CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis.

Fibroblasts are important regulators of inflammation, but whether fibroblasts change phenotype during resolution of inflammation is not clear. Here we use positron emission tomography to detect fibroblast activation protein (FAP) as a means to visualize fibroblast activation in vivo during inflammation in humans. While tracer accumulation is high in active arthritis, it decreases after tumor necrosis factor and interleukin-17A inhibition. Biopsy-based single-cell RNA-sequencing analyses in experimental arthritis show that FAP signal reduction reflects a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalization) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalization). Spatial transcriptomics of human joints indicates that pro-resolving niches of CD200+DKK3+ fibroblasts cluster with type 2 innate lymphoid cells, whereas MMP3+/IL6+ fibroblasts colocalize with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilized the type 2 innate lymphoid cell phenotype and induced resolution of arthritis via CD200-CD200R1 signaling. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.

Older adult participation in cancer clinical trials: A systematic review of barriers and interventions.

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.

The T1150A cancer mutant of the protein lysine dimethyltransferase NSD2 can introduce H3K36 trimethylation.

Protein lysine methyltransferases (PKMTs) play essential roles in gene expression regulation and cancer development. Somatic mutations in PKMTs are frequently observed in cancer cells. In biochemical experiments, we show here that the NSD1 mutations Y1971C, R2017Q, and R2017L observed mostly in solid cancers are catalytically inactive suggesting that NSD1 acts as a tumor suppressor gene in these tumors. In contrast, the frequently observed T1150A in NSD2 and its T2029A counterpart in NSD1, both observed in leukemia, are hyperactive and introduce up to three methyl groups in H3K36 in biochemical and cellular assays, while wildtype NSD2 and NSD1 only introduce up to two methyl groups. In Molecular Dynamics simulations, we determined key mechanistic and structural features controlling the product specificity of this class of enzymes. Simulations with NSD2 revealed that H3K36me3 formation is possible due to an enlarged active site pocket of T1150A and loss of direct contacts of T1150 to critical residues which regulate the product specificity of NSD2. Bioinformatic analyses of published data suggested that the generation of H3K36me3 by NSD2 T1150A could alter gene regulation by antagonizing H3K27me3 finally leading to the upregulation of oncogenes.

Falls prechemotherapy and toxicity-related hospitalization during adjuvant chemotherapy for breast cancer in older women: Results from the prospective multicenter HOPE trial.

BACKGROUND: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer. METHODS: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates. RESULTS: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003). CONCLUSIONS: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.

Outcome prioritization and preferences among older adults with cancer starting chemotherapy in a randomized clinical trial.

INTRODUCTION: Older adults with cancer facing competing treatments must prioritize between various outcomes. This study assessed health outcome prioritization among older adults with cancer starting chemotherapy. METHODS: Secondary analysis of a randomized trial addressing vulnerabilities in older adults with cancer. Patients completed three validated outcome prioritization tools: 1) Health Outcomes Tool: prioritizes outcomes (survival, independence, symptoms) using a visual analog scale; 2) Now vs. Later Tool: rates the importance of quality of life at three times-today versus 1 or 5 years in the future; and 3) Attitude Scale: rates agreement with outcome-related statements. The authors measured the proportion of patients prioritizing various outcomes and evaluated their characteristics. RESULTS: A total of 219 patients (median [range] age 71 [65-88], 68% with metastatic disease) were included. On the Health Outcomes Tool, 60.7% prioritized survival over other outcomes. Having localized disease was associated with choosing survival as top priority. On the Now vs. Later Tool, 50% gave equal importance to current versus future quality of life. On the Attitude Scale, 53.4% disagreed with the statement "the most important thing to me is living as long as I can, no matter what my quality of life is"; and 82.2% agreed with the statement "it is more important to me to maintain my thinking ability than to live as long as possible". CONCLUSION: Although survival was the top priority for most participants, some older individuals with cancer prioritize other outcomes, such as cognition and function. Clinicians should elicit patient-defined priorities and include them in decision-making.

Randomized placebo-controlled, double-blind clinical trial of nanoemulsion curcumin in women with aromatase inhibitor-induced arthropathy: an Alliance/NCORP pilot trial.

