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1.
Cell Death Dis ; 15(5): 322, 2024 May 08.
Article En | MEDLINE | ID: mdl-38719798

Metastatic dissemination from the primary tumor is a complex process that requires crosstalk between tumor cells and the surrounding milieu and involves the interplay between numerous cellular-signaling programs. Epithelial-mesenchymal transition (EMT) remains at the forefront of orchestrating a shift in numerous cellular programs, such as stemness, drug resistance, and apoptosis that allow for successful metastasis. Till date, there is limited success in therapeutically targeting EMT. Utilizing a high throughput screen of FDA-approved compounds, we uncovered a novel role of the topoisomerase inhibitor, Teniposide, in reversing EMT. Here, we demonstrate Teniposide as a potent modulator of the EMT program, specifically through an IRF7-NMI mediated response. Furthermore, Teniposide significantly reduces the expression of the key EMT transcriptional regulator, Zinc Finger E-Box Binding Homeobox 2 (ZEB2). ZEB2 downregulation by Teniposide inhibited RNA polymerase I (Pol I) activity and rRNA biogenesis. Importantly, Teniposide treatment markedly reduced pulmonary colonization of breast cancer cells. We have uncovered a novel role of Teniposide, which when used at a very low concentration, mitigates mesenchymal-like invasive phenotype. Overall, its ability to target EMT and rRNA biogenesis makes Teniposide a viable candidate to be repurposed as a therapeutic option to restrict breast cancer metastases.


Breast Neoplasms , Down-Regulation , Epithelial-Mesenchymal Transition , RNA Polymerase I , Teniposide , Zinc Finger E-box Binding Homeobox 2 , Epithelial-Mesenchymal Transition/drug effects , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Female , Zinc Finger E-box Binding Homeobox 2/metabolism , Zinc Finger E-box Binding Homeobox 2/genetics , Cell Line, Tumor , Down-Regulation/drug effects , RNA Polymerase I/metabolism , Teniposide/pharmacology , Animals , Mice , Gene Expression Regulation, Neoplastic/drug effects
2.
J Endocr Soc ; 8(6): bvae075, 2024 Apr 06.
Article En | MEDLINE | ID: mdl-38698871

Context: The risk of gestational diabetes mellitus (GDM) in twin pregnancies is more than double that of singleton pregnancies. Although twin pregnancies present unique challenges for fetal growth and prenatal management, the approach to GDM diagnosis and treatment is the same regardless of plurality. Data on pregnancy outcomes for individuals with GDM and a twin pregnancy are limited and conflicting. Objective: To describe the maternal characteristics associated with GDM in twin pregnancies and to assess the associated pregnancy outcomes compared to twin pregnancies unaffected by GDM. Methods: A retrospective cohort study was conducted at Mayo Clinic, Rochester, Minnesota, USA, and included predominantly Causasian women aged 18 to 45 years who received prenatal care for a twin pregnancy from 2017-2022. Maternal characteristics and a broad spectrum of pregnancy outcomes were evaluated. Universal GDM screening involved a 50 g oral glucose challenge test +/- a 100 g oral glucose tolerance test. Results: GDM was diagnosed in 23% pregnancies (n = 104/452). Compared to those without, women with GDM had known risk factors including a higher prepregnancy body mass index (31.1vs 26.3 kg/m2; P < .01) and a prior history of GDM (21.7 vs 5.9%; P < .01). There were no differences in maternal pregnancy complications or neonatal outcomes between groups. Attendance at postpartum glucose testing among women with GDM was poor at 27.9% (29/104). Conclusion: These data suggest that women with twin pregnancies share a similar GDM risk profile to those with singleton pregnancies and provide reassuring evidence that current management for GDM twin pregnancies produces similar outcomes to twin pregnancies without GDM.

3.
JCO Oncol Pract ; 20(3): 329-334, 2024 Mar.
Article En | MEDLINE | ID: mdl-38175994

The negative impact and management of disruptive behavior are discussed in the article by Monika Kumar, et al.


