Physics Residency Program

The POD cast focused on the two-year accredited medical physics residency at Jefferson. This program is one of the oldest clinical physicist training programs in the country and one of the earliest hub and spoke programs with an spoke program in Christiana. The Jefferson medical physics residency currently trains six residents. The director and associate director of the program discussed the program and requirements. Two current senior residents, and one former resident who is now a faculty member talked about their journey into medical physics from undergraduate to current state including clinical experience and their educational process. Each physicist gives opinions on the complexity of the field and level of math skills necessary. Finally, all members discussed our current interesting projects occurring in the clinic. Podcast: 30:0

Tunable energy transfer from d10 heterobimetallic dicyanide(I) donor ions to terbium(III) acceptor ions in luminescent Tb[AgxAu1−x(CN)2]3 (x = 0 → 1)

We report on the heterobimetallic system, Tb[AgxAu1−x(CN)2]3 (x = 0 → 1), in which sensitization of terbium luminescence occurs by energy transfer from [AgxAu1−x(CN)2]− donor excited states. The donor states have energies which are tunable and dependent on the Ag/Au stoichiometric ratio. We report on their use as donor systems with Tb(III) ions as acceptor ions in energy transfer studies. Luminescence results show that the mixed metal dicyanides with the higher silver loading have a better energy transfer efficiency than the pure and donors. The better energy transfer efficiency is due to the greater overlap between the donor emission and acceptor excitation

De Novo vs Acute-on-Chronic Presentations of Heart Failure-Related Cardiogenic Shock: Insights from the Critical Care Cardiology Trials Network Registry

BACKGROUND: Heart failure-related cardiogenic shock (HF-CS) accounts for an increasing proportion of cases of CS in contemporary cardiac intensive care units. Whether the chronicity of HF identifies distinct clinical profiles of HF-CS is unknown. METHODS AND RESULTS: We evaluated admissions to cardiac intensive care units for HF-CS in 28 centers using data from the Critical Care Cardiology Trials Network registry (2017-2020). HF-CS was defined as CS due to ventricular failure in the absence of acute myocardial infarction and was classified as de novo vs acute-on-chronic based on the absence or presence of a prior diagnosis of HF, respectively. Clinical features, resource use, and outcomes were compared among groups. Of 1405 admissions with HF-CS, 370 had de novo HF-CS (26.3%), and 1035 had acute-on-chronic HF-CS (73.7%). Patients with de novo HF-CS had a lower prevalence of hypertension, diabetes, coronary artery disease, atrial fibrillation, and chronic kidney disease (all P \u3c 0.01). Median Sequential Organ Failure Assessment (SOFA) scores were higher in those with de novo HF-CS (8; 25th-75th: 5-11) vs acute-on-chronic HF-CS (6; 25th-75th: 4-9, P \u3c 0.01), as was the proportion of Society of Cardiovascular Angiography and Intervention (SCAI) shock stage E (46.1% vs 26.1%, P \u3c 0.01). After adjustment for clinical covariates and preceding cardiac arrest, the risk of in-hospital mortality was higher in patients with de novo HF-CS than in those with acute-on-chronic HF-CS (adjusted hazard ratio 1.36, 95% confidence interval 1.05-1.75, P = 0.02). CONCLUSIONS: Despite having fewer comorbidities, patients with de novo HF-CS had more severe shock presentations and worse in-hospital outcomes. Whether HF disease chronicity is associated with time-dependent compensatory adaptations, unique pathobiological features and responses to treatment in patients presenting with HF-CS warrants further investigation

Demographics, Care Patterns, and Outcomes of Patients Admitted to Cardiac Intensive Care Units: The Critical Care Cardiology Trials Network Prospective North American Multicenter Registry of Cardiac Critical Illness.

