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Background: We have developed P10s-PADRE, a carbohydrate-mimetic-based peptide, cancer vaccine and demonstrated its safety and immunogenicity in a Phase I clinical trial performed in stage IV breast cancer patients. HR+/HER2- breast cancer is the most common form of breast cancer diagnosed in the United States. These patients face a persistent risk of distant recurrence long after completion of their treatment and new strategies to activate anti-tumor immune responses can improve outcomes of standard therapies. The current study was performed to examine the feasibility, safety and immunogenicity of adding P10s-PADRE to standard-of-care chemotherapy in HR+/HER2− early-stage breast cancer patients. Methods: Five combination schedules were designed based on the timing of immunizations relative to a standard-of-care neoadjuvant chemotherapy regimen. Induction of on-treatment antibody and cellular responses, including T-cells, natural killer (NK) cells, and cytokines was determined. Tumor-infiltrating lymphocytes were quantified in core and surgical biopsies. The data were used to define the treatment effect in general and the vaccine contribution in particular. Results: Combination of P10s-PADRE with chemotherapy was safe and immunogenic. Antibody response was superior in a particular combination schedule, called schedule C, where 3 weekly immunizations preceded the first dose of chemotherapy. We observed that the schedule C, relative to other schedules, displayed an increase in CD16 expression on NK cells, a drop in serum IFN-γ, and an increase in quantity of stromal TILs in residual tumors. Subjects demonstrated a significant reduction in the size of their primary tumor and three subjects achieved pCR. Conclusions: The timing of the immunization relative to the chemotherapy seems to define the type and strength of the immune responses elicited. A particular combination schedule, schedule C, appears promising and the results warrant the conduct of randomized phase II trials. Citation Format: Issam Makhoul, Saddam M Ibrahim, Muhammad Abu-Rmaileh, Fariba Jousheghany, Eric Siegel, Lora J Rogers, John J Lee, Sergio Pina-Oviedo, Ginell R Post, Thaddeus Beck, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi. Timing of the immunization defines immune signature of a peptide cancer vaccine combined with Neoadjuvant chemotherapy in HR+ breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-15.

Breast cancer patients diagnosed with HR+/HER2– tumors face a persistent risk of distant recurrence long after completion of their treatment. Strategies to induce anti-tumor immune responses could complement standard-of-care therapies for these patients. The current study was performed to examine the feasibility, safety and immunogenicity of adding P10s-PADRE to standard-of-care chemotherapy in HR+/HER2− early-stage breast cancer patients. Twenty-five subjects were treated in a single-arm Phase Ib clinical trial. Five different immunization schedules were considered to evaluate the feasibility of eliciting an immune response. The primary immunogenicity endpoint was antibody titer. The expression of several activation markers on natural killer (NK) cells and serum concentrations of Th1/Th2 cytokines were also examined. The percentage of tumor-infiltrating lymphocytes (TILs) was determined. Antibody response was superior in schedule C where 3 weekly immunizations preceded the first dose of chemotherapy. A significant change in CD16, NKp46 and CD94 expression levels on NK cells and a rise in serum content of IFN-γ was observed after treatment. Schedule C showed an increase in TILs in residual lesions. The combination therapy is safe and immunogenic with treatment schedule C being immunologically promising. Randomized trials focused on long-term survival outcomes are needed to evaluate clinical benefits.