PURPOSE: Aromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain. METHODS: We conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22_Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months. The primary objective was to determine the feasibility of using Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) to detect changes from 0 (T0) to 3 months (T3) of NEC treatment in AI-induced symptoms and well-being; secondary objectives included evaluation of changes in Disabilities of the Shoulder, Arm, and Hand (DASH), Brief Pain Inventory-short form (BPI-SF), grip strength, and biomarkers at T0 and T3. RESULTS: Forty-two patients were randomized to NEC or placebo; 34 women completed the 3-month study. Patient-reported outcome measures (PROMs: FACT-ES, DASH, BPI-SF) and biospecimens were collected at T0-T3 in > 80% of participants. Adherence was ≥ 90% for both arms. PROMs and grip strength did not differ significantly by treatment arm. Plasma curcumin was detected only in NEC arm participants. Serum estradiol and estrone levels were below detection or low on study agent. Gastrointestinal adverse effects were commonly reported in both arms. CONCLUSION: NEC versus placebo in a multisite randomized trial is feasible and well-tolerated. Additional studies with larger sample size are needed to further evaluate the efficacy and safety of NEC in treatment of AIIA. CLINICALTRIALS: gov Identifier: NCT03865992, first posted March 7, 2019.

Addition of PEG-interferon to long-term nucleos(t)ide analogue therapy enhances HBsAg decline and clearance in HBeAg-negative chronic hepatitis B: Multicentre Randomized Trial (PAS Study).

We studied whether 48 weeks of PEG-IFN alfa-2a add-on increases HBsAg-decline and clearance in HBeAg-negative patients on long-term nucleo(s)tide analogue (NA) therapy. In this investigator-initiated, randomized, controlled trial conducted in Europe and Canada, HBeAg-negative patients treated with NA > 12 months, with HBVDNA < 200 IU/mL, were enrolled. Patients were randomized 2:1 to 48 weeks of PEG-IFN alfa-2a add-on (180 µg per week) or continued NA-monotherapy with subsequent follow-up to Week 72. Endpoints were HBsAg decline (≥1 log10 IU/mL) and HBsAg clearance at Week 48. Of the 86 patients in the modified-intention-to-treat analysis, 58 patients received PEG-IFN add-on, and 28 continued NA monotherapy. At Week 48, 16(28%) patients achieved HBsAg decline ≥1 log10 in the add-on arm versus none on NA-monotherapy (p < .001), and HBsAg clearance was observed in 6 (10%) PEG-IFN add-on patients versus 0% NA-monotherapy (p = .01). HBVRNA was only detected in 2% after PEG-IFN treatment versus 19% in NA-monotherapy (p = .002) at Week 48. PEG-IFN add-on therapy was well tolerated in majority of patients. Low baseline HBsAg levels (<10 IU/mL) identified patients most likely to achieve HBsAg loss with PEG-IFN add-on, whereas an HBsAg level > 200 IU/mL at on-treatment Week 12 was highly predictive of non-response (NPV = 100%). Addition of PEG-IFN to long-term NA enhanced HBsAg decline and increased the chance of HBsAg clearance in HBeAg-negative patients on long-term NA. On-treatment HBsAg levels >200 IU/mL identify patients unlikely to benefit from PEG-IFN add-on and could be used as a potential stopping-rule for PEG-IFN therapy. Our findings support further exploration of immune modulation add-on to antiviral therapy, preferably using response-guided strategies, to increase functional cure rates in patients with CHB.

Depressive symptoms in adolescence and adult educational and employment outcomes: a structured life course analysis.