Importance: Single-center and claims-based studies have described substantial changes in the landscape of care in the cardiac intensive care unit (CICU). Professional societies have recommended research to guide evidence-based CICU redesigns. Objective: To characterize patients admitted to contemporary, advanced CICUs. Design, Setting, and Participants: This study established the Critical Care Cardiology Trials Network (CCCTN), an investigator-initiated multicenter network of 16 advanced, tertiary CICUs in the United States and Canada. For 2 months in each CICU, data for consecutive admissions were submitted to the central data coordinating center (TIMI Study Group). The data were collected and analyzed between September 2017 and 2018. Main Outcomes and Measures: Demographics, diagnoses, management, and outcomes. Results: Of 3049 participants, 1132 (37.1%) were women, 797 (31.4%) were individuals of color, and the median age was 65 years (25th and 75th percentiles, 55-75 years). Between September 2017 and September 2018, 3310 admissions were included, among which 2557 (77.3%) were for primary cardiac problems, 337 (10.2%) for postprocedural care, 253 (7.7%) for mixed general and cardiac problems, and 163 (4.9%) for overflow from general medical ICUs. When restricted to the initial 2 months of medical CICU admissions for each site, the primary analysis population included 3049 admissions with a high burden of noncardiovascular comorbidities. The top 2 CICU admission diagnoses were acute coronary syndrome (969 [31.8%]) and heart failure (567 [18.6%]); however, the proportion of acute coronary syndrome was highly variable across centers (15%-57%). The primary indications for CICU care included respiratory insufficiency (814 [26.7%]), shock (643 [21.1%]), unstable arrhythmia (521 [17.1%]), and cardiac arrest (265 [8.7%]). Advanced CICU therapies or monitoring were required for 1776 patients (58.2%), including intravenous vasoactive medications (1105 [36.2%]), invasive hemodynamic monitoring (938 [30.8%]), and mechanical ventilation (652 [21.4%]). The overall CICU mortality rate was 8.3% (95% CI, 7.3%-9.3%). The CICU indications that were associated with the highest mortality rates were cardiac arrest (101 [38.1%]), cardiogenic shock (140 [30.6%]), and the need for renal replacement therapy (51 [34.5%]). Notably, patients admitted solely for postprocedural observation or frequent monitoring had a mortality rate of 0.2% to 0.4%. Conclusions and Relevance: In a contemporary network of tertiary care CICUs, respiratory failure and shock predominated indications for admission and carried a poor prognosis. While patterns of practice varied considerably between centers, a substantial, low-risk population was identified. Multicenter collaborative networks, such as the CCCTN, could be used to help redesign cardiac critical care and to test new therapeutic strategies

Epidemiology of Shock in Contemporary Cardiac Intensive Care Units.

Background Clinical investigations of shock in cardiac intensive care units (CICUs) have primarily focused on acute myocardial infarction (AMI) complicated by cardiogenic shock (AMICS). Few studies have evaluated the full spectrum of shock in contemporary CICUs. Methods and Results The Critical Care Cardiology Trials Network is a multicenter network of advanced CICUs in North America. Anytime between September 2017 and September 2018, each center (n=16) contributed a 2-month snap-shot of all consecutive medical admissions to the CICU. Data were submitted to the central coordinating center (TIMI Study Group, Boston, MA). Shock was defined as sustained systolic blood pressurecardiogenic, distributive, hypovolemic, or mixed. Among 3049 CICU admissions, 677 (22%) met clinical criteria for shock. Shock type was varied, with 66% assessed as cardiogenic shock (CS), 7% as distributive, 3% as hypovolemic, 20% as mixed, and 4% as unknown. Among patients with CS (n=450), 30% had AMICS, 18% had ischemic cardiomyopathy without AMI, 28% had nonischemic cardiomyopathy, and 17% had a cardiac cause other than primary myocardial dysfunction. Patients with mixed shock had cardiovascular comorbidities similar to patients with CS. The median CICU stay was 4.0 days (interquartile range [IQR], 2.5-8.1 days) for AMICS, 4.3 days (IQR, 2.1-8.5 days) for CS not related to AMI, and 5.8 days (IQR, 2.9-10.0 days) for mixed shock versus 1.9 days (IQR, 1.0-3.6) for patients without shock (

Clinical Practice Patterns in Temporary Mechanical Circulatory Support for Shock in the Critical Care Cardiology Trials Network (CCCTN) Registry.

BACKGROUND: Temporary mechanical circulatory support (MCS) devices provide hemodynamic assistance for shock refractory to pharmacological treatment. Most registries have focused on single devices or specific etiologies of shock, limiting data regarding overall practice patterns with temporary MCS in cardiac intensive care units. METHODS: The CCCTN (Critical Care Cardiology Trials Network) is a multicenter network of tertiary CICUs in North America. Between September 2017 and September 2018, each center (n=16) contributed a 2-month snapshot of consecutive medical CICU admissions. RESULTS: Of the 270 admissions using temporary MCS, 33% had acute myocardial infarction-related cardiogenic shock (CS), 31% had CS not related to acute myocardial infarction, 11% had mixed shock, and 22% had an indication other than shock. Among all 585 admissions with CS or mixed shock, 34% used temporary MCS during the CICU stay with substantial variation between centers (range: 17%-50%). The most common temporary MCS devices were intraaortic balloon pumps (72%), Impella (17%), and veno-arterial extracorporeal membrane oxygenation (11%), although intraaortic balloon pump use also varied between centers (range: 40%-100%). Patients managed with intraaortic balloon pump versus other forms of MCS (advanced MCS) had lower Sequential Organ Failure Assessment scores and less severe metabolic derangements. Illness severity was similar at high- versus low-MCS utilizing centers and at centers with more advanced MCS use. CONCLUSIONS: There is wide variation in the use of temporary MCS among patients with shock in tertiary CICUs. While hospital-level variation in temporary MCS device selection is not explained by differences in illness severity, patient-level variation appears to be related, at least in part, to illness severity

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics