Search

Background Chemotoxicity risk scores were developed to predict grade 3-5 chemotherapy toxicity in older women with early breast cancer. However, whether these toxicity risk scores are associated with clinically meaningful decline in patient health remains unknown. Methods In a prospective study of women aged 65 years and older with stage I-III breast cancer treated with chemotherapy, we assessed chemotoxicity risk using the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score (categorized as low, intermediate, and high). We measured patient health status before (T1) and after (T2) chemotherapy using a clinical frailty index (Deficit Accumulation Index, categorized as robust, prefrail, and frail). The population of interest was robust women at T1. The primary outcome was decline in health status after chemotherapy, defined as a decline in Deficit Accumulation Index from robust at T1 to prefrail or frail at T2. Multivariable logistic regression was used to examine the association between T1 CARG-BC score and decline in health status, adjusted for sociodemographic and clinical characteristics. Results Of the 348 robust women at T1, 83 (24%) experienced declining health status after chemotherapy, of whom 63% had intermediate or high CARG-BC scores. After adjusting for sociodemographic and clinical characteristics, women with intermediate (odds ratio = 3.14, 95% confidence interval = 1.60 to 6.14, P Conclusions In this cohort of older women with early breast cancer, higher CARG-BC scores before chemotherapy were associated with decline in health status after chemotherapy independent of sociodemographic and clinical risk factors.

Although adults aged 65 years or older make up a strong majority of cancer patients, their underrepresentation in cancer clinical trials leads to the lack of representative data to guide evidence-based therapeutic decisions in this patient population. The Trial Design Working Group, convened as part of the workshop titled, Engaging Older Adults in the National Cancer Institute Clinical Trials Network: Challenges and Opportunities, recommended study designs and design elements that could improve accrual of older adults in National Cancer Institute–funded clinical trials. These include trials that are specifically designed to enroll older adults, trials that include a cohort of older patients (parallel cohort, stratified cohort, or embedded cohort), and trials with pragmatic design elements to facilitate enrollment of older adults. This manuscript provides brief descriptions of the recommended designs, examples of successful trials, and considerations for implementation of these designs. As with any clinical trial, the scientific questions and trial objectives should drive the study design, the selection of endpoints and intervention, and eligibility criteria. When designing trials that include older adults, the heterogeneity of fitness levels is an important consideration as fitness can influence accrual rates and outcomes. Appropriately incorporating geriatric assessments can help identify the optimal subset of older patients for inclusion and minimize selection bias. Incorporating pragmatic design elements to reduce the burden on trial participants as well as on accruing sites and retaining essential elements to ensure that the main goal of the trial can be accomplished can enhance enrollment without compromising the integrity of trials.

A 39-year-old previously healthy man presented with insidiously progressive paresthesia in his lower extremities and worsening of gait and balance. MRI demonstrated T2-hyperintense signal abnormalities involving the thalami, midbrain, dentate nuclei, and adjacent deep cerebellar white matter, which are characteristic of cerebrotendinous xanthomatosis (CTX) (figure). Magnetic resonance spectroscopy revealed typical lipid peaks at 0.9 and 1.3 ppm,1 and serology analysis indicated sterol 27-hydroxylase deficiency,2 confirming the diagnosis. CTX is a rare lipid storage disease with unique clinical and imaging findings, and effective treatment with positive outcomes if initiated early, raising the importance of awareness and early recognition of this disease.2

Indian language instruction and study must be fully included into K-12 and post-secondary curricula. There has to be a continual supply of high-quality learning and print materials in these languages, such as textbooks, workbooks, movies, plays, poetry, novels, magazines, etc., for them to stay relevant and dynamic. The strategy also suggests that languages should have regular, official revisions to their dictionaries and glossaries, which would be communicated to a large audience, to ensure that the latest topics and ideas may be addressed fluently in these languages. The Union Cabinet has adopted the National Education Policy (NEP) 2020, with a focus on establishing an Indian Institute of Translation and Interpretation and obligatorily emphasising Sanskrit and other Indian languages. According to NPE 2020, the Indian and regional languages must get adequate attention, and Sanskrit will be incorporated into the curriculum.

