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Background: Lapatinib in combination with capecitabine is a standard of care treatment for ErbB2+ metastatic breast cancer (MBC) patients who have progressed after anthracyclines, taxanes and trastuzumab treatment. Results from the lapatinib pivotal trial showed that the addition of lapatinib to capecitabine increased median time to progression (TTP) even among heavily pre-treated patients (median of 4 prior lines of therapy). A post-hoc exploratory sub- group analysis of this trial suggested that earlier administration of lapatinib-capecitabine in MBC patients who progress after trastuzumab may produce better clinical outcomes. The TYCO study was designed to evaluate if early initiation of lapatinib-capecitabine in patients with ErbB2+ MBC who have progressed on trastuzumab-containing regimen improves TTP in comparison with a delayed start of the therapy. Trial design: TYCO is an international, multicenter, prospective, observational study in 269 ErbB2+ MBC patients whose disease has progressed after treatment with trastuzumab in the metastatic setting. Two cohorts will be compared; Group 1: patients receiving lapatinib- capecitabine just after the first trastuzumab progression, and Group 2: patients receiving lapatinib-capecitabine after two or more lines of treatment after first trastuzumab progression. The study duration is of 12 months with data collection at baseline and approximately every 3 months thereafter. Major Eligibility Criteria: 1. Females ≥18y with confirmed ErbB2+ MBC who have progressed after a previous trastuzumab-containing regimen, 2. Pts eligible for standard therapy with lapatinib-capecitabine at approved conventional doses, as per local approved label. 3. Pts eligible to start standard treatment with Lapatinib-capecitabine at conventional doses, or receiving standard treatment with Lapatinib-capecitabine at conventional doses, for no longer than 10 weeks from the start of the treatment to the date of inclusion in the study; Aims: Primary objective of this study is to determine if early switch to lapatinib-capecitabine in patients with ErbB2+ metastatic breast cancer who have progressed on trastuzumab containing regimen improves time to disease progression as determined by treating physician either clinically or radiologically. Secondary objectives include overall response rate and overall survival. Statistical Methods: Kaplan-Meier plots will be used to describe the median TTP after start of lapatinib-capecetabine. Cox proportional hazard model will be developed to estimate the adjusted hazard ratio (and 95% confidence intervals) comparing TTP for the two treatment group using propensity score methods (trimmed sample, adjustment for the continuous propensity score measure, and doubly robust adjustment) to adjust for potential confounding by indication that may arise due to the non-randomised design. Present and Target Accrual: Enrollment began in February 2010, and as per May 2012, 266 patients have been included from Turkey, Venezuela, Argentina, Saudi Arabia and Colombia. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the oncological and genitourinary outcomes of various forms of prostate ablation for localized prostate cancer., Methods: A prospectively managed database included men with localized prostate cancer who underwent prostate ablation during January 2018-August 2023. Patients received either whole or partial-gland ablation using 1 of 3 energy modalities: cryotherapy, High Intensity Focused Ultrasound (HIFU), or Irreversible electroporation (IRE). The primary endpoints included biochemical recurrence (BCR), imaging failure (IF) and pathological failure (PF). The secondary endpoints included complication rate at 30 days and genitourinary function., Results: 150 consecutive patients were included, of them 49 (32.7%) underwent whole-gland therapy and 101 (67.3%) underwent partial-gland therapy. The whole-gland therapy subgroup included cryoablation (39, 79.6%) and HIFU (10, 20.4%) and the partial-gland therapy subgroup included cryoablation (50, 49.5%), HIFU (30, 29.7%) and IRE (21, 20.8%). The median follow-up time was 32.6 months (IQR, 19.2-47.0) and 14.8 months (IQR, 9.5-31.9) in the whole-gland and partial-gland therapy subgroups, respectively. The rate of PF was 6.1% and 16.8% in the whole and partial gland groups, respectively. Whole-gland cryoablation had the most prominent positive impact on AUA-SS score and negative impact on SHIM score. Among patients undergoing partial gland ablation there was no significant impact on urination and erections at 12 months and 90% of potent men retained their potency. Approximately one-third of the patients experienced minor postoperative complications within 30 days., Conclusion: Our findings conclude that ablation is a safe treatment option for localized prostate cancer, with satisfactory oncological outcomes and minimal short-intermediate-term morbidity., Patient Summary: In this study we looked at whole- and partial-gland ablation therapies for localized prostate cancer and found satisfactory oncological outcomes and minimal impact on urinary and sexual function with short-intermediate-term follow-up., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Abhinav Sidana reports a relationship with Sonablate that includes: consulting or advisory. Abhinav Sidana reports a relationship with AngioDynamics Inc that includes: consulting or advisory. If there are other authors, they 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 © 2024 Elsevier Inc. All rights reserved.)