Introduction Fetal intracranial hemorrhage (ICH) is a rare but serious prenatal diagnosis. Predisposing factors include maternal trauma and fetal coagulation dysfunction. Maternal vitamin K deficiency has been described as an etiology. We present a case of maternal vitamin K deficiency associated with fetal ICH after percutaneous biliary drain (PBD) placement in a complicated cholecystectomy with injury to the common bile duct. Case presentation A 21-year-old woman, G2P1, presented at 23 weeks and 3 days of gestation with epigastric pain, nausea and vomiting. Right upper quadrant ultrasound diagnosed cholelithiasis. The patient was managed conservatively and discharged. She returned four days later, at 24 weeks of gestation, with worsening symptoms and ultrasound showing acute cholecystitis. She underwent laparoscopic cholecystectomy. Increasing bilirubin and imaging showed a transected biliary duct that required percutaneous biliary drain (PBD) placement. The patient was discharged and followed up at a high-risk obstetric clinic. Prenatal ultrasound showed bilateral ventriculomegaly with features of ICH. Maternal vitamin K deficiency was confirmed with PIVKA-II testing. The patient received vitamin K supplementation with normalization of the coagulopathy. Delivery occurred at 36 weeks of gestation via cesarean delivery after preterm premature rupture of membranes for fetal macrocrania. The neonate was discharged to a hospice. Discussion Maternal and neonatal etiologies for ICH include malabsorption and coagulopathy. Maternal vitamin K deficiency should be considered when coagulopathy is present. This case highlights that maternal vitamin K deficiency due to biliary diversion and malabsorption increases the risk of fetal ICH, which impacts pregnancy and neonatal outcomes., Highlights • Maternal vitamin K deficiency due to biliary diversion and malabsorption may predisp fetal intracranial hemorrhage. • Fetal intracranial hemorrhage may impact pregnancy and neonatal outcomes, particularly if severe. • Monitoring maternal coagulation may aid in the diagnosis of maternal vitamin K deficiency.

Summary:. Traditional livestreaming of surgery to an audience requires stationary video broadcasting infrastructure, with viewers congregating in front of a screen, while audiovisual technicians provide support in the background. In recent years, livestreaming technologies from cameras to teleconference platforms have advanced dramatically, even to allow for compliance with the Health Insurance Portability and Accountability Act of 1996 with web-based encryption. The objective of this article is to show that livestreaming surgery in medical education is possible using portable devices, with the resident and medical students as audience at home interacting on their computer or smart devices. The surgeon utilizes a head-mounted camera transmitting video feed using a wireless transmitter broadcasting to a laptop computer, which is hosting a Health Insurance Portability and Accountability Act–compliant version of Zoom. The entire setup is portable, and the surgeon is tethered neither to a cord nor to the institution’s audiovisual enterprise. This prototype setup allows the surgeon to broadcast live surgery interactively at any time and from any operating room with remote medical students and surgical residents. We posit that our medical education industry would need to condense the devices into a turnkey livestreaming camera system with optimized frames per second reception.

Bilateral ureteropelvic junction (UPJ) tears are rare. Trauma can obscure this diagnosis. The objective of this case report is to highlight the rapid diagnosis of this injury and care in the case of pregnancy. A 22-year-old pregnant female was ejected from her car and presented with abdominal pain. The patient got a computed tomography (CT)-chest, abdomen, pelvis (CT-CAP) revealing bilateral ureteral injury, which was confirmed on retrograde cystoscopy. Her injuries were treated with nephrostomy tubes with plans for definitive repair after pregnancy. Fetus remained stable throughout her care and the patient was discharged with no complications. Due to the rapid diagnosis and effective stabilization, the patient and fetus recovered well from the injuries and multiple procedures. While there are many explanations for bilateral UPJ tears, deceleration and hyperextension seem to be the two major mechanisms of this injury.

Background. While pituitary tumors are well understood, little research has been done on metastasis from primary tumors into pituitary adenomas, also known as composite tumors. Because only 34 cases of composite tumors have been reported to date, we hope to better characterize these tumors by reviewing cases reported in the literature and reviewed our own documented case, which includes next-generation sequencing. Case Presentation. A 74-year-old man presented to the emergency department with left vision loss for 3 months. He had a history of colon cancer treated with colectomy and clear cell renal carcinoma treated with left nephrectomy. A preoperative MRI demonstrated growth of a peripherally enhancing, centrally necrotic mass with sellar expansion measuring 5.7×3.1×3.0 cm. Given these findings, an endoscopic endonasal transsphenoidal resection was performed. Histological assessment revealed a composite tumor: one neoplasm was a nonfunctioning pituitary adenoma, and another neoplasm was a clear cell carcinoma. Next-generation sequencing demonstrated that the tumors shared mutations in VHL and Notch2. The patient died 2 months later from systemic metastatic cancer. Conclusion. From our literature review, most metastatic lesions in these composite tumors originated from neoplasms of the lung and kidney. Approximately 63% patients presented with ophthalmoplegia as the initial symptom while 23% displayed hormonal abnormalities. Postoperative mortality had a median of 3.5 months. In our patient, the presence of VHL and Notch2 mutations in both tumors highlights the possibility of using next-generation sequencing to help identify therapeutic targets even in complex composite neoplasms.