The Journal of Thoracic and Cardiovascular Surgery, 2019
Objective: Risk-adjusted operative mortality is a key quality measure for isolated coronary arter... more Objective: Risk-adjusted operative mortality is a key quality measure for isolated coronary artery bypass grafting. Through a multicenter quality improvement initiative, we sought to improve this measure at 14 surgical programs within a large and geographically dispersed health care system. Methods: Observed mortality and combined mortality/morbidity rates for isolated coronary artery bypass grafting were collected from January 2014 to June 2017. Expected mortality and mortality/morbidity rates were determined using the Society of Thoracic Surgeons risk models. The observed/expected ratios during the baseline (2014) and final 12-month outcome period were compared. The quality improvement intervention was multifaceted and surgeon led, and consisted of (1) regular sharing of unblinded data, (2) standardized quality improvement processes, (3) regular system-wide quality improvement meetings, (4) annual observed/expected mortality targets, (5) identification of underperforming institutions and creation of nonpunitive quality improvement action plans, and (6) implementation of checklists to drive perioperative care standardization. Results: The observed/expected ratio of mortality was 1.19 during the baseline period and decreased to 0.59 for the outcome period (P ¼ .004) without a change in expected mortality or case volume. The observed/expected ratio decreased for mortality/morbidity, and mortality without antecedent morbidity was almost eliminated. Conclusions: A significant and clinically meaningful 50% reduction in the observed/expected ratio for isolated coronary artery bypass grafting mortality was observed during a multifaceted quality improvement initiative across a large multicenter health care system. Morbidity also decreased. Keys to success included surgeon leadership and engagement, frequent unblinded data sharing, development of standardized quality improvement processes, improvement and standardization of care delivery, setting of quality improvement targets, and a shared vision for improved patient outcomes.
Background: Patients with small aortic annuli (SAA) are prone to higher post-transcatheter aortic... more Background: Patients with small aortic annuli (SAA) are prone to higher post-transcatheter aortic valve replacement (TAVR) transvalvular gradients and development of prosthesis-patient mismatch (PPM). In many patients with SAA, the choice of TAVR valve commonly involves choosing between the 26-mm Medtronic Evolut 2 (ME26) or the 23-mm Edwards Sapien 3 valve (ES23). We compared echocardiographic and clinical outcomes in patients with SAA undergoing TAVR with either valve. Methods: We queried the Providence St. Joseph Health Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry database for patients undergoing TAVR with either the ES23 or ME26 between July 2015 and December 2018 at 11 hospitals. Post-TAVR echocardiographic and clinical results in-hospital, at 1 month, and at 1 year were examined. High gradient (HG) was defined as mean gradient (MG) ≥20 mm Hg. Results: We identified 1162 patients with SAA undergoing TAVR with either the ME26 (n = 233) or ES23 valve (n = 929). Baseline characteristics between groups were similar. At 1 month, the ME26 was associated with a lower MG than the ES23 (7.7 ± 4.7 mm Hg vs 13.1 ± 4.9 mm Hg; P<.001) and moderate or severe PPM (11% and 3% vs 27% and 13%; P<.001). Occurrence of HG at 1 year was lower with the ME26 valve vs the ES23 valve (0% vs 15%; P<.001). In-hospital and follow-up clinical outcomes to 1 year were similar for both groups. Conclusion: TAVR in SAA with the ME26 is associated with lower incidence of HG or PPM compared with the ES23. While clinical outcomes at 1 year were similar, the long-term implications of these findings remain unknown.
Receiver operating characteristic (ROC) curve analysis is a useful method to measure the ability ... more Receiver operating characteristic (ROC) curve analysis is a useful method to measure the ability of a clinical risk model to discriminate between hospital deaths and survivors. Its use in medicine originated as a method for synthesizing the specificity and sensitivity of diagnostic tests across a spectrum of possible cut points. The area under the ROC curve can be interpreted as
e21509 Background: Due to biologic differences, uveal melanoma patients are often excluded from c... more e21509 Background: Due to biologic differences, uveal melanoma patients are often excluded from clinical trials for cutaneous melanoma; however, many antigens are shared between the two melanoma subtypes. Thus, our vaccine trials at the University of Virginia (UVA) have allowed enrollment of high-risk uveal melanoma patients, who have substantial risk of relapse without FDA-approved adjuvant therapy available. For the present study, we hypothesized that the vaccines would be well-tolerated and immunogenic in this population. We examined the clinical, immunogenicity and safety outcomes of subjects with uveal melanoma enrolled in our adjuvant vaccine clinical studies. Methods: Patients were identified through participation in an adjuvant vaccine study at UVA between 2012-2022. Ten patients received the 6-Melanoma-Helper Peptide (6-MHP) vaccine through Mel-65 and Mel-66 clinical trials (NCT03617328 and NCT04364230) and one patient received the 12-peptide MELITAC vaccine through the Mel-58 clinical trial (NCT01585350). Clinical outcomes included relapse-free (RFS) and overall survival (OS) and trial toxicity reporting. Immunogenicity was assessed by ex vivo interferon-gamma ELISpot assay of peripheral T cells. OS and RFS were reported by Kaplan-Meier survival analysis and compared by log rank test between groups. Results: Of the 11 identified patients, nine were male (82%) and two were female (18%), with a median age of 64 years. All patients were high risk by molecular testing, the majority by Castle Bioscience DecisionDx-UM. Five were PRAME positive, five PRAME negative, and one not reported. In the cohort, three patients had uveal melanoma recurrence and one subject died from metastatic disease during the evaluation period. The 5-year RFS and OS were 71% (95% CI 43-100) and 80% (95% CI 52-100), respectively. Two patients experienced dose-limiting, grade 3 toxicities to the vaccine, requiring early trial discontinuation, including one grade 3 injection-site reaction and one grade 3 uveitis. Nine patients experienced grade 1-2 toxicities, mostly injection-site reactions and constitutional symptoms. Of nine patients with available immunogenicity data, five (55%) had direct antigen-mediated immune response to vaccine. Two patients’ responses are pending. Patients with immunogenic response had a non-significant trend toward better RFS and OS (both p = 0.22). The 3-year RFS and OS were 100% for subjects with T cell response and the RFS and OS were 50% (95% CI 13-100) for patients without T cell response. Two of the relapsed patients did not have an immune response to vaccine, and response data were not available for the third. Conclusions: Melanoma polypeptide vaccines are immunogenic and safe in patients with uveal melanoma. Our early data suggests the possibility of early benefit with direct antigen response, though longer follow up and further study will be needed to investigate these findings.
