothers in England to explore their experiences of a nationally mandated BMI screening programme in schools and how discourses shape their voices and experiences. In negotiating complex and contradictory discourses of motherhood and fatness, participants expressed a “duty to protect” their children from both fatness and fatphobia. Negotiating these responsibilities left mothers feeling guilt at their personal “failure” to protect their children from one or both harms. Mothers did not take up these discourses unproblematically; they resisted them, yet felt constrained by “expert knowledges” of fatness and motherhood that had clear consequences in responsibilising mothers for the “harm” of fatness. This analysis calls attention to how dominant discourses function personally and politically to responsibilise mothers for the harm caused by state-sanctioned fatphobia.
Frailty Affects Self-Care Behavior in Congestive Heart Failure
Authors: Li Jing , Han Jiaqi , Luo Nan , Ding Xinxin , Hao Xiaonan , Li Kun
Published: February 2022

To explore the association between frailty and self-care in older adults with congestive heart failure and analyze their influencing factors. The cross-sectional study was conducted at the department of cardiology of a hospital in China from March 2018 to November 2018. A total of 165 participants were recruited. Frailty and self-care were measured by the Tilburg Frailty Indicator, and the Self-care of Heart Failure Index (V6). The physical, psychological, and social frailty exerted a significant negative association with self-care. Exercise, income, comorbidities, and times of congestive heart failure-related hospitalizations were independent risk factors for frailty; surgical treatment, comorbidities, and income were independent risk factors for self-care. These findings help to fill the need for new approaches to identify the high risk of frailty individuals in the acute care setting for targeted intervention and tailored transitions in care to promote optimal patient quality care and biopsychosocial well-being.
Early Secondary Alveolar Bone Grafting and Facial Growth of Patients with Complete Unilateral Cleft Lip and Palate
Authors: Doucet Jean-Charles , Russell Kathleen A. , Daskalogiannakis John , Mercado Ana M. , Hathaway Ronald R. , Semb Gunvor , Shaw William C. , Long Ross E.
Published: February 2022

Objective

To investigate the craniofacial growth outcomes of early secondary alveolar bone grafting(ABG) around 6 years of age.

Design

Retrospective cohort study

Setting

1 North-American and 5 Northern-European cleft centers.

Subjects

33 subjects with CUCLP consecutively treated with secondary ABG around 6 years of age were compared to 105 subjects from 4 centers treated with late secondary ABG and 19 subjects from 1 center with primary ABG.

Methods

Preorthodontic standardized lateral cephalometric radiographs taken after 12 years of age were traced and analyzed according to the Eurocleft Study protocol. Fourteen angular and two proportional measurements were performed. Measurement means from the Study Center(SC) were compared to 5 Northern-European centers using analysis of variance and Welch's modified t-tests, and P < .05 was considered statistically significant.

Results

For the SC, the mean age ± SD at the time of bone graft was 5.85 ± 0.71 years and the mean age at the time of the lateral cephalogram was 13.4 ± 1.8 years. The sagittal maxillary prominence of the SC was favorably comparable to the 5 Northern-European centers. The mean SNA (78.1 ± 4.3) for the SC was significantly higher compared to 4 of the 5 Northern-European centers(all P < .05), and the mean ANB angle was comparable to 4 of the 5 centers. Similarly, the mean soft tissue ANB angle was not significantly different to the 5 centers. The soft tissue vertical proportions compared favorably to all 5 Northern-European centers(all P < .01).

Conclusions

Craniofacial growth outcomes of early secondary ABG around 6 years compare favorably to the outcomes of late secondary ABG.
Effects of New York City’s Neighborhood Policing Policy
Authors: Beck Brenden , Antonelli Joseph , Piñeros Gabriela
Published: February 2022

Between 2015 and 2018, New York City adopted “neighborhood policing,” an expansive policy to encourage interactions between police officers and community members. Among other changes, the initiative established hundreds of new “neighborhood-coordination” officers and gave “steady-sector” officers time away from 911 response to dedicate to resident interactions. This study evaluates the initiative’s effects on crime, complaints of police misconduct, racial disparities, and arrests. Using monthly data on New York City’s 76 police precincts between 2006 and 2019, we estimate the policy’s causal effect using high-dimensional time series models. This approach accounts for the policy’s staggered adoption, addresses potential correlation among outcomes and between precincts, and controls for unobserved precinct characteristics. We find neighborhood policing reduced misdemeanor and proactive arrests, especially in higher-poverty precincts outside of Manhattan, though it did not change the racial disparities of such arrests. The policy did not affect crime. It briefly increased complaints against police.
Music, adversity and flourishing: Exploring experiences of a community music therapy group for Australian youth
Authors: McFerran Katrina , Hunt Meagan
Published: February 2022