The H3.3 G34W mutation has been observed in 90% of the patients affected by giant cell tumor of bone (GCTB). It had been shown to reduce the activity of the SETD2 H3K36 protein lysine methyltransferase (PKMT) and lead to genome wide changes in epigenome modifications including a global reduction in DNA methylation. Here, we investigated the effect of the H3.3 G34W mutation on the activity of the H3K36me2 methyltransferase NSD1, because NSD1 is known to play an important role in the differentiation of chondrocytes and osteoblasts. Unexpectedly, we observed that H3.3 G34W has a gain-of-function effect and it stimulates K36 methylation by NSD1 by about 2.3-fold with peptide substrates and 6.3-fold with recombinant nucleosomal substrates. This effect is specific for NSD1, as NSD2 shows only a mild stimulation on G34W substrates. The potential downstream effects of the G34W induced hyperactivity of NSD1 on DNA methylation, H3K27me3, histone acetylation and splicing are discussed.

Cellular senescence and DNA methylation are primary aging mechanisms emerging as a potential means of monitoring human aging and evaluating interventions thought to either accelerate or slow an individual’s aging trajectory. However, it is largely unknown whether cellular senescence and signatures of methylation of the specific CpG islands that comprise various epigenetic clocks correlate in humans. We have measured the cellular senescence biomarker, p16 and the five most used epigenetic aging clocks in 251 patients with breast cancer, 49 age-matched non-cancer controls, and 48 patients undergoing cytotoxic chemotherapy treatment. Chemotherapy, a known clinically-relevant inducer of aging, increased expression of p16 but not levels of the most common epigenetic clocks (DNAm-Horvath, PhenoAge, GrimAge, mPoA), with the exception of DNAm-Hannum. Chemotherapy-induced changes in p16 were associated with increased levels of a subset of SASPs, PARC, TNFRII, ICAM1, and TNFa. Cross-sectionally, there was weak to no correlation between p16 expression and epigenetic clocks in cancer patients or non-cancer controls. GrimAge and PhenoAge were the most correlated with p16 (r

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 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).

Background The expansion of hematopoietic stem cells carrying recurrent somatic mutations, termed clonal hematopoiesis (CH), is common in elderly individuals and is associated with increased risk of myeloid malignancy and all-cause mortality. Though chemotherapy is a known risk factor for developing CH, how myelosuppressive therapies affect the short-term dynamics of CH remains incompletely understood. Most studies have been limited by retrospective design, heterogeneous patient populations, varied techniques to identifying CH, and analysis of single timepoints. Methods We examined serial samples from 40 older women with triple-negative or hormone receptor–positive breast cancer treated on the prospective ADjuVANt Chemotherapy in the Elderly trial to evaluate the prevalence and dynamics of CH at baseline and throughout chemotherapy (6 and 12 weeks). Results CH was detected in 44% of patients at baseline and in 53% at any timepoint. Baseline patient characteristics were not associated with CH. Over the course of treatment, mutations exhibited a variety of dynamics, including emergence, expansion, contraction, and disappearance. All mutations in TP53 (n = 3) and PPM1D (n = 4), genes that regulate the DNA damage response, either became detectable or expanded over the course of treatment. Neutropenia was more common in patients with CH, particularly when the mutations became detectable during treatment, and CH was significantly associated with cyclophosphamide dose reductions and holds (P = .02). Conclusions Our study shows that CH is common, dynamic, and of potential clinical significance in this population. Our results should stimulate larger efforts to understand the biological and clinical importance of CH in solid tumor malignancies. Trial Registration ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03858322). Clinical trial registration number: NCT03858322.

Purpose The purpose of this prospective longitudinal study was to evaluate the changes in brain surface gyrification in older long-term breast cancer survivors 5 to 15 years after chemotherapy treatment. Methods Older breast cancer survivors aged ≥ 65 years treated with chemotherapy (C+) or without chemotherapy (C-) 5–15 years prior and age & sex-matched healthy controls (HC) were recruited (time point 1 (TP1)) and followed up for 2 years (time point 2 (TP2)). Study assessments for both time points included neuropsychological (NP) testing with the NIH Toolbox cognition battery and cortical gyrification analysis based on brain MRI. Results The study cohort with data for both TP1 and TP2 consisted of the following: 10 participants for the C + group, 12 participants for the C- group, and 13 participants for the HC group. The C + group had increased gyrification in 6 local gyrus regions including the right fusiform, paracentral, precuneus, superior, middle temporal gyri and left pars opercularis gyrus, and it had decreased gyrification in 2 local gyrus regions from TP1 to TP2 (p p R = -0.76, p = 0.01). Conclusions Altered gyrification could be the neural correlate of cognitive changes in older chemotherapy-treated long-term breast cancer survivors.