Physicians , Problem Behavior , Humans , Attitude of Health Personnel
4.
JCO Oncol Pract ; 19(9): 724-730, 2023 09.
Article En | MEDLINE | ID: mdl-37441742

Cancer Morbidity, Mortality, and Improvement Rounds is a series of articles intended to explore the unique safety risks experienced by oncology patients through the lens of quality improvement, systems and human factors engineering, and cognitive psychology. For purposes of clarity, each case focuses on a single theme, although, as is true for all medical incidents, there are almost always multiple, overlapping, contributing factors. The quality improvement paradigm used here, which focuses on root cause analyses and opportunities to improve care delivery systems, was previously outlined in this journal.This article describes the care of a young patient with aggressive breast cancer, declining performance status, and multiple hospital admissions who died shortly after being discharged home without essential medications or an adequate plan for follow-up. The patient's death due to her malignancy was unavoidable, but she had inadequate resources before her death, leading to avoidable suffering. This outcome resulted from a series of minor errors attributable to inadequate handoffs, challenges establishing realistic goals of care, and hierarchy within and between medical teams that resulted in major lapses at the time of discharge. We explore these issues and discuss how this case led to the establishment of programs designed to empower health care providers and increase engagement of outpatient oncologists at critical points of patients' disease courses.


Neoplasms , Patient Discharge , Female , Humans , Inpatients , Hospitalization , Neoplasms/complications , Neoplasms/therapy
5.
J Med Educ Curric Dev ; 10: 23821205231164088, 2023.
Article En | MEDLINE | ID: mdl-37324053

OBJECTIVES: Few medical schools incorporate formal education on human trafficking (HT) and sex trafficking (ST) into their curriculum. Our objective was to develop, implement, and evaluate education on HT and ST in the first-year medical student curriculum. METHODS: The curriculum included a standardized patient (SP) experience and lecture. As part of their mandatory sexual health course, students interviewed an SP who presented with red flags for ST and then participated in a discussion led by a physician-facilitator in an observed small group setting. A multiple-choice survey to assess knowledge about HT and ST was developed and administered to students before and after the SP interview. RESULTS: Of the 50 first-year medical students, 29 (58%) participated in the survey. Compared with the students' baseline scores (according to the percentage of correct responses), scores after the educational intervention showed a significant increase in percentage correct on questions related to trafficking definition and scope (elder care, P = .01; landscaping, P = .03); victim identification (P < .001); referral to services (P < .001); legal issues (P = .01); and security (P < .001). On the basis of the feedback, a 2-hour lecture, which was adapted from the American Medical Women's Association-Physicians Against the Trafficking of Humans "Learn to Identify and Fight Trafficking" training, was presented the next year to all first-year medical students as part of their longitudinal clinical skills course and before the SP case. Curriculum objectives included learning trafficking definitions, victim/survivor identification, intersections with health care, the local impact of HT, and available resources. CONCLUSION: This curriculum fulfills course objectives and could be replicated at other institutions. Further evaluation of this pilot curriculum is necessary to evaluate its effectiveness.

6.
Future Microbiol ; 18: 427-441, 2023 May.
Article En | MEDLINE | ID: mdl-37204286

Aim: To analyze the impact of postpartum antibiotic (Ab) prophylaxis on the infant gut microbiome. Materials & methods: Whole metagenomic analysis was performed on breast milk and infant fecal samples collected from mother-infant pairs who belonged to two groups: an Ab group comprising mothers who had received a single course of Abs in the immediate postpartum period and a non-Ab group comprising mothers who had not received Abs. Results: The characteristic presence of Citrobacter werkmanii, an emerging multidrug-resistant uropathogen, and a higher relative abundance of genes encoding resistance to specific Abs were noted in samples from the Ab group compared with those from the non-Ab group. Conclusion: Policies regarding prophylactic Ab prescription across government and private health sectors in the postpartum period need to be strengthened.