Community music therapy is a widely accepted approach that has its origins in the British community music scene and was carefully developed with respect to participatory values dominant in Norwegian practice. This article describes the way an Australian community music therapy programme for youth has been experienced by a group of diverse young people participating in a programme that is for youth who share an enthusiasm and a passion for music and often bring formidable talent to the group. They are also young people who are experiencing adversity due to chronic illness, mental ill-health, unstable homes lives or acute personal crisis or challenge. Qualitative analysis of interviews identified a number of themes including It is like a family; We understand one another’s life experiences and It is good for me, and also identified that diverse group members responded first to the emphasis on the value of music-based experiences, but strongly benefitted from the understanding afforded of the challenges they faced as a result of adverse life experiences. Possible distinctions between traditional group music therapy with adolescents and community music therapy are considered, with implications for programme descriptions and the level of focus on music and support adopted by facilitators.
‘A threat to us’: The interplay of insecurity and enmity narratives in left-wing populism
Authors: Bonansinga Donatella
Published: February 2022

Left-wing populists are understudied in populism research and little is known on how enmity and insecurity narratives interplay in their rhetoric. Using a narrative framework to capture insecurity in the ‘enemification’ of elites, this article examines left-populist Jean-Luc Mélenchon and La France Insoumise. The analysis reveals a multifaceted construction of national, supranational and international elites as sources of insecurity, based on (a) the threats they pose, (b) the uncertainty they generate and (c) their failure to protect citizens. The article makes two contributions to the populism and International Relations literatures. First, it provides empirical evidence to contest the hypothesis that left populism promotes pluralist agonism rather than antagonism. Second, it shows how populists across the spectrum can use insecurity-centred narratives to delegitimise elites from speaking security and promote an agenda centred on popular sovereignty.
Borneol and Tetrandrine Modulate the Blood–Brain Barrier and Blood–Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in Brain Metastasis
Authors: Lin Jui-Feng , Liu Yen-Shuo , Huang Yu-Chuen , Chi Chih-Wen , Tsai Cheng-Chia , Tsai Tung-Hu , Chen Yu-Jen
Published: February 2022

The efficacy of chemotherapeutic drugs for the treatment of brain metastasis may be compromised by the blood–brain barrier (BBB) and blood–tumor barrier (BTB). P-glycoprotein (P-gp) is a multidrug resistance protein that potentially limits the penetration of chemotherapeutics through the BBB and BTB. 5-Fluorouracil (5-FU) is widely used to treat cancer. Bioactive constituents of medicinal herbs, such as borneol and tetrandrine, potentially improve drug penetration through the BBB and BTB. We hypothesized that borneol and tetrandrine might modulate the BBB and BTB to enhance 5-FU penetration into the brain. To investigate this, in vitro and in vivo models were developed to explore the modulatory effects of borneol and tetrandrine on 5-FU penetration through the BBB and BTB. In the in vitro models, barrier integrity, cell viability, barrier penetration, P-gp activity, and NF-κB expression were assessed. In the in vivo brain metastasis models, cancer cells were injected into the internal carotid artery to evaluate tumor growth. The experimental results demonstrated that borneol and borneol + tetrandrine reduced BBB integrity. The efflux pump function of P-gp was partially inhibited by tetrandrine and borneol + tetrandrine. In the in vivo experiment, borneol + tetrandrine effectively prolonged survival without compromising body weight. In conclusion, BBB and BTB integrity was modulated by borneol and borneol + tetrandrine. The combination of borneol and tetrandrine could be used to improve the chemotherapeutic control of brain metastasis.
Perceptions and responses of staff to the sexuality of adults with intellectual disabilities at facilities in the Western Cape Province of South Africa
Authors: Kahonde Callista K
Published: February 2022

This study explored perceptions and responses of staff members working at facilities for adults with intellectual disabilities in the Western Cape of South Africa toward the adults’ sexuality. Semi-structured interviews were conducted with 12 staff members from four facilities. The data was analyzed using reflexive thematic analysis. Perceptions of service providers were mostly determined by their facility’s ethos and policy on sexuality issues. Some staff members regarded sexuality as a human right and supported all aspects of it while others acknowledged sexuality as a right but perceived the adults as incapable and suppressed their sexuality. Attitudes of the adults with intellectual disabilities’ families were the biggest hurdle faced by the staff who supported the adults’ sexuality. Staff members from different facilities need to learn from each other and direct engagement between the facilities and families is needed to ensure support of the adults with intellectual disabilities to experience sexual autonomy.
Women Get Worse Sex: A Confound in the Explanation of Gender Differences in Sexuality
Authors: Conley Terri D. , Klein Verena
Published: February 2022

Gender differences in sexuality have gained considerable attention both within and outside of the scientific community. We argue that one of the main unacknowledged reasons for these differences is simply that women experience substantially worse sex than men do. Thus, in examinations of the etiology of gender differences in sexuality, a confound has largely been unacknowledged: Women and men are treated to different experiences of what is called “sexuality” and “having sex.” We discuss four arenas in which women’s experience of sexuality may often be worse than men’s: (a) anatomical differences, (b) sexual violence, (c) stigma, and (d) masculine cultures of sexuality. Then we consider how each disparity might explain well-known gender differences in sexuality.
What Can Patient Narratives Reveal to Us About the Experience of a Diagnosis of Myeloma? A Qualitative Scoping Review
Authors: Rubins Zoë , Gibson Barry J , Chantry Andrew
Published: February 2022