PURPOSE To assess the prevalence of positive conflict of interest (COI) disclosures in U.S.-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. Prevalence was then compared across JVIR publication subtype, categories, and whether they were device-focused with chi-squared tests. Additionally, the Web of Science database was searched for the top 10 cited studies of 10 common image-guided procedures with available U.S. physician payment data. Payments were categorized as historical (>1 year prior to publication) or active (

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 (PConclusions: 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.

PURPOSE This study determined whether an electronic version of the geriatric assessment is feasible in a multi-institutional, diverse setting. METHODs Ten sites within the Alliance for Clinical Trials in Oncology participated. Patients who had active cancer or a history of cancer and were 65 years of age or older were eligible. The geriatric assessment was completed with an electronic data capture system that had been loaded onto iPads. Feasibility was defined a priori as completion in at least 70% of patients either with or without help. To enhance racial diversity, the original sample size was later changed and augmented by 50% with the intention of increasing enrollment of older minority patients. RESULTS A total of one hundred fifty-four patients were registered with a median age of 72 years (range, 65-91 years). Forty-three (28%) identified themselves as African American or Black. One hundred forty-one patients (92%) completed the electronic geriatric assessment. Feasibility was observed across all subgroups, regardless of race, education, performance status, comorbidities, and cognition; 124 patients (81%) completed the geriatric assessment without help. Reasons for not completing the geriatric assessment are as follows: clinic visit did not occur (n = 6), no iPad connection to the Internet (n = 3), patient declined (n = 2), prolonged hospitalization (n = 1), and patient died (n = 1). Reasons for needing help, as reported by study personnel, were as follows: the patient preferred that research personnel ask the questions (n = 9), vision problem (n = 3), lack of comfort with the iPad (n = 2), questions were not clear (n = 1), less proficient in English (n = 1), and challenge in pressing the green button to go to the next question (n = 1). CONCLUSION The electronic geriatric assessment is feasible in a multi-institutional setting that includes a notable proportion of African American or Black patients.

Summary Many reservoirs exhibit multilayer behavior. Multilayer oil/gas reservoirs are usually classified as (1) systems with formation crossflow and (2) systems without formation crossflow (commingled systems). The focus in this work is the analysis of pressure transient data of commingled layers. Pressure transient analysis for multilayer reservoirs to estimate individual layer properties is usually difficult and suffers from many limiting assumptions. The available interpretation methods are usually based on a subjectively presumed model (usually homogenous and isotropic layers, and radial infinite reservoirs) that has many unknown parameters (e.g., permeabilities and skin factors) to be estimated through a history matching process. The individual layer properties obtained from such analysis methods may not be reliable. The reliable way to evaluate individual layers’ characteristics is to isolate and test each layer separately, which is challenging due to high costs and occasional operational constraints. In this work, we suggest a testing procedure and an analysis approach to analyze well test data of commingled reservoirs that allows reliable characterization of individual layers. The approach benefits from modern deconvolution techniques to eliminate the rate variation (rate transients) effects from the bottom-hole pressure signal acquired during the test. The methodology presented does not make assumptions about the individual layer reservoir models and recovers distinct pressure signals of the individual layers. The recovered pressure signals of each layer are also free of wellbore storage (WBS) effects. In addition, the individual layers’ pressure signals are stretched over the whole test duration (both drawdown and buildup periods). Successful application of deconvolution requires complete sandface rate data of the individual layers in the commingled system. However, the continuous measurement of individual layers sandface rates is usually not available. A simple model is introduced in this work to make good estimations of the layer rate profile using few measurements of the production logging tool (PLT). The developed rate profiles are then used in deconvolution and individual layer's pressure signal can be recovered for further analysis. The approach was verified against simulated cases with variety of layer models. The results obtained from the developed approach are in good agreement with the true solution. The findings of this study can be used to characterize commingled reservoir systems and determine the individual layers properties. It has applications in optimizing injection/production well performance of commingled systems.

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent. For patients with unresectable disease, evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques. Goals of locoregional therapies in HCC may include curative intent in early-stage disease, bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease, and local disease control and palliation in advanced-stage disease. This review explores the outcomes of chemoembolization, bland embolization, radioembolization, and percutaneous ablative therapies. Attention is also given to prognostic factors related to each of the respective techniques, as well as future directions of locoregional therapies for HCC.

