Medical Student Instruction in Peripheral Nerve Blockade Utilizing Fresh Cadaver Limbs in a Simulation Center.

Background: Ultrasound imaging is increasingly used in medical practice, but many institutions have room for growth regarding its incorporation into medical education. An elective hands-on course was developed for preclinical medical students using ultrasound to review and enhance their understanding of anatomy as well as to teach ultrasound-guided nerve blocks on cadaver extremities. The hypothesis was that after 3 instructional sessions students would be able to identify 6 anatomic structures, representing 3 types of tissue, in cadaver upper extremities. Methods: Students received didactic instruction on ultrasound and regional anatomy at the beginning of each class, followed by hands-on practice, including ultrasound use with phantom task trainers, live models, and fresh cadaver limbs. The primary outcome was the students' ability to correctly identify anatomic structures using ultrasound. Secondary outcomes included their ability to perform a simulated nerve block in the cadaver extremities in comparison with a standardized checklist, as well as their response to a post-course survey. Results: Overall, the students had a 91% success rate in identifying anatomic structures and showed capability of performing simulated nerve block with occasional instructor prompting. The post-course survey revealed that the students felt strongly that both the ultrasound and cadaveric components of the course were beneficial to their education. Conclusion: Ultrasound instruction with live models and fresh cadaver extremities in a medical student elective course resulted in a high degree of recognition of anatomic structures, as well as permitted a valued clinical correlation in the form of simulated peripheral nerve blockade.

Splice-switching of the insulin receptor pre-mRNA alleviates tumorigenic hallmarks in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is an aggressive pediatric tumor with a poor prognosis for metastasis and recurrent disease. Large-scale sequencing endeavors demonstrate that Rhabdomyosarcomas have a dearth of precisely targetable driver mutations. However, IGF-2 signaling is known to be grossly altered in RMS. The insulin receptor (IR) exists in two alternatively spliced isoforms, IR-A and IR-B. The IGF-2 signaling molecule binds both its innate IGF-1 receptor as well as the insulin receptor variant A (IR-A) with high affinity. Mitogenic and proliferative signaling via the canonical IGF-2 pathway is, therefore, augmented by IR-A. This study shows that RMS patients express increased IR-A levels compared to control tissues that predominantly express the IR-B isoform. We also found that Hif-1α is significantly increased in RMS tumors, portraying their hypoxic phenotype. Concordantly, the alternative splicing of IR adapts to produce more IR-A in response to hypoxic stress. Upon examining the pre-mRNA structure of the gene, we identified a potential hypoxia-responsive element, which is also the binding site for the RNA-binding protein CUG-BP1 (CELF1). We designed Splice Switching Oligonucleotides (SSO) against this binding site to decrease IR-A levels in RMS cell lines and, consequently, rescue the IR-B expression levels. SSO treatment resulted in a significant reduction in cell proliferation, migration, and angiogenesis. Our data shows promising insight into how impeding the IGF-2 pathway by reducing IR-A expression mitigates tumor growth. It is evident that Rhabdomyosarcomas use IR alternative splicing as yet another survival strategy that can be exploited as a therapeutic intervention in conjunction with already established anti-IGF-1 receptor therapies.

Case Report of Remifentanil Labor Analgesia for a Pregnant Patient With Congenital Methemoglobinemia Type 1.

Congenital methemoglobinemia is a rare disease characterized by cyanosis and a left shifting of the oxyhemoglobin dissociation curve. The disease necessitates avoidance of certain medications commonly used in obstetrics, making labor analgesia and anesthesia challenging. We present a case report of peripartum anesthetic management of a pregnant patient with congenital methemoglobinemia type 1 who received remifentanil labor analgesia and continuous methemoglobin monitoring. Continuous real-time monitoring of methemoglobin concentrations may prove to be a useful monitor in future care settings. A review of literature encompassing various perioperative and obstetric anesthesia and analgesia management considerations is presented.

Nodular Lymphocyte-Predominant Hodgkin Lymphoma in Progressive Transformation of Germinal Centers.

Nodular lymphocyte-predominant Hodgkin lymphoma is an uncommon variant of Hodgkin lymphoma. Progressive transformation of germinal centers has been associated with and can develop prior to, concurrent with, or after the diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma. We present a patient with a history of progressive transformation of germinal centers of the right parotid who presented 4 years later with ipsilateral parotid mass and cervical adenopathy. Knowledge of her previous diagnosis raised our concern for lymphoma, influenced our surgical management, and spared the patient additional surgery with risk of facial nerve injury inherent in revision parotidectomy.

Oncolytic HSV virotherapy in murine sarcomas differentially triggers an antitumor T-cell response in the absence of virus permissivity.

Multiple studies have indicated that in addition to direct oncolysis, virotherapy promotes an antitumor cytotoxic T cell response important for efficacy. To study this phenomenon further, we tested three syngeneic murine sarcoma models that displayed varied degrees of permissiveness to oncolytic herpes simplex virus replication and cytotoxicity in vitro, with the most permissive being comparable to some human sarcoma tumor lines. The in vivo antitumor effect ranged from no or modest response to complete tumor regression and protection from tumor rechallenge. The in vitro permissiveness to viral oncolysis was not predictive of the in vivo antitumor effect, as all three tumors showed intact interferon signaling and minimal permissiveness to virus in vivo. Tumor shrinkage was T-cell mediated with a tumor-specific antigen response required for maximal antitumor activity. Further analysis of the innate and adaptive immune microenvironment revealed potential correlates of susceptibility and resistance, including favorable and unfavorable cytokine profiles, differential composition of intratumoral myeloid cells, and baseline differences in tumor cell immunogenicity and tumor-infiltrating T-cell subsets. It is likely that a more complete understanding of the interplay between the immunologic immune microenvironment and virus infection will be necessary to fully leverage the antitumor effects of this therapeutic platform.