We studied the impact of antibiotics (Abs) that were taken by mothers as a preventive measure in the immediate postdelivery period on the bacterial diversity of the infant gut. All mother­infant pairs who participated in the study had undergone 'low-risk', normal delivery and practiced exclusive breastfeeding. Stool samples of the infants and breast milk samples of the corresponding mothers were collected for analysis of the pattern of microbial composition. On analysis, it was found that stool samples of the infants in the Ab group comprised opportunistic pathogens and harbored genes encoding resistance to specific Abs. There was a relatively higher abundance of beneficial bacteria in infant stool samples of the non-Ab group. This study highlights the need to reconsider the existing practice of taking Abs as a preventive measure after normal delivery to maintain health and reduce the spread of antimicrobial resistance in this particular region.


Gastrointestinal Microbiome , Female , Humans , Infant , Antibiotic Prophylaxis , Mothers , Milk, Human , Postpartum Period , Feces
7.
Prog Transplant ; 33(2): 168-174, 2023 06.
Article En | MEDLINE | ID: mdl-37013356

INTRODUCTION: Liver acceptance patterns vary significantly between transplant centers. Data pertaining to outcomes of livers declined by local and regional centers and allocated nationally remains limited. PROJECT AIM: The objective was to compare post-liver transplant outcomes between liver allografts transplanted as a result of national and local-regional allocation. DESIGN: This was a retrospective evaluation of 109 nationally allocated liver allografts used for transplant by a single center. Outcomes of nationally allocated grafts were compared to standard allocation grafts (N = 505) during the same period. RESULTS: Recipients of nationally allocated grafts had lower model for end stage liver disease scores (17 vs 22, P = .001). Nationally allocated grafts were more likely to be post-cross clamp offers (29.4% vs 13.4%, P = .001) and have longer cold ischemia times (median hours 7.8 vs 5.5, P = .001). Early allograft dysfunction was common (54.1% vs 52.5%, P = .75) and did not impact hospital length of stay (median 5 vs 6 days, P = .89). There were no differences in biliary complications (P = .11). There were no differences in patient (P = .88) or graft survival (P = .35). In a multivariate model, after accounting for differences in cold ischemia time and posttransplant biliary complications, nationally allocated grafts were not associated with increased risk for graft loss (HR 0.9, 95% CI 0.4-1.8). Abnormal liver biopsy findings (33.0%) followed by donor donation after circulatory death status (22.9%) were the most common reasons for decline by local-regional centers. CONCLUSION: Despite longer cold ischemia times, patient and graft survival outcomes remain excellent and comparable to those seen from standard allocation grafts.


End Stage Liver Disease , Liver Transplantation , Humans , Liver Transplantation/adverse effects , Cold Ischemia , End Stage Liver Disease/surgery , End Stage Liver Disease/etiology , Retrospective Studies , Severity of Illness Index , Tissue Donors , Graft Survival
8.
J Surg Res ; 288: 140-147, 2023 08.
Article En | MEDLINE | ID: mdl-36966594

INTRODUCTION: Broader use of donation after circulatory death (DCD) and nonconventional grafts for liver transplant helps reduce disparities in organ availability. Limited data, however, exists on outcomes specific to nonconventional graft utilization in older patients. As such, this study aimed to investigate outcomes specific to conventional and nonconventional graft utilization in recipients > 70 y of age. METHODS: 1-to-3 matching based on recipient sex, Model for End-Stage Liver Disease score, and donor type was performed on patients ≥70 and <70 y of age who underwent liver transplant alone at Mayo Clinic Arizona between 2015 and 2020. Primary outcomes were posttransplant patient and liver allograft survival for recipients greater than or less than 70 y of age. Secondary outcomes included grafts utilization patterns, hospital length of stay, need for reoperation, biliary complications and disposition at time of hospital discharge. RESULTS: In this cohort, 36.1% of grafts came from DCD donors, 17.4% were postcross clamp offers, and 20.8% were nationally allocated. Median recipient ages were 59 and 71 y (P < 0.01). Recipients had similar Intensive care unit (P = 0.82) and hospital (P = 0.14) lengths of stay, and there were no differences in patient (P = 0.68) or graft (P = 0.38) survival. When comparing donation after brain death and DCD grafts in those >70 y, there were no differences in patient (P = 0.89) or graft (P = 0.71) survival. CONCLUSIONS: Excellent outcomes can be achieved in older recipients, even with use of nonconventional grafts. Expanded use of nonconventional grafts can help facilitate transplant opportunities in older patients.