Evidence has begun to emerge indicating that cancer survivors experience accelerated aging. This study examines this phenomenon by evaluating trajectories of functional decline in older adults with a history of a cancer diagnosis relative to those without a history of cancer.Community dwelling healthy volunteers in the Baltimore Longitudinal Study of Aging were evaluated in the Clinical Research Unit of the National Institute on Aging Intramural Research Program. Between 2006 and 2019, 1728 men and women (aged 22-100) underwent clinical evaluation of functional status; 359 reported having a history of cancer. Longitudinal associations between self-reported cancer history and measures of functional decline were examined using generalized estimating equations. Additionally, time-to-event and Cox proportional hazards models were used to examine trajectories of decline. Where appropriate, age-stratified associations were examined, and models were adjusted for sex, body mass index, race, smoking status, education, and number of comorbid conditions.Among all participants, a history of cancer was associated with 1.42 (95% CI 1.11-1.81) greater odds of weak grip strength. Among older participants (65 years of age), those with a history of cancer had 1.61 (95% CI 1.28, 2.02) greater odds of slow gait speed and a 0.11 unit (95% CI 0.19-0.03) lower physical performance score than those with no cancer history. Time-to-event analysis showed that older individuals with a history of cancer experienced steeper decline in grip strength and gait speed than older adults with no history of cancer (p 0.01).Cancer survivors, especially older individuals, demonstrate greater odds of and accelerated functional decline, suggesting that cancer and/or its treatment may alter aging trajectories. Observational and intervention studies are needed for prevention, mitigation, and/or reversal of aging-related effects of cancer and its treatment.

Purpose To evaluate national trends in tube-related genitourinary interventions, with specific attention to primary operator specialty. Methods Using a 5% national sample of Medicare claims data from 2005 to 2015, all claims associated with nephrostomy tube, nephro-ureteral tube, and ureteral stent placement and exchange were identified. The annual volume of the nine billable procedures were analyzed to evaluate trends in the number of procedures performed and primary operator specialty over time. The Charleston Comorbidity Index (CCI) was used to evaluate patient comorbidities and to determine differences in patient populations treated by interventional radiologists and urologists. Results The total volume of tube-related genitourinary interventions has increased over the course of the study period, representing 455.0 services per 100,000 Medicare Fee-for-Service beneficiaries in 2005 to 607.2 services in 2015, an increase of 33.4%. Interventional radiologists performed the majority of all procedures in all procedure types and for each year (>90%) with the exception of nephro-ureteral catheter placement or ureteral stent placement, for which urologists performed the overwhelming majority of procedures each year (>85%). Interventional radiologists performed 63% of their total number of procedures on patients with a CCI = 3 or higher, and urologists performed 42% of their total number of procedures on patients with a CCI = 3 or higher (P Conclusion Tube-related genitourinary interventions have demonstrated persistent growth over the 2005 to 2015 decade. Interventional radiologists are the dominant providers for the majority of these interventions compared with urologists while delivering care to a patient population with a higher number of comorbidities.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Protein lysine methyltransferases have important regulatory functions in cells, but mechanisms determining their activity and specificity are incompletely understood. Naturally, SETD2 introduces H3K36me3, but previously an artificial super-substrate (ssK36) was identified, which is methylated >100-fold faster. The ssK36-SETD2 complex structure cannot fully explain this effect. We applied molecular dynamics (MD) simulations and biochemical experiments to unravel the mechanistic basis of the increased methylation of ssK36, considering peptide conformations in solution, association of peptide and enzyme, and formation of transition-state (TS) like conformations of the enzyme-peptide complex. We observed in MD and FRET experiments that ssK36 adopts a hairpin conformation in solution with V35 and K36 placed in the loop. The hairpin conformation has easier access into the active site of SETD2 and it unfolds during the association process. Peptide methylation experiments revealed that introducing a stable hairpin conformation in the H3K36 peptide increased its methylation by SETD2. In MD simulations of enzyme-peptide complexes, the ssK36 peptide approached TS-like structures more frequently than H3K36 and distinct, substrate-specific TS-like structures were observed. Hairpin association, hairpin unfolding during association, and substrate-specific catalytically competent conformations may also be relevant for other PKMTs and hairpins could represent a promising starting point for SETD2 inhibitor development.

This cross-sectional study assesses differences in clinical trial participation among older vs younger adults with cancer.