In recent years, there have been major advances in treatment options for myeloma and an improved prognosis as a result. There is a wealth of literature that explores the experience of specific treatments from a clinical perspective but there is comparatively little known about the reality of living with myeloma. This research aims to explore the experience of a myeloma diagnosis, to map out key patient experience literature, and examine common themes to support both medical practice and the planning of further research. Following a scoping review methodology, PubMed, StarPlus (the University of Sheffield online database), and Scopus were searched and 15 studies identified for analysis and qualitative synthesis. The literature indicated that myeloma was increasingly being experienced as a chronic condition rather than an acute diagnosis and that there are challenges meeting the needs of patients, understanding the overall symptom burden and the role of the family. The paper identifies emotional and psychological adjustment and coping as a potential area requiring further exploration in the context of a whole team approach to care.
Synchronous “skip” facial metastases from colorectal adenocarcinoma: a case report and review of literature
Authors: Picciariello A. , Tomasicchio G. , Lantone G. , Martines G. , Dibra R. , Trigiante G. , d’Amati A. , Piscitelli D. , Altomare D. F.
Published: February 2022

Background

Skin metastases from colorectal adenocarcinoma are rare conditions that are metachronous in most of cases and may represent the first sign of a recurrence. These lesions are usually located to the abdominal wall on postoperative scars, perineum and chest due to direct spread from the tumor or to the lymphatic and venous dissemination. We describe a rare case of synchronous skin metastases in a patient affected by sigmoid adenocarcinoma with no sign of liver and lung repetitive lesions.

Case presentation

We admitted a 59 years old male, with no relevant medical history. He was evaluated by our tertiary center of colorectal surgery complaining diarrhoea and abdominal pain. The physical examination revealed a palpable mass in left flank of the abdomen. The colonoscopy showed a sub-stenosis of the sigmoid colon (G2 adenocarcinoma). No repetitive lesions were detected by the preoperative CT scan. The patient reported a rapid grow of a soft supralabial and chin nodules in the last 2 months, which he believed to be related to the use of the mask due to COVID-19 pandemic. A laparoscopic left hemicolectomy with complete mesocolic excision and a local excision of both facial nodules were performed. The histological examination revealed a poorly differentiated signet ring cell colorectal adenocarcinoma with metastases in seven pericolic lymphonodes. The excisional biopsy of the skin nodules revealed a subcutaneous metastases from primary colorectal tumour.

Conclusions

As far as we know, synchronous facial metastases from colorectal cancer in the absence of any other metastases has never been described before. The onset of new skin nodules in patients affected by colorectal cancer should raise-up the clinical suspicion of metastatic lesions even when repetitive lesions are not detected in the liver or lungs.
A novel minimally invasive technique of inter-spinal distraction fusion surgery for single-level lumbar spinal stenosis in octogenarians: a retrospective cohort study
Authors: Chen Mengmeng , Jia Pu , Feng Fei , Tang Hai
Published: February 2022

Objective

Surgical treatment of lumbar spinal stenosis (LSS) in octogenarians (patients aged ≥ 80 years) has been a challenge. Inter-spinal distraction fusion (ISDF)—a minimally invasive procedure—was used for treating LSS in octogenarians. This retrospective cohort study aimed to investigate the clinical efficacy and safety of a minimally invasive ISDF technique for LSS in octogenarian patients.

Methods

From April 2015 to April 2019, octogenarian patients who underwent lumbar fusion surgery due to single-segment LSS were included. The patients were grouped into the ISDF group and posterior lumbar interbody fusion (PLIF) group based on the type of surgery. Clinical outcomes were evaluated using scores of the visual analog pain scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedics Association (JOA) scale. Radiographs were assessed for the intervertebral angle (IA), lumbar lordosis (LL), and posterior disc height (PDH). After 2 years postoperatively, all patients underwent computed tomography (CT) to evaluate the fusion condition. Perioperative data and related complications were recorded.

Results

Sixty-two patients were included (mean age: 82.22 ± 1.95 years). The ISDF and the PLIF groups had 34 and 28 patients, respectively. The average follow-up time was 2.1 ± 0.25 years. There was no significant difference in VAS, ODI, JOA, and PDH scores between both groups preoperatively and at each postoperative time-point. The IA and LL showed significant differences between both groups after surgery (p < 0.05). The postoperative IA in the ISDF group were significantly lower than the preoperative values, while that in the PLIF group were markedly increased. The PLIF group had an increased LL compared with that preoperatively (p < 0.05), while the LL in the ISDF did not significantly change. The operative time, blood loss, hospital stay time, and the rate of perioperative complications of the ISDF group were significantly lower than those of the PLIF group (p < 0.05). There was no significant difference in the fusion rates between both groups.