End Stage Liver Disease , Liver Transplantation , Tissue and Organ Procurement , Humans , Aged , End Stage Liver Disease/surgery , Death , Retrospective Studies , Severity of Illness Index , Tissue Donors , Graft Survival
10.
J Control Release ; 355: 474-488, 2023 03.
Article En | MEDLINE | ID: mdl-36739909

Glioblastoma Multiforme (GBM) is one of the challenging tumors to treat as it recurs, almost 100%, even after surgery, radiation, and chemotherapy. In many cases, recurrence happens within 2-3cm depth of the resected tumor margin, indicating the inefficacy of current anti-glioma drugs to penetrate deep into the brain tissue. Here, we report an injectable nanoparticle-gel system, capable of providing deep brain penetration of drug up to 4 cm, releasing in a sustained manner up to >15 days. The system consists of ∼222 nm sized PLGA nanoparticles (NP-222) loaded with an anti-glioma drug, Carmustine (BCNU), and coated with a thick layer of polyethylene glycol (PEG). Upon release of the drug from PLGA core, it will interact with the outer PEG-layer leading to the formation of PEG-BCNU nanocomplexes of size ∼33 nm (BCNU-NC-33), which could penetrate >4 cm deep into the brain tissue compared to the free drug (< 5 mm). In vitro drug release showed sustained release of drug for 15 days by BCNU-NP gel, and enhanced cytotoxicity by BCNU-NC-33 drug-nanocomplexes in glioma cell lines. Ex vivo goat-brain phantom studies showed drug diffusion up to 4 cm in tissue and in vivo brain-diffusion studies showed almost complete coverage within the rat brain (∼1.2 cm), with ∼55% drug retained in the tissue by day-15, compared to only ∼5% for free BCNU. Rat orthotopic glioma studies showed excellent anti-tumor efficacy by BCNU-NP gel compared to free drug, indicating the potential of the gel-system for anti-glioma therapy. In effect, we demonstrate a unique method of sustained release of drug in the brain using larger PLGA nanoparticles acting as a reservoir while deep-penetration of the released drug was achieved by in situ formation of drug-nanocomplexes of size <50 nm which is less than the native pore size of brain tissue (> 100 nm). This method will have a major impact on a challenging field of brain drug delivery.


Brain Neoplasms , Glioblastoma , Glioma , Nanoparticles , Rats , Animals , Glioblastoma/drug therapy , Glioblastoma/metabolism , Carmustine/therapeutic use , Delayed-Action Preparations/metabolism , Nanomedicine , Brain/metabolism , Glioma/drug therapy , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Polyethylene Glycols/therapeutic use
11.
Cancers (Basel) ; 14(23)2022 Dec 01.
Article En | MEDLINE | ID: mdl-36497435

Introduction: The full impact of COVID-19 infections on patients with cancer who are actively being treated with chemotherapy or immune checkpoint inhibitors (ICIs) has not been fully defined. Our goal was to track clinical outcomes in this specific patient population. Methods: We performed a retrospective chart review of 121 patients (age > 18 years) at the University of Alabama at Birmingham from January 2020 to December 2021 with an advanced solid malignancy that were eligible to be treated with ICIs or on current therapy within 12 months of their COVID-19 diagnosis. Results: A total of 121 patients were examined in this study, and 61 (50.4%) received immunotherapy treatment within 12 months. One quarter of the patients on ICIs passed away, compared to 13% of the post-chemotherapy cohort. Patients who were vaccinated for COVID-19 had lower mortality compared to unvaccinated patients (X2 = 15.19, p < 0.001), and patients with lower ECOG (0.98) were associated with lower mortality compared to patients with worse functional status (0.98 vs. 1.52; t = 3.20; p < 0.01). Conclusions: COVID-19-related ICI mortality was higher compared to patients receiving chemotherapy. However, ICI cessation or delay is unwarranted as long there has been a risk−benefit assessment undertaken with the patient.

12.
Semin Oncol ; 2022 Jul 08.
Article En | MEDLINE | ID: mdl-35879123

Immunotherapy for non-small cell lung cancer (NSCLC) has revolutionized treatment for those with advanced disease, and recent data have emerged providing evidence for its benefits in earlier stages of the disease. Several pivotal clinical trials provide compelling data that adaptive immune cells may be highly effective and possibly even curative for NSCLC. Immune checkpoint inhibitors (ICIs) can unleash highly reactive memory immune responses to tumor antigens with durable effects against advanced or recurrent disease. Despite these encouraging results, many critical questions remain in the field including, for example, how to identify the subsets of NSCLC patients who most benefit from ICI treatment, and how ICI efficacy might be enhanced by utilizing combinations or sequencing of agents. A deeper understanding of biological mechanisms involved in lung cancer offers a unique opportunity to further explore the interaction between the adaptive immune landscape and NSCLC. Given the high incidence of lung cancer in Veterans and many Veterans being treated with immunotherapy for this disease, it is timely to have their adequate representation in future clinical trials. New clinical trials focused on Veterans can assist in exploring ways to mitigate resistant mechanisms as well as to investigate predictive and prognostic biomarkers for response to ICIs and other treatments. This paper will review current data and indications for immunotherapy in NSCLC, introduce new areas of research within immunotherapy, and discuss its applicability to the Veteran population.

13.
Clin Lung Cancer ; 23(7): e408-e414, 2022 11.
Article En | MEDLINE | ID: mdl-35680550

OBJECTIVES: The ideal non-operative treatment for patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. To inform optimal treatment paradigms for this cohort, we examined patterns of failure and the impact of radiation therapy (RT) and chemotherapy receipt. MATERIALS AND METHODS: Node-negative NSCLC patients with 5+ cm primary tumors receiving definitive RT at our institution were identified. Sites of initial progression were analyzed. Local progression, regional/distant progression, progression-free survival, and overall survival were analyzed via cumulative incidence function and Kaplan-Meier. Associations between local vs. regional/distant progression with treatment and clinicopathologic variables were assessed via univariable and multivariable competing risks regression. RESULTS AND CONCLUSION: We identified 88 patients for analysis. Among patients with recurrent disease (N = 36), initial patterns of failure analysis showed that isolated distant (27.8%) and isolated regional progression (22.2%) were most common. Distant or regional failure as a component of initial failure was seen in 88.9% of patients who progressed, while isolated local failure was uncommon (11.1%). Univariable and multivariable competing risks regression showed that receipt of SBRT was associated with reduced risk of local progression (HR 0.23, P = .012), and receipt of chemotherapy was associated with reduced risk of regional/distant progression (HR 0.12, P = .040). In conclusion, patients with large, node-negative NSCLC treated with definitive RT are at high risk of regional and distant progression. SBRT correlates with a reduced risk of local failure while chemotherapy is associated with reduced regional/distant progression in this patient population. Ideal treatment may include SBRT when feasible with appropriate systemic therapy.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiosurgery , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/pathology , Radiosurgery/methods , Progression-Free Survival , Cohort Studies , Treatment Outcome , Retrospective Studies
14.
Clin Transplant ; 36(8): e14737, 2022 08.
Article En | MEDLINE | ID: mdl-35633507