Transdermal measurement of glomerular filtration rate (GFR) has been used to evaluate kidney function in conscious animals. This technique is well established in rodents to study acute kidney injury and chronic kidney disease. However, GFR measurement using the transdermal system has not been validated in pigs, a species with a similar renal system to humans. Hence, we investigated the effect of sepsis on transdermal GFR in anesthetized and mechanically ventilated neonatal pigs. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). The transdermal GFR measurement system consisting of a miniaturized fluorescence sensor was attached to the pig's shaved skin to determine the clearance of fluorescein-isothiocyanate (FITC) conjugated sinistrin, an intravenously injected GFR tracer. Our results show that at 12 h post-CLP, serum creatinine increased with a decrease in GFR. This study demonstrates, for the first time, the utility of the transdermal GFR approach in determining renal function in mechanically ventilated, neonatal pigs.

PURPOSE Older breast cancer survivors are at increased risk of clinical decline after adjuvant chemotherapy. This study aimed to evaluate whether inflammatory markers assessed before adjuvant chemotherapy are associated with chemotherapy-induced clinical decline in a population of fit older adults with breast cancer. METHODS In a prospective study of women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy, we measured interleukin-6 (IL-6) and C-reactive protein (CRP) prechemotherapy (T1). We assessed frailty status, using a Deficit Accumulation Index (DAI; categorized as robust, prefrail, and frail), at T1 and postchemotherapy (T2). The population of interest was robust women at T1. The primary outcome was chemotherapy-induced decline in frailty status, defined as decline in DAI from robust (T1) to prefrail or frail (T2). Multivariable logistic regression was used to examine the association between inflammatory markers and the primary outcome, adjusted for sociodemographic and clinical characteristics. RESULTS Of the 295 robust women at T1, 76 (26%) experienced chemotherapy-induced decline in frailty status, among whom 66% had high IL-6, 63% had high CRP, and 46% had high IL-6 and CRP at T1. After adjusting for sociodemographic and clinical characteristics, women with high IL-6 and CRP had a > three-fold (odds ratio, 3.52; 95% CI, 1.55 to 8.01; P = .003) odds of chemotherapy-induced decline in frailty status compared with women with low IL-6 and CRP. CONCLUSION In this cohort of older women with early breast cancer who were clinically fit before chemotherapy initiation, high IL-6 and CRP prechemotherapy were associated with chemotherapy-induced decline in frailty status independent of sociodemographic and clinical risk factors. Further research is needed to examine whether inflammatory markers can inform more personalized approaches to treating older breast cancer survivors.

As the field of interventional radiology assumes a larger role in patient care, the specialty has a growing responsibility to recognize and understand ethical dilemmas within the field. We present a case-based primer on common ethical issues in IR, including requests for potentially inappropriate procedures, surrogate decision making, informed consent, and managing conflicts of interest and procedural complications. This primer is intended to be used as a guide for discussion-based training in ethics in IR while inspiring further research in applied ethics in IR.

The role of radiology and the radiologist have evolved throughout the coronavirus disease-2019 (COVID-19) pandemic. Early on, chest computed tomography was used for screening and diagnosis of COVID-19; however, it is now indicated for high-risk patients, those with severe disease, or in areas where polymerase chain reaction testing is sparsely available. Chest radiography is now utilized mainly for monitoring disease progression in hospitalized patients showing signs of worsening clinical status. Additionally, many challenges at the operational level have been overcome within the field of radiology throughout the COVID-19 pandemic. The use of teleradiology and virtual care clinics greatly enhanced our ability to socially distance and both are likely to remain important mediums for diagnostic imaging delivery and patient care. Opportunities to better utilize of imaging for detection of extrapulmonary manifestations and complications of COVID-19 disease will continue to arise as a more detailed understanding of the pathophysiology of the virus continues to be uncovered and identification of predisposing risk factors for complication development continue to be better understood. Furthermore, unidentified advancements in areas such as standardized imaging reporting, point-of-care ultrasound, and artificial intelligence offer exciting discovery pathways that will inevitably lead to improved care for patients with COVID-19.

Eliminating wellbore storage (WBS) effects inherent in pressure transient data is one of the challenges in well test analysis. The available WBS-removal techniques are either direct or time-consuming approaches. The direct methods are mostly unstable and require accurate data with almost no noise. However, well test data often have noise in both rate and pressure measurements. This work discusses the development of a stable technique to overcome the shortcomings in the available WBS-removal methods. The technique presented here takes advantage of the recently developed stable deconvolution algorithms (e.g. von Schroeter algorithm) to achieve a stable WBS-removal process. The developed approach provides longer WBS-free reservoir response signal (extended over the entire test duration) than the previous methods. In addition, the approach introduced here can remove WBS-effects in noisy data and does not require sandface rate measurements. Different simulated and field examples were used to validate the proposed approach. The examples included data with different levels of rate and pressure measurement errors and covered wide variety of well/reservoir models. The available approaches were implemented to the same examples. A comparison of the results shows the superiority of the approach presented in this paper.