Conclusion

ISDF surgery is a viable method for octogenarian patients with LSS that provides a similar clinical efficacy, shorter operative time, less blood loss, shorter hospital stay time, and fewer complications, compared to the PLIF surgery.
CD90 is regulated by notch1 and hallmarks a more aggressive intrahepatic cholangiocarcinoma phenotype
Authors: Mancarella Serena , Serino Grazia , Gigante Isabella , Cigliano Antonio , Ribback Silvia , Sanese Paola , Grossi Valentina , Simone Cristiano , Armentano Raffaele , Evert Matthias , Calvisi Diego F. , Giannelli Gianluigi
Published: February 2022

Background

Intrahepatic Cholangiocarcinoma (iCCA) is characterized by a strong stromal reaction playing a role in tumor progression. Thymus cell antigen 1 (THY1), also called Cluster of Differentiation 90 (CD90), is a key regulator of cell–cell and cell–matrix interaction. In iCCA, CD90 has been reported to be associated with a poor prognosis. In an iCCA PDX model, we recently found that CD90 was downregulated in mice treated with the Notch γ-secretase inhibitor Crenigacestat. The study aims to investigate the role of CD90 in relation to the NOTCH pathway.

Methods

THY1/CD90 gene and protein expression was evaluated in human iCCA tissues and xenograft models by qRT-PCR, immunohistochemistry, and immunofluorescence. Notch1 inhibition was achieved by siRNA. THY1/CD90 functions were investigated in xenograft models built with HuCCT1 and KKU-M213 cell lines, engineered to overexpress or knockdown THY1, respectively.

Results

CD90 co-localized with EPCAM, showing its epithelial origin. In vitro, NOTCH1 silencing triggered HES1 and THY1 down-regulation. RBPJ, a critical transcriptional regulator of NOTCH signaling, exhibited putative binding sites on the THY1 promoter and bound to the latter, implying CD90 as a downstream NOTCH pathway effector. In vivo, Crenigacestat suppressed iCCA growth and reduced CD90 expression in the PDX model. In the xenograft model, Crenigacestat inhibited tumor growth of HuCCT1 cells transfected to overexpress CD90 and KKU-M213 cells constitutively expressing high levels of CD90, while not affecting the growth of HuCCT1 control cells and KKU-M213 depleted of CD90. In an iCCA cohort, patients with higher expression levels of NOTCH1/HES1/THY1 displayed a significantly shorter survival.

Conclusions

iCCA patients with higher NOTCH1/HES1/THY1 expression have the worst prognosis, but they are more likely to benefit from Notch signaling inhibition. These findings represent the scientific rationale for testing NOTCH1 inhibitors in clinical trials, taking the first step toward precision medicine for iCCA.
Pulmonary vein aneurysm in a New Zealand White rabbit: a case report
Authors: Kim Jong-Min , Woo Chang Gok , Kim Sa Hun , Jeong Eui-Suk , Kim Kil-Soo , Kang Byeong-Cheol
Published: February 2022

Background

Pulmonary venous aneurysm (PVA) is a rare condition characterized by aneurysmal dilatation of the pulmonary vein in humans. The diagnosis is incidental usually as there are no clinical symptoms. This case report describes a histological diagnosis of PVA in a New Zealand White rabbit.

Case presentation

A 1.5-kg male New Zealand White rabbit was acclimatized in an animal room for 5 weeks until the experiment began. However, the rabbit was found dead, with signs of nasal hemorrhage. Necropsy revealed tracheal and pulmonary hemorrhage, and the epistaxis had a pulmonary origin. PCR and ELISA to detect antigens and antibodies pertaining to the rabbit hemorrhagic disease virus showed negative results. Multiple ballooning lesions (50–200 μm size) in the pulmonary veins were observed on histological examination, and PVA was diagnosed. Death was attributed to a spontaneous rupture of the PVA and massive hemorrhage into the lung parenchyma that extended into the trachea and nasal passages.

Conclusions

To the author’s best knowledge, this is the first report of a PVA in a rabbit.
High-diagnostic accuracy of inguinal ultrasonography and fine needle aspiration followed by dynamic sentinel lymph node biopsy in men with non-palpable and palpable inguinal lymph nodes.
Authors: Lee Esther Wan Ching , Issa Allaudin , Oliveira Pedro , Lau Maurice , Sangar Vijay , Parnham Arie , Fankhauser Christian Daniel
Published: February 2022