BACKGROUND: Depression is a common mental health disorder that often starts during adolescence, with potentially important future consequences including 'Not in Education, Employment or Training' (NEET) status. METHODS: We took a structured life course modeling approach to examine how depressive symptoms during adolescence might be associated with later NEET status, using a high-quality longitudinal data resource. We considered four plausible life course models: (1) an early adolescent sensitive period model where depressive symptoms in early adolescence are more associated with later NEET status relative to exposure at other stages; (2) a mid adolescent sensitive period model where depressive symptoms during the transition from compulsory education to adult life might be more deleterious regarding NEET status; (3) a late adolescent sensitive period model, meaning that depressive symptoms around the time when most adults have completed their education and started their careers are the most strongly associated with NEET status; and (4) an accumulation of risk model which highlights the importance of chronicity of symptoms. RESULTS: Our analysis sample included participants with full information on NEET status (N = 3951), and the results supported the accumulation of risk model, showing that the odds of NEET increase by 1.015 (95% CI 1.012-1.019) for an increase of 1 unit in depression at any age between 11 and 24 years. CONCLUSIONS: Given the adverse implications of NEET status, our results emphasize the importance of supporting mental health during adolescence and early adulthood, as well as considering specific needs of young people with re-occurring depressed mood.

Inferior vena cava filter thromboprophylaxis in surgical cancer patients.

BACKGROUND AND OBJECTIVES: This study evaluated the utilization and outcomes of inferior vena cava (IVC) filters as thromboprophylaxis in cancer patients undergoing surgery. METHODS: This single-center retrospective study analyzed baseline patient characteristics and clinical outcomes of surgical cancer patients who received perioperative prophylactic IVC filters. Primary clinical endpoints included venous thromboembolism (VTE) incidence and filter complications. A statistical correlative analysis was conducted to identify risk factors related to pulmonary embolism (PE), deep vein thrombosis (DVT), and filter thrombi, as well as advanced technique filter removal and mortality at 6 months. RESULTS: A total of 252 surgical oncology patients (median age, 59; female 51%) received IVC filters for the perioperative prevention of PE. Primary surgical sites included spine (n = 91, 36%), orthopedic extremity/joint (n = 49, 19%), genitourinary (n = 47, 19%), brain/cranial (n = 40, 16%), abdominal (n = 18, 7%), multisite (n = 4, 2%), and chest (n = 3, 1%). Moreover, 15% of patients experienced DVTs in the postplacement preretrieval period, while 2% (n = 6) of patients experienced definitive PEs. A total of 36% of IVC filters were ultimately retrieved, with an average filter dwell time of 7.4 months. Complications occurred in one retrieval. CONCLUSION: Prophylactic perioperative IVC filters in surgical cancer patients resulted in minimal complications while ultimately resulting in a low incidence of PE.

Exploring the online landscape of interventional radiology: a global analysis of search trends.

PURPOSE: This study aimed to analyze the online presence of interventional radiology (IR), and its popularity over time and location, given the reported under-awareness of the specialty. MATERIALS AND METHODS: The study analyzed search volumes, searcher demographics, and query type related to IR and its four most searched procedures using Google Trends, Demographics.io, and Also Asked. Search strategies were stratified by volume and region ("Worldwide" and "United States"), and the quality of current patient materials in the first 10 Google search results was analyzed using the DISCERN instrument and Flesch Kincaid levels. RESULTS: The analyzed search trends demonstrated a slow uptrend in search volume over the past 15 years since 2013, with a CAGR rate of 0.6%. Demographics revealed that 80.9% of searchers were female and over half (51.8%) fell into the age range of 35-54 years old. Geographically, the US had the highest search volume (100) for the term "interventional radiology" and website search results mainly related to patient education about the specialty. The quality of online resources was poor with overall college-level readability, and "What is Interventional Radiology?" was the most popular query. CONCLUSIONS: There is a growing interest in IR procedures in recent years, particularly in the US, with middle-aged females being the most active demographic online. However, online resources containing information on specific IR procedures remain of poor quality. Actions should be taken to improve the quality, accessibility, and awareness of IR-related webpages to increase public knowledge of IR care in the US and abroad.

Crohn's Disease Features in Anastomotic Biopsies from Patients With and Without Crohn's Disease: Diagnostic and Prognostic Value.