Background: Safe, effective, inexpensive treatment for COVID-19 is an urgent unmet medical need. ... more Background: Safe, effective, inexpensive treatment for COVID-19 is an urgent unmet medical need. Zinc and resveratrol have been reported to have antiviral activity and resveratrol may increase zinc activity at the site of replication by increasing intracellular zinc concentrations.<br><br>Methods: A 1:1 randomized, placebo-controlled trial of zinc 150 mg plus resveratrol 4 grams daily for 5 days versus placebos in SARS-CoV-2 positive outpatients was carried out 9/21/2020 – 1/22/2021 in Seattle, Washington. Patients were enrolled within four days of testing positive if they had no chronic liver, kidney, or lung disease and did not have hypoxia requiring supplemental oxygen. Viral shedding was followed at days 1-7,10, and 14 with patient self-collected nasal and saliva samples by measuring qRT-PCR for SARS-CoV-2 N gene. Patients filled out a web-based questionnaire on days 1-14 to report symptoms, vital signs and adherence to study intervention.<br><br>Findings: 45 persons consented to enrollment, and 30 (14 treatment;16 placebo) had ≥1 day of the protocol treatment and were evaluable for the primary or secondary outcome. There was no difference in viral shedding between groups. There was a non-statistically significant trend toward more rapid decrease in symptoms in the treatment group. Viral shedding was similar between patient self-collected mid-turbinate nasal swabs and expectorated saliva samples with good correlation, R= 0.67, p<0.001.<br><br>Interpretation: SARS-CoV-2 shedding and COVID-19 symptoms were not statistically significantly decreased by treatment in this small Phase 1/2 pilot study. Viral shedding correlates well between patient-obtained home nasal swab and saliva sampling.<br><br>Clinical Trial Registration Details: Clinical Trials.gov NCT04542993<br><br>Funding Information: This study was funded by the Kaplan Cancer Research Fund.<br><br>Declaration of Interests: JDG reports research support from Lilly, Gilead, and Regeneron;grants from the NIH, BARDA (administered by Merck) and Viracor to his institution;and speaker or consulting personal fees from Lilly, Gilead, and Mylan. All other authors report no conflicts of interest.<br><br>Ethics Approval Statement: The study was approved by the Providence St Joseph Health Care System IRB. Informed consent was obtained with electronic consent forms by the principal investigator.
Background. Survival and other outcomes of nonagenarians undergoing transcatheter aortic valve re... more Background. Survival and other outcomes of nonagenarians undergoing transcatheter aortic valve replacement (TAVR) in the Medicare population are unclear. Methods. Patients aged 65 years and older who underwent TAVR from November 2011 through 2013 were considered for inclusion. Results. The study consisted of 18,283 patients and 19.3% were aged 90 years or older. Compared with patients younger than 90 years, patients 90 years or older were less likely to have a number of comorbidities, including previous myocardial infarction (17.5% versus 21.8%), previous coronary artery bypass grafting (20.0% versus 35.0%), and chronic obstructive pulmonary disease (25.4% versus 39.0%) among others. The 30-day and 1-year mortality rates were 8.4% versus 5.9% (p [ 0.0001) and 25.4% versus 21.5% (p [ 0.0001) in the older and younger groups, respectively (odds ratio [OR] 1.47, 95% confidence interval [CI]: 1.28 to 1.70, p [ 0.0001). Patients 90 years and older were more likely to undergo pacemaker insertion (11.1% versus 8.3%, p [ 0.0001). Among nonagenarians, compared with the transapical group, patients undergoing transfemoral TAVR had lower 30-day (7.2% versus 13.6%, p [ 0.0001) and 1-year (23.8% versus 31.6%, p [ 0.0001) mortality rates, were more likely to be discharged home (54.4% versus 34.1%, p [ 0.0001), and had lower 30-day readmission rates (23.8% versus 31.8%, p [ 0.0001). After adjustment for patient characteristics, transapical TAVR was an independent predictor of 30-day mortality rate (OR 1.94, 95% CI: 1.48 to 2.56, p [ 0.0001) and readmission (OR 1.46, 95% CI: 1.19 to 1.80, p [ 0.0003). Conclusions. In patients undergoing TAVR, although 30-day and 1-year mortality rates were slightly worse for nonagenarians than their younger counterparts, long-term survival was still encouraging, with 75% of nonagenarians living to 1 year. Transapical TAVR was associated with worse outcomes in nonagenarians.
Objective: This study aims to evaluate the potential impact of addressing goals-of-care (GOC) wit... more Objective: This study aims to evaluate the potential impact of addressing goals-of-care (GOC) with selected patients in the emergency department (ED), GOC documentation, hospital utilization, and patient satisfaction. Method: This is a single-center, retrospective, and prospective, observational convenience-sample study. ED registered nurses (ED RNs) received standardized GOC conversation training. Their selection criteria included a selection interview, a minimum of 3 years of ED clinical experience, and current employment in the ED. ED RNs used a standardized GOC questionnaire. Patient inclusion criteria included age ≥18 years and one or more of the following: chronic kidney disease ≥ stage III, congestive heart failure with an ejection fraction ≤ 40%, chronic obstructive pulmonary disease with home oxygen use, and/or malignancy with metastasis. GOC conversations were recorded in the electronic medical record (EMR). Physician Orders for Life-Sustaining Treatment (POLST) forms were completed as appropriate. Select individual patient data for the 12 months prior to the conversation were compared with the following 12 months. Results: Over 6 months, 94 of 133 patients who were approached consented to the GOC discussion with the RN. All 94 enrolled patients had their GOC recorded into the EMR. One-third already had a completed POLST form prior to ED arrival. 50% without a POLST on ED arrival left with a completed POLST. Eighty-four patients survived the index visit and 46 patients survived to study completion. Patient satisfaction with the interaction was high: In the cohort who survived past the index visit, 95% rated their experience at 4/5 or 5/5 (Likert scale, 5: strongly agree, 1: strongly disagree). In the survival-to-study completion cohort, 100% rated their experience as 4/5 or 5/5. Subsequent median ED visits decreased by 15% (1.0-4.0 interquartile range). There were no statistically significant changes in hospitalizations (both decreased by 25%, 0-3.0) or intensive care unit admissions (0%, 0-0). Conclusions: An ED RN-led GOC conversation had high patient satisfaction and 100% GOC documentation in the EMR. There was a significant increase in ED POLST form completion. There were no significant changes noted in subsequent hospitalizations, length of hospitalization, or intensive care unit utilization.
Background: Safe, effective, and inexpensive treatment for COVID-19 is an urgent unmet medical ne... more Background: Safe, effective, and inexpensive treatment for COVID-19 is an urgent unmet medical need. Zinc and resveratrol have been reported to have antiviral activity, and resveratrol may increase zinc activity at the site of replication by increasing intracellular zinc concentrations.Methods: A 1:1 randomized, placebo-controlled trial of zinc 150 mg plus resveratrol 4 g daily for 5 days versus placebos in outpatients with SARS-CoV-2 was carried out from 9/21/2020–1/22/2021 in Seattle, Washington. Viral shedding was followed with patient self-collected nasal and saliva samples by measuring qRT-PCR for SARS-CoV-2 N gene days 1–7, 10, and 14. Patients filled out a web-based questionnaire on days 1–14 to report symptoms, vital signs and adherence to the study intervention. The study was posted as Clinical Trials.gov NCT04542993 on 9 September 2020.Results: A total of 30 participants (14 treatment; 16 placebos) had ≥1 day of the protocol treatment and were evaluable for the primary or ...
Background. Estimated glomerular filtration rate (eGFR) before coronary artery bypass graft (CABG... more Background. Estimated glomerular filtration rate (eGFR) before coronary artery bypass graft (CABG) surgery is a key risk factor of in-hospital mortality. However, in patients with normal renal function before CABG, acute kidney injury develops after the procedure, making postoperative renal function assessment necessary for evaluation. Postoperative eGFR and its association with long-term survival have not been well studied. Methods. We studied 13,593 consecutive CABG patients in northern New England from 2001 to 2006. Patients with preoperative dialysis were excluded. Data were linked to the Social Security Association Death Master File to assess long-term survival. Kaplan-Meier and log-rank techniques were used. Patients were stratified by established categories of postoperative eGFR (90 or greater, 60 to 89, 30 to 59, 15 to 29, and less than 15 mL • min ؊1 • 1.73 m ؊2). Results. Median follow-up was 2.8 years (mean, 2.7; range, 0 to 5.5). Patients with moderate to severe acute kidney injury (less than 60) after CABG had significantly worse survival than patients with little or no acute kidney injury (90 or greater). Conclusions. Patients having moderate to severe acute kidney injury after CABG surgery had worse 5-year survival compared with patients who had normal or near-normal renal function.
Catheterization and Cardiovascular Interventions, 2019
BackgroundIntrathoracic complications (ITC) requiring emergency surgical intervention occur durin... more BackgroundIntrathoracic complications (ITC) requiring emergency surgical intervention occur during transcatheter aortic valve replacement (TAVR).ObjectivesCharacterize the incidence, outcomes and predictors of ITC in a large cohort of transfemoral (TF) TAVR cases over a 5 year period.MethodsRetrospective registry and chart review of all nonclinical trial TF‐TAVR patients from seven centers within one hospital system from 2012–2016. ITC were defined as cardiac perforation, new or worsening pericardial effusion/tamponade, annular rupture, thoracic aortic injury, aortic valve dislodgement, and coronary artery occlusion. Procedural and 30‐day outcomes and 1‐year mortality were compared between ITC and no ITC patients. Multivariable logistic regression was used to identify predictors of ITC.ResultsOver the study period, 1,581 patients had TF‐TAVR and 68 ITC occurred in 46 patients (2.9%). The most common ITCs were pericardial effusion/tamponade (59%), cardiac perforation (33%), and valve...
608 Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is der... more 608 Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is derived from a background of chronic inflammation from both viral and environmental factors. Recent data indicates that immune therapy efficacy is improved in virally mediated HCC. We sought to investigate what impact HCC etiology has on outcomes in patients treated with yttrium-90 (Y90). Methods: We conducted a retrospective review of patients with HCC treated at our institution with Y90 radiotherapy from 2005-2021. Clinical and treatment characteristics were recorded, including: age, stage, HCC etiology, performance status, Child Pugh class, liver mass/volume treated, dose, prior therapy, imaging characteristics and basic labs. Univariable (UVA) and multivariable analyses (MVA) were conducted to identify prognostic factors for local control (LC) and overall survival (OS) following Y90. Results: 67 patients and 196 distinct tumors treated with Y90 were identified. Median prescription dose ...
Objectives. This study was conducted to determine why heart teams recommended transcatheter aorti... more Objectives. This study was conducted to determine why heart teams recommended transcatheter aortic valve replacement (TAVR) versus surgical AVR (SAVR) for patients at low predicted risk of mortality (PROM) and describe outcomes of these cases. Background. Historically, referral to TAVR was based predominately on the Society of Thoracic Surgeons (STS) risk model’s PROM >3%. In selected cases, heart teams had latitude to overrule these scores. The clinical reasons and outcomes for these cases are unclear. Methods. Retrospective data were gathered for all TAVR and SAVR cases conducted by 9 hospitals between 2013 and 2017. Results. Cases included TAVR patients with STS PROM >3% (n = 2,711) and ≤3% (n = 415) and SAVR with STS PROM ≤3% (n = 1,438). Leading reasons for recommending TAVR in the PROM ≤3% group were frailty (57%), hostile chest (22%), severe lung disease (16%), and morbid obesity (13%), and 44% of cases had multiple reasons. Most postoperative and 30-day outcomes were s...
Statistics is a rapidly growing field utilizing thousands of data analysis functions, though a re... more Statistics is a rapidly growing field utilizing thousands of data analysis functions, though a relatively few are used in the majority of cardiac surgical studies. Dr. Wechsler recently published a list of the statistical terms which are important for cardiothoracic surgeons to be familiar with. These can be grouped into 3 categories: General concepts; Summary and test statistics; and Special techniques. The last category includes three techniques which are widely used to describe the long-term results of heart valve series: Hazard functions, Kaplan-Meier event-free curves, and "Actual" event-free curves. Some conclusions from a review of these techniques are: (1) an event with a non-constant hazard should not be described using "Linearized" rates (the Weibull distribution adds a parameter to accommodate changing hazard); (2) for non-fatal events, "Actual" analysis provides the true event probability, which the Kaplan-Meier overestimates. These methods ...
The Journal of Thoracic and Cardiovascular Surgery, 2014
Objective: A number of established regional quality improvement collaboratives have partnered to ... more Objective: A number of established regional quality improvement collaboratives have partnered to assess and improve care across their regions under the umbrella of the Cardiac Surgery Quality Improvement (IMPROVE) Network. The first effort of the IMPROVE Network has been to assess regional differences in potentially discretionary transfusions (<3 units red blood cells [RBCs]). Methods: We examined 11,200 patients undergoing isolated nonemergent coronary artery bypass graft surgery across 56 medical centers in 4 IMPROVE Network regions between January 2008 and June 2012. Each center submitted the most recent 200 patients who received 0, 1, or 2 units of RBC transfusion during the index admission. Patient and disease characteristics, intraoperative practices, and percentage of patients receiving RBC transfusions were collected. Region-specific transfusion rates were calculated after adjusting for pre-and intraoperative factors among region-specific centers. Results: There were small but significant differences in patient case mix across regions. RBC transfusions of 1 or 2 units occurred among 25.2% of coronary artery bypass graft procedures (2826 out of 11,200). Significant variation in the number of RBC units used existed across regions (no units, 74.8% [min-max, 70.0%-84.1%], 1 unit, 9.7% [min-max, 5.1%-11.8%], 2 units, 15.5% [min-max, 9.1%-18.2%]; P <.001). Variation in overall transfusion rates remained after adjustment (9.1%-31.7%; P <.001). Conclusions: Delivery of small volumes of RBC transfusions was common, yet varied across geographic regions. These data suggest that differences in regional practice environments, including transfusion triggers and anemia management, may contribute to variability in RBC transfusion rates.