Dual kidney transplantation (DKT), utilizing two adult kidneys from the same donor for one recipient, has been used as a way to expand the available donor pool. These kidneys often come from high Kidney Donor Profile Index donors (KDPI > 85%). Data comparing outcomes between high KDPI DKT and single kidney transplants (SKT) remain limited. We assessed outcomes of 336 high KDPI kidney transplants performed at our center; 11.0% (n = 37) were DKT. Recipients of DKT were older (P = .02) and donors had a higher KDPI score (median 96% vs. 91%, P < .0001). DKT operative time was higher compared to SKT (+1.4 hours, P < .0001). There were no differences in delayed graft function (54.1% vs. 51.5%, P = .77) and hospital length of stay (median 4.0 vs. 3.0 days, P = .21) between DKT and SKT. Grade I Clavien-Dindo complications occurred in 8.1% of DKT and 13.7% of SKT (P = .008). There were no grade IVa, IVb, or V complications in either group. DKT had more glomerulosclerosis (P = .04), interstitial fibrosis (P = .02), tubular atrophy (P = .01), and arterial thickening (P = .03) on 1-year protocol biopsies. Estimated glomerular filtration was higher for DKT at 1- (P = .004) and 2-years post-transplant (P = .01). There were no differences in patient (HR 1.3, 95% CI .5-3.3, P = .58) or graft (HR 1.1, 95% CI .5-2.3, P = .83) survival. Good outcomes can be achieved with DKT using high KDPI kidneys with moderate chronic changes. DKT is a good option to help further utilize high KDPI kidneys and minimize discard.


Kidney Diseases , Kidney Transplantation , Solitary Kidney , Transplants , Adult , Graft Survival , Humans , Kidney/pathology , Kidney/surgery , Kidney Diseases/pathology , Retrospective Studies , Solitary Kidney/pathology , Tissue Donors
15.
Liver Transpl ; 28(11): 1726-1734, 2022 11.
Article En | MEDLINE | ID: mdl-35332655

Donation after circulatory death (DCD) liver transplantation (LT) outcomes have been attributed to multiple variables, including procurement surgeon recovery techniques. Outcomes of 196 DCD LTs at Mayo Clinic Arizona were analyzed based on graft recovery by a surgeon from our center (transplant procurement team [TPT]) versus a local procurement surgeon (non-TPT [NTPT]). A standard recovery technique was used for all TPT livers. The recovery technique used by the NTPT was left to the discretion of that surgeon. A total of 129 (65.8%) grafts were recovered by our TPT, 67 (34.2%) by the NTPT. Recipient age (p = 0.43), Model for End-Stage Liver Disease score (median 17 vs. 18; p = 0.22), and donor warm ischemia time (median 21.0 vs. 21.5; p = 0.86) were similar between the TPT and NTPT groups. NTPT livers had longer cold ischemia times (6.5 vs. 5.0 median hours; p < 0.001). Early allograft dysfunction (80.6% vs. 76.1%; p = 0.42) and primary nonfunction (0.8% vs. 0.0%; p = 0.47) were similar. Ischemic cholangiopathy (IC) treated with endoscopy occurred in 18.6% and 11.9% of TPT and NTPT grafts (p = 0.23). At last follow-up, approximately half of those requiring endoscopy were undergoing a stent-free trial (58.3% TPT; 50.0% NTPT; p = 0.68). IC requiring re-LT in the first year occurred in 0.8% (n = 1) of TPT and 3.0% (n = 2) of NTPT grafts (p = 0.23). There were no differences in patient (hazard ratio [HR], 1.95; 95% confidence interval [CI], 0.76-5.03; p = 0.23) or graft (HR, 1.99; 95% CI, 0.98-4.09; p = 0.10) survival rates. Graft survival at 1 year was 91.5% for TPT grafts and 95.5% for NTPT grafts. Excellent outcomes can be achieved using NTPT for the recovery of DCD livers. There may be an opportunity to expand the use of DCD livers in the United States by increasing the use of NTPT.