Endoscopic evidence of disease activity is a critical predictor of clinical relapse in patients with Crohn's disease (CD), and histologic disease activity is evolving as a similarly important end point for patient management. However, classical morphologic features of CD may overlap with postoperative inflammatory changes, confounding the evaluation of anastomotic biopsies. There is a clear unmet need for better characterization of diagnostic and clinically significant histologic features of CD in these surgically altered sites. We evaluated ileocolonic and colocolonic/rectal anastomotic biopsies performed at 3 academic institutions in patients with and without CD. The biopsies were blindly assessed for CD histologic features and correlated to clinical and endoscopic characteristics. In CD patients, the presence of each feature was correlated with the subsequent clinical exacerbation or relapse. We obtained anastomotic biopsies from 208 patients, of which 109 were operated on for CD and 99 for another indication (neoplasia [80%], diverticular disease (11%), and other [9%]). Mean time since surgery was 10 years (0-59; 14 years for CD [1-59], 6 years for non-CD [0-33]). Endoscopic inflammation was noted in 52% of cases (68% for CD and 35% for non-CD). Microscopic inflammation was present in 74% of cases (82% for CD and 67% for non-CD). Only discontinuous lymphoplasmacytosis (P < .001) and pyloric gland metaplasia (P = .04) occurred significantly more often in CD patients. However, none of the histologic features predicted clinical disease progression. In subset analysis, the presence of histologic features of CD in nonanastomotic biopsies obtained concurrently in CD patients was significantly associated with relapse (P = .03). Due to extensive morphologic overlap between CD and postoperative changes and the lack of specific histologic features of relapse, biopsies from anastomotic sites are of no value in predicting clinical CD progression. Instead, CD activity in biopsies obtained away from anastomotic sites should be used for guiding endoscopic sampling and clinical management.

Feasibility of implementing a supervised telehealth exercise intervention in frail survivors of hematopoietic cell transplantation: a pilot randomized trial.

BACKGROUND: Patients undergoing hematopoietic cell transplantation (HCT) are at high risk of chronic health complications, including frailty and physical dysfunction. Conventional exercise programs have been shown to improve frailty in other cancer populations, but these have largely been based out of rehabilitation facilities that may act as geographic and logistical barriers. There is a paucity of information on the feasibility of implementing telehealth exercise interventions in long-term HCT survivors. METHODS: We conducted a pilot randomized trial to assess the feasibility of an 8-week telehealth exercise intervention in 20 pre-frail or frail HCT survivors. Participants were randomized to either a telehealth exercise (N = 10) or delayed control (N = 10). We administered a remote physical function assessment at baseline, followed by an 8-week telehealth exercise intervention (30-60 min/session, 3 sessions/week), and post-intervention. The primary endpoint was feasibility as determined by 1) > 70% of participants completing all remote physical functional assessments, and 2) > 70% of participants in the exercise group completing > 70% (17/24) of the prescribed exercise sessions. Exploratory outcomes included changes in gait speed, handgrip strength, and short physical performance battery. RESULTS: The mean [standard deviation] age at study enrollment was 64.7 [9.1] years old. Twelve had undergone allogenic and 8 had undergone autologous HCT at an average of 17 years from study enrollment. Both feasibility criteria were achieved. Nineteen patients (95%) completed all remote study outcome assessments at baseline and post-intervention, and nine participants in the exercise group completed > 70% of prescribed exercise sessions. Overall, no significant group x time interaction was observed on handgrip strength, fatigue, body mass index, and short physical performance battery test (P < 0.05). However, there were significant within-group improvements in four-meter gait speed (+ 13.9%; P = 0.004) and 5-minute gait speed (+ 25.4%; P = 0.04) in the exercise group whereas non-significant changes in four-meter gait speed (-3.8%) and 5-minute gait speed (-5.8%) were observed after 8 weeks. CONCLUSION: Implementing an 8-week telehealth exercise intervention for long-term HCT survivors was feasible. Our findings set the stage for innovative delivery of supervised exercise intervention that reduces the burden of frailty in HCT survivors as well as other at-risk cancer survivors. TRIAL REGISTRATION: The protocol and informed consent were approved by the institutional IRB (IRB#20731) and registered (ClinicalTrials.gov NCT04968119; date of registration: 20/07/2021).

Predicting All-Cause Mortality in Women With and Without Breast Cancer Using the Schonberg Index: A Women's Health Initiative Study.

BACKGROUND: When treating older women with breast cancer, life expectancy is an important consideration. ASCO recommends calculating 10-year mortality probabilities to inform treatment decisions. One useful tool is the Schonberg index, which predicts risk-based all-cause 10-year mortality. We investigated the use of this index in women aged ≥65 years with breast cancer in the Women's Health Initiative (WHI). METHODS: We calculated 10-year mortality risk scores for 2,549 WHI participants with breast cancer ("cases") and 2,549 age-matched breast cancer-free participants ("controls") using Schonberg index risk scoring. Risk scores were grouped into quintiles for comparisons. Risk-stratified observed mortality rates and 95% confidence intervals were compared across cases and controls. Observed 10-year mortality rates in cases and controls were also compared with Schonberg index-based predicted 10-year mortality rates. RESULTS: Compared with controls, cases were more often white (P=.005), had higher income and education levels (P<.001 for both), more often lived with their husband/partner (P<.001), scored higher on subjective health/happiness (P<.001), and needed less assistance in activities of daily living (P<.001). Participants with breast cancer had similar risk-stratified 10-year mortality rates compared with controls (34% vs 33%, respectively). Stratified results showed that cases had slightly higher mortality rates than controls in the lowest risk quintile and lower mortality rates in the 2 highest risk quintiles. Observed mortality rates in cases and controls were similar to Schonberg index-predicted mortality, with model c-indexes of 0.71 and 0.76, respectively. CONCLUSIONS: Among women aged ≥65 years with incident breast cancer, the Schonberg index-based risk-stratified 10-year mortality rates were similar to those in women without breast cancer, demonstrating a similar performance of the index among both populations. Along with other health measures, prognostic indexes can help predict survival among older women with breast cancer and support geriatric oncology guidelines that promote using life expectancy calculation tools for shared decision-making.

Public Awareness of Interventional Radiology: Population-Based Analysis of the Current State of and Pathways for Improvement.

PURPOSE: To evaluate the awareness of interventional radiology (IR) among the public and identify methods for improvement. MATERIALS AND METHODS: Participants (N = 1,000) were anonymously surveyed using Amazon's Mechanical Turk crowdsourcing platform about medical and IR-specific knowledge, preferred methods of acquisition of medical information, and suggestions for improving awareness of IR. The survey consisted of 69 questions, including both Likert Scale and free text questions. RESULTS: Of the participants, 92% preferred undergoing a minimally invasive procedure over surgery. However, 39.8% recognized IR as a medical specialty, and less than 50% of these participants correctly identified IR as procedurally oriented. Of those who discussed or underwent an IR procedure (n = 113), most were also offered to undergo the procedure performed by a surgeon (n = 66). Furthermore, 71% (n = 20) of those who underwent the procedure performed by a surgeon reported that lack of awareness of IR played a role in their decision. Almost half of the respondents (n = 458) were interested in learning more about IR, particularly the diseases treated and procedures performed (42% and 37%, respectively). Short (<10-minute) educational videos and increased patient education by primary care providers (PCPs) were among the most suggested ways to improve awareness. Regarding the ambiguity of the name "interventional radiology," most respondents (n = 555) reported this to be true, and "minimally invasive radiologist" was the most preferred alternative (21.18%). CONCLUSIONS: Lack of awareness of IR may underlie underutilization. When presented with the knowledge that IR improves patient outcomes, minimally invasive procedures by an interventional radiologist are more often desired by the public than surgical options. Educational videos and patient education by PCPs may increase awareness of IR.

A History and Modern Framework for Quality Improvement in Interventional Radiology.

Quality improvement (QI) initiatives have benefited patients as well as the broader practice of medicine. Large-scale QI has been facilitated by multi-institutional data registries, many of which were formed out of national or international medical society initiatives. With broad participation, QI registries have provided benefits that include but are not limited to establishing treatment guidelines, facilitating research related to uncommon procedures and conditions, and demonstrating the fiscal and clinical value of procedures for both medical providers and health systems. Because of the benefits offered by these databases, Society of Interventional Radiology (SIR) and SIR Foundation have committed to the development of an interventional radiology (IR) clinical data registry known as VIRTEX. A large IR database with participation from a multitude of practice environments has the potential to have a significant positive impact on the specialty through data-driven advances in patient safety and outcomes, clinical research, and reimbursement. This article reviews the current landscape of societal QI programs, presents a vision for a large-scale IR clinical data registry supported by SIR, and discusses the anticipated results that such a framework can produce.

Effects of sub-chronic CRH administration into the hypothalamic paraventricular and central amygdala nuclei in male rats with a focus on food intake biomarkers.

CRH neurons are found in the paraventricular nucleus(PVN) and central amygdala(CeA) nuclei. This study investigated the effects of sub-chronic CRH administration into the PVN and CeA nuclei on food intake biomarkers in rats divided into five groups: control, two shams, and two CRH-PVN and CRH-CeA groups(receiving CRH in nuclei for seven days). The CRH-PVN group had significantly higher cumulative food intake and food intake trends than the CRH-CeA group. The CRH-CeA and CRH-PVN groups exhibited significant increases in food intake during hours 1 and 2, respectively. Moreover, to be time-dependent, food intake is modulated by different brain nuclei. The CRH signaling pathway appeared to be activated later in the PVN than CeA. Both groups exhibited significantly higher leptin levels, the CRH-PVN group exhibited higher ghrelin levels and lower glucose levels. Repetitive administration of CRH into the PVN and CeA significantly reduced body weight differences. CRH administration into the PVN affected both leptin and ghrelin levels, but ghrelin had a greater impact on glucose variations and cumulative food intake than leptin. Finally, CRH administration into the PVN and CeA likely activated the HPA axis, and the CeA had a greater impact on the stress circuit than on food intake behavior.

Detecting and Characterizing Inferior Vena Cava Filters on Abdominal Computed Tomography with Data-Driven Computational Frameworks.

Two data-driven algorithms were developed for detecting and characterizing Inferior Vena Cava (IVC) filters on abdominal computed tomography to assist healthcare providers with the appropriate management of these devices to decrease complications: one based on 2-dimensional data and transfer learning (2D + TL) and an augmented version of the same algorithm which accounts for the 3-dimensional information leveraging recurrent convolutional neural networks (3D + RCNN). The study contains 2048 abdominal computed tomography studies obtained from 439 patients who underwent IVC filter placement during the 10-year period from January 1st, 2009, to January 1st, 2019. Among these, 399 patients had retrievable filters, and 40 had non-retrievable filter types. The reference annotations for the filter location were obtained through a custom-developed interface. The ground truth annotations for the filter types were determined based on the electronic medical record and physician review of imaging. The initial stage of the framework returns a list of locations containing metallic objects based on the density of the structure. The second stage processes the candidate locations and determines which one contains an IVC filter. The final stage of the pipeline classifies the filter types as retrievable vs. non-retrievable. The computational models are trained using Tensorflow Keras API on an Nvidia Quadro GV100 system. We utilized a fine-tuning supervised training strategy to conduct our experiments. We find that the system achieves high sensitivity on detecting the filter locations with a high confidence value. The 2D + TL model achieved a sensitivity of 0.911 and a precision of 0.804, and the 3D + RCNN model achieved a sensitivity of 0.923 and a precision of 0.853 for filter detection. The system confidence for the IVC location predictions is high: 0.993 for 2D + TL and 0.996 for 3D + RCNN. The filter type prediction component of the system achieved 0.945 sensitivity, 0.882 specificity, and 0.97 AUC score with 2D + TL and 0. 940 sensitivity, 0.927 specificity, and 0.975 AUC score with 3D + RCNN. With the intent to create tools to improve patient outcomes, this study describes the initial phase of a computational framework to support healthcare providers in detecting patients with retained IVC filters, so an individualized decision can be made to remove these devices when appropriate, to decrease complications. To our knowledge, this is the first study that curates abdominal computed tomography (CT) scans and presents an algorithm for automated detection and characterization of IVC filters.

Representation and Outcomes of Older Adults in Practice-Changing Oncology Trials in the Era of Novel Therapies: A Guideline Appraisal.