OBJECTIVE. The purpose of this study was to report national utilization trends and outcomes after percutaneous cholecystostomy, cholecystectomy, or no intervention among patients admitted to hospitals with acute cholecystitis. MATERIALS AND METHODS. The Nationwide Inpatient Sample was queried from 2005 to 2014. Admissions were identified and stratified into treatment groups of percutaneous cholecystostomy, cholecystectomy, and no intervention on the basis of International Classification of Diseases, 9th revision, codes. Outcomes, including length of stay, inpatient mortality, and complications including hemorrhage and bile peritonitis, were identified. Multivariate analysis was performed to identify mortality risk by treatment type after adjustment for baseline comorbidities and risk of mortality. RESULTS. Among 2,550,013 patients (58.6% women, 41.4% men; mean age, 55.9 years) admitted for acute cholecystitis over the study duration, 73,841 (2.9%) patients underwent percutaneous cholecystostomy, 2,005,728 (78.7%) underwent cholecystectomy, and 459,585 (18.0%) did not undergo either procedure. Use of percutaneous cholecystostomy increased from 2985 procedures in 2005 to 12,650 in 2014. The percutaneous cholecystostomy cohort had a higher mean age (70.6 years) than the other two groups (cholecystectomy, 53.8 years; no intervention, 62.5 years), a higher mean comorbidity index (cholecystostomy, 3.74; cholecystectomy, 1.77; no intervention, 2.65), and a higher mean risk of mortality index (cholecystostomy, 2.88; cholecystectomy, 1.45; no intervention, 2.07) (p < .05). Unadjusted inpatient all-cause mortality was 10.1% in the percutaneous cholecystostomy, 0.8% in the cholecystectomy, and 5.2% in the no intervention cohorts. After adjustment for baseline mortality risk, percutaneous cholecystostomy (odds ratio, 0.78; 95% CI, 0.76-0.81) and cholecystectomy (odds ratio, 0.42; 95% CI, 0.41-0.43) were associated with reduced mortality compared with no intervention. CONCLUSION. Use of percutaneous cholecystostomy is increasing among patients admitted with acute cholecystitis. After adjustment for baseline comorbidities, percutaneous cholecystostomy is associated with improved odds of survival compared with no intervention.

Chemotherapy may impair cognition and contribute to accelerated aging. The purpose of this study was to assess the effects of chemotherapy on the connectivity of the default mode network (DMN) in older women with breast cancer. This prospective longitudinal study enrolled women aged ≥ 60 years with stage I–III breast cancer (CTx group) and matched healthy controls (HC group). Study assessments, consisting of resting-state functional MRI (rs-fMRI) and the Picture Sequence Memory (psm) test for episodic memory from the NIH Toolbox for Cognition, were obtained at baseline and within one month after the completion of chemotherapy for the CTx group and at matched intervals for the HC group. Two-sample t-test and FDR multiple comparison were used for statistical inference. Our analysis of the CTx group (N = 19; 60–82 years of age, mean = 66.6, SD = 5.24) compared to the HC group (N = 14; 60–78 years of age, mean = 68.1, SD = 5.69) revealed weaker DMN subnetwork connectivity in the anterior brain but stronger connectivity in the posterior brain at baseline. After chemotherapy, this pattern was reversed, with stronger anterior connectivity and weaker posterior connectivity. In addition, the meta-level functional network connectivity (FNC) among the DMN subnetworks after chemotherapy was consistently weaker than the baseline FNC as seen in the couplings between anterior cingulate cortex (ACC) and retrosplenial (rSplenia) region, with ΔFNC(‘ACC’,’rSplenia’)=-0.14, t value=-2.44, 95 %CI=[-0.27,-0.10], pFDR

