Citations

Abstract Purpose: Diabetes care has largely focused on reducing the risk of complications by achieving hemoglobin A1c (HbA1c) targets; yet, whole-person care may be more effective and desirable. We sought to determine the nature of discussions about quality of life, burden of treatment, hypoglycemia, sexual function, and social support during diabetes-focused clinical encounters.Methods: We analyzed 41 previously recorded clinical encounters with patients with type 2 diabetes from the control arms of practice-based trials of shared decision making. Two coders evaluated videos for discussions about aspects of life with diabetes: quality of life, burden of treatment, hypoglycemia, sexual function, and social supports. When an aspect was raised, coders evaluated the nature of the conversation, clinician responses, and time spent on discussing the aspect. Results: Median length of the encounter was 15 minutes, 6 seconds (IQR: 11:16 – 20:23 minutes). Thirty five of 41 encounters (85.4%), included some discussion of quality of life (58.5%), burden of treatment (51.2%), social support (2.4%), or hypoglycemia (9.8%). Sexual function was not discussed. On average, 4.5% (1.4%-5.5%) of the encounter time involved conversations about HbA1c whereas 15.0% (0%-25%) of the encounter was spent on some aspect of quality of life, burden of treatment, social support, or hypoglycemia. If a topic related to quality of life was raised, clinicians most often responded by acknowledging patient’s concern without providing a solution (45.8%). Conclusions: A significant part of the patient-clinician encounter involves discussion of quality of life and burden of treatment, but clinicians rarely address these issues by providing solutions.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country’s fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.