Aim: Explore caregiver (i.e., person who provides direct care for a child and was present at the time of their medical visit) perspectives and preferences regarding timely access to unscheduled acute care as well as barriers and facilitators of the use of an online appointment tool (i.e., Save My Spot) in a satellite children's hospital five urgent care centers in the United States., Design: A descriptive qualitative interview study., Methods: We conducted semi-structured interviews with 49 caregivers in a private room, in person and in conjunction with medical visits from June 2023 to the end of August 2023 after obtaining institutional ethical approvals. We employed deductive and inductive content analysis and used the MAXQDA data analysis tool., Results: Average caregiver age was 37 years. Most of the caregivers were female, white, and non-Hispanic and had low income. We identified three categories: (a) Caregiver preferences for using the Save My Spot online appointment tool and their reasons for buy-in, (b) ways of promoting the Save My Spot tool and (c) enhancing the accessibility of the Save My Spot tool., Conclusion: The findings of this study suggest that when introduced successfully, caregivers adopt an online appointment tool and find it efficient in minimising wait times. Various approaches (e.g., social media, billboards) can be used to promote the tool to increase timely access to care., Impact: This study provides valuable insights into the utilisation of an online appointment tool in the two hospital-based and three stand-alone neighbourhood urgent care centers of a large urban children's hospital. Future studies capturing different tools and populations are recommended to gain diverse understanding., Reporting Methods: The study was reported following the Standards for Reporting Qualitative Research., Patient or Public Contribution: Caregivers provided their perspectives and the Paediatric Emergency Medicine Disparities Working Group contributed to the interpretation of the study findings., (© 2024 John Wiley & Sons Ltd.)

Introduction: Focal therapy (FT) is a form of ablative treatment offered to men with localized, organ-confined prostate cancer (CaP). Pelvic multiparametric magnetic resonance imaging (mpMRI) and mpMRI/transrectal ultrasound fusion (MRI-US) guidance enable the precise delivery of FT with limited ablation of adjacent benign tissue or vital genitourinary structures. This article presents our findings on using MRI-US to perform FT as a primary treatment for men with intermediate-risk CaP., Methods: Thirty-six men underwent MRI-US fusion-guided FT cryoablation at a single center from 2018 to 2023 as a primary treatment for intermediate-risk CaP. Following FT, quarterly prostate-specific antigen (PSA) testing and a 6 to 9 month mpMRI and combined MRI-US targeted and systematic biopsy were performed. Oncological outcomes were determined using several endpoints containing biochemical recurrence, imaging failure, and pathological failure. Functional outcomes were measured using reported erectile dysfunction/potency rates, urinary incontinence rates, and the American Urologic Association Symptom Score (AUA-SS) and Sexual Health Inventory for Men (SHIM) indices., Results: Median follow-up was 29.1 months, most (75%) of whom had grade group 2 CaP. Out of the 36 men, 32 (88.9%) completed the combined MRI-targeted and systematic biopsy follow-up after treatment. The study had no major complications, but 12 (33.3%) patients experienced Clavien-Dindo grade II or lower complications. For oncological outcomes, 6 (16.7%) men had biochemical recurrence, 9 (25%) showed imaging failure, and 8 (22.2%) met the criteria for positive biopsy- out-of-field vs. in-field. 88.2% of previously potent patients remained potent postoperatively at 12 months. All patients were continent at 12 months. There were no statistically significant changes in the AUA-SS and SHIM scores postoperatively., Conclusion: MRI-US-guided cryoablation to target lesions in intermediate-risk CaP appears to be a safe treatment option, with functional outcomes indicating minimal short and intermediate-term morbidity and acceptable oncological outcomes. However, despite close monitoring and follow-up, there is still a limitation in accurately predicting/detecting pathological failure after FT. The long-term durability of FT for intermediate-risk, organ-confined CaP remains uncertain., 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 © 2024 Elsevier Inc. All rights reserved.)