End Stage Liver Disease , Liver Transplantation , Surgeons , Tissue and Organ Procurement , Death , End Stage Liver Disease/surgery , Graft Survival , Humans , Ischemia , Liver Transplantation/adverse effects , Liver Transplantation/methods , Retrospective Studies , Severity of Illness Index , Tissue Donors , United States
16.
JCO Oncol Pract ; 18(4): e551-e563, 2022 04.
Article En | MEDLINE | ID: mdl-35015586

PURPOSE: The COVID-19 pandemic led to unprecedented challenges in medical training, and we sought to assess the specific impact of COVID-19 on hematology-oncology (HO) fellowship programs. METHODS: We conducted a cross-sectional anonymous online survey of 103 HO program directors (PDs) in conjunction with the American Society of Hematology (ASH) and ASCO. We sought to assess the specific impact of COVID-19 on HO fellowship programs' clinical, educational, and research activities, evaluate perceptions regarding PD and trainee emotional and mental health, and identify ways to support programs. Data were analyzed using descriptive statistics, parametric and nonparametric tests, and multivariable logistic regression models. Responses to open-ended questions were analyzed with thematic analysis. RESULTS: Significant changes to fellowship activities included transitioning fellow training from outpatient clinics to telehealth (77.7%), shifting to virtual education (94.2%), and moving to remote research work (63.1%). A minority (21.4%) of PDs reported that their fellows were redeployed to cover non-HO services. Most PDs (54.4%) believed COVID-19 had a slight negative impact on fellowship training. PD self-reported burnout increased significantly from 15.5% prepandemic to 44.7% during the pandemic, and most PDs witnessed minor signs of fellow burnout (52.4%). Common PD concerns included inadequate supervision for telehealth activities, reduced opportunities for fellow advancement and promotion, lack of professional development activities, limited research operations and funding, program financial constraints, and virtual recruitment. CONCLUSION: We encourage institutions and national societies to allocate resources and develop programs that can support fellowships and mitigate the potential negative effects of COVID-19 on trainee and PD career development.


COVID-19 , Hematology , COVID-19/epidemiology , Cross-Sectional Studies , Education, Medical, Graduate , Fellowships and Scholarships , Humans , Pandemics
17.
JCO Oncol Pract ; 18(4): e586-e599, 2022 04.
Article En | MEDLINE | ID: mdl-34990292

PURPOSE: Graduate medical and research training has drastically changed during the COVID-19 pandemic, with widespread implementation of virtual learning, redeployment from core rotations to the care of patients with COVID-19, and significant emotional and physical stressors. The specific experience of hematology-oncology (HO) fellows during the COVID-19 pandemic is not known. METHODS: We conducted a mixed-methods study using a survey of Likert-style and open-ended questions to assess the training experience and well-being of HO fellows, including both clinical and postdoctoral trainee members of the American Society of Hematology and ASCO. RESULTS: A total of 2,306 surveys were distributed by e-mail; 548 (23.8%) fellows completed the survey. Nearly 40% of fellows felt that they had not received adequate mental health support during the pandemic, and 22% reported new symptoms of burnout. Pre-existing burnout before the pandemic, COVID-19-related clinical work, and working in a primary research or nonclinical setting were associated with increased burnout on multivariable logistic regression. Qualitative thematic analysis of open-ended responses revealed significant concerns about employment after training completion, perceived variable quality of virtual education and board preparation, loss of clinical opportunities to prepare for independent clinical practice, inadequate grant funding opportunities in part because of shifting research priorities, variable productivity, and mental health or stress during the pandemic. CONCLUSION: HO fellows have been profoundly affected by the pandemic, and our data illustrate multiple avenues for fellowship programs and national organizations to support both clinical and postdoctoral trainees.