Introduction: Secondary Central Nervous System Lymphoma (SCNSL) is the spread of a lymphoma to the CNS, the primary focus of which is situated elsewhere in the body. Most commonly, it is a non-Hodgkin lymphoma which either presents as a CNS involvement due to systemic relapse or progression, or as an isolated relapse in the CNS despite systemic remission. Traditionally, it has been treated by intrathecal or systemic chemotherapy and/or WBRT (Whole-brain radiation therapy) but recently, the use of high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) has shown encouraging results. We present a systematic review of literature displaying the treatment outcomes of HDT/ASCT in SCNSL. Methods: We performed a comprehensive literature search (following PRISMA guidelines) on July 08 2020 on PubMed, Cochrane Library and Clinicaltrials.Gov by using the relevant MeSH terms of high-dose chemotherapy, autologous stem cell transplantation, CNS lymphoma, efficacy and safety. Following screening by 2 reviewers, we selected 12 published studies (n=353) and included data from these studies in our systematic review. We manually extracted data summarized the results. Results: 232/353 patients eventually underwent sequential HDT+ASCT who were evaluable for treatment response out of which 190 patients had SCNSL (see table 1). Carmustine (BCNU) based HDT: BCNU based regimens have been the most extensively studied HDT among SCNSL patients (n=81). Korfel et al. in a phase 2 trial (2013, n=30) used HDT combination of BCNU, thiotepa and etoposide followed by ASCT in SCNSL patients. No patient was given whole brain radiation therapy (WBRT). The results yielded a PR of 8%, CR of 63% and 2-year OS of 63%. 1 toxicity related mortality (TRM) was noted and >grade 4 adverse effects included infection (4%) and stomatitis (13%). Ferreri et al. (2015, n=38) in a phase 2 trial use HDT with BCNU plus thiotepa on 38 patients 20 of whom underwent subsequent ASCT. The results showed CR of 100%, event free survival (EFS) of 40% ±9% and OS of 41% ±8% at 5 years with four patients suffering TRM. Thiotepa, busulfan and cyclophosphamide (TBC) based HDT: The combination based on TBC has been a popular option for SCNSL patients (n=53). In a retrospective analysis by Welch et al. (2014, n=17), TBC combination followed by sequential ASCT was studied in both primary and SCNSL patients (primary malignancy being diffuse large B-cell lymphoma) and the collective results showed complete response (CR) of 100%, PFS of 93% (95% CI: 61-99%) and OS of 93% (95% CI: 61-99%) at 3 years. In addition to the excellent efficacy response, no TRM or grade 4 toxicities were documented. Chen et al. (2015, n=12) in a phase 2 trial used HDT with rituximab and TBC (R-TBC) combination followed by ASCT rescue in 12 SCNSL patients. At 2 years, the progression free survival (PFS) was 51% (95% CI: 18-77%) and overall survival (OS) was 83% (95% CI: 48-96%). Two patients developed neurotoxicity and one TRM was recorded. Methotrexate (MTX) based HDT: MTX based combinations have also been widely used as HDT preceding ASCT in SCNSL patients (n=51). Fischer et al. (2008, n=20) studied HDT of MTX plus ifosfamide (IFO) in a retrospective analysis which showed PR of 30%, CR of 60% and median OS of 8.7 months and two TRM (due to sepsis in neutropenia) in SCNSL patients. Lee et al. (2015, n=31) in a prospective cohort study evaluated HDT with MTX based multidrug combination with ASCT in SCNSL patients which yielded a PR of 41.6%, CR of 50% and OS of 9 months (95% CI: 5-12 months). Five patients had suffered TRM. Conclusion: The combination of HDT with ASCT has yielded promising treatment outcomes both in terms of favorable efficacy rates and reduced rates of toxicity in SCNSL patients proving to be a comparable alternative to traditionally used chemo-radiation. However, the data at present is limited to few phase 2 trials with some being displayed collectively with data of primary CNS lymphoma patients. There is an increased need to carry out randomized phase 3 trials exclusively on SCNSL patients to better predict the efficacy and safety profile of HDT/ASCT in these patients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Abstract Background Orthotopic heart transplant (OHT) is indicated in 1–8% of patients with myocarditis. However, national trends in the utilization of transplantation and outcomes in myocarditis across the United States are not well established. Purpose Our objective was to study the trends and baseline characteristic of myocarditis patients undergoing heart transplant in the United States using Healthcare Cost and Utilization Project (HCUP) National (nationwide) Inpatient Sample (NIS) from 1999 to 2014. Methods Using NIS data, we identified patients older than 18 years with myocarditis using codes ICD9 codes of 422.0 and 422.9. Among these patients, we identified those who underwent cardiac transplantation using ICD9 procedure codes 37.5 and 33.6. We presented categorical data as percentages and continuous data as mean or median as appropriate. Results We identified a total of 62,264 hospitalizations for myocarditis from 1999–2014. 430 (0.69%) myocarditis patients underwent OHT which consisted of 0.82% of all 29990 cardiac transplants identified in the same period. The trends in OHT for myocarditis is as shown in Figure 1. The mean age was 32.9±2.4 years and 51.1% (n=219) were females. 235 (54.6%) were Caucasians and 60 (13.9%) were Hispanic. Majority of the transplants were performed at medium (16%) and large sized hospitals (80.4%). Cardiac transplants were mainly done at teaching hospitals (98.9%). Further, with regards to the geographical distribution of transplant procedure, most were done in the West (37.2%) followed by South (25.3%), Northeast (21.4%) and Mid-west (16%) of the United States. Private insurance was the major payor source which covered 245 (58%) patients followed by Medicaid covering 112 (26%) patients. A total of 26 (6%) myocarditis patients died during the same hospitalization for OHT. In terms of discharge following OHT in myocarditis 85.8% (n=369) were discharged home and 8.1% (n=35) to short term hospitalization. The average length of stay for OHT for myocarditis was 64.3±6.3 days. Also, the mean cost of hospitalization for heart transplant in myocarditis when adjusted for inflation was 789,566±93,108 dollars. In-patient mortality following OHT was not significantly different in large sized hospital compared to small and medium sized hospitals (7.6% vs 5.7%, p=0.54). However, the cost of hospitalization was significantly lesser in small and medium sized hospitals (588,363±154,349 vs 826,864±106,110 dollars, p<0.0001). Conclusions Only a small percentage of OHT is done for myocarditis with high proportion done in female when compared to OHT for other etiologies. Further studies need to be done to compare long term outcomes of heart transplant in myocarditis. Funding Acknowledgement Type of funding source: None

Abstract Background Cardiac amyloidosis (CA) remains an underdiagnosed entity. Atrial fibrillation (AF) is common in patients with CA, likely owing to direct amyloid deposition in the left atrium. However, the prevalence of AF in CA and its association with in-hospital outcomes has not been studied in large populations. Purpose Our aim was to study the trends, baseline characteristics, and clinical impact of AF in patients with CA in the United States using the Healthcare Cost and Utilization Project (HCUP) National) Inpatient Sample (NIS) from 1999 to 2014. Methods We queried the NIS and identified CA using ICD-9-CM codes 277.39 and 425.7. AF in CA patients was identified using the ICD-9-CM code of 427.31. Statistical Analysis System (SAS) 9.4 was used for analysis of data. Results There were a total of 145,920 CA hospitalizations between 1999 and 2014 in the United States, of which 37,070 (25.4%) had AF. The prevalence of AF remained consistent from 27.5% in 1999 to 27.4% in 2014. The mean age of patients with AF was 72.9±28.2 years and for patients without AF was 67±31.9 years (p<0.0001). The majority of the patients with AF were male (60.3%) and the study group was predominantly white (62.8% in patients with AF and 56.4% in patients without AF). CA patients with AF suffered more from thyroid-related disease (22.5% vs 16.1%), heart failure (62.9% vs 36.5%) and renal failure (34.7% vs 30.5%) and less from hypertension (29.3% vs 34.0%) and diabetes mellitus (23.2% vs 25.2%) (p<0.0001). There was no significant difference in the Charlson comorbidity score between the groups. Inpatient mortality was significantly higher in CA patients with AF (10.4% vs 6.5%, p<0.001). However, in-patient mortality has been decreasing over the years from 10.3% in 1999 to 7.6% in 2014. Furthermore, cardiogenic shock was significantly higher in CA patients with AF (2.1% vs 1.2%, p<0.001), yet the use of mechanical circulatory support was not significantly different between the groups (0.42% vs 0.35%, p=0.375). Pacemaker implantation was also noted to be higher in CA patients with AF compared to patients without AF (2.8% vs 1.2%, p<0.0001). There was no significant difference between CA patients with and without AF in mean cost of hospitalization ($58222±10752 vs $57695±545, p=0.081) or length of stay (7.9±0.1 vs 7.7±0.1 days, p=0.7089). Conclusion CA with atrial fibrillation is a well-recognized entity, and our large scale retrospective analysis found significant association with worse in-hospital outcomes and cardiogenic shock. Interestingly, trend of in-patient mortality in CA has been decreasing over the years, likely owing to improved imaging modalities for diagnosis. Optimal management of AF in CA is imperative to improve outcomes in this population. Funding Acknowledgement Type of funding source: None

