Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer.

Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts "cold" tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.

Malposition of an Internal Aortic Annuloplasty Ring After Acute Type A Aortic Dissection Repair.

Poor tissue quality of adventitia and intima makes aortic root repair complex in patients with acute type A aortic dissection. The management of aortic root repair remains controversial. Internal aortic annuloplasty devices provide a standardized aortic valve repair technique to reduce and prevent annular dilation, while the modified Florida sleeve (mFS) procedure is an aortic root remodeling technique that does not require coronary artery reimplantation. However, little is known about the long-term durability of internal aortic annuloplasty with the hemispheric aortic annuloplasty remodeling ring (HARRT) combined with a mFS procedure in acute type A aortic dissection repair. A 52-year-old man had initial type A aortic dissection repair with an internal aortic annuloplasty ring and a mFS technique. He presented with dyspnea on exertion and intermittent chest pain one year later. Transesophageal echocardiogram revealed malposition of aortic annuloplasty ring and severe aortic insufficiency. He underwent a redo sternotomy with aortic valve replacement. Intraoperative findings demonstrated the aortic annuloplasty ring had dislodged from under the left and right coronary annulus and was adherent to the base of the noncoronary leaflet. The annuloplasty ring and aortic valve leaflets were excised and replaced with a mechanical aortic valve.

The role of the axillary Impella 5.0 device on patients with acute cardiogenic shock.

BACKGROUND: Acute cardiogenic shock is associated with high mortality rates. The Impella device is a microaxial left ventricular assist device that can be inserted through the axillary artery. The purpose of our study is to determine the role of the Axillary Impella devices on patients with acute cardiogenic shock. METHODS: A retrospective chart review was conducted to identify patients who underwent Axillary Impella device placement for acute cardiogenic shock from January 1st, 2014 to September 30th, 2018 at a single institution. In-patient records were examined to determine duration of device, length of stay (LOS), postoperative complications, and 30-day in-hospital mortality. RESULTS: A total of 40 patients, who were primarily men (N = 29) with a mean age of 61.2 ± 10.7 years old, underwent Axillary Impella placement for cardiogenic shock. The primary reasons for implant were (1) required upgraded support from an Impella CP or intra-aortic balloon pump (iabp) to Impella 5.0, (2) to treat left ventricular (LV) distention for patients on extracorporeal mechanical oxygenation (ECMO), and (3) to provide longer term support and allow for mobilization of the patients in whom a device was already indwelling. Twenty-three of the patients had previous devices already in place including a Femoral Impella CP device or an iabp and 9 patients were on ECMO support. The duration of the device was 21.05 ± 17 days with the LOS of 40.8 ± 28 days for those patients. Seventeen of the patients went on to additional surgery including (1) Heartmate 3 device placement (N = 6), (2) other cardiac procedures such as surgical revascularization (N = 9), and orthotopic heart transplantation (N = 2). A total of 21 patients of the 40 (52%) died during their hospitalization with 7 patients (17%) having complications related to the Impella device. These complications included right arm ischemia or neuropathy (N = 3) and Impella malfunction requiring device replacement (N = 4). The majority of these devices were placed in the right axillary artery (N = 38) versus the left axillary artery (N = 2). CONCLUSIONS: A total of 58% (N = 23) of the study patients had previous mechanical support and 23% (N = 9) were on ECMO demonstrating the severity of disease and accounting for the high mortality. The Axillary Impella device allows for a minimally invasively placed device that is durable with a mean duration of 3 weeks. The Axillary artery Impella 5.0 provides upgraded full cardiac support while allowing for mobilization of the patient. In addition, it treats LV distention in patients on ECMO while avoiding sternotomy. Finally, the Axillary Impella provides time for decision making for explant, additional therapy with either long-term devices or orthotopic heart transplant.

Competition as a Means for Improving Academic Scores and Attendance at Education Conference.

OBJECTIVE: To determine the effectiveness of competition on education conference attendance rate with a secondary goal of increased performance on in-service examination performance within a single academic general surgery residency. DESIGN: By using a competition-based model of learning, we aimed to increase the overall resident attendance to weekly education conference as well as performance on in-service examination. Residents were given weekly reading assignments which were supplemented with lectures from faculty with expert knowledge of a given topic on a weekly basis. The ability of the surgical resident to apply this knowledge in a board-style exam was then tested on a weekly by administering a 10-question quiz. SETTING: The program was implemented at Robert Wood Johnson Medical School, an academic surgical residency program. RESULTS: The competition-based model of learning had improved conference attendance rates from 52% to 90% Overall quiz participation rates were 90.3% (SEM = 6.32%). Of the 5 distinct postgraduate levels performing on the weekly quizzes, the postgraduate year (PGY) 3 class performed best with the highest scores through 8 weeks. The next highest scoring class was the PGY 4 class. Overall average scores were 76% (standard deviation 10%). American Board of Surgery In-Training Examination scores did not significantly change between the observed years. Overall the average percentile for 2016 American Board of Surgery In-Training Examination was 55.3 compared to 2017's 47.4 (p = 0.0906). CONCLUSIONS: After adding competition to our weekly education conference, we were able to improve our overall education conference attendance. Although this change did not have any objective changes measured on in-service examination results, we feel the increase in attendance and participation within education conference can only serve to benefit the surgical trainee. The establishment of this program has increased resident academic expectations, and a formalized guest-attending lecture schedule only drives conference participation higher. The establishment of weekly quizzes for and by residents allows the student to be more involved in their own education, and that of their peers.

Novel bone morphogenetic protein receptor inhibitor JL5 suppresses tumor cell survival signaling and induces regression of human lung cancer.

BMP receptor inhibitors induce death of cancer cells through the downregulation of antiapoptotic proteins XIAP, pTAK1, and Id1-Id3. However, the current most potent BMP receptor inhibitor, DMH2, does not downregulate BMP signaling in vivo because of metabolic instability and poor pharmacokinetics. Here we identified the site of metabolic instability of DMH2 and designed a novel BMP receptor inhibitor, JL5. We show that JL5 has a greater volume of distribution and suppresses the expression of Id1 and pTak1 in tumor xenografts. Moreover, we demonstrate JL5-induced tumor cell death and tumor regression in xenograft mouse models without immune cells and humanized with adoptively transferred human immune cells. In humanized mice, JL5 additionally induces the infiltration of immune cells within the tumor microenvironment. Our studies show that the BMP signaling pathway is targetable in vivo and BMP receptor inhibitors can be developed as a therapeutic to treat cancer patients.