Purpose Twitter is an increasingly popular social media platform within the health care community. The objective of this analysis is to characterize the profile of radiation oncology–related tweets and Twitter users over the past 6 years. Methods and Materials Using the web-based social media analytics platform Symplur Signals, we filtered tweets containing at least 1 of the following hashtags or key words: #radonc, #radiationoncology, "rad onc," or "radiation oncology." We evaluated radiation oncology–related Twitter activity between October 2014 and March 2020 for tweet frequency, tweet content, and individuals or groups posting tweets. We identified the most influential Twitter users contributing to radiation oncology–related tweets. Results From 2014 to 2020, the quarterly volume of radiation oncology–related tweets increased from 5027 to 29,763. Physicians contributed the largest growth in tweet volume. Academic radiation oncologists comprise 60% of the most influential Twitter accounts responsible for radiation oncology–related content. The number of radiation-oncology resident physicians on Twitter increased from 25 to 328 over the past 6 years, and 20% of radiation-oncology residency programs have a Twitter account. Seventy-one percent of radiation oncology–related tweets generated direct communication via mentions, and 59% of tweets contain links to external sources, including scientific articles. Conclusions The number of physicians contributing radiation oncology–related Twitter content has increased significantly in recent years. Academic radiation oncologists are the primary influencers of radiation oncology–related Twitter activity. Twitter is used by radiation oncologists to both professionally network and discuss findings related to the field. There remains the opportunity for radiation oncologists to broaden their audience on Twitter to encompass a more diverse community, including patients.

The purpose of this study was to assess the effect of chemotherapy on brain functional resting-state signal variability and cognitive function in older long-term survivors of breast cancer. This prospective longitudinal study enrolled women age ≥ 65 years of age who were breast cancer survivors after exposure to chemotherapy (CH), age-matched survivors not exposed to chemotherapy, and healthy controls. Participants completed resting-state functional brain MRI and neurocognitive testing upon enrollment (timepoint 1, TP1) and again two years later (timepoint 2, TP2). There were 20 participants in each of the three groups at TP1. The CH group showed a significant decrease in SDBOLD (blood-oxygen-level-dependent signal variability in standard deviation) in the right middle occipital gyrus (ΔSDBOLD = −0.0018, p = 0.0085, q (pFDR) = 0.043 at MNI (42, −76, 17)) and right middle temporal gyrus (ΔSDBOLD = −0.0021, p = 0.0006, q (pFDR) = 0.001 at MNI (63, −39, −12)). There were negative correlations between the crystallized composite scores and SDBOLD values at the right inferior occipital gyrus (correlation coefficient r = −0.84, p = 0.001, q (pFDR) = 0.016) and right middle temporal gyrus (r = −0.88, p = 0.000, q (pFDR) = 0.017) for the CH group at TP1. SDBOLD could be a potentially useful neuroimaging marker for older long-term survivors of breast cancer with exposure to chemotherapy.

ABSTRACT: Geothermal reservoirs are usually deep and have low permeability. Hydraulic fracturing stimulation of the production and injection wells can help increase the heat extraction from these reservoirs. However, injecting cold fluid in the hot formation can cause considerable volumetric changes in reservoir rock and pore pressure distribution in the reservoir. As a result, thermal loading occurs, and local stresses change in magnitudes and directions. Such redistribution of pore pressure, stresses, and temperature may result in an unwanted propagation of the created fractures or failure of pre-existing rock discontinuities and create an unwanted closed loop circle. In this study, we investigate the effect of heat exchange between the circulating fluid and the hot rock on redistribution of local stresses. Our approach employs the thermo-poroelasticity theory to study cold fluid injection in geothermal reservoirs. The displacement discontinuity method (DDM) is used to solve the field equations of the thermo-poroelasticity theory. The DDM is a numerical technique that belongs to the boundary element methods (BEM). This numerical technique is suitable for studying hydraulic fracture (discontinuities in displacement) simulation problems. The thermo-poroelastic theory used here accounts for three fully coupled processes (mechanical, hydraulic, and thermal) in porous media saturated with fluid. Our results show the effect of cold fluid injection on stress magnitude and orientation. Furthermore, the evolution of fracture aperture and cold fluid injection efficiency are discussed. The results presented in this work show that the difference in temperature between the cold treatment fluid and hot reservoir help create a wider fracture in less pumping time. In addition, it can cause a 90° re-orientation of the minimum principal stress direction, which controls the propagation of fractures. Also, cold fluid injection in hot formation creates thermal (tensile) stresses that can be much higher than iso-thermal fluid injection.