6

Background: Penile cancer undergoes a stepwise dissemination and metastasises first to the inguinal lymph nodes (ILN). Because men can be cured in this early stage of metastatic disease, early detection and treatment is important. Methods: We performed a retrospective analysis of men with ≥T1G2 penile cancer and negative inguinal US guided FNA undergoing DSNB. Men with suspicious US but negative FNA underwent US guided ILN excision. Men with ≥T1G2 local recurrence during follow-up and non-squamous cell histologies were excluded. Descriptive analysis was performed, and sensitivity and negative predictive values (NPV) were calculated. Results: The final cohort consisted of 403 men with a median age of 65 years (IQR 55-73) and body mass index (BMI) of 28.6 kg/m² (IQR 25-33) for this analysis. This gave 728 groins with negative FNA undergoing DSNB +/- US guided lymph node excision. At least one sentinel node (SN) was visualised in 93% during the 1st and in 7% during the 2nd lymphoscintigraphy. Median SNs visualised preoperatively was 1 and a median of 2 nodes were resected. ILN metastases were detected in 9% groins with non-palpable and in 17% with palpable lymph nodes. Stratified by non-palpable and palpable ILN, non-local recurrence despite pathologically negative DSNBs was observed in 0.5% and 0%. Limited to men with at least 24 months follow-up, non-local recurrence after negative DSNBs was observed in 0.4% and 0%. The sensitivity of DSNB was 96% and NPV was 100%. The main limitation of this analysis is its retrospective nature and inherit biases. Conclusions: Our results suggest that in a high volume centre pre-operative ultrasound +/- FNA and DSNB can be used to accurately stage men with non-palpable and palpable ILN in men with ≥T1G2 penile cancer. Further, FNA in advance of surgery provides logistical and surgical advantages. In those patients with palpable disease but negative FNA, we advocate ultrasound guided excision in case of enlarged or suspicious ILN during DSNB.[Table: see text]
Comparative ctDNA analyses of African-American and Caucasian patients with CRPC.
Authors: Jaeger Ellen B. , Caputo Sydney , Fleming William , Manogue Charlotte , Lieberman Alex , Sussman Isabelle P. , Miller Patrick , Light Malcolm , Huang Minqi , Barata Pedro C. , Lewis Brian E. , Layton Jodi Lyn , Ledet Elisa M. , Sartor A. Oliver
Published: February 2022

24

Background: Somatic genetic analyses have indicated genetic distinctions in AA as compared to C patients. In the Mahal et al. study (1) evaluating a broad spectrum of pts with tissue based assays, FOXA1 mutations were more frequent in AA men and TP53 mutations were less frequent in AA men as compared to C men. In a separate analysis by Khashab et al. (2) conducted in prostate cancer pts receiving androgen deprivation therapy, using both tissue and ctDNA assays, the authors reported AR, TP53, SPOP, and BRCA2 were more frequently mutated in AA men as compared to C men. Herein we assessed the Guardant 360 platform in assessing ctDNA differences in AA and C men, all of whom had CRPC at the time assays were performed. Methods: Guardant 360 was used to analyze ctDNA with a cut-off of >0.5% for allelic fractions for ascertaining the presence or absence of pathogenic mutations and various amplifications. Lower allelic fractions were not analyzed given these may represent less relevant mutations. Depending on the timing of the assays (2015-2021), 70-83 genes were analyzed. All pts had CRPC and all patients were treated at Tulane Cancer Center. Chi Square analyses were used to determine statistical differences. AR, BRCA2, and TP53 were assessed but SPOP and FOXA1 were not assessable in the Guardant ctDNA assay. Both mutations and amplifications were evaluated. Results: Among men with CRPC, a total of 48 AA men and 179 C men were analyzed using ctDNA. Clear distinctions were found in the alteration reported in APC, TP53, and CDK12. TP53 was less frequently mutated and other genes were more frequently altered in the AA men. Conclusions: Using Guardant ctDNA assays in men with CRPC, clear distinctions were found in AA men as compared to C men. It is unclear why these results differ from that reported by others, however distinctions in both the assays and the populations are notable.[Table: see text]
Association between health-care system and prostate cancer mortality for African American men with localized and metastatic prostate cancer.
Authors: Nelson Tyler J. , Courtney Patrick Travis , Klebaner Daniella , Guram Kripa , Sherer Michael Vincent , Rodrigues De Moraes Gustavo , Banegas Matthew P. , Stewart Tyler F. , McKay Rana R. , Garraway Isla , Murphy James , Rose Brent S.
Published: February 2022

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Background: African American (AA) men with prostate cancer (PC) present with more advanced disease and have worse survival than comparable non-Hispanic White (White) men. Recent studies suggest that receiving care within an equal access setting may attenuate these disparities. We hypothesize that AA men receiving care within the Veterans Health Administration (VHA) will have improved outcomes compared to AA men receiving care in the general population as assessed by the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We identified AA men diagnosed with PC between 2004 and 2015 in the VHA and SEER. For comparisons of covariate distributions across subgroups, we used the chi-squared test with continuity correction. We analyzed the cumulative incidence (with 95% confidence intervals (CIs)) of PC specific mortality (PCSM) in the VHA and SEER. Additionally, multivariable Cox proportional hazards models controlling for demographic information were performed. Results: The cohort included 85,409 AA men (VHA: 27,415, SEER: 57,994). Median follow-up was 4.79 years in the VHA and 5.16 years in SEER. In the VHA, AA men were more likely to present with localized disease (VHA 94.7% vs SEER 86.4%, p < 0.001) and less likely to have metastatic disease (3.2% vs 4.3%, p < 0.001). The 5-year cumulative incidence of PCSM was lower for patients in the VHA (VHA: 3.8% [CI: 3.5-4.1%] vs. SEER: 5.0% [CI: 4.8-5.2%], p < 0.001). The PCSM difference was largest in men with metastatic disease. In metastatic patients, cumulative incidence of PCSM at five years was significantly lower in the VHA (VHA 52.5% [CI: 48.0-56.5%] vs. SEER 64.8% [CI: 62.3-67.1%], p < 0.001). In contrast, AA men with localized disease had similar PCSM in the VHA and SEER (VHA 2.4% [CI: 2.2-2.6%] vs. SEER 2.6% [CI: 2.4-2.7%], p = 0.09 at five years). On multivariable analysis, VHA system was associated with lower PCSM [Hazard Ratio (HR): 0.91, p < 0.001]. There was a significant interaction between VHA system and distant metastases at diagnosis [p < 0.001] indicating larger differences in PCSM by healthcare system in metastatic patients as compared to localized patients. VHA system was associated with reduced PCSM in metastatic patients [HR 0.84, p < 0.001] but not in localized patients [HR 0.96, p = 0.13]. Conclusions: AA men in the VHA had a significantly lower incidence of PCSM than those in the SEER database, especially for those who presented with distant metastases at diagnosis. Future work should examine how cost and access to care affect disparities in outcomes for AA men.
Trends in prostate cancer mortality in the United States of America, by state and race, from 1999 to 2019: Estimates from the Centers for Disease Control WONDER database.
Authors: Jani Chinmay , Mouchati Christian , Abdallah Nour , Mariano Melissa , Jani Ruchi Tusharkumar , Salciccioli Justin D , Marshall Dominic C , Singh Harpreet , Shalhoub Joseph , McKay Rana R.
Published: February 2022

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Background: In the United States of America (USA), prostate cancer is the most common cancer in men, and it remained the second leading cause of cancer related mortality. It has a disproportionate burden of disease among minorities. In particular, African American (AA) men have a higher incidence and more aggressive disease course. Our study compares trends in prostate cancer mortality in the United States of America (USA) by race and state from 1999 to 2019. Methods: We used the Center for Disease Control (CDC) WONDER database using ICD-10 code C61 to extract mortality data for malignant prostate cancer. Age standardized death rates (ASDRs) are reported per 100,000 population using the USA standard population. ASDRs were divided into American Indian or Alaskan Native, Asian, Black or African American and, Whites and reported by year for each state. Due to the lack of available data in many states, state-wise analyses were done for white and African American men only. We used Joinpoint regression analysis for trends comparison. Results: Between 1999 and 2019, data was analyzed from 50 states of the USA, of which four started collecting data from 2000, one from 2001, one from 2008, and one from 2009. Three states had data until 2018 only. Data was missing for African American men in 17 states. In 2019, ASDR in African American (13.4/100,000) was significantly higher than Whites (7.3/100,000) (p<0.001). The highest ASDR for African American was observed in Nebraska (33.5/100,000), followed by Wisconsin (17.7/100,000). In contrast, the highest ASDR for whites was observed in Alaska (11/100,000), followed by Utah (10.5/100,000) ASDR decreased by 31.8% in White men at the national level, compared to a decline of 44.6% in African American men. ASDR decreased in all states for both races. For White men, the widest drops were in South Dakota (-45.9%) and Kentucky (-47.0%), and the lowest declines in New Hampshire (-11.5%) and Alaska (-16.0%). For African American men, the largest decreases were in Delaware (-57.8%) and Nevada (-55.3%), and the smallest declines were in Kentucky (-14.9%) and Wisconsin (-20.3%). Conclusions: During the last 20 years, the mortality rate from prostate cancer has consistently dropped in all the states of the USA and for all races. Even though a higher decrease in ASDR was observed in the African American and Asian racial groups, ASDR is still higher in African Americans as compared to Whites.[Table: see text]
Tailoring 4Kscore thresholds to multiparametric MRI results.
Authors: Nemirovsky Daniel R , Reddy Akshay G , McSweeney Benjamin , Klose Charles , Chen Joyce , Atienza Matthew , Haji-Momenian Shawn , Imtiaz Danish , Whalen Michael Joseph
Published: February 2022