The Journal of Thoracic and Cardiovascular Surgery, 2019
Objective: Risk-adjusted operative mortality is a key quality measure for isolated coronary arter... more Objective: Risk-adjusted operative mortality is a key quality measure for isolated coronary artery bypass grafting. Through a multicenter quality improvement initiative, we sought to improve this measure at 14 surgical programs within a large and geographically dispersed health care system. Methods: Observed mortality and combined mortality/morbidity rates for isolated coronary artery bypass grafting were collected from January 2014 to June 2017. Expected mortality and mortality/morbidity rates were determined using the Society of Thoracic Surgeons risk models. The observed/expected ratios during the baseline (2014) and final 12-month outcome period were compared. The quality improvement intervention was multifaceted and surgeon led, and consisted of (1) regular sharing of unblinded data, (2) standardized quality improvement processes, (3) regular system-wide quality improvement meetings, (4) annual observed/expected mortality targets, (5) identification of underperforming institutions and creation of nonpunitive quality improvement action plans, and (6) implementation of checklists to drive perioperative care standardization. Results: The observed/expected ratio of mortality was 1.19 during the baseline period and decreased to 0.59 for the outcome period (P ¼ .004) without a change in expected mortality or case volume. The observed/expected ratio decreased for mortality/morbidity, and mortality without antecedent morbidity was almost eliminated. Conclusions: A significant and clinically meaningful 50% reduction in the observed/expected ratio for isolated coronary artery bypass grafting mortality was observed during a multifaceted quality improvement initiative across a large multicenter health care system. Morbidity also decreased. Keys to success included surgeon leadership and engagement, frequent unblinded data sharing, development of standardized quality improvement processes, improvement and standardization of care delivery, setting of quality improvement targets, and a shared vision for improved patient outcomes.
Background: Patients with small aortic annuli (SAA) are prone to higher post-transcatheter aortic... more Background: Patients with small aortic annuli (SAA) are prone to higher post-transcatheter aortic valve replacement (TAVR) transvalvular gradients and development of prosthesis-patient mismatch (PPM). In many patients with SAA, the choice of TAVR valve commonly involves choosing between the 26-mm Medtronic Evolut 2 (ME26) or the 23-mm Edwards Sapien 3 valve (ES23). We compared echocardiographic and clinical outcomes in patients with SAA undergoing TAVR with either valve. Methods: We queried the Providence St. Joseph Health Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry database for patients undergoing TAVR with either the ES23 or ME26 between July 2015 and December 2018 at 11 hospitals. Post-TAVR echocardiographic and clinical results in-hospital, at 1 month, and at 1 year were examined. High gradient (HG) was defined as mean gradient (MG) ≥20 mm Hg. Results: We identified 1162 patients with SAA undergoing TAVR with either the ME26 (n = 233) or ES23 valve (n = 929). Baseline characteristics between groups were similar. At 1 month, the ME26 was associated with a lower MG than the ES23 (7.7 ± 4.7 mm Hg vs 13.1 ± 4.9 mm Hg; P<.001) and moderate or severe PPM (11% and 3% vs 27% and 13%; P<.001). Occurrence of HG at 1 year was lower with the ME26 valve vs the ES23 valve (0% vs 15%; P<.001). In-hospital and follow-up clinical outcomes to 1 year were similar for both groups. Conclusion: TAVR in SAA with the ME26 is associated with lower incidence of HG or PPM compared with the ES23. While clinical outcomes at 1 year were similar, the long-term implications of these findings remain unknown.
Receiver operating characteristic (ROC) curve analysis is a useful method to measure the ability ... more Receiver operating characteristic (ROC) curve analysis is a useful method to measure the ability of a clinical risk model to discriminate between hospital deaths and survivors. Its use in medicine originated as a method for synthesizing the specificity and sensitivity of diagnostic tests across a spectrum of possible cut points. The area under the ROC curve can be interpreted as
e21509 Background: Due to biologic differences, uveal melanoma patients are often excluded from c... more e21509 Background: Due to biologic differences, uveal melanoma patients are often excluded from clinical trials for cutaneous melanoma; however, many antigens are shared between the two melanoma subtypes. Thus, our vaccine trials at the University of Virginia (UVA) have allowed enrollment of high-risk uveal melanoma patients, who have substantial risk of relapse without FDA-approved adjuvant therapy available. For the present study, we hypothesized that the vaccines would be well-tolerated and immunogenic in this population. We examined the clinical, immunogenicity and safety outcomes of subjects with uveal melanoma enrolled in our adjuvant vaccine clinical studies. Methods: Patients were identified through participation in an adjuvant vaccine study at UVA between 2012-2022. Ten patients received the 6-Melanoma-Helper Peptide (6-MHP) vaccine through Mel-65 and Mel-66 clinical trials (NCT03617328 and NCT04364230) and one patient received the 12-peptide MELITAC vaccine through the Mel-58 clinical trial (NCT01585350). Clinical outcomes included relapse-free (RFS) and overall survival (OS) and trial toxicity reporting. Immunogenicity was assessed by ex vivo interferon-gamma ELISpot assay of peripheral T cells. OS and RFS were reported by Kaplan-Meier survival analysis and compared by log rank test between groups. Results: Of the 11 identified patients, nine were male (82%) and two were female (18%), with a median age of 64 years. All patients were high risk by molecular testing, the majority by Castle Bioscience DecisionDx-UM. Five were PRAME positive, five PRAME negative, and one not reported. In the cohort, three patients had uveal melanoma recurrence and one subject died from metastatic disease during the evaluation period. The 5-year RFS and OS were 71% (95% CI 43-100) and 80% (95% CI 52-100), respectively. Two patients experienced dose-limiting, grade 3 toxicities to the vaccine, requiring early trial discontinuation, including one grade 3 injection-site reaction and one grade 3 uveitis. Nine patients experienced grade 1-2 toxicities, mostly injection-site reactions and constitutional symptoms. Of nine patients with available immunogenicity data, five (55%) had direct antigen-mediated immune response to vaccine. Two patients’ responses are pending. Patients with immunogenic response had a non-significant trend toward better RFS and OS (both p = 0.22). The 3-year RFS and OS were 100% for subjects with T cell response and the RFS and OS were 50% (95% CI 13-100) for patients without T cell response. Two of the relapsed patients did not have an immune response to vaccine, and response data were not available for the third. Conclusions: Melanoma polypeptide vaccines are immunogenic and safe in patients with uveal melanoma. Our early data suggests the possibility of early benefit with direct antigen response, though longer follow up and further study will be needed to investigate these findings.