Background Aortic stenosis–related mortality might vary across demographic subsets, regions, and states in the United States. Methods and Results We reviewed the death certificate data from the Centers for Disease Control and Prevention Wide‐Ranging OnLine Data for Epidemiologic Research database to examine aortic stenosis–related mortality trends from 2008 to 2018. Crude and age‐adjusted mortality rates (AAMRs) per 100 000 people and annual percentage change with 95% CIs were calculated. Between 2008 and 2018, AAMR reduced from 12.7 to 11.5 (average annual percentage change, −1.0 [95% CI, −1.5 to −0.5]), because of an accelerated decline between 2015 and 2018 (annual percentage change, −4.4 [95% CI, −6.0 to −2.7]). Older (aged >85 years), male, and White patients had higher death rates than younger, female, and non‐White patients, respectively. Although mortality reduction was similar across sexes, significant mortality reduction was limited to White patients only. The AAMRs were higher in rural than urban areas. States with AAMRs >90th percentile were distributed in the West and the Northeast, and <10th percentile in the South. The AAMRs for sex and race were highest in the West and lowest in the South. None of the states located in the Midwest showed a significant reduction in mortality. Mortality remained stable for hospital setting and nursing home/long‐term care facility, except that the number of deaths increased at home and hospice facility since 2014. Conclusions The reduction in mortality in patients with aortic stenosis was not consistent among demographic subsets and states. The substantial public health and economic implications call for determination of underlying clinical and socioeconomic factors to narrow the gap.

Background The aggressive clinical behavior of poorly differentiated and anaplastic thyroid cancers (PDTC and ATC) has proven challenging to treat, and survival beyond a few months from diagnosis is rare. Although 30%–60% of these tumors contain mutations in the BRAF gene, inhibitors designed specifically to target oncogenic BRAF have shown limited and only short-lasting therapeutic benefits as single agents, thus highlighting the need for improved treatment strategies, including novel combinations. Methods Using a BRAFV600E-driven mouse model of ATC, we investigated the therapeutic efficacy of the combination of BRAF inhibition and oncolytic herpes simplex virus (oHSV). Analyses of samples from tumor-bearing mice were performed to immunologically characterize the effects of different treatments. These immune data were used to inform the incorporation of immune checkpoint inhibitors into triple combination therapies. Results We characterized the immune landscape in vivo following BRAF inhibitor treatment and detected only modest immune changes. We, therefore, hypothesized that the addition of oncolytic virotherapy to BRAF inhibition in thyroid cancer would create a more favorable tumor immune microenvironment, boost the inflammatory status of tumors and improve BRAF inhibitor therapy. First, we showed that thyroid cancer cells were susceptible to infection with oHSV and that this process was associated with activation of the immune tumor microenvironment in vivo. Next, we showed improved therapeutic responses when combining oHSV and BRAF inhibition in vivo, although no synergistic effects were seen in vitro, further confirming that the dominant effect of oHSV in this context was likely immune-mediated. Importantly, both gene and protein expression data revealed an increase in activation of T cells and natural killer (NK) cells in the tumor in combination-treated samples. The benefit of combination oHSV and BRAF inhibitor therapy was abrogated when T cells or NK cells were depleted in vivo. In addition, we showed upregulation of PD-L1 and CTLA-4 following combined treatment and demonstrated that blockade of the PD-1/PD-L1 axis or CTLA-4 further improved combination therapy. Conclusions The combination of oHSV and BRAF inhibition significantly improved survival in a mouse model of ATC by enhancing immune-mediated antitumor effects, and triple combination therapies, including either PD-1 or CTLA-4 blockade, further improved therapy.