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Background: 4Kscore was developed and validated agnostic to prostate multiparametric MRI (mpMRI) findings, with current clinical paradigms utilizing a value of 7.5% to delineate the potential for high-grade disease. A growing body of evidence suggests improved diagnostic utility when used in conjunction with mpMRI results. Incorporation of mpMRI PIRADS scores may have potential to enhance diagnostic accuracy of 4Kscore, especially for non-definitive lesions. This study aims to examine the optimal 4Kscore threshold in PIRADS 3/4 lesions to maximize test utility and help guide clinical decision-making. Methods: A single-institution review of all patients with recorded 4Kscore, prostate MRI with dominant PIRADS 3/4 lesions, and final biopsy pathology from 2016-2020 was conducted from an IRB-approved database. Clinically significant prostate cancer (csPCa) was defined as Gleason score ≥3+4 on final biopsy. Receiver operating characteristic curves were generated, and the primary data point was chosen to maximize sensitivity and specificity. Results: 88 patients with dominant PIRADS 3 (n = 40) or PIRADS 4 (n = 48) lesions were identified. For patients with PIRADS 3 lesions, area under the curve (AUC) was 0.8083 (p < 0.0039) with optimal 4Kscore threshold to detect csPCa as 18.5% (sensitivity = 70.00%, specificity = 80.00%). Negative predictive value (NPV) at 4Kscore of 18.5% in PIRADS 3 lesions was 0.93. In patients with dominant PIRADS 4 lesions, AUC was 0.7735 (p < 0.002), and optimal threshold to detect csPCa was 21.5% (sensitivity = 70.59%, specificity = 76.67%). NPV at 4Kscore of 21.5% in PIRADS 4 lesions was 0.82. Conclusions: Stratification of mpMRI PIRADS 3/4 lesions suggests that utilization of more permissive 4Kscore thresholds can improve prediction of csPCa without sacrificing NPV, especially for PIRADS 3 lesions. These findings may enhance risk-adapted prostate cancer screening, reduce unnecessary prostate biopsies, and optimize clinical management.
Outcome of patients with PSMA-PET/CT screen failure by VISION criteria and treated with 177Lu-PSMA therapy.
Authors: Hotta Masatoshi , Gafita Andrei , Czernin Johannes , Calais Jeremie
Published: February 2022

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Background: The VISION trial showed that 177Lu-PSMA can prolong survival and improve the quality of life of patients with advanced mCRPC. The VISION trial used PSMA-PET/CT to select patients for inclusion. Here, we evaluated the outcome of patients treated with 177Lu-PSMA who would have been screen failure (SF) by VISION-PET criteria. Methods: We conducted a retrospective cohort study in our institutional database of patients treated with ≥1 cycle of 177LuPSMA between November 2017 and July 2021 (n = 74) and a multicenter dataset published previously (n = 230) (Gafita A, Lancet Oncol 2021). One dual certified reader (M.H.) in nuclear medicine and radiology blinded for patient outcomes reviewed the baseline PSMA-PET/CT scans to define eligible (VISION-PET-E) vs SF (VISION-PET-SF) patients. VISION-PET- SF criteria were defined as:1) absence of metastatic lesion with uptake > liver background (i.e., low PSMA expression) or 2) presence of ≥ 1 metastatic lesion measurable by CT (≥ 1 cm for bone lesions with soft-tissue component (M1b) and solid/visceral organs lesions (M1c); ≥ 2.5 cm for lymph nodes lesions (N1-M1a)) with uptake ≤ liver background (i.e., PSMA-negative lesions). Outcome measures included PSA response rates (decline of ≥50% (PSA50RR) and any decline (anyPSARR)), PSA-progression free-survival (PSA-PFS), and overall survival (OS). Results: 3/304 patients (1%) were excluded (lost to follow-up (n = 2), missing DICOM CT images (n = 1)). 272/301 (90.4%) of the analyzed patients were VISION-PET-E while 29/301 (9.6%) were VISION-PET-SF: 8/301 (2.7%) with low PSMA expression and 21/301 (7.0%) with PSMA-negative lesions, respectively. The median follow-up time was 12.6 months (IQR: 7.0-21.3, range: 0.6-62.3). VISION-PET-SF patients had a worse PSA50RR (21% vs 50%; p = 0.005), anyPSARR (41% vs 71%; p = 0.003), median PSA PFS (2.1 months (1.1-3.3) vs. 4.1 (4.0-5.8); p = 0.023)), and tended to have a shorter median OS (9.6 months (4.7-14.0) vs. 14.2 (12.6-15.9); p = 0.16) than the VISION-PET-E patients. Patients with PSMA-negative lesion (n = 21) tended to have a worse response than those with low PSMA expression (n = 8): median OS 8.2 months (4.4-11.0) vs. NA (11.1-NA) (p = 0.034), median PSA-PFS 1.8 months (1.4-3.3) vs. 2.8 (1.1-5.7) (p = 0.44), PSA50RR 19% vs 25% (p = 1.00), and any PSARR 38% vs 50% (p = 0.68). Conclusions: Some have argued that the low SF rate of 12.6% (126/1003) in the VISION trial may obviate the need for PSMA-PET eligibility screening prior to 177Lu-PSMA. Here we report that VISION-PET-SF patients had worse outcomes than VISION-PET-E patients in response to 177Lu-PSMA therapy. The best management of patients with negative or low PSMA expressing lesions is unknown. Combining 177Lu-PSMA with external-beam RT and/or with other systemic therapy may be an effective therapeutic approach. Refinements in patient selection for 177Lu-PSMA are needed to optimize patient outcomes.
Factors associated with gene mutation testing in United States veterans with metastatic castration-resistant prostate cancer.
Authors: Hung Anna , Li Yanhong , Candelieri Danielle , Alba Patrick , Anglin-Foote Tori , Lee Kyung Min , Agiri Fatai , Perez Cristina , Li Weiyan , Amin Suvina , Jiang Shan , DuVall Scott L. , Wong Yu-Ning , Reed Shelby D. , Lynch Julie Ann
Published: February 2022