Burnout, Professional , COVID-19 , Hematology , Burnout, Professional/epidemiology , COVID-19/complications , COVID-19/epidemiology , Education, Medical, Graduate , Hematology/education , Humans , Medical Oncology/education , Pandemics
18.
Transpl Int ; 35: 10849, 2022.
Article En | MEDLINE | ID: mdl-36620699

Concerns regarding outcomes and early resource utilization are potential deterrents to broader use of kidneys at risk for delayed graft function (DGF). We assessed outcomes specific to kidneys with DGF that required early readmission following transplant. Three groups were identified: 1) recipients with DGF not requiring readmission, 2) recipients with DGF having an isolated readmission, and 3) recipients with DGF requiring ≥2 readmissions. Most recipients either required a single readmission (26.8%, n = 247) or no readmission (56.1%, n = 517); 17.1% (n = 158), had ≥2 readmissions. Recipients requiring ≥2 readmissions were likely to be diabetic (53.8%, p = 0.04) and have longer dialysis vintage (p = 0.01). Duration of DGF was longer with increasing number of readmissions (p < 0.001). There were no differences in patient survival for those with DGF and 0, 1 and ≥2 readmissions (p = 0.13). Graft survival, however, was lower for those with ≥2 readmissions (p < 0.0001). This remained true when accounting for death-censored graft loss (p = 0.0012). Additional subgroup analysis was performed on mate kidneys with and without DGF and mate kidneys, both with DGF, with and without readmissions. For these subgroups, there were no differences in patient or graft survival. As a whole, patients with DGF have excellent outcomes, however, patients with DGF requiring ≥2 readmissions have lower graft survival. A better understanding of recipient variables contributing to multiple readmissions may allow for improvements in the utilization of DGF at-risk kidneys.


Kidney Transplantation , Humans , Delayed Graft Function/etiology , Graft Survival , Kidney , Kidney Transplantation/adverse effects , Renal Dialysis , Retrospective Studies , Risk Factors , Tissue Donors , Patient Readmission
19.
JCO Glob Oncol ; 7: 1513-1521, 2021 09.
Article En | MEDLINE | ID: mdl-34714666

This report from ASCO's International Quality Steering Group summarizes early learnings on how the COVID-19 pandemic and its stresses have disproportionately affected cancer care delivery and its delivery systems across the world. This article shares perspectives from eight different countries, including Austria, Brazil, Ghana, Honduras, Ireland, the Philippines, South Africa, and the United Arab Emirates, which provide insight to their unique issues, challenges, and barriers to quality improvement in cancer care during the pandemic. These perspectives shed light on some key recommendations applicable on a global scale and focus on access to care, importance of expanding and developing new treatments for both COVID-19 and cancer, access to telemedicine, collecting and using COVID-19 and cancer registry data, establishing measures and guidelines to further enhance quality of care, and expanding communication among governments, health care systems, and health care providers. The impact of the COVID-19 pandemic on cancer care and quality improvement has been and will continue to be felt across the globe, but this report aims to share these experiences and learnings and to assist ASCO's international members and our global fight against the pandemic and cancer.


COVID-19 , Neoplasms , Delivery of Health Care , Humans , Neoplasms/epidemiology , Neoplasms/therapy , Pandemics , Quality Improvement , SARS-CoV-2
20.
Cancer ; 127(16): 2954-2965, 2021 08 15.
Article En | MEDLINE | ID: mdl-33951180

BACKGROUND: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. METHODS: This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate-specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome-wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self-identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. RESULTS: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. CONCLUSIONS: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side-effect rates than White men. This exploratory genome-wide analysis of TTP identified a possible candidate marker of ancestry-dependent treatment outcomes.


Abiraterone Acetate , Prostatic Neoplasms, Castration-Resistant , Abiraterone Acetate/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Disease-Free Survival , Humans , Male , Prednisone/adverse effects , Prospective Studies , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/genetics , Retrospective Studies , Treatment Outcome
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