Rationale and Objectives: Transgender persons often experience healthcare disparities due to lack of provider knowledge. With increasing gender diversity awareness and prevalence of gender-affirming care, radiologists-in-training need to be aware of the unique health considerations for this patient population. Radiology residents have limited exposure to dedicated teaching on transgender medical care and imaging during training. Development and implementation of a radiology-based transgender curriculum can help close this gap in radiology residency education. The aim of this study was to explore radiology resident attitudes and experiences with a novel radiology-based transgender curriculum, guided by the conceptual framework of reflective practice., Materials and Methods: A qualitative approach was employed using semi-structured interviews to explore resident perspectives of a curriculum covering transgender patient care and imaging over 4 monthly sessions. Ten residents at the University of Cincinnati radiology residency participated in interviews consisting of open-ended questions. Interviews were audiotaped, transcribed, and thematic analysis was conducted across all responses., Results: Four themes emerged through the existing framework: 1) impactful/memorable aspects; things learned; increased awareness; and suggestions/feedback. Prominent subthemes included patient panel and stories, physician experts sharing knowledge and experiences, link to radiology and imaging, novel concept, gender-affirming surgeries and anatomy, appropriate radiology reporting, and patient interactions., Conclusion: Radiology residents found the curriculum to be an effective novel educational experience that was previously unaddressed during their training. This imaging-based curriculum can be further adapted and implemented in a variety of radiology curricular settings., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Rationale and Objective: The transition to an all-virtual residency interview process, in response to the COVID-19 pandemic, has seen numerous benefits beyond applicant and program safety. These benefits include improvements in equity, access and even lowering the applicant's carbon footprint. However, a significant portion of applicants have concerns with being unable to visit a program and interact with residents and faculty in person. A second look opportunity for radiology residency applicants was developed to address applicant concerns while maintaining an equitable interview process for all., Materials and Methods: The second look opportunity took place after our program's final rank list was completed. Second look attendees completed a 10-question online survey after completion of our program's second look to ascertain financial obstacles of attending, the importance of a second look opportunity, and reasons why applicants chose to attend., Results: 24/24 (100%) of attendees completed the survey. The majority of attendees were from >100 miles away (54%). Only 21% felt that the financial burden of the second look was substantial. However, this response was more common among attendees from >100 miles away (p = 0.013). All applicants surveyed chose to attend the second look in order to see the radiology department facilities and to meet the faculty in person. All applicants agreed or strongly agreed that they learned more about the residency program through in-person discussions with residents and faculty than they were able to remotely and that the in-person second look opportunity is a valuable tool to help make an informed rank decision when interviewing virtually., Conclusion: The second look opportunity offers multiple benefits for applicants to help make an informed rank list decision during a virtual interview season., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Children have historically been underrepresented in randomized controlled trials and multi-center studies. This is particularly true for children who reside in rural and underserved areas. Conducting multi-center trials in rural areas presents unique informatics challenges. These challenges call for increased attention towards informatics infrastructure and the need for development and application of sound informatics approaches to the collection, processing, and management of data for clinical studies. By modifying existing local infrastructure and utilizing open source tools, we have been able to successfully deploy a multi-site data coordinating and operations center. We report our implementation decisions for data collection and management for the IDeA States Pediatric Clinical Trial Network (ISPCTN) based on the functionality needed for the ISPCTN, our synthesis of the extant literature in data collection and management methodology, and Good Clinical Data Management Practices., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Multiparametric magnetic resonance imaging (mpMRI) targeted biopsy has emerged as an augmentation to systematic prostate biopsy (SBx) with improved diagnostic accuracy. The purpose of this study was to determine whether biopsy modality impacted management of prostate cancer (PCa)., Methods: We performed a retrospective review of patients with newly diagnosed non-metastatic PCa at our institution (2014-2020). Either ultrasound-guided 12-core SBx or SBx plus ≥1targeted biopsy cores from identifiable lesions on mpMRI were performed. Patients were managed with active surveillance (AS), radiation therapy (RT), or radical prostatectomy (RP). Multivariate logistic and multinomial regression analyses were performed., Results: Of 578 patients, 221(38%) proceeded with AS, 121(21%) received RT, and 236(41%) underwent RP. Median age and prostate-specific antigen (PSA) were 65.4 years and 7.2 ng/mL, respectively. On multivariate analysis, biopsy type did not predict decision to pursue treatment ( p =.951). On multinomial regression analysis, biopsy type did not predict selection of AS over RP ( p =.973) or RT over RP ( p =.813). Alternatively, age, grade group, and PSA were significant predictors of management selection., Conclusions: Biopsy technique did not impact management for patients with new PCa diagnosis. Despite paradigm shifts in obtaining tissue diagnosis, age, PSA, and grade group remain valuable indices for shared decision-making and counseling patients with PCa.

