RESUMEN

The administration of 4-factor prothrombin complex concentrate (4F-PCC) has expanded beyond its Food and Drug Administration (FDA)-approved indication for the emergent reversal of vitamin K antagonists (VKAs). Therefore, this study aimed to evaluate the risks and benefits associated with the expanded use of 4F-PCC. We conducted a single-center retrospective review of 4F-PCC administrations at our university hospital. Of the 159 patients who received 4F-PCC, 76% (n = 121) and 24% (n = 38) received it for the FDA-approved indication in the vitamin K-related coagulopathy (VKA) group and for expanded use in the nonvitamin K-related coagulopathy (nVKA) group, respectively. The expanded use of 4F-PCC was associated with a less robust reduction in the international normalized ratio (INR) (INR of -0.7 ± 1.3 vs INR of -1.6 ± 1.8, P = .002), and fewer patients in the nVKA group achieved a postadministration INR of less than1.5 (11% vs 79%, P = .001) than those in the VKA group. Furthermore, the 30-day mortality rate was significantly higher in the nVKA cohort than in the VKA cohort (42% vs 20%, P = .04). Notably, based on our data, underlying differences in the patient's comorbidities, particularly advanced liver disease, may have contributed to the observed outcome variations, including mortality rate. Therefore, factors, including comorbidities and the underlying etiology of coagulopathy, should be considered when deciding on the expanded use of 4F-PCC. Further research is needed to better understand the potential risks and benefits of 4F-PCC in expanded use scenarios, and the clinical decision to use 4F-PCC outside its FDA-approved indication should be made carefully, considering this information.

Asunto(s)

Trastornos de la Coagulación Sanguínea , Hepatopatías , Humanos , Estudios Retrospectivos , Factores de Coagulación Sanguínea/farmacología , Factores de Coagulación Sanguínea/uso terapéutico , Trastornos de la Coagulación Sanguínea/inducido químicamente , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Factor IX , Hepatopatías/tratamiento farmacológico , Vitamina K , Anticoagulantes/efectos adversos , Relación Normalizada Internacional

RESUMEN

PURPOSE: Early exposure and surgical mentorship can augment interest in surgery. We evaluate the effect and feasibility of offering education and mentorship opportunities in surgery to premedical students at our institution through an undergraduate surgery interest group (USIG). MATERIALS AND METHODS: We conducted a 1-year assessment of our USIG and reviewed its organizational structure, funding resources, media promotion, and educational activities. Our USIG hosted introductory-level surgical skills workshops, guest lectures by surgeons, and various facility tours. To assess participants' interests, as well as the influences on them to pursue a surgical profession, we analyzed pre- and post-event questionnaires. Similar questionnaires were completed by medical students in our medical student surgery interest group to compare any differences in perception between premedical and medical students. RESULTS: Our USIG currently has 378 undergraduate student members, with a higher proportion of women than in our medical student surgery interest group (P < 0.003). Neurosurgery was the most popular career choice among undergraduate participants. Participants reported the highest satisfaction with suturing and high-fidelity trauma surgery skills workshops. Undergraduate participants indicated that their intrinsic interest in the sciences is the highest motivation to pursue a surgical profession. Resident lifestyle and social obligations of a surgical career were actually positive influences for undergraduate participants; in contrast, medical students viewed those variables as negative factors. CONCLUSION: Our USIG was met with enthusiasm by premedical students and faculty alike. Participation strengthened premedical students' interest in pursuing surgery and increased their understanding of the surgical profession. Early mentorship may positively influence premedical students' perception of surgical careers. USIG is economically feasible and time-efficient; we encourage other academic institutions and educators to consider investing in similar interest groups.

RESUMEN

Oncolytic adenoviruses (Ad) are promising tools for cancer therapeutics. Most Ad-based therapies utilize species C serotypes, with Adenovirus type 5 (Ad5) most commonly employed. Prior clinical trials demonstrated low efficiency of oncolytic Ad5 vectors, mainly due to the absence of Ad5 primary receptor (Coxsackie and Adenovirus Receptor, CAR) on cancer cells. Engineering serotype chimeric vectors (Ad5/3) to utilize Adenovirus type 3 (Ad3) receptors has greatly improved their oncolytic potential. Clinical translation of these infectivity-enhanced vectors has been challenging due to a lack of replication permissive animal models. In this study, we explored pigs as a model to study the performance of fiber-modified Ad5/3 chimeric vectors. As a control, the Ad5 fiber-unmodified virus was used. We analyzed binding, gene transfer, replication, and cytolytic ability of Ad5 and Ad5/3 in various non-human cell lines (murine, hamster, canine, porcine). Among all tested cell lines only porcine cells supported active binding and replication of Ad5/3. Syrian hamster cells supported Ad5 replication but showed no evidence of productive viral replication after infection with Ad5/3 vectors. Transduction and replication ability of Ad5/3 in porcine cells outperformed Ad5, a phenomenon often observed in human cancer cell lines. Replication of Ad5 and Ad5/3 was subsequently evaluated in vivo in immunocompetent pigs. Quantitative PCR analyses 7 days post infection revealed Ad5 and Ad5/3 DNA and replication-dependent luciferase activity in the swine lungs and spleen indicating active replication in these tissues. These studies demonstrated the flaws in using Syrian hamsters for testing serotype chimeric Ad5/3 vectors. This is the first report to validate the pig as a valuable model for preclinical testing of oncolytic adenoviruses utilizing Adenovirus type 3 receptors. We hope that these data will help to foster the clinical translation of oncolytic adenoviruses including those with Ad3 retargeted tropism.