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Background: Practice guidelines have been modified to recommend hereditary and tumor gene mutation testing in patients with metastatic castration-resistant prostate cancer (mCRPC) to identify patients for molecularly targeted therapies. Identifying appropriate candidates for testing can be challenging in electronic health records and claims data. In this study, we used natural language processing (NLP) algorithms to identify veterans with mCRPC, reported gene mutation testing rates and identified factors associated with testing. Methods: This is a retrospective observational cohort study using NLP to identify veterans diagnosed with mCRPC between 2016 and 2020. Patient and facility characteristics were reported descriptively. Chi-square and t-tests were used to determine whether differences were statistically significant at a significance level of 0.05 based on receipt of testing. Generalized linear mixed models with binomial error distributions and logit links accounting for clustering by facility were used to determine which factors were independently associated with testing. Results: 9,282 veterans were diagnosed with mCRPC between 2016 and 2020, as determined by NLP algorithms identifying diagnosis of metastatic disease and castration-resistant disease. Among these patients, 381 died within 45 days of their diagnosis, and were excluded from analysis. In the analytic cohort of 8,901 veterans, 1,282 (14%) patients received testing. Of these, 1,041 (81%) received tumor tissue testing and 292 (23%) received hereditary testing. In bivariate analyses, age, race, ethnicity, Commission on Cancer (COC) facility certification, and facility complexity rating differed between veterans who received the test versus who did not (mean age of 73 versus 77, p < 0.0001; 30% versus 24% Black, p < 0.0001; 93% versus 92% non-Hispanic, p = 0.04; 64% versus 63% COC-certified facility, p = 0.04; and 59% versus 52% most complex facility, p < 0.0001). In multivariate analyses, older age and lower facility complexity rating were associated with lower odds of testing (for every 10-year increase in age, adjusted odds ratio [aOR], 95% confidence interval [CI]: 0.54, 0.50-0.58; Mid-high and low complexity facilities compared to highest complexity facilities: aOR, 95% CI: 0.52, 0.32-0.85 and 0.39, 0.22-0.71, respectively). Conclusions: Gene mutation testing in veterans with mCRPC is underutilized. Older age and being seen in a lower complexity facility are independently associated with a lower odds of testing. Patient and facility barriers to testing should be identified to improve guideline concordant care.
Evaluation of compliance of next-generation sequencing (NGS) testing in stage IV genitourinary (GU) cancer patients (pts) and the effect of an EHR prompt (EP) on increasing frequency.
Authors: Cobrin Sydney E. , Yeung Percy , Cedeno Carina , Marks Stephanie , Ronnen Ellen A.
Published: February 2022

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Background: Previous reports have found that NGS testing on stage IV GU cancer patients is performed less commonly than expected based on the prevalence of GU tumors in comparison to other tumor types. In addition, most of the data on NGS testing frequency has been in the academic setting. This study will look at NGS testing in stage IV GU pts in the private practice setting. Methods: In the retrospective portion of the study, we used algorithms in Flatiron’s OncoEMR to identify baseline NGS testing frequency in all stage IV GU cancer patients. In the prospective portion, we used an EP to communicate with doctors about their stage IV GU cancer pts with upcoming appointments. Our primary endpoint was to determine the percentage of stage IV GU pts who had NGS testing; our secondary endpoint was to determine how often NGS testing would provide an alternative therapeutic option. Results: 91 stage IV GU cancer pts were identified retrospectively from 6/1/2020-12/31/2020. 20 (22%) of them had had NGS testing: 12 of 68 (18%) prostate cancer pts, 6 of 13 (46%) bladder cancer pts and 2 of 10 (20%) kidney cancer pts. Prospectively, 65 patients with Stage IV GU cancer and upcoming appointments were identified between 8/23/2021-9/13/2021. 17 (26%) had previously had NGS testing: 10 of 46 (22%) prostate pts, 4 of 9 (44%) bladder pts, and 3 of 10 (30%) kidney pts. The EP prompted additional testing of 10 pts. Of the total 27 pts, 8 (30%) were found to have actionable mutations: 7 of 17 (41%) prostate pts and 1 of 6 (17%) bladder pts. 6 of the 8 actionable mutations were either BRCA1/BRCA2 or PALB2. Conclusions: Our results supported those previously reported in academic settings which found that GU cancers were less likely than other metastatic cancers to have NGS testing performed. Prostate cancer was the least likely of the GU cancers to have NGS testing, however, the findings highlight the importance of germline testing in this population. A longer term study may have further borne out the benefits of EP. Improved communication (huddles, multidisciplinary rounds, etc.) would likely increase compliance with NGS testing as would automated order sets and “hard stops” in the EMR. As trials and standard options for GU cancers increase, physician ordering of NGS will follow. Universal NGS testing should be the goal of all stage IV GU patients to maximize therapeutic options.