Objective: This study aimed to estimate asthma control at specialist treatment centers in four Latin American countries and assess factors influencing poor asthma control. Methods: Patients aged ≥12 years with an asthma diagnosis and asthma medication prescription, followed at outpatient specialist centers in Argentina, Chile, Colombia, and Mexico, were included. The study received all applicable ethical approvals. The Asthma Control Test (ACT) was used to classify patients as having controlled (ACT 20-25) or uncontrolled (ACT ≤19) asthma. Frequency and statistical tests were used to assess the association between hospital admissions/exacerbations/emergency department (ED) visits and uncontrolled asthma; multivariate logistic regression was used to assess the association of uncontrolled asthma with clinical/demographic variables. Results: A total of 594 patients were included. Overall controlled-asthma prevalence was 43.4% (95% confidence interval [CI]: 39.0, 47.4). Patients with uncontrolled asthma were more likely to be women (adjusted odds ratio [aOR]: 1.85; p  = 0.003), non-white (aOR: 2.14; p  < 0.001), obese (aOR: 1.71; p  = 0.036), to have a low monthly family income (aOR: 1.75; p  = 0.004), to have severe asthma (aOR:1.59; p  = 0.26), and, compared with patients with controlled asthma, to have a higher likelihood of asthma exacerbations (34.5% vs. 15.9%; p  < 0.001), hospital admissions (6.9% vs. 3.1%; p  = 0.042), and ED visits (34.5% vs. 15.9%; p  < 0.001) due to asthma. Conclusions: Even in specialist ambulatory services, fewer than half of patients were classified as having controlled asthma. The proportion of uncontrolled patients varied according to clinical and demographic variables.

Background: We sought to investigate whether robotic pancreatoduodenectomy (RPD) mitigates adverse outcomes in patients with high-risk morphometric features compared to the open approach (OPD)., Methods: Morphometric parameters for RPD and OPDs were measured by two blinded radiologists. The morphometric parameter best correlating with adverse outcomes was identified and used in multivariable models to evaluate the impact of surgical approach (open vs. robotic) on outcomes of patients with high-risk morphometric features., Results: Of 282 PDs available for morphometric analysis, 134 (47.5%) underwent RPD. Average Psoas Density demonstrated the most frequent association with adverse outcomes, with correlations to prolonged LOS (ρ= -0.154, p=0.01), severe complications (ρ= -0.159, p=0.007), readmission (ρ= -0.16, p=0.007), and discharge to home (ρ= 0.2, p<0.001). On multivariable analysis of patients with high-risk morphometric features (defined as APD ≤ 50 th percentile), RPD was associated with a reduction in the likelihood of prolonged LOS (OR 0.27, p = 0.015) and a trend towards discharge home versus a rehab facility or nursing home (OR 2.26, p = 0.061)., Conclusion: This study confirms the association between morphometrics and outcomes following PD, and suggests that the robotic approach may be associated with improved outcomes in PD patients with high-risk morphometric features., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Immune modulating factors are necessary for pathogen clearance, but also contribute to host tissues damage, as those seen in periodontal diseases. Many of these responses can be exacerbated by host conditions including type 2 diabetes [T2D], where toll-like receptor 4 [TLR4] and the receptor for advanced glycated end products [RAGE] play a significant role. Here we investigate causality associated with the increase in inflammatory markers observed in periodontally diseased patients with T2D using multi-variant correlation analysis. Inflammation associated with periodontal diseases, characterized by elevated pro-inflammatory cytokines, innate immune receptor expression, and cellular infiltrate was exacerbated in patients with T2D. In addition, a feed forward loop regulated by poor glycemic control was associated with a loss of mucosal barrier integrity and accumulation of innate immune receptor ligands resulting in an exacerbation of ongoing inflammation, where RAGE and TLR4 cooperated to induce responses in oral epithelial cells, which were exacerbated by hyperglycemia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Matrix metalloproteinases (MMPs) are a family of host-derived proteinases reported to mediate multiple functions associated with periodontal destruction and inflammation. Most of the existing data have been gathered from adults with chronic periodontitis. The purpose of this study was to determine the MMP levels in a cohort of African American children with and without aggressive periodontitis., Methods: Gingival crevicular fluid (GCF) was collected in a cohort of 44 African American children, 7 to 19 years of age, with and without aggressive periodontitis (AgP) and compared to healthy unrelated children and to adults with chronic periodontitis (CP). GCF volume was determined with a calibrated gingival fluid meter. The samples were assayed for MMP-1, -2, -3, -8, -9, -12, and -13 using fluorimetric substrates., Results: The MMP levels from diseased sites in the subjects with AgP were statistically higher (P <0.05) in almost all instances than those associated with the unrelated controls or with the subjects with CP. MMP-8 was significantly elevated in the diseased sites of the children with AgP relative to non-diseased sites in the same children (P = 0.002), as well as the siblings, non-diseased controls, and subjects with CP (P < or =0.0001). There was no positive correlation between probing depth and any MMP level., Conclusions: MMP levels were elevated in AgP sites relative to non-diseased sites in the same subjects, in siblings, and in unrelated controls. MMPs associated with the AgP sites in children were generally elevated compared to an adult cohort with a history of CP.

A mutant Hadnl was induced in Drosophila melanogaster and found to be deficient in beta-hydroxy acid dehydrogenase. This mutation was utilized to study the genetics and physiological expression of Had+ . Had+ was mapped to the X chromosome at 54.4 and seems to be the structural gene for the enzyme. Enzyme activity in male and female flies indicates that the gene shows both dosage compensation independent from dose effect and differential activity during ontogeny. Electrophoretic mobility data indicate that the enzyme is a dimer which forms by random association of subunits. The fact that the mutant shows no detrimental effect implies that the enzyme is dispensable, at least under laboratory conditions. The biological and technical implications of this gene--enzyme system are discussed.

The binding and processing of plasminogen by Balb/c 3T3 and SV3T3 cells was studied using 125I-labeled canine plasinogen. Throughout a 3-day period, 125I-plasminogen in the incubation medium bound to the cells and was degraded, first to intermediate-sized macromolecules that were the same size as the large (74,600-dalton) and small (25,000-dalton) chains of active plasmin, and to smaller fragments including 3-iodo-L-tyrosine. Binding to SV3T3 cells was independent of the protease-dependent morphological change (PDMC) characteristic of these and many other transformed cells. The SV3T3, and to a somewhat lesser extent, the 3T3 cells, both accumulated and released into the incubation medium 3-iodo-L-tyrosine, a terminal lysozymal digestion product. The results of a sublethal cell-surface trypsinization assay suggest that the cell-associated plasminogen was primarily bound to the surfaces of the 3T3 and SV3T3 cells while the macromolecular degradation products including active plasmin were inside the cells. The rate of 125I plasminogen degradation exhibited by SV3T3 cells was approximately two time greater than that of 3T3 cells, which presumably reflects differences in endocytosis or lysosomal hydrolysis, or both. The rates were unaffected by addition of pancreatic or soybean trypsin inhibitor sufficient to inhibit PDMC. In the incubation medium, plasminogen was activated to plasmin by SV3T3, but not by 3T3 cells. However, 95-100% of plasmin covalently bound to a 47,000-dalton canine serum component, which could be dissociated from plasmin by hydroxylamine: 95-100% of the plasmin was inactive to reaction with DF32P. Thus the serum component is a plasmin inhibitor. The plasmin-containing complex in the medium had an apparent molecular weight of 212,000. Under denaturing conditions, the complex dissociated into two covalently modified plasmin-containing species of 153,000 and 127,000 daltons. In addition to forming a complex with a serum component, the plasmin is cleaved into two small fragments (approximately 10,000 and 12,000 daltons) by as-yet uncharacterized serum factors.