Faculty Bibliography

AIMS/OBJECTIVE:The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established. METHODS AND RESULTS/RESULTS:= 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction. CONCLUSIONS:The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19.

This Special Issue of the International Journal of Environmental Research and Public Health is dedicated to increasing the scientific information available about the long-term effects of exposure to the 2001 World Trade Center disaster [...].

Carotid Doppler ultrasound is used as a measure of fluid responsiveness, however, assessing change with statistical confidence requires an adequate beat sample size. The coefficient of variation helps quantify the number of cardiac cycles needed to adequately detect change during functional hemodynamic monitoring.

INTRODUCTION:Early hemorrhage is often missed by traditional vital signs because of physiological reserve, especially in the young and healthy. We have developed a novel, wearable, wireless Doppler ultrasound patch that tracks real-time blood velocity in the common carotid artery. MATERIALS AND METHODS:We studied eight healthy volunteers who decreased their cardiac output using a standardized Valsalva maneuver. In all eight, we simultaneously monitored the velocity time integral (VTI) of the common carotid artery (using the ultrasound patch) as well as the descending aorta (using a traditional pulsed wave duplex imaging system); the descending aortic VTI was used as a surrogate for left ventricular stroke volume (SV). Additionally, in a subset of four, we simultaneously measured SV using a noninvasive pulse contour analysis device. RESULTS:From baseline to peak effect of Valsalva, there was a statistically significant fall in descending aortic and common carotid VTI of 37% (P = 0.0005) and 23% (P < 0.0001), respectively. Both values returned to baseline on recovery. Additionally, a novel index from the carotid ultrasound patch (i.e., the heart rate divided by the carotid artery VTI) detected a 10% fall in aortic VTI with high sensitivity and specificity (100% and 100%, respectively); this novel index also accurately detected a 10% decrease in SV as measured by the noninvasive SV monitor. The mean arterial pressure, measured by the noninvasive pulse contour device, did not correctly detect the fall in SV. CONCLUSION:In summary, a novel index from a wireless Doppler ultrasound patch may be more sensitive and specific for detecting decreased cardiac output than standard vital signs in healthy volunteers.

Quantitative Doppler ultrasound of the carotid artery has been proposed as an instantaneous surrogate for monitoring rapid changes in left ventricular output. Tracking immediate changes in the arterial Doppler spectrogram has value in acute care settings such as the emergency department, operating room and critical care units. We report a novel, hands-free, continuous-wave Doppler ultrasound patch that adheres to the neck and tracks Doppler blood flow metrics in the common carotid artery using an automated algorithm. String and blood-mimicking test objects demonstrated that changes in velocity were accurately measured using both manually and automatically traced Doppler velocity waveforms. In a small usability study with 22 volunteer users (17 clinical, 5 lay), all users were able to locate the carotid Doppler signal on a volunteer subject, and, in a subsequent survey, agreed that the device was easy to use. To illustrate potential clinical applications of the device, the Doppler ultrasound patch was used on a healthy volunteer undergoing a passive leg raise (PLR) as well as on a congestive heart failure patient at resting baseline. The wearable carotid Doppler patch holds promise because of its ease-of-use, velocity measurement accuracy, and ability to continuously record Doppler spectrograms over many cardiac and respiratory cycles.

OPINION STATEMENT/UNASSIGNED:Treatment sequencing in early-stage breast cancer has significantly evolved in recent years, particularly in the triple negative (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive subsets. Instead of surgery first followed by chemotherapy, several clinical trials showed benefits to administering systemic chemotherapy (and HER2-targeted therapies) prior to surgery. These benefits include more accurate prognostic estimates based on the extent of residual cancer that can also guide adjuvant treatment, and frequent tumor downstaging that can lead to smaller surgeries in patients with large tumors at diagnosis. Patients with extensive invasive residual cancer after neoadjuvant therapy are at high risk for disease recurrence, and two pivotal clinical trials, CREATE-X and KATHERINE, demonstrated improved recurrence free survival with adjuvant capecitabine and ado-trastuzumab-emtansine (T-DM1) in TNBC and HER2-positive residual cancers, respectively. Patients who achieve pathologic complete response (pCR) have excellent long-term disease-free survival regardless of what chemotherapy regimen induced this favorable response. This allows escalation or de-escalation of adjuvant therapy: patients who achieved pCR could be spared further chemotherapy, while those with residual cancer could receive additional chemotherapy postoperatively. Ongoing clinical trials are testing this strategy (CompassHER2-pCR: NCT04266249). pCR also provides an opportunity to assess de-escalation of locoregional therapies. Currently, for patients with residual disease in the lymph nodes (ypN+), radiation therapy entails coverage of the undissected axilla, and may include supra/infraclavicular/internal mammary nodes in addition to the whole breast or chest wall, depending on the type of surgery. Ongoing trials are testing the safety of omitting post-mastectomy breast and post-lumpectomy nodal irradiation (NCT01872975) as well as omitting axillary lymph node dissection (NCT01901094) in the setting of pCR. Additionally, evolving technologies such as minimal residual disease (MRD) monitoring in the blood during follow-up may allow early intervention with "second-line systemic adjuvant therapy" for patients with molecular relapse which might prevent impending clinical relapse.

Although mutations in DNA are the best-studied source of neoantigens that determine response to immune checkpoint blockade, alterations in RNA splicing within cancer cells could similarly result in neoepitope production. However, the endogenous antigenicity and clinical potential of such splicing-derived epitopes have not been tested. Here, we demonstrate that pharmacologic modulation of splicing via specific drug classes generates bona fide neoantigens and elicits anti-tumor immunity, augmenting checkpoint immunotherapy. Splicing modulation inhibited tumor growth and enhanced checkpoint blockade in a manner dependent on host T cells and peptides presented on tumor MHC class I. Splicing modulation induced stereotyped splicing changes across tumor types, altering the MHC I-bound immunopeptidome to yield splicing-derived neoepitopes that trigger an anti-tumor T cell response in vivo. These data definitively identify splicing modulation as an untapped source of immunogenic peptides and provide a means to enhance response to checkpoint blockade that is readily translatable to the clinic.

SOURCE CITATION/UNASSIGNED:JAMA. 2021;325:476-81. 33528542.