ABSTRACT: Efficient production from tight and unconventional reservoirs requires drilling horizontal wells with an extensive network of high-quality (i.e., long, and conductive) fractures. However, the hydraulic fracturing process may be costly and may not be economically the best option when the oil and gas prices are low. The shock wave (pulsed loading) stimulation is a potential complement to traditional stimulation (e.g., hydraulic fracturing), that can add additional permeability enhancement to rock (via dynamic fracture processes) and bypass the skin region. The shock wave technique generates multiple fractures propagating in different directions around the wellbore, and is waterless, and less impacted by stress shadowing. This work presents a numerical study on the effects of rock properties (e.g., rock density, Young’s modulus, and Poisson’s ratio) on the shock wave fractures quality (e.g., length, type, and number). In addition, repetitive application of shock waves in wellbore is investigated. Pulsed fracturing in the cased and perforated wellbore is compared with open-hole situation. This work examines the effect of confining stresses and stress anisotropy. The shock wave propagation in rock along with the developed fracture types (shear and tensile) are discussed. Furthermore, the numerical results are compared with previous experimental observations. The main objective of this study is to determine the dominant parameters that influence the rock behavior in pulsed fracturing. Fracturing tight reservoirs by shock waves is an extremely high strain rate problem that we studied numerically using the combined finite discrete element method (FDEM). The results show that rock of large modulus of elasticity develops longer fractures. However, Poisson’s ratio has minor effects. Multiple application of high-rate loading can be used to control the wellbore collapse issue. The presence of wellbore casing reduces the shockwave strength and minimize the wellbore integrity issue. The confining stresses have a significant impact of the developed fractures length. However, stress anisotropy does not affect the created fracture orientations.

As part of ongoing efforts to meaningfully improve recruitment, enrollment, and accrual of older adults into cancer clinical trials, the National Cancer Institute (NCI) sponsored a workshop with experts across the country entitled Engaging Older Adults in the NCI Clinical Trials Network: Challenges and Opportunities. Three working groups, including Study Design, Infrastructure, and Stakeholders, were formed, who worked together to offer synergistic improvements in the system. Here, we summarize the workshop discussions of the Infrastructure Working Group, whose goal was to address infrastructural challenges, identify underlying resources, and offer solutions to facilitate accrual of older adults into cancer clinical trials. Based on preconference work and workshop discussions, four key recommendations to strengthen NCI infrastructure were proposed: 1) further centralize resources and expertise; 2) provide training for clinical research staff; (3) develop common data elements; and 4) evaluate what works and does not work. These recommendations provide a strategy to improve the infrastructure to enroll more older adults in cancer clinical trials.

PURPOSE Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer. METHODS Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated. RESULTS In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively ( P < .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity ( P < .01). CONCLUSION The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.

In the paper, the author analyzes the normative framework that regulates overtime work at the international and national level, but also the issue of overtime work in practice. The author puts forward the thesis that employers resort to overtime work in order to reduce labour costs, and employees agree to work overtime, even when it is illegal, due to the fear of dismissal, so by such abuse by employers, overtime work becomes a form of work exploitation. The author has conducted the research through a survey and an interview in order to determine the extent to which (illegal) overtime work is present in practice. The results of the research show that unpaid overtime work is widely present and that employees are afraid to stand up against this practice. In conclusion, there is a discrepancy between the normative and the real when it comes to overtime work.

Background The leadless Micra transcatheter-pacing system (Micra-TPS) is implanted via a femoral approach using a 27-French introducer sheath. The Micra Transcutaneous Pacing Study excluded patients with inferior vena cava (IVC) filters. Objective To examine the feasibility and safety of Micra-TPS implantation through an IVC filter. Methods This multicenter retrospective study included patients with an IVC filter who underwent a Micra-TPS implantation. Data for clinical and IVC filter characteristics, preprocedure imaging, and procedural interventions were collected. The primary outcome was a successful leadless pacemaker (LP) implantation via a femoral approach in the presence of an IVC filter. Periprocedural and delayed clinical complications were also evaluated. Results Of the 1528 Micra-TPS implants attempted, 23 patients (1.5%) had IVC filters. The majority (69.6%) of IVC filters were permanent. Six (26.1%) patients underwent preprocedural imaging to assess for filter patency. One patient's filter was retrieved before LP implantation. The primary outcome was achieved in 21 of 22 patients (95.5%) with an existing IVC filter. An occluded IVC precluded LP implantation in one patient. Difficulty advancing the stiff guidewire or the 27-Fr sheath was encountered in five patients. These cases required repositioning of the wire (n = 2), gradual sheath upsizing (n = 2), or balloon dilation of the filter (n = 1). Postprocedure fluoroscopy revealed intact filters in all cases. During a median 6-month follow-up, there were no clinical complications related to the filter or the Micra-TPS. Conclusion This multicenter experience demonstrates the feasibility and safety of Micra-TPS implantation via an IVC filter without acute procedural or delayed clinical complications.