Background: Safe, effective, inexpensive treatment for COVID-19 is an urgent unmet medical need. ... more Background: Safe, effective, inexpensive treatment for COVID-19 is an urgent unmet medical need. Zinc and resveratrol have been reported to have antiviral activity and resveratrol may increase zinc activity at the site of replication by increasing intracellular zinc concentrations.<br><br>Methods: A 1:1 randomized, placebo-controlled trial of zinc 150 mg plus resveratrol 4 grams daily for 5 days versus placebos in SARS-CoV-2 positive outpatients was carried out 9/21/2020 – 1/22/2021 in Seattle, Washington. Patients were enrolled within four days of testing positive if they had no chronic liver, kidney, or lung disease and did not have hypoxia requiring supplemental oxygen. Viral shedding was followed at days 1-7,10, and 14 with patient self-collected nasal and saliva samples by measuring qRT-PCR for SARS-CoV-2 N gene. Patients filled out a web-based questionnaire on days 1-14 to report symptoms, vital signs and adherence to study intervention.<br><br>Findings: 45 persons consented to enrollment, and 30 (14 treatment;16 placebo) had ≥1 day of the protocol treatment and were evaluable for the primary or secondary outcome. There was no difference in viral shedding between groups. There was a non-statistically significant trend toward more rapid decrease in symptoms in the treatment group. Viral shedding was similar between patient self-collected mid-turbinate nasal swabs and expectorated saliva samples with good correlation, R= 0.67, p<0.001.<br><br>Interpretation: SARS-CoV-2 shedding and COVID-19 symptoms were not statistically significantly decreased by treatment in this small Phase 1/2 pilot study. Viral shedding correlates well between patient-obtained home nasal swab and saliva sampling.<br><br>Clinical Trial Registration Details: Clinical Trials.gov NCT04542993<br><br>Funding Information: This study was funded by the Kaplan Cancer Research Fund.<br><br>Declaration of Interests: JDG reports research support from Lilly, Gilead, and Regeneron;grants from the NIH, BARDA (administered by Merck) and Viracor to his institution;and speaker or consulting personal fees from Lilly, Gilead, and Mylan. All other authors report no conflicts of interest.<br><br>Ethics Approval Statement: The study was approved by the Providence St Joseph Health Care System IRB. Informed consent was obtained with electronic consent forms by the principal investigator.
Background. Survival and other outcomes of nonagenarians undergoing transcatheter aortic valve re... more Background. Survival and other outcomes of nonagenarians undergoing transcatheter aortic valve replacement (TAVR) in the Medicare population are unclear. Methods. Patients aged 65 years and older who underwent TAVR from November 2011 through 2013 were considered for inclusion. Results. The study consisted of 18,283 patients and 19.3% were aged 90 years or older. Compared with patients younger than 90 years, patients 90 years or older were less likely to have a number of comorbidities, including previous myocardial infarction (17.5% versus 21.8%), previous coronary artery bypass grafting (20.0% versus 35.0%), and chronic obstructive pulmonary disease (25.4% versus 39.0%) among others. The 30-day and 1-year mortality rates were 8.4% versus 5.9% (p [ 0.0001) and 25.4% versus 21.5% (p [ 0.0001) in the older and younger groups, respectively (odds ratio [OR] 1.47, 95% confidence interval [CI]: 1.28 to 1.70, p [ 0.0001). Patients 90 years and older were more likely to undergo pacemaker insertion (11.1% versus 8.3%, p [ 0.0001). Among nonagenarians, compared with the transapical group, patients undergoing transfemoral TAVR had lower 30-day (7.2% versus 13.6%, p [ 0.0001) and 1-year (23.8% versus 31.6%, p [ 0.0001) mortality rates, were more likely to be discharged home (54.4% versus 34.1%, p [ 0.0001), and had lower 30-day readmission rates (23.8% versus 31.8%, p [ 0.0001). After adjustment for patient characteristics, transapical TAVR was an independent predictor of 30-day mortality rate (OR 1.94, 95% CI: 1.48 to 2.56, p [ 0.0001) and readmission (OR 1.46, 95% CI: 1.19 to 1.80, p [ 0.0003). Conclusions. In patients undergoing TAVR, although 30-day and 1-year mortality rates were slightly worse for nonagenarians than their younger counterparts, long-term survival was still encouraging, with 75% of nonagenarians living to 1 year. Transapical TAVR was associated with worse outcomes in nonagenarians.
Objective: This study aims to evaluate the potential impact of addressing goals-of-care (GOC) wit... more Objective: This study aims to evaluate the potential impact of addressing goals-of-care (GOC) with selected patients in the emergency department (ED), GOC documentation, hospital utilization, and patient satisfaction. Method: This is a single-center, retrospective, and prospective, observational convenience-sample study. ED registered nurses (ED RNs) received standardized GOC conversation training. Their selection criteria included a selection interview, a minimum of 3 years of ED clinical experience, and current employment in the ED. ED RNs used a standardized GOC questionnaire. Patient inclusion criteria included age ≥18 years and one or more of the following: chronic kidney disease ≥ stage III, congestive heart failure with an ejection fraction ≤ 40%, chronic obstructive pulmonary disease with home oxygen use, and/or malignancy with metastasis. GOC conversations were recorded in the electronic medical record (EMR). Physician Orders for Life-Sustaining Treatment (POLST) forms were completed as appropriate. Select individual patient data for the 12 months prior to the conversation were compared with the following 12 months. Results: Over 6 months, 94 of 133 patients who were approached consented to the GOC discussion with the RN. All 94 enrolled patients had their GOC recorded into the EMR. One-third already had a completed POLST form prior to ED arrival. 50% without a POLST on ED arrival left with a completed POLST. Eighty-four patients survived the index visit and 46 patients survived to study completion. Patient satisfaction with the interaction was high: In the cohort who survived past the index visit, 95% rated their experience at 4/5 or 5/5 (Likert scale, 5: strongly agree, 1: strongly disagree). In the survival-to-study completion cohort, 100% rated their experience as 4/5 or 5/5. Subsequent median ED visits decreased by 15% (1.0-4.0 interquartile range). There were no statistically significant changes in hospitalizations (both decreased by 25%, 0-3.0) or intensive care unit admissions (0%, 0-0). Conclusions: An ED RN-led GOC conversation had high patient satisfaction and 100% GOC documentation in the EMR. There was a significant increase in ED POLST form completion. There were no significant changes noted in subsequent hospitalizations, length of hospitalization, or intensive care unit utilization.
Background: Safe, effective, and inexpensive treatment for COVID-19 is an urgent unmet medical ne... more Background: Safe, effective, and inexpensive treatment for COVID-19 is an urgent unmet medical need. Zinc and resveratrol have been reported to have antiviral activity, and resveratrol may increase zinc activity at the site of replication by increasing intracellular zinc concentrations.Methods: A 1:1 randomized, placebo-controlled trial of zinc 150 mg plus resveratrol 4 g daily for 5 days versus placebos in outpatients with SARS-CoV-2 was carried out from 9/21/2020–1/22/2021 in Seattle, Washington. Viral shedding was followed with patient self-collected nasal and saliva samples by measuring qRT-PCR for SARS-CoV-2 N gene days 1–7, 10, and 14. Patients filled out a web-based questionnaire on days 1–14 to report symptoms, vital signs and adherence to the study intervention. The study was posted as Clinical Trials.gov NCT04542993 on 9 September 2020.Results: A total of 30 participants (14 treatment; 16 placebos) had ≥1 day of the protocol treatment and were evaluable for the primary or ...
Background. Estimated glomerular filtration rate (eGFR) before coronary artery bypass graft (CABG... more Background. Estimated glomerular filtration rate (eGFR) before coronary artery bypass graft (CABG) surgery is a key risk factor of in-hospital mortality. However, in patients with normal renal function before CABG, acute kidney injury develops after the procedure, making postoperative renal function assessment necessary for evaluation. Postoperative eGFR and its association with long-term survival have not been well studied. Methods. We studied 13,593 consecutive CABG patients in northern New England from 2001 to 2006. Patients with preoperative dialysis were excluded. Data were linked to the Social Security Association Death Master File to assess long-term survival. Kaplan-Meier and log-rank techniques were used. Patients were stratified by established categories of postoperative eGFR (90 or greater, 60 to 89, 30 to 59, 15 to 29, and less than 15 mL • min ؊1 • 1.73 m ؊2). Results. Median follow-up was 2.8 years (mean, 2.7; range, 0 to 5.5). Patients with moderate to severe acute kidney injury (less than 60) after CABG had significantly worse survival than patients with little or no acute kidney injury (90 or greater). Conclusions. Patients having moderate to severe acute kidney injury after CABG surgery had worse 5-year survival compared with patients who had normal or near-normal renal function.
Catheterization and Cardiovascular Interventions, 2019
BackgroundIntrathoracic complications (ITC) requiring emergency surgical intervention occur durin... more BackgroundIntrathoracic complications (ITC) requiring emergency surgical intervention occur during transcatheter aortic valve replacement (TAVR).ObjectivesCharacterize the incidence, outcomes and predictors of ITC in a large cohort of transfemoral (TF) TAVR cases over a 5 year period.MethodsRetrospective registry and chart review of all nonclinical trial TF‐TAVR patients from seven centers within one hospital system from 2012–2016. ITC were defined as cardiac perforation, new or worsening pericardial effusion/tamponade, annular rupture, thoracic aortic injury, aortic valve dislodgement, and coronary artery occlusion. Procedural and 30‐day outcomes and 1‐year mortality were compared between ITC and no ITC patients. Multivariable logistic regression was used to identify predictors of ITC.ResultsOver the study period, 1,581 patients had TF‐TAVR and 68 ITC occurred in 46 patients (2.9%). The most common ITCs were pericardial effusion/tamponade (59%), cardiac perforation (33%), and valve...
608 Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is der... more 608 Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is derived from a background of chronic inflammation from both viral and environmental factors. Recent data indicates that immune therapy efficacy is improved in virally mediated HCC. We sought to investigate what impact HCC etiology has on outcomes in patients treated with yttrium-90 (Y90). Methods: We conducted a retrospective review of patients with HCC treated at our institution with Y90 radiotherapy from 2005-2021. Clinical and treatment characteristics were recorded, including: age, stage, HCC etiology, performance status, Child Pugh class, liver mass/volume treated, dose, prior therapy, imaging characteristics and basic labs. Univariable (UVA) and multivariable analyses (MVA) were conducted to identify prognostic factors for local control (LC) and overall survival (OS) following Y90. Results: 67 patients and 196 distinct tumors treated with Y90 were identified. Median prescription dose ...
Objectives. This study was conducted to determine why heart teams recommended transcatheter aorti... more Objectives. This study was conducted to determine why heart teams recommended transcatheter aortic valve replacement (TAVR) versus surgical AVR (SAVR) for patients at low predicted risk of mortality (PROM) and describe outcomes of these cases. Background. Historically, referral to TAVR was based predominately on the Society of Thoracic Surgeons (STS) risk model’s PROM >3%. In selected cases, heart teams had latitude to overrule these scores. The clinical reasons and outcomes for these cases are unclear. Methods. Retrospective data were gathered for all TAVR and SAVR cases conducted by 9 hospitals between 2013 and 2017. Results. Cases included TAVR patients with STS PROM >3% (n = 2,711) and ≤3% (n = 415) and SAVR with STS PROM ≤3% (n = 1,438). Leading reasons for recommending TAVR in the PROM ≤3% group were frailty (57%), hostile chest (22%), severe lung disease (16%), and morbid obesity (13%), and 44% of cases had multiple reasons. Most postoperative and 30-day outcomes were s...
Statistics is a rapidly growing field utilizing thousands of data analysis functions, though a re... more Statistics is a rapidly growing field utilizing thousands of data analysis functions, though a relatively few are used in the majority of cardiac surgical studies. Dr. Wechsler recently published a list of the statistical terms which are important for cardiothoracic surgeons to be familiar with. These can be grouped into 3 categories: General concepts; Summary and test statistics; and Special techniques. The last category includes three techniques which are widely used to describe the long-term results of heart valve series: Hazard functions, Kaplan-Meier event-free curves, and "Actual" event-free curves. Some conclusions from a review of these techniques are: (1) an event with a non-constant hazard should not be described using "Linearized" rates (the Weibull distribution adds a parameter to accommodate changing hazard); (2) for non-fatal events, "Actual" analysis provides the true event probability, which the Kaplan-Meier overestimates. These methods ...
The Journal of Thoracic and Cardiovascular Surgery, 2014
Objective: A number of established regional quality improvement collaboratives have partnered to ... more Objective: A number of established regional quality improvement collaboratives have partnered to assess and improve care across their regions under the umbrella of the Cardiac Surgery Quality Improvement (IMPROVE) Network. The first effort of the IMPROVE Network has been to assess regional differences in potentially discretionary transfusions (<3 units red blood cells [RBCs]). Methods: We examined 11,200 patients undergoing isolated nonemergent coronary artery bypass graft surgery across 56 medical centers in 4 IMPROVE Network regions between January 2008 and June 2012. Each center submitted the most recent 200 patients who received 0, 1, or 2 units of RBC transfusion during the index admission. Patient and disease characteristics, intraoperative practices, and percentage of patients receiving RBC transfusions were collected. Region-specific transfusion rates were calculated after adjusting for pre-and intraoperative factors among region-specific centers. Results: There were small but significant differences in patient case mix across regions. RBC transfusions of 1 or 2 units occurred among 25.2% of coronary artery bypass graft procedures (2826 out of 11,200). Significant variation in the number of RBC units used existed across regions (no units, 74.8% [min-max, 70.0%-84.1%], 1 unit, 9.7% [min-max, 5.1%-11.8%], 2 units, 15.5% [min-max, 9.1%-18.2%]; P <.001). Variation in overall transfusion rates remained after adjustment (9.1%-31.7%; P <.001). Conclusions: Delivery of small volumes of RBC transfusions was common, yet varied across geographic regions. These data suggest that differences in regional practice environments, including transfusion triggers and anemia management, may contribute to variability in RBC transfusion rates.
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