BACKGROUND: Older adults account for 70% of cancer-related deaths, but previous studies have shown that they are underrepresented in cancer clinical trials. We sought to analyze the representation and outcomes of older adults in trials conducted in the era of novel targeted therapy and immunotherapy. METHODS: We searched the 2020 NCCN Clinical Practice Guidelines in Oncology and retrieved trials from the past 10 years leading to category 1 recommendations in the first-line metastatic setting for the 5 most common causes of cancer death. We categorized trials by cancer type, single-agent versus multiagent approach, and therapeutic class. We described the percentage of older adults (according to each trial's definition) and used a Mantel-Haenszel random-effects meta-analysis model to compare overall and progression-free survival by age. RESULTS: We identified 30 trials consisting of 24,416 patients. Across all trials, 44% of enrolled patients were older adults. Representation of older adults by cancer type within trials was 49% prostate cancer, 38% pancreatic cancer, 37% breast cancer, and 34% non-small cell lung cancer. Representation of older adults also varied by therapeutic class: 20% received immunotherapy, 44% received cytotoxic chemotherapy, 54% received targeted/hormonal therapy, and 34% received combination therapy (P<.001 for all comparisons). For each year since 2010, the percentage of older adults enrolled in trials increased by 1.9%, although this difference was not significant. We observed no difference in overall or progression-free survival between older and younger adults. In our analysis of practice-changing clinical trials, we found that 44% of clinical trial participants were older adults. Trials that included immunotherapy or a combination of therapeutic classes had a lower representation of older adults (<40%). CONCLUSIONS: We found that >40% of patients in practice-changing trials are older adults. Although they remain underrepresented in clinical trials compared with the general population, older adults in practice-changing trials seem to be better represented than in previously reported analyses of cooperative group trials.

Potential Bias in Image-Guided Procedure Research: A Retrospective Analysis of Disclosed Conflicts of Interest and Open Payment Records.

PURPOSE: To assess the prevalence of positive conflicts of interest (COI) disclosures in United States-based interventional radiology (IR) research as well as the level of agreement between disclosed financial relationships and Open Payment Data for top-cited image-guided procedure research. MATERIALS AND METHODS: All publications in volume 30 (2019) of the Journal of Vascular and Interventional Radiology (JVIR) were reviewed to estimate the prevalence of COI disclosures in IR research. Publications were categorized as primary research, systematic review, or other. The prevalence was subsequently compared across JVIR publication subtypes and categories and on the basis of whether they were device-focused publications using χ2 tests. Additionally, the Web of Science database was searched for the top 10 most cited studies of 10 common image-guided procedures with available U.S. physician payment data. The payments were categorized as historical (>1 year prior to publication) or active (<1 year prior to publication) and compared with the disclosed financial COIs using 1-way analysis of variance. RESULTS: Positive COI disclosures were present in 114 (29%) of the 397 publications in JVIR volume 30. Positive COI disclosures were most prevalent in standards of practice (50%, P = .01) and more prevalent in device-focused publications (54% vs 23%, P < .01). Among the 396 authors of 100 United States-based top-cited image-guided procedure publications, 383 (97%) failed to disclose at least 1 active financial relationship, with an average of $57,937 in undisclosed payments per publication. CONCLUSIONS: COI are prevalent in IR, similar to other areas of healthcare research, and COI in top-cited image-guided procedure research are often underreported.

Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B.

BACKGROUND: Hepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA), which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients. METHODS: HBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA <2000 IU/mL and ALT normalization at week 72. Kinetics of HBV-RNA were compared with HBV-DNA, HBsAg, and HBcrAg. RESULTS: Mean HBV-RNA at baseline was 4.4 (standard deviation [SD] 1.2) log10 c/mL. At week 12, HBV-RNA declined by -1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to nonresponders early at week 12 (-2.0 [1.2] vs -1.5 [1.1] log10 c/mL, P = .04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P = .01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (.82 and .80, P < .001) and a weak correlation with HBsAg (.25). At week 12, HBV-RNA was significantly lower among patients with lower HBsAg (<100 IU/mL) or HBsAg loss at week 144. CONCLUSIONS: During PEG-IFN treatment for HBeAg-negative CHB, HBV-RNA showed a fast and significant decline that correlates with treatment response and HBsAg loss at long-term follow-up. CLINICAL TRIALS REGISTRATION: NCT00114361.